Perfusion parameters as potential imaging biomarkers for the early prediction of radiation therapy response in a rat tumor model

Abstract

Purpose: To compare various tumor-related radiologic morphometric changes and CT perfusion parameters before and after treatment and to determine optimal imaging assessment technique for the prediction of early response in a rat tumor model treated with radiotherapy. Materials and Methods: The Animal Care and Use Committee approved this study. Among paired tumors of FN13762 murine breast cancer cells implanted in the bilateral necks of 10 Fischer rats, tumors of the right side were treated with a single 10-Gy dose of radiation therapy. Among 10 rats, two were excluded from the analysis owing to unwanted death during anesthesia for pre-treatment CT scan

thus this study results were based on those of the remaining eight rats. Perfusion CT studies were performed on days 0, 1, and 5 before dosing. Variables based on the size including the longest diameter, tumor area, and volume were measured. Quantitative perfusion analysis was performed for the whole tumor volume and values of permeability and blood volume (BV) were obtained. The area under the curve (AUC) difference in the histograms of perfusion parameters and texture analyses of uniformity and entropy were quantified. All CT parameters were compared between irradiated and nonirradiated tumors. With pathology specimens immediate after perfusion imaging on day 5, apoptotic cell density was measured with terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) staining. Correlations between apoptotic cell density and CT parameters were assessed. Results: On day 1 after radiation therapy, differences in size between irradiated and nonirradiated tumors were not significant. On day 5 after therapy, the mean size values of irradiated tumors were significantly smaller than those of nonirradiated tumors (all P < .01). In terms of percent changes in uniformity of permeability values between tumors before irradiation and on day 1 after therapy , the changes were significantly higher in irradiated tumors than those of nonirradiated tumors (P= .042). The differences in AUCs of the histogram of voxel-by-voxel vascular permeability and BV in tumors between day 0 and day 1 were significantly higher in treated tumors as compared with the control group (Ps = .030 and P= .049, respectively). Apoptotic cell density showed a significantly positive correlation with the AUC difference of BV, the percent change of uniformity in permeability and BV (Rs = .202, .644, and .202, respectively

all Ps < .05). Conclusion: By enabling earlier tumor response prediction than morphometric evaluation, histogram analysis of CT perfusion parameters appears to have a potential of providing prognostic information in an irradiated rat model.