**3. Intracranial vessels: TCCS examination**

TCCS is a reliable, safe and bedside tool to image intracranial circulation, mainly in acute stroke patients. The natural course of intracranial vessel occlusion is highly dynamic within hours and days and therefore a tool at least so much dynamic is needed in order to monitor the recanalization process.

A basic TCCS scanning is obtained from the temporal bone window in the mesencephalic axial plane, showing the full circle of Willis, as in the figure 7.

a. B-mode evaluation in gray scale with the butterfly shaped midbrain at the midline; b. corresponding Power-mode with the main vessels of the circle of Willis, tagged in c; d. waveform of the flow spectrum of ipsilateral M1 MCA (normal pattern).

Fig. 7. TCCS axial scanning from the temporal bone window, mesencephalic plane.

TCCS is a very reliable tool for imaging large intracranial vessels and for diagnosing their occlusion in the acute phase. The current guidelines about its application in clinical practice are not updated from 2004 (Sloan et al. 2004), but further data are now available from clinical studies in acute stroke patients, comparing neurosonology with neuroradiology and documenting the usefulness for monitoring the recanalization and enhance clot lysis. The

The serial ultrasound examination allowed to define the timing of recanalization: indeed the rate of complete recanalization was 16% at 1 month, 50% at 3 months, and 60% at 6 and 12 months. Therefore the recanalization process occurs mainly within the first six months, regardless the treatment. The main factor that was related to a reduced recanalization rate, was an initial occlusion of the dissected vessel, whereas the absence of stroke symptoms and the presence of local manifestations and signs as the unique clinical presentation, were

TCCS is a reliable, safe and bedside tool to image intracranial circulation, mainly in acute stroke patients. The natural course of intracranial vessel occlusion is highly dynamic within hours and days and therefore a tool at least so much dynamic is needed in order to monitor

A basic TCCS scanning is obtained from the temporal bone window in the mesencephalic

a. B-mode evaluation in gray scale with the butterfly shaped midbrain at the midline; b. corresponding Power-mode with the main vessels of the circle of Willis, tagged in c; d. waveform of the flow spectrum

TCCS is a very reliable tool for imaging large intracranial vessels and for diagnosing their occlusion in the acute phase. The current guidelines about its application in clinical practice are not updated from 2004 (Sloan et al. 2004), but further data are now available from clinical studies in acute stroke patients, comparing neurosonology with neuroradiology and documenting the usefulness for monitoring the recanalization and enhance clot lysis. The

Fig. 7. TCCS axial scanning from the temporal bone window, mesencephalic plane.

associated with an increased rate of complete recanalization.

axial plane, showing the full circle of Willis, as in the figure 7.

**3. Intracranial vessels: TCCS examination** 

the recanalization process.

of ipsilateral M1 MCA (normal pattern).

clinical indications for TCCS are basically the same of TCD for imaging of large intracranial vessels, but TCCS has the clear advantage to image the brain parenchyma and the intracranial structures, allowing also the application in neurodegenerative disease (mainly extrapiramidal disorders), the diagnosis and monitoring of hemorrhagic parenchymal transformation after treatment, the perfusional evaluation of the microcirculation, etc. The sensitivity and specificity of TCCS is not lesser than the ones of TCD and the established indication for TCD in acute stroke are also applicable to TCCS.

In a recent systematic review (Alexandrov et al. 2010) of TCD application, for patients with acute ischemic symptoms in anterior or posterior circulation who had cranial CT or MRI, the authors stated that "TCD can identify patients with proximal arterial occlusions both in anterior and posterior circulation who have the worst prognosis and can benefit the most from intravenous thrombolysis or rescue intraarterial therapies".

#### **3.1 Advantages and limitations of neurosonology**

Neurosonological tools, both TCD and TCCS are reliable and useful in acute stroke patients and have several comparative studies with MRA, CTA or DSA. The advantage of neurosonology in this setting are:


Disadvantages are mainly the operator-dependency, but it is notable that all diagnostic techniques somewhat depend on technical skills and expertise of operators, as documented by the intraoperator discordance in grading an extracranial carotid artery stenosis on NASCET study. The early diagnosis of a large vessel occlusion has a great impact on the prognosis of patient and on the choice of the proper treatment. Also in studies with an extended time window for thrombolysis up to 9 hours, because of the mismatch evaluation, only patients with residual large vessel occlusion shown a positive response to treatment and a significant improvement of disability scores (Hacke et al. 2009). Similarly persisting occlusions after reperfusion treatment have worse outcome and this information could be useful to address patients to intra-arterial clot removal or, in some cases, hemicraniectomy.

Sensitivity and specificity of neurosonological diagnosis of intracranial steno-occlusion is very high also compared to DSA (Sloan et al. 2004) (Fig. 8)

Neurosonological Evaluation of the Acute Stroke Patients 269

international experts with previous publications in the field of TCCS in acute stroke and

The examination procedure was carefully described, choosing a basic and comparable insonation modality for the anterior circulation stroke. The main examination plane is the axial transtemporal mesencephalic one (fig. 7), showing a good visualization of the circle of Willis (Malferrari et al. 2007, Wong 2003, Valaikiene et al 2008). A useful information to compare TCCS planes with the corresponding images from neuroradiological techniques, is that the transcranial axial insonation plane is usually different from the axial plane displayed with MR and CT imaging. There are also parenchymal and bone landmarks to identify the vessels and make easier to compare the oblique transcranial images with the neuroradiological images of CT or MR. The transtemporal bone window in the axial


Also the use of the coronal plane can be useful to localize and distinguish both vessel

All segments of all visible arteries should be investigated, not only by Colour- or Powermode, but especially by spectral Doppler sonography (Zipper and Stolz 2002, Baumgartner

The way to examine the entire circle of Willis by TCCS, makes unnecessary the orbital bone window, conventionally used by TCD for the exploration of the ophtalmic artery and its

About the main limitation of transcranial Doppler, i.e. the poor acoustic window, the Consensus carefully examined it. Also this review of the literature agreed with the known rate of 10% of patients with cerebrovascular diseases, where the insonation of the basal cerebral arteries is incomplete (Seidel et al. 1995; Kenton et al. 1997; Krejza et al. 2007). In this case the intravenous administration of an ultrasound contrast agent dramatically improves the insonation and therefore increases the number of conclusive ultrasound studies, allowing an adequate diagnosis in 80% to 90% of those patients with insufficient bone window before the contrast agent injection (Zunker et al. 2002; Postert et al. 1999;

branches, as stated in the above cited consensus (Nedelmann et al. 2009) (Fig. 10).

insonation plane allows to recognize the main branches of the Willis circle: - sphenoidal (M1) and insular (M2) segments of the middle cerebral artery

segments and normal from pathologic conditions (Valaikiene et al 2008).


finally collegially revised.


2004, Krejza and Baumgartner 2004).

Fig. 10. Statements 1 and 2 from Nedelmann et al 2009

artery


Fig. 8. Reliability of neurosological techniques vs DSA for diagnosis of intracranial occlusions

It can be noted that the specificity is globally very high, i.e. a negative transcranial examination can reliably exclude a large vessel occlusion, and also the sensitivity for MCA lesion is very good and it is relevant, because most strokes occur in the MCA territory through an MCA main stem occlusion or stenosis.

The reliability of this technique is also very high in the follow-up of stroke, during the monitoring of recanalization (Fig. 9) (Sloan et al. 2004)


Fig. 9. Reliability of neurosological techniques vs DSA for monitoring recanalization of intracranial occlusions

Also for monitoring the recanalization process the global reliability of TCD is high, and even higher for partial than for complete occlusion. This last feature is well understood if the extremely high dynamicity and temporal resolution of ultrasound techniques is kept in mind, because the serial use of DSA has forcedly time intervals of several hours or days between the successive examinations, and so it is easier to lose the partial recanalization step between occlusion and complete reopening of the vessel. Neurosonological techniques can be applied every minute or hour and therefore also a small variation in vessel patency is well recognized. Another partial limitation of TCCS (and even more of TCD) is the incomplete evaluation of the internal carotid artery, because of the inability to image the petrous segment. This is a partial limitation, since an hemodynamic lesion in this segment can be inferred by indirect sign, both in extracranial and intracranial ICA, if it is an acute process. The C5-C1 segment of internal carotid artery, according to angiographic terminology, can be explored by TCCS combining the axial and coronal access (Eggers et al. 2009).

#### **3.2 TCCS: How to perform the examination and the consensus statements**

TCCS is increasingly used in acute stroke patients, but it should pay for being ten years younger than TCD; therefore there are not clinical shared guidelines, as for TCD, but recently guidelines for its application in clinical trials on acute stroke have been published (Nedelmann et al 2009). Before these guidelines, there was not a systematic consensus on how TCCS examination should be performed in acute stroke patients. Furthermore standardized recommendations are needed to compare the results of TCCS studies from several centres. Therefore a systematic review of the literature on TCCS in acute stroke was performed and the resulting manuscript was corrected and commented by a panel of

It can be noted that the specificity is globally very high, i.e. a negative transcranial examination can reliably exclude a large vessel occlusion, and also the sensitivity for MCA lesion is very good and it is relevant, because most strokes occur in the MCA territory

The reliability of this technique is also very high in the follow-up of stroke, during the

Fig. 9. Reliability of neurosological techniques vs DSA for monitoring recanalization of

Also for monitoring the recanalization process the global reliability of TCD is high, and even higher for partial than for complete occlusion. This last feature is well understood if the extremely high dynamicity and temporal resolution of ultrasound techniques is kept in mind, because the serial use of DSA has forcedly time intervals of several hours or days between the successive examinations, and so it is easier to lose the partial recanalization step between occlusion and complete reopening of the vessel. Neurosonological techniques can be applied every minute or hour and therefore also a small variation in vessel patency is well recognized. Another partial limitation of TCCS (and even more of TCD) is the incomplete evaluation of the internal carotid artery, because of the inability to image the petrous segment. This is a partial limitation, since an hemodynamic lesion in this segment can be inferred by indirect sign, both in extracranial and intracranial ICA, if it is an acute process. The C5-C1 segment of internal carotid artery, according to angiographic terminology, can be explored by TCCS

Fig. 8. Reliability of neurosological techniques vs DSA for diagnosis of intracranial

through an MCA main stem occlusion or stenosis.

monitoring of recanalization (Fig. 9) (Sloan et al. 2004)

combining the axial and coronal access (Eggers et al. 2009).

**3.2 TCCS: How to perform the examination and the consensus statements** 

TCCS is increasingly used in acute stroke patients, but it should pay for being ten years younger than TCD; therefore there are not clinical shared guidelines, as for TCD, but recently guidelines for its application in clinical trials on acute stroke have been published (Nedelmann et al 2009). Before these guidelines, there was not a systematic consensus on how TCCS examination should be performed in acute stroke patients. Furthermore standardized recommendations are needed to compare the results of TCCS studies from several centres. Therefore a systematic review of the literature on TCCS in acute stroke was performed and the resulting manuscript was corrected and commented by a panel of

occlusions

intracranial occlusions

international experts with previous publications in the field of TCCS in acute stroke and finally collegially revised.

The examination procedure was carefully described, choosing a basic and comparable insonation modality for the anterior circulation stroke. The main examination plane is the axial transtemporal mesencephalic one (fig. 7), showing a good visualization of the circle of Willis (Malferrari et al. 2007, Wong 2003, Valaikiene et al 2008). A useful information to compare TCCS planes with the corresponding images from neuroradiological techniques, is that the transcranial axial insonation plane is usually different from the axial plane displayed with MR and CT imaging. There are also parenchymal and bone landmarks to identify the vessels and make easier to compare the oblique transcranial images with the neuroradiological images of CT or MR. The transtemporal bone window in the axial insonation plane allows to recognize the main branches of the Willis circle:


Also the use of the coronal plane can be useful to localize and distinguish both vessel segments and normal from pathologic conditions (Valaikiene et al 2008).

All segments of all visible arteries should be investigated, not only by Colour- or Powermode, but especially by spectral Doppler sonography (Zipper and Stolz 2002, Baumgartner 2004, Krejza and Baumgartner 2004).

The way to examine the entire circle of Willis by TCCS, makes unnecessary the orbital bone window, conventionally used by TCD for the exploration of the ophtalmic artery and its branches, as stated in the above cited consensus (Nedelmann et al. 2009) (Fig. 10).


Fig. 10. Statements 1 and 2 from Nedelmann et al 2009

About the main limitation of transcranial Doppler, i.e. the poor acoustic window, the Consensus carefully examined it. Also this review of the literature agreed with the known rate of 10% of patients with cerebrovascular diseases, where the insonation of the basal cerebral arteries is incomplete (Seidel et al. 1995; Kenton et al. 1997; Krejza et al. 2007). In this case the intravenous administration of an ultrasound contrast agent dramatically improves the insonation and therefore increases the number of conclusive ultrasound studies, allowing an adequate diagnosis in 80% to 90% of those patients with insufficient bone window before the contrast agent injection (Zunker et al. 2002; Postert et al. 1999;

Neurosonological Evaluation of the Acute Stroke Patients 271

within the M1 segment of MCA, associated with an end-diastolic ratio of < 2.5 between the contralateral and the ipsilateral M1 MCA identified branch occlusion; instead a >2.5 ratio indicated M1 occlusion. The main limitation of this study are the small sample of patients and the lack of specifications on how the criteria relate to the number of affected MCA branches. Another known pitfall is the use of contrast agents, because of the potential increase of flow velocity by 10% to 20% as compared to those assessed without contrast agents (Baumgartner et al. 1997; Khan et al. 2000). Finally it is possible that only the criterion "end-diastolic ratio < 2.5", but not the criterion "end-diastolic MCA velocity < 26 cm/sec" could be useful and exported to non-enhanced TCCS. The definite statement of the Consensus Conference about the diagnosis of MCA branch occlusion is shown in the fig. 13.

Angle-corrected measurements are more precise in the acute phase, because, in the presence of a large brain lesion, tissue edema may dynamically modify, expanding and decreasing, mainly within the first hours-days. Therefore a huge lesion in the MCA territory can displace the MCA and vary its course (Krejza et al. 2001) (example in fig. 14). The resulting change of the insonation angle on the affected side is not only different hour by hour or even minute by minute, but also it may lead to a wrong interpretation of the inter-hemispheric differences in flow velocity measurements. However this item requires other dedicated

Fig. 12. Statements 4 and 5 from Nedelmann et al 2009

Fig. 13. Statements 6 from Nedelmann et al 2009

studies and settings to solve the doubts.

Gerriets et al. 1999; Baumgartner et al. 1995; Goertler et al. 1998; Nabavi et al. 1998; Kunz et al. 2002). The shared criterion for defining sufficient the temporal bone window is the adequate displaying of the ipsilateral proximal branches of the circle of Willis, in both Colour- or Power-mode and spectral Doppler. This raises the question of the evaluation of the quality of the insonation window in a case of T-occlusion diagnosis. The Consensus Conference examined also the indication for ultrasouns contrast agents (UCA) in acute stroke in the setting of clinical trials and the Consensus Statement 3 shows the achieved agreement (Fig.11).

#### Fig. 11. Statements 3 from Nedelmann et al 2009

Another intuitive difference between TCD and TCCS is the possibility of achieving an anglecorrected flow waveform and angle-corrected flow velocity measurements. The relevance of this item comes from the anatomic course of intracranial arteries; indeed the angle between the ultrasound beam and the major intracranial arteries is not the same in each segment of the same artery and between similar segments of the arteries of both sides, mainly in acute stroke patients, because of the time changing mass effect of the ischemic lesion (Eicke et al. 1994). The diagnostic criteria for intracranial stenosis with their velocity threshold are different between TCD and TCCS, because of the angle-corrected measurements with TCCS. Angle corrected threshold have an higher sensitivity to detect arterial narrowing because of stenosis or vasospasm (Baumgartner et al. 1999), and they do not cause a decreased intrarater or interrater reproducibility, as compared to non-corrected measurements (Baumgartner et al. 1994; Maeda et al. 1990; Stolz et al. 2001). These considerations lead to the Consensus Statement 4 and 5 about angle-corrected measurements (Fig. 12).

The focus of this discussion about angle correction is its usefulness to examine patients in the acute phase of stroke, mainly MCA stroke, because the diagnosis of a distal M1 MCA or MCA branches occlusion involves the evaluation of flow velocity differences between MCA of the affected side and MCA of the contralateral side. This is because branch occlusions of MCA cannot be directly imaged by ultrasound and only indirect signs on the flow waveform could be searched, as a reduction of the M1 flow velocity compared to the contralateral side. In the literature there is a prospective TCD study, angiographycontrolled, defining the so called asymmetry index without angle correction for the diagnosis of branch occlusions (Zanette et al. 1989). According to this study it is possible to diagnose a condition of multiple MCA branch occlusions (> 3). There is only another study in the literature, addressing this item by contrast-enhanced TCCS and a comparison with angiography (Ogata et al. 2005). Its results were that an end-diastolic velocity of <26 cm/sec

Gerriets et al. 1999; Baumgartner et al. 1995; Goertler et al. 1998; Nabavi et al. 1998; Kunz et al. 2002). The shared criterion for defining sufficient the temporal bone window is the adequate displaying of the ipsilateral proximal branches of the circle of Willis, in both Colour- or Power-mode and spectral Doppler. This raises the question of the evaluation of the quality of the insonation window in a case of T-occlusion diagnosis. The Consensus Conference examined also the indication for ultrasouns contrast agents (UCA) in acute stroke in the setting of clinical trials and the Consensus Statement 3 shows the achieved

Another intuitive difference between TCD and TCCS is the possibility of achieving an anglecorrected flow waveform and angle-corrected flow velocity measurements. The relevance of this item comes from the anatomic course of intracranial arteries; indeed the angle between the ultrasound beam and the major intracranial arteries is not the same in each segment of the same artery and between similar segments of the arteries of both sides, mainly in acute stroke patients, because of the time changing mass effect of the ischemic lesion (Eicke et al. 1994). The diagnostic criteria for intracranial stenosis with their velocity threshold are different between TCD and TCCS, because of the angle-corrected measurements with TCCS. Angle corrected threshold have an higher sensitivity to detect arterial narrowing because of stenosis or vasospasm (Baumgartner et al. 1999), and they do not cause a decreased intrarater or interrater reproducibility, as compared to non-corrected measurements (Baumgartner et al. 1994; Maeda et al. 1990; Stolz et al. 2001). These considerations lead to

the Consensus Statement 4 and 5 about angle-corrected measurements (Fig. 12).

The focus of this discussion about angle correction is its usefulness to examine patients in the acute phase of stroke, mainly MCA stroke, because the diagnosis of a distal M1 MCA or MCA branches occlusion involves the evaluation of flow velocity differences between MCA of the affected side and MCA of the contralateral side. This is because branch occlusions of MCA cannot be directly imaged by ultrasound and only indirect signs on the flow waveform could be searched, as a reduction of the M1 flow velocity compared to the contralateral side. In the literature there is a prospective TCD study, angiographycontrolled, defining the so called asymmetry index without angle correction for the diagnosis of branch occlusions (Zanette et al. 1989). According to this study it is possible to diagnose a condition of multiple MCA branch occlusions (> 3). There is only another study in the literature, addressing this item by contrast-enhanced TCCS and a comparison with angiography (Ogata et al. 2005). Its results were that an end-diastolic velocity of <26 cm/sec

agreement (Fig.11).

Fig. 11. Statements 3 from Nedelmann et al 2009

within the M1 segment of MCA, associated with an end-diastolic ratio of < 2.5 between the contralateral and the ipsilateral M1 MCA identified branch occlusion; instead a >2.5 ratio indicated M1 occlusion. The main limitation of this study are the small sample of patients and the lack of specifications on how the criteria relate to the number of affected MCA branches. Another known pitfall is the use of contrast agents, because of the potential increase of flow velocity by 10% to 20% as compared to those assessed without contrast agents (Baumgartner et al. 1997; Khan et al. 2000). Finally it is possible that only the criterion "end-diastolic ratio < 2.5", but not the criterion "end-diastolic MCA velocity < 26 cm/sec" could be useful and exported to non-enhanced TCCS. The definite statement of the Consensus Conference about the diagnosis of MCA branch occlusion is shown in the fig. 13.


Fig. 12. Statements 4 and 5 from Nedelmann et al 2009


Fig. 13. Statements 6 from Nedelmann et al 2009

Angle-corrected measurements are more precise in the acute phase, because, in the presence of a large brain lesion, tissue edema may dynamically modify, expanding and decreasing, mainly within the first hours-days. Therefore a huge lesion in the MCA territory can displace the MCA and vary its course (Krejza et al. 2001) (example in fig. 14). The resulting change of the insonation angle on the affected side is not only different hour by hour or even minute by minute, but also it may lead to a wrong interpretation of the inter-hemispheric differences in flow velocity measurements. However this item requires other dedicated studies and settings to solve the doubts.

Neurosonological Evaluation of the Acute Stroke Patients 273

Fig. 15. TIBI flow grading system (adapted from Malferrari and Zedde 2008 and Malferrari

The relevance of this subclassification is that all categories has been externally validated by DSA. But, if this purpose is praiseworthy, it should also considered that only twenty-five patients were examined, half the cases were evaluated by DSA, and the time interval between the two examinations, TCD and DSA, was not short. Indeed TCD was performed at 12+16 hours and angiography at 41+57 hours after stroke onset; only 52% of studies were performed within 3 hours (Burgin et al. 2000). Although this limitations, the authors found that recanalization on TCD had the following accuracy parameters compared with


2010)

angiography: - sensitivity 91% - specificity 93%


a. left side transtemporal insonation; b. right side transtemporal insonation. The red lines show the left and right MCA course.

Fig. 14. TCCS of a patient with acute ischemic stroke in the right MCA territory.

#### **3.3 Scales and measurements in neurosonology**

Both in clinical trials and in clinical practice, the course of recanalization has been followed by ultrasound, using shared classification, for achieving a common language and easily compare the results of different centres. The first classification was derived from the angiographic classification, the so-called TICI (Thrombolysis in Cerebral Infarction) scale, which in turn was created beginning from the corresponding coronarographic reperfusion grading system, TIMI (Tomsick 2007). It was called TIBI (Thrombolysis In Brain Ischemia) score and was based on Doppler waveform; it has been widely used for the assessment of initial hemodynamics and recanalization phenomena (Alexandrov, Wojner, Grotta 2004; Demchuk et al. 2001; Molina et al. 2006). Because of the waveform-based being of the scale, it was used primary for TCD examination, and then it was transferred to TCCS, always using only the Doppler spectrum as criterion. TIMI and TICI, being angiography-based, were assumed to assess both features of flow restoration or revascularization: reopening of the originally occluded artery and restoration of effective flow or reperfusion into the distal arterial bed of the originally occluded artery. These two concepts are related each to other but not exactly the same phenomenon, because the reopening of an occluded artery does not mean automatically the restoration of an effective perfusion status in the downstream circulation, due to the duration of ischemia, the efficiency of the collateral circulation, the microembolic load, the viability of tissue, etc. Therefore, also a complete recanalization of the primarily occluded vessel may be associated to variable patterns of distal patency and perfusion/reperfusion ratios (Tomsick 2007).

The TIBI grading system refers only to recanalization process, and not to reperfusion of cerebral tissue. It is a valid and widely used tool to assess recanalization, both for TCD and for TCCS. It is shown in Fig. 15 with some examples of the Doppler spectra corresponding to each grade.

As shown in the fig. 15, this scale comprises 6 different degrees of flow abnormalities. The application of this grading system in clinical practice and in trials is sometimes difficult and there is a broad range of subjectivity, mainly in attributing grade 2 and 3. For this reason in some multicentre trials about ultrasound enhanced thrombolysis, a preliminary training was performed to guarantee the comparability of results. To avoid partially this subjectivity, flow grades are frequently separated into 3 major categories (Burgin et al. 2000), as in the angiographic classification (Fig. 16). These categories are:


a. left side transtemporal insonation; b. right side transtemporal insonation. The red lines show the left

Both in clinical trials and in clinical practice, the course of recanalization has been followed by ultrasound, using shared classification, for achieving a common language and easily compare the results of different centres. The first classification was derived from the angiographic classification, the so-called TICI (Thrombolysis in Cerebral Infarction) scale, which in turn was created beginning from the corresponding coronarographic reperfusion grading system, TIMI (Tomsick 2007). It was called TIBI (Thrombolysis In Brain Ischemia) score and was based on Doppler waveform; it has been widely used for the assessment of initial hemodynamics and recanalization phenomena (Alexandrov, Wojner, Grotta 2004; Demchuk et al. 2001; Molina et al. 2006). Because of the waveform-based being of the scale, it was used primary for TCD examination, and then it was transferred to TCCS, always using only the Doppler spectrum as criterion. TIMI and TICI, being angiography-based, were assumed to assess both features of flow restoration or revascularization: reopening of the originally occluded artery and restoration of effective flow or reperfusion into the distal arterial bed of the originally occluded artery. These two concepts are related each to other but not exactly the same phenomenon, because the reopening of an occluded artery does not mean automatically the restoration of an effective perfusion status in the downstream circulation, due to the duration of ischemia, the efficiency of the collateral circulation, the microembolic load, the viability of tissue, etc. Therefore, also a complete recanalization of the primarily occluded vessel may be associated to variable patterns of distal patency and

The TIBI grading system refers only to recanalization process, and not to reperfusion of cerebral tissue. It is a valid and widely used tool to assess recanalization, both for TCD and for TCCS. It is shown in Fig. 15 with some examples of the Doppler spectra corresponding to

As shown in the fig. 15, this scale comprises 6 different degrees of flow abnormalities. The application of this grading system in clinical practice and in trials is sometimes difficult and there is a broad range of subjectivity, mainly in attributing grade 2 and 3. For this reason in some multicentre trials about ultrasound enhanced thrombolysis, a preliminary training was performed to guarantee the comparability of results. To avoid partially this subjectivity, flow grades are frequently separated into 3 major categories (Burgin et al. 2000), as in the

Fig. 14. TCCS of a patient with acute ischemic stroke in the right MCA territory.

**3.3 Scales and measurements in neurosonology** 

perfusion/reperfusion ratios (Tomsick 2007).

angiographic classification (Fig. 16). These categories are:

each grade.

and right MCA course.



Fig. 15. TIBI flow grading system (adapted from Malferrari and Zedde 2008 and Malferrari 2010)

The relevance of this subclassification is that all categories has been externally validated by DSA. But, if this purpose is praiseworthy, it should also considered that only twenty-five patients were examined, half the cases were evaluated by DSA, and the time interval between the two examinations, TCD and DSA, was not short. Indeed TCD was performed at 12+16 hours and angiography at 41+57 hours after stroke onset; only 52% of studies were performed within 3 hours (Burgin et al. 2000). Although this limitations, the authors found that recanalization on TCD had the following accuracy parameters compared with angiography:


Neurosonological Evaluation of the Acute Stroke Patients 275

As TIBI score, also COGIF score can be applied for both baseline evaluation and assessment of the spontaneous or treatment-induced recanalization. The score comprise these major

Each grade is partially different from TIBI corresponding grade, because of the attempt to strongly reduce the subjective interpretation of the Doppler spectrum, mainly for TIBI grades 1 to 3, which are also the ones more affected by downstream and/or upstream arterial status. Furthermore, although the COGIF score, as the TIBI score, is based on the Doppler spectrum for the grading, the first one was designed for TCCS, and then some morphologic findings may play a role in achieving the waveform and in the occlusive pattern diagnosis. This score was proposed in the Consensus Conference (Nedelmann et al. 2009) primary for clinical trials, in order to make easier and reliable the assessment of recanalization grades, but its use is yet under evaluation, because of the lack, at our knowledge, of published prospective studies or retrospective evaluations, using the COGIF

Fig. 17. COGIF flow grading score: grading, hemodynamic features and examples (modified

The COGIF score was designed to better follow the recanalization process with its dynamicity and potential alternation of recanalization and reocclusion. Therefore the time

For this chapter anterior circulation stroke was described to show the usefulness and the role of sonological vascular imaging as a guide to treatment and to define the prognosis. Indeed the knowledge of vascular status in acute ischemic stroke have a clear prognostic relevance and it could be used also as a criterion to tailor the treatment and select the best reperfusion strategy for each patient, both in a single modality and in a sequential or

course of grades during serial TCCS examination was carefully encoded (Fig. 18).

from Nedelmann et al 2009 and Malferrari et al 2010)

**4. Anterior circulation stroke** 

grades (fig. 17):

score.




As previously stated in the discussion about guidelines (Sloan et al. 2004), to predict partial occlusion (TICI grade II), TCD had an high reliability (sensitivity of 100%, specificity of 76%, PPV of 44%, and NPV of 100%). Also, TCD predicted the presence of complete occlusion on DSA (TICI grade I) with lower, but yet high reliability (sensitivity of 50%, specificity of 100%, PPV of 100%, and NPV of 75%). The conclusions of the authors were that TCD flow signals correlated with angiographic occlusive pattern (Burgin et al. 2000).


Fig. 16. TIBI flow grading grouping, according to TICI scale (modified from Burgin et al 2000)

The difficulty in differentiation between TIBI grades 1 to 3 (minimal flow, blunted flow, dampened flow) and the limitation of the above cited DSA comparative study (Burgin et al. 2000) raised some questions about the usefulness and the comparability of this grading system in clinical practice. Therefore the authors of the Consensus Conference (Nedelmann et al 2009) noted that, because of the relevant effect of the upstream and downstream arterial status, flow patterns graded by TIBI could not only reflect partial recanalization of the M1 MCA, but also include different hemodynamic situations in a combination of upstream and downstream steno-occlusions (e.g. extracranial or intracranial ICA occlusion, and obstruction of MCA branches). A TIBI flow grade of 2 or 3 may be seen for example in extracranial carotid steno-occlusion without intracranial artery disease, not only during MCA recanalization process.

Based on these considerations, an evolution of the TIBI score into a TCCS-based grading system has been proposed and called COGIF (COnsensus on Grading Intracranial Flow obstruction) score (Nedelmann et al 2009) (Fig. 17).

The purpose of this scoring system is to avoid the interference of previous arterial disease, and it is exclusively based on known hemodynamic changes of the Doppler spectrum, occurring in the acute stage of stroke.

As TIBI score, also COGIF score can be applied for both baseline evaluation and assessment of the spontaneous or treatment-induced recanalization. The score comprise these major grades (fig. 17):


274 Neuroimaging for Clinicians – Combining Research and Practice

As previously stated in the discussion about guidelines (Sloan et al. 2004), to predict partial occlusion (TICI grade II), TCD had an high reliability (sensitivity of 100%, specificity of 76%, PPV of 44%, and NPV of 100%). Also, TCD predicted the presence of complete occlusion on DSA (TICI grade I) with lower, but yet high reliability (sensitivity of 50%, specificity of 100%, PPV of 100%, and NPV of 75%). The conclusions of the authors were that TCD flow

Fig. 16. TIBI flow grading grouping, according to TICI scale (modified from Burgin et al

The difficulty in differentiation between TIBI grades 1 to 3 (minimal flow, blunted flow, dampened flow) and the limitation of the above cited DSA comparative study (Burgin et al. 2000) raised some questions about the usefulness and the comparability of this grading system in clinical practice. Therefore the authors of the Consensus Conference (Nedelmann et al 2009) noted that, because of the relevant effect of the upstream and downstream arterial status, flow patterns graded by TIBI could not only reflect partial recanalization of the M1 MCA, but also include different hemodynamic situations in a combination of upstream and downstream steno-occlusions (e.g. extracranial or intracranial ICA occlusion, and obstruction of MCA branches). A TIBI flow grade of 2 or 3 may be seen for example in extracranial carotid steno-occlusion without intracranial artery disease, not only during

Based on these considerations, an evolution of the TIBI score into a TCCS-based grading system has been proposed and called COGIF (COnsensus on Grading Intracranial Flow

The purpose of this scoring system is to avoid the interference of previous arterial disease, and it is exclusively based on known hemodynamic changes of the Doppler spectrum,

signals correlated with angiographic occlusive pattern (Burgin et al. 2000).


2000)

MCA recanalization process.

occurring in the acute stage of stroke.

obstruction) score (Nedelmann et al 2009) (Fig. 17).


Each grade is partially different from TIBI corresponding grade, because of the attempt to strongly reduce the subjective interpretation of the Doppler spectrum, mainly for TIBI grades 1 to 3, which are also the ones more affected by downstream and/or upstream arterial status. Furthermore, although the COGIF score, as the TIBI score, is based on the Doppler spectrum for the grading, the first one was designed for TCCS, and then some morphologic findings may play a role in achieving the waveform and in the occlusive pattern diagnosis. This score was proposed in the Consensus Conference (Nedelmann et al. 2009) primary for clinical trials, in order to make easier and reliable the assessment of recanalization grades, but its use is yet under evaluation, because of the lack, at our knowledge, of published prospective studies or retrospective evaluations, using the COGIF score.


Fig. 17. COGIF flow grading score: grading, hemodynamic features and examples (modified from Nedelmann et al 2009 and Malferrari et al 2010)

The COGIF score was designed to better follow the recanalization process with its dynamicity and potential alternation of recanalization and reocclusion. Therefore the time course of grades during serial TCCS examination was carefully encoded (Fig. 18).
