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.

Longitudinal, in vivo assessment of invasive pulmonary aspergillosis in mice by computed tomography and magnetic resonance imaging

“…26,39 Retrospective respiratory gating resulted in four data sets per scan, corresponding to different phases of the breathing cycle. The data set obtained during the end expiratory phase of the breathing was used for further analysis.…”

Beauty is more than skin deep: a non‐invasive protocol for in vivo anatomical study using micro‐CT

“…; Vande Velde et al . ). The average radiation dose during medical μCT studies on mice falls in the range of 0·02–0·96 Gy (Table ), far below their LD 50(30) of 5–7·6 Gy (Taschereau, Chow & Chatziioannou ).…”

“…Although caution is required when high radiation doses are being used (Vande Velde et al . ), a cumulative radiation dose of ≈5 Gy appears to have no significant negative effects on tissues in mice (Detombe et al . ).…”

High Dose MicroCT Does Not Contribute Toward Improved MicroPET/CT Image Quantitative Accuracy and Can Limit Longitudinal Scanning of Small Animals

“…They predicted that for a whole body scan, the dose could vary between 80 and 133 mGy. Recently, Vande Velde et al [33], using a SkyScan Bruker microCT scanner (parameters: 50 kVp and 120 ms; 50 kVp and 450 ms) and adult mice, reported absence of radiation induced lung damage even at a high dose protocol of 450 ms, despite measured skin doses as high as 1,104 mGy and lung doses of 813 mGy. They suggested that high dose microCT is safe for longitudinal lung studies, but recognized the current limited understanding among the scientific community on the impact of high absorbed doses in small animal longitudinal studies.…”