Cerebrovascular Reactivity to Carbon Dioxide: A Theoretical Examination

Abstract

Cerebrovascular reactivity (CVR) is the ratio of cerebral blood flow (CBF) response to a vasoactive stimulus increase. Current measurement of CVR uses the BOLD MRI signal as an indicator of CBF in response to standardized changes in CO2. A step increase in PCO2 is applied and the resulting changes in CBF are assumed to be linearly related. However, this assumption of linearity may be incorrect, and the resulting CVR may be prone to errors. We therefore investigated the differential effects of gradual versus step changes in PCO2 on CVR. Two gas provocations were applied in 15 patients and 18 healthy subjects: 1) a step change from 40 to 50 mmHg and 2) a steady 4‐min ramp increase from 30 to 50 mmHg. CVR was defined on a voxel‐wise basis as %ΔBOLD MR signal/Δ PETCO2. The total brain % BOLD response to a ramp showed a sigmoidal pattern globally and in some individual voxels. CVRs calculated from the step change in PCO2 did not represent the steepest part of the sigmoidal curve in individuals whose sigmoidal inflection point was at a PCO2 less than 50 mmHg. Voxels with negative CVR values showed abrupt onset signal declines at PCO2 levels exceeding a threshold value. A more sophisticated interpretation of high resolution CVR must take into account the range of PCO2, the position and shape of the BOLD‐PCO2 sigmoidal curve, and the vasodilatory and constrictor reserve in various vascular beds.