Cerebrovascular reactivity measurements using 3T BOLD MRI and a fixed inhaled CO2 gas challenge: Repeatability and impact of processing strategy

Emilie Sleight; Michael S Stringer; Isla Mitchell; Madeleine Murphy; Ian Marshall; Joanna M Wardlaw; Michael J Thrippleton

doi:10.3389/fphys.2023.1070233

Cerebrovascular reactivity measurements using 3T BOLD MRI and a fixed inhaled CO₂ gas challenge: Repeatability and impact of processing strategy

Front Physiol. 2023 Feb 6:14:1070233. doi: 10.3389/fphys.2023.1070233. eCollection 2023.

Authors

Emilie Sleight^{1

2}, Michael S Stringer^{1

2}, Isla Mitchell³, Madeleine Murphy³, Ian Marshall^{1

2}, Joanna M Wardlaw^{1

2

3}, Michael J Thrippleton^{1

2

3}

Affiliations

¹ Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.
² UK Dementia Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
³ Edinburgh Imaging Facility, Royal Infirmary of Edinburgh, University of Edinburgh, Edinburgh, United Kingdom.

Abstract

Introduction: Cerebrovascular reactivity (CVR) measurements using blood oxygen level dependent (BOLD) magnetic resonance imaging (MRI) are commonly used to assess the health of cerebral blood vessels, including in patients with cerebrovascular diseases; however, evidence and consensus regarding reliability and optimal processing are lacking. We aimed to assess the repeatability, accuracy and precision of voxel- and region-based CVR measurements at 3 T using a fixed inhaled (FI) CO₂ stimulus in a healthy cohort. Methods: We simulated the effect of noise, delay constraints and voxel- versus region-based analysis on CVR parameters. Results were verified in 15 healthy volunteers (28.1±5.5 years, female: 53%) with a test-retest MRI experiment consisting of two CVR scans. CVR magnitude and delay in grey matter (GM) and white matter were computed for both analyses assuming a linear relationship between the BOLD signal and time-shifted end-tidal CO₂ (EtCO₂) profile. Results: Test-retest repeatability was high [mean (95% CI) inter-scan difference: -0.01 (-0.03, -0.00) %/mmHg for GM CVR magnitude; -0.3 (-1.2,0.6) s for GM CVR delay], but we detected a small systematic reduction in CVR magnitude at scan 2 versus scan 1, accompanied by a greater EtCO2 change [±1.0 (0.4,1.5) mmHg] and lower heart rate [-5.5 (-8.6,-2.4] bpm]. CVR magnitude estimates were higher for voxel- versus region-based analysis [difference in GM: ±0.02 (0.01,0.03) %/mmHg]. Findings were supported by simulation results, predicting a positive bias for voxel-based CVR estimates dependent on temporal contrast-to-noise ratio and delay fitting constraints and an underestimation for region-based CVR estimates. Discussion: BOLD CVR measurements using FI stimulus have good within-day repeatability in healthy volunteers. However, measurements may be influenced by physiological effects and the analysis protocol. Voxel-based analyses should be undertaken with care due to potential for systematic bias; region-based analyses are more reliable in such cases.

Keywords: blood oxygen-level dependent; cerebrovascular reactivity; hypercapnia; reliability; repeatability.

Grants and funding

This work was funded by the Medical Research Council (ES) and UK Dementia Research Institute (UK DRI), which receives its funding from UK DRI Ltd., which is funded by the Medical Research Council, Alzheimer’s Society and Alzheimer’s Research United Kingdom. This work also received funding from the European Union Horizon 2020 (PHC-03-15, project no. 666881 “SVDs@Target”), the Fondation Leducq Transatlantic Network of Excellence for the Study of Perivascular Spaces in Small Vessel Disease (ref. No. 16CVD 05), and the Scottish Chief Scientist Office through the NHS Lothian Research and Development Office (MJT). For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.