Ramp protocol for non-linear cerebrovascular reactivity with transcranial doppler ultrasound

Background: Cerebrovascular reactivity (CVR) reflects the ability of cerebral blood vessels to adjust their diameter in response to vasoactive stimuli, which is crucial for maintaining brain health. Traditional CVR assessments commonly use a two-point measurement, assuming a linear relationship between cerebral blood flow (CBF) and arterial CO2. However, this approach fails to capture non-linear characteristics, particularly the plateaus at extreme CO2 levels. New method: This study introduces a cost-effective, ramp-based end-tidal CO2 (PETCO2) protocol to assess nonlinear aspects of CVR. Using transcranial Doppler ultrasound, we monitored blood velocity responses to progressive increases in arterial CO2 levels in eleven healthy adults, covering a spectrum from hypocapnia to hypercapnia. Results: All eleven participants successfully completed the protocol, with an average PETCO2 range of 26 +/- 4 mmHg and blood velocity changes from -29 % to + 50 % relative to baseline. Non-linear CVR characteristics were observed in all subjects. Sigmoid models provided significantly better fits to the CVR data than linear models, while Bayesian approaches followed expected physiological ranges more accurately than least squares regression methods. Comparison with existing methods: Unlike traditional CVR methods, this ramp protocol captures the full, non-linear CVR profile. The sigmoid modeling approach offers a more accurate representation of cerebrovascular dynamics, particularly at CO2 extremes. Conclusions: The PETCO2 ramp protocol with non-linear CVR modeling shows promise as an accessible and reliable tool for assessing CBF dynamics. With high completion rates, straightforward implementation, and low equipment cost, this approach holds significant potential for clinical applications in cerebrovascular health evaluation.