Synaptic density, tau deposition and multi-parametric PET-MR after traumatic brain injury: implications for diagnosis, prognosis and development of chronic neurodegeneration.

Traumatic brain injury (TBI) is a heterogeneous condition, originating from external force impact, consisting of a broad spectrum of functional disorders with highly variable outcome. TBI incidence is rising and it forms a prominent cause of mortality and morbidity, leading to great personal suffering and high healthcare costs. Furthermore, epidemiological and postmortem studies showed that episodic and repetitive TBI can lead to a specific form of neurodegeneration known as chronic traumatic encephalopathy (CTE). Significant knowledge has been built in understanding TBI using structural and functional MRI, but currently, no reliable biomarkers are available to predict progression/recovery, or monitor therapeutic interventions in TBI nor to diagnose and monitor CTE in vivo. Two pathological hallmarks of TBI and CTE are decreased synaptic connections and tau accumulation upon injury. Recently, novel PET tracers for both synaptic density (11C-UCB-J) and tau deposits (18F-MK-6240) have been validated in Leuven. Using simultaneous PET-MR with advanced structural and functional MRI, this provides a unique set of tools to determine the value of multimodal synaptic density imaging for TBI diagnosis and progression prediction. In CTE, in vivo synaptic density and tau imaging will be combined with neurological and neuropsychological testing, to specify long-term TBI effects and identify specific risk biomarkers that allow recovery prediction or likelihood for further deterioration.