**8. Limitations of the breast MRI technique for screening in its current form**

MRI is inappropriate for women at a low lifetime risk for breast cancer. Breast MRI is not meant to replace mammography (Lee et al., 2010). Under rare circumstances, such as DCIS with typical microcalcification clusters, mammography is superior to MRI for interpretation malignancy, which produces an image that is faint or equivocal (Lee et al., 2010).

The lesion-detecting specificity of MRI is highly influenced by reacted inflammation within a month after surgery. Thus, a time period should elapse post-surgery before an MRI (Mann et al., 2008). In addition, the dynamic breast MRI is highly influenced by hormonal fluctuations during the menstrual cycle, which may cause interpretative difficulties related to the uptake of gadolinium in normal breast tissue (Delille et al., 2005; Kriege et al., 2006). The call-back and biopsy rates of MRI are higher than for mammography in high-risk populations. This is because of the increased sensitivity of MRI. The net harm, benefits, and psychological impact of higher cancer detection rates should be considered (Saslow et al., 2007). Breast MRI screening is almost 10 times more expensive than mammographic screening, and generates higher diagnostic costs (Plevritis et al., 2006). Asian countries adopting unlimited breast MRI can face a heavy financial burden. Some concern exists regarding the clinical safety of the intravenous gadolinium-based contrast media used during breast MRI. In Hong Kong, the adverse reaction rate is reported at 0.48 %, and the incidence of severe anaphylactoid reaction is approximately 0.01 %. Although most of the symptoms are mild and transient, these adverse reactions must be documented and managed accurately (Li et al., 2006).

#### **9. Advantages of a dedicated breast MRI (DBMRI) system with parameters of dynamic scan, 3D representation, and post processing techniques**

The recent recommended standard for assessing MRIs to differentiate malignancies from benign lesions is the fourth edition of a breast MR lexicon (Morphological interpretation of BRMRI images using standards of the American College of Radiology's (ACR) BI-RADS-MRI lexicon for malignancy grading) (American College of Radiology, 2003; Erguvan-Dogan et al., 2006), which is a classification scheme used for the interpretation of breast cancer. Although universal standards for integrating different MRI systems and manufacturers are lacking, overall, characteristics based on BIRADS scoring of MRI descriptions depend on certain parameters. This is a report on my experience with a specific MRI system and pulse sequence.

The DBMRI system with a Spiral RODEO pulse sequence of a 1.5 T dedicated spiral breast MRI system (Aurora System; Aurora Imaging Technology Inc., North Andover, MA, USA, using the Spiral RODEO pulse sequence) is equipped with different post-processing techniques, including early subtracted phase (ESP), post-contrast kinetic curve, and MPR with ductal orientation, which can be independently applied in a DBMRI system (Leung et al., 2010a; Leung et al., 2010b; Leung et al., 2010c; Leung et al., in press). Axial and sagittal gradient echo T1 acquisitions were performed for both breasts with a bilateral breast coil. Sequences were performed before and after the infusion of 0.2 mmol/kg gadolinium, administrated as a bolus dose with a power injector followed by a 20 mL saline flush.

detection comes with a false positive rate of 10.9 % and a relatively low risk of detecting

**8. Limitations of the breast MRI technique for screening in its current form**  MRI is inappropriate for women at a low lifetime risk for breast cancer. Breast MRI is not meant to replace mammography (Lee et al., 2010). Under rare circumstances, such as DCIS with typical microcalcification clusters, mammography is superior to MRI for interpretation

The lesion-detecting specificity of MRI is highly influenced by reacted inflammation within a month after surgery. Thus, a time period should elapse post-surgery before an MRI (Mann et al., 2008). In addition, the dynamic breast MRI is highly influenced by hormonal fluctuations during the menstrual cycle, which may cause interpretative difficulties related to the uptake of gadolinium in normal breast tissue (Delille et al., 2005; Kriege et al., 2006). The call-back and biopsy rates of MRI are higher than for mammography in high-risk populations. This is because of the increased sensitivity of MRI. The net harm, benefits, and psychological impact of higher cancer detection rates should be considered (Saslow et al., 2007). Breast MRI screening is almost 10 times more expensive than mammographic screening, and generates higher diagnostic costs (Plevritis et al., 2006). Asian countries adopting unlimited breast MRI can face a heavy financial burden. Some concern exists regarding the clinical safety of the intravenous gadolinium-based contrast media used during breast MRI. In Hong Kong, the adverse reaction rate is reported at 0.48 %, and the incidence of severe anaphylactoid reaction is approximately 0.01 %. Although most of the symptoms are mild and transient, these adverse reactions must be documented and

**9. Advantages of a dedicated breast MRI (DBMRI) system with parameters of** 

The recent recommended standard for assessing MRIs to differentiate malignancies from benign lesions is the fourth edition of a breast MR lexicon (Morphological interpretation of BRMRI images using standards of the American College of Radiology's (ACR) BI-RADS-MRI lexicon for malignancy grading) (American College of Radiology, 2003; Erguvan-Dogan et al., 2006), which is a classification scheme used for the interpretation of breast cancer. Although universal standards for integrating different MRI systems and manufacturers are lacking, overall, characteristics based on BIRADS scoring of MRI descriptions depend on certain parameters. This is a report on my experience with a specific

The DBMRI system with a Spiral RODEO pulse sequence of a 1.5 T dedicated spiral breast MRI system (Aurora System; Aurora Imaging Technology Inc., North Andover, MA, USA, using the Spiral RODEO pulse sequence) is equipped with different post-processing techniques, including early subtracted phase (ESP), post-contrast kinetic curve, and MPR with ductal orientation, which can be independently applied in a DBMRI system (Leung et al., 2010a; Leung et al., 2010b; Leung et al., 2010c; Leung et al., in press). Axial and sagittal gradient echo T1 acquisitions were performed for both breasts with a bilateral breast coil. Sequences were performed before and after the infusion of 0.2 mmol/kg gadolinium, administrated as a bolus dose with a power injector followed by a 20 mL saline flush.

**dynamic scan, 3D representation, and post processing techniques** 

malignancy, which produces an image that is faint or equivocal (Lee et al., 2010).

benign disease on biopsy (9.4 %) (Lehman et al., 2007a).

managed accurately (Li et al., 2006).

MRI system and pulse sequence.

## **10. Lesion analysis using ESP image, kinetic curve patterns, color mapping, and morphology**

In the DBMRI, for cases suspected of being malignant, an ESP image was obtained based on subtraction of the post-enhanced phase of images from 90 s non-enhanced images. Lesions that could be subtracted in the ESP (by subtraction of the post enhanced image at 90 s from the pre-contrast phase) were almost completely excluded from the possibility of being malignant (Figure 1b). Therefore, the lesions that could not be subtracted in the ESP required further analysis to assess the risk of malignancy.

Using the mean percentage calculation and comparing pre- and post-contrast kinetic data (calculated from 0 s, 90 s, and 4.5 min), the threshold point for lesion enhancement was displayed. According to the diagnostic observations of Dr. Christane Kuhl (1999), curved patterns of the plateau and washout with bound protein water and free water represent possible lesions. A stabilized enhancement without change in signal intensity between 90 s and 4.5 min was termed a "plateau" pattern. A "washout" pattern was indicated by a decline in signal intensity between 90 s and 4.5 min after the injection of contrast. Each lesion was characterized according to the strongest enhancement pattern visible over the entire lesion. Figures 1c show magnetic resonance imaging for differentiating lesions that are normal, benign, or display a washout pattern.

Fig. 3. In normal tissue, the contrast medium equally permeates in and out through the normal gaps in the vascular endothelial cells and interstitial space. In benign neoplasms, contrast does not permeate out of the microvessel to interstitial space, and the progressive accumulate increases the concentration which manifests itself in a progressively increased MRI signal.

The washout curve represents the initial increase in contrast concentration in the interstitial space and then a decrease, as it reverse permeates back through the abnormal gaps in the vascular endothelial cells. A final decreased contrast concentration in the tumor interstitial space can be detected.

The Application of Breast MRI on Asian Women (Dense Breast Pattern) 35

A lesion of < 5 mm of enhancement, even with a washout curve or mixed washout/plateau kinetic curve and reddish color mapping, was not automatically referred for biopsy. This was because a tiny spot of enhancement of < 5 mm is known as a 'focus,' as described by the ACR Breast MRI Lexicon, and has a very low possibility of being a malignancy, and is, therefore, suitable for a short-interval follow-up (Liberman et al., 2006). MRI-guided biopsy, MRI-guided localization for an excisional biopsy, sono-guided biopsy, or surgical excision biopsy is employed in cases suggestive of or strongly suspected of being a malignancy.

The interpretation of breast MRI images using early phase subtraction, kinetic curve patterns, color mapping (based on the summing up of kinetic curve data from corresponding areas), and the morphology of the MR image, is helpful in differentiating malignancies from benign lesions. Dedicated breast MRI with ESP, kinetic curve, and morphology analysis was found to have an over 95% negative predictive value of ruling out malignancy and was helpful in identifying the characteristics of early-stage malignant

The usual applications, benefits and interpretations of breast MRI images are shown as

Fig. 4. (a)

lesions.

Figure 4~13.

A color mapping method was also adopted to assess the possibility of a malignancy. This reflects the overall curved patterns of the persistent-plateau (yellow color) and plateauwashout (red color), which is depends on the permeability of contrast medium through the capillary vessel of the neoplasm (Figure 3). This provided a tool for the subtle distinction of different grades of contrast-enhanced percentages so that the kinetic curve analysis of the region of interest (ROI) would be more convenient (Figure 1,2).

Morphological interpretation of BRMRI images uses standards of the American College of Radiology's (ACR) BI-RADS-MRI lexicon for malignancy grading (x). In this study, MRI studies were interpreted in conjunction with clinical history, family history of breast cancer, age, and menstrual status. Referring MRI-detected lesions for biopsy depended on characteristics of the ESP image, post-enhanced curve pattern, color mapping, and tumor morphology, such as spiculation, irregular margins, architectural distortion, and ductal or segmental enhancement (Figure 4). The lesion configuration was classified as focal mass enhancement or non-mass-like enhancement. The morphological parameters of focal mass enhancement were evaluated by its lesion shape and mass margin. Lesion shape was classified as round, oval, lobular, and irregular. Mass margins were classified as smooth, irregular, and spiculated. Non-mass-like enhancement included linear, ductal, regional, and segmental enhancement (Figure 4).

Morphological characteristics were considered the most important determining factor for benign or malignant masses. Any suspicious MR-enhanced lesions were described based on lesion shape, borders, distribution, kinetics, and internal architecture. The final MR assessment was classified on a six-point scale, which is summarized in the following table (Table 4).


Table 4. MRI is believed to be the most sensitive and accurate screening tool for breast cancer in Asian women. Thus, no Category 0 exists in the interpretation of breast MRI, which differs from mammography or sonography.

Examinations that provided an initial assessment of incomplete or 0 received a final MR assessment of Category I-V, based on the results of follow-up procedures. A lesion was identified as suspicious if a focal mass existed with irregular or speculated margins, if enhancement had a ductal distribution, if a solid lesion showed rim enhancement, or if there was intense regional enhancement in less than one quadrant. Benign lesions were identified as having smooth or lobulated margins (Lehman et al., 2007b).

A color mapping method was also adopted to assess the possibility of a malignancy. This reflects the overall curved patterns of the persistent-plateau (yellow color) and plateauwashout (red color), which is depends on the permeability of contrast medium through the capillary vessel of the neoplasm (Figure 3). This provided a tool for the subtle distinction of different grades of contrast-enhanced percentages so that the kinetic curve analysis of the

Morphological interpretation of BRMRI images uses standards of the American College of Radiology's (ACR) BI-RADS-MRI lexicon for malignancy grading (x). In this study, MRI studies were interpreted in conjunction with clinical history, family history of breast cancer, age, and menstrual status. Referring MRI-detected lesions for biopsy depended on characteristics of the ESP image, post-enhanced curve pattern, color mapping, and tumor morphology, such as spiculation, irregular margins, architectural distortion, and ductal or segmental enhancement (Figure 4). The lesion configuration was classified as focal mass enhancement or non-mass-like enhancement. The morphological parameters of focal mass enhancement were evaluated by its lesion shape and mass margin. Lesion shape was classified as round, oval, lobular, and irregular. Mass margins were classified as smooth, irregular, and spiculated. Non-mass-like enhancement included linear, ductal, regional, and

Morphological characteristics were considered the most important determining factor for benign or malignant masses. Any suspicious MR-enhanced lesions were described based on lesion shape, borders, distribution, kinetics, and internal architecture. The final MR assessment was classified on a six-point scale, which is summarized in the following table (Table 4).

IIIa Probable benign lesion, suggest 6 months follow up with sonography

IIIb Probable benign lesion, suggest 3 months follow up with sonography

VI Malignancy. Further treatment, including surgery, adjuvant chemical therapy, or radiation therapy is suggested. Table 4. MRI is believed to be the most sensitive and accurate screening tool for breast cancer in Asian women. Thus, no Category 0 exists in the interpretation of breast MRI,

Examinations that provided an initial assessment of incomplete or 0 received a final MR assessment of Category I-V, based on the results of follow-up procedures. A lesion was identified as suspicious if a focal mass existed with irregular or speculated margins, if enhancement had a ductal distribution, if a solid lesion showed rim enhancement, or if there was intense regional enhancement in less than one quadrant. Benign lesions were identified

IV Could not rule out the possibility of malignancy, suggest biopsy V Malignancy is strongly suggested. Tumor staging and therapeutic

focused on the MRI indicated position or in the other breast

focused on the MRI indicated position or in the other breast

region of interest (ROI) would be more convenient (Figure 1,2).

**Category Interpretation and the suggestion** 

II Benign findings or benign lesions

planning suggested.

as having smooth or lobulated margins (Lehman et al., 2007b).

I Negative for malignancy

which differs from mammography or sonography.

segmental enhancement (Figure 4).

A lesion of < 5 mm of enhancement, even with a washout curve or mixed washout/plateau kinetic curve and reddish color mapping, was not automatically referred for biopsy. This was because a tiny spot of enhancement of < 5 mm is known as a 'focus,' as described by the ACR Breast MRI Lexicon, and has a very low possibility of being a malignancy, and is, therefore, suitable for a short-interval follow-up (Liberman et al., 2006). MRI-guided biopsy, MRI-guided localization for an excisional biopsy, sono-guided biopsy, or surgical excision biopsy is employed in cases suggestive of or strongly suspected of being a malignancy.

The interpretation of breast MRI images using early phase subtraction, kinetic curve patterns, color mapping (based on the summing up of kinetic curve data from corresponding areas), and the morphology of the MR image, is helpful in differentiating malignancies from benign lesions. Dedicated breast MRI with ESP, kinetic curve, and morphology analysis was found to have an over 95% negative predictive value of ruling out malignancy and was helpful in identifying the characteristics of early-stage malignant lesions.

The usual applications, benefits and interpretations of breast MRI images are shown as Figure 4~13.

Fig. 4. (a)

The Application of Breast MRI on Asian Women (Dense Breast Pattern) 37

(d)

Fig. 4. (a) Digital mammography of an Asian women with DBPP showed two indistinct ill defined dense shadows noted at superior lateral of right breast. There is no enlarged axillary lymph node could be demonstrated. (b) Breast MRI simultaneously showed an enlarged right side axillary lymphadenopathy (long white arrow); first right superior mass (black arrow) and second right superior mass (white curve arrow). (c) Breast MRI with post processing software for analysis shows the first right superior mass remains high signal under ESP and exhibits 'washout' curve pattern. Pathological report indicate a small invasive ductal carcinoma. (d) It shows the second right superior mass remains high signal

under ESP but exhibits a 'persistent' curve pattern. Pathological report as benign

fibroadenoma.

Fig. 4. (c)

Fig. 4. (b)

Fig. 4. (c)

(d)

Fig. 4. (a) Digital mammography of an Asian women with DBPP showed two indistinct ill defined dense shadows noted at superior lateral of right breast. There is no enlarged axillary lymph node could be demonstrated. (b) Breast MRI simultaneously showed an enlarged right side axillary lymphadenopathy (long white arrow); first right superior mass (black arrow) and second right superior mass (white curve arrow). (c) Breast MRI with post processing software for analysis shows the first right superior mass remains high signal under ESP and exhibits 'washout' curve pattern. Pathological report indicate a small invasive ductal carcinoma. (d) It shows the second right superior mass remains high signal under ESP but exhibits a 'persistent' curve pattern. Pathological report as benign fibroadenoma.

The Application of Breast MRI on Asian Women (Dense Breast Pattern) 39

(a) (b)

(c) (d)

Fig. 7. Breast MRI has the merit on the clinical response assessment for chemotherapy. (a)(b) A patient with a huge size tumor of IDC at the left breast; after five cycles of chemotherapy, the tumor was shrinkage. (c)(d) In another patient, a similar huge size IDC mass in right breast, is finally almost completely regress after adjuvant and targeting chemotherapy.

Fig. 5. (a) Digital mammography showed an ill defined hyperdense mass (thin arrow) locate at superior right breast, but it could not demonstrate ipsilateral axillary lymph node. (b) Breast MRI with 3D MIP (maximum intensity projection) shows the first right superior mass remains high signal under ESP and exhibits 'washout' curve pattern. Pathological report indicates a small invasive ductal carcinoma.

Fig. 6. Breast MRI image of an Asian woman with bloody discharge with clinical diagnosis as malignancy, it shows high signal intensity content within intraductal appearance under 3D MIP (a: with circle); but the signal being almost subtracted under ESP (b: arrow). Pathological report indicates benign papilloma.

(a) (b)

indicates a small invasive ductal carcinoma.

Pathological report indicates benign papilloma.

Fig. 5. (a) Digital mammography showed an ill defined hyperdense mass (thin arrow) locate at superior right breast, but it could not demonstrate ipsilateral axillary lymph node. (b) Breast MRI with 3D MIP (maximum intensity projection) shows the first right superior mass remains high signal under ESP and exhibits 'washout' curve pattern. Pathological report

 Fig. 6. Breast MRI image of an Asian woman with bloody discharge with clinical diagnosis as malignancy, it shows high signal intensity content within intraductal appearance under 3D MIP (a: with circle); but the signal being almost subtracted under ESP (b: arrow).

Fig. 7. Breast MRI has the merit on the clinical response assessment for chemotherapy. (a)(b) A patient with a huge size tumor of IDC at the left breast; after five cycles of chemotherapy, the tumor was shrinkage. (c)(d) In another patient, a similar huge size IDC mass in right breast, is finally almost completely regress after adjuvant and targeting chemotherapy.

The Application of Breast MRI on Asian Women (Dense Breast Pattern) 41

 (b) Fig. 9. Breast MRI adjunct the conventional breast modality with no limitation of breast size and breast dense pattern. (a) In this Breast MRI image of Asian woman, a 1.5 cm IDC tumor showed on left breast by all axial, sagittal and coronal views and associate 'washout' kinetic curve pattern. (b) As we retrospectively to review the digital mammography of this patient (both CC & MLO views), the mentioned mass is not capable to demonstrate due to the deep

location and dense parenchyma occult effect of the breast.

(a)

(color mapping, axial view) (color mapping, coronal view)

(color mapping, axial view) (color mapping, coronal view)

Fig. 8. By using color mapping of post processing breast MRI technique, more lively to demonstrate initial result of chemotherapy, even though the tumor size is not remarkable shrinkage. (a)(b) Red color area (represent active viable malignant cell with 'washout' contrast enhanced kinetic curve pattern) occupy the major part of the IDC tumor, in the right breast. (c)(d) After two cycles of chemotherapy, the red color shrinkage to less than 20% area of the tumor. This result encouraged both clinician and patient to continue this effective protocol of chemotherapy.

(color mapping, axial view) (color mapping, coronal view)

(color mapping, axial view) (color mapping, coronal view)

Fig. 8. By using color mapping of post processing breast MRI technique, more lively to demonstrate initial result of chemotherapy, even though the tumor size is not remarkable shrinkage. (a)(b) Red color area (represent active viable malignant cell with 'washout' contrast enhanced kinetic curve pattern) occupy the major part of the IDC tumor, in the right breast. (c)(d) After two cycles of chemotherapy, the red color shrinkage to less than 20% area of the tumor. This result encouraged both clinician and patient to continue this

effective protocol of chemotherapy.

Fig. 9. Breast MRI adjunct the conventional breast modality with no limitation of breast size and breast dense pattern. (a) In this Breast MRI image of Asian woman, a 1.5 cm IDC tumor showed on left breast by all axial, sagittal and coronal views and associate 'washout' kinetic curve pattern. (b) As we retrospectively to review the digital mammography of this patient (both CC & MLO views), the mentioned mass is not capable to demonstrate due to the deep location and dense parenchyma occult effect of the breast.

The Application of Breast MRI on Asian Women (Dense Breast Pattern) 43

(a)

Fig. 11. (a) Breast MRI have the merit on the describing multifocality and the detection of

mammography shows a single isodense palpable mass at superior of left breast (white arrow with metal beam). (b)(c)The follow up breast MRI shows another two enhanced tumor masses, with ill defined margin at superior lateral of right breast (long white arrow), which was proved as IDC. There is also a well defined enhanced mass with smooth margin,

locate at paramedial aspect of left breast (black thick arrow), which was proved as

fibroadenoma. Besides, the stronger enhancement of left axillary lymph nodes (circle on 11b) indicate the metastasis, compared with the weaker enhancement of right axillary lymph

(b) (c)

nodes (circle on 11c).

asymptomatic cancer on the contralateral breast. In this Asian patient, digital

(c)

Fig. 10. (a)(b) An Asian woman with DBPP who received digital mammography, it shows suspicious mass locate at deep superior of left breast under MLO view (white arrow), but the CC view could not demonstrate the tumor location. (c) Breast MRI (oblique view of 3D MIP) is more clearly to demonstrate multiple foci of malignant masses by different tumor location and tumor sizes . Pathological proved as IDC and DCIS.

(a) (b)

(c) Fig. 10. (a)(b) An Asian woman with DBPP who received digital mammography, it shows suspicious mass locate at deep superior of left breast under MLO view (white arrow), but the CC view could not demonstrate the tumor location. (c) Breast MRI (oblique view of 3D MIP) is more clearly to demonstrate multiple foci of malignant masses by different tumor

location and tumor sizes . Pathological proved as IDC and DCIS.

Fig. 11. (a) Breast MRI have the merit on the describing multifocality and the detection of asymptomatic cancer on the contralateral breast. In this Asian patient, digital mammography shows a single isodense palpable mass at superior of left breast (white arrow with metal beam). (b)(c)The follow up breast MRI shows another two enhanced tumor masses, with ill defined margin at superior lateral of right breast (long white arrow), which was proved as IDC. There is also a well defined enhanced mass with smooth margin, locate at paramedial aspect of left breast (black thick arrow), which was proved as fibroadenoma. Besides, the stronger enhancement of left axillary lymph nodes (circle on 11b) indicate the metastasis, compared with the weaker enhancement of right axillary lymph nodes (circle on 11c).

The Application of Breast MRI on Asian Women (Dense Breast Pattern) 45

(a)

(b) (c)

schedule of call-back mammographic guide biopsy was cancelled.

Fig. 14. Breast MRI may decrease unnecessary biopsy base on interpretation of screening mammography. In this Asian patient, digital mammography with spot compression view on left breast (a) demonstrate some cluster of faint microcalcifications. However, the follow up breast MRI shows no enhanced lesion in both 3D MIP (b) and subtracted image (c), thus, the

Fig. 12. (a) Breast MRI shows suspect enlarged lymph node at left side internal mammary chain (white arrows), (b) which proven by PET scan (black arrows).

Fig. 13. Free silicon injection with silicoma and calcified granuloma formations usually occult the possible tumor growth on mammography (a); MRI with sagittal T2 plus fat saturation (b) and post enhanced subtracted image (c) provide a satisfactory detective rate on cancer on this group of patient.

(a) (b)

chain (white arrows), (b) which proven by PET scan (black arrows).

Fig. 12. (a) Breast MRI shows suspect enlarged lymph node at left side internal mammary

(a) (b) (c)

Fig. 13. Free silicon injection with silicoma and calcified granuloma formations usually occult the possible tumor growth on mammography (a); MRI with sagittal T2 plus fat saturation (b) and post enhanced subtracted image (c) provide a satisfactory detective rate

on cancer on this group of patient.

(a)

Fig. 14. Breast MRI may decrease unnecessary biopsy base on interpretation of screening mammography. In this Asian patient, digital mammography with spot compression view on left breast (a) demonstrate some cluster of faint microcalcifications. However, the follow up breast MRI shows no enhanced lesion in both 3D MIP (b) and subtracted image (c), thus, the schedule of call-back mammographic guide biopsy was cancelled.

The Application of Breast MRI on Asian Women (Dense Breast Pattern) 47

The following figures demonstrate the application of DBMRI with the MPR technique, based on the AurorCad 4.0's oblique display protocol (Aurora System; Aurora Imaging Technology Inc., North Andover, MA, USA). The 3D maximum intensity projection (MIP) image outputs the selected plane of orientation as an oblique MPR on side-by-side display windows. The user controls the rotation of the 3D MIP from any angle, and the MPR pane is updated to match the slice, while having the same orientation as the MIP (Figures 16a &

(a) (b)

slice in the same orientation as the new orientation of the MIP (b).

of size and distribution is important.

Fig. 16. While controlling the rotation of the 3D MIP (Maximum Intensity Projection) (a) from any angle of rotation, the MPR (multi-planar reformation) pane updates to match the

Ductal carcinoma *in situ* (DCIS) is a preinvasive condition that appears as tumor lesions of the ducts with severe atypical proliferation of epithelial cells. DCIS shows different grades of malignant potential, and certain subtypes of DCIS are more likely to recur. Approximately 60 % of women with DCIS will progress to invasive ductal carcinoma (IDC) over an 8–10-year period, and poor prognostic outcomes are likely when IDC develops. Thus, the early detection of DCIS through imaging studies that permit accurate assessment

Breast MRI is a useful tool for staging invasive cancers like IDC. However, traditional breast MRI systems have limitations in the analysis of early DCIS using the sagittal and coronal planes. Although MRI provides a 3D representation of the enhanced tissues, the borders between DCIS and its surrounding benign processes are often indistinguishable, especially when DCIS is sparsely scattered. The actual size is also difficult to measure accurately during pathological examinations. This is because of the anatomy of the breast ducts are distributed in three dimensions and histological sections show only two. Measuring

16b).

#### **11. Using a dedicated breast MRI system with the application of postprocessing techniques for multiplanar reformation (MPR) on mammary ductal orientation, for three-dimensional (3D) anatomical demonstration**

Surgeons are required to localize accurately malignant tumors of the breast. Preoperative evaluation using DCIS or IDC is helpful for determining the surgical method and the necessity of lymphadectomy or preoperative chemotherapy. Compared to mammography and sonography, magnetic resonance imaging (MRI) is the most sensitive tool for breast cancer detection. Its ability for 3D anatomical representation has also become more important for pre-surgical evaluation.

Although the incidence of DCIS of the breast seems to be gradually increasing in Taiwan and other Asian countries, the proportion of small tumors detected is lower than in Western countries (Leung et al., 2010c; Huang et al., 2001; Shen et al., 2005).

The early stage of ductal carcinoma in situ (DCIS) appears as a spread-out distribution pattern, extending toward the nipple and is occasionally seen in the breast tissue peripheral to the infiltrating carcinoma. Only 3D imagery demonstrates the correlation of image and pathology. Sonography and mammography are incapable of showing the anatomical and spatial relationship between the lesion and the ductal structures within the breast (Figure 15) (Leung et al., 2010c).

Fig. 15. shows the relationship between the mammary duct, the glandular tissue, and the nipple (Leung et al., 2010c).

**postprocessing techniques for multiplanar reformation (MPR) on mammary ductal orientation, for three-dimensional (3D) anatomical demonstration** 

Surgeons are required to localize accurately malignant tumors of the breast. Preoperative evaluation using DCIS or IDC is helpful for determining the surgical method and the necessity of lymphadectomy or preoperative chemotherapy. Compared to mammography and sonography, magnetic resonance imaging (MRI) is the most sensitive tool for breast cancer detection. Its ability for 3D anatomical representation has also become more

Although the incidence of DCIS of the breast seems to be gradually increasing in Taiwan and other Asian countries, the proportion of small tumors detected is lower than in Western

The early stage of ductal carcinoma in situ (DCIS) appears as a spread-out distribution pattern, extending toward the nipple and is occasionally seen in the breast tissue peripheral to the infiltrating carcinoma. Only 3D imagery demonstrates the correlation of image and pathology. Sonography and mammography are incapable of showing the anatomical and spatial relationship between the lesion and the ductal structures within the breast (Figure

Fig. 15. shows the relationship between the mammary duct, the glandular tissue, and the

**11. Using a dedicated breast MRI system with the application of** 

countries (Leung et al., 2010c; Huang et al., 2001; Shen et al., 2005).

important for pre-surgical evaluation.

15) (Leung et al., 2010c).

nipple (Leung et al., 2010c).

The following figures demonstrate the application of DBMRI with the MPR technique, based on the AurorCad 4.0's oblique display protocol (Aurora System; Aurora Imaging Technology Inc., North Andover, MA, USA). The 3D maximum intensity projection (MIP) image outputs the selected plane of orientation as an oblique MPR on side-by-side display windows. The user controls the rotation of the 3D MIP from any angle, and the MPR pane is updated to match the slice, while having the same orientation as the MIP (Figures 16a & 16b).

Fig. 16. While controlling the rotation of the 3D MIP (Maximum Intensity Projection) (a) from any angle of rotation, the MPR (multi-planar reformation) pane updates to match the slice in the same orientation as the new orientation of the MIP (b).

Ductal carcinoma *in situ* (DCIS) is a preinvasive condition that appears as tumor lesions of the ducts with severe atypical proliferation of epithelial cells. DCIS shows different grades of malignant potential, and certain subtypes of DCIS are more likely to recur. Approximately 60 % of women with DCIS will progress to invasive ductal carcinoma (IDC) over an 8–10-year period, and poor prognostic outcomes are likely when IDC develops. Thus, the early detection of DCIS through imaging studies that permit accurate assessment of size and distribution is important.

Breast MRI is a useful tool for staging invasive cancers like IDC. However, traditional breast MRI systems have limitations in the analysis of early DCIS using the sagittal and coronal planes. Although MRI provides a 3D representation of the enhanced tissues, the borders between DCIS and its surrounding benign processes are often indistinguishable, especially when DCIS is sparsely scattered. The actual size is also difficult to measure accurately during pathological examinations. This is because of the anatomy of the breast ducts are distributed in three dimensions and histological sections show only two. Measuring

The Application of Breast MRI on Asian Women (Dense Breast Pattern) 49

Non-DCIS early ductal lesions, including intraductal papilloma, ductal hyperplasia, and early focal IDC, can be visualized using MPR with ductal orientation. Although certain characteristics of the lesion morphology (Figure 18) are similar to the pictures in terms of tumor size and the spreading along glandular tissue, not all lesions exhibit a ductogram appearance. However, additional analysis using early subtracted image and a post-contrast

Fig. 18. Three types of non-DCIS lesions, both benign and malignant, under MPR with ductal orientation. (a) MPR shows enhanced thick strip-like intensity with an irregular contour, which spreads along the intraductal structure (arrow) and within the network (intraductal papilloma). (b) MPR shows an enhanced and well-defined smooth nodular lesion with a tadpole morphology, which occupies the intraductal area of the non-dilated side (ductal hyperplasia; arrow). (c) MPR shows a focal lesion with enhancement (arrow), which crosses over the ducts of the surrounding glandular structures and is not continuous

A traditional MRI system can provide coronal, sagittal, and coronal images of the whole breast and is capable of visualizing lesions (Menellet et al., 2005). However, the borders between DCIS and its surrounding benign processes are often indistinguishable, especially when DCIS is sparsely scattered. The actual size, based on the pathologic examination, is also difficult to accurately measure. This is because the anatomy of the breast ducts is distributed in three dimensions, while histological sections are in two dimensions. Measuring scattered and widely distributed DCIS is difficult, which is one possible explanation for the frequent mismatch between MRI and pathologically determined tumor size. In addition, heterogeneous DCIS lesions more often exist alongside benign active tissue or lesions, such as adenosis, sclerosing adenosis, inflammation, and proliferative fibrocystic

with the ductal structures (early focal intraductal carcinoma).

kinetic curve may further confirm the image diagnosis.

scattered and widely distributed DCIS is difficult, which is one possible explanation for the frequent mismatch between MRI and pathological findings.

Screening for cases with ductogram appearance were performed to find if a significant correlation between DCIS and ductograms exists. The term 'ductogram' was used for image phenomenon that occurred when peri-ductal infiltration in the tissues immediately adjacent to the mammary duct was observed. The ductogram image shows non-contrast ductal structures differing from the enhanced periductal tumor infiltration if the ductal orientation is in phase using multiplanar reformation (MPR) (Leung et al., 2010c) (Figure 17).

Fig. 17. (a) A characteristic ductogram appearance (long arrow) is visualized in case 1. (b) A characteristic ductogram appearance (long arrow) is visualized in case 2. (c) Case 3 shows characteristics of a ductogram pattern along the lactiferous sinus and duct to the areola, within a background of stripping and non-mass signal intensity. (d) Case 4 shows that pure DCIS is an intermediate grade of malignancy with delayed surgical treatment, in which the ductogram appearance is preserved. The MPR for ductal orientation is visualized by a nonmass with strip appearance, and lesion cross-over glandular tissue. (e) Case 5 shows pure DCIS visualized by its non-mass like intensity (curved arrow) and ductogram appearance. (f) Case 6 shows pure DCIS appearing with non-mass of intensity (arrow is the true DICIS area). The MRI overestimates tumor size over pathological size by over 200% (the curved arrow shows the false area).

scattered and widely distributed DCIS is difficult, which is one possible explanation for the

Screening for cases with ductogram appearance were performed to find if a significant correlation between DCIS and ductograms exists. The term 'ductogram' was used for image phenomenon that occurred when peri-ductal infiltration in the tissues immediately adjacent to the mammary duct was observed. The ductogram image shows non-contrast ductal structures differing from the enhanced periductal tumor infiltration if the ductal orientation

Fig. 17. (a) A characteristic ductogram appearance (long arrow) is visualized in case 1. (b) A characteristic ductogram appearance (long arrow) is visualized in case 2. (c) Case 3 shows characteristics of a ductogram pattern along the lactiferous sinus and duct to the areola, within a background of stripping and non-mass signal intensity. (d) Case 4 shows that pure DCIS is an intermediate grade of malignancy with delayed surgical treatment, in which the ductogram appearance is preserved. The MPR for ductal orientation is visualized by a nonmass with strip appearance, and lesion cross-over glandular tissue. (e) Case 5 shows pure DCIS visualized by its non-mass like intensity (curved arrow) and ductogram appearance. (f) Case 6 shows pure DCIS appearing with non-mass of intensity (arrow is the true DICIS area). The MRI overestimates tumor size over pathological size by over 200% (the curved

arrow shows the false area).

is in phase using multiplanar reformation (MPR) (Leung et al., 2010c) (Figure 17).

frequent mismatch between MRI and pathological findings.

Non-DCIS early ductal lesions, including intraductal papilloma, ductal hyperplasia, and early focal IDC, can be visualized using MPR with ductal orientation. Although certain characteristics of the lesion morphology (Figure 18) are similar to the pictures in terms of tumor size and the spreading along glandular tissue, not all lesions exhibit a ductogram appearance. However, additional analysis using early subtracted image and a post-contrast kinetic curve may further confirm the image diagnosis.

Fig. 18. Three types of non-DCIS lesions, both benign and malignant, under MPR with ductal orientation. (a) MPR shows enhanced thick strip-like intensity with an irregular contour, which spreads along the intraductal structure (arrow) and within the network (intraductal papilloma). (b) MPR shows an enhanced and well-defined smooth nodular lesion with a tadpole morphology, which occupies the intraductal area of the non-dilated side (ductal hyperplasia; arrow). (c) MPR shows a focal lesion with enhancement (arrow), which crosses over the ducts of the surrounding glandular structures and is not continuous with the ductal structures (early focal intraductal carcinoma).

A traditional MRI system can provide coronal, sagittal, and coronal images of the whole breast and is capable of visualizing lesions (Menellet et al., 2005). However, the borders between DCIS and its surrounding benign processes are often indistinguishable, especially when DCIS is sparsely scattered. The actual size, based on the pathologic examination, is also difficult to accurately measure. This is because the anatomy of the breast ducts is distributed in three dimensions, while histological sections are in two dimensions. Measuring scattered and widely distributed DCIS is difficult, which is one possible explanation for the frequent mismatch between MRI and pathologically determined tumor size. In addition, heterogeneous DCIS lesions more often exist alongside benign active tissue or lesions, such as adenosis, sclerosing adenosis, inflammation, and proliferative fibrocystic

The Application of Breast MRI on Asian Women (Dense Breast Pattern) 51

1993). Breast neoplasm is a developing disease, and initially the possible risk cannot be precisely determined by a single biopsy result. A study conducted by Liberman el al. demonstrated that 24% of all breast MRI cases studied were interpreted as 'probably benign' in the initial readings. Within seven months, however, nearly 10% of them were subsequently proven to be malignancies (Buadu et al., 1996). One study based on over 120,000 individual cases collected in ten years that received breast biopsies, had been diagnosed as benign disease. However, 50% of the lesions were associated proliferative changes, of which nearly 10% had atypical ductal hyperplasia. Within this latter group, 15% eventually developed invasive carcinoma (London et al., 1992). Atypical hyperplasia and other benign results at the first time of biopsied, is significantly increased risk of breast cancer (London et al., 1992). In another study, about 2% of cases interpreted as probably

Accordingly, we cannot negate the possibility to those probably benign lesions or suspected malignant lesions that based on MRI's interpretation that initially proven to be benign(as false positive lesions) may further malignant development, although it is not yet to have a precise predictive percentage value. Thus, of the proven benign cases, it is essential to have long-term imaging follow-up. To our limited knowledge, not able to explain the possible reasons of false positive interpretation of MRI, there is still lack of study on direct biomolecular correlation with MRI images. In the future, we believe that further understanding of tumor transformation will improve our interpretation of dynamically enhanced breast MRI, according to the kinetic curve analysis. This will help in evaluating lesions as well as identifying angiogenesis, microvessel density, and microvascular endothelial permeabilities. The investigation should also include image-pathology correlations of tumor behavior, biological activity, nuclear pleomorphism, mitotic count, and histological grading (Bone et al., 1998; Mussurakis et al., 1997; Narisada et al., 2006;

DBMRI can differentiate breast glandular tissue and pathological lesions from silicone/saline bag implants. It can also better visualize intracapsular rupture of breast implantation. Breast augmentation has become popular among different age groups in Asia, especially in the developed countries. In our breast image center, over 30% of breast MRI candidates have received at least one or two different types of breast implant surgery. Silicon can cause major complications. Silicone compounds primarily consist of fluids, gels, rubbers, sponges, foams, and resins (Ojo-Amaize et al., 1994). Although silicone is relatively inert and biocompatible with biological tissue, it is polymeric, has hydrophobic characteristics, and possesses electrostatic charges. The organic side groups have potentially immunogenic factors, especially over the long-term. Silicone induces inflammatory responses in women with breast implants who have several types of autoantibodies against different self-antigens (Van Gilset al., 1999). The symptoms and signs of preoperative diagnosis for breast implant rupturing based on physical examination are usually vague, especially when the fibrous capsule encloses the rupture. This situation may become complicated when active inflammation and malignancy are suspected. Image studies are, then, necessary for localization and preoperative

benign were subsequently identified as malignancies (Liberman et al., 2003).

**13. Screening by DBMRI with breast augmentations** 

differentiation (Scaranelo et al., 2004).

Szabo et al., 2003).

changes. Therefore, the image size acquired in DBMRI is usually overestimated and larger than the actual pathological size of the lesion. MPR with a ductal orientation for anatomical localization and 3D demonstration was found to be a useful technique for increasing the detection rate for early stage DCIS. Detection is performed using characteristic findings that include a strip morphology, the spreading along glandular tissue, and a ductogram appearance. Moreover, MPR is excellent for visualizing the anatomical pattern of spreading early intraductal carcinoma which extends towards the nipple. In addition, MPR can show the spatial relationship between the carcinoma and the surrounding breast tissue. These findings should be considered for surgical strategy in segmental resections or partial mastectomy. Breast MRI with MPR for ductal orientation improves the early detection rate and exhibits higher specificity because of improved anatomical interpretation of mammary ducts. However, the existence of adenosis, fibroadenomas, and some specific benign proliferative processes may still interfere with the characteristic pattern of the MRI findings. This can lead to an overestimation of the true size and scope of the distribution (Viehweg et al., 2000). For cases of IDC with a DCIS component, distinguishing the DCIS from the IDC region is difficult. Some pitfalls exist when matching the three-dimensional DCIS distribution with the routine two-dimensional histology sectioning. Using a DBMRI system with Spiral Rodeo pulse sequence, those lesions that could be subtracted in the ESP were almost completely excluded from the possibility of being a malignancy (Figure 6b).

To improve the correlation between image diagnosis of tumor size and pathological size, the pathologist should be notified of the MRI findings, the estimated lesion size, and the mammary ductal orientation before planning sectioning of a specimen that is scheduled for microscopic study. In the future, better integration of radiologists, surgeons, and pathologists to propose working guidelines would create an environment for better correlation of imaging studies and pathology. The accumulation of experience will provide a more accurate estimation of the DCIS volume and improve preoperative image assessment (Mariano et al., 2005; Neubauer et al., 2003).

#### **12. Probably benign interpretations of Breast MRI and False positive biopsy results base on MRI interpretation**

Breast MRI is a very sensitive modality for breast lesion, but the specificity for real malignancy is the issue that long been concerned. People may think breast MRI can pick up a lot of things, but these things are not necessarily abnormal. Besides malignant lesions, Breast MRI may also highlight fibrocysts, fibroadenomas, and other benign conditions. Breast MRI reported to have false positive rate, range from 13% to 83% (Hoogerbrugge et al., 2008), which means that it may misdiagnosis for lesions that not cancer. Breast MRI reading radiologists have the responsibility, through restlessly of receiving new MRI knowledge and collecting clinical experience, to achieve higher specificity of tumor differentiation and image diagnosis. By our self assessment in Taipei Medical University hospital, benign lesions reported by pathology accounted for 15.2%, which were initially suspected of being malignancy based on the MRI. In our experience, the pathological results of those false positive MRI interpretations are included atypical ductal hyperplasia, adenosis/apocrine metaplasia, radial scar, sclerosing adenosis, phylloides tumor, infectious mastitis and fat necrosis with hemorrhage.

In both North America and in Asia, the frequency of benign proliferative breast lesions, particularly among women under 40 years of age, is progressively increasing (Schnitt et al.,

changes. Therefore, the image size acquired in DBMRI is usually overestimated and larger than the actual pathological size of the lesion. MPR with a ductal orientation for anatomical localization and 3D demonstration was found to be a useful technique for increasing the detection rate for early stage DCIS. Detection is performed using characteristic findings that include a strip morphology, the spreading along glandular tissue, and a ductogram appearance. Moreover, MPR is excellent for visualizing the anatomical pattern of spreading early intraductal carcinoma which extends towards the nipple. In addition, MPR can show the spatial relationship between the carcinoma and the surrounding breast tissue. These findings should be considered for surgical strategy in segmental resections or partial mastectomy. Breast MRI with MPR for ductal orientation improves the early detection rate and exhibits higher specificity because of improved anatomical interpretation of mammary ducts. However, the existence of adenosis, fibroadenomas, and some specific benign proliferative processes may still interfere with the characteristic pattern of the MRI findings. This can lead to an overestimation of the true size and scope of the distribution (Viehweg et al., 2000). For cases of IDC with a DCIS component, distinguishing the DCIS from the IDC region is difficult. Some pitfalls exist when matching the three-dimensional DCIS distribution with the routine two-dimensional histology sectioning. Using a DBMRI system with Spiral Rodeo pulse sequence, those lesions that could be subtracted in the ESP were

almost completely excluded from the possibility of being a malignancy (Figure 6b).

(Mariano et al., 2005; Neubauer et al., 2003).

**results base on MRI interpretation** 

necrosis with hemorrhage.

To improve the correlation between image diagnosis of tumor size and pathological size, the pathologist should be notified of the MRI findings, the estimated lesion size, and the mammary ductal orientation before planning sectioning of a specimen that is scheduled for microscopic study. In the future, better integration of radiologists, surgeons, and pathologists to propose working guidelines would create an environment for better correlation of imaging studies and pathology. The accumulation of experience will provide a more accurate estimation of the DCIS volume and improve preoperative image assessment

**12. Probably benign interpretations of Breast MRI and False positive biopsy** 

Breast MRI is a very sensitive modality for breast lesion, but the specificity for real malignancy is the issue that long been concerned. People may think breast MRI can pick up a lot of things, but these things are not necessarily abnormal. Besides malignant lesions, Breast MRI may also highlight fibrocysts, fibroadenomas, and other benign conditions. Breast MRI reported to have false positive rate, range from 13% to 83% (Hoogerbrugge et al., 2008), which means that it may misdiagnosis for lesions that not cancer. Breast MRI reading radiologists have the responsibility, through restlessly of receiving new MRI knowledge and collecting clinical experience, to achieve higher specificity of tumor differentiation and image diagnosis. By our self assessment in Taipei Medical University hospital, benign lesions reported by pathology accounted for 15.2%, which were initially suspected of being malignancy based on the MRI. In our experience, the pathological results of those false positive MRI interpretations are included atypical ductal hyperplasia, adenosis/apocrine metaplasia, radial scar, sclerosing adenosis, phylloides tumor, infectious mastitis and fat

In both North America and in Asia, the frequency of benign proliferative breast lesions, particularly among women under 40 years of age, is progressively increasing (Schnitt et al., 1993). Breast neoplasm is a developing disease, and initially the possible risk cannot be precisely determined by a single biopsy result. A study conducted by Liberman el al. demonstrated that 24% of all breast MRI cases studied were interpreted as 'probably benign' in the initial readings. Within seven months, however, nearly 10% of them were subsequently proven to be malignancies (Buadu et al., 1996). One study based on over 120,000 individual cases collected in ten years that received breast biopsies, had been diagnosed as benign disease. However, 50% of the lesions were associated proliferative changes, of which nearly 10% had atypical ductal hyperplasia. Within this latter group, 15% eventually developed invasive carcinoma (London et al., 1992). Atypical hyperplasia and other benign results at the first time of biopsied, is significantly increased risk of breast cancer (London et al., 1992). In another study, about 2% of cases interpreted as probably benign were subsequently identified as malignancies (Liberman et al., 2003).

Accordingly, we cannot negate the possibility to those probably benign lesions or suspected malignant lesions that based on MRI's interpretation that initially proven to be benign(as false positive lesions) may further malignant development, although it is not yet to have a precise predictive percentage value. Thus, of the proven benign cases, it is essential to have long-term imaging follow-up. To our limited knowledge, not able to explain the possible reasons of false positive interpretation of MRI, there is still lack of study on direct biomolecular correlation with MRI images. In the future, we believe that further understanding of tumor transformation will improve our interpretation of dynamically enhanced breast MRI, according to the kinetic curve analysis. This will help in evaluating lesions as well as identifying angiogenesis, microvessel density, and microvascular endothelial permeabilities. The investigation should also include image-pathology correlations of tumor behavior, biological activity, nuclear pleomorphism, mitotic count, and histological grading (Bone et al., 1998; Mussurakis et al., 1997; Narisada et al., 2006; Szabo et al., 2003).

#### **13. Screening by DBMRI with breast augmentations**

DBMRI can differentiate breast glandular tissue and pathological lesions from silicone/saline bag implants. It can also better visualize intracapsular rupture of breast implantation. Breast augmentation has become popular among different age groups in Asia, especially in the developed countries. In our breast image center, over 30% of breast MRI candidates have received at least one or two different types of breast implant surgery. Silicon can cause major complications. Silicone compounds primarily consist of fluids, gels, rubbers, sponges, foams, and resins (Ojo-Amaize et al., 1994). Although silicone is relatively inert and biocompatible with biological tissue, it is polymeric, has hydrophobic characteristics, and possesses electrostatic charges. The organic side groups have potentially immunogenic factors, especially over the long-term. Silicone induces inflammatory responses in women with breast implants who have several types of autoantibodies against different self-antigens (Van Gilset al., 1999). The symptoms and signs of preoperative diagnosis for breast implant rupturing based on physical examination are usually vague, especially when the fibrous capsule encloses the rupture. This situation may become complicated when active inflammation and malignancy are suspected. Image studies are, then, necessary for localization and preoperative differentiation (Scaranelo et al., 2004).

The Application of Breast MRI on Asian Women (Dense Breast Pattern) 53

Harris et al., 1993; Venta et al., 1996). There is limitation for sonogram to rule out extracapsular rupture, but accurate diagnosis requires magnetic resonance imaging (Chung et al., 1996; Harris et al., 1993; Venta et al., 1996). As a result, the FDA has recommended that MRIs be considered for use in screening for silent ruptures starting at three years after implantation, and every two years thereafter (Allergan, 2006; FDA, 2004). The following figures show a special case with initially neither breast sonography nor mammography was able to detect the intracapsular rupture of the implant. Although mammography reveals microcalcifications that might be malignancy, but the final suggestion for surgery is based on MRI images. In our opinion, MRI should be a first-line diagnostic tool for implant

rupture when coexisting malignancy is suspected (Paetau et al., 2010) (Figure 19).

(a) (b)

(c) (d)

Intense images followed up with sonography may find minor changes in implanted breast pathology. However, in most situations, breast sonography provided no definite way to differentiate benign from malignant conditions. When mammography is arranged, welltrained radiological technicians may help provide good quality pictures as the implantation is being compressed and differentiate the implant from normal breast glandular tissue, in order to detect possible lesions. Poor technique for patients with breast implants are increase the risk of iatrogenic ruptures. In this situation, sonographic guided or mammographic guided biopsy may be indicated. If DBMRI is available, further analysis with noninvasive techniques is preferred before a biopsy is suggested.

In our center, a breast MRI with a dedicated breast acquisition system was arranged using the Aurora Spiral Rodeo pulse sequence (Figure 19). The Silicone and water Rodeo image mode was adopted to subtract implanted silicone and water bag material as low signal intensity background before and after contrast injection. Post processing of the images could be performed using silicon and water material subtraction techniques followed by the AurorCad 4.0's color mapping display protocol. The same procedure may also apply to other breast augmentation material, such as hyaluronic acid (HA) and an individual's own breast tissue.

Although it is difficult to identify the malignancies when the rupture of implants was coexisted, MRI is considered the most accurate modality for detecting breast cancer in the presence of silicone (Azavedo & Bone, 1999). The MR images of ruptured implants usually showed low-signal-intensity bands, linguine appearance, and a mass within the gel of the implants, while of malignancies were irregular margin and showed reddish of color mapping. However, free silicone may be hypothesized to induce a foreign body reaction with dense fibrosis and granulomatous formations. In this situation, distinction of inflammation areas and malignancies remains problematic.

In case of rupture, silicone from an implant can leak out into the space around the implant. An intracapsular rupture (silicone contained within the fibrous capsule) can progress to the outside of the, becoming an extracapasular rupture (silicone present outside the fibrous capsule) (Everson et al., 1994). These conditions indicate the need for removal of the implant. Previous study results establish a rupture rate of 8.0 percent at 11 years for silicone breast implants (Hedén et al., 1994). If clinical examination by a skillful surgeon is the only diagnostic tool for identifying implant rupture, it is not reliable, and neither the sensitivity nor the specificity is acceptable (Holmich et al., 2005). Physical examination is inadequate to evaluate a suspected rupture, as experienced plastic surgeons accurately detect only 30% of ruptures in asymptomatic patients, compared to 86% detected by MRI (Hedén et al., 1994). Mammography is a highly sensitive and specific modality for diagnosing extracapasular silicone rupture, and it can detect silicone gel migration through the glandular parenchyma. On the other hand, the diagnosis of intracapsular rupture is difficult to detect via mammography (Gorczyca et al., 1994; Scaranelo et al., 1994). A change in implant shape is the most important mammographic pattern (Gorczyca et al., 1994). Breast sonography has been used in breast implant integrity evaluation for several years. A great variety of sonography signs detect anywhere from 10% to 17% of ruptured implants (Scaranelo et al., 1994). Breast sonography can be the first test in the assessment of breast implants in asymptomatic patients, followed by mammography. This is because breast sonography has greater ability to detect intracapsular rupture than mammography does (Chung et al., 1996;

Intense images followed up with sonography may find minor changes in implanted breast pathology. However, in most situations, breast sonography provided no definite way to differentiate benign from malignant conditions. When mammography is arranged, welltrained radiological technicians may help provide good quality pictures as the implantation is being compressed and differentiate the implant from normal breast glandular tissue, in order to detect possible lesions. Poor technique for patients with breast implants are increase the risk of iatrogenic ruptures. In this situation, sonographic guided or mammographic guided biopsy may be indicated. If DBMRI is available, further analysis with noninvasive

In our center, a breast MRI with a dedicated breast acquisition system was arranged using the Aurora Spiral Rodeo pulse sequence (Figure 19). The Silicone and water Rodeo image mode was adopted to subtract implanted silicone and water bag material as low signal intensity background before and after contrast injection. Post processing of the images could be performed using silicon and water material subtraction techniques followed by the AurorCad 4.0's color mapping display protocol. The same procedure may also apply to other breast augmentation material, such as hyaluronic acid (HA) and an individual's own

Although it is difficult to identify the malignancies when the rupture of implants was coexisted, MRI is considered the most accurate modality for detecting breast cancer in the presence of silicone (Azavedo & Bone, 1999). The MR images of ruptured implants usually showed low-signal-intensity bands, linguine appearance, and a mass within the gel of the implants, while of malignancies were irregular margin and showed reddish of color mapping. However, free silicone may be hypothesized to induce a foreign body reaction with dense fibrosis and granulomatous formations. In this situation, distinction of

In case of rupture, silicone from an implant can leak out into the space around the implant. An intracapsular rupture (silicone contained within the fibrous capsule) can progress to the outside of the, becoming an extracapasular rupture (silicone present outside the fibrous capsule) (Everson et al., 1994). These conditions indicate the need for removal of the implant. Previous study results establish a rupture rate of 8.0 percent at 11 years for silicone breast implants (Hedén et al., 1994). If clinical examination by a skillful surgeon is the only diagnostic tool for identifying implant rupture, it is not reliable, and neither the sensitivity nor the specificity is acceptable (Holmich et al., 2005). Physical examination is inadequate to evaluate a suspected rupture, as experienced plastic surgeons accurately detect only 30% of ruptures in asymptomatic patients, compared to 86% detected by MRI (Hedén et al., 1994). Mammography is a highly sensitive and specific modality for diagnosing extracapasular silicone rupture, and it can detect silicone gel migration through the glandular parenchyma. On the other hand, the diagnosis of intracapsular rupture is difficult to detect via mammography (Gorczyca et al., 1994; Scaranelo et al., 1994). A change in implant shape is the most important mammographic pattern (Gorczyca et al., 1994). Breast sonography has been used in breast implant integrity evaluation for several years. A great variety of sonography signs detect anywhere from 10% to 17% of ruptured implants (Scaranelo et al., 1994). Breast sonography can be the first test in the assessment of breast implants in asymptomatic patients, followed by mammography. This is because breast sonography has greater ability to detect intracapsular rupture than mammography does (Chung et al., 1996;

techniques is preferred before a biopsy is suggested.

inflammation areas and malignancies remains problematic.

breast tissue.

Harris et al., 1993; Venta et al., 1996). There is limitation for sonogram to rule out extracapsular rupture, but accurate diagnosis requires magnetic resonance imaging (Chung et al., 1996; Harris et al., 1993; Venta et al., 1996). As a result, the FDA has recommended that MRIs be considered for use in screening for silent ruptures starting at three years after implantation, and every two years thereafter (Allergan, 2006; FDA, 2004). The following figures show a special case with initially neither breast sonography nor mammography was able to detect the intracapsular rupture of the implant. Although mammography reveals microcalcifications that might be malignancy, but the final suggestion for surgery is based on MRI images. In our opinion, MRI should be a first-line diagnostic tool for implant rupture when coexisting malignancy is suspected (Paetau et al., 2010) (Figure 19).

The Application of Breast MRI on Asian Women (Dense Breast Pattern) 55

Boyd, N.F., Rommens, J.M., Vogt, K., Lee, V., Hopper, J.L., Yaffe, M.J. and Peterson, A.D.

Buadu, L.D., Murakami, J., Murayama, S., Hashiguchi, N., Sakai, S., Masuda, K., Toyoshima,

Chen, C.Y., Tzeng, W.S., Tsai, C.C., Mak, C.W., Chen, C.H. & Chou, M.C. (2008). Adjusting

Population. *Journal of the American College of Radiology,* Vol. 5, pp. 978-985. Chung, K.C., Wilkins, E.G., Beil, R.J., Helvie, M.A., Ikeda, D.M., Oneal, R.M., Forrest, M.E. &

Delille, J.P., Slanetz, P.J., Yeh, E.D., Kopans, D.B. & Garrido, L. (2005). Physiologic Changes

Dorrius, M.D., Pijnappel, R.M. & Oudkerk, M. (2009). Breast Magnetic Resonance Imaging

Dorrius, M.D., Pijnappel, R.M., Sijens, P.E., van der Weide, M.C. & Oudkerk, M. (2011). The

Egan, R.L. & Mosteller, R.C. (1977). Breast Cancer Mammography Patterns. *Cancer,* Vol. 40,

Erguvan-Dogan, B., Whitman, G.J., Kushwaha, A.C., Phelps, M.J. & Dempsey, P.J. (2006). BI-

Everson, L.I., Parantainen, H., Detlie, T., Stillman, A.E., Olson, P.N., Landis, G., Foshager,

Gorczyca, D.P., DeBruhl, N.D., Ahn, C.Y., Hoyt, A., Sayre, J.W., Nudell, P., McCombs, M.,

Gram, I.T., Funkhouser, E. & Tabar, L. (1997). The Tabar Classification of Mammographic Parenchymal Patterns. *European Journal of Radiology*, Vol. 24, No. 2, pp.131-136. Harris, K.M., Ganott, M.A., Shestak, K.C., Losken, H.W. & Tobon, H. (1993). Silicone Implant Rupture: Detection with US. *Radiology*, Vol. 187, No. 3, pp. 761-768.

Tissue. *The Breast Journal,* Vol. 11, No. 4, pp. 236-241.

BIRADS 3 lesions. *European Journal of Radiology,* in press.

*of Roentgenology,* Vol. 163, No. 1, pp. 57-60, ISSN 0361-803X.

Cancer. *Lancet Oncology*, Vol. 6, pp. 798-808, ISSN 1470-2045.

200, No.3, pp. 639-649.

133-139.

129.

pp. 2087-2090.

W160, ISSN 0361-803X.

190, No. 1, pp. 227-232.

FDA. (2004). *FDA Breast Implant Consumer Handbook.* 

(2005). Mammographic Breast Density as an Intermediate Phenotype for Breast

S., Kuroki, S. & Ohno, S. (1996). Breast Lesions: Correlation of Dynamic Contrast Enhancement Patterns on MR Images with Tumor Angiogenesis. *Radiology*, Vol.

Mammography-Audit Recommendations in a Lower-Incidence Taiwanese

Smith, D.J. (1996). Diagnosis of Silicone Gel Breast Implant Rupture by Ultrasonography. *Plastic and Reconstructive Surgery,* Vol. 97, No. 1, pp. 104-109. Chuwa, E.W., Yeo, A.W., Koong, H.N., Wong, C.Y., Yong, W.S., Tan, P.H., Ho, J.T., Wong,

J.S. & Ho, G.H. (2009). Early Detection of Breast Cancer through Population-Based Mammographic Screening in Asian Women: A Comparison Study between Screen-Detected and Symptomatic Breast Cancers. *The Breast Journal*, Vol. 15, No. 2, pp.

in Breast Magnetic Resonance Imaging during the Menstrual Cycle: Perfusion Imaging, Signal Enhancement, and Influence of the T1 Relaxation Time of Breast

as a Problem-Solving Modality? *Imaging Decisions MRI*, Vol. 13, No. 3-4, pp. 126-

negative predictive value of breast Magnetic Resonance Imaging in noncalcified

RADS-MRI: A Primer. *American Journal of Roentgenology,* Vol. 187, No. 2, pp. W152-

M.C., Cunningham, B. & Griffiths, H.J. (1994). Diagnosis of Breast Implant Rupture: Imaging Findings and Relative Efficacies of Imaging Techniques. *American Journal* 

Shaw, W.W. & Bassett, L.W. (1994). Silicone Breast Implant Ruptures in An animal Model: Comparison of Mammography, MR Imaging, US, And CT. *Radiology,* Vol.

Fig. 19. (a) The breast MRI showed an ill-defined, non-mass enhanced area with red under color mapping, located in the deep superior anterior portion of the left breast (region1); the silicon implantation is showed by white arrow. (b) The breast MRI showed an enhanced focus with heterogenous red and yellow color mapping (marked by blue circle) at about 9 o'clock from the nipple of the left breast (region2); Blue area (by curved arrow) respresents intracapsular rupture within the implanted silicon bag (white arrow). (c) The mass (region1) of irregular red and yellow by color mapping (by white arrow) showed by DBMRI is corresponding to the excised specimen and is palpable as firm mass by surgeon (by white arrow). (d) Pathological results revealed a mass of invasive ductal carcinoma (IDC) on the region 1. (e) Pathological results also showed extensive high-grade ductal carcinoma in situ (DCIS) on region 2.

#### **14. Reference**


(e) Fig. 19. (a) The breast MRI showed an ill-defined, non-mass enhanced area with red under color mapping, located in the deep superior anterior portion of the left breast (region1); the silicon implantation is showed by white arrow. (b) The breast MRI showed an enhanced focus with heterogenous red and yellow color mapping (marked by blue circle) at about 9 o'clock from the nipple of the left breast (region2); Blue area (by curved arrow) respresents intracapsular rupture within the implanted silicon bag (white arrow). (c) The mass (region1) of irregular red and yellow by color mapping (by white arrow) showed by DBMRI is corresponding to the excised specimen and is palpable as firm mass by surgeon (by white arrow). (d) Pathological results revealed a mass of invasive ductal carcinoma (IDC) on the region 1. (e) Pathological results also showed extensive high-grade ductal carcinoma in situ

Agarwal, G., Pradeep, P.V., Aggarwal, V., Yip, C.H. & Cheung, P.S. (2007). Spectrum of

Allergan. (2006). *Important Information for Women about Breast Augmentation with INAMED* 

American College of Radiology. (2003). *Breast imaging reporting and data system (BIRADS),*

Amr, S.S., Sa'di, A.R., Ilahi, F. & Sheikh, S.S. (1995). The Spectrum of Breast Diseases in

Azavedo, E. & Bone, B. (1999). Imaging Breasts with Silicone Implants. *European Radiology*,

Bone, B., Aspelin, P., Bronge, L. & Veress, B. (1998). Contrast-enhanced MR imaging as a

Boyd, N.F., Lockwood, G.A., Byng, J.W., Tritchler, D.L. & Yaffe, M.J. (1998). Mammographic

*Medicine*, Vol. 15, No. 2, pp. 125-132 , ISSN 0256-4947.

Breast Cancer in Asian Women. *World Journal of Surgery,* Vol. 31, No. 5, pp. 1031-

Saudi Arab Females: A 26 Year Pathological Survey at Dhahran. *Annals of Saudi* 

prognostic indicator of breast cancer. *Acta Radiologica,* Vol. 39, No. 3, pp. 279-284,

Densities and Breast Cancer Risk. *Cancer Epidemiology, Biomarkers & Prevention,* Vol.

(DCIS) on region 2.

1040, ISSN 0364-2313.

*Silicone-Filled Breast Implants.* 

(fourth ed.), Reston, VA.

Vol. 9, No. 2, pp. 349-355.

ISSN 0284-1851.

7, pp. 1133-1144.

**14. Reference** 


FDA. (2004). *FDA Breast Implant Consumer Handbook.* 


The Application of Breast MRI on Asian Women (Dense Breast Pattern) 57

Lee, C.H., Dershaw, D.D., Kopans, D., Evans, P., Monsees, B., Monticciolo, D., Brenner, R.J.,

Lehman, C.D., Gatsonis, C., Kuhl, C.K., Hendrick, R.E., Pisano, E.D., Hanna, L., Peacock, S.,

Lehman, C.D., Isaacs, C., Schnall, M.D., Pisano, E.D., Ascher, S.M., Weatherall, P.T.,

Leung, G.M., Lam, T.H., Thach, T.Q. & Hedley, A.J. (2002). Will Screening Mammography in

Leung, T.K., Chu, J.S., Huang, P.J., Lee, C.M., Lin, Y.H., Chen, C.S., Tai, C.J. & Wu, C.H.

Leung, T.K., Huang, P.J., Chen, C.S., Lin, Y.H., Wu, C.H. & Lee, C.M. (2010). Is Breast MRI

Leung, T.K., Huang, P.J., Lee, C.M. & Chen, C.S. Silicone Breast Implant with Intracapsular

Leung, T.K., Huang, P.J., Lee, C.M., Chen, C.S., Wu, C.H. & Chao, J.S. (2010). Can Breast

Li, A., Wong, C.S., Wong, M.K., Lee, C.M. & Yeung, M.C. (2006). Acute Adverse Reactions to

Liberman, L., Mason, G., Morris, E.A. & Dershaw, D.D. (2006). Does Size Matter? Positive

Liberman, L., Morris, E.A., Benton, C.L., Abramson, A.F. & Dershaw, D.D. (2003). Probably

London, S.J., Connolly, J.L., Schnitt, S.J. & Colditz GA. (1992). A Prospective Study of Benign

Screening Study. *Radiology,* Vol. 244, No. 2, pp. 381-388.

*Experimental & Clinical Medicine,* Vol. 2, No. 5, pp. 245-250.

*American Journal of Roentgenology,* Vol. 186, No. 2, pp. 426-30.

High-Risk Women. *Cancer*, Vol. 98, No. 2, pp. 377-388.

No. 1, pp. 18-27.

11, pp. 1841-1846.

No. 3, pp. 143-149.

*Radiology,* Vol. 79, No. 941, pp. 368-371.

*Association*, Vol. 267, No. 7, pp. 941-944.

Vol. 16, No. 6, pp. 652-653.

1295-1303.

Bassett, L., Berg, W., Feig, S., Hendrick, E., Mendelson, E., D'Orsi, C., Sickles, E. & Burhenne, L.W. (2010). Breast Cancer Screening with Imaging: Recommendations from the Society of Breast Imaging and the ACR on the Use of Mammography, Breast MRI, Breast Sonography, and Other Technologies for the Detection of Clinically Occult Breast Cancer. *Journal of the American College of Radiology,* Vol*.* 7,

Smazal, S.F., Maki, D.D., Julian, T.B., DePeri, E.R., Bluemke, D.A. & Schnall, M.D. (2007). MRI Evaluation of the Contralateral Breast in Women with Recently Diagnosed Breast Cancer. *The New England Journal of Medicine,* Vol. 356, No. 13, pp.

Bluemke, D.A., Bowen, D.J., Marcom, P.K., Armstrong, D.K., Domchek, S.M., Tomlinson, G., Skates, S.J. & Gatsonis, C. (2007). Cancer Yield of Mammography, MR, and US in High-Risk Women: Prospective Multi-Institution Breast Cancer

the East Do More Harm Than Good? *American Journal of Public Health,* Vol. 92, No.

(2010). Breast MRI for Monitoring Images of an 'Adenomyoepithelioma with Malignant Features', Before, During, and After Chemotherapy. *The Breast Journal,* 

Screening More Effective Than Digital Mammography in Asian Women? *Journal of* 

Rupture Coexisting with Locally Advanced Carcinoma. *The Breast Journal,* in press.

Magnetic Resonance Imaging Demonstrate Characteristic Findings of Preoperative Ductal Carcinoma In Situ in Taiwanese Women? *Asian Journal of Surgery,* Vol. 33,

Magnetic Resonance Contrast Media--Gadolinium Chelates. *British Journal of* 

Predictive Value of MRI-Detected Breast Lesions as a Function of Lesion Size.

Benign Lesions at Breast Magnetic Resonance Imaging Preliminary Experience in

Breast Disease and the Risk of Breast Cancer. *Journal of the American Medical* 


Hartman, A.R., Daniel, B.L., Kurian, A.W., Mills, M.A., Nowels, K.W., Dirbas, F.M.,

Genetic Risk for Breast Carcinoma. *Cancer,* Vol. 100, No. 3, pp. 479-489. Hedén, P., Nava, M.B., van Tetering, J.P., Magalon, G., Fourie le, R., Brenner, R.J., Lindsey,

Vol. 54, No. 6, pp. 583-589.

Kong Hospital Authority, Hong Kong.

*Breast Disease,* Vol. 13, pp. 41-48.

*Oncology,* Vol. 28, No. 9, pp. 1450-1457.

5771.

No. 1, pp. 165-175.

pp. 101-110.

Limited. *Annals of Oncology*, Vol. 19, No. 4, pp. 655-659.

Kingham, K.E., Chun, N.M., Herfkens, R.J., Ford, J.M. & Plevritis, S.K. (2004). Breast Magnetic Resonance Image Screening and Ductal Lavage in Women at High

L.E., Murphy, D.K. & Walker, P.S. (2006). Prevalence of Rupture in Inamed Silicone Breast Implants. *Plastic and Reconstructive Surgery,* Vol. 118, No. 2, pp. 303-308. Holmich, L.R., Fryzek, J.P., Kjoller, K., Breiting, V.B., Jorgensen, A., Krag, C. & McLaughlin,

J.K. (2005). The Diagnosis of Silicone Breast-Implant Rupture: Clinical Findings Compared with Findings at Magnetic Resonance Imaging. *Annals of Plastic Surgery,*

Bonenkamp, H.J., de Hullu, J.A., Ligtenberg, M.J. & Boetes, C. (2008). The Impact of a False-Positive MRI on the Choice for Mastectomy in BRCA Mutation Carriers is

Patterns and Risk of Breast Cancer at and After a Prevalence Screen in Singaporean Women. *International Journal of Epidemiology,* Vol. 29, No. 1, pp. 11-19, ISSN 0300-

Mammography, Physical Examination, and Breast US and Evaluation of Factors that Influence Them: An Analysis of 27,825 Patient Evaluations. *Radiology,* Vol. 225,

Manoliu, R., Besnard, A., Tilanus-Linthorst, M., Seynaeve, C., Bartels, C., Kaas, R., Meijer, S., Oosterwijk, J., Hoogerbrugge, N., Tollenaar, R., Rutgers, E., Koning, H. & Klijn, J. (2006). Factors Affecting Sensitivity and Specificity of Screening Mammography and MRI in Women with an Inherited Risk for Breast Cancer.

C., Rieber-Brambs, A., Nordhoff, D., Heindel, W., Reiser, M. & Schild, H.H. (2010). Prospective multicenter cohort study to refine management recommendations for women at elevated familial risk of breast cancer: the EVA trial. *Journal of Clinical* 

H.H. (1999). Dynamic Breast MR Imaging: Are Signal Intensity Time Course Data Useful for Differential Diagnosis of Enhancing Lesions? *Radiology,* Vol. 211, No. 1,

than Age 40: Are They Different from Their Older Counterparts? *World Journal of* 

Hong Kong Cancer Registry. (2004). *Cancer Registry Annual Report,* Hong Kong SAR: Hong

Hoogerbrugge, N., Kamm, Y.J., Bult, P., Landsbergen, K.M., Bongers, E.M., Brunner, H.G.,

Huang, C.S., Chang, K.J. & Shen, C.Y. (2001). Breast Cancer Screening in Taiwan and China.

Jakes, R.W., Duffy, S.W., Ng, F.C., Gao, F. & Ng, E.N. (2000). Mammographic Parenchymal

Kolb, T.M., Lichy, J. & Newhouse, J.H. (2002). Comparison of the Performance of Screening

Kriege, M., Brekelmans, C., Obdeijn, I., Boetes, C., Zonderland, H., Muller, S., Kok, T.,

Kuhl, C., Weigel, S., Schrading, S., Arand, B., Bieling, H., König, R., Tombach, B., Leutner,

Kuhl, C.K., Mielcareck, P., Klaschik, S., Leutner, C., Wardelmann, E., Gieseke, J. & Schild,

Kwong, A., Cheung, P., Chan, S. & Lau, S. (2008). Breast Cancer in Chinese Women Younger

*Surgery,* Vol. 32, No. 12, pp. 2554-2561, ISSN 0364-2313.

*Breast Cancer Research and Treatment*, Vol. 100, No. 1, pp. 109-119.


The Application of Breast MRI on Asian Women (Dense Breast Pattern) 59

Plevritis, S.K., Kurian, A.W., Sigal, B.M., Daniel, B.L., Ikeda, D.M., Stockdale, F.E. & Garber,

Ryu, E., Ahn, O., Baek, S.S., Jeon, M.S., Han, S.E., Park, Y.R. & Ham, M.Y. (2008). Predictors

Saslow, D., Boetes, C., Burke, W., Harms, S., Leach, M.O., Lehman, C.D., Morris, E., Pisano,

Advisory Group. *A Cancer Journal for Clinicians*, Vol. 57, No. 2, pp. 75-89. Scaranelo, A.M., Marques, A.F., Smialowski, E.B. & Lederman, H.M. (2004). Evaluation of

Scaranelo, A.M., Marques, A.F., Smialowski, E.B. & Lederman, H.M. (2004). Evaluation of

Schnitt, S.J., Jimi, A. & Kojiro, M. (1993). The Increasing Prevalence of Benign Proliferative Breast Lesions in Japanese Women. *Cancer*, Vol. 71, No. 8, pp. 2528-2531. Shen, Y.C., Chang, C.J., Hsu, C., Cheng, C.C., Chiu, C.F. & Cheng, A.L. (2005). Significant

Shibuya, K., Mathers, C.D., Boschi-Pinto, C., Lopez, A.D. & Murray, C.J. (2002). Global and

Global Burden of Disease 2000. *BMC Cancer*, Vol. 2, No. 37, ISSN 1471-2407. Son, B.H., Kwak, B.S., Kim, J.K., Kim, H.J., Hong, S.J., Lee, J.S., Hwang, U.K., Yoon, H.S. &

Szabo, B.K., Aspelin, P., Kristoffersen, W.M., Tot, T. & Boné, B. (2003). Invasive breast

Thompson, J., Leach, M.O., Kwan-Lim, G., Gayther, S.A., Ramus, S.J.,Warsi, I., Lennard, F.,

*Epidemiology, Biomarkers & Prevention,* Vol. 14, No. 8, pp. 1986-1990.

*Advanced Nursing,* Vol. 64, No. 2, pp. 168-175, ISSN 0309-2402.

Findings. *Sao Paulo Medical Journal,* Vol. 122, No. 2, pp. 41-47.

findings. *Sao Paulo Medical Journal,* Vol. 122, No. 2, 41-47.

295, No. 20, pp. 2374-2384.

No. 2, pp. 155-160.

Radiology, Vol. 13, No. 11, pp. 2425-2435.

*Prevention,* Vol. 15, No. 7, pp. 1301-1305.

A.M. (2006). Cost-Effectiveness of Screening BRCA1/2 Mutation Carriers with Breast Magnetic Resonance Imaging. *Journal of the American Medical Association,* Vol.

of Mammography Uptake in Korean Women Aged 40 Years and Over. *Journal of* 

E., Schnall, M., Sener, S., Smith, R.A., Warner, E., Yaffe, M., Andrews, K.S. & Russell, C.A. (2007). American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. American Cancer Society Breast Cancer

the Rupture of Silicone Breast Implants by Mammography, Ultrasonography and Magnetic Resonance Imaging in Asymptomatic Patients: Correlation with Surgical

the rupture of silicone breast implants by mammography, ultrasonography and magnetic resonance imaging in asymptomatic patients: correlation with surgical

Difference in the Trends of Female Breast Cancer Incidence between Taiwanese and Caucasian Americans: Implications from Age-Period-Cohort Analysis. *Cancer* 

Regional Estimates of Cancer Mortality and Incidence by Site: II. Results for the

Ahn, S.H. (2006). Changing Patterns in the Clinical Characteristics of Korean Patients with Breast Cancer during the Last 15 Years. *Archives of Surgery,* Vol. 141,

cancer: correlation of dynamic MR features with prognostic factors. European

Khazen, M., Bryant, E., Reed, S., Boggis, C.R., Evans, D.G., Eeles, R.A., Easton, D.F. & Warren, R.M. (2009). Assessing the Usefulness of a Novel Mribased Breast Density Estimation Algorithm in a Cohort of Women at High Genetic Risk of Breast Cancer: The UK MARIBS Study. *Breast Cancer Research,* Vol. 11, No. 6, pp. R80. Tseng, M., Byrne, C., Evers, K.A., London, W.T., Daly, M.B. (2006). Acculturation and Breast

Density in Foreign-Born, U.S. Chinese Women. *Cancer Epidemiology, Biomarkers &* 


Mann, R.M., Kuhl, C.K., Kinkel, K. & Boetes, C. (2008). Breast MRI: Guidelines from the

Mariano, M.N., van den Bosch, M.A., Daniel, B.L., Nowels, K.W., Birdwell, R.L., Fong, K.J.,

Maskarineca, G., Menga, L. & Ursinb, G. (2001). Ethnic differences in mammographic densities. *International Journal of Epidemiology,* Vol. 30, pp. 959-965, ISSN 0300-5771. McCormack, V.A. & dos Santos, S. (2006). Breast Density and Parenchymal Patterns as

Menell, J.H., Morris, E.A., Dershaw, D.D., Abramson, A.F., Brogi, E. & Liberman, L. (2005).

Morimoto, T., Sasa, M., Yamaguchi, T., Harada, K. & Sagara, Y. (1994). High Detection Rate

Mussurakis, S., Buckley, D.L. & Horsman, A. (1997). Dynamic MR Imaging of Invasive

Nagata, C., Matsubara, T., Fujita, H., Nagao, Y., Shibuya, C., Kashiki, Y. & Shimizu, H.

Narisada, H., Aoki, T., Sasaguri, T., Hashimoto, H., Konishi, T., Morita, M. & Korogi, Y.

Neubauer, H., Li, M., Kuehne-Heid, R., Schneider, A. & Kaiser, W.A. (2003). High Grade and

Ng, E.H., Ng, F.C., Tan, P.H., Low, S.C., Chiang, G., Tan, K.P., Seow, A., Emmanuel, S., Tan,

Singapore Breast Screening Project. *Cancer,* Vol. 82, No. 8, pp. 1521-1528. Ojo-Amaize, E.A., Conte, V., Lin, H.C., Brucker, R.F., Agopian, M.S. & Peter, J.B. (1994).

*Journal of Radiology*, Vol 70, No. 833, pp. 446-451, ISSN 0007-1285.

*of Roentgenology,* Vol. 187, No. 2, pp. 297-306, ISSN 0361-803X.

Enhancement. *British Journal of Radiology,* Vol. 76, No. 901, pp. 3-12.

520-526.

pp. 382-390.

*Prevention,* Vol. 15, No. 6, pp. 1159-1169.

*of Cancer Research*, Vol. 85, No. 12, pp. 1193-1195.

*British Journal of Cancer,* Vol. 92, No. 12, pp. 2102-2106.

No, 3, pp. 830-835, ISSN 0032-1052.

European Society of Breast Imaging. *European Radiology,* Vol. 18, No. 7, pp. 1307-18.

Desmond, P.S., Plevritis, S., Stables, L.A., Zakhour, M., Herfkens, R.J. & Ikeda, D.M. (2005). Contrastenhanced MRI of Ductal Carcinoma *In Situ*: Characteristics of a New Intensity-Modulated Parametric Mapping Technique Correlated with Histopathologic Findings. *Journal of Magnetic Resonance Imaging,* Vol. 22, No. 4, pp.

Markers of Breast Cancer Risk: A Meta-Analysis. *Cancer Epidemiology, Biomarkers &* 

Determination of the Presence and Extent of Pure Ductal Carcinoma in Situ by Mammography and Magnetic Resonance Imaging. *The Breast Journal,* Vol. 11, No. 6,

of Breast Cancer by Mass Screening Using Mammography in Japan. *Japanese Journal* 

Breast Cancer: Correlation with Tumor Grade and Other Histologic Factors. *British* 

(2005). Mammographic Density and the Risk of Breast Cancer in Japanese Women.

(2006). Correlation between Numeric Gadolinium-Enhanced Dynamic MRI Ratios and Prognostic Factors and Histologic Type of Breast Carcinoma. *American Journal* 

Non-High Grade Ductal Carcinoma *in Situ* on Dynamic MR Mammography: Characteristic Findings for Signal Increase and Morphological Pattern of

C.H., Ho, G.H., Ng, L.T. & Wilde, C.C. (1998). Results of Intermediate Measures from A Population-Based, Randomized Trial of Mammographic Screening Prevalence and Detection of Breast Carcinoma Among Asian Women: The

Silicone-Specific Blood Lymphocyte Response in Women with Silicone Breast Implants. *Clinical and Diagnostic Laboratory Immunology*, Vol. 1, No. 6, pp. 689-695. Paetau, A.A., McLaughlin, S.A., McNeil, R.B., Sternberg, E., TerKonda, S.P., Waldorf, J.C. &

Perdikis, G. (2010). Capsular Contracture and Possible Implant Rupture: Is Magnetic Resonance Imaging Useful? *Plastic and Reconstructive Surgery,* Vol. 125,


**3** 

*Greece* 

**Scintimammography - Molecular Imaging: Value** 

Breast cancer is the most common non-skin cancer and the second leading cause of cancer death in women. Despite advances in the adjuvant treatment of early stage disease, many women will have breast cancer relapse that often is not amenable to complete surgical excision [Eubank et al., 2005]. There are 40,000 women per year dying of breast cancer in the

Currently, the detection and staging of breast cancer involves physical examination, fine needle aspiration (FNA) biopsy and imaging methods, namely mammography, ultrasonography, breast magnetic resonance imaging (MRI) and scintimammography. Screening mammography is widely available and evaluates patients with low cost, yet it bears a sensitivity ranging from 45% to 90% and low specificity, especially in cases of dense breasts, fibrocystic change and scars. Ultrasonography differentiates cystic from solid masses. Scintimammography by the use of various common radiotracers such as technetium-99m hexakis 2-methoxyisobutyl isonitrile (99mTc-sestamibi), 99mTc-6,9-bis (2 ethoxyethyl)-3, 12-dioxo-6, 9-diphosphatetradecane (99mTc-tetrofosmin), thallium-201 chloride (201TlCl), 99mTc-methylene diphosphonate (99mTc-MDP) and pentavalent 99mTcdimercaptosuccinic acid [99mTc(V)-DMSA], constitutes not only a complementary modality, but a significant method of choice in particular clinical settings, as summarized in Table 1. Nuclear medicine methods enormously contribute to breast cancer clinical management due to the following reasons: (a) the recent technological advance in the detection and processing systems. Single photon emission computed tomography (SPECT) is progressively used more often in parallel with traditional planar scintigraphy with considerable improvement of the resolution and sensitivity of the scintigraphic image, mainly pertaining to lymph node involvement. The detection limit regarding malignant lesions approaches the corresponding one obtained by traditional radiological methods. Another important innovative improvement is positron emission tomography (ΡΕΤ), a technique which is based on the use of precursor metabolites (amino acids, hormones, monosaccharites), which are labelled with isotopes with very short half life that emit positrons. The pioneer characteristics of this technique enable the study of tumor biology accurately and non-invasively, providing interesting perspectives for research and clinical applications. PET is gradually used more extensively in oncology and seems to have particular value in breast cancer; (b) the introduction of new radiotracers has allowed the

United States, and most breast cancer victims die of progressive metastatic disease.

**1. Introduction** 

**and New Perspectives with 99mTc(V)-DMSA** 

Vassilios Papantoniou, Pipitsa Valsamaki and Spyridon Tsiouris

*University General Hospital "Alexandra", Athens* 

