Multiparametric MR diffusion-weighted imaging for monitoring the ultra-early treatment effect of sorafenib in human hepatocellular carcinoma xenografts.

PURPOSE: To investigate the value of multiparametric magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI) for monitoring the ultra-early (within 24 hours) treatment effect of sorafenib in human hepatocellular carcinoma (HCC) xenografts.

MATERIALS AND METHODS: With institutional Animal Care and Use Committee approval, 16 BALB/c nude mice bearing subcutaneous HCC xenografts underwent serial Gaussian and non-Gaussian DWI at baseline and 1, 3, 6, 12, and 24 hours posttreatment using a 1.5T whole-body MRI system. Gaussian-DWI-derived apparent diffusion coefficient (ADC), D, D*, and f, and non-Gaussian-DWI-derived MD, MK, DDC, and α were calculated and compared between the control (n = 6) and sorafenib-treated groups (n = 10) with respect to each timepoint using Mann-Whitney or Wilcoxon signed-rank test. Results were validated by pathology.

RESULTS: Compared to baseline, ADC and D at 1 hour posttreatment (P = 0.005 and P = 0.013, respectively) and MD and DDC at 3 hours posttreatment (P = 0.009 and P = 0.005, respectively) significantly decreased and remained lower through 12 hours of follow-up (P = 0.005-0.022), followed by recovery to baseline levels at 24 hours posttreatment (P = 0.139-0.646). MK significantly increased at 1 hour posttreatment (P = 0.013) and remained higher through 24 hours of follow-up (P = 0.009-0.028). No significant differences were found in D*, f, and α at different timepoints (P = 0.188-0.714). Light microscopy did not reveal abnormal findings until 3 hours posttreatment, when central patchy necrosis was observed; more prominent diffuse necrosis was observed at 24 hours. Electron microscopy revealed swollen mitochondria at 1 hour posttreatment and accumulation of intracellular autophagosomes from 3 to 24 hours posttreatment.

CONCLUSION: Multiparametric DWI might evaluate therapeutic effects of sorafenib in HCC, where metrics of ADC, D, and MK could potentially serve as imaging biomarkers for monitoring therapeutic effects as early as 1 hour after treatment. Level of Evidence 1 Technical Efficacy: Stage 4 J. MAGN. RESON. IMAGING 2017;46:248-256.