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

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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.