In vivo Investigation of Virtual Hypoxia in Multiple Sclerosis Progression

The NeuroSchool PhD Program of Aix-Marseille University (France) has launched its annual calls for PhD contracts for students with a master's degree in a non-French university. 

This project is one of the proposed projects. Not all proposed projects will be funded, check our website for details.

State of the art: Progression in multiple sclerosis (MS) is the main driver of irreversible disability and cannot be fully explained by inflammatory demyelination. Increasing evidence supports the concept of “virtual hypoxia”, whereby demyelination increases axonal energy demand while oxidative stress impairs mitochondrial ATP production. This mismatch leads to intracellular sodium accumulation, calcium influx and axonal degeneration. Chronic active lesions and cortical pathology may contribute to progression but likely converge toward a common pathway of energetic failure. Identifying in vivo biomarkers of this metabolic impairment is therefore a major neuroscientific challenge. Ultra-high field (7T) MRI enables non-invasive investigation of brain energy metabolism using complementary approaches: sodium MRI, reflecting ionic homeostasis disturbances, and phosphorus MR spectroscopy, probing high-energy phosphate metabolism.  ndwriting (based on Alhaddad et al. 2024) in patients and matched controls to determine the processes which depend on somatosensory feedback. At this point, 11 patients have agreed to participate: although this number is limited, it is at least 5 times greater than in most studies with such rare patients. A motion-capture device will be used to acquire kinematic data during handwriting. Specific statistical tests will be used to infer about differences between patients and controls. Clinical and detailed sensory examination will be performed by collaborators to strengthen the project. The second phase will tackle neurophysiological underpinnings of handwriting by using EEG as already done in our group (Zuo et al., in revision). We will quantify the oscillatory dynamics of neural signals associated to tracing movements of varying difficulty.  

Objectives: To develop robust quantitative 7T sodium MRI biomarkers of virtual hypoxia in MS and to assess their association with clinical progression. Within the broader of an ANR program (ICE4MS), the candidate will focus on optimizing the sodium imaging component to obtain reliable multiparametric accumulation.

Methods: The project will optimize multi-echo radial sodium sequences at 7T using a newly acquired 32-channel sodium coil. The candidate will implement B1 inhomogeneity correction, multi-channel signal combination and quantitative calibration strategies, and develop processing pipelines in Python including denoising and multi-exponential modeling. The optimized protocol will be applied to MS patients from the ICE4MS cohort.  

Expected results: The project should establish reproducible quantitative sodium MRI methodology at 7T and improve correction of ultra-high field artifacts. We expect intracellular-weighted sodium metrics to be associated with disability, supporting energetic failure as a key mechanism of progression. 

Feasibility:  The study is conducted at CRMBM (Marseille) on a researchdedicated 7T MRI system with multinuclear capability and a newly funded 32-channel sodium coil (Amidex Equipex). MS patients are recruited within the ICE4MS program. Ethical approval has been obtained for the protocol. 

Within Aix Marseille Université, NeuroMarseille brings together 8 research laboratories and NeuroSchool, a graduate school in neuroscience, to increase the attractiveness of the university, international collaborations, interdisciplinarity, links with the clinical and industrial worlds and the integration of students into professional life. 

Launched in July 2018, NeuroSchool unifies and harmonizes the training of the third year of the Bachelor of Life Sciences (Neuroscience track), the Master's and the PhD in Neuroscience. 

• Expected candidate profile : The candidate must demonstrate: (1) strong training in MRI physics, (2) advanced expertise in signal processing and  quantitative modeling, (3) solid programming skills in Python, and (4) experience with Siemens IDEA sequence development. An interest in translational neuroscience and neurodegenerative diseases is expected.