Synaptic density, tau and multiparametric PET-MR for quantitative functional assessment and prognosis in stroke and mild cognitive impairment

There are no reliable biomarkers to predict recovery, assess prognosis or objectively monitor interventions in stroke and amnestic mild cognitive impairment (aMCI) due to Alzheimer’s disease. Two major, related pathological hallmarks common to these disorders are a decrease in synaptic connectivity, which may involve various neurotransmitters, and an accumulation of tau protein deposits. These are associated with disturbances in white matter integrity and regional network dysfunction, before finally neuronal death and atrophy occur. Simultaneous PET-MR allows quantitative imaging of these hallmarks in only two sessions, to determine their respective contribution and chronological dependence in vivo. Using novel highly specific and sensitive radioligands for synaptic density (synaptic vesicle glycoprotein (SV2a), 11CUCB-J) and tau deposits (18F-MK-6240), together with advanced MR measures of white matter tract integrity, resting-state fMRI network analysis and structural MR metrics, we want to assess their individual and combined diagnostic, prognostic and monitoring value to measure functional disease burden in relation to cognitive and behavioural dysfunction. This will be done in a longitudinal study with two-year follow-up, using advanced voxel-based quantification and multiparametric graphbased analysis tools.