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Repeated Contrast-Enhanced Micro-CT Examinations Decrease Animal Welfare and Influence Tumor Physiology. 重复对比增强微CT检查降低动物福利并影响肿瘤生理。

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

发表日期:2022 Oct 25
作者: Jasmin Baier, Anne Rix, Milita Darguzyte, Renée Michèle Girbig, Jan-Niklas May, Rupert Palme, René Tolba, Fabian Kiessling
来源: INVESTIGATIVE RADIOLOGY

摘要:

计算机断层扫描(CT)成像被认为相对安全,常用于临床前研究探究生理过程。但是,低剂量辐射、麻醉和动物操作的累加可能对动物福利和生理参数产生影响。这在重复进行CT检查的纵向研究中尤为重要。因此,我们研究了反应利妥班治疗和未治疗的肿瘤鼠重复进行原始和增强(CE)CT对动物福利和肿瘤生理的影响。4T1乳腺癌鼠分为5组:(1)无成像(2)仅异氟醚麻醉,(3)4mGy CT,(4)50 mGy CT,(5)CE-CT(碘普罗)。此外,每组一半的鼠标接受多激酶抑制剂反应利妥班治疗。在异氟醚麻醉下,鼠标进行了3次影像。通过评分表评估、旋转杆测试、心率测量和粪便皮质酮代谢产物分析研究了行为变化。每日用卡尺测量肿瘤生长。实验结束时切除肿瘤并进行了细胞增殖、血管密度和灌注的组织学检查。根据评分表,动物在麻醉和成像后负担更重(P<0.001)。原始CT不会影响运动协调,但是与肿瘤治疗相结合的CE-CT会显著降低运动协调(P<0.001)。尽管麻醉或成像不会影响肿瘤生长和血管密度,但CT扫描的动物肿瘤灌注更高(P<0.001),细胞增殖更低(P<0.001),这适用于两种辐射剂量。控制组和CE-CT组之间的差异最为显著。反复进行(CE-)CT检查可能会导致麻醉动物的运动协调障碍,从而影响动物福利。此外,这些标准CT协议似乎能够在重复应用时诱导肿瘤生理学的变化。在临床前肿瘤学研究中应谨慎考虑原始和CE-CT的这些潜在影响。版权所有 © 2022 Wolters Kluwer Health,Inc.
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.Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.