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Magnetic resonance imaging remains the main neuroimaging method in multiple sclerosis. Modern MRI, however, can assess not only the number of lesions but also their structure, location, evolution over time, relationship to small veins, signs of chronic inflammation, and gradual tissue loss in the brain and spinal cord.
Some radiological biomarkers are already used routinely, others acquired a new role in the 2024 McDonald criteria, while some measures are still used mainly in research and specialized centers.
Lesion location, shape and distribution are assessed and, when needed, more specific features such as the central vein sign or a paramagnetic rim.
The scan is assessed for new or enlarging T2/FLAIR lesions and, when indicated, gadolinium-enhancing lesions.
Persistent T1-hypointense lesions, cortical involvement, atrophy and spinal cord changes are considered.
Paramagnetic rim lesions, slowly expanding lesions and quantitative atrophy measures may provide additional information.
| Biomarker | What it reflects | Diagnosis | Activity | Progression | Use |
|---|---|---|---|---|---|
| New or enlarging T2/FLAIR lesions | New focal inflammatory activity | Yes | Yes | Limited | Routine |
| Gadolinium-enhancing lesions | Recent blood–brain barrier disruption | Yes | Yes | Not directly | When clinically indicated |
| Central vein sign (CVS) | Characteristic perivenular lesion architecture | Yes | No | Not established | Specialized MRI |
| Paramagnetic rim lesions (PRL) | Chronic inflammation at the lesion edge | Yes, in selected situations | Chronic activity | Has prognostic value | Specialized MRI |
| Cortical lesions | Cerebral cortical involvement | Additional information | Limited | Has prognostic value | Detection depends on protocol |
| Slowly expanding lesions (SEL) | Gradual enlargement of a subset of chronic lesions | No | Chronic activity | Promising marker | Mainly research |
| Persistent T1-hypointense lesions (T1 black holes) | More severe irreversible tissue injury | Limited | Not a primary marker | Associated with severity of tissue damage | Visible on standard MRI |
| Brain atrophy | Accumulated loss of nervous tissue | No | Not directly | Yes, at group level | Quantitative clinical use remains limited |
| Spinal cord atrophy | Structural spinal cord injury | No | Not directly | Important prognostic value | Not yet a routine quantitative measure |
| Leptomeningeal enhancement (LME) | Possible meningeal inflammation | No | Under study | Under study | Research measure |
The development of advanced neuroimaging has not reduced the importance of conventional standardized MRI. New or enlarging lesions are still among the findings that most directly influence assessment of treatment effectiveness.
A new lesion or definite enlargement of a pre-existing lesion indicates new inflammatory activity when studies were performed with comparable protocols.
Contrast enhancement reflects temporary blood–brain barrier disruption and identifies recent inflammatory activity.
The absence of enhancement does not mean that no new activity occurred during the previous months.
Persistent low signal on T1-weighted images may reflect more severe loss of myelin and axons and structural tissue destruction.
These lesions are not used as a stand-alone criterion for switching treatment.
Many MS lesions develop around small veins. When an MRI sequence is sufficiently sensitive to magnetic susceptibility, a vein running through the lesion can be visualized.
Perivenular architecture is characteristic of many MS lesions and can help distinguish them from some nonspecific white-matter abnormalities seen in migraine, vascular risk factors and other conditions.
Susceptibility-sensitive sequences are used, including susceptibility-weighted imaging (SWI).
For most clinical tasks, a good-quality 3-Tesla scanner is sufficient. A 7-Tesla MRI is not required for routine diagnosis.
After the acute inflammatory phase has resolved, some MS lesions do not become completely inactive. Activated microglia and macrophages containing iron may persist at the lesion edge.
On susceptibility-sensitive MRI, this may appear as a characteristic dark rim around the lesion.
Paramagnetic rim lesions are much more common in MS than in most disorders that can mimic it on MRI.
This is why PRL acquired a diagnostic role in the revised 2024 McDonald criteria.
A paramagnetic rim is associated with persistent inflammation at the periphery of a chronic lesion after acute blood–brain barrier disruption has subsided.
In research studies, PRL are associated with more severe tissue injury and less favorable disease characteristics.
However, there is no universal number of PRL that automatically requires a treatment change.
Multiple sclerosis affects more than white matter. Lesions within the cerebral cortex are an important part of the disease and may occur even at early stages.
Cortical involvement is associated with cognitive impairment, gray-matter atrophy and disability accumulation.
Cortical lesions may also provide additional diagnostic information.
Their small size and low contrast with normal cortex make many cortical lesions difficult to detect on conventional MRI.
Double inversion recovery (DIR) and phase-sensitive inversion recovery (PSIR) may improve detection.
Spinal cord involvement has particularly high clinical relevance: even a relatively small lesion can cause substantial motor, sensory or bladder and bowel dysfunction.
Typical MS lesions are usually relatively short and do not occupy the entire cross-sectional area of the cord.
Their shape and length also help in differential diagnosis from NMOSD, MOGAD, vascular and compressive lesions.
New lesions may indicate ongoing disease activity and can be highly relevant when assessing treatment effectiveness.
Reduction in spinal cord area or volume is associated with gait impairment, motor disability and progression.
Quantitative assessment remains technically more difficult than conventional lesion detection.
In the 2024 McDonald criteria, the optic nerve became a fifth anatomical location that may contribute to demonstrating dissemination of a demyelinating process in space.
When optic neuritis is suspected, dedicated sequences can demonstrate characteristic optic nerve involvement.
Dedicated optic nerve imaging does not need to be added to every routine follow-up MRI in a patient with already established MS.
The need depends on the clinical question.
One of the major goals of modern neuroimaging is to visualize processes that continue after acute contrast enhancement has disappeared.
In a chronic active lesion, the center may already contain substantially damaged tissue, while slow inflammation involving microglia and macrophages persists at the edge.
Defined by susceptibility-related MRI features and associated with iron-containing cells at the edge of a chronic lesion.
Defined by gradual enlargement of a pre-existing lesion on quantitative analysis of several serial MRI scans.
Some older T2 lesions may expand very slowly over several years without gadolinium enhancement and without appearing active on routine visual comparison.
Not simply by viewing two scans side by side, but by computational registration of multiple studies and analysis of changes in lesion borders over time.
In several studies, SEL are associated with more severe microstructural injury, axonal loss and less favorable longitudinal changes.
Different algorithms and thresholds are used to define SEL. Standardization is not yet sufficient for routine individual monitoring.
In multiple sclerosis, the volume of some central nervous system structures may decline faster than with normal aging. Atrophy is associated with accumulation of irreversible tissue injury and long-term disability.
An important outcome in clinical trials and associated with long-term prognosis.
Atrophy of gray matter and deep gray structures may be associated with motor and cognitive impairment.
Cervical spinal cord atrophy is particularly closely associated with gait impairment and motor disability.
Changing the scanner, coil, reconstruction software or acquisition protocol can affect quantitative results.
Age, hydration and other biological factors can influence volume measurements.
After starting effective anti-inflammatory treatment, brain volume may temporarily decrease because inflammatory edema resolves rather than because neurodegeneration accelerates.
New T2/FLAIR lesions and gadolinium enhancement are good markers of focal inflammatory activity. They are much less informative about processes that cause gradual disability accumulation without relapses.
This is why other measures are being studied in progression independent of relapse activity (PIRA).
May reflect persistent chronic inflammation in old lesions.
Characterize long-term evolution of a subset of chronic lesions.
Reflects accumulated tissue loss in the brain and spinal cord.
Cortical lesions and gray-matter atrophy are associated with chronic injury and disability.
Thalamic and other deep gray-matter atrophy are of particular interest, but individual interpretation remains limited.
Spinal cord atrophy may be especially closely linked to motor deterioration.
Modern neuroimaging can assess not only lesion shape and volume, but also tissue microstructure, iron, myelin and diffuse injury outside visible lesions.
Provides quantitative assessment of tissue magnetic susceptibility and is used to study iron and chronic active lesions.
Assesses water diffusion properties and can detect microstructural white-matter abnormalities, including in regions that appear normal on conventional MRI.
Used for indirect assessment of tissue macromolecular changes and myelin integrity.
Being developed as a more specific way to estimate myelin content and study demyelination and remyelination.
Can automatically identify lesion number and volume and compare them across serial scans.
May help detect new lesions, assess atrophy and automate parts of quantitative analysis.
AI does not replace clinical interpretation by a neurologist and neuroradiologist.
May reflect inflammatory processes in the meninges and is discussed as a possible marker of compartmentalized inflammation.
The method is not standardized enough for routine monitoring.
Quantitative techniques show that MS-related tissue injury may extend far beyond visible T2 lesions.
7-Tesla MRI can show some cortical lesions, central veins and fine structure of chronic lesions more clearly.
It remains a specialized tool rather than a required component of routine MS monitoring.
For clinical practice, the goal is not the maximum number of advanced sequences, but a high-quality reproducible protocol that allows reliable comparison over time.
It should be clear which prior MRI was used to compare the new images.
The report should state whether new or enlarging T2/FLAIR lesions are present.
If gadolinium was given, the report should state whether enhancing lesions are present.
Periventricular, cortical or juxtacortical, infratentorial and spinal locations are relevant.
If lesion morphology or distribution is not typical for MS, this is important for further differential diagnosis.
When appropriate sequences are available, the central vein sign and paramagnetic rim lesions can be assessed.
One of the main objective signs of persistent focal inflammatory activity during treatment.
Indicates recent inflammation and must be interpreted in relation to the timing of treatment initiation or switching.
May have particularly high clinical relevance because of the functional importance of spinal pathways.
These measures provide important information about chronic tissue injury and are gradually expanding our understanding of MS progression.
However, there is not yet a simple widely accepted algorithm that allows treatment to be changed automatically on the basis of one of these findings.
The central vein sign, paramagnetic rim lesions and cortical lesions may increase diagnostic specificity.
This can be especially useful when migraine, vascular risk factors or multiple nonspecific white-matter lesions are present.
Vascular and other nonspecific white-matter abnormalities become more common with age, which can make conventional MRI more difficult to interpret.
When PIRA is suspected, it is particularly important to assess the spinal cord, functional evolution and possible signs of chronic tissue injury.
Expert re-evaluation of the original images using modern diagnostic criteria may sometimes provide more information than simply repeating another standard MRI.