Neuroinflammation at the Grey-White Matter Interface in Active-Duty United States Special Operations Forces

Emerging evidence from autopsy studies indicates that interface astroglial scarring (IAS) at the grey-white matter junction is a pathological signature of repeated blast brain injury in military personnel. However, there is currently no neuroimaging test that detects IAS, which is a major barrier to diagnosis, prevention, and treatment. In 27 active-duty United States Special Operations Forces personnel with high levels of cumulative blast exposure, we performed translocator protein (TSPO) positron emission tomography (PET) using [11C]PBR28 to detect neuroinflammation at the cortical grey-white matter interface, a neuroanatomic location where IAS has been reported in autopsy studies. TSPO signal in individual Operators was compared to the mean TSPO signal in a control group of 9 healthy civilian volunteers. We identified five Operators with TSPO signal at the cortical grey-white matter interface that was more than two standard deviations above the control mean. Cumulative blast exposure, as measured by the Generalized Blast Exposure Value, did not differ between the five Operators with elevated TSPO signal and the 22 Operators without elevated TSPO signal. While the pathophysiologic link between neuroinflammation and IAS remains uncertain, these observations provide the basis for further investigation into TSPO PET as a potential biomarker of repeated blast brain injury. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by the U.S. Department of Defense (USSOCOM Contract No. H9240520D0001) and Navy SEAL Foundation ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Institutional Review Board of Mass General Brigham and the United States Special Operations Command Human Research Protections Office gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes United States Special Operations Command (USSOCOM) regulations prevent public release of the data generated for the current study. Future requests for these data may be submitted to the corresponding author and will then need to be vetted by USSOCOM.