title: Multiparametric MR diffusion-weighted imaging for monitoring the ultra-early treatment effect of sorafenib in human hepatocellular carcinoma xenografts.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.|Department of Radiology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China.
authors: Xin
authors: X
authors: Chen
authors: Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
authors: Zelan
authors: Z
authors: Ma
authors: Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
authors: Yanqi
authors: 0000-0002-0286-3964
authors: Y
authors: Huang
authors: Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.|School of Medicine, South China University of Technology, Guangzhou, China.
authors: Lan
authors: L
authors: He
authors: Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
authors: Cuishan
authors: C
authors: Liang
authors: Medical Imaging Center, First Affiliated Hospital, Jinan University, Guangzhou, China.
authors: Changzheng
authors: C
authors: Shi
authors: GE Healthcare China, Guangzhou, China.
authors: Zhongping
authors: Z
authors: Zhang
authors: Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
authors: Changhong
authors: C
authors: Liang
authors: Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
authors: Zaiyi
authors: Z
authors: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods*; D055088:Early Detection of Cancer / Q000379:methods; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D008113:Liver Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D064847:Multimodal Imaging / Q000379:methods; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D000077157:Sorafenib; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib
keywords: hepatocellular carcinoma (HCC); multiparametric diffusion-weighted imaging; treatment response