Dynamic fractal signature dissimilarity analysis for therapeutic response assessment using dynamic contrast-enhanced...

To develop a dynamic fractal signature dissimilarity (FSD) method as a novel image texture analysis technique for the quantification of tumor heterogeneity information for better therapeutic response assessment with dynamic contrast-enhanced (DCE)-MRI.

A small animal antiangiogenesis drug treatment experiment was used to demonstrate the proposed method. Sixteen LS-174T implanted mice were randomly assigned into treatment and control groups (n = 8/group). All mice received bevacizumab (treatment) or saline (control) three times in two weeks, and one pretreatment and two post-treatment DCE-MRI scans were performed. In the proposed dynamic FSD method, a dynamic FSD curve was generated to characterize the heterogeneity evolution during the contrast agent uptake, and the area under FSD curve (AUCFSD) and the maximum enhancement (MEFSD) were selected as representative parameters. As for comparison, the pharmacokinetic parameter K(trans) map and area under MR intensity enhancement curve AUCMR map were calculated. Besides the tumor's mean value and coefficient of variation, the kurtosis, skewness, and classic Rényi dimensions d1 and d2 of K(trans) and AUCMR maps were evaluated for heterogeneity assessment for comparison. For post-treatment scans, the Mann-Whitney U-test was used to assess the differences of the investigated parameters between treatment/control groups. The support vector machine (SVM) was applied to classify treatment/control groups using the investigated parameters at each post-treatment scan day.

The tumor mean K(trans) and its heterogeneity measurements d1 and d2 values showed significant differences between treatment/control groups in the second post-treatment scan. In contrast, the relative values (in reference to the pretreatment value) of AUCFSD and MEFSD in both post-treatment scans showed significant differences between treatment/control groups. When using AUCFSD and MEFSD as SVM input for treatment/control classification, the achieved accuracies were 93.8% and 93.8% at first and second post-treatment scan days, respectively. In comparison, the classification accuracies using d1 and d2 of K(trans) map were 87.5% and 100% at first and second post-treatment scan days, respectively.

As quantitative metrics of tumor contrast agent uptake heterogeneity, the selected parameters from the dynamic FSD method accurately captured the therapeutic response in the experiment. The potential application of the proposed method is promising, and its addition to the existing DCE-MRI techniques could improve DCE-MRI performance in early assessment of treatment response.