PET with [18F]Flumazenil As an Index of Neurodegeneration in MS

Overview

Beyond white matter pathology, grey matter damage is considered as a key player in disability onset and progression in Multiple Sclerosis (MS). The underlying substratum of grey matter damage is complex and pluriform, ranging from cortical demyelinating lesions, synapse and dendrite disappearance to neuronal cell death. Current Magnetic Resonance Imaging MRI techniques fail to fully assess and quantify grey matter pathology in this disease. The development of a quantitative marker of neurodegeneration for MS patients would allow: (i) to better understand the pathophysiological mechanisms underlying the distinct forms of MS; (ii) to stratify patients according to their prognosis; and (iii) to evaluate new therapies aimed at promoting neuroprotection. would allow to better understand the mechanisms underlying the distinct forms of MS, to stratify patients according to their prognosis, and to evaluate new therapies aimed at promoting neuroprotection.

The investigators have recently shown that PET (Tomographie par Émission de Positrons) with \[11C\]Flumazenil (\[11C\]FMZ), that binds to the benzodiazepine site of GABA-A receptors, allowed to quantify and map neuronal damage in MS patients. In the present project, the investigators will assess neuronal damage in MS using PET with \[18F\]Flumazenil (\[18F\]FMZ), at the early phase of either relapsing or primary progressive MS, and investigate the pathophysiological meaning of this neuronal damage by combining PET with Flumazenil with MRI at 7T and 3T. The main objective will be to quantify and map \[18F\]FMZ binding changes in the grey matter of MS patients compared to controls, both at the group and the individual level. Secondary and exploratory objectives will be to investigate the relationship between Flumazenil binding changes and: i) cortical demyelinating lesions identified by several 7T MRI sequences ; ii) dendritic arborisation assessed by 3T DWI; ii) available MRI metrics obtained on a clinical 3T scan (grey matter atrophy MTR modifications, resting state connectivity); iv) clinical metrics. This study will develop and assess a new imaging biomarker that has the potential to be used as an index of neurodegeneration in MS.