Stromal collagen content in breast tumors correlates with in vivo diffusion-weighted imaging: A comparison of multi b-value DWI with histologic specimen from benign and malignant breast lesions

Background:Increased deposition and reorientation of stromal collagenfibers are associated with breast cancer progres-sion and invasiveness. Diffusion-weighted imaging (DWI) may be sensitive to the collagenfiber organization in the stromaand could provide important biomarkers for breast cancer characterization.Purpose:To understand how collagenfibers influence water diffusion in vivo and evaluate the relationship between colla-gen content and the apparent diffusion coefficient (ADC) and the signal fractions of the biexponential model using a highb-value scheme.Study Type:Prospective.Subjects/Specimens:Forty-five patients with benign (n= 8), malignant (n= 36), and ductal carcinoma in situ (n= 1) breasttumors. Lesions and normalfibroglandular tissue (n= 9) were analyzed using sections of formalin-fixed, paraffin-embeddedtissue stained with hematoxylin, erythrosine, and saffron.Field Strength/Sequence:MRI (3T) protocols:Protocol I:Twice-refocused spin-echo echo-planar imaging with: echo time(TE) 85 msec; repetition time (TR) 9300/11600 msec; matrix 90×90×60; voxel size 2×2×2.5 mm3;b-values: 0 and700 s/mm2.Protocol II:Stejskal–Tanner spin-echo echo-planar imaging with: TE: 88 msec; TR: 10600/11800 msec, matrix90×90×60; voxel size 2×2×2.5 mm3;b-values [0, 200, 600, 1200, 1800, 2400, 3000] s/mm2.Assessment:Area fractions of cellular and collagen content in histologic sections were quantified using whole-slide imageanalysis and compared with the corresponding DWI parameters.Statistical Tests:Correlations were assessed using Pearson’sr. Univariate analysis of group median values was done usingthe Mann–WhitneyU-test.Results:Collagen content correlated with the fast signal fraction (r= 0.67,P< 0.001) and ADC (r= 0.58,P< 0.001) andwas lower (P< 0.05) in malignant lesions than benign and normal tissues. Cellular content correlated inversely with the fastsignal fraction (r=–0.67,P< 0.001) and ADC (r=–0.61,P< 0.001) and was different (P< 0.05) between malignant,benign, and normal tissues.Data Conclusion:Ourfindings suggest stromal collagen content increases diffusivity observed by MRI and is associatedwith higher ADC and fast signal fraction of the biexponential mode