Evaluation of the effect of transcytolemmal water exchange analysis for therapeutic response assessment using DCE-MRI: a comparison study

Abstract

This study compares the shutter-speed (SS) and the Tofts models as used in assessing therapeutic response in a longitudinal DCE-MRI experiment. Sixteen nu/nu mice with implanted colorectal adenocarcinoma cell line (LS-174T) were randomly assigned into treatment/control groups (n = 8/group) and received bevacizumab/saline twice weekly (Day1/Day4/Day8). All mice were scanned at one pre- (Day0) and two post-treatment (Day2/Day9) time points using a high spatiotemporal resolution DCE-MRI pulse sequence. The CA extravasation rate constant from the Tofts/SS model and the mean intracellular water residence time from the SS model were analyzed. A biological subvolume (BV) within the tumor was identified based on the intensity distribution, and the SS model parameters within the BV ( and ) were analyzed. It is found that and have a similar spatial distribution in the tumor volume. The Bayesian information criterion results show that the SS model was a better fit for all scans. At Day9, the treatment group had significantly higher tumor mean (p = 0.021), (p = 0.021) and (p = 0.045). When BV from transcytolemmal water exchange analysis was adopted, the treatment group had higher mean at both Day2 (p = 0.038) and Day9 (p = 0.007). Additionally, at Day9, the treatment group had higher mean (p = 0.045) and higher spatial heterogeneity indices (Rényi dimensions) d1 (p = 0.010) and d2 (p = 0.021). When mean and its coefficient of variation (CV) were used to separate treatment/control group samples using supporting vector machine, the accuracy of treatment/control classification was 68.8% at Day2 and 87.5% at Day9; in contrast, the Day2/Day9 accuracy were 62.5%/87.5% using tumor mean and its CV and were 50.0%/87.5% using tumor mean and its CV, respectively. These results suggest that the SS model parameters outperformed the Tofts model parameters in terms of capturing bevacizumab therapeutic effect in this longitudinal experiment.