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Role of diffusion-weighted MRI: predicting axillary lymph node metastases in breast cancer Jin Chung, Ji Hyun Youk, Jeong-Ah Kim, Hye Mi Gweon, Eun-Kyung Kim, Young Hoon Ryu and Eun Ju Son Acta Radiol 2014 55: 909 originally published online 14 November 2013 DOI: 10.1177/0284185113509094 The online version of this article can be found at: http://acr.sagepub.com/content/55/8/909
Published by: http://www.sagepublications.com
On behalf of: Nordic Society of Medical Radiology
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Original Article
Role of diffusion-weighted MRI: predicting axillary lymph node metastases in breast cancer
Acta Radiologica 2014, Vol. 55(8) 909–916 ! The Foundation Acta Radiologica 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0284185113509094 acr.sagepub.com
Jin Chung1,2, Ji Hyun Youk2, Jeong-Ah Kim2, Hye Mi Gweon2, Eun-Kyung Kim2, Young Hoon Ryu3 and Eun Ju Son2
Abstract Background: Ultrasound (US) is probably the standard imaging procedure in most centers, and US-guided fine needle aspiration can be added if suspicious lymph nodes are found. However, US-guided fine needle aspiration is an invasive method to diagnose a metastasis and has showed relatively low sensitivity. In general, diffusion-weighted (DW) magnetic resonance imaging (MRI) has become an emerging technique for discriminating benign from malignant breast lesions in a short imaging acquisition time. Purpose: To evaluate the potential for using DW MRI with an apparent diffusion coefficient (ADC) value to predict axillary lymph node metastases in patients with invasive breast cancer. Material and Methods: This study enrolled 110 axillary lymph nodes from 110 consecutive women who were diagnosed with invasive breast cancer for preoperative breast MRI and US. The largest enhancing ipsilateral axillary lymph nodes were included in this study, and benign and metastatic axillary lymph nodes were compared according to the pathologic reports. The cut-off ADC value to differentiate between benign and metastatic axillary lymph nodes was evaluated with receiver-operating characteristic curve analysis. Diagnostic performance of ultrasound and DW MRI was calculated for enhancing lymph node in dynamic contrast-enhanced MRI. Results: Nodal metastases were documented in 68 (62%) axillary lymph nodes. The mean size of metastatic axillary lymph nodes was larger than that of benign axillary lymph nodes (15.5 mm vs. 10.9 mm, P < 0.001). The mean ADC value (0.69 103 mm2/s) of the metastases was significantly lower than that of the benign axillary lymph nodes (1.04 103 mm2/s) (P < 0.001). The ADC value cut-off between metastatic and benign axillary lymph nodes was 0.90 103 mm2/s. Using ADC cut-off, sensitivity, specificity, and accuracy of DW MRI were 100%, 83.3%, and 93.6%, respectively. The sensitivity, specificity, and accuracy of US showed 94.1%, 54.8%, and 79.1%, respectively. Conclusion: DW MRI of axillary lymph nodes can provide reliable information for the differentiation of benign from metastatic axillary lymph nodes in invasive breast cancer patients.
Keywords Breast cancer, magnetic resonance imaging (MRI), diffusion, apparent diffusion coefficient (ADC), axillary lymph node, ultrasound (US) Date received: 28 March 2013; accepted: 24 September 2013
Introduction The accurate prediction of axillary lymph node (ALN) status is essential to make a plan of treatment for patients with breast cancer (1). The presence of metastases in ALN is the most important single predictor of long-term survival in primary breast cancer patients (2).
1 Department of Radiology, Ewha Womans University, School of Medicine, Seoul, Republic of Korea 2 Department of Radiology, Yonsei University, College of Medicine, Seoul, Republic of Korea 3 Department of Nuclear Medicine, Yonsei University, College of Medicine, Seoul, Republic of Korea
Corresponding author: Eun Ju Son, Department of Radiology, Yonsei University, College of Medicine, Gangnam Severance Hospital, Eonjuro, 211, Gangnam-gu, Seoul, Republic of Korea. Email: [email protected]
Downloaded from acr.sagepub.com at Wissenschaftliche Bibliothek on November 5, 2014
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Acta Radiologica 55(8)
A variety of methods have been used for the preoperative staging of ALN. Clinical examination, mammography, and ultrasonography (US) have been used to predict ALN status. However, the diagnostic accuracy of predicting ALN metastases has not been satisfactory (3–5). The reported sensitivities and specificities of axillary US are in the range of 45.2–100% and 50– 89%, respectively (6–9). The overall sensitivity and specificity of fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) for ALN metastases range from 20–100% and 65–100%, respectively (7,10,11). In terms of magnetic resonance imaging (MRI) studies, the enhancement pattern of primary breast cancer after gadopentetate dimeglumine injection has also been noted with metastatic ALN (12–14). According to previous studies, metastatic ALNs on MRI show eccentric cortical thickening, round shape, a short-axis dimension of 10 mm or larger and irregular margin (12–14). While the dynamic contrast-enhanced (DCE) MRI has a relatively high sensitivity of 79–100%, the specificity (56–93%) is relatively low (1–14). Axillary US with US-guided fine needle aspiration (FNA) has become an accepted method of preoperative assessment of the axilla as a means for diagnosing metastases (15–17). When preoperative US-guided FNA is positive for metastasis, patients are spared an unnecessary sentinel lymph node biopsy (SLNB) and dissection of ALN is performed directly. However, US-guided FNA is an invasive method to diagnose metastases. In addition, the sensitivity of US-guided FNA is relatively low (39.5–86%), although specificity is high (95.7–100%) (8,15–17). Diffusion-weighted (DW) MRI is an unenhanced MRI sequence that has shown promising results for discriminating benign from malignant breast lesions in a short imaging acquisition time (18,19). DW MRI might yield information different from and complementary to that obtained with DCE MRI due to its sensitivity to tissue characteristics such as cell density, membrane integrity, and microstructure (20). Previous studies of DW MRI of the breast have shown that the apparent diffusion coefficient (ADC) is significantly lower in malignant tumors than in benign breast lesions and normal tissues (18,19). Recent several studies have showed variable sensitivities (53.8–94.7%) and specificities (77–91.7%) of DW MRI for ALN metastases (21–23). However, these recent studies had small numbers of metastatic lymph nodes (19–28 metastatic lymph nodes), lacking in comparison of US features (21–23). Also, benign ALN can show strong enhancement with wash-out kinetic pattern in DCE MRI (24).Therefore, the purpose of this study was to evaluate the potential of using DW MRI with an ADC value to predict ALN
metastases in patients with invasive ductal carcinoma, comparing with US features.
Material and Methods This retrospective study was approved by our institutional review board, which waived the requirement for informed patient consent.
Patients Between June 2009 and October 2010, 197 women underwent mastectomy or breast-conserving surgery with SLNB and/or ALN dissection due to invasive ductal carcinomas of the breast at our institute. Of these 197 patients, 190 underwent preoperative breast MRI and US. MRI and US were retrospectively reviewed by two radiologists in consensus (EJS and JC, with 12 and 2 years of experience interpreting breast MR images, respectively). Among them, 87 patients were excluded because they had undergone preoperative MRI at other institutions (n ¼ 7, 3.6%), without having enhancing ALN in their breast MRIs (n ¼ 74, 37.6%), or for the lack of subsequent surgery at our institution (n ¼ 6, 3.1%) (Fig. 1). Ipsilateral ALNs with breast cancer were included in this study. If multiple enhancing lymph nodes had been presented in the same axilla, the largest lymph node was included in this study. Finally, 110 patients (mean age, 49 years; age range, 27–80 years) with 110 ALNs were included in this study.
MRI technique MRI was performed using a 1.5-T system (Magnetom Avanto; Siemens, Erlangen, Germany) in 38 lesions and a 3.0-T system (Intera Achieva; Philips Medical Systems, Best, The Netherlands) in 72 lesions; both systems used dedicated four-channel phased array breast coils (MATRIX Breast Coil, Siemens; SENSE Breast Coil, Philips Medical Systems). Patients were examined in the prone position. The baseline MRI examination for the two systems consisted of turbo spin-echo T1- and T2-weighted sequences, single-shot spin-echo planar diffusion-weighted sequence, and 3D DCE sequence. All pulse sequence parameters are listed in Table 1. Before the contrast material injection, DW MRI was performed in the axial plane on both breasts, with the diffusion gradient applied along the orthogonal direction. DW MRI was performed with b values of 0 and 1000 mm2/s, and the mean acquisition time was 170 s. The DCE sequence was performed with axial imaging, with one as precontrast and five as postcontrast dynamic series performed at 90, 150, 210, 270, and 330 s
Downloaded from acr.sagepub.com at Wissenschaftliche Bibliothek on November 5, 2014
Chung et al.
911
Fig. 1. Flowcharts of the study group.
Table 1. MRI protocols in 1.5 T and 3.0 T units according to sequence. MRI acquisition sequences
MR parameter
Axial TSE T1-w-MRI
Axial TSE T2-w MRI
Axial SSSEP DWI
3D-axial DCE MRI
1.5T
1.5T
1.5T
1.5T
3.0T
3.0T
3.0T
3.0T
Echo time (ms)
11
10
100
100
91
70
1.34
1.67
Repetition time (ms)
500
526
5000
5266
9700
8496
3.7
4.5
185
65 12 3
Inversion time (ms) Flip angle (degree) Slice thickness (mm)
3
3
3
3
3
3
12 1.5
Slice gap (mm)
3
3
3
3
4.5
3
1.5
1.5
Slices (n)
48
48
48
48
30
30
88
88
Field of view (mm mm)
330
200 340
330
200 340
340
320 150
330
340 340
Image matrix (mm mm)
192 384
332 332
192 384
332 332
88 180
96 142
425 512
516 484
Bandwidth (Hz/pixel)
151
217.8
151
217.8
1634
30.7
410
385.4
Turbo factor
5
3
17
16 0, 1000
0, 1000
B-vales (mm2/s)
3D, three-dimensional; DCE, dynamic contrast-enhanced; DWI, diffusion weighted MRI; SSSEP, single-shot spin-echo planar; T1-w, T1-weighted; TSE, turbo spin-echo.
after contrast injection. The final delayed DCE sequence was also performed with sagittal imaging at 440 s after injection. Gadopentetate dimeglumine (Bono-I; Central Medical Service, Seoul, South Korea) was injected into an antecubital vein with an automated power injector at a dose of 0.1 mmol per kg of body weight and at a rate of 2 mL/s. This was followed by an 18 mL saline flush.
Ultrasound technique Ultrasound examinations were performed by one of five board-certified radiologists with 1 to 13 years of
experience in breast imaging, using 5 to 12 MHz linear probe (iU22, Philips Medical Systems, Bothell, WA, USA).
Imaging analysis Breast MRI and US were retrospectively reviewed on a picture archiving and communication system workstation monitor by two radiologists in consensus (EJS and JC with 13 and 3 years of experience interpreting breast images, respectively). Both reviewers were blinded to the final pathologic results of the ALNs.
Downloaded from acr.sagepub.com at Wissenschaftliche Bibliothek on November 5, 2014
912
Acta Radiologica 55(8)
The largest ipsilateral enhancing ALNs on DCE MRI were included in this study. Each lesion was identified both on subtracted DCE MRI and DW MRI. If there were multiple lymph nodes presented in the same axilla, the largest node was selected. Suspicious MR features of ALNs were as follows: eccentric cortical thickenings (3 mm or more, including loss of fatty hilum), round shapes (long/short axis ratio of 0.5 cm of ALNs was serially sectioned transversely; those
Role of diffusion-weighted MRI: predicting axillary lymph node metastases in breast cancer Jin Chung, Ji Hyun Youk, Jeong-Ah Kim, Hye Mi Gweon, Eun-Kyung Kim, Young Hoon Ryu and Eun Ju Son Acta Radiol 2014 55: 909 originally published online 14 November 2013 DOI: 10.1177/0284185113509094 The online version of this article can be found at: http://acr.sagepub.com/content/55/8/909
Published by: http://www.sagepublications.com
On behalf of: Nordic Society of Medical Radiology
Additional services and information for Acta Radiologica can be found at: Email Alerts: http://acr.sagepub.com/cgi/alerts Subscriptions: http://acr.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav
>> Version of Record - Sep 16, 2014 OnlineFirst Version of Record - Nov 14, 2013 What is This?
Downloaded from acr.sagepub.com at Wissenschaftliche Bibliothek on November 5, 2014
Original Article
Role of diffusion-weighted MRI: predicting axillary lymph node metastases in breast cancer
Acta Radiologica 2014, Vol. 55(8) 909–916 ! The Foundation Acta Radiologica 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0284185113509094 acr.sagepub.com
Jin Chung1,2, Ji Hyun Youk2, Jeong-Ah Kim2, Hye Mi Gweon2, Eun-Kyung Kim2, Young Hoon Ryu3 and Eun Ju Son2
Abstract Background: Ultrasound (US) is probably the standard imaging procedure in most centers, and US-guided fine needle aspiration can be added if suspicious lymph nodes are found. However, US-guided fine needle aspiration is an invasive method to diagnose a metastasis and has showed relatively low sensitivity. In general, diffusion-weighted (DW) magnetic resonance imaging (MRI) has become an emerging technique for discriminating benign from malignant breast lesions in a short imaging acquisition time. Purpose: To evaluate the potential for using DW MRI with an apparent diffusion coefficient (ADC) value to predict axillary lymph node metastases in patients with invasive breast cancer. Material and Methods: This study enrolled 110 axillary lymph nodes from 110 consecutive women who were diagnosed with invasive breast cancer for preoperative breast MRI and US. The largest enhancing ipsilateral axillary lymph nodes were included in this study, and benign and metastatic axillary lymph nodes were compared according to the pathologic reports. The cut-off ADC value to differentiate between benign and metastatic axillary lymph nodes was evaluated with receiver-operating characteristic curve analysis. Diagnostic performance of ultrasound and DW MRI was calculated for enhancing lymph node in dynamic contrast-enhanced MRI. Results: Nodal metastases were documented in 68 (62%) axillary lymph nodes. The mean size of metastatic axillary lymph nodes was larger than that of benign axillary lymph nodes (15.5 mm vs. 10.9 mm, P < 0.001). The mean ADC value (0.69 103 mm2/s) of the metastases was significantly lower than that of the benign axillary lymph nodes (1.04 103 mm2/s) (P < 0.001). The ADC value cut-off between metastatic and benign axillary lymph nodes was 0.90 103 mm2/s. Using ADC cut-off, sensitivity, specificity, and accuracy of DW MRI were 100%, 83.3%, and 93.6%, respectively. The sensitivity, specificity, and accuracy of US showed 94.1%, 54.8%, and 79.1%, respectively. Conclusion: DW MRI of axillary lymph nodes can provide reliable information for the differentiation of benign from metastatic axillary lymph nodes in invasive breast cancer patients.
Keywords Breast cancer, magnetic resonance imaging (MRI), diffusion, apparent diffusion coefficient (ADC), axillary lymph node, ultrasound (US) Date received: 28 March 2013; accepted: 24 September 2013
Introduction The accurate prediction of axillary lymph node (ALN) status is essential to make a plan of treatment for patients with breast cancer (1). The presence of metastases in ALN is the most important single predictor of long-term survival in primary breast cancer patients (2).
1 Department of Radiology, Ewha Womans University, School of Medicine, Seoul, Republic of Korea 2 Department of Radiology, Yonsei University, College of Medicine, Seoul, Republic of Korea 3 Department of Nuclear Medicine, Yonsei University, College of Medicine, Seoul, Republic of Korea
Corresponding author: Eun Ju Son, Department of Radiology, Yonsei University, College of Medicine, Gangnam Severance Hospital, Eonjuro, 211, Gangnam-gu, Seoul, Republic of Korea. Email: [email protected]
Downloaded from acr.sagepub.com at Wissenschaftliche Bibliothek on November 5, 2014
910
Acta Radiologica 55(8)
A variety of methods have been used for the preoperative staging of ALN. Clinical examination, mammography, and ultrasonography (US) have been used to predict ALN status. However, the diagnostic accuracy of predicting ALN metastases has not been satisfactory (3–5). The reported sensitivities and specificities of axillary US are in the range of 45.2–100% and 50– 89%, respectively (6–9). The overall sensitivity and specificity of fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) for ALN metastases range from 20–100% and 65–100%, respectively (7,10,11). In terms of magnetic resonance imaging (MRI) studies, the enhancement pattern of primary breast cancer after gadopentetate dimeglumine injection has also been noted with metastatic ALN (12–14). According to previous studies, metastatic ALNs on MRI show eccentric cortical thickening, round shape, a short-axis dimension of 10 mm or larger and irregular margin (12–14). While the dynamic contrast-enhanced (DCE) MRI has a relatively high sensitivity of 79–100%, the specificity (56–93%) is relatively low (1–14). Axillary US with US-guided fine needle aspiration (FNA) has become an accepted method of preoperative assessment of the axilla as a means for diagnosing metastases (15–17). When preoperative US-guided FNA is positive for metastasis, patients are spared an unnecessary sentinel lymph node biopsy (SLNB) and dissection of ALN is performed directly. However, US-guided FNA is an invasive method to diagnose metastases. In addition, the sensitivity of US-guided FNA is relatively low (39.5–86%), although specificity is high (95.7–100%) (8,15–17). Diffusion-weighted (DW) MRI is an unenhanced MRI sequence that has shown promising results for discriminating benign from malignant breast lesions in a short imaging acquisition time (18,19). DW MRI might yield information different from and complementary to that obtained with DCE MRI due to its sensitivity to tissue characteristics such as cell density, membrane integrity, and microstructure (20). Previous studies of DW MRI of the breast have shown that the apparent diffusion coefficient (ADC) is significantly lower in malignant tumors than in benign breast lesions and normal tissues (18,19). Recent several studies have showed variable sensitivities (53.8–94.7%) and specificities (77–91.7%) of DW MRI for ALN metastases (21–23). However, these recent studies had small numbers of metastatic lymph nodes (19–28 metastatic lymph nodes), lacking in comparison of US features (21–23). Also, benign ALN can show strong enhancement with wash-out kinetic pattern in DCE MRI (24).Therefore, the purpose of this study was to evaluate the potential of using DW MRI with an ADC value to predict ALN
metastases in patients with invasive ductal carcinoma, comparing with US features.
Material and Methods This retrospective study was approved by our institutional review board, which waived the requirement for informed patient consent.
Patients Between June 2009 and October 2010, 197 women underwent mastectomy or breast-conserving surgery with SLNB and/or ALN dissection due to invasive ductal carcinomas of the breast at our institute. Of these 197 patients, 190 underwent preoperative breast MRI and US. MRI and US were retrospectively reviewed by two radiologists in consensus (EJS and JC, with 12 and 2 years of experience interpreting breast MR images, respectively). Among them, 87 patients were excluded because they had undergone preoperative MRI at other institutions (n ¼ 7, 3.6%), without having enhancing ALN in their breast MRIs (n ¼ 74, 37.6%), or for the lack of subsequent surgery at our institution (n ¼ 6, 3.1%) (Fig. 1). Ipsilateral ALNs with breast cancer were included in this study. If multiple enhancing lymph nodes had been presented in the same axilla, the largest lymph node was included in this study. Finally, 110 patients (mean age, 49 years; age range, 27–80 years) with 110 ALNs were included in this study.
MRI technique MRI was performed using a 1.5-T system (Magnetom Avanto; Siemens, Erlangen, Germany) in 38 lesions and a 3.0-T system (Intera Achieva; Philips Medical Systems, Best, The Netherlands) in 72 lesions; both systems used dedicated four-channel phased array breast coils (MATRIX Breast Coil, Siemens; SENSE Breast Coil, Philips Medical Systems). Patients were examined in the prone position. The baseline MRI examination for the two systems consisted of turbo spin-echo T1- and T2-weighted sequences, single-shot spin-echo planar diffusion-weighted sequence, and 3D DCE sequence. All pulse sequence parameters are listed in Table 1. Before the contrast material injection, DW MRI was performed in the axial plane on both breasts, with the diffusion gradient applied along the orthogonal direction. DW MRI was performed with b values of 0 and 1000 mm2/s, and the mean acquisition time was 170 s. The DCE sequence was performed with axial imaging, with one as precontrast and five as postcontrast dynamic series performed at 90, 150, 210, 270, and 330 s
Downloaded from acr.sagepub.com at Wissenschaftliche Bibliothek on November 5, 2014
Chung et al.
911
Fig. 1. Flowcharts of the study group.
Table 1. MRI protocols in 1.5 T and 3.0 T units according to sequence. MRI acquisition sequences
MR parameter
Axial TSE T1-w-MRI
Axial TSE T2-w MRI
Axial SSSEP DWI
3D-axial DCE MRI
1.5T
1.5T
1.5T
1.5T
3.0T
3.0T
3.0T
3.0T
Echo time (ms)
11
10
100
100
91
70
1.34
1.67
Repetition time (ms)
500
526
5000
5266
9700
8496
3.7
4.5
185
65 12 3
Inversion time (ms) Flip angle (degree) Slice thickness (mm)
3
3
3
3
3
3
12 1.5
Slice gap (mm)
3
3
3
3
4.5
3
1.5
1.5
Slices (n)
48
48
48
48
30
30
88
88
Field of view (mm mm)
330
200 340
330
200 340
340
320 150
330
340 340
Image matrix (mm mm)
192 384
332 332
192 384
332 332
88 180
96 142
425 512
516 484
Bandwidth (Hz/pixel)
151
217.8
151
217.8
1634
30.7
410
385.4
Turbo factor
5
3
17
16 0, 1000
0, 1000
B-vales (mm2/s)
3D, three-dimensional; DCE, dynamic contrast-enhanced; DWI, diffusion weighted MRI; SSSEP, single-shot spin-echo planar; T1-w, T1-weighted; TSE, turbo spin-echo.
after contrast injection. The final delayed DCE sequence was also performed with sagittal imaging at 440 s after injection. Gadopentetate dimeglumine (Bono-I; Central Medical Service, Seoul, South Korea) was injected into an antecubital vein with an automated power injector at a dose of 0.1 mmol per kg of body weight and at a rate of 2 mL/s. This was followed by an 18 mL saline flush.
Ultrasound technique Ultrasound examinations were performed by one of five board-certified radiologists with 1 to 13 years of
experience in breast imaging, using 5 to 12 MHz linear probe (iU22, Philips Medical Systems, Bothell, WA, USA).
Imaging analysis Breast MRI and US were retrospectively reviewed on a picture archiving and communication system workstation monitor by two radiologists in consensus (EJS and JC with 13 and 3 years of experience interpreting breast images, respectively). Both reviewers were blinded to the final pathologic results of the ALNs.
Downloaded from acr.sagepub.com at Wissenschaftliche Bibliothek on November 5, 2014
912
Acta Radiologica 55(8)
The largest ipsilateral enhancing ALNs on DCE MRI were included in this study. Each lesion was identified both on subtracted DCE MRI and DW MRI. If there were multiple lymph nodes presented in the same axilla, the largest node was selected. Suspicious MR features of ALNs were as follows: eccentric cortical thickenings (3 mm or more, including loss of fatty hilum), round shapes (long/short axis ratio of 0.5 cm of ALNs was serially sectioned transversely; those
