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 KTtrans/KStrans from the Tofts/SS model and the mean intracellular water residence time τi from the SS model were analyzed. A biological subvolume (BV) within the tumor was identified based on the τi intensity distribution, and the SS model parameters within the BV ( KS,BVtrans and τi,BV) were analyzed. It is found that KStrans and KTtrans have a similar spatial distribution in the tumor volume. The Bayesian information criterion (BIC) results show that the SS model was a better fit for all scans. At Day9, the treatment group had significantly higher tumor mean KTtrans (p=0.021), KStrans (p=0.021) and τi (p=0.045). When BV from transcytolemmal water exchange analysis was adopted, the treatment group had higher mean KS,BVtrans at both Day2 (p=0.038) and Day9 (p=0.007). Additionally, at Day9, the treatment group had higher mean τi,BV (p=0.045) and higher KS,BVtrans spatial heterogeneity indices (Rényi dimensions) d1 (p=0.010) and d2 (p=0.021). When mean KS,BVtrans and its coefficient of variation (CV) were used to separate treatment/control group samples using supporting vector machine (SVM), 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 KStrans and its CV and were 50.0%/87.5% using tumor mean KTtrans 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.

Multi‐parametric MRI (mpMRI) for treatment response assessment of radiation therapy

“…The elegant two‐compartment model design assumes infinite transcytolemmal water exchange, which may not be true, particularly with high CA concentration 233 . Comparison studies showed that K trans derived with and without infinite transcytolemmal water exchange assumptions had different performances in capturing anti‐vascular treatment effect 234 . Understanding the limitations of physiological assumptions is also critical in optimizing a data analysis method.…”

“…233 Comparison studies showed that K trans derived with and without infinite transcytolemmal water exchange assumptions had different performances in capturing anti-vascular treatment effect. 234 Understanding the limitations of physiological assumptions is also critical in optimizing a data analysis method. Similarly, in a DWI study using different b values, when high b values were used as acquisition parameters for imaging, results indicated extra pathology results and suggested different modeling for more adequate interpretation.…”