Micro-CT and 18 F-FDG micro-PET of pulmonary fibrosis in mice induced by adenoviral gene transfer of TGF-β1

Introduction: The morphological and functional information provided by micro-CT and micro-PET allows monitoring of acute and chronic disease states in small laboratory animals. We examined in-vivo micro-CT and micro-PET as non-invasive tools to assess pulmonary fibrosis in mice. Material/Methods: Pulmonary fibrosis was induced in mice by intratracheal delivery of an adenoviral gene vector encoding biologically active TGF-β1. Respiratory gated and ungated micro-CT was performed in 18 mice at 1 to 4 weeks after pulmonary adenoviral gene vector delivery. In 5 additional mice 18 F-FDG micro-PET and micro-CT was performed. Imaging was correlated to histopathology and findings in animals exposed to a control vector. Radiation doses were measured using thermoluminescence dosimeters. Results: Significant correlation between Ashcroft histology scoring and micro-CT was found for visual assessment scoring (p<0.001) and automated quantification by a region growing segmentation algorithm (p=0.004 for gated and p=0.006 for ungated exams). 18 F-FDG micro-PET showed slight increase of glucose metabolism in the consolidated lung areas determined by micro-CT, which was coregistered to the micro-PET data using anatomical landmarks. Radiation doses for micro-CT ranged from 174 to 277 mSv. For micro-PET an expected dose of 140 mSv was calculated from the measurements. Conclusion: Micro-CT and micro-PET allow valid visualisation of morphology and metabolism for the assessment of fibrosis in mice. The measured radiation doses allow serial examinations without deterministic radiation effects.