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

Abstract 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 (ΔPO2) to CO2 (ΔPCO2) 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 ΔPO2, ΔPCO2, and bER were computed, and their cross-correlation with regional change in BOLD (ΔBOLD) 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 ΔBOLD 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 ΔBOLD with ΔPO2 and ΔPCO2. The averaged changes in bER (ρ=0.79, p=0.01) and ΔPO2 (ρ=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.