Validating the biological origin of in vivo fractional intracellular volume from VERDICT-MRI in the prostate
TL;DR
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.
Abstract
Noninvasive microstructure estimates using magnetic resonance imaging (MRI) show potential in improving prostate cancer (PCa) diagnosis; however, histological validation is necessary. 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). 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). VERDICT fIC showed clinical potential as a biomarker of epithelial cell density. 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. 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.