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.
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: 1. 3 Tesla Connectome MRI to detect structural disruption of brain networks 2. 7 Tesla MRI to detect functional disruption of brain networks 3. Translocator protein (TSPO) PET - ligand \[11C\]-PBR28 to detect neuroinflammation 4. Tau PET - ligand \[18F\]-MK6240 to detect tau deposition 5. Neurocognitive assessments to detect signs of cognitive/behavioral dysfunction 6. Self-report indicators of cognitive/behavioral dysfunction 7. 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.
Study Type
OBSERVATIONAL
Enrollment
30
MRI scan of structural connectivity
MRI scan of functional connectivity
PET scan of neuroinflammation
Massachusetts General Hospital
Boston, Massachusetts, United States
Diffusion MRI structural connectivity
measured by white matter tractography
Time frame: Day 1
fMRI resting state functional connectivity
measured by default mode network connectivity
Time frame: Day 2
PET Neuroinflammation
measured by standardized uptake value ratio of TSPO ligand \[11C\]PBR28
Time frame: Day 1
PET Tau deposition
measured by standardized uptake value ratio of \[18F\]MK6240
Time frame: Day 2
Neurofilament Light Chain
measured by serum concentration of neurofilament light chain
Time frame: Day 1, after 6-8 hour fasting
Cognitive Function
measured by the Trail Making Test
Time frame: Day 1
Behavioral symptoms
measured by the Neurobehavioral Symptom Inventory
Time frame: Day 2
Physical symptoms
measured by the Neurobehavioral Symptom Inventory
Time frame: Day 2
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PET scan of tau deposition
Assessments of memory, attention, complex reasoning, mood and other cognitive/behavioral domains
Blood-based assessments of proteomic and metabolic biomarkers of brain injury