Intravoxel Incoherent Motion (IVIM) Diffusion-Weighted Imaging to Assess Treatment Response of Choline Kinase Inhibition on GL261 Mouse Glioblastoma

Abstract AIMS To monitor changes in IVIM parameters in response to JAS239 treatment in preclinical glioblastoma models. METHOD C57BL/6 mice were injected intracranially with 5x105 GL261 glioblastoma cells and tumours were observed on T2 weighted MRI. Mice were imaged on day 0 (T0, baseline), day 3 (T3), 6 (T6) of treatment and post-treatment day 10 (T10). IVIM DWI was performed using a single-shot spin-echo echo planar sequence and processed using Matlab to acquire IVIM parameters of f, D, and D*. RESULTS Percentage changes in values with respect to baseline from saline treated control mice were compared to JAS239 treated animals with respect to baseline. Treated mice showed a slight increase in ADC and pseudo-diffusion on day 3 and day 6, with an increase in the perfusion fraction on day 6. However, no statistically significant difference between the two groups with respect to all 3 parameters (P>0.05). Analysis of the change in parameters post treatment (T10) also showed no statistically (P>0.05) significant difference between the mice treated with JAS239 and the control group treated with saline. CONCLUSION In this study of the IVIM based parameters, we observed no significant differences in these parameters which indicates that JAS329 may be ineffective in the treatment of GL261 tumours. There was no significant change in the diffusion and perfusion related parameters in the tumour region. IVIM parameters may be useful in studying the tumour microenvironment, however, these may not be sensitive in detecting tumour resistance to ChoK inhibitor therapies.