List of Abbreviations

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.

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.

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 ) .

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).

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.

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.

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.

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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