title: Longitudinal in vivo microcomputed tomography of mouse lungs: No evidence for radiotoxicity.
abstract: Before microcomputed tomography (micro-CT) can be exploited to its full potential for longitudinal monitoring of transgenic and experimental mouse models of lung diseases, radiotoxic side effects such as inflammation or fibrosis must be considered. We evaluated dose and potential radiotoxicity to the lungs for long-term respiratory-gated high-resolution micro-CT protocols. Free-breathing C57Bl/6 mice underwent four different retrospectively respiratory gated micro-CT imaging schedules of repeated scans during 5 or 12 wk, followed by ex vivo micro-CT and detailed histological and biochemical assessment of lung damage. Radiation exposure, dose, and absorbed dose were determined by ionization chamber, thermoluminescent dosimeter measurements and Monte Carlo calculations. Despite the relatively large radiation dose delivered per micro-CT acquisition, mice did not show any signs of radiation-induced lung damage or fibrosis when scanned weekly during 5 and up to 12 wk. Doubling the scanning frequency and once tripling the radiation dose as to mimic the instant repetition of a failed scan also stayed without detectable toxicity after 5 wk of scanning. Histological analyses confirmed the absence of radiotoxic damage to the lungs, thereby demonstrating that long-term monitoring of mouse lungs using high-resolution micro-CT is safe. This opens perspectives for longitudinal monitoring of (transgenic) mouse models of lung diseases and therapeutic response on an individual basis with high spatial and temporal resolution, without concerns for radiation toxicity that could potentially influence the readout of micro-CT-derived lung biomarkers. This work further supports the introduction of micro-CT for routine use in the preclinical pulmonary research field where postmortem histological approaches are still the gold standard.
authors.affiliation: Biomedical MRI Unit/MoSAIC, Department Imaging & Pathology, KU Leuven, Leuven, Belgium;
authors.forename: Greetje
authors.initials: G
authors.lastname: Vande Velde
authors.affiliation: Laboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Center, Department of Development and Regeneration, KU Leuven, Leuven, Belgium; Division of Rheumatology, University Hospitals Leuven, Flanders, Belgium;
authors.forename: Ellen
authors.initials: E
authors.lastname: De Langhe
authors.affiliation: Biomedical MRI Unit/MoSAIC, Department Imaging & Pathology, KU Leuven, Leuven, Belgium;
authors.forename: Jennifer
authors.initials: J
authors.lastname: Poelmans
authors.affiliation: Bruker microCT, Kontich, Belgium;
authors.forename: Peter
authors.initials: P
authors.lastname: Bruyndonckx
authors.affiliation: SB Dosimetry and Calibration, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre, SCK·CEN, Mol, Belgium;
authors.forename: Emiliano
authors.initials: E
authors.lastname: d'Agostino
authors.affiliation: Translational Cell and Tissue Research, Department Imaging and Pathology, KU Leuven, Leuven, Belgium; and.
authors.forename: Erik
authors.initials: E
authors.lastname: Verbeken
authors.affiliation: Laboratory of Experimental Radiotherapy, Department of Oncology, KU Leuven, Leuven, Belgium.
authors.forename: Ria
authors.initials: R
authors.lastname: Bogaerts
authors.affiliation: Laboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Center, Department of Development and Regeneration, KU Leuven, Leuven, Belgium; Division of Rheumatology, University Hospitals Leuven, Flanders, Belgium; rik.lories@med.kuleuven.be.
authors.forename: Rik
authors.initials: R
authors.lastname: Lories
authors.affiliation: Biomedical MRI Unit/MoSAIC, Department Imaging & Pathology, KU Leuven, Leuven, Belgium;
authors.forename: Uwe
authors.initials: U
authors.lastname: Himmelreich
mesh_terms: D000818:Animals; D004307:Dose-Response Relationship, Radiation; D008168:Lung / Q000000981:diagnostic imaging / Q000473:pathology / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055114:X-Ray Microtomography / Q000009:adverse effects*
keywords: Monte Carlo; dosimetry; in vivo lung imaging; radiation safety