Quantitative Analysis With Time-Dependent Diffusion MRI for Assessing WHO/ISUP Tumor Grade in Clear Cell Renal Cell Carcinoma

To investigate the feasibility of time-dependent diffusion-weighted imaging (td-dMRI) in assessing the pathological World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade of clear cell renal cell carcinoma (ccRCC). A total of 138 patients (median age, 58 years [interquartile range, 51-64 years]; 89 males) with surgically confirmed ccRCC, comprising 48 high-grade (WHO/ISUP grade III/IV) and 90 low-grade (WHO/ISUP grade I/II) tumors, were included in the study among patients who underwent preoperative td-dMRI for suspected RCC between May 2022 and May 2024. The td-dMRI microstructural parameters, including cell diameter (d), intracellular volume fraction (fin), cellularity, and extracellular diffusivities (Dex), were quantified using a two-compartment model. The solid tumor area was manually annotated to extract the mean values from each parameter map. We analyzed the differences in td-dMRI parameters between the high- and low-grade tumors and evaluated the ability of these parameters to distinguish between the two tumor groups. High-definition hematoxylin-and-eosin-stained slides were obtained from 92 patients. We assessed the correlation between td-dMRI parameters and pathologic nuclear fraction, which was quantified using an automated nucleus segmentation model (Hover-Net). Compared to high-grade tumors, low-grade tumors exhibited lower cellularity and fin and higher diameter and Dex. For differentiation between low- and high-grade ccRCC, the fin exhibited the highest diagnostic performance (areas under the receiver operating characteristic curve [AUC] = 0.943; 95% confidence interval, 0.906-0.980), followed by cellularity (AUC = 0.931; 0.887-0.976), Dex (AUC = 0.863; 0.800-0.926), and diameter (AUC = 0.690; 0.596-0.784). The nuclei on pathology slides were automatically segmented, and the nuclear fraction exhibited a moderate correlation with fin (r = 0.65, P < 0.001). td-dMRI parameters show potential for assessing pathological WHO/ISUP grades and may serve as promising noninvasive biomarkers for characterizing RCC.