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

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结构性脑病变相关。此外，局灶性脑损伤并不总是与神经心理缺陷有关。目前尚不可能在SAH后早期发现神经退行性变化。正电子发射断层扫描（PET）和18F标记氨基酸顺-4-[18F]氟- d -脯氨酸（cisF18DPro）放射自显像已被证明是检测大鼠皮质梗死和脑肿瘤模型尾状核、丘脑和海马继发性退行性过程的非常敏感的方法。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检测常规MRI无法看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近年来已成为科学界关注的焦点。其神经保护作用已在不同的实验模型中得到证实；此外，与氙气不同，它在常压条件下没有镇静副作用，并且获取成本低。本研究的目的是探讨SAH后继发性神经退行性变是否可以在疾病早期通过cisF18DPro-PET或放射自显影和先进的MRI方法检测到。在不同时间点（3,6,9天）使用MRI， PET和放射自显像分析创伤。通过将结果与参考示踪剂（3h -脱氧葡萄糖）和免疫荧光的摄取结果进行比较，我们打算确定上述成像方法在继发性神经退行性损伤检测中的价值。此外，我们想探讨在SAH早期用氩气治疗是否对继发性损伤有有益的影响，以及是否可以通过上述成像方法检测和跟踪它们。本研究旨在建立新的PET和功能性MRI诊断方法，作为早期无创检测SAH患者继发性神经元损伤的诊断工具，探讨氩气的神经保护作用，以优化SAH患者的治疗和诊断，改善其预后。

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.