Multimodal Imaging Signatures of the Biological Mechanisms Underlying Neurodegeneration in Multiple Sclerosis

Multiple sclerosis (MS) is a chronic disease of the central nervous system characterised by multi-focal inflammatory and demyelinating lesions disseminated in the brain and in the spinal cord. Impressive advancements in the treatment of the autoimmune component of the disease have been achieved during the last decades, leading to a drastic reduction of white matter lesion accumulation and relapse rate along the disease course. However, the development of treatments effective for preventing or delaying the neurodegenerative component of the disease, that underly disability accrual and progression of the disease, remains a major challenge. The development of novel therapeutic strategies for neuroprotection that target all patients with MS is a priority objective for research in the next years. The critical steps towards identifying treatments that prevent neuro-axonal damage include a deep understanding of the mechanisms underlying neurodegeneration and the development of reliable biomarkers for assessing the efficacy of emerging drugs and for accelerating their translation to clinical use.

The team of Prof. Stankoff has pioneered an innovative imaging approach combining positron emission tomography and MRI, and succeeded in generating individual maps or key biological processes such as endogenous remyelination, neuroinflammation, or early damage preceding lesion formation. Using these approaches, it has been shown that these mechanisms were influencing disability worsening over the disease course, but the investigators still lack long term longitudinal studies for the validation of these advanced imaging metrics as prognosis markers. Recently, preliminary results have also suggested that a multimodal combination of advanced MRI sequences may have the potential to reproduce some PET results.

In this project the investigators propose to unravel the predictive value of individual maps of tremyelination, neuroinflammation, and early tissue damage, on long term disability worsening and to develop a novel imaging approach that aims to capture remyelination of lesions, ongoing inflammation invisible on T1 and T2 MRI sequences (subacute/chronic active lesions) and to predict short-term future disease activity (identify prelesional areas), from a single multimodal MRI acquisition in patients with MS.

MS patient already included in previous studies using MRI and/or PET-MR (INFLASEP (NCT02305264), FLUMATEP (NCT01651520) or SHADOWTEP) will be proposed a long-term follow up study.

Participants will undergo :

* a full neurological examination including EDSS
* medical history and comorbidities (including smoking)
* concomitant and MS treatments
* neuropsychological testing
* Blood sample for serum biobanking
* multimodal MRI

Eligibility Criteria:
Inclusion Criteria:

* Multiple Sclerosis Patient already enrolled in one of those 3 protocols since 8 years or more: INFLASEP, FLUMATEP 1-2 or SHADOWTEP
* Adult patient
* Affiliation to a social security scheme or beneficiary of such a scheme (Except "Aide Médicale d'Etat")
* Consent obtained

Exclusion Criteria:

* Any reasons, which does not allow to perform MRI, including claustrophobia, the implant of a pace maker or the presence of an intra-ocular foreign body (a contra- indication questionnaire will be filled in beforehand)
* Pregnancy, breast-feeding, lack of efficient contraception
* Current symptoms of severe or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary or cardiac disease, or any other chronic neurological diseases
* Unwillingness to be informed in case of abnormal MRI (with a significant medical anomaly)
* Enrolment in another interventional study protocol for the duration of his or her participation without physician's agreement
* Patient under legal protection