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In diffusion-weighted MRI (DW-MRI), choice of b-value influences apparent diffusion coefficient (ADC) values by probing different aspects of the tissue microenvironment. As a secondary analysis of the multicenter ECOG-ACRIN A6698 trial, the purpose of this study was to investigate the impact of alternate b-value combinations on the performance and repeatability of tumor ADC as a predictive marker of breast cancer treatment response. The final analysis included 210 women who underwent standardized 4-b-value DW-MRI (b = 0/100/600/800 s/mm2) at multiple timepoints during neoadjuvant chemotherapy treatment and a subset (n = 71) who underwent test−retest scans. Centralized tumor ADC and perfusion fraction (fp) measures were performed using variable b-value combinations. Prediction of pathologic complete response (pCR) based on the mid-treatment/12-week percent change in each metric was estimated by area under the receiver operating characteristic curve (AUC). Repeatability was estimated by within-subject coefficient of variation (wCV). Results show that two-b-value ADC calculations provided non-inferior predictive value to four-b-value ADC calculations overall (AUCs = 0.60−0.61 versus AUC = 0.60) and for HR+/HER2− cancers where ADC was most predictive (AUCs = 0.75−0.78 versus AUC = 0.76), p < 0.05. Using two b-values (0/600 or 0/800 s/mm2) did not reduce ADC repeatability over the four-b-value calculation (wCVs = 4.9−5.2% versus 5.4%). The alternate metrics ADCfast (b ≤ 100 s/mm2), ADCslow (b ≥ 100 s/mm2), and fp did not improve predictive performance (AUCs = 0.54−0.60, p = 0.08−0.81), and ADCfast and fp demonstrated the lowest repeatability (wCVs = 6.71% and 12.4%, respectively). In conclusion, breast tumor ADC calculated using a simple two-b-value approach can provide comparable predictive value and repeatability to full four-b-value measurements as a marker of treatment response.

Diagonal diffusion-weighted imaging (dDWI) uses simultaneous maximized application of 3 orthogonal gradient systems as opposed to sequential acquisition in 3 directions in conventional 3-scan trace DWI (tDWI). Several theoretical advantages of dDWI vs. tDWI include reduced artifacts and increased sharpness. We compared apparent diffusion coefficient (ADC) quantification and image quality between monopolar dDWI and tDWI in a dedicated diffusion phantom (b = 0/500/900/2000 s/mm 2 ) and in the abdomen (b = 50/400/800 s/mm 2 ) and pelvis (b = 50/1000/1600 s/mm 2 ) of 2 male volunteers at 1.5 T and 3.0 T. Phantom estimated signal-to-noise ratio (eSNR) was also measured. Two independent observers assessed the image quality on a 5-point scale. In the phantom, image quality was similar between tDWI and dDWI, with equivalent ADC quantification (mean coefficient of variation [CV] between sequences: 1.4% ± 1.2% at 1.5 T and 0.7% ± 0.7% at 3.0 T). Phantom eSNR was similar for both tDWI and dDWI, except for a significantly lower eSNR for b900 of dDWI at 3.0 T ( P = .006). In the volunteers, the CV values between tDWI and dDWI were higher than those in the phantom (CV range: abdominal organs, 1.3%-13.3%; pelvic organs, 0.6%-5.7%). A trend toward significant better image quality for dDWI compared with tDWI was observed for b800 (abdomen) at 3.0 T and for b1000 and b1600 (pelvis) at 1.5 T ( P = .063 to .066). Our data suggest that dDWI may provide better image quality than tDWI without affecting ADC quantification, needing confirmation in a future clinical study.