In this study we plan to image the compartmentalized inflammation in MS using molecular imaging by positron emission tomography (PET) with a very highly resolutive camera. Two tracers will be studied and compared: i) [18F]DPA-714, which bind to the peripheral benzodiazepine receptor (PBR), a target mainly expressed by activated microglial cells. This new ligand for PBR displays several advantages compared to the existing reference compound PK11195 in term of brain entrance, signal to noise ratio, and radiolabelling possibility with [18F] ii) [18F]-fluoro-desoxy-glucose ([18F]FDG), which should reflect glucose metabolism in activated immune cells in the white matter. Progressive MS patients (secondary progressive and primary progressive) will be compared to relapsing-remitting patients and to healthy volunteers. All subjects will pass a complete neurological evaluation and a multimodal MRI to document clinical disability and tissue injury. A clinical and radiological follow up will then be performed for a 2-year period. This study should help to understand the contribution of the intracerebral inflammation on the progression of disability and could provide a surrogate marker for further therapeutic trials in chronic progressive MS.

Study design This study is a prospective cross-sectional controlled multicentric clinical study in 45 MS patients and 20 controls.

Four groups of person will be included and compared:

• Group I: 20 healthy volunteers aging from 18 to 65 years. These healthy volunteers will be matched for age and sex with patients (1/2).
• Group II: 15 patients aging from 18 to 65 years with relapsing-remitting (RRMS), with less than 10 years of evolution since the first manifestation and no recent relapse.
• Group III: 15 patients aging from 18 to 65 years with secondary progressive MS (SPMS), with less than 10 years of evolution since the occurrence of the secondary progressive phase.
• Group III: 15 patients aging from 18 to 65 years with primary progressive MS (PPMS) diagnosed since less than 10 years.

Study centres MS patients and the 20 healthy volunteers will be recruited in the Hospital Pitie-Salpetriere

MS patients will be recruited in the Hospital Tenon

This study will be performed by complementary teams already collaborating on molecular imaging trials in MS (which assess neuronal loss or demyelination/remyelination): i) the "Centre d'Investigation Clinique" (Salpetriere hospital, Paris), which is strongly experienced in the coordination of clinical and translational research on MS; ii) the CENIR (centre for neuroimaging research, Salpetriere hospital, Paris) a specialized MRI centre for research on neurological diseases; iii) the SHFJ (DSV, CEA, ORSAY) which is a world class molecular imaging centre;

Study duration Per patient the study will last two years Per control the study will last up to 8 weeks

Inclusion criteria

Healthy volunteers (group I, n=20)

• Aged 18-65 years;
• Able to understand the objectives and procedures of the study, and who give inform consent.

Patients with relapsing-remitting MS (group II, n=15)

• Aged 18-65 years
• Clinically definite MS according to McDonald revised criteria
• Less than 10 year of evolution
• No clinical relapse during the past 3 months
• Able to understand the objectives and procedures of the study, and who give inform consent

Patients with progressive MS (group III and IV, n=15 per group)

• Aged 18-65 years
• Clinically definite MS according to McDonald revised criteria
• SPMS evolving since more than 10 years for group III (n = 15).
• PPMS evolving since less than 10 years for group IV (n=15).
• Each progressive patient should have experienced a significant progression during the 2 years preceding the inclusion (with an estimated progression of the EDSS score of at least 0.5 point).
• No clinical relapse during the past 3 months
• Able to understand the objectives and procedures of the study, and who give inform consent.

Exclusion criteria

• Any reason, which does not allow performing MRI: claustrophobia, pace-maker or intra-ocular foreign body for example.
• For women: pregnancy, lactation, lack of efficient contraception. At visit 2, a positive pregnancy test will lead to exclude the patient.
• Uncontrolled diabetes
• Current symptoms of severe or uncontrolled renal, hepatic, hematological, gastrointestinal pulmonary or cardiac disease.
• Positive HIV test
• Prior participation in other research protocols or clinical care in the last year such that radiation exposure would exceed the annual guidelines.
• Other chronic neurological disease.