Cerebrovascular Reserve Measurements in Sickle Cell Disease

Study Overview
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Brief Summary
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The primary aim of this study is to evaluate MRI-based cerebrovascular reserve (CVR) measurements in adult patients with Sickle Cell Disease (SCD). The primary objective is to assess whether there is a correlation between CVR and silent cerebral infarcts (SCIs).

Detailed Description
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CVR is hypothesized to be impaired in SCD patients and could account for the white matter hyperintensities seen on MRI in these patients. Cerebral blood flow (CBF) alone is not sufficient to provide insight into the hemodynamic status of the brain. CVR allows us to gain insight into the capacity of the cerebrovasculature to respond to increased CBF. Vasculopathy is common in SCD and the caliber of the vessels can be assessed with 4D Flow MRI in response to actue and chronic changes in the velocity and wall shear stress on the intracranial arteries in the Circle of Willis. This study will be performed as a single center, patient-control, cross-sectional, observational study in patients with steady-state SCD and controls. The investigators expect that patients with impaired CVR will have a greater number and/or volume of SCIs.

Official Title
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Cerebrovascular Reserve Measurements in Sickle Cell Disease: an MRI Study

Conditions
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Sickle Cell Disease

Intervention / Treatment
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* Drug: Acetazolamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Patient group: Sickle cell disease; either homozygous sickle cell disease (HbSS), or HbSβ0 thalassemia 18 years of age or older Informed consent Inclusion Criteria Control group: Similar ethnic background as Patient group 18 years of age or older Informed consent Exclusion Criteria Patient group and Control group: Inability of the patient to provide informed consent or legally incompetent/incapacitated to do so Contraindications for MRI, such as pregnancy, claustrophobia or the presence of metal in the body Sickle cell crisis at the moment of participation History of cerebral pathology that compromises measurements, such as cerebral palsy, brain tumour,meningitis, overt infarct Brain surgery performed in the last 3 months Severe liver, heart or renal dysfunction (clearance < 10 mL/min) Allergy to sulphonamide Breastfeeding Use of phenytoin, procaine or acetylsacylic acid (Ascal/aspirin) Risk of hypokalaemia (use of diuretics, primary hyperaldosteronism) Addison's Disease Severe asthma or emphysema

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients<br>CVR assessment consists of CBF measurement with arterial spin labelling (ASL)-MRI before and after intravenous administration of 16mg/kg acetazolamide (Diamox) | Drug: Acetazolamide<br>* Acetazolamide is administered to all participants to induce vasodilation, in order to assess the physiologic response on cerebral blood flow.<br>* Other names: Diamox;|
| Controls<br>CVR assessment consists of CBF measurement with arterial spin labelling (ASL)-MRI before and after intravenous administration of 16mg/kg acetazolamide (Diamox) | Drug: Acetazolamide<br>* Acetazolamide is administered to all participants to induce vasodilation, in order to assess the physiologic response on cerebral blood flow.<br>* Other names: Diamox;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cerebrovascular Reserve (CVR) from arterial spin labelling-MRI in patients compared to controls | Cerebral blood flow (CBF mL/100g/min) measurement before, during, and after, an intravenous administration of 16mg/kg acetazolamide. The percentage change in CBF will be used as a measure for CVR (%). | 20 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cerebral Metabolic Rate of Oxygen in patients and controls | Oxygen extraction fraction and cerebral blood flow are proportional to the cerebral metabolic rate of oxygen. Using the CBF from the primary outcome, and having measured the T2 of blood (which is dependent on oxygen), we can derive the oxygen extraction fraction, which allows us to calculate the cerebral metabolic rate of oxygen (CMRO2) and compare patients with controls. | 2 minutes | 
| Blood markers relating to anemia will be related to MRI findings | Hematocrit, hemoglobin, hemolysis, red blood cell count, mean corpuscular hemoglobin concentration. | Through study completion, an average of 1 year | 
| Velocity in the circle of willis assessed with 4D Flow MRI | Velocity (m/s) before and after acetazolamide challenge will be used to indicate cerebrovascular reserve and compared between patients and controls | 10 minutes | 
| Silent Cerebral Infarct (SCI) on T2-weighted FLAIR MRI | Volume of SCIs will be assessed in relation to CVR | 10 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sickle Cell Anemia, Cerebrovascular Reserve, Perfusion, Vasculopathy, Magnetic Resonance Imaging