title: Chemotherapy response evaluation in a mouse model of gastric cancer using intravoxel incoherent motion diffusion-weighted MRI and histopathology.
abstract: OBJECTIVE
  To determine the role of intravoxel incoherent motion (IVIM) diffusion-weighted (DW) magnetic resonance imaging (MRI) using a bi-exponential model in chemotherapy response evaluation in a gastric cancer mouse model.
  
  
  METHODS
  Mice bearing MKN-45 human gastric adenocarcinoma xenografts were divided into four treated groups (TG1, 2, 3 and 4,n= 5 in each group) which received Fluorouracil and Calcium Folinate and a control group (CG,n= 7). DW-MRI scans with 14 b-values (0-1500 s/mm2) were performed before and after treatment on days 3, 7, 14 and 21. Fast diffusion component (presumably pseudo-perfusion) parameters including the fast diffusion coefficient (D*) and fraction volume (fp), slow diffusion coefficient (D) and the conventional apparent diffusion coefficients (ADC) were calculated by fitting the IVIM model to the measured DW signals. The median changes from the baseline to each post-treatment time point for each measurement (ΔADC, ΔD* and Δfp) were calculated. The differences in the median changes between the two groups were compared using the mixed linear regression model by the restricted maximum likelihood method shown as z values. Histopathological analyses including Ki-67, CD31, TUNEL and H&E were conducted in conjunction with the MRI scans. The median percentage changes were compared with the histopathological analyses between the pre- and post-treatment for each measurement.
  
  
  RESULTS
  Compared with the control group, D* in the treated group decreased significantly (ΔD*treated% = -30%, -34% and -20%, with z = -5.40, -4.18 and -1.95.P= 0.0001, 0.0001 and 0.0244) andfpincreased significantly (Δfptreated% = 93%, 113% and 181%, with z = 4.63, 5.52, and 2.12,P= 0.001, 0.0001 and 0.0336) on day 3, 7 and 14, respectively. Increases in ADC in the treated group were higher than those in the control group on days 3 and 14 (z = 2.44 and 2.40,P= 0.0147 andP= 0.0164).
  
  
  CONCLUSIONS
  Fast diffusion measurements derived from the bi-exponential IVIM model may be more sensitive imaging biomarkers than ADC to assess chemotherapy response in gastric adenocarcinoma.
authors.affiliation: Jin Cheng, Yi Wang, Wei-Zhen Wu, Feng Pan, Nan Hong, Department of Radiology, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Jin Cheng, Yi Wang, Wei-Zhen Wu, Feng Pan, Nan Hong, Department of Radiology, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Jin Cheng, Yi Wang, Wei-Zhen Wu, Feng Pan, Nan Hong, Department of Radiology, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Chun-Fang
authors.initials: CF
authors.lastname: Zhang
authors.affiliation: Jin Cheng, Yi Wang, Wei-Zhen Wu, Feng Pan, Nan Hong, Department of Radiology, Peking University People's Hospital, Beijing 100044, China.
authors.forename: He
authors.initials: H
authors.lastname: Wang
authors.affiliation: Jin Cheng, Yi Wang, Wei-Zhen Wu, Feng Pan, Nan Hong, Department of Radiology, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Wei-Zhen
authors.initials: WZ
authors.lastname: Wu
authors.affiliation: Jin Cheng, Yi Wang, Wei-Zhen Wu, Feng Pan, Nan Hong, Department of Radiology, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Pan
authors.affiliation: Jin Cheng, Yi Wang, Wei-Zhen Wu, Feng Pan, Nan Hong, Department of Radiology, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Hong
authors.affiliation: Jin Cheng, Yi Wang, Wei-Zhen Wu, Feng Pan, Nan Hong, Department of Radiology, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Deng
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D004195:Disease Models, Animal; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007091:Image Processing, Computer-Assisted; D020287:In Situ Nick-End Labeling; D002955:Leucovorin / Q000008:administration & dosage / Q000627:therapeutic use; D016013:Likelihood Functions; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011897:Random Allocation; D013274:Stomach Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D000964:Antimetabolites, Antineoplastic; D002955:Leucovorin; D005472:Fluorouracil
keywords: Chemotherapy; Gastric adenocarcinoma; Intravoxel incoherent diffusion-weighted magnetic resonance imaging; Treatment response; Xenografts