Imaging in the context of 3R: chances and threats

3R 背景下的成像：机遇与威胁

• 批准号: 329693114
• 负责人: Professor Dr. Fabian Kiessling
• 金额: --
• 依托单位: Institut für Experimentelle Molekulare Bildgebung (ExMI)
• 依托单位国家: 德国
• 项目类别: Research Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/329693114?language=en
• 关键词: Imaging; context; 3R; chances; threats

During the previous funding periods, we gained important insights into the effects of imaging techniques (Magnetic Resonance Imaging (MRI), Ultrasound (US), and Computed Tomography (CT)) on animal welfare and study outcomes in healthy and tumor-bearing mice. The tested imaging protocols were well tolerated according to our severity tests. However, CT and contrast-enhanced US induced changes in tumor physiology (esp. tumor perfusion and immune reactions), which were further investigated through a systematic review. Another question was whether state of the art severity tests are sensitive enough to detect even mild burdens and tissue reactions and whether this can be refined by imaging applications. Therefore, we implemented an imaging concept for the simultaneous detection of pain ([18F]Fluspidine-PET-CT) and tissue damage ([99mTc]-Duramycin-SPECT-CT). By using this new concept, we have already validated the suitability of a postoperative analgesia protocol in a rat model of partial liver resection. The results indicate that our approach can significantly enhance pain monitoring in future preclinical studies and be a reference for other severity assessment tools. Currently, we are investigating the suitability of these tracers in models of neuropathic pain. The 3rd funding period will focus on an in-depth analysis of previously collected behavioral and physiological welfare data. Thereby, the data will be re-analyzed to significantly improve the generalizability and robustness of the RElative Severity Assessment (RELSA) tool. Additionally, we plan to utilize the RELSA tool to design and publish appropriate score sheets for imaging protocols. By comparing these datasets with those from other working groups within our consortium and conducting further systematic reviews (e.g., CT effects on tumor physiology), we aim to develop comprehensive recommendations for “refining” imaging techniques (e.g., appropriate anesthesia protocols). During the previous funding periods, we have already published some of the imaging data as a CT reference database, making it freely accessible to the scientific community in accordance to FAIR criteria. In the 3rd funding period, we plan to create an expanded and comprehensive imaging database comprising data from various imaging modalities and disease models. This database will be easily accessible and enable data reuse, thereby promoting the long-term reduction of laboratory animals. Lastly, we aim to develop comprehensive recommendations for the efficient and reliable use of imaging for the refinement of experiments and the assessment of their severity. We will accomplish this by detailed comparison of our pre-existing data, focusing on the sensitivity of our imaging protocols in contrast to conventional methods.

在前面的资金期间，我们对成像技术（磁共振成像（MRI），超声（US）和计算机断层扫描（CT））对动物福利的影响进行了重要见解。根据我们的严重性测试，经过测试的成像方案良好。然而，CT和对比增强的US诱导了肿瘤生理学的变化（尤其是肿瘤灌注和免疫学反应），通过系统的综述进一步研究了肿瘤生理学的变化。另一个问题是，最严重的测试状态是否足够敏感，甚至可以检测到轻度的燃烧和组织反应，以及是否可以通过成像应用来完善这种反应。因此，我们实现了一个成像概念，以简单检测疼痛（[18F] fluspidine-pet-ct）和组织损伤（[99mtc] -duramycin-spect-ct）。通过使用这个新概念，我们已经验证了部分肝切除大鼠模型中术后镇痛方案的适用性。结果表明，我们的方法可以显着增强未来临床前研究的疼痛监测，并参考其他严重评估工具。目前，我们正在研究这些示踪剂在神经性疼痛模型中的适用性。第三筹时期将重点介绍对先前收集的行为和生理福利数据的深入分析。因此，将重新分析数据，以显着提高相对严重性评估（RERSA）工具的普遍性和鲁棒性。此外，我们计划利用RERSA工具设计和发布适当的成像协议得分表。通过将这些数据集与联盟中其他工作组的数据集进行比较，并进行了进一步的系统评价（例如，CT对肿瘤生理的影响），我们旨在为“完善”成像技术（例如，适当的麻醉协议）提出全面的建议。在过去的资金期间，我们已经将一些成像数据作为CT参考数据库发布，使其根据公平的标准免费访问科学界。在第三筹时期，我们计划创建一个扩展而全面的成像数据库，从各种成像方式和疾病模型中填写数据。该数据库将易于访问并启用数据库，从而促进了实验室动物的长期减少。最后，我们旨在为有效，可靠的成像使用进行实验的细化及其严重性评估，为有效和可靠的成像使用。我们将通过详细比较我们先前存在的数据来实现这一目标，并以与常规方法相比，重点介绍了成像协议的敏感性。