Prediction of Delayed Cerebral Ischemia After Subarachnoid Hemorrhage Using Dynamic 18F-FDG PET/CT

Study Overview
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Brief Summary
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A pilot trial for assessing early microvascular alterations after aneurysmal subarachnoid hemorrhage using dynamic 18F-FDG PET/CT. The primary endpoint will be the measure of early changes in cerebral glucose uptake reflecting microperfusion.

Detailed Description
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We hypothesize that an early irreversible microvascular deterioration following initial bleeding could contribute to DCI occurrence. More precisely, we suspect that DCI areas are somehow overlaps of regions in which microperfusion is precociously altered, shortening circulatory reserves, and territories of secondarily spasmed arteries further lowering blood flow, resulting in ischemia. We aim to explore the potential microvasculature alteration through cerebral glucose perfusion and metabolism assessment using early dynamic 18F-fluorodesoxyglucose Positron Emission Tomography/Computer Tomography (dynamic 18F-FDG PET/CT). If our hypothesis turned out to be valid, we would at the same time be able to determine risk factors for this unpredictable complication and gain remarkable insight into DCI pathophysiology. Thus, the purpose of this trial is to demonstrate, in patients affected by SAH, the correlation between early cerebral glucose uptake defects in 18F-FDG PET/CT and delayed cerebral infarction in magnetic resonance imaging (MRI).

Official Title
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Prediction and Unraveling of Delayed Cerebral Ischemia in Patients With Subarachnoid Hemorrhage Using Early Dynamic 18F-FDG PET/CT Assessment of Cerebral Glucose Uptake (PREDISP)

Conditions
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Aneurysmal Subarachnoid Haemorrhage

Intervention / Treatment
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* Other: Early dynamic 18F-FDG PET/CT assessment of cerebral glucose uptake


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: written informed consent to participate in the study must be obtained from the subject or proxy/legal representative prior to enrollment. males and females aged 18 years and older. SAH proven by computed tomography (CT) and that has occurred within the last 72 hours. ruptured saccular aneurysm angiographically confirmed by digital subtraction angiogram or CT angiogram, which has been successfully secured by surgical clipping or endovascular coiling. high-risk subjects for DCI: thick clot on the hospital admission CT (grade 3 or grade 4 on the modified Fisher Scale). a woman of childbearing potential is eligible only if the serum pregnancy test performed during the screening period is negative. Exclusion Criteria: PET/CT contradications MRI contradications gadolinium or meglumine hypersensitivity glomerular filtration rate <30mL/min SAH due to other causes than ruptured saccular aneurysm. post-HSA cardiac arrest. high sustained ICP ( >20mmHg lasting >20min) despite optimal treatment. significant and concomitant organ failure amongst the following: hypotension with systolic blood pressure <90mmHg refractory to treatment; unresolved pulmonary edema or pneumonia with severe hypoxia defined as PaO2/FiO2 <150; severe cardiac failure requiring inotropic support. patients with do-not-resuscitate orders, withdrawal of care situation, dying patient. vulnerable patient populations (minor, legal vulnerability, prisoner) pregnant and nursing mothers.

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention Group<br>All participants will receive study intervention | Other: Early dynamic 18F-FDG PET/CT assessment of cerebral glucose uptake<br>* The intervention will consist in a dynamic cerebral 18F-FDG PET study performed at D2+/-1. Kinetic modeling will be performed using in-house software at the global, regional, and voxel level. In addition, cerebral perfusion and blood-brain-barrier permeability will be assessed at D4+/- 1 using perfusion MRI and permeability MRI.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantification of K1 parameter. | A kinetic modeling for cerebral glucose uptake will be performed using in-house software in order to provide the K1 parameter (in min-1) in every voxel reflecting the cerebral blood flow (in mL/min). | Day 2 +/- 1 day after the initial bleeding | 
| Quantification of Ki parameter. | A kinetic modeling for cerebral glucose uptake will be performed using in-house software in order to provide the Ki parameter (in min-1) in every voxel reflecting the cerebral metabolic rate of glucose in µmol/100g/min. | Day 2 +/- 1 day after the initial bleeding | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delayed cerebral ischemic regions. | Delayed cerebral ischemic lesions will be ascertained by routine MRI scans until the end of the period of time in which the subject may present DCI (D21+/-3). | From day 2 to day 21 +/- 3 days after the initial bleeding | 
| Delayed spasmed arteries territories. | Occurence of vasospasm will be determined on routine angiograms until the end of the period of time in which the subject may present vasospasm (D21+/-3). | From day 2 to day 21 +/- 3 days after the initial bleeding | 
| Quantification of cerebral blood flow using DSC-MRI | Cerebral blood flow in mL/100g/min will be measured using DSC-MRI (Dynamic Susceptibility Contrast Magnetic Resonance Imaging) | At day 4 +/- 1 day after the initial bleeding | 
| Quantification of cerebral blood flow using ASL-MRI | Cerebral blood flow in mL/100g/min will be measured using ASL-MRI (Arterial Spin Labelling Magnetic Resonance Imaging) | At day 4 +/- 1 day after the initial bleeding | 
| Quantification of blood-brain-barrier permeability using DSC-MRI | The blood-brain barrier permeability will be measured using DSC-MRI. A kinetic modeling will be performed in order to provide the leakage parameter K2 (in min-1) in every voxel. | At day 4 +/- 1 day after the initial bleeding | 
| Quantification of blood-brain-barrier permeability using DCE-MRI | The blood-brain barrier permeability will be measured using DCE-MRI (Dynamic Contrast-Enhanced Magnetic Resonance Imaging). A kinetic modeling will be performed in order to provide the leakage parameter Ktrans (in min-1) in every voxel. | At day 4 +/- 1 day after the initial bleeding | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aneurysmal subarachnoid haemorrhage, Delayed Cerebral Ischemia, Positron emission tomography, Cerebral microcirculation