Synaptic Density, Tau and Multiparametric PET-MR in Brain Trauma, Stroke and Mild Cognitive or Behavioral Impairment.

Alzheimer's disease, stroke and TBI are frequently observed brain disorders, causing significant morbidity. For none of these disorders, there are in vivo diagnostic biomarkers available that allow determination of disease burden, patient-specific prognosis and therapy follow-up. However, they all share a similar mechanism that may cause accumulation of tau oligomers in the brain, synaptic dysfunction and cognitive and/or behavioral impairment. Until recently, the only way to quantify synaptic density and tau deposition was using post-mortem immunohistochemistry. Now, in vivo Positron Emission Tomography (PET) imaging of synaptic density has become possible trough development of 11C-UCB-J, a levetiracetam-based radioligand, expressing high affinity and specificity for SV2A. Furthermore, the novel radioligand 18F-MK-6240, specifically targeting tau deposits, was clinically implemented in our center. Through PET-MR, we can visualize the cascade of tau deposition, synaptic loss and degeneration of grey and white matter and relate these pathologic features to cognitive and behavioral deterioration. The goal of the study is to: 1) measure tau deposition and loss of synaptic density in these conditions as a potential measure for disease load 2) determination of the mid-term (2 years) monitoring capacity of combined functional-structural PET-MR imaging 3) relate progression of the imaging markers to cognitive and/or behavioral decline and 4) determination of the optimal combination of PET-MR metrics for early identification and risk-stratification of cognitive and/or behavioral dysfunction in de novo patients.