PET Imaging in Chronic Traumatic Encephalopathy

Objective: To determine if the PET radioligand \[11C\]PBB3 can detect aggregates of tau protein in the brains of patients with history of traumatic brain injury (TBI) and suspected chronic traumatic encephalopathy (CTE). Study population: The proposed study will include 40 subjects. Twenty will be patients with history of TBI and suspected CTE and 20 will be healthy cognitively normal volunteers without history of TBI. Design: Subjects will undergo medical screening and have brain MRI and neuropsychological testing performed. Subjects will undergo one brain PET scan with \[11C\]PBB3 to detect aggregates of tau protein. Subjects will also have one brain PET scan with \[11C\]Pittsburgh compound B (PIB) to detect amyloid plaques. Subjects will be asked to have a lumbar puncture to measure CSF tau concentrations. Outcome measures: The primary outcome measure will be the amount of \[11C\]PBB3 binding in the brain. We will quantify the radioligand s brain uptake, washout, plasma clearance, and distribution volume using compartmental modeling. Distribution volume of \[11C\]PBB3 is proportional to the density of insoluble paired helical filaments of tau and is equal to the ratio at equilibrium of uptake in brain to the concentration of parent radiotracer in plasma. As an exploratory measure, we will determine if there is a relationship between \[11C\]PBB3 binding in brain and gray matter loss on MRI. We will also measure the amount of \[11C\]PIB binding in the brain using the Logan reference tissue method with cerebellum as reference.