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

Abstract

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.

Evaluation of fNIRS Signal Components Elicited by Cognitive and Hypercapnic Stimuli

“…In fact, hemisphere was not a significant predictor for hypercapnic task. This is supported by CVR literature, which suggests that PaCO2 is a global stimulus that induces similar magnitude of change in CBF across all regions of PFC to a fixed input 71 . For cognitive task, significant differences in activity were observed only in VLF band of long-SDS measurements.…”

“…This statement is further supported by the fact that during cognitive tasks HbR has higher correlation with BOLD-fMRI than HbO or HbT 108 . Higher correlations between HbR and BOLD-fMRI during CO2 tasks have also been reported 71,99 . However, due to its low dynamic range, HbR is more prone to motion artifacts and therefore results in an underestimation of hemodynamic activity associated with NVC or CVR 30 .…”

“…1B). Detailed description of instrumentation set up and how the protocol was administered can be found in 71 .…”

“…This experiment was chosen because preliminary results has shown strong NVC activity in left and right PFC regions associated with working memory and sustained attention 72 . In the second study, hypercapnia was the chosen stimulus, since it is known to result in a homogenous effect across all regions of PFC, does not require subject engagement and does not induce evoked NVC 71 . More importantly, the hypercapnic task allows for quantification of PaCO2's effect.…”

Multifactorial and closed head impact traumatic brain injuries cause distinct tactile hypersensitivity profiles

“…This translates to an annual cost of ~$80 billion, with TBI as the leading cause of death in adults under 45 years of age [18; 31; 43]. After the initial physical injury, TBI involves a complex secondary response with prolonged immune reactivity [55], neurodegeneration [46], mitochondrial dysfunction [24], and cerebrovascular compromise [1]. An estimated 70-90% of TBIs are mild [6; 10; 53], defined as suffering from momentary changes in consciousness and scoring between 13 and 15 on the Glasgow Coma Scale [48].…”