Application of ihMT MRI in Multiple Sclerosis

Study Overview
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Brief Summary
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The development of in vivo biomarkers sensitive to myelin disruption represents a major clinical need to be able to monitor the demyelination processes as well as the effect of remyelinating therapies in multiple sclerosis. The investigators recently proposed a technique, derived from the conventional magnetisation transfer (MT): inhomogeneous Magnetisation Transfer (ihMT). In preliminary studies, this simple-to-implement and robust technique has shown great sensitivity for evaluating the demyelination processes. The goal of the project is to evaluate the ability of ihMT to measure and describe the spontaneous demyelination and remyelination processes involved in active lesions in a population of patients with MS at the the disease onset.

Detailed Description
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The development of in vivo biomarkers sensitive to myelin disruption (demyelination and remyelination) represents a major clinical need to be able to monitor the demyelination processes as well as the effect of remyelinating therapies in multiple sclerosis. The investigators recently proposed a technique, derived from the conventional magnetisation transfer (MT): inhomogeneous Magnetisation Transfer (ihMT). In preliminary studies, this simple-to-implement and robust technique has shown great sensitivity for evaluating the demyelination processes. The goal of the project is to evaluate the ability of ihMT to measure and describe the spontaneous demyelination and remyelination processes involved in active lesions in a population of patients with MS at the the disease onset.

Official Title
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Application of the Inhomogeneous Magnetisation Transfer MRI (ihMT) Technique, a New Myelin-specific MRI Technique, in Multiple Sclerosis

Conditions
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Sclerosis, Multiple

Intervention / Treatment
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* Device: inhomogeneous Magnetisation Transfer (ihMT) sequence
* Device: inhomogeneous Magnetisation Transfer (ihMT) sequence at 3T


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For Patients and Controls : Adult patient, male and female, age 18 to 45 Patient affiliated with health insurance coverage, Patient who signed a free and informed consent after receiving detailed, understandable and honest information, For patients only : Patient with relapsing-remitting multiple sclerosis according to the McDonald 2010 criteria Disease duration of less than 5 years Patients treated or not treated with first-line disease modifying therapy Detection of at least one post-Gadolinium injection active lesion identified on the initial brain MRI (T0) Exclusion Criteria: For patients only : • Patients with a progressive form of MS other than the early relapsing-remitting form (primary progressive or secondary progressive) For Patients and Controls : Patients with the usual contraindications for MRI (pacemaker, agitation, metal shards, claustrophobia) Patients at risk of non-compliance to the exam: basic problems with understanding, confusion, involuntary movements, poor tolerance of prolonged supine position Patients who are unable to give their consent: problems with understanding, lack of vigilance, confusion Woman who is pregnant and breastfeeding Patients with a history of neurological or psychiatric condition Patients under guardianship or trusteeship

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: experimental group 1.5T<br>Population of patients with myelin syndrome (MS) at the the disease onset with active lesions inhomogeneous Magnetisation Transfer (ihMT) sequence will be performed. | Device: inhomogeneous Magnetisation Transfer (ihMT) sequence<br>* robust technique has shown great sensitivity for evaluating the demyelination processes using MRI at 1.5T<br>|
| Active Comparator: control group 1.5 T<br>healthy volunteers matched in sex and age inhomogeneous Magnetisation Transfer (ihMT) sequence will be performed. | Device: inhomogeneous Magnetisation Transfer (ihMT) sequence<br>* robust technique has shown great sensitivity for evaluating the demyelination processes using MRI at 1.5T<br>|
| Experimental: experimental group 3T<br>Population of patients with myelin syndrome (MS) at the the disease onset with active lesions inhomogeneous Magnetisation Transfer (ihMT) sequence at 3T will be performed. | Device: inhomogeneous Magnetisation Transfer (ihMT) sequence at 3T<br>* robust technique has shown great sensitivity for evaluating the demyelination processes using MRI at 3T<br>|
| Active Comparator: control group 3T<br>inhomogeneous Magnetisation Transfer (ihMT) sequence will be performed. inhomogeneous Magnetisation Transfer (ihMT) sequence at 3T will be performed. | Device: inhomogeneous Magnetisation Transfer (ihMT) sequence at 3T<br>* robust technique has shown great sensitivity for evaluating the demyelination processes using MRI at 3T<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ihMTR ratio at 1.5TMRI | ihMT 3D technique at 1.5TMRI on active lesions with baseline measurements | 1 year | 
| Magnetic transfert (MT) at 1.5TMRI | relative signal variations of the conventional magnetization transfer (MT) | 1 year | 
| Myelin water fraction at 1.5TMRI | myelin water fraction (MWF), an MRI biomarker of myelin, in new MS lesions | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ihMTR ratio at 3TMRI | Relative variations in ihMTR ratio measured at 3T will be compared to those measured at 1.5T at the same points in time to opmtimize 3D ihMT technique at 3TMRI | 1 year | 
| Evaluate the predictive value of ihMT | Evaluate the predictive value of the measured dynamics with respect to the final progression of the lesions | 1 year |