Repeated Contrast-Enhanced Micro-CT Examinations Decrease Animal Welfare and Influence Tumor Physiology

Author:

Baier Jasmin1,Rix Anne1,Darguzyte Milita1,Girbig Renée Michèle1,May Jan-Niklas1,Palme Rupert2,Tolba René3,Kiessling Fabian1

Affiliation:

1. Institute for Experimental Molecular Imaging, Medical Faculty, RWTH Aachen International University, Aachen, Germany

2. Department of Biomedical Sciences, University of Veterinary Medicine Vienna, Vienna, Austria

3. Institute for Laboratory Animal Science and Experimental Surgery, Medical Faculty, RWTH Aachen International University, Aachen, Germany.

Abstract

Objectives Computed tomography (CT) imaging is considered relatively safe and is often used in preclinical research to study physiological processes. However, the sum of low-dose radiation, anesthesia, and animal handling might impact animal welfare and physiological parameters. This is particularly relevant for longitudinal studies with repeated CT examinations. Therefore, we investigated the influence of repeated native and contrast-enhanced (CE) CT on animal welfare and tumor physiology in regorafenib-treated and nontreated tumor-bearing mice. Material and Methods Mice bearing 4T1 breast cancer were divided into 5 groups: (1) no imaging, (2) isoflurane anesthesia only, (3) 4 mGy CT, (4) 50 mGy CT, and (5) CE-CT (iomeprol). In addition, half of each group was treated with the multikinase inhibitor regorafenib. Mice were imaged 3 times within 1 week under isoflurane anesthesia. Behavioral alterations were investigated by score sheet evaluation, rotarod test, heart rate measurements, and fecal corticosterone metabolite analysis. Tumor growth was measured daily with a caliper. Tumors were excised at the end of the experiment and histologically examined for blood vessel density, perfusion, and cell proliferation. Results According to the score sheet, animals showed a higher burden after anesthesia administration and in addition with CT imaging (P < 0.001). Motor coordination was not affected by native CT, but significantly decreased after CE-CT in combination with the tumor therapy (P < 0.001). Whereas tumor growth and blood vessel density were not influenced by anesthesia or imaging, CT-scanned animals had a higher tumor perfusion (P < 0.001) and a lower tumor cell proliferation (P < 0.001) for both radiation doses. The most significant difference was observed between the control and CE-CT groups. Conclusion Repeated (CE-) CT imaging of anesthetized animals can lead to an impairment of animal motor coordination and, thus, welfare. Furthermore, these standard CT protocols seem to be capable of inducing alterations in tumor physiology when applied repetitively. These potential effects of native and CE-CT should be carefully considered in preclinical oncological research.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Radiology, Nuclear Medicine and imaging,General Medicine

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