title: Separate calculation of DW-MRI in assessing therapeutic effect in liver tumors in rats.
abstract: OBJECTIVE
  To explore whether the antitumor effect of a vascular disrupting agent (VDA) would be enhanced by combining with an antiangiogenic agent, and whether such synergistic effects can be effectively evaluated with separate calculation of diffusion weighted magnetic resonance imaging (DW-MRI).
  
  
  METHODS
  Thirty-seven rats with implanted liver tumors were randomized into the following three groups: (1) ZD6126, a kind of VDA; (2) ZDTHA, ZD6126 in combination with an antiangiogenic, thalidomide; and (3) control. Morphological DW-MRI were performed and quantified before, 4 h and 2 d after treatment. The apparent diffusion coefficient (ADC) values were calculated separately for low b values (ADC(low)), high b values (ADC(high)) and all b values (ADC(all)). The tissue perfusion contribution, ADC(perf), was calculated as ADC(low)-ADC(high). Imaging findings were finally verified by histopathology.
  
  
  RESULTS
  The combination therapy with ZDTHA significantly delayed tumor growth due to synergistic effects by inducing cumulative tumor necrosis. In addition to delaying tumor growth, ZDTHA caused tumor necrosis in an additive manner, which was verified by HE staining. Although both ADC(high) and ADC(all) in the ZD6126 and ZDTHA groups were significantly higher compared to those in the control group on day 2, the entire tumor ADC(high) of ZDTHA was even higher than that of ZD6126, but the significant difference was not observed for ADC(all) between ZDTHA and ZD6126. This indicated that the perfusion insensitive ADC(high) values calculated from high b value images performed significantly better than ADC(all) for the monitoring of tumor necrosis on day 2. The perfusion sensitive ADC(perf) derived from ADC(low) by excluding high b value effects could better reflect the reduction of blood flow due to the vessel shutdown induced by ZD6126, compared to the ADC(low) at 4 h. The ADC(perf) could provide valuable perfusion information from DW-MRI data.
  
  
  CONCLUSIONS
  The separate calculation of ADC is more useful than conventional averaged ADC in evaluating the efficacy of combination therapy with ZD6126 and thalidomide for solid tumors.
authors.affiliation: Feng Chen, Department of Radiology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.affiliation: Feng Chen, Department of Radiology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Frederik
authors.initials: F
authors.lastname: De Keyzer
authors.affiliation: Feng Chen, Department of Radiology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Yuan-Bo
authors.initials: YB
authors.lastname: Feng
authors.affiliation: Feng Chen, Department of Radiology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Marlein Miranda
authors.initials: MM
authors.lastname: Cona
authors.affiliation: Feng Chen, Department of Radiology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yu
authors.affiliation: Feng Chen, Department of Radiology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Guy
authors.initials: G
authors.lastname: Marchal
authors.affiliation: Feng Chen, Department of Radiology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Raymond
authors.initials: R
authors.lastname: Oyen
authors.affiliation: Feng Chen, Department of Radiology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Ni
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D038524:Diffusion Magnetic Resonance Imaging; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D009336:Necrosis; D009943:Organophosphorus Compounds / Q000008:administration & dosage; D011237:Predictive Value of Tests; D051381:Rats; D012208:Rhabdomyosarcoma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D013792:Thalidomide / Q000008:administration & dosage; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; C455219:N-acetylcochinol-O-phosphate; D009943:Organophosphorus Compounds; D013792:Thalidomide
keywords: Animal model; Antiangiogenic agent; Diffusion weighted imaging; Liver tumor; Magnetic resonance imaging; Rats; Rodents; Therapeutic assessment; Vascular disrupting agent