Detection of secondary neurodegeneration after subarachnoid hemorrhage in the rat using the PET tracer cis-4-[18F]fluoro-D-proline and functional MRI, and investigation of the neuroprotective effect of argon

使用 PET 示踪剂 cis-4-[18F]氟-D-脯氨酸和功能 MRI 检测大鼠蛛网膜下腔出血后继发性神经变性，并研究氩气的神经保护作用

• 批准号: 412303240
• 负责人: Professor Dr. Mark Coburn
• 金额: --
• 依托单位: Institut für Neuropathologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/412303240?language=en
• 关键词: Detection; secondary; neurodegeneration; after; subarachnoid

The patients’ impairments after a subarachnoid hemorrhage (SAH) cannot always be associated with focal structural brain lesions that could be detected by computer tomography (CT) or conventional magnetic resonance imaging (MRI). Furthermore, focal brain lesions are not always linked to neuropsychological deficits. The detection of neurodegenerative changes at an early stage after SAH is not possible at the moment.Positron emission tomography (PET) and autoradiography with the 18F-labeled amino acid cis-4-[18F]fluoro-D-proline (cisF18DPro) have proven to be very sensitive methods for the detection of secondary degenerative processes in caudate nucleus, thalamus and hippocampus in rat models of cortical infarction and brain tumor. Moreover, advanced MRI-methods like sodium imaging, water mapping and diffusion-weighted MRI offer new opportunities to detect subtle pathologic events in brain diseases that are not visible in conventional MRI at an early stage of disease.Furthermore, the biologically active noble gas argon has recently come into scientific focus. Its neuroprotective effects have been shown in different experimental models; moreover, unlike xenon, it lacks sedative side effects under normobaric conditions and has low acquisition costs.The aim of the present study is to investigate whether secondary neurodegeneration after SAH can be detected by cisF18DPro-PET or autoradiography and advanced MRI methods in an early stage of the disease. The trauma will be analyzed after different time points (3, 6, 9 days) using MRI, PET and autoradiography. By comparing the results with the uptake of a reference tracer (3H-deoxyglucose) and immunofluorescence, we intend to determine the value of the above mentioned imaging methods with regard to the detection of secondary neurodegenerative injuries. Moreover, we want to explore whether a treatment with argon at an early stage of SAH has beneficial effects on secondary damages and whether they can be detected and followed by the imaging methods mentioned above.The study aims at establishing novel PET and functional MRI methods as diagnostic tools for the early and non-invasive detection of secondary neuronal damage in patients with SAH and to investigate the neuroprotective effect of argon with the aim of optimizing the therapy and diagnosis, and to improve the prognosis in patients with SAH.

蛛网膜下腔出血（SAH）后患者的损伤并不总是与计算机断层扫描（CT）或常规磁共振成像（MRI）可以检测到的局灶性脑结构病变相关。此外，局灶性脑损伤并不总是与神经心理缺陷有关。正电子发射断层扫描（PET）和放射自显影与18 F-标记的氨基酸顺式-4-[18 F]氟-D-脯氨酸（cisF 18 DPro）已被证明是非常敏感的方法检测继发性变性过程中的尾状核，丘脑和海马在大鼠模型的皮层梗死和脑肿瘤后的神经退行性变化在SAH后的早期阶段是不可能的。此外，先进的MRI方法，如钠成像、水成像和弥散加权MRI，为在疾病的早期阶段发现传统MRI无法观察到的脑部疾病的细微病理事件提供了新的机会。此外，具有生物活性的惰性气体氩气最近成为科学关注的焦点。它的神经保护作用已被证明在不同的实验模型，此外，不像氙，它缺乏镇静的副作用在常压条件下，并具有低收购costs.The本研究的目的是调查是否继发性神经退行性变后SAH可以检测到cisF 18 DPro-PET或放射自显影和先进的MRI方法在疾病的早期阶段。将在不同时间点（3、6、9天）后使用MRI、PET和放射自显影术分析创伤。通过比较的结果与参考示踪剂（3 H-脱氧葡萄糖）和免疫荧光的摄取，我们打算确定上述成像方法的继发性神经退行性损伤的检测方面的价值。此外，委员会认为，我们想探索在SAH早期用氩气治疗是否对继发性损伤有有益的影响，以及它们是否可以通过上述成像方法检测和跟踪。本研究旨在建立新的PET和功能MRI方法作为诊断早期和非SAH的工具。有创检测SAH患者继发性神经元损伤，并研究氩的神经保护作用，以优化治疗和诊断，改善SAH患者的预后。