Validating the biological origin of in vivo fractional intracellular volume from VERDICT-MRI in the prostate

Reliable imaging biomarkers are needed to characterize clinically significant prostate cancer (csPCa). The clinically established measure, apparent diffusion coefficient (ADC) from multiparametric (mp)MRI, lacks specificity to key histological features. The fractional intracellular volume (fIC) from in vivo Vascular, Extracellular, and Restricted Diffusion for Cytometry in Tumors (VERDICT)-MRI has shown improved detection of csPCa. This prospective study (NCT04792138) quantifies the accuracy of fIC as a measure of prostate epithelial cell density. Fifty-two participants (mean age, 65 years ± 6; Gleason grades ≥ 3 + 4) with biopsy-confirmed PCa underwent mpMRI and VERDICT-MRI before radical prostatectomy. Personalized molds from preoperative mpMRI enabled histology to MRI correspondence. Comparisons between histological epithelial density measures and MR markers were made on a region of interest (ROI) basis using Pearson’s correlation coefficient. VERDICT fIC corresponded more strongly with epithelial fraction, cell density and epithelial density (r = 0.784, 0.711, 0.747) than both VERDICT derived ADC (r=-0.639, -0.587, -0.609) and mpMRI ADC (r-0.353, -0.273, -0.326). Differences between benign tissue and csPCa in VERDICT fIC (0.16 ± 0.10 vs 0.51 ± 0.13) were similar to epithelial fraction (0.21 ± 0.08 vs 0.43 ± 0.12). These findings support in vivo VERDICT fIC as a marker of epithelial cell density and show promise for wider clinical use.