This study investigates whether an advanced MRI technique called Quantitative Susceptibility Mapping (QSM) can improve the differentiation of white matter lesions in people aged 50-70 years with multiple sclerosis (MS). In older individuals with MS, white matter changes seen on MRI may be related to MS or to other types of white matter changes, most commonly age-related changes or chronic small vessel disease. These conditions can appear similar on conventional MRI scans, making interpretation challenging.

Participants will undergo routine clinical MRI, including a short additional QSM sequence, as well as brief cognitive and physical assessments. A comparison group with cerebral small vessel disease will also be included.

The goal of the study is to determine whether QSM can provide more precise lesion characterization and support more accurate clinical interpretation of MRI findings in older patients with MS.

Magnetic resonance imaging (MRI) is central to the diagnosis and monitoring of multiple sclerosis (MS). In individuals above 50 years of age, interpretation of white matter lesions becomes increasingly complex because lesions visible on conventional T2-weighted and FLAIR MRI may reflect MS-related demyelination, chronic cerebral small vessel disease (cSVD), or nonspecific age-related white matter changes. Conventional MRI has limited specificity in differentiating between these entities, which may complicate assessment of disease activity and progression.

Quantitative Susceptibility Mapping (QSM) is an advanced MRI technique that quantifies tissue magnetic susceptibility and provides complementary information to conventional imaging. Differences in susceptibility characteristics may reflect underlying tissue composition and microstructural properties, potentially allowing improved differentiation between demyelinating and vascular white matter lesions.

This prospective observational cohort study includes individuals aged 50-70 years with established MS undergoing routine clinical MRI follow-up, as well as an age-comparable cohort with clinical and radiological evidence of cSVD. Participants with MS will undergo longitudinal follow-up through routine clinical MRI and clinical assessments, whereas participants in the cSVD cohort will undergo a single study visit including MRI and standardized clinical testing. MRI examinations include standard clinical sequences with the addition of a short QSM acquisition. Clinical assessment includes brief standardized measures of cognitive processing speed, executive function, and physical function performed in conjunction with clinical visits.

Imaging analyses will focus on lesion-level and participant-level susceptibility characteristics and their distribution patterns across cohorts. Associations between QSM-derived measures and clinical function will be explored. The study is designed to evaluate the diagnostic utility and clinical relevance of QSM-based lesion characterization in older individuals with MS.

Inclusion Criteria Multiple Sclerosis (MS) cohort (AgeMS):

• Age 50-70 years
• Clinically confirmed diagnosis of multiple sclerosis
• Participation in the AgeMS study at Oslo University Hospital

Inclusion Criteria Cerebral Small Vessel Disease (cSVD) control cohort:

• Age 50-80 years
• Radiological evidence of hypertensive small vessel disease on MRI
• Good clinical recovery following transient ischemic attack (TIA), minor stroke, or stroke mimic diagnosis

Exclusion Criteria Multiple Sclerosis (MS) cohort:

• MRI contraindications
• Severe psychiatric comorbidity
• Major functional disability unrelated to MS or CSVD

Exclusion Criteria Cerebral Small Vessel Disease (cSVD) control cohort:

• MRI contraindications
• Probable or definite cerebral amyloid angiopathy according to Boston criteria 2.0
• Genetic or inflammatory vasculopathies
• Persistent neurological deficits
• Severe psychiatric comorbidity
• Major functional disability unrelated to CSVD

The study population consists of two cohorts recruited at Oslo University Hospital.

The multiple sclerosis (MS) cohort includes participants aged 50-70 years with a clinically confirmed MS diagnosis enrolled in the AgeMS study, an ongoing longitudinal study of older individuals with MS. Eligible participants are invited to participate by letter. Participants undergo semiannual MRI examinations and standardized neurological, cognitive, and patient-reported assessments through 2030.

The cerebral small vessel disease (cSVD) control cohort includes patients aged 50-80 years with radiological evidence of hypertensive small vessel disease identified on MRI and recruited from the Stroke Unit. Eligible participants are approached during hospital admission and invited to participate. Eligible participants are approached during hospital admission and invited to participate. These participants undergo a single MRI session and standardized clinical testing.

Individual participant data (IPD) will not be shared. The study involves sensitive clinical and neuroimaging data collected under specific ethical approvals and data protection regulations. In accordance with institutional policies and regulatory requirements, individual-level data cannot be made publicly available.