Pre-Clinical White Matter Changes and Associated Connectivity Effects in Fabry Disease

Study Overview
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Brief Summary
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The purpose of this research project is: to use an advanced quantitative MRI technique (FBFI) to detect and quantify brain lesion in patients with FD to use fMRI to identify altered brain function to use FBFI and fMRI together to map altered connectivity in response to brain lesions

Detailed Description
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Fabry disease (FD) is a lysosomal storage disease caused by a deficiency in an enzyme that degrades components of the outer cell wall. A deficiency of this enzyme in humans has been associated with stroke. In males with FD, 6.9% have a stroke by 39 years of age. In females with FD, 4.3% have a stroke by 46 years of age. Magnetic resonance imaging (MRI) is the main tool for studying stroke in FD. Importantly, MRI has identified other types of lesions in the brain beyond that caused by stroke. These additional lesions may herald stroke or be a different manifestation of FD in the brain. These lesions are seen in >50% of men and women with FD. Diffusion-based imaging MRI has been the leading approach for studying these lesions in FD. However, these lesions that appear to be specific to FD are difficult to quantify, analyze, and interpret using this and other current MRI methods. The Investigators would like to use a form of MRI called fast bound-pool fraction imaging (FBFI), which is a technique better suited to capture and quantify these lesions, to study these lesions in patients with FD. In parallel, the investigators would like to use functional MRI (fMRI) to study how these lesions alter brain function and connectivity in FD. The combination of these techniques (FBFI + fMRI) will also provide us the opportunity to study brain plasticity in response to injury as Fabry disease is slowly progressive over decades allowing the brain to remodel connections to maintain function.

Official Title
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Pre-Clinical White Matter Changes and Associated Connectivity Effects in Fabry Disease

Conditions
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Fabry Disease

Intervention / Treatment
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* Other: Functional MRI and fast bound-pool fraction imaging


Participation Criteria
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Eligibility Criteria
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Fabry Cohort Inclusion Criteria: Have Fabry Disease Must be 18yrs or older Exclusion Criteria: Subjects who are claustrophobic have metal implants Cannot pass the MRI safety screening questionnaire. Unaffected Controls Inclusion Criteria: Must be 18yrs or older unaffected with Fabry Disease considered healthy with no previous history of stroke, multiple sclerosis, diabetes mellitus, or other neurologic disease. Exclusion Criteria: Subjects who are claustrophobic have metal implants Cannot pass the MRI safety screening questionnaire.

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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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: 20 patients with Fabry and 20 unaffected
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Fabry<br>Must be 18 or older and able to have an MRI. | Other: Functional MRI and fast bound-pool fraction imaging<br>* Use a form of MRI called fast bound-pool fraction imaging (FBFI), which is a technique better suited to capture and quantify these lesions, to study these lesions in patients with FD. In parallel, we would like to use functional MRI (fMRI) to study how these lesions alter brain function and connectivity in FD. Neuropsychological assessements will include Wechsler Adult Intelligence Scale, WAIS-III (Digit Span, Symbol-Digit/Coding, and Symbol Search), the Connors Continous Performance text (CPT-II). The Health Questionnaire form, the Center for Epidemiologic Studies Depression Scale (CES-D), the RAND 36-Item Health Survey.<br>* Other names: Neuropsychological assessments;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FBFI MRI using advanced MRI technique | advanced quantitative MRI technique (FBFI) to detect and quantify brain lesion in patients with FD | 6 months after enrollment closes | 
| Identify difference between patients with Fabry disease and healthy controls in brain function as measured and quantified by functional MRI | identify altered brain function | 6 months after enrollment closes | 
| use FBFI and fMRI to map | together to map altered connectivity in response to brain lesions | 6 months after enrollment closes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fabry, MRI (Magnetic resonance imaging), Fabry brain lesions