Purpose: To characterize the diffusion properties of prostate epithelium and stroma in benign tissue and cancer.
Methods: Paired MR microscopy (20 μm) and multidimensional diffusion MRI (dMRI) (160 μm, b = 1000-2000 s/mm2, ∆ = 15-120 ms) were performed at 16.4 T on 17 fixed prostate tissue samples (14× benign, 2× Gleason 3 + 3, 1× Gleason 4 + 4). MR microscopy images were used to segment epithelial, stromal, and luminal components in each sample. For each dMRI sequence, aggregate epithelial and stromal signal contributions in benign tissue were estimated using a linear epithelium-stroma-lumen signal model. Four diffusion signal models were fit to these aggregate signals. Quality-of-fit was assessed using the small-sample corrected Akaike Information Criterion (AICc). Voxel-wise model fitting was also performed to compare parameter estimates in benign tissue and cancer.
Results: Aggregate dMRI signal estimates for both epithelium and stroma were best described by the Ball + Sphere model (lowest AICc). A higher sphere fraction (0.278 vs. 0.175) and lower ball-compartment diffusivity (0.611 vs. 0.943 μm2/ms) were estimated for epithelium compared to stroma. The ADC model provided the worst fit in both cases (highest AICc). For Gleason 3 + 3 cancer, ADC and Ball + Sphere parameter estimates were consistent with the values found for benign epithelium and stroma; however, raised sphere fraction estimates were seen in Gleason 4 + 4 cancer.
Conclusion: Direction-averaged diffusion in fixed prostate epithelium and stroma is well described by the Ball + Sphere model. The diffusion properties of epithelium in Gleason 3 + 3 cancer and benign tissue appear to be similar; however, a marked increase to the volume fraction of restricted water was found for Gleason 4 + 4 epithelium.
© 2026 The Author(s). Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.