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

NCT07202494 | Recruiting

• 1 other identifier: RCAPHM23_0203
• Study Type: observational
• Target: 700
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Multiple Sclerosis; Neuromyelitis Optica Spectrum Disorders; Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD); Alzheimer Disease; Parkinson Disease; Amyotrophic Lateral Sclerosis (ALS); Temporal Lobe Epilepsy; Epilepsy; Mild Traumatic Brain Injury; Healthy Aging

Outcome Measures

Primary Outcomes (2)

• Nodal Connectivity measured by resting-state BOLD fMRI and diffusion MRI tractography (graph-theoretical metrics)

  Nodal connectivity will be assessed using graph-theoretical measures (in-degree, out-degree, and strength).

  Baseline and 24 months (longitudinal follow-up)

• Sodium Concentration as Indicators of Neuronal Energy Failure

  Baseline and 24 months (longitudinal follow-up)

Secondary Outcomes (5)

• Regional sodium concentration and phosphorus metabolism in brain and spinal cord measured by 23Na-MRI and 31P-MRI

  Baseline and 24 months (longitudinal follow-up)

• Network Metrics

  Baseline and 24 months (longitudinal follow-up)

• distance between the gray matter-white matter boundary and the pial surface (outer cortical surface). (Cortical Thickness)

  Baseline and 24 months (longitudinal follow-up)

• Iron Accumulation (Concentration) in Cortical Layers

  Baseline and 24 months (longitudinal follow-up)

• Cortical thickness measured by structural MRI (MP2RAGE) and processed with FreeSurfer

  Baseline and 24 months (longitudinal follow-up)

Study Arms (10)

Healthy controls

(160 participants, split by age and sex)

Other: Imaging Techniques (MRI 3T & 7T, Functional, Structural, and Metabolic Imaging)

Multiple Sclerosis

Other: Imaging Techniques (MRI 3T & 7T, Functional, Structural, and Metabolic Imaging)

Neuromyelitis Optica Spectrum Disorder (NMOSD)

Other: Imaging Techniques (MRI 3T & 7T, Functional, Structural, and Metabolic Imaging)

Myelin Oligodendrocyte Glycoprotein Antibody Disease (MOGAD)

Other: Imaging Techniques (MRI 3T & 7T, Functional, Structural, and Metabolic Imaging)

Alzheimer's Disease

Other: Imaging Techniques (MRI 3T & 7T, Functional, Structural, and Metabolic Imaging)

Parkinson's Disease

Other: Imaging Techniques (MRI 3T & 7T, Functional, Structural, and Metabolic Imaging)

Amyotrophic Lateral Sclerosis (ALS)

Other: Imaging Techniques (MRI 3T & 7T, Functional, Structural, and Metabolic Imaging)

Temporal Epilepsy

Other: Imaging Techniques (MRI 3T & 7T, Functional, Structural, and Metabolic Imaging)

Non-Temporal Epilepsy

Other: Imaging Techniques (MRI 3T & 7T, Functional, Structural, and Metabolic Imaging)

Mild Traumatic Brain Injury (mTBI)

Other: Imaging Techniques (MRI 3T & 7T, Functional, Structural, and Metabolic Imaging)

Interventions

Imaging Techniques (MRI 3T & 7T, Functional, Structural, and Metabolic Imaging) OTHER

Functional MRI (fMRI) Diffusion Tensor Imaging (DTI) Sodium Imaging (23Na-MRI) Phosphorus Imaging (31P-MRI)

Alzheimer's Disease; Amyotrophic Lateral Sclerosis (ALS); Healthy controls; Mild Traumatic Brain Injury (mTBI); Multiple Sclerosis; Myelin Oligodendrocyte Glycoprotein Antibody Disease (MOGAD); Neuromyelitis Optica Spectrum Disorder (NMOSD); Non-Temporal Epilepsy; Parkinson's Disease; Temporal Epilepsy

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population includes 540 patients with various neurological diseases-multiple sclerosis (stratified by disability level), NMOSD/MOGAD, Alzheimer's disease, Parkinson's disease, ALS, epilepsy (temporal and non-temporal), and mild traumatic brain injury-and 160 healthy volunteers aged 18 to 90 years, evenly distributed by sex and age decade. All participants must provide informed consent, be free of major MRI contraindications, and have no uncontrolled somatic or psychiatric conditions. A subset of participants, including those with progressive conditions and healthy aging individuals, will undergo longitudinal follow-up at 1 and 2 years. The study aims to explore structural, functional, and metabolic brain changes across the lifespan and disease spectrum using ultra-high field MRI.

You may qualify if:

• 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.

You may not qualify if:

• 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.).

Sponsors & Collaborators

• Assistance Publique Hopitaux De Marseille: lead

Study Sites (1)

Chu Timone

Marseille, France

RECRUITING

MeSH Terms

Conditions

Multiple Sclerosis; Neuromyelitis Optica; Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease; Alzheimer Disease; Parkinson Disease; Amyotrophic Lateral Sclerosis; Epilepsy, Temporal Lobe; Epilepsy; Brain Concussion

Interventions

X-Rays; Functional Status

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Myelitis, Transverse; Optic Neuritis; Optic Nerve Diseases; Cranial Nerve Diseases; Eye Diseases; Dementia; Brain Diseases; Central Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Spinal Cord Diseases; Motor Neuron Disease; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Epilepsies, Partial; Epileptic Syndromes; Brain Injuries, Traumatic; Brain Injuries; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds and Injuries; Wounds, Nonpenetrating

Intervention Hierarchy (Ancestors)

Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing; Activities of Daily Living; Rehabilitation; Health Services; Health Care Facilities Workforce and Services; Health Status; Demography; Epidemiologic Measurements; Public Health; Environment and Public Health

Study Officials

• François CREMIEUX

  Assistance Publique - Hôpitaux de Marseille

  STUDY CHAIR

Central Study Contacts

Jan-Patrick STELLMANN

CONTACT

+33 (0) 4 91 38 48 07; jan-patrick.stellmann@ap-hm.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2025
• First Posted: October 1, 2025
• Study Start: May 19, 2025
• Primary Completion (Estimated): May 18, 2030
• Study Completion (Estimated): May 18, 2030
• Last Updated: October 1, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)