Cerebrovascular responses to O2-CO2 exchange ratio under brief breath-hold challenge in patients with chronic mild traumatic brain injury

Breath-by-breath O2-CO2 exchange ratio (bER) is a respiratory gas exchange (RGE) metric, which is the ratio of the changes in the partial pressure of O2 ({Delta}PO2) to CO2 ({Delta}PCO2) between endinspiration and end-expiration, has been demonstrated to characterize the cerebrovascular responses to breath-hold challenge in healthy individuals. We aimed to explore if bER could characterize cerebrovascular responses in patients with chronic mild traumatic brain injury (mTBI) under breath-hold challenge. We also investigated the correlation between bER and the severity of post-concussion symptoms. Blood-oxygenation-level-dependent (BOLD) images were acquired using functional magnetic resonance imaging (fMRI) on eleven patients with chronic mTBI and eleven controls without brain injury history when performing a breath-hold task. Time series of RGE metrics of {Delta}PO2, {Delta}PCO2, and bER were computed, and their cross-correlation with regional change in BOLD ({Delta}BOLD) was calculated. Symptom burden was assessed using the Rivermead Post Concussion Questionnaire (RPQ), and its correlation with RGE changes was also measured. Compared with controls, a diffuse decrease in the correlation between regional {Delta}BOLD and bER was found in the brain of mTBI patients (pfdr<0.05). No significant difference was found between patients and controls for the correlation of regional {Delta}BOLD with {Delta}PO2 and {Delta}PCO2. The averaged changes in bER ({rho}=0.79, p=0.01) and {Delta}PO2 ({rho}=0.70, p=0.03) in breath-hold epochs decreased with increased symptom severity indicated by RPQ scores. Our imaging and symptom severity findings suggest that bER can be used to characterize cerebrovascular responses to breath-hold in mTBI patients. RGE may contribute to the post-concussive symptom severity.