From the Institute for Experimental Molecular Imaging, Medical Faculty, RWTH Aachen International University, Aachen, Germany.
Department of Biomedical Sciences, University of Veterinary Medicine Vienna, Vienna, Austria.
Invest Radiol. 2023 May 1;58(5):327-336. doi: 10.1097/RLI.0000000000000936. Epub 2022 Oct 25.
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.
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.
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.
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.
计算机断层扫描（CT）成像被认为相对安全，常用于临床前研究以研究生理过程。然而，低剂量辐射、麻醉和动物处理的总和可能会影响动物福利和生理参数。对于重复 CT 检查的纵向研究，这一点尤其重要。因此，我们研究了重复进行原生和对比增强（CE）CT 对接受和未接受regorafenib 治疗的荷瘤小鼠的动物福利和肿瘤生理学的影响。
携带 4T1 乳腺癌的小鼠分为 5 组：（1）无成像，（2）仅异氟烷麻醉，（3）4 mGy CT，（4）50 mGy CT 和（5）CE-CT（碘普罗胺）。此外，每组的一半接受多激酶抑制剂regorafenib 治疗。在异氟烷麻醉下，小鼠在 1 周内进行 3 次成像。通过评分表评估、转棒试验、心率测量和粪便皮质酮代谢物分析来研究行为改变。每天用卡尺测量肿瘤生长。实验结束时切除肿瘤，并进行组织学检查以评估血管密度、灌注和细胞增殖。
根据评分表，动物在麻醉后和 CT 成像后表现出更高的负担（P<0.001）。原生 CT 不影响运动协调，但与肿瘤治疗联合使用 CE-CT 后显著降低（P<0.001）。虽然麻醉或成像对肿瘤生长和血管密度没有影响，但 CT 扫描动物的肿瘤灌注更高（P<0.001），且细胞增殖率更低（P<0.001），两种辐射剂量均如此。在对照组和 CE-CT 组之间观察到最显著的差异。
对麻醉动物进行重复（CE-）CT 成像会导致动物运动协调受损，从而影响动物福利。此外，当重复应用这些标准 CT 方案时，它们似乎有能力引起肿瘤生理学的改变。在临床前肿瘤学研究中，应仔细考虑原生和 CE-CT 的这些潜在影响。
