Influence of longitudinal radiation exposure from microcomputed tomography scanning on skeletal muscle function and metabolic activity in female CD-1 mice.

John S Mikhaeil,Sandra M Sacco,Cameron R Giles,William Gittings,Caitlin Saint,Jordan Bunda,Paul J Leblanc,Val Andrew Fajardo,Rene Vandenboom,Wendy E Ward

doi:10.14814/phy2.13338

Abstract

Microcomputed tomography (μ CT) is an imaging technology to assess bone microarchitecture, a determinant of bone strength. When measured in vivo, μ CT exposes the skeletal site of interest to a dose of radiation, in addition to nearby skeletal muscles as well. Therefore, the aim of this study was to determine the effects of repeated radiation exposure from in vivo μ CT on muscle health – specifically, muscle morphometrics, contractile function, and enzyme activity. This study exposed the right hind limb of female mice to either a low (26 cGy) or moderate (46 cGy) dose, at 2, 4, and 6 months of age, while the left hind limb of the same animal was exposed to a single dose at 6 months to serve as a nonirradiated control. Muscle weight, cross‐sectional area, isometric contractile function, and representative maximal enzyme activities of amino acid, fatty acid, glucose, and oxidative metabolism in extensor digitorum longus (EDL) and soleus were assessed. Low‐dose radiation had no effect. In contrast, moderate‐dose radiation resulted in a 5% increase in time‐to‐peak tension and 16% increase in half‐relaxation time of isometric twitches in EDL, although these changes were not seen when normalized to force. Moderate‐dose radiation also resulted in an ~33% decrease in citrate synthase activity in soleus but not EDL, with no changes to the other enzymes measured. Thus, three low doses of radiation over 6 months had no effect on contractile function or metabolic enzyme activity in soleus and EDL of female mice. In contrast, three moderate doses of radiation over 6 months induced some effects on metabolic enzyme activity in soleus but not EDL. Future studies that wish to investigate muscle tissue that is adjacent to scanned bone should take radiation exposure dose into consideration.

Highlights

In vivo microcomputed tomography is a threedimensional imaging technology used to provide a longitudinal assessment of bone structure in mice (Sacco et al 2017) and rats (Longo et al 2017)
The only study to examine an X-ray dose similar to this study looked at markers of mouse-mixed hind limb protein synthesis and degradation after a single dose of 50 cGy, demonstrating increased muscle turnover (Fix et al 2016)
Our findings demonstrate that exposure to low dose radiation had no effect on skeletal muscle contractile function, and maximal enzyme activity

Summary

Introduction

In vivo microcomputed tomography (lCT) is a threedimensional imaging technology used to provide a longitudinal assessment of bone structure in mice (Sacco et al 2017) and rats (Longo et al 2017). This technology lends for a more powerful study design because it minimizes the number of animals required for a study. Recent work from our laboratory has shown that longitudinal assessment of bone structure in male and female mice at low to moderate doses of radiation (26–46 cGy) over longer periods of time (4 months) with longer scanning intervals (2 months) does not affect bone structure (Sacco et al 2017). Low to moderate radiation doses at longer intervals and over a longer period provide a reasonable image quality of the bone microarchitecture without affecting the structural properties of the bone tissue under examination

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