Diffusion MRI as a Stand-Alone Unenhanced Approach for Breast Imaging and Screening





List of Abbreviations



ADC


apparent diffusion coefficient


BI-RADS


Breast Imaging Reporting and Data System


BPS


background parenchymal signal


DCE


dynamic contrast-enhanced


DCIS


ductal carcinoma in situ


DWIST


Diffusion-Weighted Magnetic Resonance Imaging Screening Trial


DW MRI


diffusion-weighted MRI


EPI


echo-planar imaging


MIP


maximum intensity projection



Although dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) is highly sensitive and endorsed by multinational organizations as a supplemental screening tool for high-risk women, widespread implementation of DCE MRI is limited by high cost and uncertain long-term effects of gadolinium retention from contrast administration. In addition, the cost-effectiveness of DCE MRI in intermediate risk patients, such as those with history of breast cancer and dense breasts, remains unclear. Therefore there is great interest in identifying an affordable, unenhanced imaging modality suitable for breast cancer screening. Diffusion-weighted (DW) MRI has emerged as one of the leading options, owing to its short scan time, relative availability and promising sensitivity for identifying breast cancer. DW MRI enables detection of breast malignancies without the need for administering a contrast agent, based instead on microstructural characteristics (e.g., cellular density), as reflected by endogenous diffusional water movement ( Fig. 6.1 ). To date, most experimental and clinical uses of DW MRI have been as an adjunct to DCE MRI in lesion assessment, for preoperative staging of ipsilateral and contralateral breasts, and for evaluating the response to neoadjuvant chemotherapy. However, there is increasing interest in exploring the use of DW MRI as a stand-alone tool for breast cancer detection.




Fig. 6.1


Invasive breast cancer detectable at DW MRI.

Postcontrast T1-weighted image (A) in a 37-year-old woman demonstrates a 33-mm irregular mass in the anterior left breast, corresponding to biopsy-proven invasive lobular carcinoma. On DW MRI, the lesion exhibits reduced diffusivity compared with normal breast parenchyma, appearing hyperintense on b = 1000 s/mm 2 diffusion-weighted image (B, arrow ) and hypointense on the ADC 0–800 map (calculated from b = 0, 800 s/mm 2 ) (C, arrow ). ADC , Apparent diffusion coefficient; DW , diffusion weighted; MRI , magnetic resonance imaging.

(Reprinted with permission from Partridge SC, Amornsiripanitch N. The role of DWI in the assessment of breast lesions. Top Magn Reson Imaging . 2017;26(5):201–209.)


This chapter summarizes the evidence for DW MRI in cancer detection and describes the optimal unenhanced breast cancer screening methods. In addition, the chapter discusses ongoing multicenter DW MRI screening trials and issues associated with clinical implementation.


Current Evidence for DW MRI as a Stand-Alone Modality


Real-world performance of DW MRI for noncontrast cancer detection in the clinical screening setting has been investigated in a variety of reader studies, most of which were performed retrospectively. The readers in these studies assessed only unenhanced MRI sequences (i.e., DW MRI with or without anatomical nonenhanced T1- or T2-weighted sequences) for suspicious findings and were blinded to DCE MRI. They assigned either a binary category (suspicious vs. benign/negative) or a number on a scale corresponding to the level of suspicion, similar to the Breast Imaging Reporting and Data System (BI-RADS) categories. Study designs ranged from inclusion of only asymptomatic intermediate- to high-risk patients, patients with suspicious imaging or clinical symptoms, to those with known malignancy; some studies included a combination of more than one of the above.


DW MRI cancer detection performance across these various studies is summarized in Table 6.1 . The mean sensitivity was 81% (range 44%–97%), and the mean specificity was 88% (range 73%–96%). However, among studies that simulated clinical screening experience by including negative/benign cases, mean sensitivity was 76% (range 45%–100%), and the mean specificity was 89% (range 79%–95%). Variation in the reported sensitivities is likely due to the inclusion criteria, imaging, and interpretation protocol. The study with the lowest sensitivity included only mammographically occult cancer and used relatively low maximum b values (600–800 s/mm 2 ), whereas some studies with higher sensitivities evaluated only (previously biopsied) known malignancy, used advanced imaging acquisition techniques, or performed double reading.



Table 6.1

Blinded Reader Studies Evaluating DW MRI Performance for Breast Cancer Detection












































































































































































































Study Total Women Cancer Prevalence Field Strength (tesla) Max b Value(s/mm 2 ) MRI Sequences Evaluated Study Population Sensitivity Specificity
70


  • 100% a



  • (70/70)

1.5 1000 ssEPI, STIR, ADC Known malignancy 97 N/A
48


  • 100% a



  • (48/48)

1.5 800 ssEPI, T1WI, T2WI Known malignancy 94 N/A
80


  • 67% b



  • (54/81)

1.5 1000 ssEPI, T2WI, ADC Suspicious mammographic or ultrasound findings and/or clinical symptoms


  • 91 *



  • (87–94)




  • 85 *



  • (85–85)

63


  • 67% a



  • (42/63)

1.5 1000 ssEPI, T2WI DCE MRI detected asymptomatic malignancy + negative controls 50 95
46


  • 27% c



  • (25/92)

1.5 800 ssEPI, T2WI ADC Under 50 years of age with known malignancy + negative controls 74 93
58


  • 45% b



  • (29/65)

3 750 ssEPI, T2WI Suspicious mammographic or ultrasound findings of <2 cm


  • 90 *



  • (86–93)




  • 88 *



  • (81–94)

67


  • 32% c



  • (37/116)

1.5 1000 ssEPI, T1WI, STIR, ADC Known malignancy, patients with suspicious mammographic or ultrasound findings, and intermediate- to high-risk screening


  • 77 *



  • (76–78)




  • 90 *



  • (90–90)

280


  • 46% a



  • (129/280)

1.5 1000 DWIBS, T2WI, STIR, ADC Suspicious mammographic or ultrasound findings and high-risk screening 94 79
50


  • 48% a



  • (24/50)

1.5 1500 DWIBS MIP, T2WI Suspicious mammographic or ultrasound findings 92 94
118


  • 45% c



  • (104/233)

1.5 1000 ssEPI, STIR, ADC Known malignancy and patients with suspicious mammographic or ultrasound findings


  • 77 *



  • (77–78)




  • 96 *



  • (96–96)

61


  • 44% a



  • (27/61)

1.5 1150 ss-EPI Suspected breast pathology 44
87


  • 83% b



  • (107/129)

3 1000 rs-EPI, T1WI, rs-EPI fused to T1WI, ADC Known malignancy


  • 89 *



  • (85–92)




  • 88 *



  • (82–96)

48


  • 25% c



  • (24/95)

1.5, 3 600, 800 ssEPI, T2WI, T1WI, ADC Asymptomatic high-risk with dense breast tissue with mammographically occult cancer + negative controls 45 91
343


  • 2.5% d



  • (9/358)

3 1000 rs-EPI MIP, rs-EPI fused to T1WI Asymptomatic with history of breast cancer and no known active malignancy


  • 93 *



  • (89–100)




  • 94 *



  • (93–95)

113


  • 59% a



  • (67/113)

3 850 rs-EPI, ADC Suspicious mammographic or ultrasound findings


  • 91 *



  • (91–91)




  • 73 *



  • (71–75)

106


  • 63% b



  • (69/110)

3 850 ss-EPI, ADC Suspicious mammographic or ultrasound findings


  • 82 *



  • (78–84)




  • 87 *



  • (85–90)

166


  • 54% b



  • (95/176)

3 800 ss-EPI, TIRM, ADC Dense breast and suspicious mammographic and/or MRI findings 94 84
378


  • 25% a



  • (96/378)

1.5 1000 ss-EPI, ADC Known malignancy, suspicious mammographic or ultrasound findings and/or clinical symptoms, and intermediate- to high-risk screening 93 § 86 §
1130


  • 1.9% c



  • (21/1130)

3.0 1000 ss-EPI, ADC Contralateral breast of women with newly diagnosed unilateral breast cancer 77.8 87.3

ADC, Apparent diffusion coefficient; DWIBS, diffusion-weighted MRI with background suppression; MIP, maximum intensity projection; rs-EPI, readout-segmented echo-planar diffusion-weighted imaging; ssEPI, single-shot echo planar imaging; STIR, short TI inversion recovery; T2WI, T2-weighted imaging; T1WI, T1-weighted imaging; N/A, not available.

* Mean sensitivity and specificity for multiple readers was not reported in the original article and was calculated by the authors.


Cancer prevalence calculations vary by study based on per a patient, b lesion, c breast, or d examination (as indicated) in order to match the performance metrics reported in the study.


Quantitative ADC measurement was used as part of noncontrast imaging analysis.


§ Calculated from double reading.



Some previous studies have reported on the performance of DW MRI versus other imaging modalities, including mammography, DCE MRI, abbreviated breast MRI, and ultrasound. Compared with mammography, DW MRI was found to be more sensitive (mean sensitivity across studies 78% vs. 59% for DW MRI vs. mammogram, respectively). Compared with DCE MRI, DW MRI was found to be less sensitive (mean sensitivity across studies 81% vs. 95% for DW MRI vs. DCE MRI, respectively). No studies directly compared blinded DW MRI performance with that of screening whole-breast ultrasonography; however, a nonblinded study of 60 mammographically occult cancers showed that more cancers were detectable on DW MRI (78%) compared with MRI-guided focused ultrasound (63%). In another study of 1146 women with newly diagnosed breast cancer, DW MRI of the contralateral breast showed higher sensitivity than mammography (77% and 30%, respectively) or combined mammography and ultrasound (40%) in detecting clinically occult cancer. The cancer detection rate (20 per 1000 examinations) and positive predictive value (42%) for biopsy recommendation of DW MRI was also higher compared with combined mammography and ultrasound (10 per 1000 examinations and 19%, respectively; Fig. 6.2 ) .




Fig. 6.2


Cancer yield of different imaging methods.

Of the 30 contralateral breast cancers, DW MRI detected 23 (76.7%) cancers (11 invasive and 12 DCIS), whereas mammography combined with ultrasound detected 12 (40.0%) cancers (five invasive and seven DCIS; P = .009). The bar graph shows the number of clinically occult contralateral cancers detected in 1146 women. DCIS , Ductal carcinoma in situ; DW , diffusion weighted; MRI , magnetic resonance imaging. MG, mammography; US, ultrasound.

(Reprinted with permission from Ha SM, Chang JM, Lee SH, et al. Detection of contralateral breast cancer using diffusion-weighted magnetic resonance imaging in women with newly diagnosed breast cancer: comparison with combined mammography and whole-breast ultrasound. Korean J Radiol. 2021;22(6):867–879.)


Common false-negative lesions in DW MRI include ductal carcinoma in situ (DCIS), mucinous carcinomas, and cancers presenting as nonmass enhancement and small masses. DCIS was more likely to be missed by DW MRI than invasive ductal carcinoma. DCIS commonly presents as a nonmass enhancement on DCE MRI with higher apparent diffusion coefficient (ADC) than invasive carcinomas, making it difficult to detect ( Fig. 6.3 ), with false-negative rates reported as high as 86% using this technique. Tumors with high liquid content, such as mucinous cancers and necrotic triple-negative cancers, can also exhibit a high ADC. Mucinous carcinoma was frequently missed on DW MRI ( Fig. 6.4 ), with a false-negative rate as high as 100%. Finally, small cancers (<10–12 mm) and invasive lobular cancer were also frequently missed ( Fig. 6.5 ). This was due to the low spatial resolution of conventional DW MRI techniques, which may lead to partial volume averaging, producing results that are not significantly better than the standard in-plane resolution and slice thickness (commonly 2 × 2 mm 2 and 3–5 mm, respectively). Expected false negative lesions on DW MRI also could include tumors with a low water content (e.g., low cellularity cancers with extensive desmoplastic stromal fibrosis).




Fig. 6.3


Microinvasive ductal carcinoma not detectable at DW MRI.

(A) Left craniocaudal magnification mammography in a 67-year-old woman shows 25-mm segmental pleomorphic calcifications in the left outer breast. DCE MR image (B) shows a 20-mm nonmass-enhancing lesion in the 3 o’clock position of the left breast (arrow) , which is not detected on either DW MRI at b = 1000 s/mm 2 (C) or ADC 0–1000 map (D). This was proven to be a 17-mm microinvasive ductal carcinoma. ADC , Apparent diffusion coefficient; DCE , dynamic-contrast enhanced; DW , diffusion weighted; MRI , magnetic resonance imaging.



Fig. 6.4


A 45-year-old woman with mucinous carcinoma.

(A) DCE MRI shows marked diffuse background parenchymal enhancement, and there was no abnormal focal-enhancing lesion in the right breast. (B)–(D) DW MRI shows an irregular, not circumscribed, heterogeneous high signal intensity mass in the right breast, in which signals gradually decrease with increasing b values from 0 to 1200 s/mm 2 . (E) The diffusion level of this mass is very high on the ADC 0–800 map (calculated from b = 0, 800 s/mm 2 ), and the ADC value was 2.35 × 10 −3 mm 2 /s. This was proven to be a 20-mm mucinous carcinoma with nuclear and histological grade 1. ADC , Apparent diffusion coefficient; DCE , dynamic-contrast enhanced; DW , diffusion weighted; MRI , magnetic resonance imaging.



Fig. 6.5


A 61-year-old woman with a small invasive cancer.

(A) DCE MR image shows a 7-mm irregular enhancing mass (arrow) in the right breast. (B)–(D) There is no abnormal focal lesion visible in the corresponding area on either the b = 0 (B) or 800 s/mm 2 (C) DW MR images (B, C, respectively), although there is subtle diffusion restriction on the ADC 0–800 map (ADC = 0.86 × 10 −3 mm 2 /s, arrow ) calculated from b = 0 and 800 s/mm 2 (D). (E) and (F) This small mass is also not detected on the precontrast T2- or T1-weighted images, respectively. This lesion was proven to be 10-mm mixed invasive ductal and lobular carcinoma, which was considered a false negative. ADC , Apparent diffusion coefficient; DCE , dynamic-contrast enhanced; DW , diffusion weighted; MR , magnetic resonance.


The notable false positives using DW MRI included complicated/proteinaceous cysts, fibroadenomas, and artifactual “lesions.” Complicated/proteinaceous cysts, which are known to exhibit restricted diffusion ( Fig. 6.6 ), represent the majority of DW MRI false positives in some settings. Similarly, fibroadenomas may be mistaken as a suspicious finding due to the wide range of possible ADC values. More than a third of fibroadenomas have ADCs in the same range as those of malignancies. Finally, false positives can be produced by artifactual signal, such as near the nipple-areolar complex, an area known to be prone to susceptibility-based distortion in DW MRI.




Fig. 6.6


A 59-year-old woman with an invasive cancer in the left breast and a complicated cyst in the right breast.

(A) DCE MRI shows a 15-mm irregular enhancing mass in the posterior left breast. (B) T1-weighted image shows no abnormal focal lesion in either breast. (C) T2-weighted image shows a small intermediate signal intensity lesion in the right central breast (arrow) , which is considered a complicated cyst on ultrasound and did not change over 18 months. (D) DW MRI for b = 0 s/mm 2 shows no abnormal focal lesion in either breast. (E) On DW MRI for b = 1200 s/mm 2 , there is a small oval, circumscribed, homogeneous signal intensity mass with very low diffusion level in the right breast (arrow) and a round, not circumscribed, homogeneous mass with low diffusion level in the left breast (circle) . (F) ADC 0–800 map (calculated from b = 0 and 800 s/mm 2 ) shows both lesions exhibit diffusion restriction; ADC values are 0.64 × 10 −3 mm 2 /s for the right breast lesion and 1.25 × 10 −3 mm 2 /s for the left breast lesion. The small mass in the right breast was considered a false positive, and a mass in the left breast was proven to be a 15-mm invasive ductal carcinoma. ADC , Apparent diffusion coefficient; DCE , dynamic-contrast enhanced; DW , diffusion weighted; MRI , magnetic resonance imaging.


Technical Requirements as an Unenhanced Screening Modality


Expert consensus from the European Society of Breast Imaging (EUSOBI) recommended standardized parameters for high-quality breast DW MRI, which were extended specifically for the application of unenhanced breast cancer screening in a DW trial protocol ( Table 6.2 ).



Table 6.2

Standardized Breast DW MRI Acquisition Parameters




















































































Minimum Requirement From EUSOBI Acquisition Parameter From DWIST
Study Purpose Tumor Characterization Cancer Detection
Equipment
Magnet field strength ≥1.5 T 3.0 T
Type of coil Dedicated breast coil with ≥4 channels 16 or 18 channels
Timing of acquisition Before contrast injection, when possible Before contrast injection
Acquisition Parameter
Type of sequence EPI based EPI based
Orientation Axial Axial
Field of view Both breasts with or without covering the axillary region Both breasts with covering the axillary region
In-plane resolution ≤2×2 mm 2 ≤1.3×1.3 mm 2
Slice thickness ≤4 mm ≤3 mm
Number of b values 2 3
Lowest b value 0 s/mm 2 (not exceeding 50 s/mm 2 ) 0 s/mm 2
High b value 800 s/mm 2 800 s/mm 2 and additional acquisition of 1200 s/mm 2
Fat saturation SPAIR SPAIR or STIR
Echo time (ms) Minimum possible Minimum possible
Repetition time (ms) ≥3000 ≥6000
Acceleration factor ≥2 ≥2
Postprocessing Generation of ADC maps Generation of computed multiple b values MIP series and ADC map

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Oct 30, 2022 | Posted by in MAGNETIC RESONANCE IMAGING | Comments Off on Diffusion MRI as a Stand-Alone Unenhanced Approach for Breast Imaging and Screening
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