title: Intratumor Heterogeneity of Perfusion and Diffusion in Clear-Cell Renal Cell Carcinoma: Correlation With Tumor Cellularity.
abstract: 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.
  
  
  
  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).
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Department of Radiology, UT Southwestern Medical Center, Dallas, TX.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Department of Pathology, UT Southwestern Medical Center, Dallas, TX; Department of Urology, UT Southwestern Medical Center, Dallas, TX; Kidney Cancer Program, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX.
authors.forename: Payal
authors.initials: P
authors.lastname: Kapur
authors.affiliation: Department of Radiology, UT Southwestern Medical Center, Dallas, TX.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Radiology, UT Southwestern Medical Center, Dallas, TX.
authors.forename: Yin
authors.initials: Y
authors.lastname: Xi
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, MA.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Carvo
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, MA.
authors.forename: Sabina
authors.initials: S
authors.lastname: Signoretti
authors.affiliation: Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX; Philips Medical Systems, Cleveland, OH.
authors.forename: Ivan E
authors.initials: IE
authors.lastname: Dimitrov
authors.affiliation: Department of Radiology, UT Southwestern Medical Center, Dallas, TX; Department of Urology, UT Southwestern Medical Center, Dallas, TX; Kidney Cancer Program, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Cadeddu
authors.affiliation: Department of Urology, UT Southwestern Medical Center, Dallas, TX; Kidney Cancer Program, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Margulis
authors.affiliation: Kidney Cancer Program, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX; Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX.
authors.forename: James
authors.initials: J
authors.lastname: Brugarolas
authors.affiliation: Department of Radiology, UT Southwestern Medical Center, Dallas, TX; Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX.
authors.forename: Ananth J
authors.initials: AJ
authors.lastname: Madhuranthakam
authors.affiliation: Department of Radiology, UT Southwestern Medical Center, Dallas, TX; Kidney Cancer Program, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX; Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX. Electronic address: ivan.pedrosa@UTSouthwestern.edu.
authors.forename: Ivan
authors.initials: I
authors.lastname: Pedrosa
mesh_terms: D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000098:blood supply / Q000000981:diagnostic imaging / Q000473:pathology* / Q000601:surgery; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011446:Prospective Studies; D013113:Spin Labels; D059016:Tumor Microenvironment
chemical_list: D018952:Antigens, CD34; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D013113:Spin Labels
keywords: Arterial spin labeling; Clear-cell RCC; Diffusion weighted imaging; Tumor vascularity and cellularity; Tumor heterogeneity