Mapping the Zonal Organization of Tumor Perfusion and Permeability in a Rat Glioma Model by Using Dynamic Contrast-enhanced Synchrotron Radiation CT

Abstract

To depict and analyze in vivo the tumor zone organization of C6 gliomas depicted on quantitative parametric maps obtained with dynamic contrast material-enhanced synchrotron radiation computed tomography (CT) in a tightly controlled data-processing protocol. Animal use was compliant with official French guidelines and was assessed by the local Internal Evaluation Committee for Animal Welfare and Rights. Fifteen Wistar rats with orthotopically implanted gliomas were studied at monochromatic synchrotron radiation CT after receiving a bolus injection of contrast material. The iodine concentration maps were analyzed by using a compartmental model selected from among a package of models. Choice of model and assessment of the relevance of the model were guided by quality criteria. Tissue blood flow (F(T)), tissue blood volume fraction (V(T)), permeability-surface area product (PS), artery-to-tissue delay (D(A-T)), and vascular mean transit time (MTT) maps were obtained. Parametric map findings were compared with histologic findings. Local regions of interest were selected in the contralateral hemisphere and in several tumor structures to characterize the tumor microvasculature. Differences in parameter values between regions were assessed with the Wilcoxon method. Whole-tumor parameters were expressed as means +/- standard errors of the mean: Mean F(T), V(T), PS, and D(A-T) values and MTT were 61.4 mL/min/100 mL +/- 15.3, 2.4% +/- 0.4, 0.37 mL/min/100 mL +/- 0.11, 0.24 second +/- 0.06; and 3.9 seconds +/- 0.83, respectively. MTT and mean PS were significantly lower (P < .01) in the normal contralateral tissue: 1.10 seconds +/- 0.06 and < or = 10(-5) mL/min/100 mL, respectively. Tumor regions were characterized by significantly different (P < .05) F(T) and V(T) pairs: 108 mL/min/100 mL and 3.66%, respectively, at the periphery; 45.9 mL/min/100 mL and 1.91%, respectively, in the intermediate zone; 5.1 mL/min/100 mL and 0.42%, respectively, in the center; and 210 mL/min/100 mL and 6.82%, respectively, in the maximal value region. Fine mapping of the glioma microcirculation is feasible with dynamic contrast-enhanced synchrotron radiation CT performed with well-controlled analytic protocols. http://radiology.rsnajnls.org/cgi/content/full/2501071929/DC1.