PurposeTo investigate the diagnostic value of multi-model high-resolution diffusion-weighted MR imaging (DWI) in breast lesions, with a comparison of simultaneous multi-slice readout-segmented echo-planar imaging (SMS rs-EPI) and single-shot EPI (ss-EPI). Materials and MethodsThis retrospective study was approved by the institutional ethics committee and included 120 patients with 122 breast lesions (25 benign and 97 malignant). All patients underwent breast DWI with multi-b values (0, 50, 100, 200, 400, 800, 1200, and 2000 s/mm2) based on both SMS rs-EPI and ss-EPI on a 3.0 T MR scanner. Quantitative DWI-derived parameters including ADC, MK, MD, D, D*, and f were calculated based on mono-exponential (Mono), intravoxel incoherent motion (IVIM), diffusion kurtosis (DKI) models. Meanwhile, both DWI sequences were qualitatively evaluated with respect to overall image quality, lesion conspicuity, image artifact, geometric distortion, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and lesion contrast. The differences in DW-derived parameters, image quality, and diagnostic performance were statistically compared between SMS rs-EPI and ss-EPI groups. ResultsThe SMS rs-EPI produced higher Contrast, CNR and lower SNR than ss-EPI (p < 0.01). The image quality of SMS rs-EPI was superior to ss-EPI either in subjective or objective evaluation. There was no significant difference between the SMS rs-EPI and ss-EPI for either MD or the D* (p > 0.05). However, the MK and f between the two sequences showed significant differences (p < 0.05). Spearman’s correlation coefficient displayed good linear correlation for MK values (r = 0.73, 95% CI 0.617–0.857), MD values (r = 0.88, 95% CI 0.814–0.926), ADC values (r = 0.93, 95% CI 0.869–0.948) and D values (r = 0.93, 95% CI 0.856–0.948) between SMS rs-EPI and ss-EPI. Spearman’s correlation coefficient for f values (r = 0.25, 95% CI 0.226–0.559) and D* values (r = 0.22, 95% CI 0.025–0.348) were fair and no correlation between the two sequences. MK values have the highest diagnostic value in differentiating benign and malignant breast lesions. ConclusionsHigh-resolution multi-model DWI based on SMS rs-EPI technique can provide superior image quality and lesion characterization, with comparable diagnostic performance as compared with ss-EPI DWI in differentiating benign and malignant breast lesions. Of different DWI-derived parameters, MK values showed the best diagnostic performance.