Macromolecular Imaging of White and Gray Matter Pathology in Multiple Sclerosis

Study Overview
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Brief Summary
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The overall purpose of this research is to determine whether new macromolecular measures optimized for whole brain (gray matter and white matter) magnetic resonance imaging (MRI), predict neuro-cognitive impairment in multiple sclerosis (MS) patients.

Detailed Description
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MRI is a vital component of a MS work-up, providing noninvasive evidence of MS lesions, detecting active inflammatory lesions, and measuring brain atrophy to assess neurodegeneration. Recent years of MRI research have generated strong evidence of gray matter (GM) involvement in MS, resulting in the reclassification of MS as a whole-brain disease. Similar to white matter (WM), a primary target of MS pathology in GM is myelin, the protective sheath insulating the penetrating axons within GM and extending brain connectivity all the way to the neuronal bodies. This aim of this research is to examine if the associations between imaging measures of GM disease and cognitive performance can establish GM-based imaging correlates predicting the disease course and accurately assessing treatment results. This observational research will enroll adults diagnosed with MS both with and without cognitive impairment. Subjects will be asked to complete a single research visit that includes the administration of a MRI scan and a neuro-cognitive testing session.

Official Title
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Macromolecular Imaging of White and Gray Matter Pathology in Multiple Sclerosis

Conditions
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MS, Multiple Sclerosis

Intervention / Treatment
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* Diagnostic Test: MRI
* Diagnostic Test: Neuropsychological Testing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinically definite MS Adult age 18 to 60 Exclusion Criteria: Contraindication to MRI Changes in MS therapy in the last 6 months Less than 6 weeks after relapse or corticosteroid use Currently taking medication that may affect cognition (e.g. donepezil, rivastigmine, adderall) History of significant alcohol or drug abuse Current or recent significant migraines Confounding neurological or cognitive disorders or deficits (stroke, Parkinson's disease, Alzheimer's disease, epilepsy) Sensory or physical impairments that might interfere significantly with cognitive testing History of developmental or learning disability or attention-deficit/hyperactivity disorder.\ Exclusion Criteria for Healthy Controls: history of alcohol/drug abuse history of migraines developmental or learning disability/attention-deficit/hyperactivity disorder currently pregnant/breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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 |
| --- | --- |
| Cognitive Impairment<br>Adults diagnosed with MS that have evidence of cognitive decline. | Diagnostic Test: MRI<br>* The MRI protocol will include conventional testing for MS lesion detection and functional MR imaging to localize associated neurocognitive domains in each subject.<br>* Other names: Functional MRI;Diagnostic Test: Neuropsychological Testing<br>* A comprehensive battery of neuropsychological tests will be administered to assess memory, new learning, spatial processing and higher executive function.<br>|
| No Cognitive Impairment<br>Adults diagnosed with MS that have no evidence of cognitive decline. | Diagnostic Test: MRI<br>* The MRI protocol will include conventional testing for MS lesion detection and functional MR imaging to localize associated neurocognitive domains in each subject.<br>* Other names: Functional MRI;Diagnostic Test: Neuropsychological Testing<br>* A comprehensive battery of neuropsychological tests will be administered to assess memory, new learning, spatial processing and higher executive function.<br>|
| Healthy Controls<br>Healthy adult volunteers will form a control group matched for age, gender, education, handedness | Diagnostic Test: MRI<br>* The MRI protocol will include conventional testing for MS lesion detection and functional MR imaging to localize associated neurocognitive domains in each subject.<br>* Other names: Functional MRI;Diagnostic Test: Neuropsychological Testing<br>* A comprehensive battery of neuropsychological tests will be administered to assess memory, new learning, spatial processing and higher executive function.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of macromolecular proton content (MPC) by Magnetic resonance imaging | Macromolecular Proton Fraction (MPF) is calculated from several specially acquired MR images and is characterized by high degree of sensitivity and specificity to tissue macromolecules, which are the main target of pathological process in neurodegenerative diseases including multiple sclerosis (MS). These properties of MPF are in contrast with standard MR images, which are primarily sensitive to tissue water molecules. | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurocognitive performance as measured by Minimal Assessment of Cognitive Function in MS (MACFIMS) battery of neuropsychological (NP) tests | The results of Minimal Assessment of Cognitive Function in MS (MACFIMS) battery of neuropsychological (NP) tests will form the secondary outcome measure. The NP scores will be correlated with MPF to study association between macromolecular tissue damage and neurocognitive performance. | 24 hours | 
| Neurocognitive performance as measured by the Montreal Cognitive Assessment (MoCA) score | Neurocognitive performance will be measured by Montreal Cognitive Assessment. MoCA scores range from 0 to 30, higher values corresponding to better cognitive performances. | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Magnetic resonance imaging