# #"# (20)

*i S Q a* ν*p*

<sup>2</sup> ( 1) 1 1

And the concept of vector velocity profile described above. But with the addition of a time frame provided by the STIC algorithm, which means a continuous sum of velocity profiles,

∈

The mathematical background of this study was based on flow calculation:

giving us a new profile of the area, represented as:

And to the velocity profile, expressed also as

( )

Where N is the entire amount of frames included in a cardiac cycle.

made offline.

model was designed

matrix of data:

*N*

Fig. 10. Screen snapshot of descending aorta plane with selected volume of evaluation. Right side of the image is the VOI containing the *v1*…*vn* information. A set of voxels like this one was added to the matrix, since *t1* till *tn* where n=end of the cardiac cycle. (Actual experiment added measurements from the aortic isthmus, this image is for illustrative purposes)

Fig. 11. Colour deconvolution algorithm as delivered by the Mathematica software ®

Future Uses of Three/Four Dimensional Power Doppler Signal in Fetal Medicine 267

Alcázar, Juan Luis & Jurado, M., 2011. Three-dimensional ultrasound for assessing women

Bello-Muñoz, J. et al., 2009. OP23.05: A three-dimensional power Doppler algorithm for

Bellotti, M, Pennati, G. & Ferrazzi, E., 2007. Re: ductus venosus shunting in growth-

Bellotti, M et al., 2000. Role of ductus venosus in distribution of umbilical blood flow in

Bellotti, Maria et al., 2004. Simultaneous measurements of umbilical venous, fetal hepatic,

Bendick, P.J. et al., 1998. Three-dimensional vascular imaging using Doppler ultrasound.

Berg, S. et al., 2000. Volumetric blood flow measurement with the use of dynamic 3-

Bozkurt, N., Başgül Yigiter, A., et al., 2010. Correlations of fetal-maternal outcomes and first

Burns, P.N., 1992. Measuring volume flow with Doppler ultrasound-an old nut. Ultrasound

Cruz-Martinez, R et al., 2011. Normal reference ranges of fetal regional cerebral blood

Cruz-Martinez, Rogelio et al., 2009. Cerebral blood perfusion and neurobehavioral

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102.

Official Journal of the International Society of Ultrasound in Obstetrics and

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human fetuses during second half of pregnancy. American Journal of Physiology.

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Regression analysis showed a strong correlation between actual measurement of Combined cardiac Output as obtained by invasive methods and the estimated flow 4D PD dataset as calculated by the authors. The reference polynomial equation and plot is showed in Figure 11

Fig. 12. Polinomial regression plot

#### **4. Conclusion**

Three dimensional power Doppler (3D PD), in its current state has no correlation with actual flow measurements, since there is no way of involving the time as a magnitude. Four dimensional power Doppler, by adding the surface integration of velocity vectors from power Doppler signal, and the Spatio Time Image correlation (STIC) might improve significantly its potential. An important amount of additional research on this field is mandatory in order to grant its utility in clinical conditions. But 4D PD could be, in the near future, the most reliable tool for non invasive assessment of physiological intrauterine magnitudes, as Cardiac Output, vascular shunting and flow variations, in normal as well as in pathological conditions

#### **5. Acknowledgment**

The authors wish to thank Drs Marielle Estevez and Carla Fonseca from the animal house of the Institut de Recerca de l'Hospital Universitari Vall d'Hebron for their invaluable help in animal care and preparation. They also wish to express their gratitude to Dr Jose Lluis Peiró for his surgical intervention on the mother sheep and the instrumentation of foetuses as well as for his generous teaching and support.

#### **6. References**

Alcázar, J L, 2008. Three-dimensional power Doppler derived vascular indices: what are we measuring and how are we doing it? Ultrasound in Obstetrics & Gynecology: The

Regression analysis showed a strong correlation between actual measurement of Combined cardiac Output as obtained by invasive methods and the estimated flow 4D PD dataset as calculated by the authors. The reference polynomial equation and plot is showed in Figure

Three dimensional power Doppler (3D PD), in its current state has no correlation with actual flow measurements, since there is no way of involving the time as a magnitude. Four dimensional power Doppler, by adding the surface integration of velocity vectors from power Doppler signal, and the Spatio Time Image correlation (STIC) might improve significantly its potential. An important amount of additional research on this field is mandatory in order to grant its utility in clinical conditions. But 4D PD could be, in the near future, the most reliable tool for non invasive assessment of physiological intrauterine magnitudes, as Cardiac Output, vascular shunting and flow variations, in normal as well as

The authors wish to thank Drs Marielle Estevez and Carla Fonseca from the animal house of the Institut de Recerca de l'Hospital Universitari Vall d'Hebron for their invaluable help in animal care and preparation. They also wish to express their gratitude to Dr Jose Lluis Peiró for his surgical intervention on the mother sheep and the instrumentation of foetuses as well

Alcázar, J L, 2008. Three-dimensional power Doppler derived vascular indices: what are we

measuring and how are we doing it? Ultrasound in Obstetrics & Gynecology: The

11

Fig. 12. Polinomial regression plot

**4. Conclusion** 

in pathological conditions

**5. Acknowledgment** 

**6. References** 

as for his generous teaching and support.

Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology, 32(4), págs.485-487.


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**1. Introduction** 

propagation.

today.

interventions aimed at diminishing inflammation.

**2. Historical aspects of ultrasound** 

**16** 

*Austria* 

**Thyroid Sonography in** 

Roy Moncayo and Helga Moncayo

*WOMED, Innsbruck,* 

**3D with Emphasis on Perfusion** 

Ultrasound examination of the thyroid gland is an essential diagnostic element in daily clinical practice. The aim of this chapter is to describe the advanced clinical value of conducting 3D ultrasound examinations putting emphasis on the quantitative evaluation of perfusion characteristics of the thyroid gland and to relate these results to therapeutic

The term echo (Greek: Hχώ, *Ēkhō*; "Sound") refers to the persistence of sound after its source has stopped. Greek mythology tells from an Oread (a mountain nymph) who pined away for love of Narcissus (in Ovid, Metamorphoses). The phenomenon of air being sent back by a wall was described by Aristotles (384-322 BCE). The Greek word echo came into German writings in the 16th century. Athanasius Kircher (1602 – 1680) used the principle of "Echometria" to determine the depth of a well. His book was entitled: "Neue Hall- und Thon-Kunst oder Mechanische Gehaim-Verbindung der Kunst und Natur durch Stimme und Hall" and appeared 1684. At this time he was able to measure the speed of sound

On May 25th, 1842 Christian Doppler (born in Salzburg, Austria) presented in Prague his talk on "Abhandlung Über das farbige Licht der Doppelsterne und einiger anderer Gestirne des Himmels" (Eng. *On the coloured light of the binary stars and some other stars of the heavens)* at the Prague Polytechnic [1]. The Doppler effect is a main stand of many examinations

In 1880 Pierre and Jacques Curie discovered the piezoelectric effect and postulated the generation of ultrasound waves [2]. They found that applying an electric current to a crystal would produce a vibration which could in turn produce sound waves. In turn, sound waves striking a crystal would produce an electric voltage. In 1917 Langevin constructed for the first time a piezoelectric ultrasound transducer based on quartz elements and which was called sandwich-style. This product was oriented towards military use in World War I, i.e. the detection of submarines. The Langevin-type transducers were utilized in depth sounding devices [3]. More details on the work of Langevin is found elsewhere [4]. In 1921 Behm in Vienna described the Echolot which was used to determine the water depth for ships [5].

Yigiter, A.B. et al., 2011. Placental volume and vascularization flow indices by 3D power Doppler US using VOCAL technique and correlation with IGF-1, free beta-hCG, PAPP-A, and uterine artery Doppler at 11-14 weeks of pregnancy. Journal of Perinatal Medicine, 39(2), págs.137-141.

### **Thyroid Sonography in 3D with Emphasis on Perfusion**

Roy Moncayo and Helga Moncayo *WOMED, Innsbruck, Austria* 

#### **1. Introduction**

272 Sonography

Yigiter, A.B. et al., 2011. Placental volume and vascularization flow indices by 3D power

Perinatal Medicine, 39(2), págs.137-141.

Doppler US using VOCAL technique and correlation with IGF-1, free beta-hCG, PAPP-A, and uterine artery Doppler at 11-14 weeks of pregnancy. Journal of

> Ultrasound examination of the thyroid gland is an essential diagnostic element in daily clinical practice. The aim of this chapter is to describe the advanced clinical value of conducting 3D ultrasound examinations putting emphasis on the quantitative evaluation of perfusion characteristics of the thyroid gland and to relate these results to therapeutic interventions aimed at diminishing inflammation.

#### **2. Historical aspects of ultrasound**

The term echo (Greek: Hχώ, *Ēkhō*; "Sound") refers to the persistence of sound after its source has stopped. Greek mythology tells from an Oread (a mountain nymph) who pined away for love of Narcissus (in Ovid, Metamorphoses). The phenomenon of air being sent back by a wall was described by Aristotles (384-322 BCE). The Greek word echo came into German writings in the 16th century. Athanasius Kircher (1602 – 1680) used the principle of "Echometria" to determine the depth of a well. His book was entitled: "Neue Hall- und Thon-Kunst oder Mechanische Gehaim-Verbindung der Kunst und Natur durch Stimme und Hall" and appeared 1684. At this time he was able to measure the speed of sound propagation.

On May 25th, 1842 Christian Doppler (born in Salzburg, Austria) presented in Prague his talk on "Abhandlung Über das farbige Licht der Doppelsterne und einiger anderer Gestirne des Himmels" (Eng. *On the coloured light of the binary stars and some other stars of the heavens)* at the Prague Polytechnic [1]. The Doppler effect is a main stand of many examinations today.

In 1880 Pierre and Jacques Curie discovered the piezoelectric effect and postulated the generation of ultrasound waves [2]. They found that applying an electric current to a crystal would produce a vibration which could in turn produce sound waves. In turn, sound waves striking a crystal would produce an electric voltage. In 1917 Langevin constructed for the first time a piezoelectric ultrasound transducer based on quartz elements and which was called sandwich-style. This product was oriented towards military use in World War I, i.e. the detection of submarines. The Langevin-type transducers were utilized in depth sounding devices [3]. More details on the work of Langevin is found elsewhere [4]. In 1921 Behm in Vienna described the Echolot which was used to determine the water depth for ships [5].

Thyroid Sonography in 3D with Emphasis on Perfusion 275

Source: http://en.wikipedia.org/wiki/File:Christian\_Doppler.jpg

extremities.

Fig. 2. C. Doppler, born november 29th, 1803 in Salzburg, public domain

Beyme [8]. Additional information has been obtained via Wikipedia.

**2.1 Modern history of ultrasound including thyroid examinations** 

physics of ultrasound have been presented by Kossoff [13].

thyroid carcinoma where liver metastases were present.

Following these fundamental developments, clinical applications began to develop. The first clinical applications of ultrasound are credited to the Austrian neurologist Karl Theo Dussik [6]. In the introduction of his article he mentions that he was motivated to investigate the medical importance of ultrasound in 1937 after having read a review on use of underwater ultrasound techniques (Echolotung) as well as the use of ultrasound for the detection of material flaws in industrial settings by Sokolov [7]. He goes on to discuss the properties of auscultation, which in the end works because changes in tissue density, relative water content, and colloidal structure have occured. Further references on the basic physics of ultrasound can be found in the paper. The initial clinical indications according to Dussik were the ventricle system of the brain and the spinal bones in a procedure called hyperphonography. Further fields of application were liver, kidneys, testicles, and the

Some of the data mentioned above have been extracted from the publication by Frentzel-

General articles on the historical aspects and developments of ultrasound can be found in recent publications [8-10]. In addition to this some useful clinical publications on thyroid examinations are those of Ruchala and Szczepanek [11] and Sholosh and Borhani [12]. The

In the 1950's Howry and Bliss presented their device which was used for the ultrasonic visualization of body soft tissue structures [14,15]. Some interesting images can be found in their publication [15]: Figure 3 shows the apparatus called "Somascope". Due to its use of a cattle drink tank it was also called the "cattle tank scanner". Figure 4 in shows the anatomical structures of the neck at the C5 level. Figure 5 depicts the findings of a case

Source: http://echo.mpiwg-berlin.mpg.de/ECHOdocuView?url=/mpiwg/online/permanent/library/ 1EZGRF6Y/pageimg&viewMode=images&pn=6&mode=imagepath

Fig. 1. An image from Kircher's book depicting air reflection

Source: http://echo.mpiwg-berlin.mpg.de/ECHOdocuView?url=/mpiwg/online/permanent/library/

1EZGRF6Y/pageimg&viewMode=images&pn=6&mode=imagepath Fig. 1. An image from Kircher's book depicting air reflection

Source: http://en.wikipedia.org/wiki/File:Christian\_Doppler.jpg Fig. 2. C. Doppler, born november 29th, 1803 in Salzburg, public domain

Following these fundamental developments, clinical applications began to develop. The first clinical applications of ultrasound are credited to the Austrian neurologist Karl Theo Dussik [6]. In the introduction of his article he mentions that he was motivated to investigate the medical importance of ultrasound in 1937 after having read a review on use of underwater ultrasound techniques (Echolotung) as well as the use of ultrasound for the detection of material flaws in industrial settings by Sokolov [7]. He goes on to discuss the properties of auscultation, which in the end works because changes in tissue density, relative water content, and colloidal structure have occured. Further references on the basic physics of ultrasound can be found in the paper. The initial clinical indications according to Dussik were the ventricle system of the brain and the spinal bones in a procedure called hyperphonography. Further fields of application were liver, kidneys, testicles, and the extremities.

Some of the data mentioned above have been extracted from the publication by Frentzel-Beyme [8]. Additional information has been obtained via Wikipedia.

#### **2.1 Modern history of ultrasound including thyroid examinations**

General articles on the historical aspects and developments of ultrasound can be found in recent publications [8-10]. In addition to this some useful clinical publications on thyroid examinations are those of Ruchala and Szczepanek [11] and Sholosh and Borhani [12]. The physics of ultrasound have been presented by Kossoff [13].

In the 1950's Howry and Bliss presented their device which was used for the ultrasonic visualization of body soft tissue structures [14,15]. Some interesting images can be found in their publication [15]: Figure 3 shows the apparatus called "Somascope". Due to its use of a cattle drink tank it was also called the "cattle tank scanner". Figure 4 in shows the anatomical structures of the neck at the C5 level. Figure 5 depicts the findings of a case thyroid carcinoma where liver metastases were present.

Thyroid Sonography in 3D with Emphasis on Perfusion 277

Fig. 5 (a-f). Case 3. Both lobes of a normal thyroid shown in gray, color, and power Doppler modus. The VFI value of 0.09 is reflected by the almost complete absence of perfusion signs.

Such cases do not require quantitative evaluation of perfusion

Fig. 3. Case 1. Normal thyroid seen in 3-D power Doppler modus using a vaginal transducer. The thick vessel corresponds to a laryngeal artery

Fig. 4. Case 2. Chronic recurrent thyroiditis in 3-D power Doppler modus using a vaginal transducer. Note the increased vascularity as compared to Figure. 3

Fig. 3. Case 1. Normal thyroid seen in 3-D power Doppler modus using a vaginal

Fig. 4. Case 2. Chronic recurrent thyroiditis in 3-D power Doppler modus using a vaginal

transducer. Note the increased vascularity as compared to Figure. 3

transducer. The thick vessel corresponds to a laryngeal artery

Fig. 5 (a-f). Case 3. Both lobes of a normal thyroid shown in gray, color, and power Doppler modus. The VFI value of 0.09 is reflected by the almost complete absence of perfusion signs. Such cases do not require quantitative evaluation of perfusion

Thyroid Sonography in 3D with Emphasis on Perfusion 279

(g) (h)

(i) (j)

The gray value is relatively low due to the increased vascular density

Fig. 6. (continued) Case 4. The same patient shown in Figure 4 examined with the RSP5-12 transducer. a-c: the hypoechogenic structure of the thyroid. d-e: single slice in color mode showing several vessels. f: the 3D image reconstruction using VOCAL. g: the final 3D image showing total thyroid vascularity. Note the almost total absence of underlying thyroid tissue. h-i: segmented imaging of the thyroid. This procedure is important in order to detect any nodular changes within the gland. j: The parameters obtained after the VOCAL analysis.

In 1967 Fujimoto et al. published their data on US examination of the thyroid [16]. The authors described 4 basic echo patterns: cystic, sparsely spotted, strong internal echoes, and the lack of internal echoes. In 1971 the first paper by Blum et al. documented the use of Amode sonography [17]. In 1972 Blum [18] published an article entitled: "Clinical applications of thyroid echography" which described the data on 122 patients who had had thyroid surgery. Both A-mode and B-mode sonography was done with a 5 megahertz apparatus. In the one dimensional A-mode imaging a water-soluble gel was interposed between the transducer and the skin. For 2-dimensional B-mode imaging a mineral oil was used as coupling agent. During the examination the gain was changed in order to detect structures that had a maximal reflection while using low-sensitivity and finally high gain in order to detect lower amplitude echoes. Examples of these examinations can be seen in Figures 2-5 [18]. Acoustic dense structures were described in an adenoma (Fig. 6). Solid masses (benign or malignant) as well as thyroiditis appeared to be sonographically indistinguishable.

Fig. 6. (continues on next page) Case 4. The same patient shown in Figure. 4 examined with the RSP5-12 transducer. a-c: the hypoechogenic structure of the thyroid. d-e: single slice in color mode showing several vessels. f: the 3D image reconstruction using VOCAL. g: the final 3D image showing total thyroid vascularity. Note the almost total absence of underlying thyroid tissue. h-i: segmented imaging of the thyroid. This procedure is important in order to detect any nodular changes within the gland. j: The parameters obtained after the VOCAL analysis. The gray value is relatively low due to the increased vascular density

(a) (b)

(c) (d)

(e) (f)

analysis. The gray value is relatively low due to the increased vascular density

Fig. 6. (continues on next page) Case 4. The same patient shown in Figure. 4 examined with the RSP5-12 transducer. a-c: the hypoechogenic structure of the thyroid. d-e: single slice in color mode showing several vessels. f: the 3D image reconstruction using VOCAL. g: the final 3D image showing total thyroid vascularity. Note the almost total absence of underlying thyroid tissue. h-i: segmented imaging of the thyroid. This procedure is important in order to detect any nodular changes within the gland. j: The parameters obtained after the VOCAL

Fig. 6. (continued) Case 4. The same patient shown in Figure 4 examined with the RSP5-12 transducer. a-c: the hypoechogenic structure of the thyroid. d-e: single slice in color mode showing several vessels. f: the 3D image reconstruction using VOCAL. g: the final 3D image showing total thyroid vascularity. Note the almost total absence of underlying thyroid tissue. h-i: segmented imaging of the thyroid. This procedure is important in order to detect any nodular changes within the gland. j: The parameters obtained after the VOCAL analysis. The gray value is relatively low due to the increased vascular density

In 1967 Fujimoto et al. published their data on US examination of the thyroid [16]. The authors described 4 basic echo patterns: cystic, sparsely spotted, strong internal echoes, and the lack of internal echoes. In 1971 the first paper by Blum et al. documented the use of Amode sonography [17]. In 1972 Blum [18] published an article entitled: "Clinical applications of thyroid echography" which described the data on 122 patients who had had thyroid surgery. Both A-mode and B-mode sonography was done with a 5 megahertz apparatus. In the one dimensional A-mode imaging a water-soluble gel was interposed between the transducer and the skin. For 2-dimensional B-mode imaging a mineral oil was used as coupling agent. During the examination the gain was changed in order to detect structures that had a maximal reflection while using low-sensitivity and finally high gain in order to detect lower amplitude echoes. Examples of these examinations can be seen in Figures 2-5 [18]. Acoustic dense structures were described in an adenoma (Fig. 6). Solid masses (benign or malignant) as well as thyroiditis appeared to be sonographically indistinguishable.

Thyroid Sonography in 3D with Emphasis on Perfusion 281

In subacute thyroiditis and Graves' disease the authors found very uniform low-amplitude echoes which were only visible at high-gain setting in the A-mode. The image of B-mode was described as having a very fine stippling. According to Blum the basic purposes for conducting thyroid ultrasound examinations were: to determine whether a solitary cold nodule was cystic or solid, to document changes in size of solitary nodules even under suppressive therapy, to evaluate the depth dimension [18]. According to Australian specialists the development of ultrasound techniques for thyroid examinations is based on a breast ultrasound examination apparatus installed at the Royal North Shore Hospital in

After the first definitions on the use of ultrasound for thyroid investigations, the notion of adding data on the depth of the nodule was presented by Thijs et al. [20]. The authors combined digital scintigraphy with ultrasound. The classification of nodules into hot, warm, cool, and cold was also advanced. The feature of sonolucent halo of adenomatous nodules was demonstrated by Scheible et al. in 1979 [21]. In 1988 Ralls et al. coined the term "thyroid inferno" to describe the characteristics of color-flow Doppler sonography in patients with Graves' disease [22]. Their study did not include patients with thyroiditis nor with latent hypothyroidism. In 1992 Miyakawa et al. described a pattern of decreased echogenicity in

In 1994-1995 Rubin reported the development of Power Doppler technology [24,25]. This development was considered an improvement of color Doppler which can detect fractional moving blood volume. A demonstration of the applicability of this technique for the detection of inflammatory changes in joints was already published 1994 [26]. The authors described increased blood flow as being suggestive of mild inflammation of the tendon examined, and marked hyperemia with vascular blush in severe changes (Fig. 2 in [26]).

The following general considerations on the characteristics of ultrasound investigations are taken from Rose and Nelson [27]. In brightness mode or gray scale US the velocity of US wave propagation in fluids and soft tissues is approximately 1540 meters per second. The time delay between the pulse sent and that of the returned wave is the basis for the determination of the reflector depth. The intensity of the reflected US wave is given as brightness of the image. Spatial resolution is dependent on the wavelength of the US wave. US attenuation increases with increased frequency. Deep structures require low frequencies in the range of 2.5-3.5 MHz, while superficial structures can be investigated within the range of 7-10 MHz. Signals are transmitted by the transducer and at the same time echo reflections are registered. According to the structure of the tissues, some portions of the sound is reflected back to the surface. Dense echoes are reflected from structures with different acoustic densities. Homogeneous liquids transmit sound without reflections. Air-filled structures do not transmit ultrasound. Attenuation of waves can be due to body fat and fascial structures

[27]. In thyroid examinations such attenuation can occur due to the cervical fasciae.

The beginnings of Kretz can be traced back to early 1947 when the company started the production of resistance-welded wired goods. The founder of the company was engineer Paul Kretz. Some of the products included glass balloon baskets, milk bottle carriers and potato baskets. The company started in the old rooms of the old brewery in Zipf, Austria. In

**2.2 Historical aspects of 3D ultrasound – The Kretz story** 

1952 the first own building was built.

Sydney. The publication by Crocker and Jellins appeared in 1978 [19].

cases of silent thyroiditis. Such patients had a high T3 to T4 ratio [23].

(a) (b)

(c) (d)

(e)

Fig. 7. Case 5. A female patient with a cystic nodule. The cyst has clear limits, no vessels penetrate the cavity. a: the 3D image set. b: enlarged view of the 3D reconstruction. c-e: segmentation of the cyst

(a) (b)

(c) (d)

(e)

Fig. 7. Case 5. A female patient with a cystic nodule. The cyst has clear limits, no vessels penetrate the cavity. a: the 3D image set. b: enlarged view of the 3D reconstruction.

c-e: segmentation of the cyst

In subacute thyroiditis and Graves' disease the authors found very uniform low-amplitude echoes which were only visible at high-gain setting in the A-mode. The image of B-mode was described as having a very fine stippling. According to Blum the basic purposes for conducting thyroid ultrasound examinations were: to determine whether a solitary cold nodule was cystic or solid, to document changes in size of solitary nodules even under suppressive therapy, to evaluate the depth dimension [18]. According to Australian specialists the development of ultrasound techniques for thyroid examinations is based on a breast ultrasound examination apparatus installed at the Royal North Shore Hospital in Sydney. The publication by Crocker and Jellins appeared in 1978 [19].

After the first definitions on the use of ultrasound for thyroid investigations, the notion of adding data on the depth of the nodule was presented by Thijs et al. [20]. The authors combined digital scintigraphy with ultrasound. The classification of nodules into hot, warm, cool, and cold was also advanced. The feature of sonolucent halo of adenomatous nodules was demonstrated by Scheible et al. in 1979 [21]. In 1988 Ralls et al. coined the term "thyroid inferno" to describe the characteristics of color-flow Doppler sonography in patients with Graves' disease [22]. Their study did not include patients with thyroiditis nor with latent hypothyroidism. In 1992 Miyakawa et al. described a pattern of decreased echogenicity in cases of silent thyroiditis. Such patients had a high T3 to T4 ratio [23].

In 1994-1995 Rubin reported the development of Power Doppler technology [24,25]. This development was considered an improvement of color Doppler which can detect fractional moving blood volume. A demonstration of the applicability of this technique for the detection of inflammatory changes in joints was already published 1994 [26]. The authors described increased blood flow as being suggestive of mild inflammation of the tendon examined, and marked hyperemia with vascular blush in severe changes (Fig. 2 in [26]).

The following general considerations on the characteristics of ultrasound investigations are taken from Rose and Nelson [27]. In brightness mode or gray scale US the velocity of US wave propagation in fluids and soft tissues is approximately 1540 meters per second. The time delay between the pulse sent and that of the returned wave is the basis for the determination of the reflector depth. The intensity of the reflected US wave is given as brightness of the image. Spatial resolution is dependent on the wavelength of the US wave. US attenuation increases with increased frequency. Deep structures require low frequencies in the range of 2.5-3.5 MHz, while superficial structures can be investigated within the range of 7-10 MHz. Signals are transmitted by the transducer and at the same time echo reflections are registered. According to the structure of the tissues, some portions of the sound is reflected back to the surface. Dense echoes are reflected from structures with different acoustic densities. Homogeneous liquids transmit sound without reflections. Air-filled structures do not transmit ultrasound. Attenuation of waves can be due to body fat and fascial structures [27]. In thyroid examinations such attenuation can occur due to the cervical fasciae.

#### **2.2 Historical aspects of 3D ultrasound – The Kretz story**

The beginnings of Kretz can be traced back to early 1947 when the company started the production of resistance-welded wired goods. The founder of the company was engineer Paul Kretz. Some of the products included glass balloon baskets, milk bottle carriers and potato baskets. The company started in the old rooms of the old brewery in Zipf, Austria. In 1952 the first own building was built.

company.

technology.

Thyroid Sonography in 3D with Emphasis on Perfusion 283

In 1950 the company started to develop Echolot (echo sounding) machines for the purpose of material testing. By 1957 the material testing machines became the main stand of the

In 1962 medical professionals start tests on the clinical use of the available material test apparatus. One of the first users was Prof. Kratochwil who used the technology for gynecological examinations, i.e. "ultrasonic placentography" (1962) [28]. In the time between 1967 and 1977 the ultrasound machines were used in gynecology, ophthalmology, neurology, and radiology based on A-mode, B-mode, time-motion and Doppler techniques. Some of the early models which were developed were: Combison 200 (1975-1978), and the improved Combison 202/R, the Minifason (1973-1977) – a hand-held Doppler for fetal heart investigations. The Combison 100 (1977) was the first real-time sector scanner of the world equipped with the first single element rotating transducer. The Combison 310 released in 1987 was a compact ultrasound machine. The following Combison 320 included computer

In 1987 the first images of 3D scanning began. This technology was included in the first generation of 3D machines, having the Combison 330 in 1989. In 1992 the Combison 520 appeared. This was the 2nd generation of 3D machines to be produced in series. Between 1996 and 2001 Kretztechnik and Medison (Korea) fused and brought out the Voluson 530D in 1997. In 2001 Kretztechnik was taken over by G.E. The Austrian press reported: "Medical Systems, a subsidiary of US group General Electric (GE), acquired a 65.4% majority in Austrian Kretztechnik from Korean Medison. GE paid EUR 97.5mn, or EUR 12 per share, for Medison's stake. GE offers to buy widespread shares for EUR 17 per share in the coming two weeks. Zipf-based Kretztechnik is the world market leader for modern ultrasound systems, i.e. three-dimensional real-time imaging systems". The following models were

The accomplishments of Carl Kretz were honored in 1999 when he received the Ian Donald Gold Medal for Technical Development by the International Society of Ultrasound in Obstetrics and Gynecology [29]. The publication by Chiou et al. on 3D thyroid investigations provides some additional information as to the development of 3D imaging in general [30].

those of the Voluson 730 series. In 2011 the Voluson S8 and S6 were released.

(a) (b)

Fig. 9. Case 7. A female patient with Graves' disease presenting bilateral thyroid associated

ophthalmopathy. a: 3D reconstruction. b: detail of the 3D reconstruction. VFI 14.8

(a) (b)

(c) (d)

(e)

Fig. 8. Case 6. A female patient with a compensated autonomous adenoma. a: demonstration of the vessels surrounding the adenoma. In gray modus these vessels appear as a halo. b-e: segmentation of the nodule that shows lack of vascularity within the nodule

(a) (b)

(c) (d)

Fig. 8. Case 6. A female patient with a compensated autonomous adenoma. a: demonstration of the vessels surrounding the adenoma. In gray modus these vessels appear as a halo. b-e: segmentation of the nodule that shows lack of vascularity within the nodule

(e)

In 1950 the company started to develop Echolot (echo sounding) machines for the purpose of material testing. By 1957 the material testing machines became the main stand of the company.

In 1962 medical professionals start tests on the clinical use of the available material test apparatus. One of the first users was Prof. Kratochwil who used the technology for gynecological examinations, i.e. "ultrasonic placentography" (1962) [28]. In the time between 1967 and 1977 the ultrasound machines were used in gynecology, ophthalmology, neurology, and radiology based on A-mode, B-mode, time-motion and Doppler techniques. Some of the early models which were developed were: Combison 200 (1975-1978), and the improved Combison 202/R, the Minifason (1973-1977) – a hand-held Doppler for fetal heart investigations. The Combison 100 (1977) was the first real-time sector scanner of the world equipped with the first single element rotating transducer. The Combison 310 released in 1987 was a compact ultrasound machine. The following Combison 320 included computer technology.

In 1987 the first images of 3D scanning began. This technology was included in the first generation of 3D machines, having the Combison 330 in 1989. In 1992 the Combison 520 appeared. This was the 2nd generation of 3D machines to be produced in series. Between 1996 and 2001 Kretztechnik and Medison (Korea) fused and brought out the Voluson 530D in 1997. In 2001 Kretztechnik was taken over by G.E. The Austrian press reported: "Medical Systems, a subsidiary of US group General Electric (GE), acquired a 65.4% majority in Austrian Kretztechnik from Korean Medison. GE paid EUR 97.5mn, or EUR 12 per share, for Medison's stake. GE offers to buy widespread shares for EUR 17 per share in the coming two weeks. Zipf-based Kretztechnik is the world market leader for modern ultrasound systems, i.e. three-dimensional real-time imaging systems". The following models were those of the Voluson 730 series. In 2011 the Voluson S8 and S6 were released.

The accomplishments of Carl Kretz were honored in 1999 when he received the Ian Donald Gold Medal for Technical Development by the International Society of Ultrasound in Obstetrics and Gynecology [29]. The publication by Chiou et al. on 3D thyroid investigations provides some additional information as to the development of 3D imaging in general [30].

Fig. 9. Case 7. A female patient with Graves' disease presenting bilateral thyroid associated ophthalmopathy. a: 3D reconstruction. b: detail of the 3D reconstruction. VFI 14.8

Thyroid Sonography in 3D with Emphasis on Perfusion 285

3D-Ultrasound examinations in this paper were done using a General Electrics Voluson 730 Pro ultrasound machine equipped with a RealTime 4D linear transducer (RSP5-12, GE Healthcare, Waukesha, WI 53188, USA). Data analysis was done using the VOCALTM software (4DView Version 5.x, GE Medical Systems - Kretztechnik GmbH & Co OHG) installed on the ultrasound machine. Both the gray-scale values and the color values were normalized from 0 to 100, 100 being the highest intensity. The analysis of the 3D Doppler data sets provided the following indexes: VI, FI, and VFI [31]. The examination was done with the patients lying supine and with a light hyperextension of the neck. The transducer was placed on the midline of the neck having the whole gland inside the field of view. The mean time of data acquisition for the thyroid studies was approximately 20 seconds. The study had to be repeated only when movement artifacts arising from the patients (coughing or swallowing) had occurred. The drawing of the area of the thyroid gland was carried out using manual trace at 15° steps [34]. During drawing care was taken not to include laryngeal

vessels which are typically seen on the medial border of the thyroid.

(a) (b)

Fig. 11. Case 8. A female patient with Graves' disease after treatment with selenomethionine

and Mg. a-b: normal echogenic signal of the thyroid. c: demonstration of less total

(c)

vascularity, VOCAL reconstruction, VFI 3.49

**3. 3D-Ultrasound thyroid examination** 

(c)

Fig. 10. Case 8. A female patient with Graves' disease prior to treatment with selenomethionine and Mg. a-b: low echogenic signal of the thyroid. c: demonstration of increased total vascularity, VOCAL reconstruction, VFI 10.91

The paper describing the characteristics of quantified blood flow analysis using these machines was published by Pairleitner in 1999 [31]. The original definition of the indices states: "VI measures the number of color voxels in the cube, representing the vessels in the tissue (Figure 3). FI, a mean color value of all blood flow or induced flow intensities, represents the intensity of flow at the time of the three dimensional sweep. FI is not an indicator of perfusion, so it cannot give information on the volume of blood pumped through the vessels during a certain period of time. VFI is a combination of vascularization and flow information relating the weighted color values (weighted by their amplitudes) to the cube. Therefore, VFI represents both blood flow and vascularization". The automatic procedure for the quantification of vascularization indices was called VOCALTM. VOCAL stands for the 3D virtual organ computer-aided analysis program developed by Kretz. Data on the reliability of the VOCAL analysis as well as on the parametric setting for the examinations in gynecological applications have been presented by Bordes and Raine-Fenning [32,33].

#### **3. 3D-Ultrasound thyroid examination**

284 Sonography

(a) (b)

Fig. 10. Case 8. A female patient with Graves' disease prior to treatment with

selenomethionine and Mg. a-b: low echogenic signal of the thyroid. c: demonstration of

The paper describing the characteristics of quantified blood flow analysis using these machines was published by Pairleitner in 1999 [31]. The original definition of the indices states: "VI measures the number of color voxels in the cube, representing the vessels in the tissue (Figure 3). FI, a mean color value of all blood flow or induced flow intensities, represents the intensity of flow at the time of the three dimensional sweep. FI is not an indicator of perfusion, so it cannot give information on the volume of blood pumped through the vessels during a certain period of time. VFI is a combination of vascularization and flow information relating the weighted color values (weighted by their amplitudes) to the cube. Therefore, VFI represents both blood flow and vascularization". The automatic procedure for the quantification of vascularization indices was called VOCALTM. VOCAL stands for the 3D virtual organ computer-aided analysis program developed by Kretz. Data on the reliability of the VOCAL analysis as well as on the parametric setting for the examinations in gynecological applications have been presented by Bordes and Raine-

(c)

Fenning [32,33].

increased total vascularity, VOCAL reconstruction, VFI 10.91

3D-Ultrasound examinations in this paper were done using a General Electrics Voluson 730 Pro ultrasound machine equipped with a RealTime 4D linear transducer (RSP5-12, GE Healthcare, Waukesha, WI 53188, USA). Data analysis was done using the VOCALTM software (4DView Version 5.x, GE Medical Systems - Kretztechnik GmbH & Co OHG) installed on the ultrasound machine. Both the gray-scale values and the color values were normalized from 0 to 100, 100 being the highest intensity. The analysis of the 3D Doppler data sets provided the following indexes: VI, FI, and VFI [31]. The examination was done with the patients lying supine and with a light hyperextension of the neck. The transducer was placed on the midline of the neck having the whole gland inside the field of view. The mean time of data acquisition for the thyroid studies was approximately 20 seconds. The study had to be repeated only when movement artifacts arising from the patients (coughing or swallowing) had occurred. The drawing of the area of the thyroid gland was carried out using manual trace at 15° steps [34]. During drawing care was taken not to include laryngeal vessels which are typically seen on the medial border of the thyroid.

Fig. 11. Case 8. A female patient with Graves' disease after treatment with selenomethionine and Mg. a-b: normal echogenic signal of the thyroid. c: demonstration of less total vascularity, VOCAL reconstruction, VFI 3.49

Table 1.

60.00

50.00

40.00

30.00

**VFI**

20.00

10.00

0.00

Thyroid Sonography in 3D with Emphasis on Perfusion 287

Case Sex Diagnosis VFI 1 m Normal thyroid – (study done with a vaginal transducer) n.d. 2 f Chronic recurrent thyroiditis – (study done with a vaginal transducer) n.d. 3 m Normal thyroid 0.09 4 f Chronic recurring thyroiditis 23.97 5 f Cystic adenoma n.d. 6 f Autonomous adenoma n.d. 7 f Graves' disease and thyroid associated orbitopathy 14.8 8 f Graves' disease pre-treatment 10.91 9 f Graves' disease after treatment 3.49 10 f Latent hypothyroidism pre-treatment 4.22 11 f Latent hypothyroidism post-treatment 1.21

82

Fig. 14. The VFI value in different thyroid conditions. The first two bars correspond to single observations. The following groups of 2-bars each demonstrate the VFI changes following

Based on the results of previous investigations [36-40] supportive treatment included selenomethionine and Mg-citrate. Supplementation with selenomethionine (200 µg/d, Pure

therapy with selenomethionine and Mg citrate (p<0.01)

83

 normal hypothyroid hyperthyroid treated thyroiditis treated hyperthyroid thyroiditis

**Dg**

#### **4. Clinical cases: Normal thyroid, nodular disease, cystic disease, latent hypothyroidism, hypothyroidism, hyperthyroidism**

The ultrasound data presented here have been obtained during examinations carried out at our Institution WOMED in Innsbruck, Austria. A total of 140 examinations were carried out. The procedures were carried in accordance with the Declaration of Helsinki [35]. The list of representative demonstration cases presented in this chapter is shown in the Table. The initial ultrasound examinations (cases 1 and 2) were done by both authors based on the previous experience of HM in the field of reproductive medicine. These first 2 studies were carried out using a vaginal transducer. Two cases with nodular disease are presented in order to demonstrate the capability of 3-volume visualization of the thyroid. The most relevant perfusion parameter for hypo- and hyperthyroidism, i.e. VFI, is shown.

Fig. 12. Case 9. A female patient with latent hypothyroidism prior to treatment with selenomethionine and Mg. a: 3D reconstruction. b: 3D VOCAL reconstruction, VFI 4.22. Compare with Figure 13 (post-treatment images)

Fig. 13. Case 9. A female patient with latent hypothyroidism after treatment with selenomethionine and Mg. a: 3D reconstruction. b: 3D VOCAL reconstruction, VFI 1.21. Compare with Figure 12 (pre-treatment images)


Table 1.

286 Sonography

The ultrasound data presented here have been obtained during examinations carried out at our Institution WOMED in Innsbruck, Austria. A total of 140 examinations were carried out. The procedures were carried in accordance with the Declaration of Helsinki [35]. The list of representative demonstration cases presented in this chapter is shown in the Table. The initial ultrasound examinations (cases 1 and 2) were done by both authors based on the previous experience of HM in the field of reproductive medicine. These first 2 studies were carried out using a vaginal transducer. Two cases with nodular disease are presented in order to demonstrate the capability of 3-volume visualization of the thyroid. The most

**4. Clinical cases: Normal thyroid, nodular disease, cystic disease, latent** 

relevant perfusion parameter for hypo- and hyperthyroidism, i.e. VFI, is shown.

(a) (b)

(a) (b)

Fig. 13. Case 9. A female patient with latent hypothyroidism after treatment with selenomethionine and Mg. a: 3D reconstruction. b: 3D VOCAL reconstruction, VFI 1.21.

Compare with Figure 13 (post-treatment images)

Compare with Figure 12 (pre-treatment images)

Fig. 12. Case 9. A female patient with latent hypothyroidism prior to treatment with selenomethionine and Mg. a: 3D reconstruction. b: 3D VOCAL reconstruction, VFI 4.22.

**hypothyroidism, hypothyroidism, hyperthyroidism** 

**Dg**

Fig. 14. The VFI value in different thyroid conditions. The first two bars correspond to single observations. The following groups of 2-bars each demonstrate the VFI changes following therapy with selenomethionine and Mg citrate (p<0.01)

Based on the results of previous investigations [36-40] supportive treatment included selenomethionine and Mg-citrate. Supplementation with selenomethionine (200 µg/d, Pure

Thyroid Sonography in 3D with Emphasis on Perfusion 289

degree of vascularization. The VFI values seen in thyroiditis and Graves' disease are generally higher than in different conditions of ovarian function. These differences cannot be taken as absolute ones. Data variability between different publications has 2 main sources of error. The first one is the use of different Kretz machines (Combison, Voluson). The second one is the fact that each investigator or each machine has different examination settings for carrying out the studies. We recommend the continuous use of the same settings in order to produce comparable results. These facts have been mentioned by de Ziegler [46]. De Ziegler points out the weakness of early studies which were arbitrary and subjective in interpretation [46]. Some of the open expectations mentioned by de Ziegler included the "desire for an understanding of the mechanisms at play" as well as whether ovarian function had a relation to perfusion values. As we show in Figure 12, the relevant parameter VFI decreases significantly following the combined treatment with selenomethionine and magnesium. We postulate that the VFI represents an inflammatory process that is present in several thyroid entities. Initially we had described this as a "low grade connective tissue inflammation" in patients with thyroid associated ophthalmopathy [39]. In this publication we discussed amply the role of Se in inflammation. Data concerning Mg and inflammation can be found in the literature [47-60]. The initial invitation of the Editors of this book was

Increased perfusion characteristics in 3D modus provide an exact picture of the underlying inflammatory changes in the thyroid. This description is better than that of indirect signs said to be associated with such changes (simple Doppler imaging, pulsed Doppler). This technical enhancement will allow the clinician to gain immediate access to the basic underlying processes of thyroid disease, i.e. inflammation. This process of inflammation is directly related to the available body resources of substances that regulate inflammatory processes. Effectiveness of treatment can be uniquely evaluated by the quantitative 3D

Historical data on the development of GE Kretztechnik was kindly provided by GE Austria.

[1] Doppler C: Abhandlung Über das farbige Licht der Doppelsterne und einiger anderer

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[3] Mason WP: Piezoelectricity, its history and applications. *J Acoust Soc Am* 1981, 70: 1561-1566. [4] Paty P: Paul Langevin (1872-1946), la relativité et les quanta. *Bull Soc Fr Phys* 1999, 119: 15-20.

[6] Dussik KT: Über die Möglichkeit, hochfrequente mechanische Schwingungen als

[7] Sokolov SY: On the problem of the propagation of ultrasonic oscillations in various

diagnostisches Hilfsmittel zu verwerten. *Z Gesamte Neurol Psychatr* 1941, 174: 153-168.

Gestirne des Himmels. *Abh K Bohm Ges Wissen Prag* 1842, 465-482.

hemidres a faces inclinees. *C R Acad Sci Paris* 1880, 91: 294-295.

[5] Behm A: Das Behm-Echolot. *Ann Hydrogr* 1921, 49: 241-247.

bodies. *Elek Nachr Tech* 1929, 6: 454-460.

indeed to elaborate on these pathophysiological connections.

power Doppler perfusion study of the thyroid.

**6. Conclusions** 

**7. Acknowledgements** 

**8. References** 

Encapsulations ©, pro medico HandelsGmbH, Graz Austria) was prescribed if the serum levels were less than 80µg/l. Magnesium substitution was prescribed if the serum level was lower than 0.8 mmol/l (Magnesium Verla©, 60mg of Mg-citrate/Mg-L-glutamate, Kwizda Pharma GmbH, Vienna) at a dose of 360mg/day. This treatment was given over a period of 3 months in cases 8 and 10. The changes in thyroid morphology and VFI are given as cases 9 and 11. Statistical analysis of the 140 observations revealed that VFI was the most relevant parameter showing significant changes after our therapy approach (Figure 14).

#### **5. Discussion**

Studies with 3D technology concerning thyroid function are scarce. Only 2 publications have addressed this issue [30,41]. The paper by Chiou et al. is the first one in the literature to deal with the same technology as us [30]. This study included patients with Hashimoto's disease as well as Graves' disease. In Figure 1 the authors present the VFI value of a patient with Graves' disease (VFI = 30.7). This value is similar that the ones we have obtained. Unfortunately further individual data are not presented. The authors present exhaustive data on correlation analyses. The second publication on 3D ultrasound of the thyroid by Slapa et al. is centered on nodular thyroid disease [41]. This publication has no comparable data to our results. All together it can be said that 3D perfusion studies of the thyroid are rare.

3D perfusion studies, however, has found much wider application in the field of reproductive medicine since the original publication of the qualitative analysis method by Pairleitner et al. [31]. Data on the reliability of the VOCAL analysis as well as on the parametric setting for the examinations have been presented by Bordes and Raine-Fenning [32,33]. Concerns regarding power Doppler signal attenuation as discussed by Raine-Fenning [33] should not be relevant in thyroid examinations since the distance between the transducer and the organ is relatively constant (app. 1 to 1.5 cm).

Since more data is available from the gynecological field we will mention some data related to ovarian perfusion studies. Examination of the ovaries as reported by in Rainne-Fenning [33] revealed mean VFI values for the ovary of 2.076 and 2.074 (2 observers). Changes in ovarian vascularization during the menstrual cycle has been reported by Järvelä et al. [42]. In Table 2 of [42] a comparison of vascularization parameters between the right and left ovaries is shown. The mean values for VI, FI, VFI, and mean grayness were: 6.2/7.4, 43.4/46.5, 2.8/3.7, and 45.8/46.0, respectively. In 2002 Pan et al. compared the vascularization characteristics between patients with polycystic ovarian syndrome and controls [43]. The mean values for VI, FI, and VFI for normals and PCO patients were: 0.8/2.1, 44.44/50.26, and 1.44/3.99, respectively. In 2003 Pan et al. [44] described a stimulatory effect of HRT on the ovarian vascularization parameters in postmenopausal women (!). The mean values for VI, FI, and VFI before and after HRT were: 0.31/1.12, 30.47/38.41, and 0.13/0.59, respectively. This finding implies a stimulatory effect of conjugated equine estrogen on these parameters. The same group of investigators described increased vascularization parameters in women that showed a hyperresponse to stimulation protocols for IVF [45]. Hyperresponders had higher levels of estradiol (>3000 pg/ml) or had more than 15 oocytes retrieved. The mean values for VI, FI, and VFI for patients with a "normal" and patients with an increased response to stimulation were: 1.25/2.27, 43.19/50.23, and 0.63/1.18, respectively.

Comparing the image material presented in the above mentioned citations with our images, it can be clearly recognized that the thyroid gland has a wider range of variation in the degree of vascularization. The VFI values seen in thyroiditis and Graves' disease are generally higher than in different conditions of ovarian function. These differences cannot be taken as absolute ones. Data variability between different publications has 2 main sources of error. The first one is the use of different Kretz machines (Combison, Voluson). The second one is the fact that each investigator or each machine has different examination settings for carrying out the studies. We recommend the continuous use of the same settings in order to produce comparable results. These facts have been mentioned by de Ziegler [46]. De Ziegler points out the weakness of early studies which were arbitrary and subjective in interpretation [46]. Some of the open expectations mentioned by de Ziegler included the "desire for an understanding of the mechanisms at play" as well as whether ovarian function had a relation to perfusion values. As we show in Figure 12, the relevant parameter VFI decreases significantly following the combined treatment with selenomethionine and magnesium. We postulate that the VFI represents an inflammatory process that is present in several thyroid entities. Initially we had described this as a "low grade connective tissue inflammation" in patients with thyroid associated ophthalmopathy [39]. In this publication we discussed amply the role of Se in inflammation. Data concerning Mg and inflammation can be found in the literature [47-60]. The initial invitation of the Editors of this book was indeed to elaborate on these pathophysiological connections.

#### **6. Conclusions**

288 Sonography

Encapsulations ©, pro medico HandelsGmbH, Graz Austria) was prescribed if the serum levels were less than 80µg/l. Magnesium substitution was prescribed if the serum level was lower than 0.8 mmol/l (Magnesium Verla©, 60mg of Mg-citrate/Mg-L-glutamate, Kwizda Pharma GmbH, Vienna) at a dose of 360mg/day. This treatment was given over a period of 3 months in cases 8 and 10. The changes in thyroid morphology and VFI are given as cases 9 and 11. Statistical analysis of the 140 observations revealed that VFI was the most relevant

Studies with 3D technology concerning thyroid function are scarce. Only 2 publications have addressed this issue [30,41]. The paper by Chiou et al. is the first one in the literature to deal with the same technology as us [30]. This study included patients with Hashimoto's disease as well as Graves' disease. In Figure 1 the authors present the VFI value of a patient with Graves' disease (VFI = 30.7). This value is similar that the ones we have obtained. Unfortunately further individual data are not presented. The authors present exhaustive data on correlation analyses. The second publication on 3D ultrasound of the thyroid by Slapa et al. is centered on nodular thyroid disease [41]. This publication has no comparable data to our results. All together it can be said that 3D perfusion studies of the thyroid are rare.

3D perfusion studies, however, has found much wider application in the field of reproductive medicine since the original publication of the qualitative analysis method by Pairleitner et al. [31]. Data on the reliability of the VOCAL analysis as well as on the parametric setting for the examinations have been presented by Bordes and Raine-Fenning [32,33]. Concerns regarding power Doppler signal attenuation as discussed by Raine-Fenning [33] should not be relevant in thyroid examinations since the distance between the

Since more data is available from the gynecological field we will mention some data related to ovarian perfusion studies. Examination of the ovaries as reported by in Rainne-Fenning [33] revealed mean VFI values for the ovary of 2.076 and 2.074 (2 observers). Changes in ovarian vascularization during the menstrual cycle has been reported by Järvelä et al. [42]. In Table 2 of [42] a comparison of vascularization parameters between the right and left ovaries is shown. The mean values for VI, FI, VFI, and mean grayness were: 6.2/7.4, 43.4/46.5, 2.8/3.7, and 45.8/46.0, respectively. In 2002 Pan et al. compared the vascularization characteristics between patients with polycystic ovarian syndrome and controls [43]. The mean values for VI, FI, and VFI for normals and PCO patients were: 0.8/2.1, 44.44/50.26, and 1.44/3.99, respectively. In 2003 Pan et al. [44] described a stimulatory effect of HRT on the ovarian vascularization parameters in postmenopausal women (!). The mean values for VI, FI, and VFI before and after HRT were: 0.31/1.12, 30.47/38.41, and 0.13/0.59, respectively. This finding implies a stimulatory effect of conjugated equine estrogen on these parameters. The same group of investigators described increased vascularization parameters in women that showed a hyperresponse to stimulation protocols for IVF [45]. Hyperresponders had higher levels of estradiol (>3000 pg/ml) or had more than 15 oocytes retrieved. The mean values for VI, FI, and VFI for patients with a "normal" and patients with an increased response to stimulation were:

Comparing the image material presented in the above mentioned citations with our images, it can be clearly recognized that the thyroid gland has a wider range of variation in the

transducer and the organ is relatively constant (app. 1 to 1.5 cm).

1.25/2.27, 43.19/50.23, and 0.63/1.18, respectively.

parameter showing significant changes after our therapy approach (Figure 14).

**5. Discussion** 

Increased perfusion characteristics in 3D modus provide an exact picture of the underlying inflammatory changes in the thyroid. This description is better than that of indirect signs said to be associated with such changes (simple Doppler imaging, pulsed Doppler). This technical enhancement will allow the clinician to gain immediate access to the basic underlying processes of thyroid disease, i.e. inflammation. This process of inflammation is directly related to the available body resources of substances that regulate inflammatory processes. Effectiveness of treatment can be uniquely evaluated by the quantitative 3D power Doppler perfusion study of the thyroid.

#### **7. Acknowledgements**

Historical data on the development of GE Kretztechnik was kindly provided by GE Austria.

#### **8. References**


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**17** 

Thomas Scholbach *Chemnitz Clinics, Chemnitz* 

*Germany* 

**Dynamic Tissue Perfusion Measurement** 

Perfusion is a fundamental prerequisite for all living tissues to meet their needs in terms of supply of oxygen, nutrients, hormones, messenger substances and other necessary dilutes. Dynamic Tissue Perfusion Measurement (DTPM) was developed to quantify the perfusion of tissues and organs by means of colour Doppler sonography. Perfusion is perceived as a certain amount of blood passing through a defined region of interest (ROI) in a certain

Colour Doppler sonography is universally used to visualize blood flow inside tissues. The velocity of moving red blood cells is depicted as coloured pixels on the background of uncoloured, black and white pixels, which describe parts of tissues without detectable blood flow. The colouration differs according to the velocity and direction of flow. A colour scale within each image shows the spectrum of reddish and bluish colours used to differentiate the direction (reddish hues describe flow which is reversely directed to bluish flow, in most cases the machine is set to depict flow towards the transducer in red). In both directions, lighter shades describe higher velocities than darker shades. A wall filter is used to exclude extremely low velocity signals from imaging, which mostly emanate from vessel wall vibrations and do not add to real blood flow. The colour scale or colour bar thus gives a visual clue to assign velocity signals from zero to a maximum value to certain vessels inside a tissue. At both ends of the colour scale, the maximum flow velocities for red and blue colour are depicted. These values are determined by the actual pulse repetition frequency and the applied ultrasound frequency. They correspond to the outermost hue on each side of the colour bar whereas the minimum flow is determined by the hue next to the black line

Both parameters change during the heart cycle. A third prerequisite is thus to take into account these rhythmic changes and to refer them to their basic rhythm which is a full heart

(indicating the wall filter) separating blue and red hues from each other. To calculate perfusion in a certain ROI two parameters must be known:

1. The flow velocity in all vessels within the ROI 2. The area of all vessel transsections in this ROI

**1. Introduction 1.1 Rationale** 

time.

cycle.

**– Basics and Applications** 


### **Dynamic Tissue Perfusion Measurement – Basics and Applications**

Thomas Scholbach *Chemnitz Clinics, Chemnitz Germany* 

#### **1. Introduction**

#### **1.1 Rationale**

292 Sonography

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from a population-based cohort. *Am J Clin Nutr* 2006, 84: 1062-1069. [52] Guerrero-Romero F, Rodríguez-Morán M: Hypomagnesemia, oxidative stress, inflammation, and metabolic syndrome. *Diabetes Metab Res Rev* 2006, 22: 471-476. [53] Almoznino-Sarafian D, Berman S, Mor A, Shteinshnaider M, Gorelik O, Tzur I *et al*.:

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reduces free radicals in an in vivo coronary occlusion-reperfusion model. *J Am Coll* 

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inflammatory response: potential physiopathological implications. *Arch Biochem* 

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grade inflammation impaired postprandial stimulation of muscle protein synthesis

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polycystic ovary syndrome using three-dimensional power Doppler ultrasonography:

Doppler signals in postmenopausal women receiving hormone replacement

signal in hyperresponders during in vitro fertilization treatment using threedimensional power Doppler ultrasonography. *Ultrasound Med Biol* 2003, 29: 921-927. [46] de Ziegler D: Uterine Doppler studies: technology driven data, or answers to our

> Perfusion is a fundamental prerequisite for all living tissues to meet their needs in terms of supply of oxygen, nutrients, hormones, messenger substances and other necessary dilutes. Dynamic Tissue Perfusion Measurement (DTPM) was developed to quantify the perfusion of tissues and organs by means of colour Doppler sonography. Perfusion is perceived as a certain amount of blood passing through a defined region of interest (ROI) in a certain time.

> Colour Doppler sonography is universally used to visualize blood flow inside tissues. The velocity of moving red blood cells is depicted as coloured pixels on the background of uncoloured, black and white pixels, which describe parts of tissues without detectable blood flow. The colouration differs according to the velocity and direction of flow. A colour scale within each image shows the spectrum of reddish and bluish colours used to differentiate the direction (reddish hues describe flow which is reversely directed to bluish flow, in most cases the machine is set to depict flow towards the transducer in red). In both directions, lighter shades describe higher velocities than darker shades. A wall filter is used to exclude extremely low velocity signals from imaging, which mostly emanate from vessel wall vibrations and do not add to real blood flow. The colour scale or colour bar thus gives a visual clue to assign velocity signals from zero to a maximum value to certain vessels inside a tissue. At both ends of the colour scale, the maximum flow velocities for red and blue colour are depicted. These values are determined by the actual pulse repetition frequency and the applied ultrasound frequency. They correspond to the outermost hue on each side of the colour bar whereas the minimum flow is determined by the hue next to the black line (indicating the wall filter) separating blue and red hues from each other.

To calculate perfusion in a certain ROI two parameters must be known:


Both parameters change during the heart cycle. A third prerequisite is thus to take into account these rhythmic changes and to refer them to their basic rhythm which is a full heart cycle.

Dynamic Tissue Perfusion Measurement – Basics and Applications 295

values (v) which are a product of the cosine of the Doppler angle (α) and the true velocity

fd = 2\* fo \* vt/c \*cos α

This means that in many cases the tissue microvasculature colouration shows velocity values which are smaller than real. To overcome this, an angle correction for each vessel would be necessary. This cannot be done yet in two-dimensional images. With 3D imaging, such a correction is already feasible (see below in section "foetus"). In 2D images, thus an error occurs with DTPM, which must be kept constant to allow comparisons between

1. A chaotic vessel architecture without predominant vessel diameters and Doppler angles

In the latter case, the orientation on anatomical landmarks offers a sufficient framework to find the vascular patterns, which are typical for a certain organ (fig. 2). An example how to

Fig. 1. Example of tumor perfusion measurement. Two concentric ROIs are separately investigated. The vessel architecture is irregular or chaotic (center). No specific prevailing vessel size or orientation can be stated. Left: comparisons of perfusion intensities in the periphery (red column) and the center (green column). Center: Display of the ROIs and false color maps with perfusion intensity curves. Right: time course of the relevant perfusion

In both cases, the inevitable error of impossible individual Doppler angle correction for each

For all these considerations, it is crucial to achieve comparable conditions for depicting the vessels in a certain ROI. In the kidney the ROI should be placed inside the outer cortex, in a layer stretching from the outer border of the medullary pyramids to the renal surface and laterally from the watershed of two neighbouring segments to the opposite watershed (see chapter: kidney). In the lymph node and thyroid lobes, a longitudinal section trough the

vessel is held constant. Comparisons of different examinations thus become possible.

2. A regular vessel architecture, which can be reliably retrieved (kidney type).

with: fd: Doppler shift, fo: insonation frequency, c: sound velocity

investigations. This can be achieved under following circumstances:

choose relevant landmarks is given for the kidney below.

(vt), according to the Doppler principle:

(type tumour perfusion) (fig. 1)

parameters (from [2])

DTPM makes use of the data offered by any colour Doppler machine, namely the real time depiction of rhythmically changing coloured pixels and the colour scale to gauge them. To achieve this each hue at the scale is assigned a specific velocity value. This value is calculated by the DTPM-software (PixelFlux, Chameleon-Software, Germany [1]) from a linear correlation of all colours from zero (the lower end of the scale) to the actual maximum value (which is depicted numerically at the outer end of the scale and corresponds to the lightest reddish and bluish shades of the scale). The PixelFlux-software also calculates the area of all coloured pixels inside the ROI. Thus, each coloured pixel is evaluated by assigning a specific velocity and area to it. This is possible only after calibrating the image.

Distance calibration is also done automatically by use of the DICOM data, which are delivered along with the image by the ultrasound machine. A so-called DICOM- header file accompanying each image contains non-visible data such as the type of the ultrasound machine, the transducer, the preset information, the patient data and the distance calibration among many other data.

The mean flow intensity (Q) inside a ROI with the area (AROI) is then automatically calculated by assigning each colour pixel a velocity (v) and area (A) value according to the following equation:

$$\mathbf{Q}\begin{bmatrix}\text{cm/s}\end{bmatrix} = \mathbf{v}\begin{bmatrix}\text{cm/s}\end{bmatrix}^\* \mathbf{A}\begin{bmatrix}\text{cm}^2\end{bmatrix} / \mathbf{A}\_{\text{ROI}}\begin{bmatrix}\text{cm}^2\end{bmatrix}$$

#### **2. Standardized video acquisition**

An indispensable precondition for reliable measurements is the use of comparable videos in terms of the imaging conditions applied to the investigated tissue. Only by keeping the fundamental circumstances of data acquisition constant, it is possible to compare the measurement results. Such parameters which need to be held constant are colour Doppler frequency and gain, type and software of the ultrasound machine, transducer type, persistence, wall filter, smoothing, type of the colour scale, preference for spatial versus time-resolution and others, depending on the actual configuration of the ultrasound machine. These parameters are summarized and stored as a certain preset of the machine and must be recalled at the beginning of an ultrasound investigation. This step is a widely used practice in order to maintain optimum imaging conditions also in examinations, where a measurement of image data is not a priori planned. The prepared preset is then reinstituted before recording videos for DTPM.

#### **3. Setting the region of interest (ROI) and Doppler angle correction**

The ROI is that area inside an ultrasound image, where tissue perfusion measurement is scheduled. The selection of the ROI depends on the type of tissue, structure of the organ and aim of the investigation. The following principles and physical restrictions should be kept in mind in defining the ROI.

In 2D-images, vessels are encoded in colour depending on the angle, which they have with the ultrasound wave. This propagation line of waves is oriented perpendicular to the transducer surface. The colouration represents the exact velocity value only in vessels running straight towards the transducer, i.e. parallel to the course of the sound wave propagation line. All other vessels are encoded with colour hues representing velocity

DTPM makes use of the data offered by any colour Doppler machine, namely the real time depiction of rhythmically changing coloured pixels and the colour scale to gauge them. To achieve this each hue at the scale is assigned a specific velocity value. This value is calculated by the DTPM-software (PixelFlux, Chameleon-Software, Germany [1]) from a linear correlation of all colours from zero (the lower end of the scale) to the actual maximum value (which is depicted numerically at the outer end of the scale and corresponds to the lightest reddish and bluish shades of the scale). The PixelFlux-software also calculates the area of all coloured pixels inside the ROI. Thus, each coloured pixel is evaluated by assigning a specific velocity and area to it. This is possible only after calibrating the image. Distance calibration is also done automatically by use of the DICOM data, which are delivered along with the image by the ultrasound machine. A so-called DICOM- header file accompanying each image contains non-visible data such as the type of the ultrasound machine, the transducer, the preset information, the patient data and the distance calibration

The mean flow intensity (Q) inside a ROI with the area (AROI) is then automatically calculated by assigning each colour pixel a velocity (v) and area (A) value according to the

Q [cm/s] = v [cm/s]\* A [cm²]/AROI [cm²]

An indispensable precondition for reliable measurements is the use of comparable videos in terms of the imaging conditions applied to the investigated tissue. Only by keeping the fundamental circumstances of data acquisition constant, it is possible to compare the measurement results. Such parameters which need to be held constant are colour Doppler frequency and gain, type and software of the ultrasound machine, transducer type, persistence, wall filter, smoothing, type of the colour scale, preference for spatial versus time-resolution and others, depending on the actual configuration of the ultrasound machine. These parameters are summarized and stored as a certain preset of the machine and must be recalled at the beginning of an ultrasound investigation. This step is a widely used practice in order to maintain optimum imaging conditions also in examinations, where a measurement of image data is not a priori planned. The prepared preset is then re-

**3. Setting the region of interest (ROI) and Doppler angle correction** 

The ROI is that area inside an ultrasound image, where tissue perfusion measurement is scheduled. The selection of the ROI depends on the type of tissue, structure of the organ and aim of the investigation. The following principles and physical restrictions should be kept in

In 2D-images, vessels are encoded in colour depending on the angle, which they have with the ultrasound wave. This propagation line of waves is oriented perpendicular to the transducer surface. The colouration represents the exact velocity value only in vessels running straight towards the transducer, i.e. parallel to the course of the sound wave propagation line. All other vessels are encoded with colour hues representing velocity

among many other data.

**2. Standardized video acquisition** 

instituted before recording videos for DTPM.

mind in defining the ROI.

following equation:

values (v) which are a product of the cosine of the Doppler angle (α) and the true velocity (vt), according to the Doppler principle:

$$\text{fd} = 2^\* \text{ for } ^\*\text{v}\_t / \text{c } ^\*\text{cos } \alpha.$$

with: fd: Doppler shift, fo: insonation frequency, c: sound velocity

This means that in many cases the tissue microvasculature colouration shows velocity values which are smaller than real. To overcome this, an angle correction for each vessel would be necessary. This cannot be done yet in two-dimensional images. With 3D imaging, such a correction is already feasible (see below in section "foetus"). In 2D images, thus an error occurs with DTPM, which must be kept constant to allow comparisons between investigations. This can be achieved under following circumstances:


In the latter case, the orientation on anatomical landmarks offers a sufficient framework to find the vascular patterns, which are typical for a certain organ (fig. 2). An example how to choose relevant landmarks is given for the kidney below.

Fig. 1. Example of tumor perfusion measurement. Two concentric ROIs are separately investigated. The vessel architecture is irregular or chaotic (center). No specific prevailing vessel size or orientation can be stated. Left: comparisons of perfusion intensities in the periphery (red column) and the center (green column). Center: Display of the ROIs and false color maps with perfusion intensity curves. Right: time course of the relevant perfusion parameters (from [2])

In both cases, the inevitable error of impossible individual Doppler angle correction for each vessel is held constant. Comparisons of different examinations thus become possible.

For all these considerations, it is crucial to achieve comparable conditions for depicting the vessels in a certain ROI. In the kidney the ROI should be placed inside the outer cortex, in a layer stretching from the outer border of the medullary pyramids to the renal surface and laterally from the watershed of two neighbouring segments to the opposite watershed (see chapter: kidney). In the lymph node and thyroid lobes, a longitudinal section trough the

Dynamic Tissue Perfusion Measurement – Basics and Applications 297

TPI(velocity *or intensity or area*) = maximum mean velocity *or* intensity *or* area of the ROI during one heart cycle – minimum mean velocity *or intensity or area* of the ROI during one heart cycle divided by mean mean velocity *or intensity or area* of the ROI during one heart cycle

Fig. 3. Example of DTPM output. Overview of the most important output features of a DTPM measurement. Comparison of the proximal and distal cortical ROIs. False color maps (areas

A dynamic perfusion map is generated to pinpoint the local perfusion in a sub-millimetre graded fashion numerically with false colours (fig. 2 and 13). Moreover, the distribution of perfusion intensities according to the whole spectrum of occurring intensities, which are assigned to one of 33 intensity classes, is calculated and diagrammatically displayed. Thus, tissues may be compared according to their content of stronger or weaker perfused areas and vessels (fig. 2, fig. 11). This allows insights into the microarchitecture of a tissue's vascular tree and its changes over time, which is helpful in chronic diseases and tumours. These intensity distribution curves are further described mathematically with the

Altogether more than 50 parameters are calculated to describe the tissue perfusion numerically. The most important is perfusion intensity to give a general measure of tissue

shaded in white, red and grey hues), perfusion intensities' distribution curves and additional parameters (upper line). Time curves of the basic perfusion parameters and perfusion intensities (below). Comparison of the overall perfusion intensities in both sub-

parameters kurtosis and skewness according to their bulging and asymmetry.

ROIs (lower line center)

centre of the ovoid shaped organ should be used as definite transsection plane. In the bowel wall, a longitudinal cut perpendicular to the proximal wall is the best. Tumours should be cut centrally in two perpendicular planes.

Fig. 2. Example for regular vessel architecture in a renal transplant – see also figure 3. The sub-ROIs are highlighted: P50 – proximal 50% of the outer cortex. D50- distal 50% of the outer cortex. False color map and distribution curve of perfusion intensities are displayed

#### **4. Reading the results**

Figure 3 gives an overview of the most important output features in a typical DTPM measurement. In DTPM all data are derived from the basic parameters mean flow velocity, mean perfused area and their change during the heart beat with reference to the entire ROI [2, 3]. In three-dimensional images, the spatial angle correction adds to the primary 2D measurement inside the horizontal plane.

In addition to mean perfusion intensity, calculation parameters are generated to describe the dynamics of perfusion. Examples are Tissue Resistance Index (TRI) and Tissue Pulsatility Index (TPI). TRI and TPI may refer to velocity, intensity and perfused area according to the following formulas:

TRI(velocity *or intensity or area*) = maximum mean velocity *or* intensity *or* area of the ROI during one heart cycle – minimum mean velocity *or intensity or area* of the ROI during one heart cycle divided by maximum mean velocity *or intensity or area* of the ROI during one heart cycle

centre of the ovoid shaped organ should be used as definite transsection plane. In the bowel wall, a longitudinal cut perpendicular to the proximal wall is the best. Tumours should be

Fig. 2. Example for regular vessel architecture in a renal transplant – see also figure 3. The sub-ROIs are highlighted: P50 – proximal 50% of the outer cortex. D50- distal 50% of the outer cortex. False color map and distribution curve of perfusion intensities are displayed

Figure 3 gives an overview of the most important output features in a typical DTPM measurement. In DTPM all data are derived from the basic parameters mean flow velocity, mean perfused area and their change during the heart beat with reference to the entire ROI [2, 3]. In three-dimensional images, the spatial angle correction adds to the primary 2D

In addition to mean perfusion intensity, calculation parameters are generated to describe the dynamics of perfusion. Examples are Tissue Resistance Index (TRI) and Tissue Pulsatility Index (TPI). TRI and TPI may refer to velocity, intensity and perfused area according to the

TRI(velocity *or intensity or area*) = maximum mean velocity *or* intensity *or* area of the ROI during one heart cycle – minimum mean velocity *or intensity or area* of the ROI during one heart cycle divided by maximum mean velocity *or intensity or area* of the ROI during one heart cycle

cut centrally in two perpendicular planes.

**4. Reading the results** 

following formulas:

measurement inside the horizontal plane.

TPI(velocity *or intensity or area*) = maximum mean velocity *or* intensity *or* area of the ROI during one heart cycle – minimum mean velocity *or intensity or area* of the ROI during one heart cycle divided by mean mean velocity *or intensity or area* of the ROI during one heart cycle

Fig. 3. Example of DTPM output. Overview of the most important output features of a DTPM measurement. Comparison of the proximal and distal cortical ROIs. False color maps (areas shaded in white, red and grey hues), perfusion intensities' distribution curves and additional parameters (upper line). Time curves of the basic perfusion parameters and perfusion intensities (below). Comparison of the overall perfusion intensities in both sub-ROIs (lower line center)

A dynamic perfusion map is generated to pinpoint the local perfusion in a sub-millimetre graded fashion numerically with false colours (fig. 2 and 13). Moreover, the distribution of perfusion intensities according to the whole spectrum of occurring intensities, which are assigned to one of 33 intensity classes, is calculated and diagrammatically displayed. Thus, tissues may be compared according to their content of stronger or weaker perfused areas and vessels (fig. 2, fig. 11). This allows insights into the microarchitecture of a tissue's vascular tree and its changes over time, which is helpful in chronic diseases and tumours. These intensity distribution curves are further described mathematically with the parameters kurtosis and skewness according to their bulging and asymmetry.

Altogether more than 50 parameters are calculated to describe the tissue perfusion numerically. The most important is perfusion intensity to give a general measure of tissue

Dynamic Tissue Perfusion Measurement – Basics and Applications 299

Single point measurement

Appreciation of heart beat specific flow dynamics

enddiastolic velocities are

Use of unmodified flow

No age limitation No age limitation Not universally licensed for

Resistance index (RI) measurements are widely used to extract a handy quantitative measure from PW (pulsed wave) – Doppler investigations by using to velocity measurements, peak systolic (vs) and enddiastolic velocity (vd) from a single site inside a vessel according to the equation: RI = vs-vd/vs. Despite its broad use the theoretical basis for perfusion quantification remains weak and not surprisingly leads to misleading conclusions. A high RI is commonly linked to a high downstream resistance against flow – often raising the suspicion of a suppressed perfusion while normal RI measurements are referred to as a sign of normal perfusion. Figure 4 clearly demonstrates that this fundamental theoretical misconception also might have obvious practical implications. In the upper line spectral analysis of three peripheral arterial branches of a renal transplant with a stark reduction of peripheral cortical microvessels are shown – averaging to a RI of 0.66. The same value is calculated in the lower line, which stems from another transplant with much better function (serum creatinine 70 vs. 231 µmol/l in the upper line) and abundant vascular signals in the outer cortical periphery. A decision based on RI would attest both transplants a normal "perfusion". DTPM brings out the difference clearly (fig. 5): Perfusion intensity is eight times higher in the proximal cortex in the transplant with a

normal function. The insufficient transplant has no peripheral perfusion at all.

Non-invasive Non-invasive Injection necessary No side effects No side effects Rarely side effects No running costs No running costs Additional costs for

in colored vessels

Only systolic and

volume)

measured

data

Measurement of flow velocities only in some pixels of a vessel (sample

**RI measurement Contrast enhanced** 

**sonography** 

No flow velocity measurement

calculated

€ per vial)

paediatric use

ROI

Measurement of contrast enhancement in a larger

Loss of heart beat dynamics – saturation curves are

Perfusion intensity is evaluated indirectly from contrast enhancer influx curves (steepness of influx and level of saturation)

Contrast enhancer as additional source of error

contrast enhancer (about 92

**Dynamic tissue perfusion** 

Measurement of perfusion intensity in all vessels of a

Appreciation of heart beat specific flow dynamics

All relevant raw data (i.e. velocities and areas of perfusion) are measured directly during complete

Use of unmodified flow

**6. Comparison to RI measurements** 

Measurement of flow velocities of all pixels in all vessels' transsection

**measurement** 

larger ROI

heart cycles

data

perfusion. Very instructive too is the distribution curve, outlined below the false colour map (fig. 11). Here shifts within the microvessel population can be reviewed at a glance. This is further underlined with the distribution parameters skewness and kurtosis, which describe the shape of this curve numerically. Statistical comparison of microvessel arrangement thus becomes feasible, permitting the follow up of slight changes of an organ's chronic vascular changes, which begin in the periphery. Another important feature is the false colour map. This map stains the ROI according to the local perfusion intensities over the entire length of the colour Doppler sonographic video clip. The information added to the anatomical structures displayed by the ultrasound image can be helpful in differentiating parts of the tissue with respect to their vascular structures. The flow of the hepatic artery can be separated from the same coloured flow of the portal vein in this way, which might be welcome in the follow up of liver transplants. Another possible application might be the differentiation of local tissue disturbances, as caused by tumour infiltration or scarring or inflammation. To perform an automatic angle correction of all vessels 3D images are used. Here the spatial angel is calculated from both the angle in the frontal and in the sagittal plane. This angle then is applied to calculate true spatially angle corrected flow velocities and vessel diameters. Both are distorted in the original frontal view and can be corrected for 3D flow calculations in so doing. Another important feature is the use of predefined relational sub-ROIs to describe the blood flow on its way through the tissue. Gradients of perfusion can be used to quantify the dampening of perfusion in the depth of a vascular tree. This can be used to detect the very early loss of the tiniest vessels in a tissue, which are often the first to be damaged due to their small lumen. So a chronic pathological process can be discovered in the very beginning and treatment can be started preventing further damage in stages, where the organ's compensatory capacity is still strong enough to recover.

#### **5. Differences to existing methods of sonographic perfusion evaluation**

Today RI and PI calculations are the most widely used techniques to quantify flow velocity changes [4-10]. They do not allow conclusions as for the perfusion intensity or volume since the perfused area of the vessel under investigation is not included in the calculation. Even the exact velocities of flow do not need to be measured since the formula refers to two (RI) or three (PI) velocities only which are related to each other to define the velocity change throughout the heart cycle instead of exact velocities. RI = peak systolic velocity - end diastolic velocity / peak systolic velocity and PI = peak systolic velocity - end diastolic velocity / mean velocity of the entire heart cycle.

Contrast enhanced ultrasound (CEUS) can describe the perfusion of larger regions inside organs and thus deliver precise images of typical perfusion patterns of e.g. liver tumours or renal transplant cortical perfusion [11-13]. External influences are relevant concerning the reproducible influx of the contrast enhancer from the injection site to the ROI [14, 15]. The perfusion in CEUS is calculated as the velocity of contrast saturation. The pulsatility of perfusion is not depicted. CEUS thus delivers two parameters to measure: level of saturation and the velocity to reach this level.

The advantages of dynamic tissue perfusion measurement over conventional resistance index measurements and contrast-enhanced sonography (CEUS) are summarized below:

perfusion. Very instructive too is the distribution curve, outlined below the false colour map (fig. 11). Here shifts within the microvessel population can be reviewed at a glance. This is further underlined with the distribution parameters skewness and kurtosis, which describe the shape of this curve numerically. Statistical comparison of microvessel arrangement thus becomes feasible, permitting the follow up of slight changes of an organ's chronic vascular changes, which begin in the periphery. Another important feature is the false colour map. This map stains the ROI according to the local perfusion intensities over the entire length of the colour Doppler sonographic video clip. The information added to the anatomical structures displayed by the ultrasound image can be helpful in differentiating parts of the tissue with respect to their vascular structures. The flow of the hepatic artery can be separated from the same coloured flow of the portal vein in this way, which might be welcome in the follow up of liver transplants. Another possible application might be the differentiation of local tissue disturbances, as caused by tumour infiltration or scarring or inflammation. To perform an automatic angle correction of all vessels 3D images are used. Here the spatial angel is calculated from both the angle in the frontal and in the sagittal plane. This angle then is applied to calculate true spatially angle corrected flow velocities and vessel diameters. Both are distorted in the original frontal view and can be corrected for 3D flow calculations in so doing. Another important feature is the use of predefined relational sub-ROIs to describe the blood flow on its way through the tissue. Gradients of perfusion can be used to quantify the dampening of perfusion in the depth of a vascular tree. This can be used to detect the very early loss of the tiniest vessels in a tissue, which are often the first to be damaged due to their small lumen. So a chronic pathological process can be discovered in the very beginning and treatment can be started preventing further damage in stages, where the organ's

compensatory capacity is still strong enough to recover.

velocity / mean velocity of the entire heart cycle.

and the velocity to reach this level.

**5. Differences to existing methods of sonographic perfusion evaluation** 

Today RI and PI calculations are the most widely used techniques to quantify flow velocity changes [4-10]. They do not allow conclusions as for the perfusion intensity or volume since the perfused area of the vessel under investigation is not included in the calculation. Even the exact velocities of flow do not need to be measured since the formula refers to two (RI) or three (PI) velocities only which are related to each other to define the velocity change throughout the heart cycle instead of exact velocities. RI = peak systolic velocity - end diastolic velocity / peak systolic velocity and PI = peak systolic velocity - end diastolic

Contrast enhanced ultrasound (CEUS) can describe the perfusion of larger regions inside organs and thus deliver precise images of typical perfusion patterns of e.g. liver tumours or renal transplant cortical perfusion [11-13]. External influences are relevant concerning the reproducible influx of the contrast enhancer from the injection site to the ROI [14, 15]. The perfusion in CEUS is calculated as the velocity of contrast saturation. The pulsatility of perfusion is not depicted. CEUS thus delivers two parameters to measure: level of saturation

The advantages of dynamic tissue perfusion measurement over conventional resistance index measurements and contrast-enhanced sonography (CEUS) are summarized below:


#### **6. Comparison to RI measurements**

Resistance index (RI) measurements are widely used to extract a handy quantitative measure from PW (pulsed wave) – Doppler investigations by using to velocity measurements, peak systolic (vs) and enddiastolic velocity (vd) from a single site inside a vessel according to the equation: RI = vs-vd/vs. Despite its broad use the theoretical basis for perfusion quantification remains weak and not surprisingly leads to misleading conclusions. A high RI is commonly linked to a high downstream resistance against flow – often raising the suspicion of a suppressed perfusion while normal RI measurements are referred to as a sign of normal perfusion. Figure 4 clearly demonstrates that this fundamental theoretical misconception also might have obvious practical implications. In the upper line spectral analysis of three peripheral arterial branches of a renal transplant with a stark reduction of peripheral cortical microvessels are shown – averaging to a RI of 0.66. The same value is calculated in the lower line, which stems from another transplant with much better function (serum creatinine 70 vs. 231 µmol/l in the upper line) and abundant vascular signals in the outer cortical periphery. A decision based on RI would attest both transplants a normal "perfusion". DTPM brings out the difference clearly (fig. 5): Perfusion intensity is eight times higher in the proximal cortex in the transplant with a normal function. The insufficient transplant has no peripheral perfusion at all.

Dynamic Tissue Perfusion Measurement – Basics and Applications 301

considered drawback of RI measurements inside tissues is that thin arteries can only be located to interrogate the flow as long as the vessel is still coloured. If perfusion drops significantly, colour signals become weak and disappear at all. These vessels, the most affected, are excluded from evaluation by RI altogether. This must distort the overall

Fig. 6. Misleading RI measurements in a kidney af a child affected by haemolytic-ureamic syndrome. During the same investigation strikingly different RIs are found in intimate

The only way out of this dilemma is a method that takes into account simultaneously all flow signals in all vessels inside a larger ROI instead of single vessels, which also takes into account non-perfused areas. These are the fundamentals of DTPM, referring all flow signals inside an entire ROI thus reflecting properly vessel and flow intensity loss in chronic disease. It is just in chronic disease where remaining vessels amidst fibrosed tissue try to compensate the loss of neighbouring vessels by dilatation to feed the "thirsting" periphery

A phantom was built to measure the volume flow under externally controlled conditions consisting of a Teflon tube with an internal diameter of 2.0 mm that was placed into a water basin and fixed in a way that the tube was running straight in a steep angle towards the ultrasound transducer that was fixed to a tripod. The tube was perfused with a watery

Colour Doppler videos were recorded under standardized imaging conditions (ultrasound device: S2000, Siemens, Germany, linear transducer, colour Doppler frequency 4 MHz, the angle of the tube towards the ultrasound propagation line was 36°). The pump rate was

Two separate investigators independently performed these PixelFlux-measurements from 87 datasets (mean values based on altogether 191 recordings) at 22 different pump rates.

Phantom flow measurements showed an excellent correlation to pump rates (fig. 7) with a Pearson correlation coefficient of pump rate and investigator 1 of 0,987 and 0,991 for

changed; repeated colour Doppler recordings were made and measured by DTPM.

investigator 2. Both investigators measurements correlated with 0,997.

evaluation of tissue perfusion if RI measurements are its basis.

and thus exhibit a lower RI than under normal conditions (fig. 5).

**7. Phantom flow measurements** 

homogeneous rice starch solution.

neighborhood

Fig. 4. Two renal transplants compared: upper line insufficient kidney with serum creatinine of 231 µmol/l and normal kidney with a serum creatinine of 70 µmol/l in the lower line. Left: RI measurement in three cortical arteries. Right: Color Doppler sonograms. Insufficient kidney displays a pronounced loss of peripheral perfusion despite more sensible color Doppler setting compared to the kidney below. RI mean values are 0,66 for both transplants

Fig. 5. Same transplants as in fig. 3. DTPM is able to demonstrate a massive difference of tissue perfusion in contrary to RI measurements

Another example for the low power of RI evaluations is figure 6. In a child with acute renal insufficiency due to a hemolytic-uraemic syndrome (HUS), two neighbouring cortical arteries demonstrate vastly different RIs. Depending on which arteries the investigator selects, contradictory conclusions must be drawn from such evaluations. Another seldom-

Fig. 4. Two renal transplants compared: upper line insufficient kidney with serum creatinine of 231 µmol/l and normal kidney with a serum creatinine of 70 µmol/l in the lower line. Left: RI measurement in three cortical arteries. Right: Color Doppler sonograms. Insufficient kidney displays a pronounced loss of peripheral perfusion despite more sensible color Doppler setting compared to the kidney below. RI mean values are 0,66 for both transplants

Fig. 5. Same transplants as in fig. 3. DTPM is able to demonstrate a massive difference of

Another example for the low power of RI evaluations is figure 6. In a child with acute renal insufficiency due to a hemolytic-uraemic syndrome (HUS), two neighbouring cortical arteries demonstrate vastly different RIs. Depending on which arteries the investigator selects, contradictory conclusions must be drawn from such evaluations. Another seldom-

tissue perfusion in contrary to RI measurements

considered drawback of RI measurements inside tissues is that thin arteries can only be located to interrogate the flow as long as the vessel is still coloured. If perfusion drops significantly, colour signals become weak and disappear at all. These vessels, the most affected, are excluded from evaluation by RI altogether. This must distort the overall evaluation of tissue perfusion if RI measurements are its basis.

Fig. 6. Misleading RI measurements in a kidney af a child affected by haemolytic-ureamic syndrome. During the same investigation strikingly different RIs are found in intimate neighborhood

The only way out of this dilemma is a method that takes into account simultaneously all flow signals in all vessels inside a larger ROI instead of single vessels, which also takes into account non-perfused areas. These are the fundamentals of DTPM, referring all flow signals inside an entire ROI thus reflecting properly vessel and flow intensity loss in chronic disease. It is just in chronic disease where remaining vessels amidst fibrosed tissue try to compensate the loss of neighbouring vessels by dilatation to feed the "thirsting" periphery and thus exhibit a lower RI than under normal conditions (fig. 5).

#### **7. Phantom flow measurements**

A phantom was built to measure the volume flow under externally controlled conditions consisting of a Teflon tube with an internal diameter of 2.0 mm that was placed into a water basin and fixed in a way that the tube was running straight in a steep angle towards the ultrasound transducer that was fixed to a tripod. The tube was perfused with a watery homogeneous rice starch solution.

Colour Doppler videos were recorded under standardized imaging conditions (ultrasound device: S2000, Siemens, Germany, linear transducer, colour Doppler frequency 4 MHz, the angle of the tube towards the ultrasound propagation line was 36°). The pump rate was changed; repeated colour Doppler recordings were made and measured by DTPM.

Two separate investigators independently performed these PixelFlux-measurements from 87 datasets (mean values based on altogether 191 recordings) at 22 different pump rates.

Phantom flow measurements showed an excellent correlation to pump rates (fig. 7) with a Pearson correlation coefficient of pump rate and investigator 1 of 0,987 and 0,991 for investigator 2. Both investigators measurements correlated with 0,997.

Dynamic Tissue Perfusion Measurement – Basics and Applications 303

there the lower border of the ROI extends to the left pyramid to reach its centre point on its outer border. This is the left lower corner of the parallelogram. This way a symmetric distribution pattern of all branches of this vascular segment is achieved [19]. This parallelogram is divided into horizontal layers (e.g. p50 and d50) encompassing the proximal 50% (p50) or distal 50% (d50) of the ROI's height. Any other layer thickness can be chosen to meet the needs of the investigation (for instance 10 layers with the thickness of 1/10 of the ROI (fig. 13)). These layers thus have a thickness that refers to the overall dimensions of the ROI and are therefore relational layers. In thicker cortices, the layers are thicker than in thinner cortices. Nevertheless, the layers of different kidneys are comparable to each other since they comprise the comparable level of the cortical vascular tree (fig. 8).

Fig. 8. Example of placing of a ROI in a kidney with indication of the anatomical landmarks

Own investigations yielded a decline of renal cortical perfusion with compromised creatinine clearance (fig. 9). Normal kidneys display a decline of cortical perfusion intensity from central to peripheral cortex (fig. 10) [19]. Inflammation causes a strong hyperperfusion (fig. 11). DTPM can help to differentiate the affection of either right or left kidney – helpful in children and non-communicating patients. Moreover, the different effects of hydronephrotic perfusion loss even in a state of general hyperperfusion due to inflammation can be demonstrated (fig. 11). In kidneys with vesico-ureteral reflux, we found a decline of perfusion inside the peripheral cortical layers, which corresponded to the reflux degree (low

In nutcracker phenomenon, a frequent anatomical variant of the course of the left renal vein with sharp narrowing of the vessel between the superior mesenteric artery and the

to guide the setting

grade vs. high-grade reflux) (fig. 12).

Fig. 7. In a perfusion phantom\* DTPM measurements of two investigators were compared. An excellent correlation in-between both investigators and of both investigators to the externally measured flow rate was found. \* Homogenized rice starch solution pumped by a precision laboratory pump, Flow volumes measured constantly by a laboratory balance

#### **8. Dynamic tissue perfusion measurement – Applications**

#### **8.1 Kidneys**

Kidneys are abundantly perfused and are second only to the brain with respect to their blood supply in the systemic circulation [16, 17]. Perfusion measurement is important to detect changes, which precede function loss – the so-called creatinine blind stage of renal insufficiency [18]. For reliable kidney perfusion measurements, it is necessary to adjust the ROI to the typical anatomical pattern of the renal microvessel architecture. The kidney consists of segments, each with an individual blood supply via an interlobar artery. This vessel is crossing the inner parenchyma in-between two neighbouring medullary pyramids to branch off symmetrically into arcuate arteries from which in a brush-like manner interlobular arteries emanate. Such a segment is chosen as the ROI in a way that the feeding interlobar artery runs straight towards the transducer.

The ROI itself is a parallelogram adjusted to the individual kidney's anatomical landmarks, which are as follows: the left upper corner of the parallelogram lies at the renal surface on the watershed line between two segments (i.e. where the interlobular arteries from two neighbouring segments seem to touch each other). The right upper corner then is fixed at the right border of the segment under investigation with the same premises as the first corner. The right lower corner then lies on the right watershed line, which is extended to the surface of the medullary pyramid and ends at the centre of the outer edge of the pyramid. From

Fig. 7. In a perfusion phantom\* DTPM measurements of two investigators were compared. An excellent correlation in-between both investigators and of both investigators to the externally measured flow rate was found. \* Homogenized rice starch solution pumped by a precision laboratory pump, Flow volumes measured constantly by a laboratory balance

Kidneys are abundantly perfused and are second only to the brain with respect to their blood supply in the systemic circulation [16, 17]. Perfusion measurement is important to detect changes, which precede function loss – the so-called creatinine blind stage of renal insufficiency [18]. For reliable kidney perfusion measurements, it is necessary to adjust the ROI to the typical anatomical pattern of the renal microvessel architecture. The kidney consists of segments, each with an individual blood supply via an interlobar artery. This vessel is crossing the inner parenchyma in-between two neighbouring medullary pyramids to branch off symmetrically into arcuate arteries from which in a brush-like manner interlobular arteries emanate. Such a segment is chosen as the ROI in a way that the feeding

The ROI itself is a parallelogram adjusted to the individual kidney's anatomical landmarks, which are as follows: the left upper corner of the parallelogram lies at the renal surface on the watershed line between two segments (i.e. where the interlobular arteries from two neighbouring segments seem to touch each other). The right upper corner then is fixed at the right border of the segment under investigation with the same premises as the first corner. The right lower corner then lies on the right watershed line, which is extended to the surface of the medullary pyramid and ends at the centre of the outer edge of the pyramid. From

**8. Dynamic tissue perfusion measurement – Applications** 

interlobar artery runs straight towards the transducer.

**8.1 Kidneys** 

there the lower border of the ROI extends to the left pyramid to reach its centre point on its outer border. This is the left lower corner of the parallelogram. This way a symmetric distribution pattern of all branches of this vascular segment is achieved [19]. This parallelogram is divided into horizontal layers (e.g. p50 and d50) encompassing the proximal 50% (p50) or distal 50% (d50) of the ROI's height. Any other layer thickness can be chosen to meet the needs of the investigation (for instance 10 layers with the thickness of 1/10 of the ROI (fig. 13)). These layers thus have a thickness that refers to the overall dimensions of the ROI and are therefore relational layers. In thicker cortices, the layers are thicker than in thinner cortices. Nevertheless, the layers of different kidneys are comparable to each other since they comprise the comparable level of the cortical vascular tree (fig. 8).

Fig. 8. Example of placing of a ROI in a kidney with indication of the anatomical landmarks to guide the setting

Own investigations yielded a decline of renal cortical perfusion with compromised creatinine clearance (fig. 9). Normal kidneys display a decline of cortical perfusion intensity from central to peripheral cortex (fig. 10) [19]. Inflammation causes a strong hyperperfusion (fig. 11). DTPM can help to differentiate the affection of either right or left kidney – helpful in children and non-communicating patients. Moreover, the different effects of hydronephrotic perfusion loss even in a state of general hyperperfusion due to inflammation can be demonstrated (fig. 11). In kidneys with vesico-ureteral reflux, we found a decline of perfusion inside the peripheral cortical layers, which corresponded to the reflux degree (low grade vs. high-grade reflux) (fig. 12).

In nutcracker phenomenon, a frequent anatomical variant of the course of the left renal vein with sharp narrowing of the vessel between the superior mesenteric artery and the

Dynamic Tissue Perfusion Measurement – Basics and Applications 305

**Normal left kidney**

**Hydronephrotic right kidney**

Fig. 11. Differing response of both kidneys towards an bacterial infection in a patient with a right sided hydronephrosis Perfusion intensity in the proximal cortex. MAG3 scintigraphy right kidney: 30% of both kidneys' function. Renal perfusion in a child with a normal kidney on the left and a hydronephritc kidney on the other side. Inflammation due to bacterial infection causes an initial perfusion increase (2007/04/28). With recovery perfusion drops in both kidneys (from 2007/05/02 to 2007/05/09). The decline is more pronounced in the hydronephrotic kidney. Perfusion intensity distribution curves differ markedly between both kidneys pointing to the damage of the microvasculature in the hydronephrotic kidney and a compensatory hyperperfusion trough dilated microvasculature on the left side

Cortical layer: distal 50%

p=0,035

cm/s 2,5

2,0

1,5

1,0

0,5

0,0


Compromise of perfusion dependent on degree of reflux

N= 56 35 16

p=0,03

healthy VUR 1-3º VUR 4-5º

Fig. 12. Diminished perfusion of kidney in vesico-ureteral reflux compared to healthy ones.

p=0,001

Date 2007/04/28 2007/05/02 2007/05/09 Perfusion 1,949 cm/s 1,722 cm/s 1,254 cm/s

Date 2007/04/28 2007/05/02 2007/05/09 Perfusion 0,737 cm/s 0,570 cm/s 0,212 cm/s

Fig. 9. Constant decline of cortical perfusion with progression of renal insufficiency. Left: proximal cortex. Right: distal cortex

Fig. 10. Decline of renal cortical perfusion from the inner to the outer cortex

abdominal aorta, a venous congestion of the left kidney ensues. Its consequences are often misinterpreted from conventional imaging alone but are nonetheless often disabling for the affected ones. Many patients suffer from chronic and exacerbating abdominal fits of cramping pain. The congested kidney is often swollen and less perfused than the right one. This can be easily demonstrated by DTPM (fig. 13). Perfusion diminution is a signal of insufficient collateral pathways to drain the renal blood from the left side. A treatment with aspirin can either alleviate or often abolish pain and functional disturbances of the congested organs, which have to deal with the massive venous overflow from the left renal vein. Simultaneously with the clinical improvement, a significant increase of left kidney's perfusion can also be measures by DTPM (fig. 14) [20].

Fig. 9. Constant decline of cortical perfusion with progression of renal insufficiency. Left:

p20 p50 d50

abdominal aorta, a venous congestion of the left kidney ensues. Its consequences are often misinterpreted from conventional imaging alone but are nonetheless often disabling for the affected ones. Many patients suffer from chronic and exacerbating abdominal fits of cramping pain. The congested kidney is often swollen and less perfused than the right one. This can be easily demonstrated by DTPM (fig. 13). Perfusion diminution is a signal of insufficient collateral pathways to drain the renal blood from the left side. A treatment with aspirin can either alleviate or often abolish pain and functional disturbances of the congested organs, which have to deal with the massive venous overflow from the left renal vein. Simultaneously with the clinical improvement, a significant increase of left kidney's

Fig. 10. Decline of renal cortical perfusion from the inner to the outer cortex

Layer

proximal cortex. Right: distal cortex

Perfusion intensity (cm/s)

5

4

3

2

1

0


perfusion can also be measures by DTPM (fig. 14) [20].

Fig. 11. Differing response of both kidneys towards an bacterial infection in a patient with a right sided hydronephrosis Perfusion intensity in the proximal cortex. MAG3 scintigraphy right kidney: 30% of both kidneys' function. Renal perfusion in a child with a normal kidney on the left and a hydronephritc kidney on the other side. Inflammation due to bacterial infection causes an initial perfusion increase (2007/04/28). With recovery perfusion drops in both kidneys (from 2007/05/02 to 2007/05/09). The decline is more pronounced in the hydronephrotic kidney. Perfusion intensity distribution curves differ markedly between both kidneys pointing to the damage of the microvasculature in the hydronephrotic kidney and a compensatory hyperperfusion trough dilated microvasculature on the left side

Fig. 12. Diminished perfusion of kidney in vesico-ureteral reflux compared to healthy ones. Compromise of perfusion dependent on degree of reflux

Dynamic Tissue Perfusion Measurement – Basics and Applications 307

In a preliminary study, we compared kidneys from children with juvenile diabetes of varying duration of disease to kidneys from healthy children with respect to the perfusion drop from central to peripheral cortical layers. Even in an early stage of disease, (no child had microalbuminuria) a highly significant peripheral perfusion loss could be demonstrated

> 20,00 17,50 15,00 12,50 10,00 7,50 5,00 2,50 0.00

**Perfusion gradient from proximal 50% to distal 50%**

20,00 17,50 15,00 12,50 10,00 7,50 5,00 2,50 0

**Perfusion gradient from proximal 20% to distal 50%**

Fig. 15. DTPM discloses a significant reduction of peripheral to central cortical perfusion in diabetic children compared to healthy ones. The effect is more pronounced when comparing the proximal 20%/distal 50%-ratio (lower diagram) then in proximal 50%/distal 50%-ratio

Renal transplants are subject to chronic immunological attacks as well as toxic effects of immunosuppressive treatment. Repeated biopsies are today the only way to clarify the creeping changes within the renal parenchyma. We conducted a study on 75 renal transplant recipients, which had a DTPM immediately before their biopsy. Banff criteria were correlated to DTPM results. Some of the very important histological features correlated significantly with perfusion changes [21], pointing to the potential of DTPM for renal transplant long term follow up. RI values were much less instructive (insignificant differences) than DTPM measurements (significant differences) to discriminate varying

**healty diabetic**

**healty diabetic**

p < 0,001

p < 0,001

in diabetic kidneys (fig. 15).

Data origin

healthy

Median Std Deviation N Median Std Deviation N

diabetic

(upper diagram)

**9. Renal transplants** 

 Perfusion gradient from proximal 50 % to distal 50%

**Report**

 3,1813 1,91990 110 5,5230 16,10524 57  Perfusion gradient from proximal 20 % to distal 50%

> 3,5306 2,31465 110 6,9531 28,99295 57

Fig. 13. The nutcracker phenomenon of the left kidney often causes depression of left renal perfusion. Left: Sub-millimeter layers show very precisely the potential of DTPM to describe microvascular perfusion in an unprecedented subtlety. Right: Heavily depressed perfusion of the left kidney in nutcracker phenomenon

Fig. 14. Effect of aspirin (acetylsalicylic acid: ASA) onto the perfusion of the left kidney. The ratio of left to right kidney perfusion is displayed. After aspirin treatment a significant increase of this ratio can be stated. From [21]

Fig. 13. The nutcracker phenomenon of the left kidney often causes depression of left renal perfusion. Left: Sub-millimeter layers show very precisely the potential of DTPM to describe microvascular perfusion in an unprecedented subtlety. Right: Heavily depressed perfusion

**Renal cortical perfusion ratio left/right**

means and standard error of the mean

p = 0.021

1.24

at beginning at first effect **ASA therapy**

Fig. 14. Effect of aspirin (acetylsalicylic acid: ASA) onto the perfusion of the left kidney. The ratio of left to right kidney perfusion is displayed. After aspirin treatment a significant

n = 16 n = 16

before and with ASA

0.79

p010 p020 p030 p040 p050 p060 p070 p080 p090 p100 p010 p020 p030 p040 p050 p060 p070 p080 p090 p100

left kidney right kidney

Slicewise measurement of cortical perfusion

of the left kidney in nutcracker phenomenon

 **Renal cortical perfusion ratio**

**at proximal 20% of cortex (left/right kidney)**

1.00

0.50

0.00

increase of this ratio can be stated. From [21]

1.6 1.4 1.2 1 0.8 0.6 0.4 0.2 0 Perfusion (cm/s)

10.1 mm

left right kidney

Comparison of global perfusion

5.7 mm

0.53 0.52 0.51 0.5 0.49 0.48 0.47 0.46 0.45 0.44 Perfusion (cm/s)

In a preliminary study, we compared kidneys from children with juvenile diabetes of varying duration of disease to kidneys from healthy children with respect to the perfusion drop from central to peripheral cortical layers. Even in an early stage of disease, (no child had microalbuminuria) a highly significant peripheral perfusion loss could be demonstrated in diabetic kidneys (fig. 15).

Fig. 15. DTPM discloses a significant reduction of peripheral to central cortical perfusion in diabetic children compared to healthy ones. The effect is more pronounced when comparing the proximal 20%/distal 50%-ratio (lower diagram) then in proximal 50%/distal 50%-ratio (upper diagram)

### **9. Renal transplants**

Renal transplants are subject to chronic immunological attacks as well as toxic effects of immunosuppressive treatment. Repeated biopsies are today the only way to clarify the creeping changes within the renal parenchyma. We conducted a study on 75 renal transplant recipients, which had a DTPM immediately before their biopsy. Banff criteria were correlated to DTPM results. Some of the very important histological features correlated significantly with perfusion changes [21], pointing to the potential of DTPM for renal transplant long term follow up. RI values were much less instructive (insignificant differences) than DTPM measurements (significant differences) to discriminate varying

**Perfusion intensity (cm/s)**

**0,175**

**p < 0,001**

**p = 0,003**

**n= 98**

**n= 35**

**0,150**

**0,125**

**0,100**

**0,075**

0,160

0,140

0,120

0,100

0,080

**Perfusion intensity [cm/s]**

0,060

0,040

0,020

0,000

segments in IBD patients

**11. Lymph nodes** 

**n= 97**

increase in wall perfusion

Dynamic Tissue Perfusion Measurement – Basics and Applications 309

**0,140**

**p < 0,001**

**n= 64**

**p = 0,018**

**n= 75**

**0,120**

**0,100**

**0,080**

**0,060**

**n= 92**

**Neutrophils Intramural lymphocytes**

**0 1 2 0 1 2**

Terminal ileum Descendent colon Terminal ileum

Fig. 17. Synopsis of DTPM measurements (red columns) histological images, color Doppler sonograms and colonoscopic images from three IBD patients and different sites. DTPM differentiates better than all other methods between acutely inflamed and resting bowel

Lymph node perfusion measurement helps to tell inflammatory changes and can provide insight into the dynamics of progression or retreat of the underlying process. Normal lymph

Fig. 16. Large bowel wall perfusion in ulcerative colitis. In ulcerative colitis an increasing score of granulocytic (left) and lymphocytic (right) wall infiltration is reflected by significant

stages of peritubular inflammation. Varying grades of transplant Polyomavirus infection were marked with significant increases of cortical tissue perfusion [21]. In another study, we found in children a marked decline of cortical perfusion in allograft cortices beginning already one year after transplantation [22] while the pulsatility of cortical perfusion rose significantly [23]. Recently, it was shown, that intrinsic donor-derived factors are associated with GFR and cortical parenchymal perfusion intensity, measured by DTPM, but not the RI of segmental arteries in renal allografts [24].

#### **10. Bowel**

A main area of interest for DTPM is chronic inflammatory bowel diseases. In Crohn disease as well as in ulcerative colitis inflammatory hyperperfusion of the bowel wall could be demonstrated.

Patients with Crohn disease irrespective of disease activity had higher blood flow intensity compared to healthy probands. Mean small bowel wall perfusion intensity was 0.025 cm/s in healthy probands whereas in patients with Crohn disease 0.095 cm/s was found [25]. Large bowel wall perfusion intensity in healthy probands was distinctively less than in patients with Crohn disease (0.012 cm/s vs. 0.082 cm/s, p < 0.001) [25]. Conventional evaluation of disease activity by means of activity indices did not clearly distinguish patients with high from those with less pronounced inflammatory hyperperfusion. The correlation of bowel wall perfusion and PCDAI-values was weak albeit significant (r = 0.349, p = 0.001) [25]. The individual effect of TNF-alpha antibody treatment can be closely followed and treatment regimes can be tailored according to DTPM. Inflammatory activity in fistulas can be measured even after closure of the cutaneous orifice. DTPM can also be used to locate the focus of an abdominal inflammatory process by comparing the perfusion of different structures, which may be involved, but in different extent and activity. So lymph nodes, vermiform appendix, cecum and terminal ileum can be evaluated separately and clear decisions on the main source of complaints can be made. Unnecessary appendectomies can be avoided based on an imaging and perfusion measurements guided approach.

In ulcerative colitis, 14 histological criteria (changes of crypt architecture, depletion of goblet cells, Paneth cells distal of the left colon flexure, lymphocyte infiltration, plasma cells, eosinophils, unspecific inflammatory infiltrates, granulocytes in the lamina propria and lamina epithelialis, crypt abscesses, oedema, erosions or ulcerations, regenerative epithelium , fibrosis, increased cryptal distance to muscularis mucosae) of disease activity were compared to the local perfusion state of the bowel wall. Scores of neutrophil as well as lymphocytic invasion of the wall, crypt abscesses and wall oedema were significantly correlated (in oedema inversely) to the local wall perfusion (fig. 16) [26]. DTPM can add more differentiated and important numerical data, which make imaging data comparable and thus a tool for decision making in a clinical setting. Figure 17 compares histological images, colonoscopic photographs, colour Doppler sonographic images and the results of DTPM at the site where the images stem from. A convincing differentiation of these three bowel segments can be demonstrated by the different perfusion intensities.

Faingold et al. found a trend to decreased intestinal wall perfusion (0.040±0.015 cm/s vs. 0.052±0.029 cm/s) in neonates that died due to hypoxic ischemic injury [27].

stages of peritubular inflammation. Varying grades of transplant Polyomavirus infection were marked with significant increases of cortical tissue perfusion [21]. In another study, we found in children a marked decline of cortical perfusion in allograft cortices beginning already one year after transplantation [22] while the pulsatility of cortical perfusion rose significantly [23]. Recently, it was shown, that intrinsic donor-derived factors are associated with GFR and cortical parenchymal perfusion intensity, measured by DTPM, but not the RI

A main area of interest for DTPM is chronic inflammatory bowel diseases. In Crohn disease as well as in ulcerative colitis inflammatory hyperperfusion of the bowel wall could be

Patients with Crohn disease irrespective of disease activity had higher blood flow intensity compared to healthy probands. Mean small bowel wall perfusion intensity was 0.025 cm/s in healthy probands whereas in patients with Crohn disease 0.095 cm/s was found [25]. Large bowel wall perfusion intensity in healthy probands was distinctively less than in patients with Crohn disease (0.012 cm/s vs. 0.082 cm/s, p < 0.001) [25]. Conventional evaluation of disease activity by means of activity indices did not clearly distinguish patients with high from those with less pronounced inflammatory hyperperfusion. The correlation of bowel wall perfusion and PCDAI-values was weak albeit significant (r = 0.349, p = 0.001) [25]. The individual effect of TNF-alpha antibody treatment can be closely followed and treatment regimes can be tailored according to DTPM. Inflammatory activity in fistulas can be measured even after closure of the cutaneous orifice. DTPM can also be used to locate the focus of an abdominal inflammatory process by comparing the perfusion of different structures, which may be involved, but in different extent and activity. So lymph nodes, vermiform appendix, cecum and terminal ileum can be evaluated separately and clear decisions on the main source of complaints can be made. Unnecessary appendectomies can be avoided based on an imaging and perfusion measurements guided

In ulcerative colitis, 14 histological criteria (changes of crypt architecture, depletion of goblet cells, Paneth cells distal of the left colon flexure, lymphocyte infiltration, plasma cells, eosinophils, unspecific inflammatory infiltrates, granulocytes in the lamina propria and lamina epithelialis, crypt abscesses, oedema, erosions or ulcerations, regenerative epithelium , fibrosis, increased cryptal distance to muscularis mucosae) of disease activity were compared to the local perfusion state of the bowel wall. Scores of neutrophil as well as lymphocytic invasion of the wall, crypt abscesses and wall oedema were significantly correlated (in oedema inversely) to the local wall perfusion (fig. 16) [26]. DTPM can add more differentiated and important numerical data, which make imaging data comparable and thus a tool for decision making in a clinical setting. Figure 17 compares histological images, colonoscopic photographs, colour Doppler sonographic images and the results of DTPM at the site where the images stem from. A convincing differentiation of these three

Faingold et al. found a trend to decreased intestinal wall perfusion (0.040±0.015 cm/s vs.

bowel segments can be demonstrated by the different perfusion intensities.

0.052±0.029 cm/s) in neonates that died due to hypoxic ischemic injury [27].

of segmental arteries in renal allografts [24].

**10. Bowel** 

demonstrated.

approach.

Fig. 16. Large bowel wall perfusion in ulcerative colitis. In ulcerative colitis an increasing score of granulocytic (left) and lymphocytic (right) wall infiltration is reflected by significant increase in wall perfusion

Fig. 17. Synopsis of DTPM measurements (red columns) histological images, color Doppler sonograms and colonoscopic images from three IBD patients and different sites. DTPM differentiates better than all other methods between acutely inflamed and resting bowel segments in IBD patients

#### **11. Lymph nodes**

Lymph node perfusion measurement helps to tell inflammatory changes and can provide insight into the dynamics of progression or retreat of the underlying process. Normal lymph

Dynamic Tissue Perfusion Measurement – Basics and Applications 311

Thyroid nodules differed with respect to their distribution of perfusion according to their biological behaviour. Comparison of perfusion intensities obtained from peripheral and central parts of the nodules revealed that, in non-neoplastic nodules the peripheral flow was more intense than the central flow and, on the contrary central flow was more prominent

 Press-ups ergometer cycling wall sitting auxotonic isometric

Fig. 19. Significant muscle perfusion increase in 13 athletes – maximal exercise. DTPM reflects the perfusion in muscles before, during and after physical exercise in various settings. Auxotonic as well as isometric exercises cause a strong perfusion increase. After

Fig. 20. Correlation of quadriceps perfusion during ergometer cycling. Exercise induced

muscle perfusion correlates significantly to duration of exercise and heart rate

than the peripheral flow in neoplastic nodules (p<0.005) [29].

exercise perfusion drops sharply

Triceps Quadriceps

nodes in the neck have a minute but always detectable perfusion, which can be measured accurately. In upper airway infections, lymph nodes do not react with a hyperperfusion whereas lymphotropic EBV infection resulted in a marked increase of perfusion (fig. 18) [28].

Fig. 18. Lymph node perfusion as seen in DTPM: no differences exist between longitudinal (long) and transverse (trans) sections of the nodes. Infectious mononucleosis raises cervical node perfusion significantly (green symbols) compared to nodes from healthy probands (yellow) in contrast to nodes in acute upper airway infections (pink). Insets: left: normal node in color Doppler Right: Node in infectious mononucleosis (EBV-infection)

#### **12. Muscle**

A muscle perfusion measurement is feasible with the demonstration of a marked increase during exercise and steep decline afterwards in athletes (fig. 19). The perfusion was measured in the M. rectus femoris in a horizontal section before during and after exercise along with the measurement of serum lactate and a self-estimation of subjective workload (fig. 20).

In aged patients, an increase of muscle perfusion of the M. biceps brachii was demonstrated during an exercise program to foster rehabilitation.

#### **13. Thyroid**

Reproducibility of thyroid DTPM between two investigators is significant (fig. 21).

Thyroid perfusion is strongly increased in thyreoiditis (fig. 22). It is not yet clear however, if the amount of perfusion is paralleled by conventional laboratory parameters or clinical symptoms.

nodes in the neck have a minute but always detectable perfusion, which can be measured accurately. In upper airway infections, lymph nodes do not react with a hyperperfusion whereas lymphotropic EBV infection resulted in a marked increase of perfusion (fig. 18)

> trans long trans long trans long healthy inf. mononucleosis upper airway infection

Fig. 18. Lymph node perfusion as seen in DTPM: no differences exist between longitudinal (long) and transverse (trans) sections of the nodes. Infectious mononucleosis raises cervical node perfusion significantly (green symbols) compared to nodes from healthy probands (yellow) in contrast to nodes in acute upper airway infections (pink). Insets: left: normal

A muscle perfusion measurement is feasible with the demonstration of a marked increase during exercise and steep decline afterwards in athletes (fig. 19). The perfusion was measured in the M. rectus femoris in a horizontal section before during and after exercise along with the measurement of serum lactate and a self-estimation of subjective workload

In aged patients, an increase of muscle perfusion of the M. biceps brachii was demonstrated

Thyroid perfusion is strongly increased in thyreoiditis (fig. 22). It is not yet clear however, if the amount of perfusion is paralleled by conventional laboratory parameters or clinical

Reproducibility of thyroid DTPM between two investigators is significant (fig. 21).

node in color Doppler Right: Node in infectious mononucleosis (EBV-infection)

during an exercise program to foster rehabilitation.

healthy node inf. mononucleosis

[28].

0,90 0,80 0,70 0,60 0,50 0,40 0,30 0,20 0,10 0,00

Perfusion intensity (cm/s)

**12. Muscle** 

(fig. 20).

**13. Thyroid** 

symptoms.

Thyroid nodules differed with respect to their distribution of perfusion according to their biological behaviour. Comparison of perfusion intensities obtained from peripheral and central parts of the nodules revealed that, in non-neoplastic nodules the peripheral flow was more intense than the central flow and, on the contrary central flow was more prominent than the peripheral flow in neoplastic nodules (p<0.005) [29].

Fig. 19. Significant muscle perfusion increase in 13 athletes – maximal exercise. DTPM reflects the perfusion in muscles before, during and after physical exercise in various settings. Auxotonic as well as isometric exercises cause a strong perfusion increase. After exercise perfusion drops sharply

Fig. 20. Correlation of quadriceps perfusion during ergometer cycling. Exercise induced muscle perfusion correlates significantly to duration of exercise and heart rate

Dynamic Tissue Perfusion Measurement – Basics and Applications 313

Tumour perfusion evaluation by DTPM is also feasible and defined regions such as tumour core and periphery, whose size can be predefined, e.g. as concentric regions. This can uncover central tumour necrosis or ischemia, which might be relevant for treatment decisions. Hypoxia due to ischemia is a factor of chemo- and radioresistance of tumours [30-

In a series of metastatic tumours of the neck, a direct correlation of tumour perfusion measured by means of DTPM and directly measured tumour oxygenation could be demonstrated (fig. 23) [33]. In hypoxic tumours perfusion was significantly lower compared to normally oxygenated ones (fig. 24). Moreover, the pulsatility of tumour perfusion differed significantly between groups with different stages of metastasis (fig. 25) [33]. These results may be interpreted as a change of tumour stroma. The more densely packed the stroma is the higher the pulsatility is, since the distension of small vessels is influenced by the pressure change during a heart cycle on the one hand but on the other hand by the resistance against the widening of a vessel by the surrounding structures and their stiffness.

Fig. 23. Significant correlation between directly measured hypoxic volumes in metastatic

The foetal perfusion has to meet the needs of the rapidly growing organism, to deliver oxygen and nutrients in order to permit a normal intrauterine growth. Among other causes placental insufficiency is an important reason for disturbed intrauterine growth, resulting in intrauterine growth retardation (IUGR) and postnatal complications. The evaluation of foetal perfusion today is based in daily practice on the calculation of RI and PI in large arteries, mainly the umbilical, the cerebral arteries and the aorta, sometimes supplemented by flow pattern evaluations in the venous duct [34, 35]. In the eighties of the last century, first

lymph node tumors of the neck (Eppendorf histiograph) and DTPM (from [2])

32]. Therefore, it might be useful to monitor tumour perfusion in separated shells.

**14. Tumours** 

**15. Foetus** 

Fig. 21. Thyroid perfusion in 1142 measurements – low interobserver variation and highly significant correlation between both investigators

Fig. 22. Example of ample perfusion increase in thyroiditis – color Doppler sonograms and corresponding DTPM values are displayed

#### **14. Tumours**

312 Sonography

**Comparability Thyroid perfusion (cm/s) investigator J**

> Factor 1,125 Constant 0,57

Spearman r = 0,870 p < 0,001 N = 1442

Observed Linear

0,000 0,200 0,400 0,600 0,800 1,000 1,200 **Thyroid perfusion (cm/s) investigator M**

Fig. 21. Thyroid perfusion in 1142 measurements – low interobserver variation and highly

Thyreoiditis Normal thyroid gland

Perfusion (cm/s)

Fig. 22. Example of ample perfusion increase in thyroiditis – color Doppler sonograms and

**0,86**

Normal thyroid gland

**0,04**

1,250

1,000

0,750

0,500

0,250

0,000

significant correlation between both investigators

0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 0

corresponding DTPM values are displayed

Tumour perfusion evaluation by DTPM is also feasible and defined regions such as tumour core and periphery, whose size can be predefined, e.g. as concentric regions. This can uncover central tumour necrosis or ischemia, which might be relevant for treatment decisions. Hypoxia due to ischemia is a factor of chemo- and radioresistance of tumours [30- 32]. Therefore, it might be useful to monitor tumour perfusion in separated shells.

In a series of metastatic tumours of the neck, a direct correlation of tumour perfusion measured by means of DTPM and directly measured tumour oxygenation could be demonstrated (fig. 23) [33]. In hypoxic tumours perfusion was significantly lower compared to normally oxygenated ones (fig. 24). Moreover, the pulsatility of tumour perfusion differed significantly between groups with different stages of metastasis (fig. 25) [33]. These results may be interpreted as a change of tumour stroma. The more densely packed the stroma is the higher the pulsatility is, since the distension of small vessels is influenced by the pressure change during a heart cycle on the one hand but on the other hand by the resistance against the widening of a vessel by the surrounding structures and their stiffness.

Fig. 23. Significant correlation between directly measured hypoxic volumes in metastatic lymph node tumors of the neck (Eppendorf histiograph) and DTPM (from [2])

#### **15. Foetus**

The foetal perfusion has to meet the needs of the rapidly growing organism, to deliver oxygen and nutrients in order to permit a normal intrauterine growth. Among other causes placental insufficiency is an important reason for disturbed intrauterine growth, resulting in intrauterine growth retardation (IUGR) and postnatal complications. The evaluation of foetal perfusion today is based in daily practice on the calculation of RI and PI in large arteries, mainly the umbilical, the cerebral arteries and the aorta, sometimes supplemented by flow pattern evaluations in the venous duct [34, 35]. In the eighties of the last century, first

Dynamic Tissue Perfusion Measurement – Basics and Applications 315

attempts tried to quantify the umbilical venous flow volume with the aim to evaluate the foetal perfusion in quantitative terms [36, 37]. These studies were not continued because of limited reproducibility [38]. Nevertheless, these studies targeted at a parameter – volume flow –, which has a much better rationale than the popular and easy to measure RI and PI. The early studies were flawed mainly by two limitations, which could not be overcome with two-dimensional sonographic techniques. First the angle correction of flow velocity in space

Spatial angle correction is but pivotal in this setting, because the UV is continuously winding around the umbilical arteries and the whole cord is irregularly bent within the amniotic cavity. Two-dimensional images thus may allow an angle correction within the frontal plane but this can be vastly misleading. Depending on the sagittal angle the true and only relevant spatial angle can differ substantially thus leading to unpredictable errors of the volume flow calculation, when unknown. The second source of error was the universal assumption, that the UV is a round tube. The investigators tried to depict a straight running venous segment with parallel borders to apply the formula for circular area calculation in order to multiply this area with the mean flow velocity which was traced with a pulsed-

These sources of error combined in an unpredictable manner and caused the refusal of this

The technique of DTPM combined with the modern three-dimensional imaging techniques can resolve all of these imponderabilities. We developed the three-dimensional, spatial

angle corrected umbilical vein flow volume measurement, which is outlined below.

Fig. 26. Example of a spatially angle corrected fetal volume flow measurement in the umbilical vein. A 3D-dataset is shown displaying three perpendicular imaging planes. The horizontal plane is used for DTPM (right lower quarter): False color map of the venous flow.

From these data the flow volume is directly calculated by the PixelFlux-software

and second the non-circular shape of the transsection of the umbilical vein (UV).

wave- Doppler instrument in the centre of the vein.

approach.

Fig. 24. Oxygenation differences in relation to tumor perfusion. Less perfused metastatic lymph nodes in the neck (cut off in DTPM: 0,05 cm/s) have a significantly higher hypoxic volume than well perfused nodes (from [2])

Fig. 25. The Tissue Perfusion Pulsatility Index (TPI) falls significantly with increasing N-stages of the nodes (from [2])

Fig. 24. Oxygenation differences in relation to tumor perfusion. Less perfused metastatic lymph nodes in the neck (cut off in DTPM: 0,05 cm/s) have a significantly higher hypoxic

**Node Stage**

0 1 2 3

Fig. 25. The Tissue Perfusion Pulsatility Index (TPI) falls significantly with increasing

volume than well perfused nodes (from [2])

2,50

2,00

1,50

1,00

0,50

N-stages of the nodes (from [2])

**Tissue PI**

attempts tried to quantify the umbilical venous flow volume with the aim to evaluate the foetal perfusion in quantitative terms [36, 37]. These studies were not continued because of limited reproducibility [38]. Nevertheless, these studies targeted at a parameter – volume flow –, which has a much better rationale than the popular and easy to measure RI and PI. The early studies were flawed mainly by two limitations, which could not be overcome with two-dimensional sonographic techniques. First the angle correction of flow velocity in space and second the non-circular shape of the transsection of the umbilical vein (UV).

Spatial angle correction is but pivotal in this setting, because the UV is continuously winding around the umbilical arteries and the whole cord is irregularly bent within the amniotic cavity. Two-dimensional images thus may allow an angle correction within the frontal plane but this can be vastly misleading. Depending on the sagittal angle the true and only relevant spatial angle can differ substantially thus leading to unpredictable errors of the volume flow calculation, when unknown. The second source of error was the universal assumption, that the UV is a round tube. The investigators tried to depict a straight running venous segment with parallel borders to apply the formula for circular area calculation in order to multiply this area with the mean flow velocity which was traced with a pulsedwave- Doppler instrument in the centre of the vein.

These sources of error combined in an unpredictable manner and caused the refusal of this approach.

The technique of DTPM combined with the modern three-dimensional imaging techniques can resolve all of these imponderabilities. We developed the three-dimensional, spatial angle corrected umbilical vein flow volume measurement, which is outlined below.

Fig. 26. Example of a spatially angle corrected fetal volume flow measurement in the umbilical vein. A 3D-dataset is shown displaying three perpendicular imaging planes. The horizontal plane is used for DTPM (right lower quarter): False color map of the venous flow. From these data the flow volume is directly calculated by the PixelFlux-software

Dynamic Tissue Perfusion Measurement – Basics and Applications 317

26). In this plane both velocity as displayed by a certain colour hue and shape of the vessel's cross section are distorted by a stretching factor which is equal to the cosine of the spatial angle between vessel's course and the ultrasound waves' propagation line – the so called Doppler angle α. While the area is stretched by the reciprocal of cos α the velocity is virtually reduced by the by multiplication with cos α (proof see chapter 18. Addendum on page 27). Therefore, direct calculation of true flow volumes directly from measurements within the horizontal plane is possible. This is accomplished by the DTPM software PixelFlux. The reproducibility of these measurements in a clinical situation lies in the range of around 6 % and less, if exclusively data with steep spatial Doppler angles are allowed (own unpublished data).

A significant correlation of such volume flow measurements with fetal weight could be demonstrated (fig. 27) [41] that was the better the steeper the spatial angle could be arranged. Moreover, in a preliminary study a significantly diminished flow volume per

In animal models, numerous reports underscore the interest in DTPM, especially in the field of theriogenology. The functional status of the bovine ovary (evaluated by the plasma progesterone concentration during the oestrous cycle) could be better correlated to luteal blood flow than to luteal size ([39]. The course of luteal perfusion mirrored progesterone levels much more readily than the sheer size of the corpus luteum. The perfusion measurement of the ovary in cows could differentiate between varying courses of progesterone plasma levels [41]. Perfusion measurements of the follicle, the corpus luteum and the uterus yielded differing responses in cows undergoing synchronization of ovulation [42]. They helped to explain the effect of human chorionic gonadotropin onto the progesterone synthesis and luteal blood flow [43], were useful in monitoring luteal perfusion during pregnancy and after embryonic loss [44] and could be used to tackle a variety of interactions between hormone production, luteal blood flow and gene expressions

In another study on the regulation of follicular development in cows DTPM demonstrated significant correlation with the follicular NO concentration and Estradiol (E2)/Progesterone (P4) ratio in those follicles, which developed to the dominant follicle in the ovary [46].

In milking of cows, a significant increase of utter perfusion was measured after 15 – 30 min to settle down after 45 min to the basic, pre-milking values. These basic values but differed

DTPM helped to describe the periurethral vascularity in women [3], was used to estimate the effect of periprostatic vascularity on the effect of HIFU in prostate cancer [48], proved to be more sensitive than computer assisted B-mode image analysis in testicular torsion and

Perfusion measurements of the basal ganglia using DTPM in neonates with hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia demonstrated significantly higher perfusion values in neonates that died compared to the survivors (0.226± 0.221 cm/s vs. 0.111±0.082 cm/sec; p=0.02) (fig. 29). DTPM values also were higher

showed clearly a perfusion decline within two hours after torsion [49].

gram fetal weight could be shown (fig. 28).

**16. Miscellaneous** 

in luteal tissue [45].

considerably among the animals [47].

Fig. 27. DTPM reveals a significant correlation of fetal volume flow and fetal weight. This correlation improves significantly with reduction of the spatial angle (specified within each diagram)

Fig. 28. A significant reduction of fetal perfusion per gram fetal weight could be demonstrated by DTPM in fetuses with intrauterine growth retardation (IUGR) compared to normal children

To achieve best results the umbilical cord should be recorded in a 3D-colour Doppler sweep so that the vein is running in a steep angle towards the transducer. The data block is then scanned with a 3D-manipulation software (4Dview, GE) by parallel shifts of the frontal and sagittal images to search for a transsection of the UV in the horizontal plane, which is clearly cut, has distinct borders and is not taken from a segment of the vein with strong bending (fig. 26). In this plane both velocity as displayed by a certain colour hue and shape of the vessel's cross section are distorted by a stretching factor which is equal to the cosine of the spatial angle between vessel's course and the ultrasound waves' propagation line – the so called Doppler angle α. While the area is stretched by the reciprocal of cos α the velocity is virtually reduced by the by multiplication with cos α (proof see chapter 18. Addendum on page 27). Therefore, direct calculation of true flow volumes directly from measurements within the horizontal plane is possible. This is accomplished by the DTPM software PixelFlux. The reproducibility of these measurements in a clinical situation lies in the range of around 6 % and less, if exclusively data with steep spatial Doppler angles are allowed (own unpublished data).

A significant correlation of such volume flow measurements with fetal weight could be demonstrated (fig. 27) [41] that was the better the steeper the spatial angle could be arranged. Moreover, in a preliminary study a significantly diminished flow volume per gram fetal weight could be shown (fig. 28).

#### **16. Miscellaneous**

316 Sonography

Fig. 27. DTPM reveals a significant correlation of fetal volume flow and fetal weight. This correlation improves significantly with reduction of the spatial angle (specified within each

 **Perfusion volume [ml/min] Perfusion per weight [ml/g\*min]** 

Fig. 28. A significant reduction of fetal perfusion per gram fetal weight could be demonstrated by DTPM in fetuses with intrauterine growth retardation (IUGR) compared to normal children

To achieve best results the umbilical cord should be recorded in a 3D-colour Doppler sweep so that the vein is running in a steep angle towards the transducer. The data block is then scanned with a 3D-manipulation software (4Dview, GE) by parallel shifts of the frontal and sagittal images to search for a transsection of the UV in the horizontal plane, which is clearly cut, has distinct borders and is not taken from a segment of the vein with strong bending (fig.

diagram)

In animal models, numerous reports underscore the interest in DTPM, especially in the field of theriogenology. The functional status of the bovine ovary (evaluated by the plasma progesterone concentration during the oestrous cycle) could be better correlated to luteal blood flow than to luteal size ([39]. The course of luteal perfusion mirrored progesterone levels much more readily than the sheer size of the corpus luteum. The perfusion measurement of the ovary in cows could differentiate between varying courses of progesterone plasma levels [41]. Perfusion measurements of the follicle, the corpus luteum and the uterus yielded differing responses in cows undergoing synchronization of ovulation [42]. They helped to explain the effect of human chorionic gonadotropin onto the progesterone synthesis and luteal blood flow [43], were useful in monitoring luteal perfusion during pregnancy and after embryonic loss [44] and could be used to tackle a variety of interactions between hormone production, luteal blood flow and gene expressions in luteal tissue [45].

In another study on the regulation of follicular development in cows DTPM demonstrated significant correlation with the follicular NO concentration and Estradiol (E2)/Progesterone (P4) ratio in those follicles, which developed to the dominant follicle in the ovary [46].

In milking of cows, a significant increase of utter perfusion was measured after 15 – 30 min to settle down after 45 min to the basic, pre-milking values. These basic values but differed considerably among the animals [47].

DTPM helped to describe the periurethral vascularity in women [3], was used to estimate the effect of periprostatic vascularity on the effect of HIFU in prostate cancer [48], proved to be more sensitive than computer assisted B-mode image analysis in testicular torsion and showed clearly a perfusion decline within two hours after torsion [49].

Perfusion measurements of the basal ganglia using DTPM in neonates with hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia demonstrated significantly higher perfusion values in neonates that died compared to the survivors (0.226± 0.221 cm/s vs. 0.111±0.082 cm/sec; p=0.02) (fig. 29). DTPM values also were higher

Dynamic Tissue Perfusion Measurement – Basics and Applications 319

DTPM offers a universally applicable approach to tissue perfusion measurement as far as sonographic depiction of tissues is possible. So far, inaccessible details of perfusion intensity, perfusion distribution, perfusion gradients within a certain vasculature open a widow to an individualized evaluation of the specific pathophysiological situation. Treatment efforts can be evaluated according to their effect on perfusion. Besides these intrinsic advantages, the technique requires no additional hardware, is non-invasive, needs no specific preparation of

**18. Addendum: Proof of the congruence of the true flow volume and the flow volume calculated from the horizontally projected velocity and area of any** 

True volume flow calculation becomes feasible with three-dimensional colour Doppler data. True volume flow calculation means the exact calculation of the blood flow volume running

Our method of true volume perfusion measurement in vessels cut by the horizontal plane in

The spatial angle, which is the angle between the vessel and the ultrasound propagation line, influences simultaneously the stretching of the shape of the vessels' cross-sectional area as well as the change of the recorded flow velocity. Figure 30 displays the respective situation schematically. The blood vessel (yellow rectangle) runs with the Doppler angle α towards the ultrasound propagation line (blue line). The horizontal imaging plane, which is calculated during the three-dimensional ultrasound imaging, cuts the vessel. Line *a*′ is the stretched vessel's diameter as it can be seen in the horizontal plane. Vector b is the original flow velocity within the vessel. Due to the Doppler angle α the recorded velocity is displayed with the value for vector b'. This means, the color hue of b' is darker, representing a lower velocity as if vector b would be displayed in its appropriate color. This is the well

α

*Vt a a b* = π

The oblique transsection of a round vessel, a vessel running not perpendicularly towards the horizontal plane, results in stretching of the circular vessel's round cross-sectional area in the direction of the projection vector of the spatial angle of this vessel with the horizontal plane. This results in an ellipse which longer axis is represented by *a*′ , the stretched projection of a onto the horizontal plane (Fig. 30). The shorter axis is equal to the original

It is therefore possible to consider the change of diameter *a* towards *a*′ , the long axis of the ellipse in order to describe the change of the horizontally projected cross-sectional area of

4 ∗ ∗*a a* calculates the circular area of the perpendicularly cut vessel

diameter of the vessel. It remains unstretched since no angulation occurs.

<sup>4</sup> ∗∗∗ <sup>G</sup>

) , which reduces the recorded velocity

(1)

the patient and thus can be recommended for a broad array of clinical applications.

through any vessel which is cut perpendicularly.

any spatial angle is described and proven below.

known Doppler effect ( *fd fo v c* =∗ ∗ ∗ 2 c *<sup>t</sup>* os

The real flow volume per time (V) of a circular vessel is calculated as

according to the cosine of α.

// π

**17. Summary** 

**vessel** 

in nine neonates with MRI showing moderate to severe injury (0.142±0.070 cm/s vs. 0.072±0.080 cm/s; p=0.04). DTPM opens a window to better understand reperfusion injury in HIE [49].

Fig. 29. Example of a DTPM of basal ganglia in a newborn. Upper part: false color map of the basal ganglia and distribution curve. Lower part: Perfusion intensity course during one examination. (Image and measurement courtesy of Dr. Ricardo Faingold, Montreal)

#### **17. Summary**

318 Sonography

in nine neonates with MRI showing moderate to severe injury (0.142±0.070 cm/s vs. 0.072±0.080 cm/s; p=0.04). DTPM opens a window to better understand reperfusion injury

Intensity

0 5 10 15 20 25 30 35 40 video images Fig. 29. Example of a DTPM of basal ganglia in a newborn. Upper part: false color map of the basal ganglia and distribution curve. Lower part: Perfusion intensity course during one examination. (Image and measurement courtesy of Dr. Ricardo Faingold, Montreal)

red blue

in HIE [49].

0.80 0.75 0.70 0.65 0.60 0.55 0.50 0.45 0.40

cm/s

DTPM offers a universally applicable approach to tissue perfusion measurement as far as sonographic depiction of tissues is possible. So far, inaccessible details of perfusion intensity, perfusion distribution, perfusion gradients within a certain vasculature open a widow to an individualized evaluation of the specific pathophysiological situation. Treatment efforts can be evaluated according to their effect on perfusion. Besides these intrinsic advantages, the technique requires no additional hardware, is non-invasive, needs no specific preparation of the patient and thus can be recommended for a broad array of clinical applications.

#### **18. Addendum: Proof of the congruence of the true flow volume and the flow volume calculated from the horizontally projected velocity and area of any vessel**

True volume flow calculation becomes feasible with three-dimensional colour Doppler data.

True volume flow calculation means the exact calculation of the blood flow volume running through any vessel which is cut perpendicularly.

Our method of true volume perfusion measurement in vessels cut by the horizontal plane in any spatial angle is described and proven below.

The spatial angle, which is the angle between the vessel and the ultrasound propagation line, influences simultaneously the stretching of the shape of the vessels' cross-sectional area as well as the change of the recorded flow velocity. Figure 30 displays the respective situation schematically. The blood vessel (yellow rectangle) runs with the Doppler angle α towards the ultrasound propagation line (blue line). The horizontal imaging plane, which is calculated during the three-dimensional ultrasound imaging, cuts the vessel. Line *a*′ is the stretched vessel's diameter as it can be seen in the horizontal plane. Vector b is the original flow velocity within the vessel. Due to the Doppler angle α the recorded velocity is displayed with the value for vector b'. This means, the color hue of b' is darker, representing a lower velocity as if vector b would be displayed in its appropriate color. This is the well known Doppler effect ( *fd fo v c* =∗ ∗ ∗ 2 c *<sup>t</sup>* osα ) , which reduces the recorded velocity according to the cosine of α.

The real flow volume per time (V) of a circular vessel is calculated as

$$V/t = \pi/4 \ast a \ast a \ast \vec{b} \tag{1}$$

// π4 ∗ ∗*a a* calculates the circular area of the perpendicularly cut vessel

The oblique transsection of a round vessel, a vessel running not perpendicularly towards the horizontal plane, results in stretching of the circular vessel's round cross-sectional area in the direction of the projection vector of the spatial angle of this vessel with the horizontal plane. This results in an ellipse which longer axis is represented by *a*′ , the stretched projection of a onto the horizontal plane (Fig. 30). The shorter axis is equal to the original diameter of the vessel. It remains unstretched since no angulation occurs.

It is therefore possible to consider the change of diameter *a* towards *a*′ , the long axis of the ellipse in order to describe the change of the horizontally projected cross-sectional area of

Dynamic Tissue Perfusion Measurement – Basics and Applications 321

This means, that it is possible to calculate the true flow volume of all vessels cut horizontally from the depicted flow velocities1 and the pixelwise calculated cross-sectional areas2 directly, thus compensating any spatial angle. Both measurements (1 and 2), are carried out automatically by the PixelFlux-software, which delivers thus true flow volumes of all vessels in any tissue section cut horizontally in three-dimensional color Doppler ultrasound data.

Blood vessel

90°

90°

Fig. 30. Schematical depiction of a horizontally cut vessel in a 3D-color Doppler sonographic

[2] Scholbach T., DiMartino E., Scholbach J. "Dynamic color Doppler sonographic tissue

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perfusion measurement in tumors" in Cancer imaging (2 volumes) (Elsevier/

Doppler endovaginal ultrasonography: preliminary report. *Pelviperineology* 2009.

identification and prediction of diabetic nephropathy*. Nutr Metab Cardiovasc Dis*,

a

β

A

α

β

b'

F

D

[1] Chameleon-Software, *PixelFlux.* 2011.

28: p. 59-61.

2009. 19(5): p. 358-64.

dataset

**19. References** 

E

green: horizontal imaging plane

α

http://www.chameleon-software.de/index-de.html.

Academic Press, 2008) ed by M.A. Hayat

*N Engl J Med*, 2003. 349(2): p. 115-24.

*Journal of Medical Ultrasound*, 2009. 17( 1): p. 9-16.

b' b

blue: ultrasound propagation line

C

B

90°

a'

a

α β

90°

Transducer surface

the vessel. The change of the circular area towards the elliptical area is thus equal to the stretching factor *a a* ′ .

The other relevant change is the reduction of the displayed flow velocity compared to the original velocity b, the reduction factor is *b b* ′ .

It is now claimed, that the flow volume V' per time, which is passing through the horizontal plane in direction of the vessel, calculated by multiplying the elliptical area ( *A* = ∗∗ π 4 *a a*′) with the flow velocity b' of the vessel in the horizontal plane is equal to V per time, the flow volume passing through the perpendicularly cut vessel in the same time.

Claim:

$$V' = V \tag{2}$$

Proof:

$$\mathbb{E}V'/t = \pi/4 \ast a \ast a' \ast \overline{b'} \tag{3}$$

// π 4 ∗ ∗*a a*′ calculates the elliptic area of the horizontally cut vessel *a* : short axis of the ellipse

*a*′ : long axis of the ellipse

The depiction of the horizontally cut vessel shows the velocity *b*′ JG and a stretched vessel diameter *a*′ .

The triangle ABC is rectangular, since the blood vessel is a rectangle, a perpendicularly cut circular straight vessel. Doppler angle α is complemented to 90° by the angles DAB and FAC since the ultrasound propagation line (blue line running through F) runs perpendicular to the transducer's surface and thus the horizontal imaging plane. Both angles are thus equal and named β. Angles FAC and CAB add to 90° since again the ultrasound propagation line runs perpendicular to the horizontal imaging plane. Thus angle CAB is α again, the Doppler angle.

$$a' = a \nmid \cos a \tag{4}$$

$$
\overrightarrow{b'} = \overrightarrow{b} \* \cos \alpha \tag{5}
$$

by inserting (3) and (4) into (2) results (5)

$$V' = \pi/4 \ast a \ast a / \cos a \ast \vec{b} \ast \cos a \tag{6}$$

which is (6) after cancelling cos α

$$V' = \pi/4 \ast a \ast a \ast \vec{b} = V \cdot \text{sec (1)}\tag{7}$$

thus

$$V' = V \tag{8}$$

q.e.d.

This means, that it is possible to calculate the true flow volume of all vessels cut horizontally from the depicted flow velocities1 and the pixelwise calculated cross-sectional areas2 directly, thus compensating any spatial angle. Both measurements (1 and 2), are carried out automatically by the PixelFlux-software, which delivers thus true flow volumes of all vessels in any tissue section cut horizontally in three-dimensional color Doppler ultrasound data.

Fig. 30. Schematical depiction of a horizontally cut vessel in a 3D-color Doppler sonographic dataset

#### **19. References**

320 Sonography

the vessel. The change of the circular area towards the elliptical area is thus equal to the

The other relevant change is the reduction of the displayed flow velocity compared to the

It is now claimed, that the flow volume V' per time, which is passing through the horizontal plane in direction of the vessel, calculated by multiplying the elliptical area ( *A* = ∗∗

with the flow velocity b' of the vessel in the horizontal plane is equal to V per time, the flow

*Vt a a b* ′ = π

The triangle ABC is rectangular, since the blood vessel is a rectangle, a perpendicularly cut circular straight vessel. Doppler angle α is complemented to 90° by the angles DAB and FAC since the ultrasound propagation line (blue line running through F) runs perpendicular to the transducer's surface and thus the horizontal imaging plane. Both angles are thus equal and named β. Angles FAC and CAB add to 90° since again the ultrasound propagation line runs perpendicular to the horizontal imaging plane. Thus angle CAB is α again, the Doppler

*a a* ′ = /cos

*b b* ′ = ∗ cos

*V aa b* ′ = ∗∗ ∗∗

*V aab V* ′ =

 4 cos cos α

π

π

α

α

 α

<sup>4</sup> ∗∗ ∗′ ′ JG

volume passing through the perpendicularly cut vessel in the same time.

4 ∗ ∗*a a*′ calculates the elliptic area of the horizontally cut vessel

The depiction of the horizontally cut vessel shows the velocity *b*′

π4 *a a*′)

and a stretched vessel

*V V* ′ = (2)

JG

(3)

(4)

<sup>G</sup> (6)

JG G (5)

<sup>4</sup> ∗∗∗=G see (1) (7)

*V V* ′ = (8)

stretching factor *a a* ′ .

Claim:

Proof:

// π

diameter *a*′ .

angle.

thus

q.e.d.

original velocity b, the reduction factor is *b b* ′ .

*a* : short axis of the ellipse *a*′ : long axis of the ellipse

by inserting (3) and (4) into (2) results (5)

which is (6) after cancelling cos α

[1] Chameleon-Software, *PixelFlux.* 2011.

http://www.chameleon-software.de/index-de.html.


Dynamic Tissue Perfusion Measurement – Basics and Applications 323

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**1. Introduction** 

on harmonious fetal cerebral development.

**18** 

*France* 

**Fetal Yawning** 

*Family Physician. Private Practice* 

The introduction of ultrasound exploration during pregnancy has led to very important conclusions concerning fetal behavioural milestones. For example, the development of oral sensorimotor functions such as swallowing (essential for survival) can be assessed from normal or abnormal neurobehavioral development during the fetal period. While the assessment of these functions takes a long time, another daily behaviour can be detected during an ultrasound examination: yawning. Before the development of real-time imaging techniques, it was impossible to assess facial movements, swallowing and thus yawning. Only the overall movements of the trunk and limbs could be perceived by the mother or by someone touching her belly with their hand. In this chapter, we will show the usefulness of ultrasound in exploring facial mobility, particularly yawning, and in drawing conclusions

The phenomenon of yawning is just as intriguing and fascinating as sleep, yet understanding of its causes and consequences has defied the human mind for centuries. Phylogenetically and ontogenetically primitive, this motor behaviour has been remarkably well preserved during evolution and is nearly universal in vertebrates. It appears closer to an emotional stereotypy than to a reflex. Yawning is a stereotyped and often repetitive motor act characterized by gaping of the mouth accompanied by a long inspiration of air or fluid, followed by a brief acme and a short expiration. It is not merely a simple opening of the mouth, but a complex coordinated movement bringing together a flexion followed by an extension of the neck, a wide dilatation of the laryngopharynx with strong stretching of the diaphragm and anti-gravity muscles. Highly stereotypical because no environmental input changes the sequence of movements, it is observed in cold-blooded and warm-blooded vertebrates, from reptiles with rudimentary 'archaic' brains to human primates, in water, air and land environments. The ethology, neurophysiology and neuropsychology literature describes yawning as a transitional behaviour associated with wake/sleep rhythms and hunger/satiety fluctuations, where it externalizes a group of possible vigilance-stimulating mechanisms and attests to the central role of the diencephalon and notably the

All the movements that a newborn is able to produce originate during the fetal phase and are performed throughout the life span. The fetus exhibits a wide range of behaviours starting with slow flexion and extension of the spine and limbs at around 7 weeks gestation. The variety of movements increases rapidly over the next three to four weeks and many

hypothalamus in homeostasis (Walusinski, 2004; Guggisberg, 2010).

Olivier Walusinski


### **18**

### **Fetal Yawning**

Olivier Walusinski *Family Physician. Private Practice France* 

#### **1. Introduction**

324 Sonography

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sonography in neonates with hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia. *Pediatr Radiol* 2011. 41(Suppl 1): p. S250-S310 NE2-3.

The introduction of ultrasound exploration during pregnancy has led to very important conclusions concerning fetal behavioural milestones. For example, the development of oral sensorimotor functions such as swallowing (essential for survival) can be assessed from normal or abnormal neurobehavioral development during the fetal period. While the assessment of these functions takes a long time, another daily behaviour can be detected during an ultrasound examination: yawning. Before the development of real-time imaging techniques, it was impossible to assess facial movements, swallowing and thus yawning. Only the overall movements of the trunk and limbs could be perceived by the mother or by someone touching her belly with their hand. In this chapter, we will show the usefulness of ultrasound in exploring facial mobility, particularly yawning, and in drawing conclusions on harmonious fetal cerebral development.

The phenomenon of yawning is just as intriguing and fascinating as sleep, yet understanding of its causes and consequences has defied the human mind for centuries. Phylogenetically and ontogenetically primitive, this motor behaviour has been remarkably well preserved during evolution and is nearly universal in vertebrates. It appears closer to an emotional stereotypy than to a reflex. Yawning is a stereotyped and often repetitive motor act characterized by gaping of the mouth accompanied by a long inspiration of air or fluid, followed by a brief acme and a short expiration. It is not merely a simple opening of the mouth, but a complex coordinated movement bringing together a flexion followed by an extension of the neck, a wide dilatation of the laryngopharynx with strong stretching of the diaphragm and anti-gravity muscles. Highly stereotypical because no environmental input changes the sequence of movements, it is observed in cold-blooded and warm-blooded vertebrates, from reptiles with rudimentary 'archaic' brains to human primates, in water, air and land environments. The ethology, neurophysiology and neuropsychology literature describes yawning as a transitional behaviour associated with wake/sleep rhythms and hunger/satiety fluctuations, where it externalizes a group of possible vigilance-stimulating mechanisms and attests to the central role of the diencephalon and notably the hypothalamus in homeostasis (Walusinski, 2004; Guggisberg, 2010).

All the movements that a newborn is able to produce originate during the fetal phase and are performed throughout the life span. The fetus exhibits a wide range of behaviours starting with slow flexion and extension of the spine and limbs at around 7 weeks gestation. The variety of movements increases rapidly over the next three to four weeks and many

Fetal Yawning 327

yawning cycle. After reaching its maximum opening, the mouth remains wide open for 5 to 15 s and returns to its resting closed position within seconds. This harmonious sequence is markedly different from a brief swallowing episode. Using a colour Doppler technique, it is possible to observe the flow of amniotic fluid through the fetal mouth, oropharynx and trachea to the lungs. Contrary to adults, yawning is non-repetitive in the fetus. It is part of a generalized stretch, not just a matter of opening one's mouth. It especially involves the muscles of the respiratory tract (diaphragm, intercostals), face and neck. Fetal yawning can be recognized as one of the movement patterns consistently present starting at around 11-12 weeks of pregnancy (fig. 2). The frequency of yawning gradually increases between 12 and 24 weeks (fig. 3 and 4). During this time, it is possible to observe 40 to 60 yawns per day, and it is the best time to assess yawning with ultrasound examination. A plateau is reached, after which the number of yawns decreases slightly until term. Thus, yawning occurs regularly at a rate of about 1 to 3 yawns per hour. It is obviously by chance or after a long investigation that a yawn can be observed. Furthermore, occiput anterior fetal position unfortunately impedes adequate observation of yawning (Sepulveda, 1995; Masuzaki, 1996).

Yawning is a phylogenetically old, stereotyped phenomenon. Its survival without evolutionary variations suggests a particular importance as far as development. The strong muscular contraction during yawning has a metabolically high cost. If we agree with Darwin's evolutionary propositions, the costs of brain activity must be outweighed by the developmental advantages. Thus, one structural hypothesis is activation of neurotrophins, which leads to a cascade of new synapse formation or recruitment as well as activation through the diencephalon, brainstem and spinal cord. Activity-dependent development has been clearly shown to be one mechanism by which early sensory or motor experience can affect the course of neural development. This mechanism may be a ubiquitous process in brain maturation, by which activity in one brain region can influence development of other regions. Fetal yawning can be seen as a mechanism that influences functional determination of the moving parts of the musculoskeletal system and contributes to joint development and

Fetal movements become more regular and coordinated as a result of increased maturation of the nervous system. At the beginning of the third month, the embryo becomes a fetus with the occurrence of the first oral and pharyngeal motor sequences, controlled by neurological brainstem development and the development of the suction-swallowing activity and yawning. Indeed, suction and yawning have the same embryological origin, which shows the importance of the brainstem in the neurophysiological development of oropharyngeal activity coordinated by respiratory, cardiac and digestive regulations, which have the same neuroanatomical location. The cephalic pole comprises an original embryological encephalo-facial and encephalo-cervical segmentation with a strict topographical correspondence: the naso-frontal and premaxillary structures are connected to the forebrain; the maxillo-mandibular and anterior cervical structures are connected to the 41 brainstem and its nerves. The major structures of the brainstem are formed by the 7- 8th postconceptional week, although brainstem maturation continues until the 8th postconceptional month. In addition to its many subnuclei, the brainstem gives rise to a variety of descending spinal motor tracts and hosts the nuclei of five cranial nerves (VIII-XII). Formation of the pons begins almost simultaneously, but its maturation is more prolonged. The structures of the pons include cranial nerves V-VIII and the medial

**3. Yawning and neurodevelopmental assessments** 

maintenance.

different movement patterns have been described, including breathing, truncal rotation, limb flexion/extension, sucking and yawning (de Vries, 1982).

#### **2. How to recognize a fetal yawn during ultrasound examination**

During ultrasound facial examination, yawning can be seen accidentally. Yawning consists of a slow opening of the mouth with simultaneous downward movements of the tongue and is usually combined with retroflexion of the head. This phase occupies 50 to 75% of the

Fig. 1. Development of brain and fetal central nervous system and chronology of the functional development of fetal movements

different movement patterns have been described, including breathing, truncal rotation,

During ultrasound facial examination, yawning can be seen accidentally. Yawning consists of a slow opening of the mouth with simultaneous downward movements of the tongue and is usually combined with retroflexion of the head. This phase occupies 50 to 75% of the

Fig. 1. Development of brain and fetal central nervous system and chronology of the

functional development of fetal movements

limb flexion/extension, sucking and yawning (de Vries, 1982).

**2. How to recognize a fetal yawn during ultrasound examination** 

yawning cycle. After reaching its maximum opening, the mouth remains wide open for 5 to 15 s and returns to its resting closed position within seconds. This harmonious sequence is markedly different from a brief swallowing episode. Using a colour Doppler technique, it is possible to observe the flow of amniotic fluid through the fetal mouth, oropharynx and trachea to the lungs. Contrary to adults, yawning is non-repetitive in the fetus. It is part of a generalized stretch, not just a matter of opening one's mouth. It especially involves the muscles of the respiratory tract (diaphragm, intercostals), face and neck. Fetal yawning can be recognized as one of the movement patterns consistently present starting at around 11-12 weeks of pregnancy (fig. 2). The frequency of yawning gradually increases between 12 and 24 weeks (fig. 3 and 4). During this time, it is possible to observe 40 to 60 yawns per day, and it is the best time to assess yawning with ultrasound examination. A plateau is reached, after which the number of yawns decreases slightly until term. Thus, yawning occurs regularly at a rate of about 1 to 3 yawns per hour. It is obviously by chance or after a long investigation that a yawn can be observed. Furthermore, occiput anterior fetal position unfortunately impedes adequate observation of yawning (Sepulveda, 1995; Masuzaki, 1996).

#### **3. Yawning and neurodevelopmental assessments**

Yawning is a phylogenetically old, stereotyped phenomenon. Its survival without evolutionary variations suggests a particular importance as far as development. The strong muscular contraction during yawning has a metabolically high cost. If we agree with Darwin's evolutionary propositions, the costs of brain activity must be outweighed by the developmental advantages. Thus, one structural hypothesis is activation of neurotrophins, which leads to a cascade of new synapse formation or recruitment as well as activation through the diencephalon, brainstem and spinal cord. Activity-dependent development has been clearly shown to be one mechanism by which early sensory or motor experience can affect the course of neural development. This mechanism may be a ubiquitous process in brain maturation, by which activity in one brain region can influence development of other regions. Fetal yawning can be seen as a mechanism that influences functional determination of the moving parts of the musculoskeletal system and contributes to joint development and maintenance.

Fetal movements become more regular and coordinated as a result of increased maturation of the nervous system. At the beginning of the third month, the embryo becomes a fetus with the occurrence of the first oral and pharyngeal motor sequences, controlled by neurological brainstem development and the development of the suction-swallowing activity and yawning. Indeed, suction and yawning have the same embryological origin, which shows the importance of the brainstem in the neurophysiological development of oropharyngeal activity coordinated by respiratory, cardiac and digestive regulations, which have the same neuroanatomical location. The cephalic pole comprises an original embryological encephalo-facial and encephalo-cervical segmentation with a strict topographical correspondence: the naso-frontal and premaxillary structures are connected to the forebrain; the maxillo-mandibular and anterior cervical structures are connected to the 41 brainstem and its nerves. The major structures of the brainstem are formed by the 7- 8th postconceptional week, although brainstem maturation continues until the 8th postconceptional month. In addition to its many subnuclei, the brainstem gives rise to a variety of descending spinal motor tracts and hosts the nuclei of five cranial nerves (VIII-XII). Formation of the pons begins almost simultaneously, but its maturation is more prolonged. The structures of the pons include cranial nerves V-VIII and the medial

Fetal Yawning 329

Fig. 4. Fetal yawn at 23 weeks of pregnancy (2D). Fetus weighing 200g

alveoli by the inspired fluid is possible (Marder, 2005).

**4. Yawning as a testimony to safe neurological development** 

In pregnant women, the methods of assessing fetal wellbeing include the biophysical profile; however, this method is limited. Thus, infants must develop safe and effective

longitudinal fasciculus (MLF), pontine tegmentum, raphe nucleus and locus coeruleus, which exert widespread influence on arousal, including the sleep-wake cycle. Therefore, these structures exert tremendous influence on gross body movements, head turning, heart rate, and respiratory movements, as well as swallowing, yawning, suckling, hiccups, and 7 facial grimacing movements (Santagati, 2003; Kontges, 1996; Jacob, 2000; Sadler, 2009) (Fig. 1). The emergence of different behavioural states is one of the most significant aspects of early brain maturation in the fetus. In early intra-uterine life, a diffuse collection of phasic and cyclic motor events occur that gradually coalesce. For the fetus, wakefulness and sleep are reliably characterized, respectively, by periods of myoclonic twitching and movements of the limbs against a background of muscle atonia. Periods of twitching are almost always followed by the abrupt onset of high-amplitude, wakeful behaviours. The emergence of distinct states is followed by dramatic changes in the level, duration and cyclicity. An ultradian rhythm may be observed: during a 60 to 90 minute period, there is an alternation of movement characterized by motor activity and movement characterized by rest, as in newborns. The switchover from periods of rest to periods of activity is accompanied by a yawn. Thus, a periodicity of one or two yawns per hour can be seen. Repetitive motions gradually determine the shape and composition of moving structures, as well as their associated neural control pathways. The precociousness and stability of yawning suggest that these characteristics contribute to such development. Furthermore, since a forced inspiration is a critical component of yawning, a potential role for expanding fetal terminal

Fig. 2. Fetal yawn at 12 weeks of pregnancy (3D). Fetus weighing 80g

Fig. 3. Fetal yawn at 23 weeks of pregnancy (3D). Fetus weighing 200g

Fig. 2. Fetal yawn at 12 weeks of pregnancy (3D). Fetus weighing 80g

Fig. 3. Fetal yawn at 23 weeks of pregnancy (3D). Fetus weighing 200g

Fig. 4. Fetal yawn at 23 weeks of pregnancy (2D). Fetus weighing 200g

longitudinal fasciculus (MLF), pontine tegmentum, raphe nucleus and locus coeruleus, which exert widespread influence on arousal, including the sleep-wake cycle. Therefore, these structures exert tremendous influence on gross body movements, head turning, heart rate, and respiratory movements, as well as swallowing, yawning, suckling, hiccups, and 7 facial grimacing movements (Santagati, 2003; Kontges, 1996; Jacob, 2000; Sadler, 2009) (Fig. 1).

The emergence of different behavioural states is one of the most significant aspects of early brain maturation in the fetus. In early intra-uterine life, a diffuse collection of phasic and cyclic motor events occur that gradually coalesce. For the fetus, wakefulness and sleep are reliably characterized, respectively, by periods of myoclonic twitching and movements of the limbs against a background of muscle atonia. Periods of twitching are almost always followed by the abrupt onset of high-amplitude, wakeful behaviours. The emergence of distinct states is followed by dramatic changes in the level, duration and cyclicity. An ultradian rhythm may be observed: during a 60 to 90 minute period, there is an alternation of movement characterized by motor activity and movement characterized by rest, as in newborns. The switchover from periods of rest to periods of activity is accompanied by a yawn. Thus, a periodicity of one or two yawns per hour can be seen. Repetitive motions gradually determine the shape and composition of moving structures, as well as their associated neural control pathways. The precociousness and stability of yawning suggest that these characteristics contribute to such development. Furthermore, since a forced inspiration is a critical component of yawning, a potential role for expanding fetal terminal alveoli by the inspired fluid is possible (Marder, 2005).

#### **4. Yawning as a testimony to safe neurological development**

In pregnant women, the methods of assessing fetal wellbeing include the biophysical profile; however, this method is limited. Thus, infants must develop safe and effective

Fetal Yawning 331

Although no data has actually been collected, we have made a non-exhaustive inventory of







An entirely new paradigm has emerged in fetal medicine, given that the advances in prenatal imaging allow one to see and diagnose disease not previously detected. Clinicians can better plan for the delivery of the neonate, with identified anomalies being optimally managed and the impact on the neonate's health minimized. There exists a sound rationale for including systematic observations of spontaneous motor activity in the neurological assessment of fetuses. Yawning, as spontaneous motility linked to brainstem activities, appears to be a good parameter for indicating such wellbeing and harmonious development. Thus, brainstem maturation could be associated with changes in the yawning pattern. A difficult task is qualitative evaluation of general and partial movements in order to distinguish normal from abnormal performance. Yawning is a basic behaviour that is easy to recognize and highly valuable in assessing brainstem activity. It is advisable to include the fetal yawning examination in the systematic week 23 ultrasound scan. Future studies will improve its diagnostic value in detecting neuromuscular developmental

A complete review on yawning can be founded in the book: "The Mystery of Yawning in


syndrome, Goldenhar syndrome, Richner-Hanhart syndrome.

congenital pathologies in which yawning research is relevant:

classified into congenital and developmental types:

cleft, and the primordia of the temporal bone.

eye and tongue movements, and hypotonia.

syndrome, Stüve-Wiedemann syndrome, etc.

abnormalities as well as fetal behavioural abnormalities.

Physiology and Disease". Walusinski O. ed. Basel. Karger. 2010. 160p.

constant.

**6. Conclusion** 

respiration and oral feeding skills after birth if they are to survive. For this to occur, infants must have the necessary anatomical structures and adequate central control to coordinate swallowing, ventilation, sleep and arousal. Yawning is associated with all of these behaviours and thus is useful to observe. Fetal facial expressions and movements are known to be an indirect expression of cerebral functional maturity during the fetal period. Facial expressions during this period correspond to facial expression during the neonatal period. Ultrasound has become essential for assessing neurophysiological development as well as detecting anatomical pathology. 4D ultrasound makes it straightforward to comprehend morphological dynamics such as yawning or sucking. As we have seen, yawning can provide information about neurodevelopment and the development of behavioural rhythms (alternation between motor activity, rest and sleep). When fetal activity appears abnormal, nervous system development may be disturbed. Yawning indicates harmonious development of both the brainstem and the peripheral neuromuscular function, testifying to the induction of an ultradian rhythm of vigilance (Rogers, 2005; Einspieler, 2005; Kurjak, 2008). (Ultradian rhythms are recurrent periods or cycles repeated throughout a 24-hour circadian day. In contrast, infradian rhythms, such as the human menstrual cycle, have periods longer than a day. The descriptive term ultradian is used in sleep research in reference to the 90–120 minute cycling of the sleep stages during human sleep).

#### **5. Fetal pathologies assessed by yawning exploration**

Yawns recur regularly, about one or two per hour. When a yawn is observed during a 4D US examination, it is obviously by chance or after very long investigation. Yawning appears preferentially after a period of rest, and indicates waking. If normal swallowing is seen (much more frequent), yawning seems of no additional interest with regard to harmonious brainstem maturation. Inversely, the lack or dysfunction of swallowing requires taking the time to understand the set of phasic and cyclic motor events characterizing the ultradian fetal rhythm, thereby increasing the opportunity to observe a yawn. If the ultrasound examination suggests the absence of yawning and swallowing, it is imperative to search for developmental and anatomical abnormalities (van Woerden, 1988).

The lack of fetal yawning, frequently simultaneous to the lack of associated swallowing may be a key to predicting brainstem dysfunction after birth. It is thus imperative to search for mandibular hypoplasia and glossoptosis, often associated with cleft palate (Luedders, 2011; Palit, 2008). For example, Pierre Robin sequence is characterized by a posterior U-shaped cleft palate, retrognatia and glossoptosis. Several arguments favour an embryonic origin consisting of an anomaly in caudal hind brain development. Feeding disorders are the most important functional symptom. Mother testimonies are consistent with the lack of yawning at birth and its progressive appearance during the first year of life, simultaneous to the acquisition of the swallowing reflex necessary for feeding. Pierre Robin syndrome can be seen as the prenatal brainstem dysfunction responsible for orofacial maldevelopment, which can be diagnosed at 23 weeks gestation during a 4D ultrasound examination (Bromley, 1994; Rotten, 2001).

Petrikovsky et al. (1999) report that clusters of yawns were observed in a series of anaemic fetuses and suggest that yawning repetitiveness helps to track fetal anaemia, although fetal yawning has no effect on O2 pressure. Yawning can be seen as the exteriorization of a homeostatic process, the balance between adrenergic and cholinergic stimulation of the autonomic nervous system. We believe this function is already active in the fetus.

respiration and oral feeding skills after birth if they are to survive. For this to occur, infants must have the necessary anatomical structures and adequate central control to coordinate swallowing, ventilation, sleep and arousal. Yawning is associated with all of these behaviours and thus is useful to observe. Fetal facial expressions and movements are known to be an indirect expression of cerebral functional maturity during the fetal period. Facial expressions during this period correspond to facial expression during the neonatal period. Ultrasound has become essential for assessing neurophysiological development as well as detecting anatomical pathology. 4D ultrasound makes it straightforward to comprehend morphological dynamics such as yawning or sucking. As we have seen, yawning can provide information about neurodevelopment and the development of behavioural rhythms (alternation between motor activity, rest and sleep). When fetal activity appears abnormal, nervous system development may be disturbed. Yawning indicates harmonious development of both the brainstem and the peripheral neuromuscular function, testifying to the induction of an ultradian rhythm of vigilance (Rogers, 2005; Einspieler, 2005; Kurjak, 2008). (Ultradian rhythms are recurrent periods or cycles repeated throughout a 24-hour circadian day. In contrast, infradian rhythms, such as the human menstrual cycle, have periods longer than a day. The descriptive term ultradian is used in sleep research in reference to the 90–120

Yawns recur regularly, about one or two per hour. When a yawn is observed during a 4D US examination, it is obviously by chance or after very long investigation. Yawning appears preferentially after a period of rest, and indicates waking. If normal swallowing is seen (much more frequent), yawning seems of no additional interest with regard to harmonious brainstem maturation. Inversely, the lack or dysfunction of swallowing requires taking the time to understand the set of phasic and cyclic motor events characterizing the ultradian fetal rhythm, thereby increasing the opportunity to observe a yawn. If the ultrasound examination suggests the absence of yawning and swallowing, it is imperative to search for

The lack of fetal yawning, frequently simultaneous to the lack of associated swallowing may be a key to predicting brainstem dysfunction after birth. It is thus imperative to search for mandibular hypoplasia and glossoptosis, often associated with cleft palate (Luedders, 2011; Palit, 2008). For example, Pierre Robin sequence is characterized by a posterior U-shaped cleft palate, retrognatia and glossoptosis. Several arguments favour an embryonic origin consisting of an anomaly in caudal hind brain development. Feeding disorders are the most important functional symptom. Mother testimonies are consistent with the lack of yawning at birth and its progressive appearance during the first year of life, simultaneous to the acquisition of the swallowing reflex necessary for feeding. Pierre Robin syndrome can be seen as the prenatal brainstem dysfunction responsible for orofacial maldevelopment, which can be diagnosed at 23 weeks gestation during a 4D ultrasound examination (Bromley, 1994;

Petrikovsky et al. (1999) report that clusters of yawns were observed in a series of anaemic fetuses and suggest that yawning repetitiveness helps to track fetal anaemia, although fetal yawning has no effect on O2 pressure. Yawning can be seen as the exteriorization of a homeostatic process, the balance between adrenergic and cholinergic stimulation of the

autonomic nervous system. We believe this function is already active in the fetus.

minute cycling of the sleep stages during human sleep).

**5. Fetal pathologies assessed by yawning exploration** 

developmental and anatomical abnormalities (van Woerden, 1988).

Rotten, 2001).

Although no data has actually been collected, we have made a non-exhaustive inventory of congenital pathologies in which yawning research is relevant:

	- Mandibulofacial dysostosis with a variety of limb abnormalities

#### **6. Conclusion**

An entirely new paradigm has emerged in fetal medicine, given that the advances in prenatal imaging allow one to see and diagnose disease not previously detected. Clinicians can better plan for the delivery of the neonate, with identified anomalies being optimally managed and the impact on the neonate's health minimized. There exists a sound rationale for including systematic observations of spontaneous motor activity in the neurological assessment of fetuses. Yawning, as spontaneous motility linked to brainstem activities, appears to be a good parameter for indicating such wellbeing and harmonious development. Thus, brainstem maturation could be associated with changes in the yawning pattern. A difficult task is qualitative evaluation of general and partial movements in order to distinguish normal from abnormal performance. Yawning is a basic behaviour that is easy to recognize and highly valuable in assessing brainstem activity. It is advisable to include the fetal yawning examination in the systematic week 23 ultrasound scan. Future studies will improve its diagnostic value in detecting neuromuscular developmental abnormalities as well as fetal behavioural abnormalities.

A complete review on yawning can be founded in the book: "The Mystery of Yawning in Physiology and Disease". Walusinski O. ed. Basel. Karger. 2010. 160p.

**1. Introduction** 

**19** 

*Australia* 

Madeleine Shanahan

*School of Medical Sciences, RMIT University* 

**Professional Learning in Sonography** 

The healthcare system is in a state of constant and rapid change as a result of the increase in scientific knowledge and rapid technological advances. To provide the best possible healthcare health practitioners must continue to learn throughout their working life. The notion that professionals must continually update their knowledge is not a new concept (1,

*A highly trained person must constantly renew his knowledge. The goal is not merely to keep knowledge already acquired during the period of formal education. Much more than this—for past knowledge may become outdated—the aim is … self-renewal by keeping abreast of new knowledge that is constantly being added to by research and publication.* 

The rate of change of knowledge is increasing and this is reflected in the decreasing 'halflife' of knowledge. The term half-life, borrowed from the field of nuclear physics, represents the process of decay of knowledge such that a half-life of five years indicates that after five years only 50 percent of the body of knowledge acquired at a given point remains relevant to the work task (3). The half-life of knowledge continues to decrease, with, for example, the half-life of medical and scientific knowledge estimated to be between 18 months and three years (4, 5). Akin to medical and scientific knowledge having a short half-life, the knowledge of health professionals is also considered to have a shorthalf life. Professional obsolescence was the term utilised by Dubin (1) to describe the professionals' reduction in competence to meet the demands of their profession with time. Professional obsolescence, Dubin argues is "almost inevitable … without continuous updating … [as] people will carry on their work with increasingly outdated techniques and hypotheses, ignorant of new data, techniques, and principles" (3, p.10). By updating knowledge, professionals grow or appreciate their existing knowledge with new knowledge (3, 6, 7). In essence, to remain competent in their practice, health professionals must advance their knowledge at the same rate as knowledge advances in their field and

The introduction of CPD requirements within professions formalises the need to update knowledge and counterbalance the effect of professional obsolescence (1, 6). CPD requirements are now common and for many health professionals updating knowledge is now a requirement for practice. The Health Professions Council (HPC) in the United Kingdom regulates 15 health professions and introduced mandatory Continuing

Professional Development (CPD) requirements in 2006 (8). The HPC states:

2). For example, Dubin (1 p.486) wrote of professionals:

thus avoid professional obsolescence.

#### **7. References**


### **Professional Learning in Sonography**

#### Madeleine Shanahan

*School of Medical Sciences, RMIT University Australia* 

#### **1. Introduction**

332 Sonography

Bromley B, Benacerraf BR. Fetal Micrognathia: Associated Anomonalies and Outcome.

de Vries JI, Visser GH, Prechtl FM. The emergence of fetal behaviour. *Early Hum Dey*

Einspieler C, Prechtl HF. Prechtl's assessment of general movements: a diagnostic tool for

Guggisberg AG, Mathis J, Schnider A, Hess CW. Why do we yawn? *Neurosci Biobehav Rev.*

Jacob J, Gutrhie S. Facial visceromotor neurons display specific rhombomere origin and

Kontges G, Lumsden A. Rhombencephalic neural crest segmentation is preserved

Kurjak A, Tikvica A, Stanojevic M, Miskovic B, Ahmed B, Azumendi G, Di Renzo GC. The

Luedders DW, Bohlmann MK, Germer U, Axt-Fliedner R, Gembruch U, Weichert J. Fetal

Marder E, Rehm KJ. Development of central pattern generating circuits. *Curr Opin Neurobiol*.

Masuzaki H, Masuzaki M. Color Doppler imaging of fetal yawning. *Ultrasound Obstet* 

Palit G, Jacquemyn Y, Kerremans M. An objective measurement to diagnose micrognathia

Petrikovsky BM, Kaplan GP, Holsten N. Fetal yawning activity in normal and high-risk fetuses: a preliminary observation. *Ultrasound Obstet Gynecol* 1999;13:127-130. Rogers B, Arvedson J.Assessment of infant oral sensorimotor and swallowing function. *Ment* 

Rotten D, Levaillant JM, Martinez H., Ducou le Pointe H, Vicaut E. The fetal mandible: a 2D

Sadler, T.W. Langman's Medical Embriology. Williams & Wilkins, Baltimore. 2009. 414p. Santagati F, Rijli F. Cranial neural crest and the building of the vertebrate head. *Nature Rev* 

Sepulveda W, Mangiamarchi M. Fetal yawning. Ultrasound Obstet Gynecol 1995;5:57-59. van Woerden EE, van Geijn HP, Caron FJ, van der Valk AW, Swartjes JM, Arts NF. Fetal

Walusinski 0, Deputte B. The phylogeny, ethology and nosogeny of yawning. *Rev Neurol*

Yigiter AB, Kavak ZN. Normal standards of fetal behavior assessed by four-dimensional

sonography. *J Matern Fetal Neonatal Med*. 2006;19:707-721.

and 3D sonographic approach to the diagnosis of retrognathia and micrognathia.

mouth movements during behavioural states 1F and 2F. *Europ J Obstet Gynecol*

on prenatal ultrasound. *Clin Exp Obstet Gynecol*. 2008;35:121-123.

Rose RJ. Prenatal programming of behavior. *Neurosci Biobehav Rev*. 2005;29:321-327.

assessment of fetal neurobehavior by three-dimensional and four-dimensional

micrognathia: objective assessment and associated anomalies on prenatal sonogram.

throughout craniofacial ontogeny. *Development* 1996,122:3229-3242.

axon pathfinding behavior. *J Neuosci* 2000;20:7664-7671.

ultrasound. *J Matern Fetal Neonatal Med*. 2008;21:675-684.

the functional assessment of the young nervous system. *Ment Retard Dev Disabil Res* 

**7. References** 

*J Ultrasound Med*. 1994;13:529-533.

1982;7:301-322.

*Rev*. 2005;11:61-67.

2010;34:1267-1276

2005;15:86-93.

*Gynecol* l996;8:355-356.

*Neurosci* 2003;4:806-8l8.

*Reprod Biol* 1988;29:97-105.

2004;l60:1011-1021.

*Prenat Diagn*. 2011;31:1461-51.

*Retard Dev Disabil Res Rev*. 2005;11:74-82.

*Ultrasound Obstet Gynecol*. 2002;19:122-130.

The healthcare system is in a state of constant and rapid change as a result of the increase in scientific knowledge and rapid technological advances. To provide the best possible healthcare health practitioners must continue to learn throughout their working life. The notion that professionals must continually update their knowledge is not a new concept (1, 2). For example, Dubin (1 p.486) wrote of professionals:

*A highly trained person must constantly renew his knowledge. The goal is not merely to keep knowledge already acquired during the period of formal education. Much more than this—for past knowledge may become outdated—the aim is … self-renewal by keeping abreast of new knowledge that is constantly being added to by research and publication.* 

The rate of change of knowledge is increasing and this is reflected in the decreasing 'halflife' of knowledge. The term half-life, borrowed from the field of nuclear physics, represents the process of decay of knowledge such that a half-life of five years indicates that after five years only 50 percent of the body of knowledge acquired at a given point remains relevant to the work task (3). The half-life of knowledge continues to decrease, with, for example, the half-life of medical and scientific knowledge estimated to be between 18 months and three years (4, 5). Akin to medical and scientific knowledge having a short half-life, the knowledge of health professionals is also considered to have a shorthalf life. Professional obsolescence was the term utilised by Dubin (1) to describe the professionals' reduction in competence to meet the demands of their profession with time. Professional obsolescence, Dubin argues is "almost inevitable … without continuous updating … [as] people will carry on their work with increasingly outdated techniques and hypotheses, ignorant of new data, techniques, and principles" (3, p.10). By updating knowledge, professionals grow or appreciate their existing knowledge with new knowledge (3, 6, 7). In essence, to remain competent in their practice, health professionals must advance their knowledge at the same rate as knowledge advances in their field and thus avoid professional obsolescence.

The introduction of CPD requirements within professions formalises the need to update knowledge and counterbalance the effect of professional obsolescence (1, 6). CPD requirements are now common and for many health professionals updating knowledge is now a requirement for practice. The Health Professions Council (HPC) in the United Kingdom regulates 15 health professions and introduced mandatory Continuing Professional Development (CPD) requirements in 2006 (8). The HPC states:

Professional Learning in Sonography 335

Learning involving the use of information sources is theorised as an activity mediated by tools (19-21). In this mediated learning act, tools such as information sources create a learning environment where higher mental function is achievable than when the learner is left to their own unmediated mental functions (21-23). Learning mediated by tools can be represented by Vygotsky's triangular model. The Vygotskian model of mediated learning has three central elements – subject, tool and object. The *subject* is the learner. *Tools* are utilised by the learner to support the learning process. Tools may be external or internal. External tools are humanly created tools, which support learning such as information sources. Internal tools include processes utilised by individual to support learning such as mnemonic techniques and schemas of events or practice (21, 24). The *object* is the goal or motive (22) of the learning activity. Goals may be set by the individual or by some other such as employer or workplace trainer. In the Vygotskian triad, the learner does not simply react to the external world, a recognised limitation of behaviourist learning theories (24, 25) but is viewed as an active agent purposefully utilising external means or mediating tools to achieve their learning goal (26). The application of the Vygotskian model to health professionals updating their knowledge in diagnostic ultrasound is shown in Figure 1.

Fig. 1. Adaptation of Vygotskian model of the health professional utilising information sources as a mediating tool to update their knowledge in diagnostic ultrasound

**Mediating Tool** 

diagnostic ultrasound

Information sources containing new disciplinary knowledge in

providing the patient with the best possible healthcare.

**Subject** 

Health professional with their existing knowledge

Consider the case where the subject is a health professional involved in sonographic practice. To avoid professional obsolescence this health professional utilises information sources that contain new disciplinary knowledge as mediating tools to update their knowledge in diagnostic ultrasound. As a consequence of this activity the health professional's clinical sonographic practice is based on the latest disciplinary knowledge

**Object** 

Updated knowledge in diagnostic ultrasound

Disciplinary knowledge is made public via information sources through a succession of stages (27-30). For example Garvey and Griffith (28) developed a model of knowledge

**3. Learning mediated by information sources** 

*Put simply, CPD is the way health professionals continue to learn and develop throughout their careers so they keep their skills and knowledge up to date and are able to work safely, legally and effectively. (8)* 

In Australia, CPD linked to registration occurred more recently. For example, the Australian Health Ministerial Council (9) approved the *Continuing professional development registration standard*. This standard took effect from 1 July 2010 for ten health professions and a further four health professionals are to be included from 1 July 2012 (10). Health professions that now have mandated CPD requirements include for example, medicine, medical imaging and nursing and members of these professions perform sonography. With the profound changes in diagnostic ultrasound imaging shown throughout this book, updating knowledge relevant to sonography is an issue of increasing significance for many health professionals. Indeed to provide the best possible sonographic practice, all professionals performing sonography must inform and enhance their individual knowledge with the rapidly changing sonographic discipline knowledge.

#### **2. Professional knowledge**

The knowledge base of a profession is composed of the public body of discipline knowledge and the individual knowledge of professionals (11). This distinction between public and individual knowledge is not new. Sir Karl Popper (12) in his writings of the way in which knowledge is created and extended in the scientific community recognised publicly communicated knowledge and the knowledge of the individual. Popper utilised the term objective knowledge to describe publicly shared knowledge artefacts or products and the term subjective knowledge to represent the knowledge of individuals that has not been publicly shared. Other authors (see for example 11, 13-17) have also separated public and individual forms of knowledge. They utilise terms such as explicit, codified or scientific knowledge to describe discipline knowledge that has been communicated, in for example books, journals and conferences. The knowledge of the individual is commonly referred to as tacit knowledge. Higgs and Titchen (17) sub-divide tacit knowledge used by professionals into two categories, professional craft knowledge and personal knowledge. Professional craft knowledge is gained through experience and "embedded in practice" (p.5) and is akin to Schon's (18) 'knowing-in-action' (p.50) and Eraut's (11) process knowledge or 'knowing how' (p.107). Higgs and Titchen (17) contend that through articulation, sharing and critical review, at for example conferences and in journal articles, professional craft knowledge can be transformed from tacit knowledge to public discipline knowledge. According to Higgs and Titchen (17), the second form of tacit knowledge utilised by health professionals, is personal knowledge. This form of knowledge is gained through life experiences, allowing the health professional to "enter the life-world of their patients" (p.6) providing empathic care tailored to the needs of their patient.

Professionals integrate public discipline knowledge and their tacit knowledge in clinical practice (11, 16, 17). As previously noted, public discipline knowledge is communicated through information sources such as books, journals and conferences. With the rapid rate of change of knowledge in diagnostic ultrasound, health professionals must therefore engage in a continuing process of accessing new knowledge disseminated through information sources, internalising it into their tacit knowledge and then utilising it in clinical practice.

*Put simply, CPD is the way health professionals continue to learn and develop throughout their careers so they keep their skills and knowledge up to date and are able to work safely,* 

In Australia, CPD linked to registration occurred more recently. For example, the Australian Health Ministerial Council (9) approved the *Continuing professional development registration standard*. This standard took effect from 1 July 2010 for ten health professions and a further four health professionals are to be included from 1 July 2012 (10). Health professions that now have mandated CPD requirements include for example, medicine, medical imaging and nursing and members of these professions perform sonography. With the profound changes in diagnostic ultrasound imaging shown throughout this book, updating knowledge relevant to sonography is an issue of increasing significance for many health professionals. Indeed to provide the best possible sonographic practice, all professionals performing sonography must inform and enhance their individual knowledge with the

The knowledge base of a profession is composed of the public body of discipline knowledge and the individual knowledge of professionals (11). This distinction between public and individual knowledge is not new. Sir Karl Popper (12) in his writings of the way in which knowledge is created and extended in the scientific community recognised publicly communicated knowledge and the knowledge of the individual. Popper utilised the term objective knowledge to describe publicly shared knowledge artefacts or products and the term subjective knowledge to represent the knowledge of individuals that has not been publicly shared. Other authors (see for example 11, 13-17) have also separated public and individual forms of knowledge. They utilise terms such as explicit, codified or scientific knowledge to describe discipline knowledge that has been communicated, in for example books, journals and conferences. The knowledge of the individual is commonly referred to as tacit knowledge. Higgs and Titchen (17) sub-divide tacit knowledge used by professionals into two categories, professional craft knowledge and personal knowledge. Professional craft knowledge is gained through experience and "embedded in practice" (p.5) and is akin to Schon's (18) 'knowing-in-action' (p.50) and Eraut's (11) process knowledge or 'knowing how' (p.107). Higgs and Titchen (17) contend that through articulation, sharing and critical review, at for example conferences and in journal articles, professional craft knowledge can be transformed from tacit knowledge to public discipline knowledge. According to Higgs and Titchen (17), the second form of tacit knowledge utilised by health professionals, is personal knowledge. This form of knowledge is gained through life experiences, allowing the health professional to "enter the life-world of their patients" (p.6)

Professionals integrate public discipline knowledge and their tacit knowledge in clinical practice (11, 16, 17). As previously noted, public discipline knowledge is communicated through information sources such as books, journals and conferences. With the rapid rate of change of knowledge in diagnostic ultrasound, health professionals must therefore engage in a continuing process of accessing new knowledge disseminated through information sources, internalising it into their tacit knowledge and then utilising it in

*legally and effectively. (8)* 

**2. Professional knowledge** 

clinical practice.

rapidly changing sonographic discipline knowledge.

providing empathic care tailored to the needs of their patient.

#### **3. Learning mediated by information sources**

Learning involving the use of information sources is theorised as an activity mediated by tools (19-21). In this mediated learning act, tools such as information sources create a learning environment where higher mental function is achievable than when the learner is left to their own unmediated mental functions (21-23). Learning mediated by tools can be represented by Vygotsky's triangular model. The Vygotskian model of mediated learning has three central elements – subject, tool and object. The *subject* is the learner. *Tools* are utilised by the learner to support the learning process. Tools may be external or internal. External tools are humanly created tools, which support learning such as information sources. Internal tools include processes utilised by individual to support learning such as mnemonic techniques and schemas of events or practice (21, 24). The *object* is the goal or motive (22) of the learning activity. Goals may be set by the individual or by some other such as employer or workplace trainer. In the Vygotskian triad, the learner does not simply react to the external world, a recognised limitation of behaviourist learning theories (24, 25) but is viewed as an active agent purposefully utilising external means or mediating tools to achieve their learning goal (26). The application of the Vygotskian model to health professionals updating their knowledge in diagnostic ultrasound is shown in Figure 1.

Fig. 1. Adaptation of Vygotskian model of the health professional utilising information sources as a mediating tool to update their knowledge in diagnostic ultrasound

Consider the case where the subject is a health professional involved in sonographic practice. To avoid professional obsolescence this health professional utilises information sources that contain new disciplinary knowledge as mediating tools to update their knowledge in diagnostic ultrasound. As a consequence of this activity the health professional's clinical sonographic practice is based on the latest disciplinary knowledge providing the patient with the best possible healthcare.

Disciplinary knowledge is made public via information sources through a succession of stages (27-30). For example Garvey and Griffith (28) developed a model of knowledge

Professional Learning in Sonography 337

major online health resource for professionals employed in the public health sector in the Australian state of Victoria. This study (n=233) reported that the four most frequently utilised information sources to refresh knowledge were workshops and seminars (85%), conferences (83%), textbooks (73%) and print journals (72%). When the activity was background research, these health professionals utilise print journals (66%), academic based websites (65%), Internet search engines (61%) and electronic journals (57%). In contrast, when the activity was to assist with clinical diagnosis, the information sources utilised were consultation with colleagues (59%), textbooks (58%), print journals (43%), and academic based websites (36%). Three important aspects of information source use by health professionals at the beginning of the 21st century are demonstrated in this study. First, this study demonstrates that the selection of information sources, or as represented in the Vygotskian model mediating tools, are dependent on purpose of use, or object of activity. Second, seminars and conferences, as identified in the Garvey and Griffth model (28), remain important information sources for updating knowledge. This is evidenced by workshops, seminars and conferences being the top information sources utilised to "refresh knowledge". Third, print journals were, at the time of the study, utilised by a larger number of respondents than electronic journals. Other studies have also demonstrated that health professionals prefer print based information sources such as journals. Davies (47) identified eight studies in which medical practitioners ranked their preference for or identified their use of print and electronic information sources. Each of these studies, published between 2002 and 2005, reported that print-based information sources were preferred or utilised over electronic information sources by medical practitioners. The continued preference for or use of print-based information sources such as journals appears counterintuitive in the digital era where electronic information sources made available through the Internet are considered central to communicating new knowledge (30, 48) and more generally learning (13, 49, 50). None of the reviewed studies specifically identified health professionals engaged in sonographic practice and so it is not known what information sources they utilise as mediating tools to update their professional knowledge in diagnostic ultrasound. The following section provides research data investigating the use of information sources as

mediating tools in professional updating activity by Australian Sonographers.

The following section discusses research findings from a larger study investigating professional updating activity by Australian Medical Imaging Workers (MIWs). MIWs includes Radiographers, Radiation Therapists, Nuclear Medicine Technologists and Sonographers (51, 52). There were over 10,477 Medical Imaging Workers in Australia in 2006 and of these 2127 were Sonographers. The number of Sonographers increased by 50% between 2001 and 2006 (52) demonstrating one of the most rapid rates of growth of any health profession in Australia. The need to understand how this rapidly growing profession maintains currency of professional knowledge thus is of increasing significance in the 21st

This study utilised a two-phase sequential exploratory design (53, 54). This two-phase design collected and analysed qualitative data (Phase 1), which was used to inform the

**4. Professional updating activity of Australian Sonographers** 

century.

**4.1 Research study** 

dissemination based on the psychology profession. This study identified a succession of stages through which new research findings are communicated within the profession. Initially research findings are disseminated orally through for example seminars and then to larger audiences at state or national meeting of their professional society. Many psychologists then utilise feedback from seminars and conferences to prepare the manuscript for submission to a journal. Finally, Garvey and Griffith contend that new research findings are cited in other journal articles and appear in books and this stage represents the assimilation of new research into the discipline's public knowledge base. Whilst the Garvey-Griffith model was developed from research based on the psychology profession, the succession of stages is similar across many professional fields (27, 29). The Garvey-Griffith model was developed before the Internet and the World Wide Web transformed the scientific communication process. Describing the Garvey-Griffith model as a model of scientific communication for the print era, Hurd (30) adapted the model for the digital era. Whereas the Garvey-Griffith model had professionals disseminating research findings initially through face-to-face seminars and annual conferences and then through print journals, the Hurd model showed the initial phase of research dissemination occurring primarily through Internet-enabled tools such as listservs, web pages and e-conferences.

The Internet is recognised as an important information source for health professional offering immediate access to the most current health and medical information. Web sites of professional, government, education and commercial organisations are utilised by health professionals to access online journals, health and medical databases, practice guidelines, image banks and case studies as well as information on professional development activities (see for example 31, 32-39). Internet based communication tools of e-mail, listservs and discussion forums are used by health professionals to consult with colleagues nationally and internationally (31, 32, 34, 35, 39).

Whilst the Internet offers access to large quantities of information the lack of quality control over information on the Internet means that its use as a major information source for health professionals has been limited (40). To take advantage of the perceived accessibility of electronic information whilst overcoming the disadvantages of variable quality of information, governments in Australia and internationally have developed Electronic Information Portals to provide health professionals with up-to-date information to inform their clinical practice. Examples of these portals include NHS-net (Internet access for the National Health System) in the UK; National electronic Library for Health (NeLH) in the UK; Hospital Authority Library Information Systems (HALIS) in Hong Kong; Clinical Information Access Program (CIAP), New South Wales, Australia, Clinicians Health Channel, Victoria; Australia and Clinicians Knowledge Network, Queensland, Australia. These portals provide health professionals with access to a range of information sources including health and medical databases, e-journals, e-books and clinical guidelines have also been identified by health professionals as an important information source for updating their professional knowledge (41-46).

The Hurd model and the proliferation of electronic media suggests that to update knowledge in the 21st century health professionals would favour and utilise Internet-based tools over both traditional face-to-face conferences and seminars. However, research examining the use of information sources by health professionals does not support this contention. Keppell and colleagues (45) investigated the use of Clinicians Health Channel, a

dissemination based on the psychology profession. This study identified a succession of stages through which new research findings are communicated within the profession. Initially research findings are disseminated orally through for example seminars and then to larger audiences at state or national meeting of their professional society. Many psychologists then utilise feedback from seminars and conferences to prepare the manuscript for submission to a journal. Finally, Garvey and Griffith contend that new research findings are cited in other journal articles and appear in books and this stage represents the assimilation of new research into the discipline's public knowledge base. Whilst the Garvey-Griffith model was developed from research based on the psychology profession, the succession of stages is similar across many professional fields (27, 29). The Garvey-Griffith model was developed before the Internet and the World Wide Web transformed the scientific communication process. Describing the Garvey-Griffith model as a model of scientific communication for the print era, Hurd (30) adapted the model for the digital era. Whereas the Garvey-Griffith model had professionals disseminating research findings initially through face-to-face seminars and annual conferences and then through print journals, the Hurd model showed the initial phase of research dissemination occurring primarily through Internet-enabled tools such as listservs, web pages and e-conferences.

The Internet is recognised as an important information source for health professional offering immediate access to the most current health and medical information. Web sites of professional, government, education and commercial organisations are utilised by health professionals to access online journals, health and medical databases, practice guidelines, image banks and case studies as well as information on professional development activities (see for example 31, 32-39). Internet based communication tools of e-mail, listservs and discussion forums are used by health professionals to consult with colleagues nationally and

Whilst the Internet offers access to large quantities of information the lack of quality control over information on the Internet means that its use as a major information source for health professionals has been limited (40). To take advantage of the perceived accessibility of electronic information whilst overcoming the disadvantages of variable quality of information, governments in Australia and internationally have developed Electronic Information Portals to provide health professionals with up-to-date information to inform their clinical practice. Examples of these portals include NHS-net (Internet access for the National Health System) in the UK; National electronic Library for Health (NeLH) in the UK; Hospital Authority Library Information Systems (HALIS) in Hong Kong; Clinical Information Access Program (CIAP), New South Wales, Australia, Clinicians Health Channel, Victoria; Australia and Clinicians Knowledge Network, Queensland, Australia. These portals provide health professionals with access to a range of information sources including health and medical databases, e-journals, e-books and clinical guidelines have also been identified by health professionals as an important information source for updating

The Hurd model and the proliferation of electronic media suggests that to update knowledge in the 21st century health professionals would favour and utilise Internet-based tools over both traditional face-to-face conferences and seminars. However, research examining the use of information sources by health professionals does not support this contention. Keppell and colleagues (45) investigated the use of Clinicians Health Channel, a

internationally (31, 32, 34, 35, 39).

their professional knowledge (41-46).

major online health resource for professionals employed in the public health sector in the Australian state of Victoria. This study (n=233) reported that the four most frequently utilised information sources to refresh knowledge were workshops and seminars (85%), conferences (83%), textbooks (73%) and print journals (72%). When the activity was background research, these health professionals utilise print journals (66%), academic based websites (65%), Internet search engines (61%) and electronic journals (57%). In contrast, when the activity was to assist with clinical diagnosis, the information sources utilised were consultation with colleagues (59%), textbooks (58%), print journals (43%), and academic based websites (36%). Three important aspects of information source use by health professionals at the beginning of the 21st century are demonstrated in this study. First, this study demonstrates that the selection of information sources, or as represented in the Vygotskian model mediating tools, are dependent on purpose of use, or object of activity. Second, seminars and conferences, as identified in the Garvey and Griffth model (28), remain important information sources for updating knowledge. This is evidenced by workshops, seminars and conferences being the top information sources utilised to "refresh knowledge". Third, print journals were, at the time of the study, utilised by a larger number of respondents than electronic journals. Other studies have also demonstrated that health professionals prefer print based information sources such as journals. Davies (47) identified eight studies in which medical practitioners ranked their preference for or identified their use of print and electronic information sources. Each of these studies, published between 2002 and 2005, reported that print-based information sources were preferred or utilised over electronic information sources by medical practitioners. The continued preference for or use of print-based information sources such as journals appears counterintuitive in the digital era where electronic information sources made available through the Internet are considered central to communicating new knowledge (30, 48) and more generally learning (13, 49, 50).

None of the reviewed studies specifically identified health professionals engaged in sonographic practice and so it is not known what information sources they utilise as mediating tools to update their professional knowledge in diagnostic ultrasound. The following section provides research data investigating the use of information sources as mediating tools in professional updating activity by Australian Sonographers.

#### **4. Professional updating activity of Australian Sonographers**

The following section discusses research findings from a larger study investigating professional updating activity by Australian Medical Imaging Workers (MIWs). MIWs includes Radiographers, Radiation Therapists, Nuclear Medicine Technologists and Sonographers (51, 52). There were over 10,477 Medical Imaging Workers in Australia in 2006 and of these 2127 were Sonographers. The number of Sonographers increased by 50% between 2001 and 2006 (52) demonstrating one of the most rapid rates of growth of any health profession in Australia. The need to understand how this rapidly growing profession maintains currency of professional knowledge thus is of increasing significance in the 21st century.

#### **4.1 Research study**

This study utilised a two-phase sequential exploratory design (53, 54). This two-phase design collected and analysed qualitative data (Phase 1), which was used to inform the

Professional Learning in Sonography 339

something like that but it is a large, it is a constant sort of impact on you in the fact that it's

Non-teaching hospital

Graduate Diploma/ Cert

Associate Diploma / Cert

b The responses to this organisation factor exclude Sonographers who indicated they worked in more

**Mediating tool Percent a (No.)** 

National conference of professional society 97 (59) Journals 95 (58) Internet search engines 95 (56) Web pages 95 (56) Text and reference books 89 (54) Health and medical databases 84 (48) Seminars 68 (41) Government Electronic Health Information Portal eg CHC, CKN 18 (10) International conference 10 ( 6)

Table 2. Information sources utilised by Sonographers to update professional knowledge

Rural and remote

26 (46) 33 (54)

28 (48) 8 (14) 22 (38)

32 (53) 19 (31) 10 (16)

 6 (10) 12 (20) 9 (15) 34 (56)

 0 ( 0) 9 (15) 43 (71) 3 ( 5) 5 ( 8) 1 ( 2)

44 (73) 16 (27)

 6 (10) 19 (31) 21 (34) 12 (20) 3 ( 5)

**Characteristic No. (%)a**

Private

Clinic

Regional

< 5 years 5 – 10 years 11- 15 years >15 years

Master

Bachelor Diploma

Male

30 – 39 40 – 49 50 – 60 >60

a Percentages are based upon number of respondents answering each question.

Table 1. Demographic characteristics of respondent Sonographers (n=61)

a Percentages are based upon number of respondents answering each question.

than one type of these environment and those who selected "other"

learning day after day".

Years of professional

experience

Employer Public

Work environment b Teaching hospital

Geographic location Metropolitan

Level of education Doctorate

Gender Female

Age (years) 20 – 29

quantitative phase (Phase 2) of data collection and analysis (54-56). In the context of this study, interviews were conducted with 28 Medical Imaging Workers, six of whom specialised in Sonography. Interview data was utilised to develop the four-page questionnaire mailed to a random sample of 1142 practitioners holding registration with an Australian Medical Radiation Technologists Board (MRTB). Surveys were returned from 362 MIWs with analysis demonstrating that the sample was representative for area of specialisation and gender (39). Sixty-one survey respondents specialised in Sonography.

The survey data were entered into SPSS 17.0® and descriptive and inferential statistics were used for analysis. Percentages were used to describe survey findings. The collected data allowed for differences between groups to be examined using chi-square analysis using Fisher's exact test. In particular, this paper examines the value Sonographers (N=67) attribute to information sources as tools for updating professional knowledge, frequency of use of these tools within the context of professional knowledge updating activity and identifies factors that afford or constrain access to these information sources,

#### **4.2 Results and discussion**

Table 1 displays the demographic characteristics of Sonographers who participated in the survey component of the study. All age ranges were represented in the respondents with 65% of responding Sonographers aged between 30-49 years. This figure is consistent with data from Australian Health and Community Labour Force statistics where the average age for Sonographers was 39 years (52). Over half (56%) of respondents had professional experience of more than 15 years. The majority of Sonographers were female (72.4%), a finding consistent with gender data from Australian Health and Community Labour Force statistics where females account for 77% of Sonographers. The highest qualification for the majority of responding Sonographers practitioners was at the post-graduate level (86%) with 15% (n=9) of respondents undertaking further study. A majority of Sonographers were employed in metropolitan locations (53%) and in the Private Sector (54%).

Almost all Sonographers (97%, n=59)) held membership with one (38%) or more (59%) professional societies. Of the Sonographers holding membership with an Australian professional society, 85% held membership with the Australian Sonographers Association and 46% with Australian Society of Ultrasound in Medicine. Nine percent (n=5) held membership with an overseas professional society. Ninety-three percent (n=57) of responding Sonographers reported they were enrolled in a CPD program.

#### **Mediating tools in professional updating activity**

Survey data was examined to determine use of a range of information sources as mediating tools to update professional knowledge. The results are summarised in Table 2.

#### **Conferences**

Ninety-seven percent (n=59) of Sonographers identified that they attend national conferences of professional societies, with 51% attending one (36%) or more (15%) conferences each year. Ten percent (n=6) reported attending international conferences to update their professional knowledge with half (n=3) attending at least every second year. Conferences were valued for the intense nature of learning that they enabled "it was 7 in the morning til - we went to lectures until 6 at night and I found that invaluable going to

quantitative phase (Phase 2) of data collection and analysis (54-56). In the context of this study, interviews were conducted with 28 Medical Imaging Workers, six of whom specialised in Sonography. Interview data was utilised to develop the four-page questionnaire mailed to a random sample of 1142 practitioners holding registration with an Australian Medical Radiation Technologists Board (MRTB). Surveys were returned from 362 MIWs with analysis demonstrating that the sample was representative for area of specialisation and gender (39). Sixty-one survey respondents specialised in Sonography.

The survey data were entered into SPSS 17.0® and descriptive and inferential statistics were used for analysis. Percentages were used to describe survey findings. The collected data allowed for differences between groups to be examined using chi-square analysis using Fisher's exact test. In particular, this paper examines the value Sonographers (N=67) attribute to information sources as tools for updating professional knowledge, frequency of use of these tools within the context of professional knowledge updating activity and

Table 1 displays the demographic characteristics of Sonographers who participated in the survey component of the study. All age ranges were represented in the respondents with 65% of responding Sonographers aged between 30-49 years. This figure is consistent with data from Australian Health and Community Labour Force statistics where the average age for Sonographers was 39 years (52). Over half (56%) of respondents had professional experience of more than 15 years. The majority of Sonographers were female (72.4%), a finding consistent with gender data from Australian Health and Community Labour Force statistics where females account for 77% of Sonographers. The highest qualification for the majority of responding Sonographers practitioners was at the post-graduate level (86%) with 15% (n=9) of respondents undertaking further study. A majority of Sonographers were

Almost all Sonographers (97%, n=59)) held membership with one (38%) or more (59%) professional societies. Of the Sonographers holding membership with an Australian professional society, 85% held membership with the Australian Sonographers Association and 46% with Australian Society of Ultrasound in Medicine. Nine percent (n=5) held membership with an overseas professional society. Ninety-three percent (n=57) of responding

Survey data was examined to determine use of a range of information sources as mediating

Ninety-seven percent (n=59) of Sonographers identified that they attend national conferences of professional societies, with 51% attending one (36%) or more (15%) conferences each year. Ten percent (n=6) reported attending international conferences to update their professional knowledge with half (n=3) attending at least every second year. Conferences were valued for the intense nature of learning that they enabled "it was 7 in the morning til - we went to lectures until 6 at night and I found that invaluable going to

tools to update professional knowledge. The results are summarised in Table 2.

identifies factors that afford or constrain access to these information sources,

employed in metropolitan locations (53%) and in the Private Sector (54%).

Sonographers reported they were enrolled in a CPD program.

**Mediating tools in professional updating activity** 

**Conferences** 

**4.2 Results and discussion** 

something like that but it is a large, it is a constant sort of impact on you in the fact that it's learning day after day".


a Percentages are based upon number of respondents answering each question.

b The responses to this organisation factor exclude Sonographers who indicated they worked in more than one type of these environment and those who selected "other"

Table 1. Demographic characteristics of respondent Sonographers (n=61)


a Percentages are based upon number of respondents answering each question.

Table 2. Information sources utilised by Sonographers to update professional knowledge

Professional Learning in Sonography 341

Sonographers report having access to print (97%, n=58) and electronic journals (93%, n=54) in their workplace. Sonographers also identified that there are a number of journals of relevance to diagnostic ultrasound that they could not currently access but needed access. The journal titles and the percent of respondents were: Journal of Diagnostic Medical Ultrasound (43%), American Journal of Obstetrics & Gynaecology (41%), Ultrasound in Obstetrics & Gynaecology (39%), Journal of Vascular Ultrasound (34%), Journal of Ultrasound in Medicine (33%), Journal of Clinical Ultrasound (32%), Ultrasonic Imaging (29%), Seminars in Ultrasound, CT & MRI (28%), and Obstetric & Gynecology Clinics of North America (27%). It is important that professionals engaging in diagnostic ultrasound have access to disciplinary knowledge disseminated through journals. This study identifies that there is a need to review the journals available in the workplace and determine if journals available are meeting the needs of health professionals performing the range of

The majority of Sonographers (95%, n=56) used web sites to update their professional knowledge. National and international professional organisation web sites were valued by Sonographers as they provided access to needed resources "so you can get every article that has been published on the web if you are a member" and "they have guidelines for particular scans that they update so they give you information about minimum requirements for certain types of scans". In addition Sonographers valued online discussion forums "if anyone has a question you have an open forum where you ask how do you deal with things, has anyone seen this before, those sort of daily information, they put it on the website and its open for discussion". Web sites were also valued for providing access to "very good images" demonstrating normal anatomy and pathology. Internet search engines such as Google (95%) and to a lesser extent Google Scholar (40%, n=21) were also utilised to update knowledge. Search engines were used to obtain information on pathologies "we look up various things on the Internet because very often in daily scanning pathology comes through that we are not familiar with and I find I sit down at the computer and look it up". Sonographers also searched for "examples of pictures of what a particular pathology looks

like and more information about that pathology" to inform their clinical practice.

learning through the universal inclusion of the Internet onto all computers.

The majority of Sonographers (94%, n=57) indicated that there was access to the Internet in the workplace. Half (51%) of the respondents indicated that the Internet was available on all workplace computers. Two-thirds (66%) of Sonographers who reported Internet access on all workplaces computers undertake Internet searches for professional reasons several times a week. However, in workplaces where the Internet was restricted to Offices (17%), only 22% of respondents undertook Internet searches several times a week. As one Sonographer commented "I do have Internet access here but we, this particular practice we just have the one computer, it's the same one that we use for typing our reports and everything so we don't tend to get on that very often". Workplaces can therefore support professional

Eighty-nine percent (n=54) of Sonographers read text and reference books to update their professional knowledge, with 79% using these books at least several times a month. All responding Sonographers reported that they had access to text and reference books in their

diagnostic ultrasound procedures undertaken in their practice.

**Internet web pages and search engines** 

**Books** 

Ninety percent (n=55) of respondents reported that their workplace provided them with leave to attend conferences. The financial cost of attending conferences was shared primarily by the Sonographer who self-funded 45% (Mean) of the cost of attendance and the workplace who provided 45% (Mean) of the cost of conference attendance. Financial support was also received from professional societies, (8% Mean). Difference in support by the workplace, through the provision of leave and financial support to attend conference, was not statistically significant (p>.05) across health sector (public, private), geographic location (Metropolitan, regional, rural or remote) or workplace type (teaching hospital, nonteaching hospital, clinic).

#### **Searching for and reading professional literature**

The vast majority of Sonographers (98%, n=60) report that they search for and read information on a weekly basis to update professional knowledge. Seventy-four percent (n=45) report reading for one hour or more per week to update their professional knowledge, with 28% (n=17) reading three or more hours per week. Eighty-two percent (n=49) of Sonographers identified that their workplace did not provide dedicated time during work hours to undertake professional reading activities. The greatest variance in the provision of time for professional reading activities by workplaces existed across health sector with 94% (n=30) of Sonographers employed in the private sector not receiving dedicated time for this activity compared to 68% (n=19) of those employed in the public sector, with the difference trending toward statistical significance (Fisher's Exact Test = 6.553, p=.057). Sonographers identified that whilst valuable information sources were available in the workplace they lacked time to use them, stating for example, "No time to access the journals at work".

Time is recognised as a major barrier to updating professional knowledge by health professionals (33, 34, 57-59). In recent studies of Australian health professionals the provision of protected time, that is time during work hours when health professionals are not engaged in clinical or teaching duties, have been reported. For example, 58.1% of Australian and New Zealand Radiation Oncologists reported they had access to 'protected time' for non-clinical or teaching activities such as professional reading (60). Over half (52%) of Australian Radiation Therapists reported that they were provided with 'protected time' for professional reading activity (61), a level quite similar to that reported by Radiation Oncologists. In contrast, a minority (20.6%) of Australian Radiographers were provided with 'protected time' to engage in professional reading activity (62). It is apparent from this study that the provision of 'protected time' to Sonographers is low with just 18% reporting that their workplace provides this support. Whilst variation in support across health sector was evident (6-32%), the level of support for 'protected time' for Sonographers was much lower than their colleagues working in Radiation Oncology and Radiation Therapy. Greater provision of 'protected time' for Sonographers should be investigated.

As displayed in Table 2, Sonographers read journals (95%), Internet web pages (95%) and text and reference books (89%) to update their knowledge and they search for professional information using Internet search engines (95%) and health and medical databases (84%).

#### **Journals**

Ninety-five percent (n=58) of Sonographers read journals to update their professional knowledge, with 56% reading journals at least several times a month. The majority of

Ninety percent (n=55) of respondents reported that their workplace provided them with leave to attend conferences. The financial cost of attending conferences was shared primarily by the Sonographer who self-funded 45% (Mean) of the cost of attendance and the workplace who provided 45% (Mean) of the cost of conference attendance. Financial support was also received from professional societies, (8% Mean). Difference in support by the workplace, through the provision of leave and financial support to attend conference, was not statistically significant (p>.05) across health sector (public, private), geographic location (Metropolitan, regional, rural or remote) or workplace type (teaching hospital, non-

The vast majority of Sonographers (98%, n=60) report that they search for and read information on a weekly basis to update professional knowledge. Seventy-four percent (n=45) report reading for one hour or more per week to update their professional knowledge, with 28% (n=17) reading three or more hours per week. Eighty-two percent (n=49) of Sonographers identified that their workplace did not provide dedicated time during work hours to undertake professional reading activities. The greatest variance in the provision of time for professional reading activities by workplaces existed across health sector with 94% (n=30) of Sonographers employed in the private sector not receiving dedicated time for this activity compared to 68% (n=19) of those employed in the public sector, with the difference trending toward statistical significance (Fisher's Exact Test = 6.553, p=.057). Sonographers identified that whilst valuable information sources were available in the workplace they lacked time to use them, stating for example, "No time to

Time is recognised as a major barrier to updating professional knowledge by health professionals (33, 34, 57-59). In recent studies of Australian health professionals the provision of protected time, that is time during work hours when health professionals are not engaged in clinical or teaching duties, have been reported. For example, 58.1% of Australian and New Zealand Radiation Oncologists reported they had access to 'protected time' for non-clinical or teaching activities such as professional reading (60). Over half (52%) of Australian Radiation Therapists reported that they were provided with 'protected time' for professional reading activity (61), a level quite similar to that reported by Radiation Oncologists. In contrast, a minority (20.6%) of Australian Radiographers were provided with 'protected time' to engage in professional reading activity (62). It is apparent from this study that the provision of 'protected time' to Sonographers is low with just 18% reporting that their workplace provides this support. Whilst variation in support across health sector was evident (6-32%), the level of support for 'protected time' for Sonographers was much lower than their colleagues working in Radiation Oncology and Radiation Therapy. Greater

As displayed in Table 2, Sonographers read journals (95%), Internet web pages (95%) and text and reference books (89%) to update their knowledge and they search for professional information using Internet search engines (95%) and health and medical databases (84%).

Ninety-five percent (n=58) of Sonographers read journals to update their professional knowledge, with 56% reading journals at least several times a month. The majority of

provision of 'protected time' for Sonographers should be investigated.

teaching hospital, clinic).

access the journals at work".

**Journals** 

**Searching for and reading professional literature** 

Sonographers report having access to print (97%, n=58) and electronic journals (93%, n=54) in their workplace. Sonographers also identified that there are a number of journals of relevance to diagnostic ultrasound that they could not currently access but needed access. The journal titles and the percent of respondents were: Journal of Diagnostic Medical Ultrasound (43%), American Journal of Obstetrics & Gynaecology (41%), Ultrasound in Obstetrics & Gynaecology (39%), Journal of Vascular Ultrasound (34%), Journal of Ultrasound in Medicine (33%), Journal of Clinical Ultrasound (32%), Ultrasonic Imaging (29%), Seminars in Ultrasound, CT & MRI (28%), and Obstetric & Gynecology Clinics of North America (27%). It is important that professionals engaging in diagnostic ultrasound have access to disciplinary knowledge disseminated through journals. This study identifies that there is a need to review the journals available in the workplace and determine if journals available are meeting the needs of health professionals performing the range of diagnostic ultrasound procedures undertaken in their practice.

#### **Internet web pages and search engines**

The majority of Sonographers (95%, n=56) used web sites to update their professional knowledge. National and international professional organisation web sites were valued by Sonographers as they provided access to needed resources "so you can get every article that has been published on the web if you are a member" and "they have guidelines for particular scans that they update so they give you information about minimum requirements for certain types of scans". In addition Sonographers valued online discussion forums "if anyone has a question you have an open forum where you ask how do you deal with things, has anyone seen this before, those sort of daily information, they put it on the website and its open for discussion". Web sites were also valued for providing access to "very good images" demonstrating normal anatomy and pathology. Internet search engines such as Google (95%) and to a lesser extent Google Scholar (40%, n=21) were also utilised to update knowledge. Search engines were used to obtain information on pathologies "we look up various things on the Internet because very often in daily scanning pathology comes through that we are not familiar with and I find I sit down at the computer and look it up". Sonographers also searched for "examples of pictures of what a particular pathology looks like and more information about that pathology" to inform their clinical practice.

The majority of Sonographers (94%, n=57) indicated that there was access to the Internet in the workplace. Half (51%) of the respondents indicated that the Internet was available on all workplace computers. Two-thirds (66%) of Sonographers who reported Internet access on all workplaces computers undertake Internet searches for professional reasons several times a week. However, in workplaces where the Internet was restricted to Offices (17%), only 22% of respondents undertook Internet searches several times a week. As one Sonographer commented "I do have Internet access here but we, this particular practice we just have the one computer, it's the same one that we use for typing our reports and everything so we don't tend to get on that very often". Workplaces can therefore support professional learning through the universal inclusion of the Internet onto all computers.

#### **Books**

Eighty-nine percent (n=54) of Sonographers read text and reference books to update their professional knowledge, with 79% using these books at least several times a month. All responding Sonographers reported that they had access to text and reference books in their

Professional Learning in Sonography 343

Table 3. Ordered ranking of importance of information sources for professional updating

The difference in ranking across information sources was statistically significant

The rapidly changing science and technology underpinning diagnostic ultrasound imaging require professionals to engage in a continued process of updating their knowledge. This process utilises information sources as mediating tools in learning. This study identifies that a range of information sources are utilised to update professional knowledge, with seminars and conferences ranked as most important. A number of recommendations were also identified to support professional updating activity. These include: workplaces examine the journals available to determine if they have adequate coverage of diagnostic ultrasound; universal inclusion of Internet access onto workplace computers; provision of remote access to workplace electronic resources such as journals; greater provision of 'protected time' to support professional learning activities; and professional development activities focused on extending knowledge of electronic resources. As this study was conducted in Australia, the results may not have validity in other settings outside of Australia. The author encourages other researchers to build upon this work so that the body of knowledge on professional

[1] Dubin SS. Obsolescence or lifelong education: A choice for the professional. American

[2] Houle CO. Continuing learning in the professions. San Francisco: Jossey-Bass Inc.; 1980.

 = = ≤ 47.784, 6, .001 *df p* . Seminars, conferences and text and reference books were ranked as the top three information sources for professional updating activity, respectively. This top three ranking is in accord with the study by Keppell and colleagues (45) where health professionals ranked the importance of information sources they used to "refresh knowledge". When we consider the traditional model of scientific communication has new knowledge disseminated initially through seminars and conferences and then through journals and books (27-29), the importance Sonographers attribute to seminars and conferences for updating professional knowledge is not then surprising. Despite the 21st century being described as the electronic age, it is important to recognise that non-electronic information sources continue to be highly valued and used by health professionals to

Importance of seminars 2.97 Importance of conference 3.46 Importance of text and reference books 3.56 Importance of Internet 4.08 Importance of print journals 4.38 Importance of electronic journals 4.73 Importance of databases 4.82

activity

χ

( ) <sup>2</sup>

update their professional knowledge.

learning in Sonography is developed.

Psychologist 1972;27(5):486-498.

**5. Conclusion** 

**6. References** 

Mean Rank

workplace. Sonographers identified there "are still very good textbooks" but were also cautious about using books stating "by the time the text books are out the information is a couple of years old" and "by the time they are printed the images are fairly old".

#### **Health and medical databases**

Eighty-four percent of respondents report utilising health and medical databases to update knowledge. The most commonly utilised databases were Medline (70%, n=40), PubMed (62%, n=36), Informit or Meditext (23%, n=11), Cochrane Library (20%, n=11) and CINAHL (Cumulative Index of Nursing and Allied Health, 16%, n=9). Apart from Medline where only 8% of respondents were unaware of the resource, a large number of Sonographers were unaware of other health and medical databases, EMBASE (88%), CINAHL (77%), Cochrane Library (70%) Informit or Meditext (71%) and PubMed (27%).

Eighteen percent of Sonographers reported that they use government provided electronic health information portals such as Clinicians Knowledge Network (CKN) and Clinicians Health Channel (CHC). Amongst respondents, there was a low level of awareness (33%, n=18) of these government portals. Use of these government health information portals was higher amongst Sonographers employed in the public sector (36%, n=9) compared to the private sector (3%, n=1). This finding is not surprising, as these resources are made available to employees in the public sector only.

Given the low level of awareness of health and medical databases and government electronic information portals, there is an immediate need for professional development activities aimed at expanding the knowledge base of health professionals so they can more fully engage with the electronic health information world that is available.

The majority of Sonographers (69%, n=38) were not able to remotely access electronic information resources available in the workplace such as journals and databases from home. Sonographers identified that professionally relevant information sources could be made more available through the facility of remote access to workplace resources. As the vast majority of Sonographers had Internet access at home (97%), remote access to workplace e-resources would be a useful feature providing these professionals with greater flexibility in terms of when and where they can access needed information sources.

#### **Seminars**

Sixty-eight percent of Sonographers attended seminars to update their knowledge. Fifty percent (n=30) attended seminars conducted by a professional society, 22% (n=13) attended seminars organised by their workplace and 15% (n=9) attended seminars organised by Vendors. Seminars were valued as they provided information on "applications for their equipment" and also provided Sonographers with access to leaders in their field "people who do cutting edge stuff and that sort of spreads the word … in seminars rather than in publishing, here in Australia"

#### **Importance of information sources**

A Friedman Test was conducted on survey data (N=61) to determine an ordered ranking for the importance of information sources for professional updating activity. The results are displayed in Table 3.

workplace. Sonographers identified there "are still very good textbooks" but were also cautious about using books stating "by the time the text books are out the information is a

Eighty-four percent of respondents report utilising health and medical databases to update knowledge. The most commonly utilised databases were Medline (70%, n=40), PubMed (62%, n=36), Informit or Meditext (23%, n=11), Cochrane Library (20%, n=11) and CINAHL (Cumulative Index of Nursing and Allied Health, 16%, n=9). Apart from Medline where only 8% of respondents were unaware of the resource, a large number of Sonographers were unaware of other health and medical databases, EMBASE (88%), CINAHL (77%), Cochrane

Eighteen percent of Sonographers reported that they use government provided electronic health information portals such as Clinicians Knowledge Network (CKN) and Clinicians Health Channel (CHC). Amongst respondents, there was a low level of awareness (33%, n=18) of these government portals. Use of these government health information portals was higher amongst Sonographers employed in the public sector (36%, n=9) compared to the private sector (3%, n=1). This finding is not surprising, as these resources are made available

Given the low level of awareness of health and medical databases and government electronic information portals, there is an immediate need for professional development activities aimed at expanding the knowledge base of health professionals so they can more

The majority of Sonographers (69%, n=38) were not able to remotely access electronic information resources available in the workplace such as journals and databases from home. Sonographers identified that professionally relevant information sources could be made more available through the facility of remote access to workplace resources. As the vast majority of Sonographers had Internet access at home (97%), remote access to workplace e-resources would be a useful feature providing these professionals with greater flexibility in terms of when and where they can access needed information

Sixty-eight percent of Sonographers attended seminars to update their knowledge. Fifty percent (n=30) attended seminars conducted by a professional society, 22% (n=13) attended seminars organised by their workplace and 15% (n=9) attended seminars organised by Vendors. Seminars were valued as they provided information on "applications for their equipment" and also provided Sonographers with access to leaders in their field "people who do cutting edge stuff and that sort of spreads the word … in seminars rather than in

A Friedman Test was conducted on survey data (N=61) to determine an ordered ranking for the importance of information sources for professional updating activity. The results are

fully engage with the electronic health information world that is available.

couple of years old" and "by the time they are printed the images are fairly old".

Library (70%) Informit or Meditext (71%) and PubMed (27%).

**Health and medical databases** 

to employees in the public sector only.

sources. **Seminars** 

publishing, here in Australia"

displayed in Table 3.

**Importance of information sources** 


Table 3. Ordered ranking of importance of information sources for professional updating activity

The difference in ranking across information sources was statistically significant ( ) <sup>2</sup> χ = = ≤ 47.784, 6, .001 *df p* . Seminars, conferences and text and reference books were ranked as the top three information sources for professional updating activity, respectively. This top three ranking is in accord with the study by Keppell and colleagues (45) where health professionals ranked the importance of information sources they used to "refresh knowledge". When we consider the traditional model of scientific communication has new knowledge disseminated initially through seminars and conferences and then through journals and books (27-29), the importance Sonographers attribute to seminars and conferences for updating professional knowledge is not then surprising. Despite the 21st century being described as the electronic age, it is important to recognise that non-electronic information sources continue to be highly valued and used by health professionals to update their professional knowledge.

#### **5. Conclusion**

The rapidly changing science and technology underpinning diagnostic ultrasound imaging require professionals to engage in a continued process of updating their knowledge. This process utilises information sources as mediating tools in learning. This study identifies that a range of information sources are utilised to update professional knowledge, with seminars and conferences ranked as most important. A number of recommendations were also identified to support professional updating activity. These include: workplaces examine the journals available to determine if they have adequate coverage of diagnostic ultrasound; universal inclusion of Internet access onto workplace computers; provision of remote access to workplace electronic resources such as journals; greater provision of 'protected time' to support professional learning activities; and professional development activities focused on extending knowledge of electronic resources. As this study was conducted in Australia, the results may not have validity in other settings outside of Australia. The author encourages other researchers to build upon this work so that the body of knowledge on professional learning in Sonography is developed.

#### **6. References**


Professional Learning in Sonography 345

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### *Edited by Kerry Thoirs*

Medical sonography is a medical imaging modality used across many medical disciplines. Its use is growing, probably due to its relative low cost and easy accessibility. There are now many high quality ultrasound imaging systems available that are easily transportable, making it a diagnostic tool amenable for bedside and office scanning. This book includes applications of sonography that can be used across a number of medical disciplines including radiology, thoracic medicine, urology, rheumatology, obstetrics and fetal medicine and neurology. The book revisits established applications in medical sonography such as biliary, testicular and breast sonography and sonography in early pregnancy, and also outlines some interesting new and advanced applications of sonography.

Sonography

Sonography

*Edited by Kerry Thoirs*

Photo by kalus / iStock