From the Institute for Experimental Molecular Imaging.
Department of Biomedical Sciences, Unit of Physiology, Pathophysiology and Experimental Endocrinology, University of Veterinary Medicine Vienna, Vienna, Austria.
Invest Radiol. 2020 Aug;55(8):507-514. doi: 10.1097/RLI.0000000000000669.
Magnetic resonance imaging (MRI) is considered to be well tolerated by laboratory animals. However, no systematic study has been performed yet, proving this assumption. Therefore, the aim of this study was to investigate the possible effects of longitudinal native and contrast-enhanced (CE) 1-T and 7-T MRI examinations on mouse welfare as well as 4T1 breast cancers progression and therapy response.
Forty-seven healthy and 72 breast cancer-bearing mice (4T1) were investigated. One-Tesla (ICON) and 7-T (Biospec) MRI measurements were performed thrice per week under isoflurane anesthesia in healthy BALB/c mice for 4 weeks and 3 times within 2 weeks in tumor-bearing animals. Animal welfare was examined by an observational score sheet, rotarod performance, heart rate measurements, and assessment of fecal corticosterone metabolites. Furthermore, we investigated whether CE-MRI influences the study outcome. Therefore, hemograms and organ weights were obtained, and 4T1 tumor growth, perfusion, immune cell infiltration, as well as response to the multikinase inhibitor regorafenib were investigated. Statistical comparisons between groups were performed using analysis of variance and Tukey or Bonferroni post hoc tests.
Mice showed no alterations in the observational score sheet rating, rotarod performance, heart rate, and fecal corticosterone metabolites (P > 0.05) after repeated MRI at both field strengths. However, spleen weights were reduced in all healthy mouse groups that received isoflurane anesthesia (P < 0.001) including the groups investigated by 1-T and 7-T MRI (P = 0.02). Neither tumor progression nor response to the regorafenib treatment was affected by isoflurane anesthesia or CE-MRI monitoring. Furthermore, immunohistological tumor analysis did not indicate an effect of isoflurane and MRI on macrophage infiltration of tumors, perfusion of tumor vessels, and apoptotic cell rate (P > 0.05).
Repeated MRI did not influence the welfare of mice and did not affect tumor growth and therapy response of 4T1 tumors. However, systemic immunological effects of isoflurane anesthesia need to be considered to prevent potential bias.
磁共振成像（MRI）被认为是实验室动物能够很好耐受的。然而，目前还没有进行系统的研究来证明这一假设。因此，本研究的目的是调查纵向原生和对比增强（CE）1-T 和 7-T MRI 检查对小鼠福利以及 4T1 乳腺癌进展和治疗反应的可能影响。
共研究了 47 只健康小鼠和 72 只乳腺癌荷瘤（4T1）小鼠。健康 BALB/c 小鼠每周进行 3 次 1-Tesla（ICON）和 7-T（Biospec）MRI 测量，共进行 4 周；荷瘤动物在 2 周内进行 3 次。通过观察评分表、转棒性能、心率测量和粪便皮质酮代谢物评估来检查动物福利。此外，我们还研究了 CE-MRI 是否会影响研究结果。因此，我们获得了血液学参数和器官重量，并研究了 4T1 肿瘤生长、灌注、免疫细胞浸润以及对多激酶抑制剂regorafenib 的反应。使用方差分析和 Tukey 或 Bonferroni 事后检验对组间进行了统计学比较。
在两种场强下重复 MRI 后，小鼠在观察评分表评分、转棒性能、心率和粪便皮质酮代谢物方面均无变化（P > 0.05）。然而，所有接受异氟烷麻醉的健康小鼠组的脾脏重量均降低（P < 0.001），包括接受 1-T 和 7-T MRI 检查的组（P = 0.02）。异氟烷麻醉或 CE-MRI 监测均未影响肿瘤进展或regorafenib 治疗的反应。此外，免疫组织学肿瘤分析表明，异氟烷和 MRI 对肿瘤内巨噬细胞浸润、肿瘤血管灌注和细胞凋亡率没有影响（P > 0.05）。
重复 MRI 不会影响小鼠的福利，也不会影响 4T1 肿瘤的生长和治疗反应。然而，需要考虑异氟烷麻醉的全身免疫效应，以防止潜在的偏倚。
