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

Abstract Objective Noninvasive microstructure estimates using magnetic resonance imaging (MRI) show potential in improving prostate cancer (PCa) diagnosis; however, histological validation is necessary. Materials and methods We used data from the Histo-MRI trial (NCT04792138). Participants with biopsy-confirmed PCa underwent multiparametric (mp) MRI and “vascular, extracellular, and restricted diffusion for cytometry in tumors” (VERDICT)-MRI before radical prostatectomy. Personalized molds enabled matching prostatectomy histology with corresponding VERDICT-MRI images. Comparisons between histological epithelial cell density measures and MRI were made on a region-of-interest (ROI) basis using Pearson correlation coefficient ( r ) with 95% confidence interval (CI). Differences between benign tissue and clinically significant PCa were analyzed using the area under the receiver operating characteristic curve (AUC). Results Fifty-two participants, aged 65 ± 6 years (mean ± standard deviation), with Gleason grade ≥ 3 + 4, were included. ROI analysis showed stronger correlations of VERDICT fractional intracellular volume (fIC) with epithelial fraction, epithelial cell density, and cell density ( r = 0.784 [0.70, 0.84], 0.747 [0.66, 0.81], 0.711 [0.60, 0.79] than VERDICT ADC ( r = -0.639 [-0.54, -0.71], -0.609 [-0.51, -0.69], -0.587 [-0.45, -0.69]), or mpMRI ADC ( r = -0.357 [-0.18, -0.51], -0.315 [-0.15, -0.46], -0.266 [-0.08, -0.43]), respectively ( p < 0.001). VERDICT fIC showed similar differences between benign and clinically significant PCa (0.16 ± 0.10 to 0.51 ± 0.13, AUC = 0.99, p < 0.001) to epithelial fraction (0.21 ± 0.08 to 0.43 ± 0.12, AUC = 0.94, p < 0.001). Conclusion VERDICT fIC showed clinical potential as a biomarker of epithelial cell density. Key Points Question Can VERDICT-MRI fIC provide a biologically interpretable, noninvasive imaging biomarker of epithelial cell density in the prostate? Findings VERDICT fIC showed stronger correlations with histological epithelial fraction, cell density, and epithelial density than both VERDICT-derived ADC and mpMRI ADC. Relevance statement These findings support in vivo VERDICT fIC as a noninvasive biomarker of prostate epithelial microstructure and show promise for wider clinical use, improving the detection rate of clinically significant PCa, reducing unnecessary biopsies, and allowing better risk stratification.