Apparent diffusion coefficient and kurtosis parameters show early response to anti-angiogenic therapy in patients with colorectal liver metastases

Abstract Background To investigate whether the diffusion kurtosis imaging (DKI) technique can identify tumour response to an anti-angiogenic therapy in a pilot study of patients with RAS-mutant colorectal liver metastases. Methods This prospective imaging study enrolled 20 participants receiving Regorafenib treatment. A target metastasis > 2 cm in each patient was imaged before and at 15 days after treatment on a 1.5T MR scanner using a coronal, free-breathing DKI protocol. Data were motion-corrected and modelled using both the mono-exponential and DKI models. Median values derived from voxel-wise analysis of the whole delineated tumour were reported for three parameters apparent diffusion coefficient (ADC, 10 − 3 mm 2 /s), apparent kurtosis (K, a.u.) and kurtosis-corrected apparent diffusion (D, 10 − 3 mm 2 /s) before and after treatment. A 5-patient supplementary cohort was used to assess the repeatability of DKI parameters using the Bland-Altman analysis. Changes in pre- and post-treatment measurements of the three parameters were assessed using Wilcoxon signed-rank tests ( P < 0.05 was considered significant). Diffusion weighted imaging (DWI) and DKI parameter correlations were evaluated with Spearman tests. Functional MR parameters were also compared against Response Evaluation Criteria In Solid Tumours v.1.1 (RECIST) evaluations. Results Significant treatment-induced changes across the cohort were observed for all parameters: K decrease (0.907 vs. 0.786, P < 0.01; 13.3%), D increase (1.256 vs. 1.386 × 10 − 3 mm 2 /s, P < 0.001; 10.4%) and ADC increase (0.910 vs. 1.035 × 10 − 3 mm 2 /s, P < 0.001; 13.7%). For both visits, Spearman correlation tests found a moderate negative correlation between K and D, ( r =-0.70; P < 0.001 and r =-0.58; P < 0.01) and a strong positive correlation ( r = 0.84 and 0.88; P < < 0.001) between ADC and D. The repeatability R was lowest for K (51%), followed by D (12%), and ADC (9.4%). When compared to RECIST v.1.1 evaluations, K identified no clinical responders, whilst D and ADC identified 7/12 and 11/12 responders. Conclusions Both ADC and DKI parameters showed a significant early cohort change to the anti-angiogenic effects of Regorafenib treatment in RAS-mutant colorectal liver metastases. The ADC parameter performed better than the K parameter in identifying patients benefitting from the treatment. Trial registration NCT03010722 clinicaltrials.gov; registration date 6 th January 2015.