title: Fully-automated, high-throughput micro-computed tomography analysis of body composition enables therapeutic efficacy monitoring in preclinical models.
abstract: BACKGROUND
  The ability to non-invasively measure body composition in mouse models of obesity and obesity-related disorders is essential for elucidating mechanisms of metabolic regulation and monitoring the effects of novel treatments. These studies aimed to develop a fully automated, high-throughput micro-computed tomography (micro-CT)-based image analysis technique for longitudinal quantitation of adipose, non-adipose and lean tissue as well as bone and demonstrate utility for assessing the effects of two distinct treatments.
  
  
  METHODS
  An initial validation study was performed in diet-induced obesity (DIO) and control mice on a vivaCT 75 micro-CT system. Subsequently, four groups of DIO mice were imaged pre- and post-treatment with an experimental agonistic antibody specific for anti-fibroblast growth factor receptor 1 (anti-FGFR1, R1MAb1), control immunoglobulin G antibody, a known anorectic antiobesity drug (rimonabant, SR141716), or solvent control. The body composition analysis technique was then ported to a faster micro-CT system (CT120) to markedly increase throughput as well as to evaluate the use of micro-CT image intensity for hepatic lipid content in DIO and control mice. Ex vivo chemical analysis and colorimetric analysis of the liver triglycerides were performed as the standard metrics for correlation with body composition and hepatic lipid status, respectively.
  
  
  RESULTS
  Micro-CT-based body composition measures correlate with ex vivo chemical analysis metrics and enable distinction between DIO and control mice. R1MAb1 and rimonabant have differing effects on body composition as assessed by micro-CT. High-throughput body composition imaging is possible using a modified CT120 system. Micro-CT also provides a non-invasive assessment of hepatic lipid content.
  
  
  CONCLUSIONS
  This work describes, validates and demonstrates utility of a fully automated image analysis technique to quantify in vivo micro-CT-derived measures of adipose, non-adipose and lean tissue, as well as bone. These body composition metrics highly correlate with standard ex vivo chemical analysis and enable longitudinal evaluation of body composition and therapeutic efficacy monitoring.
authors.affiliation: Department of Biomedical Imaging, Genentech, Inc., South San Francisco, CA, USA.
authors.forename: S K
authors.initials: SK
authors.lastname: Wyatt
authors.affiliation: Department of Biomedical Imaging, Genentech, Inc., South San Francisco, CA, USA.
authors.forename: K H
authors.initials: KH
authors.lastname: Barck
authors.affiliation: Department of Biomedical Imaging, Genentech, Inc., South San Francisco, CA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Kates
authors.affiliation: Department of Biomedical Imaging, Genentech, Inc., South San Francisco, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Zavala-Solorio
authors.affiliation: Department of Biomedical Imaging, Genentech, Inc., South San Francisco, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Ross
authors.affiliation: Department of Biomedical Imaging, Genentech, Inc., South San Francisco, CA, USA.
authors.forename: G
authors.initials: G
authors.lastname: Kolumam
authors.affiliation: Department of Molecular Biology, Genentech, Inc., South San Francisco, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Sonoda
authors.affiliation: Department of Biomedical Imaging, Genentech, Inc., South San Francisco, CA, USA.
authors.forename: R A D
authors.initials: RA
authors.lastname: Carano
mesh_terms: D000273:Adipose Tissue / Q000000981:diagnostic imaging / Q000473:pathology*; D000818:Animals; D001823:Body Composition; D004195:Disease Models, Animal; D007090:Image Interpretation, Computer-Assisted; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000473:pathology*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D055114:X-Ray Microtomography