Assessment of cerebrovascular dysfunction after traumatic brain injury with fMRI and fNIRS

Traumatic cerebral vascular injury (TCVI) is a frequent, but under-recognized, endophenotype of traumatic brain injury (TBI).  It likely contributes to functional deficits after TBI and TBI-related chronic disability, and represents an attractive target for targeted therapeutic interventions. The aim of this prospective study is to assess microvascular injury/dysfunction in chronic TBI by measuring cerebral vascular reactivity (CVR) by 2 methods, functional magnetic resonance imaging (fMRI) and functional Near InfraRed Spectroscopy (fNIRS) imaging, as each has attractive features relevant to clinical utility. 42 subjects (27 chronic TBI, 15 age- and gender-matched non-TBI volunteers) were enrolled and underwent outpatient CVR testing by 2 methods, MRI-BOLD and fNIRS, each with hypercapnia challenge, a neuropsychological testing battery, and symptom survey questionnaires. Chronic TBI subjects showed a significant reduction in global CVR compared to HC (p < 0.0001). Mean CVR measures by fMRI were 0.225 ± 0.014 and 0.183 ± 0.026 %BOLD/mmHg for non-TBI and TBI subjects respectively and 12.3 ± 1.8 and 9.2 ± 1.7 mM/mmHg by fNIRS for non-TBI versus TBI subjects respectively. Global CVR measured by fNIRS imaging correlates with results by MRI-BOLD (R = 0.5). Focal CVR deficits seen on CVR maps by fMRI are also observed in the same areas by fNIRS in the frontal regions. Global CVR is significantly lower in chronic TBI patients and is reliably measured by both fMRI and fNIRS, the former with better spatial and the latter with better temporal resolution.  Both methods show promise as non-invasive measures of CVR function and microvascular integrity after TBI.