Neuroinflammation at the Gray-White Matter Interface in Active-Duty U.S. Special Operations Forces

Abstract

Emerging evidence from autopsy studies indicates that interface astroglial scarring (IAS) at the gray-white matter junction is a pathological signature of repeated blast brain injury in military personnel. However, there is currently no in vivo neuroimaging test that detects IAS, which is a major barrier to diagnosis, prevention, and treatment. In 27 active-duty U.S. 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 gray-white matter interface, a neuroanatomic location where IAS has been reported in autopsy studies. TSPO signal in individual Operators was compared with the mean TSPO signal in a control group of nine healthy civilian volunteers. We identified five Operators (18.5%) with TSPO signal at the cortical gray-white matter interface that was more than 2 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 preliminary observations provide the basis for further investigation into TSPO PET as a potential biomarker of repeated blast brain injury.

Keywords: blast overpressure; interface astroglial scarring; special operations forces.

FIG. 1.

Translocator protein (TSPO) positron emission tomography (PET) detects neuroinflammation at the cortical gray–white matter interface in individual Operators. Axial images of TSPO PET data are shown for the five individual Operators with elevated TSPO signal at the cortical gray–white matter interface, compared with the 22 Operators without elevated TSPO signal and to a control group of nine healthy civilians. For the control group and the 22 Operators without elevated TSPO signal, the mean TSPO PET signal map is shown in MNI standard space. The intensity of the TSPO signal at the cortical gray–white matter interface is indicated by the color bar. L, left; R, right; SUVR_60–90, standardized uptake value normalized by whole brain mean, based on emission data collected from 60–90 min post-radioligand injection for [¹¹C]PBR28.

FIG. 2.

Translocator protein (TSPO) positron emission tomography (PET) z-score distributions for special operations forces and civilian controls. All TSPO measurements were performed at the gray–white matter interface of the cerebral cortex. Z-Scores represent the number of standard deviations that an individual’s TSPO signal differs from that of the control mean.