Cerebrovascular reactivity assessment with O2-CO2 exchange ratio under brief breath hold challenge
Hypercapnia during breath holding is believed to be the dominant driver behind the modulation of cerebral blood flow (CBF). Here we showed that the cerebrovascular responses to brief breath hold epochs were coupled not only with increased partial pressure of carbon dioxide (PCO2), but also with a decrease in partial pressure of oxygen (PO2). We used transcranial Doppler ultrasound to evaluate the CBF changes during breath holding by measuring the cerebral blood flow velocity (CBFv) in the middle cerebral arteries, a pair of cerebral arteries that supply most parts of the brain. The regional CBF changes during breath hold epochs were mapped with blood oxygenation level dependent (BOLD) signal changes as surrogate of CBF changes using functional magnetic resonance imaging (fMRI) technique. Given the interdependence of the dynamic changes between PCO2 and PO2, we found that the breath-by-breath O2-CO2 exchange ratio (bER), namely the ratio of changes in PO2 ({Delta}PO2) to changes in PCO2 ({Delta}PCO2) between end inspiration and end expiration, was superior to either {Delta}PO2 or {Delta}PCO2 alone in coupling with the changes of CBFv and BOLD signals under breath hold challenge. The regional cerebrovascular reactivity (CVR) results derived by regressing BOLD signal changes on bER under breath hold challenge resembled those derived by regressing BOLD signal changes on end-tidal partial pressure of CO2 (PETCO2) under exogenous CO2 challenge. Our findings provide a novel insight on the potential of using bER to better quantify CVR changes under breath hold challenge, although the physiological mechanisms of cerebrovascular changes underlying breath hold and exogenous CO2 challenges are potentially different.