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Abstract This work presents a biophysical model of diffusion and relaxation MRI for prostate called relaxation vascular, extracellular and restricted diffusion for cytometry in tumours (rVERDICT). The model includes compartment-specific relaxation effects providing T1/T2 estimates and microstructural parameters unbiased by relaxation properties of the tissue. 44 men with suspected prostate cancer (PCa) underwent multiparametric MRI (mp-MRI) and VERDICT-MRI followed by targeted biopsy. We estimate joint diffusion and relaxation prostate tissue parameters with rVERDICT using deep neural networks for fast fitting. We tested the feasibility of rVERDICT estimates for Gleason grade discrimination and compared with classic VERDICT and the apparent diffusion coefficient (ADC) from mp-MRI. The rVERDICT intracellular volume fraction fic discriminated between Gleason 3 + 3 and 3 + 4 (p = 0.003) and Gleason 3 + 4 and ≥ 4 + 3 (p = 0.040), outperforming classic VERDICT and the ADC from mp-MRI. To evaluate the relaxation estimates we compare against independent multi-TE acquisitions, showing that the rVERDICT T2 values are not significantly different from those estimated with the independent multi-TE acquisition (p > 0.05). Also, rVERDICT parameters exhibited high repeatability when rescanning five patients (R2 = 0.79–0.98; CV = 1–7%; ICC = 92–98%). The rVERDICT model allows for accurate, fast and repeatable estimation of diffusion and relaxation properties of PCa sensitive enough to discriminate Gleason grades 3 + 3, 3 + 4 and ≥ 4 + 3.

False positives on multiparametric MRIs (mp-MRIs) result in many unnecessary invasive biopsies in men with clinically insignificant diseases. This study investigated whether quantitative diffusion MRI could differentiate between false positives, true positives and normal tissue non-invasively. Thirty-eight patients underwent mp-MRI and Vascular, Extracellular and Restricted Diffusion for Cytometry in Tumors (VERDICT) MRI, followed by transperineal biopsy. The patients were categorized into two groups following biopsy: (1) significant cancer—true positive, 19 patients; (2) atrophy/inflammation/high-grade prostatic intraepithelial neoplasia (PIN)—false positive, 19 patients. The clinical apparent diffusion coefficient (ADC) values were obtained, and the intravoxel incoherent motion (IVIM), diffusion kurtosis imaging (DKI) and VERDICT models were fitted via deep learning. Significant differences (p < 0.05) between true positive and false positive lesions were found in ADC, IVIM perfusion fraction (f) and diffusivity (D), DKI diffusivity (DK) (p < 0.0001) and kurtosis (K) and VERDICT intracellular volume fraction (fIC), extracellular–extravascular volume fraction (fEES) and diffusivity (dEES) values. Significant differences between false positives and normal tissue were found for the VERDICT fIC (p = 0.004) and IVIM D. These results demonstrate that model-based diffusion MRI could reduce unnecessary biopsies occurring due to false positive prostate lesions and shows promising sensitivity to benign diseases.