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

作者：Chen, Xin; Ma, Zelan; Huang, Yanqi; He, Lan; Liang, Cuishan; Shi, Changzheng; Zhang, Zhongping; Liang, Changhong; Liu, Zaiyi^*

来源：Journal of Magnetic Resonance Imaging, 2017, 46(1): 248-256.

DOI：10.1002/jmri.25527

• hepatocellular carcinoma (HCC)
• treatment response
• multiparametric diffusion-weighted imaging

PurposeTo 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 MethodsWith 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 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. @@@ ResultsCompared 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 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. @@@ ConclusionMultiparametric 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

• 出版日期2017-7
• 单位广州医科大学; 暨南大学; 南方医科大学; 广东省人民医院; 华南理工大学