Premium
Multiparametric MR diffusion‐weighted imaging for monitoring the ultra‐early treatment effect of sorafenib in human hepatocellular carcinoma xenografts
Author(s) -
Chen Xin,
Ma Zelan,
Huang Yanqi,
He Lan,
Liang Cuishan,
Shi Changzheng,
Zhang Zhongping,
Liang Changhong,
Liu Zaiyi
Publication year - 2017
Publication title -
journal of magnetic resonance imaging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.563
H-Index - 160
eISSN - 1522-2586
pISSN - 1053-1807
DOI - 10.1002/jmri.25527
Subject(s) - medicine , sorafenib , hepatocellular carcinoma , effective diffusion coefficient , diffusion mri , magnetic resonance imaging , nuclear medicine , mann–whitney u test , urology , pathology , radiology
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