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.

在之前的资助期间，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))对动物福利的影响以及对健康和荷瘤小鼠的研究结果获得了重要的见解。根据我们的严重性测试，测试的成像方案耐受性良好。然而，CT和增强超声可引起肿瘤生理学改变(尤其是。肿瘤灌注和免疫反应)，通过系统回顾进一步研究。另一个问题是，最先进的严重性测试是否足够敏感，可以检测到即使是轻微的负担和组织反应，以及是否可以通过成像应用来改进这一点。因此，我们实施了一种同时检测疼痛([18F]氟比丁-PET-CT)和组织损伤([99mTc]-杜拉霉素-SPECT-CT)的成像概念。通过使用这一新概念，我们已经在大鼠肝部分切除模型中验证了术后止痛方案的适用性。结果表明，我们的方法可以在未来的临床前研究中显著加强疼痛监测，并为其他严重程度评估工具提供参考。目前，我们正在研究这些示踪剂在神经病理性疼痛模型中的适用性。第三个资助期将重点对之前收集的行为和生理福利数据进行深入分析。因此，将对数据进行重新分析，以显著提高相对严重性评估(RELSA)工具的概括性和稳健性。此外，我们计划利用RELSA工具为成像协议设计和发布适当的计分表。通过将这些数据集与我们联盟内其他工作组的数据集进行比较，并进行进一步的系统评估(例如，CT对肿瘤生理学的影响)，我们的目标是为“改进”成像技术(例如，适当的麻醉方案)开发全面的建议。在之前的供资期间，我们已经将一些成像数据作为CT参考数据库发布，使科学界能够按照公平的标准免费获取这些数据。在第三个资助期，我们计划创建一个扩展和全面的成像数据库，包括来自各种成像模式和疾病模型的数据。这个数据库将很容易访问，并使数据能够重复使用，从而促进长期减少实验动物。最后，我们的目标是为有效和可靠地使用成像来改进实验和评估其严重性而制定全面的建议。我们将通过详细比较我们以前存在的数据来实现这一点，重点是我们的成像协议与传统方法相比的敏感性。