MICA: Assessing tau levels after traumatic brain injury (TBI) using [18F]T807 positron emission tomography (PET)

外伤性脑损伤（TBI）是指大脑因身体损伤而受损，例如车祸、跌倒或运动损伤。这是非常常见的，患有TBI的患者通常会有长期的残疾，这些残疾会产生深远的影响，比如失业或关系破裂。我们目前没有很好的方法来治疗这些长期问题，甚至没有准确的方法来预测它们是否会发生。创伤性脑损伤后的长期结果实际上是非常难以预测的，许多患者的情况非常糟糕。格拉斯哥的一项大型研究对1995年受伤的患者进行了跟踪调查。在最后一次评估时，大约有40%的人已经死亡，在那些幸存的人中，许多人在受伤后很长一段时间内继续恶化。其原因尚不清楚，但越来越多的证据表明，创伤性脑损伤会引发脑细胞的逐渐死亡，这是阿尔茨海默病等疾病的特征。事实上，严重的头部损伤使你更有可能在多年后患上阿尔茨海默病。阿尔茨海默病和其他类型的痴呆症的一个特征是存在一种名为tau的异常蛋白质。这种蛋白质在受影响的脑细胞中形成团块或“缠结”，这被认为是导致这些脑细胞死亡或“神经变性”的重要因素。脑外伤后也会出现tau蛋白异常，这为多年后发生的脑损伤和神经退行性变提供了明显的联系。问题是，如果没有脑组织在显微镜下观察，很难识别和研究tau病理学。现在需要的是一种检测异常tau蛋白存在的方法，而不需要患者进行手术。一种叫做正电子发射断层扫描（PET）的脑成像技术为这个问题提供了一个潜在的解决方案。早期的研究表明，一种特殊类型的PET可以用来证明tau异常。该方法已成功用于阿尔茨海默氏症患者，这开启了一种令人兴奋的可能性，即PET可用于检测其他神经系统疾病（如TBI）中的异常tau蛋白。我们建议研究PET是否可以用于识别TBI后的异常tau。该项目是一些具有互补专业知识的研究和商业团体之间的合作。我们将调查来自格拉斯哥的一组患者，他们已经被证明有非常不同的结果，并且已经进行了多年的详细随访。除了PET扫描，患者还将接受详细的临床和心理测试，以及另一种脑部扫描（MRI），可以确定创伤性脑损伤后的脑损伤程度。我们将测试受伤后表现不佳的患者是否有高水平的异常tau蛋白，以及这是否与特定的脑损伤模式和心理问题有关。这将是第一次在TBI中尝试这项工作。我们希望这项工作能让我们识别出有神经退化迹象的患者，这些患者有心理问题、痴呆和早逝的风险。最终，这将有助于医生对TBI患者进行早期诊断，并使我们能够更有效地在最有可能从中受益的TBI患者群体中进行新疗法的试验。

Traumatic Brain Injury (TBI) happens when the brain is damaged by physical injury, for example, after a car crash, a fall or a sporting injury. It is very common, and patients who have TBI often have long-term disabilities that have far-reaching consequences, such as job-loss or relationship breakdown. We currently do not have good treatments for these long-term problems, or even accurate ways of predicting whether they might occur.The long-term outcome after TBI is actually very unpredictable, and many patients do surprisingly badly. A large study in Glasgow has followed-up patients since their injuries in 1995. At the time of the last assessment about 40% had died, and of the ones who survived many had continued to deteriorate long after their injuries. The reasons for this are unclear, but there is growing evidence that TBI can trigger the kind of gradual death of brain cells that is characteristic of conditions like Alzheimer's Disease. In fact, a significant head injury makes it much more likely that you will develop Alzheimer's Disease many years later.One characteristic feature of Alzheimer's Disease and other types of dementia is the presence of an abnormal type of a protein called tau. The protein forms clumps or 'tangles' in affected brain cells, and this is thought to be an important factor in the death or 'neurodegeneration' of these brain cells. Abnormalities of tau are also seen following TBI, and this provides an obvious link between a head injury and neurodegeneration that occurs many years later. The problem has been that it is very difficult to identify and study tau pathology without having brain tissue to look at under the microscope. What is needed is a way of testing for the presence of abnormal tau protein, without patients needing to have an operation.A brain imaging technique called positron emission tomography (PET) provides a potential solution to the problem. Early studies show that a particular type of PET can be used to demonstrate tau abnormalities. The method has been successfully used in patients with Alzheimer's Disease, and this opens the exciting possibility that PET could be used to test for abnormal tau in other neurological conditions such as TBI.We proposed investigating whether PET can be used to identify abnormal tau following TBI. The project is a collaboration between a number of research and commercial groups who have complementary expertise. We will investigate the group of patients from Glasgow who have already been shown to have extremely variable outcome, and who have had detailed follow up for many years. In addition to PET scanning, patients will have detailed clinical and psychological testing, as well as another type of brain scanning (MRI) that allows the amount of brain injury after TBI to be determined. We will test whether patients who have done badly after their injuries have high levels of abnormal tau protein, and whether this is associated with particular patterns of brain injury and psychological problems.This will be first time this work has been attempted in TBI. We hope the work will allow us to identify patients with evidence of neurodegeneration, who are at risk of psychological problems, dementia and early death. Ultimately this will assist doctors in making an early diagnosis in TBI patients, and will allow us to more efficiently conduct trials of new treatments in groups of TBI patients who are most likely to benefit from them.