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Sickle cell cerebrovascular reactivity to a CO2 stimulus: Too little, too slow
Stéphanie Forté1,2,3, Olivia Sobczyk4,5, Julien Poublanc4
1Division of Medical Oncology and Hematology, Departement of Medicine, Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada.
Insights
Cerebrovascular reactivity and speed of response are reduced in sickle cell disease (SCD) patients, indicating compromised brain blood flow despite increased flow. This highlights potential stroke risks in SCD.
Area of Science:
- Neurology
- Vascular Biology
- Hematology
Background:
- Sickle cell disease (SCD) patients experience cerebral infarcts despite elevated cerebral blood flow (CBF).
- This suggests that increased CBF may not meet metabolic demands due to impaired cerebral vasodilatory capacity.
Purpose of the Study:
- To investigate cerebrovascular reactivity (CVR) and the speed of vasodilatory response (tau) in adult SCD patients compared to healthy controls.
- To determine if CVR and tau are reduced in SCD patients, indicating compromised cerebral blood flow regulation.
Main Methods:
- Retrospective review of functional brain imaging in adult SCD patients.
- Calculation of CVR using BOLD-MRI signal change in response to CO2 stimulus.
- Determination of response speed (tau) by fitting CO2 levels to BOLD signal, normalized against a healthy control atlas.
Main Results:
- Fifteen SCD patients were analyzed, showing reduced CVR in grey and white matter (mean CVR Z-scores -0.5 and -0.6).
- Lengthened tau Z-scores in grey and white matter (+0.9 and +0.8) indicated a slower vasodilatory response.
- Hematocrit was the sole significant independent predictor of CVR in multivariable regression.
Conclusions:
- Both CVR and tau are attenuated in SCD patients compared to controls, signifying impaired cerebrovascular health.
- CVR shows promise as a tool for assessing SCD disease state, stroke risk, and treatment efficacy.
- Further investigation into CVR and tau in SCD is warranted.
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.
