DS0407 - Exploration du système nerveux dans son fonctionnement normal et pathologique

New strategies to quantify in vivo intra-cellular brain sodium concentrations using ultra-high field (7T) MRI in humans. Application to cortical and sub-cortical neurodegeneration in multiple sclerosis – NEUROintraSOD-7T

Submission summary

Sodium (23Na) MRI provides a unique and non-invasive way to detect and quantify in vivo sodium concentrations. Pathological studies have evidenced that mitochondrial dysfunction results in intra-axonal sodium accumulation leading to neuronal injury, responsible for irreversible disability. To date, four studies including two from our group have demonstrated the great potential of this technique as a quantitative biomarker of neuronal degeneration in multiple sclerosis (MS) patients by assessing the total sodium concentration that is an average of intracellular and extracellular sodium. Interestingly, brain sodium accumulation was mainly located in the grey matter (GM) and associated with disability. These results highlight the critical involvement of neurodegenerative process in GM, playing a key role in the pathogenesis of MS as suggested by recent pathological findings. Despite this, there are several technical drawbacks to study more accurately GM at 3T (low spatial resolution, low sensitivity and no differentiation between intracellular and extracellular compartment). There is a crucial need to explore efficiently GM neurodegenerative process at higher field.
This proposal aims to develop new methodological strategies to quantify in vivo intra-cellular brain sodium concentrations using ultra-high field (7T) MRI in humans and apply to study cortical and sub-cortical neurodegeneration and its clinical impact on disability in MS patients.
The relationship between sodium accumulation and cortical lesions will be assessed using optimised proton MRI sequences in the new 7T whole-body MRI system in the laboratory. In addition, we will evaluate the clinical impact (physical and cognitive) of cortical sodium accumulation and neurodegeneration.
This project is believed to provide the first in vivo, non-invasive biomarker specific of neurodegeneration based on the assessment of brain intracellular sodium concentration using high-resolution quantitative triple quantum filtered and/or inversion recovery sodium MRI. This biomarker could potentially serve as a primary endpoint for the future definition of optimal therapeutic windows for new neuroprotective drugs.

Project coordination

Wafaa ZAARAOUI (CENTRE DE RESONANCE MAGNETIQUE BIOLOGIQUE ET MEDICALE)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

CRMBM CENTRE DE RESONANCE MAGNETIQUE BIOLOGIQUE ET MEDICALE

Help of the ANR 199,626 euros
Beginning and duration of the scientific project: February 2016 - 36 Months

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