SU-F-J-155: Evaluation of Transcytolemmal Water Exchange Analysis For Therapeutic Response Assessment Using Dynamic Contrast-Enhanced MRI.

PURPOSE: To compare the performance of shutter-speed(SS) model with transcytolemmal water exchange analysis against the Tofts model in the study of the efficacy of an anti-angiogenesis drug METHODS: 16 mice with LS-174T implanted were randomly assigned into treatment/control groups (n=8/group) and received bevacizumab/saline three times (Day1/Day4/Day8). All mice received one pre- (Day0) and two post-treatment (Day2/Day9) DCE scans. For each scan, the CA extravasation rate constant KT(trans) /KS(trans) from the Tofts/SS model were calculated. The intracellular water residence time τi which reflects limited transcytolemmal water exchange between cell and extravascular-extracellular-space were also analyzed using SS model. A biological subvolume(BV) within the tumor was automatically segmented based on the τi intensity distribution, and the SS model parameters within the BV (KS,BV(trans) and τi, BV ) were analyzed. Rank-sum tests were conducted to assess the differences of each parameter's statistics (mean value/coefficient-of-variation (CV) /kurtosis/skewness/heterogeneity indices d1 and d2 ) between treatment/control groups. Experiment using support vector machine in a leave-one-out approach were performed to validate the use of the analyzed biomarkers for treatment/control classification.

RESULTS: The SS model was a better fit for all scans in terms of Bayesian information criterion. At Day9, the treatment group had significantly higher mean KT(trans) (p=0.021), KS(trans) (p=0.021) and τi (p=0.045). In the identified BV, the treatment group had significantly higher mean KS,BV(trans) at both Day2(p=0.038) and Day9(p=0.007). Additionally, at Day9, the treatment group had significantly higher mean τi , BV (p=0.045) and higher KS,BV(trans) heterogeneity indices d1 (p=0.010) and d2 (p=0.021) values. When using KS,BV(trans) statistics for treatment/control group classification, the highest accuracy was 68.8%/87.5% at Day2/Day9; this result was better than the result of 62.5%/87.5% using KS(trans) statistics and 50.0%/87.5% using KT(trans) statistics.

CONCLUSION: The SS model parameters may be more reliable than the Tofts model parameters for therapeutic assessment. The proposed biological subvolume in this work may be useful for early therapeutic effect monitoring.