Integrating Metabolism, Connectivity, and Mesoscale Imaging at Ultra-high Field to Decipher Mechanisms of Resilience and Neurodegeneration in Neurological Diseases and Healthy Aging

Integrating Metabolism, Connectivity, and Mesoscale Imaging at Ultra-high Field to Decipher Mechanisms of Resilience and Neurodegeneration in Neurological Diseases and Healthy Aging

The MESO7 study is a prospective observational research project designed to investigate the mechanisms of resilience and neurodegeneration in neurological diseases and healthy aging. It leverages advanced multiparametric brain and spinal cord imaging at high (3T) and ultra-high magnetic fields (7T) to assess structural, functional, metabolic, and mesoscale changes in the central nervous system (CNS). Particular emphasis is placed on sodium (23Na-MRI) and phosphorus (31P-MRI) imaging, along with layer-dependent brain connectivity analysis.

The primary objective is to evaluate the impact of neuronal energy failure, measured via sodium concentration, on functional and structural reorganization in both healthy individuals and patients with various neurological conditions. Directed brain network models will be constructed from MRI data to quantify the connectivity strength (in- and out-degree) of cortical nodes. These connectivity metrics will be correlated with sodium concentrations to assess energy failure and its role in network reorganization. Longitudinal follow-up over two years is planned for subgroups with clinically progressive diseases.

Secondary objectives include decoding metabolic, microstructural, and functional signatures of successful aging at the laminar level; characterizing disease-specific patterns of cortical and spinal microstructure associated with physical and cognitive dysfunction; describing longitudinal mesoscale and metabolic changes; and generating representative normative imaging datasets for the neuroscience community.

The study plans to enroll a total of 540 patients across 9 neurological conditions:Multiple Sclerosis (MS), Neuromyelitis Optica Spectrum Disorders (NMOSD), MOG Antibody Disease (MOGAD), Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis (ALS), temporal and non-temporal epilepsy, and mild traumatic brain injury (mTBI),in addition to 160 age- and sex-matched healthy controls, totaling 700 participants. Imaging and clinical assessments will be performed at the CEMEREM center at Timone University Hospital, AP-HM, Marseille, France.

Each participant will undergo multiparametric brain and spinal cord MRI, including DTI, BOLD, MP2RAGE, SWI, quantitative sodium and phosphorus imaging, and functional assessments including neuropsychological testing, visual and motor function tests. Disease-specific assessments such as OCT, evoked potentials, and disability scores (e.g., EDSS for MS) will also be included when appropriate.

The study is expected to improve understanding of CNS adaptation mechanisms and support the development of more accurate diagnostic and prognostic tools for neurodegenerative diseases

Inclusion Criteria:

• Age:Female or male, aged 18 years or older.
• Health Status: No uncontrolled general diseases, such as cancer, autoimmune diseases, liver failure, severe or untreated high blood pressure, or severe rhythm disorders. No chronic psychiatric illnesses, including severe dementia.
• MRI Compatibility: No contraindications for MRI exams (e.g., claustrophobia, metal foreign bodies, pacemakers, severe kidney failure).
• Social Security Coverage: Participants must have social security coverage.
• Informed Consent: The participant must have read, understood, and signed the informed consent after being adequately informed about the study.
• Specific Disease Criteria (For Disease Groups): Specific inclusion criteria apply to each pathology, such as MS (based on McDonald criteria), NMOSD (Wingerchuk 2015), Alzheimer's (meeting NINCDS-ADRDA criteria), etc.

Exclusion Criteria:

• Pregnancy: Pregnant women are excluded from the study.
• Inability to Provide Informed Consent:
• Any participant who refuses to sign the informed consent or is unable to do so due to mental or physical conditions.
• Refusal of MRI: Individuals who refuse to undergo brain MRI.
• Contraindications for MRI:Participants with contraindications for MRI exams, such as claustrophobia, metal foreign bodies, pacemakers, or severe kidney failure.
• Medical Conditions: Known allergy to Dotarem (contrast agent) for neuroinflammatory patients. Individuals with severe renal insufficiency or other conditions that prevent MRI scanning.

Cognitive or Psychiatric Issues:

Chronic psychiatric conditions, including severe dementia or cognitive dysfunction that could hinder participation.

Legal or Institutional Restrictions:

Adults under legal protection (e.g., under guardianship or curatorship). Individuals deprived of their liberty.

Other Medical Conditions:

Individuals with neurological diseases such as ischemic accidents, brain trauma, or encephalitis.

Patients on treatments that would interfere with the study, as outlined for each disease.

Allergy to Contrast Agent:

Allergy to Dotarem for neuroinflammatory patients (MS, NMOSD, etc.).

Inability to Adhere to Protocol:

Participants who are unable or unwilling to comply with the study protocol.