Intratumor Heterogeneity of Perfusion and Diffusion in Clear-Cell Renal Cell Carcinoma: Correlation With Tumor Cellularity

Abstract

Background: Magnetic resonance imaging (MRI) has the potential to noninvasively provide information about the tumor microenvironment. A correlation between arterial spin-labeled (ASL) MRI and tumor vasculature has been previously demonstrated; however, its correlation with tumor cellularity is unknown. We sought to assess intratumor heterogeneity of perfusion and diffusion in vivo in clear-cell renal cell carcinoma (ccRCC) using MRI and to correlate these findings with tumor vascularity and cellularity at histopathology.

Patients and methods: Twenty-three ccRCC patients underwent ASL and diffusion-weighted MRI before surgery after signing an informed consent in this prospective institutional review board-approved, HIPAA (Insurance Portability and Accountability Act)-compliant study. Quantitative ASL perfusion and diffusion were measured in 2 areas within the same tumor with high and low perfusion. Microvessel density (MVD) on CD31 and CD34 immunostains and tumor cellularity in anatomically coregistered tissue samples were correlated to MRI measurements (Spearman; P < .05 statistically significant).

Results: ASL perfusion (P < .0001), CD31 MVD (P = .02), CD34 MVD (P = .04), and cellularity (P = .002) from high and low perfusion areas were significantly different across all tumors. There were positive correlations between tumor cellularity and CD31 MVD (ρ = 0.350, P = .021), CD31 and CD34 MVD (ρ = 0.838, P < .0001), ASL perfusion and cellularity (ρ = 0.406, P = .011), and ASL perfusion and CD31 MVD (ρ = 0.468, P = .003), and a negative correlation between tissue diffusion coefficient and cellularity (ρ = -0.316, P = .039).

Conclusion: Tumor areas with high ASL perfusion exhibit higher cellularity and MVD compared to areas with low perfusion in the same tumor. A positive correlation between tumor vascularity and cellularity in ccRCC is newly reported. A negative correlation between tumor diffusion and cellularity is confirmed.

Keywords: Arterial spin labeling; Clear-cell RCC; Diffusion weighted imaging; Tumor vascularity and cellularity; Tumor heterogeneity.