Protocol-dependence of middle cerebral artery dilation to modest hypercapnia

There is a need for improved understanding of how different cerebrovascular reactivity (CVR) protocols affect vascular cross-sectional area (CSA) to reduce error in CVR calculations when measures of vascular CSA are not feasible. In human participants, we delivered ∼±4 mm Hg end-tidal partial pressure of CO₂ (P_ETCO₂) relative to baseline through controlled delivery, and measured changes in middle cerebral artery (MCA) CSA (7 Tesla magnetic resonance imaging (MRI)), blood velocity (transcranial Doppler and Phase contrast MRI), and calculated CVR based on a 3-minute steady-state (+4 mm Hg P_ETCO₂) and a ramp (-3 to +4 mm Hg of P_ETCO₂). We observed that (1) the MCA did not dilate during the ramp protocol (slope for CSA across time P > 0.05; R² = 0.006), but did dilate by ∼7% during steady-state hypercapnia (P < 0.05); and (2) MCA blood velocity CVR was not different between ramp and steady-state hypercapnia protocols (ramp: 3.8 ± 1.7 vs. steady-state: 4.0 ± 1.6 cm/s/mm Hg), although calculated MCA blood flow CVR was ∼40% greater during steady-state hypercapnia than during ramp (P < 0.05) with the discrepancy due to MCA CSA changes during steady-state hypercapnia. We propose that a ramp model, across a delta of -3 to +4 mm Hg P_ETCO₂, may provide an alternative approach to collecting CVR measures in young adults with transcranial Doppler when CSA measures are not feasible. Novelty: We optimized a magnetic resonance imaging sequence to measure dynamic middle cerebral artery (MCA) cross-sectional area (CSA). A ramp model of hypercapnia elicited similar MCA blood velocity reactivity as the steady-state model while maintaining MCA CSA.