The proposal includes a comprehensive battery of assessments characterized by high-field neuroimaging, proteomics, and experimental cognitive and neurobehavioral evaluations, which will be implemented alongside standardized clinical diagnostic tools. The results will inform the design of a larger trial to validate the diagnostic utility of these biomarkers as well as their ability to predict RLLBE-related clinical outcomes. A secondary aim will be to define the underlying mechanisms, risk and resilience factors, and clinical phenotypes associated with RLLBE.~Biomarkers assessed over the course of a two-day evaluation will include:~3 Tesla Connectome MRI to detect structural disruption of brain networks~7 Tesla MRI to detect functional disruption of brain networks~Translocator protein (TSPO) PET - ligand [11C]-PBR28 to detect neuroinflammation~Tau PET - ligand [18F]-MK6240 to detect tau deposition~Neurocognitive assessments to detect signs of cognitive/behavioral dysfunction~Self-report indicators of cognitive/behavioral dysfunction~Blood biomarkers to detect evidence of blast injury using proteomics and metabolomics~We hypothesize that a multimodal assessment using Connectome MRI, 7 Tesla MRI, TSPO PET, Tau PET, cognitive/behavioral tests, proteomics and metabolomics will identify biomarkers of RLLBE-related brain injury.
This is a pilot study to identify biomarkers that individually, and in combination, demonstrate the greatest sensitivity to repetitive, low-level blast exposure (RLLBE) neurotrauma in Special Operations Forces (SOF) personnel. The proposed cross-sectional, multimodal study will elucidate the potential effects of long-term RLLBE by comparing biomarkers across subjects.