The within‐ and between‐day reliability of cerebrovascular reactivity using traditional and novel analytical approaches

Abstract

Cerebrovascular reactivity (CVR) of middle cerebral artery velocity (MCAv) to CO 2 is a common method to assess cerebrovascular function. Yet, the approaches used to calculate CVR outcomes vary. The aim of this study was to explore the withinand between-day reliability of traditional CVR outcomes. The second aim was to explore the reliability of novel kinetic-based analyses. Healthy adults (n = 10, 22.3 ± 3.4 years) completed assessments of CVR over 4 min using a fixed fraction of inspired CO 2 (6%). This was repeated across four separate visits (between-day), and on one visit measures were repeated 2.5 h later (within-day). No mean biases were present between assessments for traditional CVR metrics, expressed as absolute (cm/s/mmHg) or relative (%/mmHg) outcomes (minute 3, minute 4, peak 1 s, peak 30 s) (betweenday: P > 0.14, η p 2 < 0.20; within-day: P > 0.22, d > 0.27). Absolute, rather than relative, CVR yielded the most reproducible parameters (coefficient of variation: 8.1-13.2%vs. 14-83%, respectively). There were significant differences between CVR outcomes (P < 0.001, η p 2 > 0.89) dependent on the time point used to determine CVR, as a steady state MCAv response was rarely observed. Furthermore, the MCAv response was not reproducible within an individual (κ = 0.15, P = 0.09). No mean differences were present for novel kinetic outcomes (amplitude, time-delay, time constant) (between-day: P > 0.05, d < 0.33; within-day: P > 0.38, d < 0.25). The results support the need for standardisation and indicate CVR should be defined as a dynamic peak, rather than a set time point for increased reliability. For novel kinetic outcomes variability was greater (CV: 8.7-120.9%) due to the nature of time-based metrics.

The effect of exercise intensity and cardiorespiratory fitness on the kinetic response of middle cerebral artery blood velocity during exercise in healthy adults

“…In addition, appropriate test-retest reproducibility of the MCAv kinetic response was observed in the present study, with the coefficient of variation for MCAv kinetics parameters (baseline, amplitude, and MRT) similar to Billinger et al (2). These levels of reproducibility are also in-line with, or smaller than, kinetics parameters of MCAv to CO 2 breathing, and typical for studies utilizing kinetics analyses (27).…”

The relationships between age, sex, and cerebrovascular reactivity to hypercapnia using traditional and kinetic-based analyses in healthy adults

“…Data were baseline corrected for the 120 s preceding hypercapnia and analyzed using a monoexponential model with time delay using GraphPad Prism ( Fig. 1 ) (GraphPad Software, San Diego, CA) as follows: MCAv( t ) = ΔMCAvA[1 – e –( t − TD/ τ ) ], where MCAv( t ) is the MCAv at a given time ( t ), ΔMCAvA is the amplitude change of MCAv from baseline to its asymptote, TD is the time delay, and τ is the time constant, in accordance with kinetic modeling in previous work ( 29 , 30 ). Mean response time (MRT) was calculated as the sum of the model derived τ and the TD.…”

“…Cardiorespiratory parameters were simultaneously determined throughout the protocol, as described in Cardiorespiratory Measures . Hypercapnia was chosen as the stimulus because of its sensitivity to disease risk ( 42 ) and the availability of reliability data on this outcome ( 30 ).…”

“…Calculation of CVR to hypercapnia was expressed as the absolute change from baseline MCAv per unit increase (mmHg) in . This response was quantified as the peak rolling 30-s average during hypercapnia, wherever this occurred ( 30 ). CVR was calculated in this way as the most reliable analysis method to address recent concerns on the variability of changes in MCAv during open-circuit breathing ( 30 , 48 ).…”

“…Recent research has highlighted the importance of investigating dynamic kinetic-based analyses on cerebrovascular regulation, in addition to traditional amplitude-based inferences ( 29 ). This can be achieved using a monoexponential model, where the time delay, time constant, and mean response time can provide additional information on the speed of the response ( 29 , 30 ). These outcomes have been shown to be indicative of regulatory responses during exercise stressors ( 31 , 32 ) but have yet to be applied to examine the effect of age and sex on cerebrovascular responses to hypercapnia.…”