Sickle cell cerebrovascular reactivity to a CO2 stimulus: Too little, too slow

Stéphanie Forté; Olivia Sobczyk; Julien Poublanc; James Duffin; Gregory M T Hare; Joseph Arnold Fisher; David Mikulis; Kevin H M Kuo

doi:10.3389/fphys.2022.886807

Sickle cell cerebrovascular reactivity to a CO₂ stimulus: Too little, too slow

Front Physiol. 2022 Aug 19:13:886807. doi: 10.3389/fphys.2022.886807. eCollection 2022.

Authors

Stéphanie Forté^{1

2

3}, Olivia Sobczyk^{4

5}, Julien Poublanc⁴, James Duffin^{6

7}, Gregory M T Hare^{6

7

8}, Joseph Arnold Fisher^{5

7}, David Mikulis⁴, Kevin H M Kuo^{2

3

9}

Affiliations

¹ Division of Medical Oncology and Hematology, Departement of Medicine, Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada.
² Division of Medical Oncology and Hematology, Department of Medicine, University Health Network, Toronto, ON, Canada.
³ Division of Hematology, Department of Medicine, University of Toronto, Toronto, ON, Canada.
⁴ Joint Department of Medical Imaging, University Health Network, Toronto, ON, Canada.
⁵ Department of Anaesthesia and Pain Medicine, University Health Network, Toronto, ON, Canada.
⁶ The Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.
⁷ Department of Physiology, University of Toronto, Toronto, ON, Canada.
⁸ Department of Anesthesia, St. Michael's Hospital, Toronto, ON, Canada.
⁹ Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.

Abstract

Background: Despite increased cerebral blood flow (CBF), cerebral infarcts occur in patients with sickle cell disease (SCD). This suggests increased CBF does not meet metabolic demand possibly due to compromised cerebral vasodilatory response. Hypothesis: In adult SCD patients, cerebrovascular reactivity (CVR) and speed of vasodilatory response (tau) to a standardized vasodilatory stimulus, are reduced compared to normal subjects. Methods: Functional brain imaging performed as part of routine care in adult SCD patients without known large vessel cerebral vasculopathy was reviewed retrospectively. CVR was calculated as the change in CBF measured as the blood-oxygenation-level-dependent (BOLD)-magnetic resonance imaging signal, in response to a standard vasoactive stimulus of carbon dioxide (CO₂). The tau corresponding to the best fit between the convolved end-tidal partial pressures of CO₂ and BOLD signal was defined as the speed of vascular response. CVR and tau were normalized using a previously generated atlas of 42 healthy controls. Results: Fifteen patients were included. CVR was reduced in grey and white matter (mean Z-score for CVR -0.5 [-1.8 to 0.3] and -0.6 [-2.3 to 0.7], respectively). Tau Z-scores were lengthened in grey and white matter (+0.9 [-0.5 to 3.3] and +0.8 [-0.7 to 2.7], respectively). Hematocrit was the only significant independent predictor of CVR on multivariable regression. Conclusion: Both measures of cerebrovascular health (CVR and tau) in SCD patients were attenuated compared to normal controls. These findings show that CVR represents a promising tool to assess disease state, stroke risk, and therapeutic efficacy of treatments in SCD and merits further investigation.

Keywords: cerebral blood flow (CBF); cerebral hemodynamics; cerebrovascular disorders; cerebrovascular reactivity (CVR); cerebrovascular reactivity to carbon dioxide; functional magnetic resonance imaging (fMRI); sickle cell disease (SCD).