Dynamic association between perfusion and white matter integrity across time since injury in Veterans with history of TBI

OBJECTIVE: Cerebral blood flow (CBF) plays a critical role in the maintenance of neuronal integrity, and CBF alterations have been linked to deleterious white matter changes. Although both CBF and white matter microstructural alterations have been observed within the context of traumatic brain injury (TBI), the degree to which these pathological changes relate to one another and whether this association is altered by time since injury have not been examined. The current study therefore sought to clarify associations between resting CBF and white matter microstructure post-TBI. METHODS: 37 veterans with history of mild or moderate TBI (mmTBI) underwent neuroimaging and completed health and psychiatric symptom questionnaires. Resting CBF was measured with multiphase pseudocontinuous arterial spin labeling (MPPCASL), and white matter microstructural integrity was measured with diffusion tensor imaging (DTI). The cingulate cortex and cingulum bundle were selected as a priori regions of interest for the ASL and DTI data, respectively, given the known vulnerability of these regions to TBI. RESULTS: Regression analyses controlling for age, sex, and posttraumatic stress disorder (PTSD) symptoms revealed a significant time since injury × resting CBF interaction for the left cingulum (p < 0.005). Decreased CBF was significantly associated with reduced cingulum fractional anisotropy (FA) in the chronic phase; however, no such association was observed for participants with less remote TBI. CONCLUSIONS: Our results showed that reduced CBF was associated with poorer white matter integrity in those who were further removed from their brain injury. Findings provide preliminary evidence of a possible dynamic association between CBF and white matter microstructure that warrants additional consideration within the context of the negative long-term clinical outcomes frequently observed in those with history of TBI. Additional cross-disciplinary studies integrating multiple imaging modalities (e.g., DTI, ASL) and refined neuropsychiatric assessment are needed to better understand the nature, temporal course, and dynamic association between brain changes and clinical outcomes post-injury.