MRI-markers to Monitor Small Vessel Disease Dynamics in the Prognosis of Small Vessel Disease-associated, Cerebrovascular Events

Study Overview
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Brief Summary
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This is a nested cohort study in the PRO-SVD cohort. Small vessel disease is a chronic disease and is thought to progress over time. MRI is the gold standard to diagnose small vessel disease, but data on MRI-visible disease progression are scarce. Complications of small vessel disease as well as location pattern, distribution and severity of these MRI small vessel disease markers differ according to the underlying phenotype. The primary aim of this project is to investigate individual small vessel disease burden progression detected by MRI in survivors or intracerebral hemorrhage.

Official Title
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MRI-markers to Monitor Small Vessel Disease Dynamics in the Prognosis of Small Vessel Disease-associated, Cerebrovascular Events - a Prospective Cohort Study

Conditions
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Intracerebral Hemorrhage, CAA - Cerebral Amyloid Angiopathy, Cerebral Small Vessel Diseases

Intervention / Treatment
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* Diagnostic Test: Combined 3- and 7 Tesla-MRI


Participation Criteria
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Eligibility Criteria
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For patients with intracerebral hemorrhage Inclusion Criteria: Patient participating in the PRO-SVD cohort Symptomatic intracranial hemorrhage Written informed consent provided by patient or next-of-kin No contraindications against MRI Exclusion Criteria: Patient unsuitable for MRI follow-ups (e.g. claustrophobia) Patients unlikely to attend 1-year follow-up For healthy controls Inclusion Criteria: Clinically healthy person ≥ 55 years Written informed consent provided by the healthy control No contraindications against MRI Exclusion Criteria: Known or suspected cerebral small vessel diseases or presence of concurrent diseases potentially mimicking small vessel disease (e.g. multiple sclerosis, previous heart surgery etc.) Pre-existing dementia, cognitive decline or disorder of the central nervous system.

Ages Eligible for Study
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Minimum Age: 16 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 with intracerebral hemorrhage<br>Patients with symptomatic intracranial hemorrhage (defined as non-traumatic intracerebral hemorrhage or convexity, non-aneurysmal subarachnoid hemorrhage) enrolled in the PRO-SVD study | Diagnostic Test: Combined 3- and 7 Tesla-MRI<br>* 7 Tesla-MRI including the following sequences: susceptibility weighted imaging (SWI), T1, T2, FLAIR, quantitative mapping sequences (T1mapping, qSM)<br>|
| Healthy controls<br>Clinically healthy persons of at least 55 years of age | Diagnostic Test: Combined 3- and 7 Tesla-MRI<br>* 7 Tesla-MRI including the following sequences: susceptibility weighted imaging (SWI), T1, T2, FLAIR, quantitative mapping sequences (T1mapping, qSM)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease progression | Composite endpoint of a new, clinically symptomatic ischaemic or haemorrhagic event as defined by the treating physician and/or any increase in small vessel disease and/or cerebral amyloid angiopathy burden according to small vessel disease burden score (range 0-4 points, higher score means higher small vessel disease burden) or cerebral amyloid angiopathy burden score (range 0-6 points, higher score means higher cerebral amyloid angiopathy burden), respectively. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MRI-defined disease progression | Any increase in small vessel disease (SVD) and/or cerebral amyloid angiopathy (CAA) burden according to small vessel disease burden score (range 0-4 points, higher score means higher small vessel disease burden) or cerebral amyloid angiopathy burden score (range 0-6 points, higher score means higher cerebral amyloid angiopathy burden), respectively. | 24 months | 
| Increase in number of SVD-attributable, ischaemic lesions | Composite outcome defined as any increase in numeric count for lacunes and/or increase in perivascular space severity scale (0/1-10 PVS/11-20 PVS/21-40 PVS/>40 PVS) and/or increase in periventricular or deep separate white matter Fazekas scale. | 24 months | 
| Increase in number of SVD-attributable, haemorrhagic lesions | Composite outcome defined as any increase in numeric count for cerebral microbleeds and/or increase in cortical superficial siderosis multifocality score. | 24 months | 
| Increase in perivascular space severity scale | Defined as any increase in perivascular space (PVS) severity scale (0/1-10 PVS/11-20 PVS/21-40 PVS/>40 PVS, higher number of PVS means higher small vessel disease burden). | 24 months | 
| Clinical, vascular outcome event | Composite endpoint including any of the following, clinically apparent events: ischaemic stroke as diagnosed by CT or MRI and causing a corresponding clinical deficit (as assessed by the treating physician) intracerebral haemorrhage as diagnosed by CT or MRI and causing a corresponding clinical deficit (as assessed by the treating physician) systemic vascular event defined as radiological or clinical evidence of arterial hypoperfusion and judged by the treating physician to be due to an atherosclerotic or embolic cause. | 24 months | 
| Functional outcome | Modified Rankin Scale (ordinal scale, range 0-6 with 0 corresponding to no symptoms at all and 6 corresponding to death). | 24 months | 
| New cognitive impairment | Montreal Cognitive Assessment (MoCA, range 0-30 points) < 26 points (corresponding to impaired cognitive function) and/or new impairment in activities of daily living as defined by the treating physician . | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intracerebral hemorrhage, Ischemic stroke, Cerebral amyloid angiopathy, Hypertensive deep perforator arteriopathy, 7 Tesla-MRI, Cerebral small vessel disease, Ultra high-field MRI