Non-invasive methods to study changes in the tumor microstructure would enable early assessment of treatment response and thus facilitate personalized treatment. The aim of this study was to evaluate the diffusion MRI model Vascular, Extracellular and Restricted Diffusion for Cytometry in Tumors (VERDICT) for early response assessment to external radiation treatment and to compare the results to those of more studied sets of parameters derived from diffusion-weighted MRI data. Mice xenografted

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... ith human small intestine tumors were treated with external radiation treatment, and diffusion MRI experiments were performed on the day before and up to two weeks after treatment. The diffusion models VERDICT, ADC, IVIM, and DKI were fitted to MRI data, and the treatment response of each tumor was calculated based on pre-treatment tumor growth and post-treatment tumor volume regression. Linear regression and correlation analysis were used to evaluate each model and their respective parameters for explaining the treatment response. VERDICT analysis showed significant changes from day -1 to day 3 for the intracellular and extracellular volume fraction, as well as the cell radius index (P < 0.05; Wilcoxon signed-rank test). The strongest correlation between the diffusion model parameters and the tumor treatment response was seen for the ADC, kurtosis-corrected diffusion coefficient, and intracellular volume fraction on day 3 (τ = 0.47, 0.52, and -0.49 respectively, P < 0.05; Kendall rank correlation coefficient). Of all tested models, VERDICT held the strongest explanatory value for the tumor treatment response on day 3 (R2 = 0.75, P < 0.01; linear regression). In conclusion, VERDICT holds potential for early assessment of external radiation treatment and may provide further insight into the underlying biological effects of radiation on tumor tissue. In addition, the results suggested that the time window for assessment of treatment response using dMRI may be narrow.