2024+MAGNIMS／CMSC／NAIMS共识建议：MRI在多发性硬化症诊断中的应用

2024 MAGNIMS-CMSC-NAIMS consensus recommendations on the use of MRI for the diagnosis of multiple sclerosis

Frederik Barkhof*,Daniel S Reich*,Jiwon Oh,Maria A Rocca,David K BLi,Pascal Sati,Christina J Azevedo,Francesca Bagnato,Peter A Calabresi,Olga Ciccarelli,Michael G Dwyer,Gabriele C DeLuca,Nicola De Stefano,Christian Enzinger,Massimo Filippi,Cristina Granziera,June Halper,Roland G Henry,Claudio Gasperini,Susan Gauthier,Ludwig Kappos,Cornelia Laule,Scott D Newsome,Xavier Montalban,Sarah A Morrow,Menno M Schoonheim,Nancy Sicotte,Ahmed Toosy,Jeffrey Wilken,Tarey Yousy,Jaime Sastre-Garriga,Anthony Traboulsee*,Daniel Ontaneda*,Alex Rovira* on behalf of the Magnetic Resonance Imaging Network in Multiple Sclerosis, the Consortium of Multiple Sclerosis Centers, and North American Imaging in Multiple Sclerosis Cooperative MRI guidelines working group+

Lancet Neurol 2025; 24: 866-79 See Comment page 808 See Position Paper page 850 and Personal View page 880*Contributed equally MtMembers listed in the appendix(p 1)Department of Radiology and Nuclear Medicine,Amsterdam UMC,Vrije Universiteit,Amsterdam, Netherlands(Prof F Barkhof);Queen Square Institute of

University College London, UK;Translational Neurorelativity Section,National Institute of Neurological Disorders and Stroke,National Institutes of Health,Bethesda,MD,USA(Prof D S Reich MD); Division of Neurology, Department of Medicine,St Michael's Hospital, University of Toronto,Toronto,ON,Canada(John OHD);Departments of Radiology and Medicine(Neurology),University of British Columbia,Vancouver,BC,Canada(Prof D KB Li MD); Department of Neurology, Cedars-Sinai Medical Center,Los Angeles,CA, USA Medicine, University of Southern California,Los Angeles,CA, USA(CJ Azevedo MD); Neurology Department, Nashville Veterans Affairs Medical Center,Nashville,TN, USA F(Bagnato);Department, Vanderbilt University Medical Center,Nashville,TN,USA(F Bagnato);Department of Neurology, John Hopkins University School of Medicine, Baltimore,MD,USA(Prof P A Calabresi MD)S D Newsome MD; Queen

MRI plays an increasingly important role in the diagnosis of multiple sclerosis. We discuss the expanded role of MRI in the 2024 McDonald diagnostic criteria for multiple sclerosis, which include the optic nerve as a fifth anatomical location, in addition to the periventricular, juxtaportical or cortical- or horizontal, and spinal cord regions. The diagnosis of multiple sclerosis can now be confirmed when the criteria of dissemination in space are fulfilled with the detection of typical lesions in at least four locations without additional evidence. We recommend appropriate imaging strategies and MRI acquisition protocols for all aspects of multiple sclerosis diagnosis, including fat-saturated sequences for detection of symptomatic optic nerve lesions. Diagnostic imaging should always cover the brain and spinal cord and include susceptibility-sensitive sequences for the assessment of the central vein sign and paramagnetic rim lesions, which can be especially helpful in cases when conventional imaging findings are insufficient to establish a diagnosis. We discuss how to handle the diagnosis of radiologically isolated presentations of multiple sclerosis,which are included in the 2024 criteria. We present recommendations for image interpretation and avoidance of misdiagnosis, and extend the diagnosis of the use of the diagnosis of multiple sclerosis in older people, children, people with vascular comorbidities or migraine, and people living outside Europe and North America. Finally, we provide recommendations for standardisation of MRI acquisition and communication of results to enable an earlier diagnosis while maintaining high diagnostic specificity.

Introduction

existing guidelines for MRI in the diagnostic setting is needed. Appropriate use of MRI becomes key to obtaining the earliest possible diagnosis and avoiding diagnosis, ${}^{61}$ including differentiation from myelin oligodendrocyte glycoprotein antibody disease(MOGAD) and aquaporin-4 antibody-positive neurolyitis optica spectrum disorder(AQP4+ NMOSD).

The 2024 McDonald criteria are presented in a Position Paper by Montalban and colleagues.1 In this Personal View, we provide practical recommendations for imaging strategies and acquisition MRI protocols for all aspects of multiple sclerosis diagnosis(including sequences for the detection of optic nerve lesions and susceptibility-sensitive sequences for the assessment of the CVS and PRL),image interpretation, avoidance of misdiagnosis,standardsisation of MRI acquisition, and communication of results.

Methods

Representatives of the Magnetic Resonance Imaging Network in Multiple Sclerosis(MAGNIMS), North American Imaging in Multiple Sclerosis Cooperative(NAIMS), and Consortium of Multiple Sclerosis Centers(CMSC) networks discussed updated guidance over a series of meetings on the best imaging strategy,acquisition protocols, image interpretation, and radiological reporting strategies for multiple sclerosis diagnosis. The core writing group(FB, DSR, MR, DL,JG,AT,DO,and AR) made proposals that were reviewed

Since the 2024 McDonald diagnostic criteria involve major changes to MRI findings, reconsidering the

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by all authors; open issues were resolved by consensus in a meeting including all members.

# The use of MRI in the 2024 McDonald diagnostic criteria for multiple sclerosis

In the 2024 McDonald diagnostic criteria,'typical lesions with DIS are the cornerstone of the diagnosis. A key(and often the first) diagnostic step remains the exclusion of better alternative explanations for clinical or imaging findings. Multiple sclerosis can now be diagnosed when MRI lesions are demonstrated in at least four typical anatomical locations without further evidence in patients with attack or progression onset. In cases with lesions in fewer anatomical locations, a diagnosis of multiple sclerosis requires demonstration of dissemination in time(DIT; ie, presence of enhancing and non-enhancing lesions on a single scan or accumulation of new lesions on subsequent MRI), lesions that are highly specific for multiple sclerosis on MRI(ie, presenting the CVS or having a paramagnetic rim), or CSF findings. The additional information needed for a diagnosis of multiple sclerosis in case of lesions in fewer than four MRI typical anatomical locations, depends on the number of these locations affected(table 1).

# Recommended imaging strategy

The recommendations in this Personal View are designed for use in both clinical and research settings. We recognise that some methods(particularly susceptibility-sensitive imaging) might not yet be widely available.Optimisation of clinical protocols and radiologist training to achieve sufficient confidence for image interpretation might be required.

In patients with the suspicion of multiple sclerosis, we recommend imaging the brain and the whole spinal cord to reach a diagnosis, exclude other diagnoses, inform prognosis, and serve as a reference for comparisons with follow-up imaging. This initial examination should include administration of intravenous gadolinium-based contrast agents for detection of enhancing lesions and evaluation of differential diagnoses. The detection of concomitant contrast-enhancing and non-enhancing lesions allows the fulfillment of the DIT criteria. Imaging of the spinal cord at the time of diagnosis should be done

routinely,not only because the spinal cord is an anatomical location for DIS but also because spinal cord lesions have important prognostic value.

Spinal cord MRI is particularly important for individuals with spinal cord symptoms to confirm the presence of a demyelinating lesion and rule out other potential causes. Spinal cord MRI is also valuable in adults older than 50 years and people with cerebrovascular pathology, as age-related or vascular white matter abnormalities that mimic multiple sclerosis are rarely associated with spinal cord lesions.' Beyond increasing sensitivity and specificity of multiple sclerosis diagnosis,the presence of spinal cord lesions portends a poor prognosis and might thus inform treatment decisions.Finally, should an indication for spinal cord imaging arise during follow-up, it is helpful to have an initial examination to enable the assessment of any new lesions.

Optic nerve MRI is recommended if there is an initial presentation of optic neuritis, especially if other sources of objective confirmation(ie, optical coherence tomography and visual evoked potentials) are not available or equivocal. Demonstrating a typical demyelinating lesion in the optic nerve will confirm the clinical suspicion of optic neuritis. Such a lesion can be used to show one of the five anatomical locations for DIS, even in individuals without a clinical history of optic neuritis. An optic nerve lesion, if it is it new or enhances with gadolinium-based contrast agents, can also be used to fulfil the criteria for DIT(figure 1). Optic nerve MRI is optional in non-optic neuritis cases, as the diagnostic yield of finding asymptomatic lesions is low.In cases when no gadolinium-enhancing lesions on the initial examination are present and no evidence from the CSF or demonstration of the CVSs are available, repeated

In cases when no gadolinium-enhancing lesions on the initial examination are present and no evidence from the CSF or demonstration of the CVSs are available, repeated imaging should be considered to demonstrate DIT(table 1). Repeat brain imaging can be done without gadolinium-based contrast agents administration, as new T2-weighted fluid-attenuated inversion recovery(FLAIR) lesions will suffice to show DIT. The chances of finding isolated new spinal cord lesions(ie, without associated new brain lesions) are low, and therefore repeat spinal cord imaging is not routinely recommended.

Susceptivity-sensitive imaging is now recommended for routine use to show the presence of lesions with the

||Relapse or progressive onset|RIS and other non-specific presentations| |---|---|---| |Four or five|No further evidence needed|Any one of: DIT*,CSF,or CVS$| |Two or three|Any one of: DIT,CSF, or CVS|Any one of: DIT,CSF,or CVS$| |One|Combination of the following: DIT or CSF; and CVS or PRL$, In patients with progression from onset(≥12 months), at least two spinal cord lesions and any one of: DIT,CSF, or CVS|Not able to make diagnosis| |0|Not able to make diagnosis|Not able to make diagnosis| |CVS=central vein sign.DIT=dissemination in time.PRL=paramagnetic rim lesion.RIS=radiologically isolated syndrome.*Second clinical attack or simultaneous presence of gadolinium-enhancing and non-enhancing lesions at any time or a new T2-hyperintense or gadolinium-enhancing lesion on follow-up MRI.1P positive for oligolocan bands or kappa free-light chains.$Select 6 is considered positive when six or more white matter lesions are CVS positive; if fewer than white matter lesions are detected on MRI, the number of CVS positive lesions should be the majority.$Presence of at least one lesion with a paramagnetic rim.||| |Table 1: Requirements for a diagnosis of multiple sclerosis depending on the number of anatomical locations affected|||

Square MS Centre, Department of Neuroinflammation, Queen Square Institute of Neurology,London,UK(Prof O Ciccarelli, Prof A Toosy PhD); National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre, London, UK(Prof O Ciccarelli); Department of Neurology,Jacobs School of Medicine, State University of New York at Buffalo, Buffalo,NY,USA(M G Dwyer PhD);Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK(Prof G C DeLuca MD);Department of Medicine,Surgery and Neuroscience, University of Siena, Siena, Italy(Prof N De Stefano MD);Department of Neurology,Medical University of Graz,Graz,Austria(C Enzinger MD);Neurology Unit(Prof M Filippi,M Rocca MD),IRCCS San Raffaele Scientific Institute,Milan,Italy;Vita-Salute San Raffaele University,Milan,Italy(Prof M Filippi,

Milan,Italy(Prof M Filippi,M Rocca); Department of Neurology, University Hospital and University of Basel,Basel, Switzerland Neuroimmunology and Neuroscience,Basel, University of Basel,Switzerland Neuroscience, Basel, University of Basel,Basel, University of Basel,Switzerland Technology,�F,Lkposc);Translational Imaging in Neurology Basel, Department of Biomedical Engineering,Faculty of Medicine, University Hospital Basel and University of Basel, Basel,Switzerland Hospital Basel, Basel, Switzerland Prof C Granziera, Prof L Kappos);Faculty of Medicine, University Hospital Basel and University of Basel, Basel, Switzerland Prof C Granziera, Prof L Kappos);Faculty of Medicine, University Hospital Basel and University of Basel, Basel, Switzerland Prof C Granziera, Prof L Kappos);Faculty of Medicine, University Hospital Basel and University of Basel, Basel, Switzerland Prof C Granziera, Prof L Kappos);Faculty of Medicine, University of MS Centers,Hackensack, NJ, USA(J Halper MSN++); Departments of Neurology, Radiology and Biomedical Imaging, Weill Institute for Neurosciences,University of California,San Francisco,CA,USA(Prof R G Henry PhD);Department of Neuroscience,S Camilloanini Hospital,Rome,Italy(C Gasperini MD);Department of Neurology,Weill Cornell Medicine,New York,NY,USA(S Gauthier DO); Departments of Radiology, Pathology&Laboratory Medicine, Physics&Astronomy,International Collaboration on Repair

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 Figure 1: Case study to illustrate the value of optic nerve imaging

A previously healthy woman aged 33 years presented with left-sided optic neuritis.(A) Brain MRI(axial 3D T2-FLAIR) showed multiple periventricular lesions but no cortical or juxtaportical lesions or infratentorial lesions.(B) Since spinal cord imaging(STIR sequence) was also unremarkable, a diagnosis of multiple sclerosis would not have been possible according to the 2017 McDonald diagnostic criteria. Orbital imaging showed increased signal in the left optic nerve(C) on coronal fat-suppressed T2-weighted,(D) with enhancement after gadolinium administration. Collectively, these images show evidence of dissemination in space(two of five anatomical locations) and dissemination in time(enhancing and non-enhancing lesions), allowing a diagnosis of multiple sclerosis to be made according to the revised 2024 criteria.

British Columbia, Vancouver, BC,Canada(Claule PhD); Multiple Sclerosis Centre of Catalonia and Department of Neurology Hospital Universitat Autonoma de Barcelona, Barcelona, Spain(Prof X Montalban, Ltd)Aitalunada,Carleola,Spain Universitat de Vic-Carna:Barcelona,Barcelona,Spain Universitat de Vic-Carna:Barcelona,Spain Universitat de Vic-Carna:Barcelona,Spain Universitat de Vic-Carna:Barcova,Barcova,Spain Universitat de Vic-Carna:Barcova,Barcova,Spain Universitat de Vic-Carna:Barcova,Barcova,Spain Universitat de Vic-Carna:Barcova,Barcova,Spain Universitat de Vic-Carna:Barcova,Barcova,Spain Universitat de Vic-Carna:Barcova,Barcova,Spain Universitat de Vic-Carna:Barcova,Barcova,Spain Universitat de Vic-Carna:Barcova,Barcova,Spain Universitat de Vic-Carna:Barcova,Barcova,Spain Universitat de Vic-Carna:Barcova,Barcova,Spain Universitat de Vic-Carna:Barcova,Barcova,Spain Universitat de Vic-Carna:Barcova,Barcova,Spain Universitat de Vic-Carna:Barcova,Barcova,Spain Universitat de Vic-Carna:Barcova,Barcova,Spain Universitat de Vic-Carna:Barcova,Barcova,Spain Universitat de Vic-Carna:Barcova,

CVS.' Identifying CVS' M identifying CVS might eliminate the need for a CSF examination or follow-up scanning to establish DIT if the initial scan does not reveal both enhancing successful lesions. We recognise that routinely performing susceptibility-sensitive imaging might not be feasible on all scanners, but whenever possible acquisition should be included in the initial diagnostic protocol to avoid repeat scanning. Additional sequences specifically designed for PRL detection remain optional given that they are less relevant for diagnosis(table 1),although PRL also have prognostic relevance. On many scanners, phase images can be reconstructed from the same sequences used for CVS detection, allowing for PRL detection. It is important to note that demonstration of CVS or PRL is not required to make a diagnosis of multiple sclerosis.

Guidelines for standardised MRI protocols for the brain, optic nerve, and spinal cord

The recommended MRI protocol for clinical use in the diagnosis of multiple sclerosis includes the core set of sequences that is minimally required for the diagnostic investigation and serves as a reference for comparison with follow-up examinations. These sequences will generally fit within the clinical workflow for scanner time and radiologist review(table 2).

MRI systems with commonly available field strength(ei,1·5 Tesla[T] or 3] should provide adequate signal-to-noise ratio and in-plane resolution(pixel size) of maximum 1x1 mm. Consistion repositioning of axial slices along the subcalalline line(or, alternatively, the

anterior-posterior commmissure) and image registration are essential for detecting changes in follow-up imaging(eg, new T2 lesions). 3D acquisitions with isotropic voxels(equal≤1 mm dimensions) allow for a good realignment with previous scans. Older scanners should acquire contiguous 2D slices with maximum thickness of 3 mm.

The core MRI protocol of the brain includes the following sequences: T2-weighted FLAIR sequences(preferably acquired in 3D) for identification of lesions;axial T2-weighted sequences(with single or dual echo)for identification or confirmation of posterior fossa lesions; susceptibility-sensitive sequences for CVS identification that can also be used, if phase images are saved, for PL identification; and mildly T1-weighted sequences after the injection of a standard dose(usually 0·1 mmol/kg bodyweight) of gadolinium-based contrast agents. Given that multiple sclerosis lesions are rarely spontaneously T1-hyperintense, routinely acquiring pre-contrast T1-weighted sequences is not needed. After gadolinium-based contrast agents injection, a minimum delay of 5 min(which might be used to acquire FLAIR and susceptibility-sensitive sequences) is needed before obtaining T1-weighted sequences.Macrocyclic gadolinium-based contrast agents are strongly preferred due to less risk of gadolinium deposition, lessening the need to check renal function. Gadolinium-based contrast agents administration is considered safe during breastfeeding but should be avoided in pregnancy unless clinically essential.10

CVS can be detected on various gradient-echo MRI sequences, providing that there is sufficient susceptibility or T2*) weighting and maximum 1·0 mm isotropic spatial resolution. One highly efficient approach uses 3D segmented echo-planar imaging, which is now available on several commercial platforms.12 Voxel-wise multiplication of 3D segmented echo-planar imaging and T2-FLAIR images allows identification of both vein and lesion in a single image termed FLAIR*13, which simplifies reading images for CVS.14 Gradient-echo sequences to detect CVS can also be used with susceptibility-weighted image processing.15 In case T2 lesions appear isointense or hypointense on susceptibility-sensitive images, arithmetic combination or superimposition of T2-FLAIR and susceptibility-weighted images are recommended for accurate CVS detection. A meta-analysis has shown increased CVS detection at higher field strengths(ie, 3·0 and 7·0 T)compared with lower field strengths(ie, 1·5 T).16 Administration of gadolinium-based contrast agents immediately before or during acquisition of susceptibility-sensitive sequences improves detection of the CVS and is especially recommended at 1·5 T.18

Other potentially useful brain 3D sequences include double inversion recovery(DIR), ${}^{19}$ phase-sensitive inversion recovery(PSIR), ${}^{20}$ or heavily T1-weighted gradient-echo(eg,magnetisation-prepared rapid gradient

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||Brain|Spinal cord|Optic nerve| |---|---|---|---| |Field strength|≥1.5T|≥1.5T|≥1.5T| |Acquisition|3D preferred|2D or 3D|2D or 3D| |Slice thickness|3D:1mm isotropic,# 2D:≤ 3mm, no gap|Sagittal≤3mm,no gap;axial≤5mm,no gap|≤2-3mm,no gap| |In-plane resolution|≤1mmx1mm|≤1mmx1mm|≤1mmx1mm| |Coverage|Whole brain|Whole cord|||Optic nerves and optic chiasm| |Axial scan orientation|Subcallosal or anterior-posterior commissure planet|Perpendicular to sagittal as spinal cord orientation|Align to optic nerve and optic chiasm| |Core sequences|3D T2 FLAIR; axial T2-weighted(single or dual echo) 3D T2* gradient-recalled-echo(echo- planar imaging or optimised SWI)## for CVS; and post-gadolinium-based contrast agent axial mildly T1-weighted#|Two complementary sagittal sequences (ie,T2-weighted, proton density, short tau inversion recovery, PSIR, or MP[2]RAGE); axial 2D T2-weighted spin echo/gradient echo (or multiplanar reconstruction from MPRAGE) at least covering the cervical segment; post- gadolinium-based contrast agent sagittal moderately T1-weighted;§5 note: do not use FLAIR or myelographic sequences(very heavily T2-weighted, eg, CISS)|Coronal fat suppressed T2-weighted or short tau inversion recovery; post-gadolinium-based contrast agent coronal fat suppressed T1-weighted| |Additional sequences|3D T2* gradient-recalled-echo(3D-echo- planar imaging or SWI) for PRL;↑↑↑↑↑|After 100000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000||

CISS=constructive interference in steady state.CVS=central vein sign. DR=double-inversion recovery. DML=diffusion-weighted imaging. FLAIR=f-attenuated inversion recovery. MPRAGE=magnetisation-prepared rapid acquisition gradient echo. MP2RAGE=magnetisation prepared 2 rapid acquisition gradient echo. SWI=susceptibility-weighted imaging. PRL=paramagnetic rim lesions.PSIR=phase sensitive inversion recovery. 3D=3 dimensional. 2D=2 dimensional. 3D=500 of 3T compared with 1.5T for spinal cord imaging. Isotropic preferif, if over-contiguous(through-plane and in plane) then not more than 1.5 mm with 0.75 mm overlap.$Diffusion-weighted imaging. slice thickness should be at least 5 mm with more than 10-5% slice. Gap in asseorii as much of the cervical cord as possible.[1.77] and thororobalombar spinal cord, including conus. $\dagger$ 2D acquisition(prescribed) or 3D reconstruction(reformatted) for axial oblique slice. $\ddagger$ Reconstructed as sagittal and axial. $\S$ The 3D gradient-recalled echo should have sufficient T2* weighting and resolution to detect central veins and a low flip angle to ensure lesions are visible. if SWI post-processing is used,enhanced magnitude images are optimal for CVS detection. FLAIR* postprocessing can null high signal in CSF for better conuscity of lesions. Filtered phase or quantitative susceptibility mapping postprocessing of the same acquired images allows detection of PRL and is recommended to avoid subsequent rescanning. The CVS is best detected at field strengths of at least 3T but can also be seen at 3T can also be seen at 1.5 T, especially when scanned after gadolinium-based contrast agent administration. For details see appendix(5p,6,10).100.101.100/kg bodyweight gadolinium-based contrast agent. Ensure an at least 5 min delay. Additional gadolinium-based contrast agent is not needed if cord imaging follows brain imaging.|||If not already performed. Filtered phase or quantitative susceptibility mapping images are necessary for PRL detection. A low flip angle is not required but can help with lesion detection on accompanying magnitude or enhanced magnitude images. PRL are best detected at field strengths of at least 3T but can also be seen at 5T. GADolinium-based contrast agent is not required(appendix p 5). DIR or PSIR use for cortical lesion detection.

Table 2: Standardised MRI protocol parameters

echo)21 for identifying cortical lesions and monitoring brain volume changes, and diffusion-weighted imaging,which can identify acute ischaemia as a differential diagnosis. However, diffusion-weighted imaging might not be specific, as acute multiple sclerosis ions can also show diffusion restriction as detected in acute ischaemia.22

Full spinal cord coverage(cervical to conus) is recommended with field strength of at least 1·5 T, slice thickness of 3 mm, and in-plane resolution of maximum 1x1 mm.Spinal cord imaging is technically demanding,requiring multi-array coils and prevertebral saturation slabs. Two complementary sagittal sequences(any combination of: T2 fast-spin-echo, proton density, short tau inversion recovery, and 3D inversion-prepared T1 are essential to distinguish small multiple sclerosis lesions from artifact, with axial slices at least through the cervical region with moderately T2-weighted spin-echo or T2* gradient echo.° FLAIR and heavily T2-weighted sequences(ie, sequences used for MRI myelography)should be avoided for spinal lesion detection.No additional gadolinium-based contrast agents

administration is required if the spinal cord imaging is done immediately after gadolinium-based contrast agents-enhanced brain imaging, and moderately T1-weighted sequences are recommended to demonstrate gadolinium-based contrast agents-enhancing lesions.

Optic nerve MRI sequences, required if there is an initial presentation of optic neuritis, include at minimum coronal fat-suppressed T2-weighted or short tau inversion recovery sequences. When gadolinium-based contrast agents are given in cases of acute optic neuritis, post-gadolinium-based contrast agents coronal fat-suppressed T1-weighted sequences are recommended.Coverage should include the optic nerve and the optic chiasm, with coronal planes oriented perpendicular to the optic nerve. When axial images are added, they should align with the optic nerve and chiasm. In-plane resolution should be maximum 1x1 mm, with slices of thickness of maximum 2-3 mm and no gap. For improved lesion detection, additional sequences, such as 3D-DIR, can be incorporated, which might increase sensitivity particularly for asymptomatic lesions.24-26

Neuroradiology, University College London Hospitals,National Hospital for Neurology and Neurosurgery,Neuroradiological Academic Unit, University College London, Institute of Neurology,London,UK(Prof T Yousy MD); Department of Medicine(Neurology),University of British Columbia,Vancouver,BC,Canada(Prof A Traboulsee MD); Mellen Center for Multiple Sclerosis,Department of Neurology,Cleveland Clinic Lnered College of Medicine of Case Western Reserve University, Cleveland,OH,USA(Prof D Ontaneda MD);Section of Neuroradiology,Department of Radiology,Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona,Barcelona,Spain(A Rovira MD)

Correspondence to:Prof Frederik Barkhof,Department of Radiology and Nuclear Medicine,Amsterdam UMC,Vrije Universiteit,Amsterdam, Netherands f.barkhof@amsterdamum.cnl\# Drar Halper died See Online for appendix For more on safety administration of contrast see https://www.esur.org/esur-guidelines-on-on-contrast-agents/

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Guidelines for the interpretation of MRI findings

The most usual source of misdiagnosis of multiple sclerosis is misinterpretation of MRI findings." Given the increasing reliance on MRI, in this section, we define the relevant imaging characteristics of MRI lesions in multiple sclerosis to help avoid misinterpretation. ${}^{28}$

MRI characteristics of typical brain multiple sclerosis lesions and their diagnostic use

Brain multiple sclerosis lesions asymmetrically affect the white matter of the cerebral hemispheres, the

brainstem, and the cerebellum, and involve the cortical and deep grey matter(mainly the thalamus; figure 2,appendix[pp 2-4]).29.30 Typically lesions are smaller than 1cm in diameter, although larger lesions can also occur.Lesions should generally be at least 3 mm in longest diameter. However, the required length of lesions depends on the location. For example, lesions of less than 3 mm located at the floor of the fourth ventricle, the outer margin of the pons, or in the corpus callosum can be considered demyelinating.32 Lesions smaller than 3 mm, rounded, deep in the white matter, especially in basal frontal areas and not demonstrating CVS, are non-specific(appendix p 9). Perivenular lesions might be ovoid in shape in the axial plane(Dawson's fingers),with their long axis perpendicular to the lateral ventricles.33 Periventricular lesions are in direct contact with the lateral ventricles, without intervening normal appearing white matter. Periventricular lesions include corpus callosum lesions that abut the ventricles. However,lesions that abut the lateral ventricles but are in the deep grey matter(eg, thalamus) are not considered periventricular.

Periventricular lesions are in direct contact with the lateral ventricles, without intervening normal appearing white matter. Periventricular lesions include corpus callosum lesions that abut the ventricles. However,lesions that abut the lateral ventricles but are in the deep grey matter(eg, thalamus) are not considered periventricular.

Juxtacortical or cortical lesions with typical morphology are a hallmark feature of multiple sclerosis and are rarely encountered in other conditions.29.34 Juxtacortical lesions affect the U-fibres, which are typically not affected in ischaemia. Cortical lesions that do not involve juxtacortical white matter are difficult to identify on conventional MRI, even at 3 T." 3D sequences such as DIR, PSIR, or MPRAGE can improve their visualisation.20.21

Infratentorial lesions involve the brainstem, cerebellar peduncles, and cerebellum. They preferentially affect the floor of the fourth ventricle, surface of the pons, intra-pontine trigeminal tracts, middle and superior cerebellar peduncles, periaqueductal grey matter, cerebellar matter and cortex, and medullary pyramids. ${}^{35}$

Deep white matter lesions are common in multiple sclerosis, but given their low specificity, the deep white matter is not considered as one of the characteristic anatomical locations within the diagnostic criteria for demonstrating DIS. Such lesions can, however,contribute to the diagnosis when they are gadolinium-based contrast agents-enhancing(which signifies DIT),harbour a CVS, or have a paramagnetic rim.

Gadolinium-based contrast agents enhancement in active multiple sclerosis lesions is a transient feature(median duration<4 weeks) that rarely persists beyond 2-3 months. ${}^{\circ}$ Lesions with enhancement for longer than 3 months should prompt consideration of an alternative diagnosis(eg, capillary telangiectasia). Enhancing lesions have a nodular or ring-like pattern; the ring can be partly open." Large enhancing lesions sometimes have a pseudotumour appearance, indicating the presence of mass effect(displacement) on nearby structures.The pattern of gadolinium-based contrast agents

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enhancement also depends on lesion age and timing after gadolinium-based contrast agents injection.

Finding non-enhancing and enhancing lesions on any scan indicates DIT. Finding new T2 lesions at any time during follow-up imaging also indicates DIT. New lesions should meet the size and other criteria discussed in this section, and care should be taken that they are not an artifact due to changes in MRI protocol or slice positioning. New T2 lesions do not necessarily have to be in the anatomical locations described for the fulfilment of the DIS criteria. When new T2 lesions are only found in the deep white matter, they ideally should be ovoid,involve specific regions such as the corpus callosum or temporal lobe,39 have a CVS, or be a paramagnetic rim,particularly in patients older than 50 years or with vascular risk factors.

Characteristics of the CVS and its use in the diagnosis of multiple sclerosis

The CVS identifies the perivenous distribution of multiple sclerosis lesions and can be detected with susceptibility-sensitive MRI sequences.40 The CVS is found in most multiple sclerosis lesions and is present early in the disease, including in clinically isolated syndrome(CIS),“RIS,” and in paediatric multiple sclerosis.43 Conversely, white matter lesions in common radiological mimickers of multiple sclerosis, including cerebral small vessel disease, AQP4+NMOSD, and migraine rate. rarely show the presence of a central vein.“

The CVS is defined as a thin(<2 mm diameter)hypointense line or dot, present in two perpendicular planes and running partially or entirely through the centre of a lesion(figure 2P, appendix p 10).45 The CVS should not be assessed in lesions of less than 3 mm in size, confluent lesions that contain multiple veins, or where veins are poorly visible(panel). Submillimetre isotropic acquisition is helpful for multiplanar visualisation of even the smallest lesions. ${}^{\text{{45}}}$

An optimal cutoff of at least 40-46% CVS-positive lesions best differentiates multiple sclerosis from common mimickers in meta-analysis studies. ${}^{16,47}$ Assessing the presence of the CVS in only a subset of lesions is recommended for efficiency of interpretation.The Select 6 method is considered positive when six or more white matter lesions are CVS positive; if fewer than ten white matter lesions are detected on MRI, the number of CVS positives lesions should be the majority.Select 6 shows good sensitivity and excellent specificity for multiple sclerosis. ${}^{48}$ In RIS, 95% of patients studied fulfilled the Select 6 rule. ${}^{48}$

The 2024 McDonald diagnostic criteria for multiple sclerosis incorporate the Select 6 rule as a highly specific method that can support a multiple sclerosis diagnosis in several scenarios: DIS with two or three anatomical locations, a single anatomical location in combination with either positive CSF or DIT, and in RIS with at least two anatomical locations(table 1). The Select 6 rule was

 Figure 2: Examples of brain MRI lesions in patients with multiple sclerosis

(A) Perventricular and typical ovoid shaped.(B) Periventricular anterior temporal lobe.(C) Pseudotumoural.(D) Callosal-septal(arrow).(E) Jxtacortical(arrow).(F) Intracortical(arrow).(G) Periauleductal(arrow).(H) Periphery of the pons and floor of the fourth ventricle(arrows).(I) Pyramids(arrow).(J) Deep white matter in the cerebellar hemisphere(arrow).(K) Middle cerebellar peduncle(arrow).(L) Thalamus(arrow).(M) Nodular enhancement.(N) Ring enhancement.(O) Open-irriengment enhancement.(P,Q) Central vein sign positive lesion on axial 3D segmented echo-planar imaging fluid-attenuated inversion recovery(FLAIR*(yellow square).(R) Sagittal 3D segmented echo-planar imaging FLAIR* and(5) corresponding axial native FLAIR.(T,U) Paramagnetic rim lesion on axial 3D segmented echo-planar imaging phase image(yellow square).(V) Axial FLAIR and(W) axial post-gadolinium-based contrast agent T1-weighted images(no enhancement detected).

incorporated as it was deemed feasible in clinical practice while retaining high specificity. Given the high prevalence of CVS-positive lesions in multiple sclerosis,most patients with DIS(ie, lesions in at least two anatomical locations) meet the Select 6 rule, which can be used in place of CSF positivity or DIT on initial MRI scan to make the diagnosis. On the other hand, it should be noted that the diagnostic criteria do not require assessment of CVS criteria; the diagnosis of

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Panel: Definition of central vein sign and paramagnetic rim lesions

Central vein sign(CVS)45

•Detected using magnitude susceptibility-sensitive images

•Appears as a single thin(<2 mm) hypointense line or small hypointense dot

•Can be visualised in at least two perpendicular MRI planes,and appears as a thin line or dot in at least one plane

Runs partly or entirely through the lesion

Is positioned centrally in the lesion(that is, located approximately equidistant from the lesion's edges and passing through the edge at no more than two places),regardless of the lesion's shape

•Exclusion criteria: lesion is<3 mm in diameter in all planes;lesion merges with another lesion(confluent lesions); lesion has multiple distinct veins; or lesion is poorly visible(owing to motion or other MRI-related artefacts)

Paramagnetic rim lesions46

•Detected using phase susceptibility-sensitive images

•A discrete rim with paramagnetic properties that is continuous around at least two-thirds of the outer edge of the white matter portion of the lesion(excluding any cortical or ependymal border), on the slice of maximum visibility

The rim colocalises with the edge of all or part of a lesion core that is hyperintense on T2-weighted images; in case of

large T2-lesions, detection of the paramagnetic rim lesion core can be facilitated by also looking at a more discernible hypointense core on T1-weighted images

● The rim(or part of it) is discernible on at least two consecutive slices(2D acquisition) or in two orthogonal planes(3D acquisition)

● The core of the lesion colocalises with all or part of a T2-hyperintense lesion that does not enhance on T1-weighted post-gadolinium-based contrast agent images*

● Exclusion criteria: veins running alongside the rim that might resemble a rim. Red flags and cautions: small paramagnetic or diamagnetic structures(eg, iron-laden ferritin or hemosiderin dots, veins, and myelin debris);lesions showing magnetic dipole artefacts(often best seen in coronal or sagittal reformations); and anatomical regions with susceptibility artefacts(much of the anterior temporal lobes, orbitofrontal cortices, and infratentorial brain)

*If post-gadolinium-based contrast agent MRI is not available, a paramagnetic rim lesion should only be defined as such when the corresponding lesion was already present on a T2-weighted scan acquired at least 3 months before. If both post-gadolinium-based contrast agent MRI and a previous scan are not available, a paramagnetic rim lesion should be marked as possible, and its chronicity should be confirmed with a scan acquired at least 3 months later.

multiple sclerosis can be established even if the Select 6 rule is not met. However, given the data on CVS prevalence, we urge caution in diagnosing multiple sclerosis if only a minority of lesions are CVS positive.A recommended MRI protocol for CVS detection is provided in table 2 and the appendix(pp 5-6, 10-12).

Characteristics of paramagnetic rim lesions and their use in the diagnosis of multiple sclerosis

PRL are a distinctive feature of multiple sclerosis(figure 2T-X, appendix pp 11, 12, table 3), reflecting iron-containing microglia surrounding chronic-active white matter lesions, and portendp poor prognosis.They are highly specific to multiple sclerosis.50 The formation of the paramagnetic rim occurs within months after lesion inception, with larger lesions and lesions appearing in older individuals more likely to be a paramagnetic rim.51 PRL have also been documented in cases of paediatric-onset multiple sclerosis,52 and in individuals with RIS.53 Once established, PRL tend to persist, with an estimated half-life of 7-10 years."Detection of PRL is most efficient using high-field MRI scanners, particularly at 3 T, although they are also discernible at 1·5 T.55

Susceptibility-sensitivity imaging for PRL necessitates the use of gradient-echo pulse sequences, with phase images being recommended alongside magnitude or phase-enhanced magnitude images. Variants of

susceptibility-sensitive imaging, as a standard product sequence on major MRI platforms, can detect PRL.Nevertheless, saving phase images alongside susceptibility-weighted imaging-type reconstructions,which combine magnitude and phase images, is advised. We provide a recommended MRI protocol for PRL detection(appendix pp 5-6, 11-12).

For diagnostic purposes, only unequivocal PRL should be considered,6 as defined in the panel. Despite evidence for the specificity of PRL,50,56 considering that the experience of neuroradiologists in identifying such lesions is not yet widespread, their inclusion in the 2024 criteria is limited to an adjunctive role, in combination with CSF findings or DIT, when lesions in only a single anatomical location are present. PRL are not required to be in one of the typical anatomical locations of the DIS criteria, and PRL in the deep white matter, which are relatively common,56 can be considered.

MRI characteristics of optic nerve lesions and differentiation from other diseases

Although optic neuritis is usually diagnosed clinically,imaging of the optic nerve can be valuable to rule out alternative diagnoses and inform about the severity of optic nerve damage. Optic nerve imaging is particularly relevant when the clinical presentation deviates from typical multiple sclerosis-related presentations, such as absence of pain, severe visual loss, simultaneous

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|Location|Multiple sclerosis|AQP4+NMOSD|MOGAD| |---|---|---|---| |Optic nerve|Unilateral involvement(bilateral in<5\%; short lesions; anterior involvement(intraorbital and intracanalular segments); optic nerve swelling at lesion site frequent in the acute phase; optic disc swelling or lesion site frequent in the acute phase; optic disc swelling or lesion site frequent in the acute phase; optic disc swelling at lesion site very frequent in the acute phase; optic disc swelling or enhancement infrequent; and perineuritis extremely rare|Simultaneous bilateral involvement(15-35% of patients); longitudinally extensive(more than 50% of the optic nerve length); posterior involvement(mainly the intracranial segment); optic nerve swelling at lesion site very frequent in the acute phase; optic disc swelling or enhancement infrequent; and perineuritis extremely rare|simultaneously bilateral involvement(30-60% of cases); longitudinally extensive(>50% of the optic nerve length); anterior involvement(intraorbital segment) with variable extension to other optic nerve segments(intracanalicular, in the acute phase; optic disc swelling at lesion site frequent in the acute phase; optic disc swelling or enhancement(20-50% of cases); and perineuritis with orbital fat stranding(50% of cases)| |Optic chiasm|Rarely involved|Occasional(20%), usually isolated|Occasional(15% of patients) and often as a result of extension of a longitudinally extensive optic nerve lesion| |Associated brain lesions|Common and with typical multiple sclerosis|Frequent, rarely showing multiple sclerosis-|Normal brain MRI in approximately 50% of cases, rarely showing multiple sclerosis-typical features| |AQP4+NMOSD=aquaporin-4 antibody positive neuromyelitis optica spectrum disorder.MOGAD=myelin oligodendrocyte glycoprotein antibody-associated disease. Table 3: Characteristic MRI features of the anterior optical pathways that differentiate multiple sclerosis, AQP4+NMOSD, and MOGAD||||

bilateral involvement, progression of visual loss or pain beyond 2 weeks, or insufficient recovery after three weeks.

Imaging of the optic nerves in acute and subacute optic neuritis typically reveals increased T2-weighted signal intensity, often accompanied by swelling,particularly when done within 3 weeks of onset. These MRI features, which reflect demyelination and inflam-mation, can be observed in more than 90% of people with acute optic neuritis. MRI lesions in multiple sclerosis-related optic neuritis typically involve a unilateral short segment of the optic nerve(<50% of the optic nerve length).88 Optic nerve MRI lesions primarily affect the intracarialcular and intraorbital segments but rarely involve the intracarialcular segment or the optic chiasm. The presence of longitudinally extensive lesions, chiasmal involvement,or theirneuritis should raise suspicion of alternative diagnoses, such as AQP4+NMOSD or MOGAD.

More sensitive MRI sequences than conventional fat-saturated T2-weighted or STIR sequences might enhance the detection of demyelinating lesions in the optic nerves. 3D-DIR seems particularly effective,showing high sensitivity and specificity in identifying both acute and chronic optic nerve inflammatory demyelinating lesions in individuals with a history of acute or previous episodes of optic neuritis.24,25 Additionally, 3D-DIR can detect optic nerve signal abnormalities in approximately 40% of individuals with multiple sclerosis who have no previous clinical history of optic neuritis.25,59,60 However, 3D-DIR cannot be considered as a core sequence in the MRI protocol for optic nerve imaging as it is not universally available.

Gadolinium-based contrast agents-enhanced fat-suppressed T1-weighted images are useful in evaluating multiple sclerosis-related acute optic neuritis cases. The pattern and extent of enhancement can help suggest alternative diagnoses, such as AQP4+NMOSD or MOGAD, and non-inflammatory conditions like extrinsic or compressive lesions.61 We provide an overview of the characteristic MRI findings in the

anterior optical pathway that help differentiate between multiple sclerosis, AQP4+NMOSD, and MOGAD(table 3, appendix p 13).

Characteristics of MRI spinal cord lesions and differentiation from other diseases

Spinal cord lesions are hyperintense on proton density, T2-weighted, T2*-weighted, and STIR pages and hypointense on heavily T1-weighted images such as MPRAGE and PSIR. Spinal cord lesions can occur at any level and usually span less than one vertebral segment on sagittal images. Multiple short-segment lesions are typical lesions of multiple sclerosis and do not occur in normal aging or people with cerebrovascular disease.7 Multiple sclerosis cord lesions are typically sharply demarcated and can have associated localised spinal cord volume loss. However, acute inflammatory lesions can also be ill-defined and have mild localised mass effect. By contrast, active lesions in AQP4+NMOSD and MOGAD tend to be longitudinally extensive(>3 vertebral segments) and are ill-defined with associated mass effect. Involvement of the conus is suggestive of MOGAD(table 3).

On axial T2-weighted and T2*-weighted images,multiple sclerosis spinal cord lesions are often round or wedge-shaped, involve the peripheral white matter, and might extend into the central grey matter. By contrast,ions in AQP4+NMOSD and MOGAD are located centrally in the cord, spare the peripheral white matter,and might even be limited to the central grey matter-the so-called H-sign seen especially in MOGAD in the acute phase. In AQP4+NMOSD, there might be cyst-like components, referred to as bright spotty lesions. ${}^{63}$

Gadolinium-based contrast agents enhancement of active spinal cord multiple sclerosis can appear nodular or ring-like. AQP4+NMOSD lesions can show an elongated ring-like enhancement in the sagittal plane. MOGAD lesions can have ring-like or patchy enhancement.In the acute phase,enhancement is less frequent in MOGAD than in AQP4+NMOSD or

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multiple sclerosis.62 Enhancement in spondylotic spinal cord compression can be persistent and limited to a horizontal band throughout the spinal cord(pancake sign)“ or at the periphery of one side of the spinal cord(croissant sign).65 In neurosarcoidosis, enhancement might extend longitudinally, mostly affects the pia and adjacent spinal cord tissue, and can invade the posterior sulcus, which is best seen on axial images(trident sign).66 Neurosarcoid-related enhancement might persist for several months.

For the fulfilment of the 2024 McDonald diagnostic criteria for multiple sclerosis, finding at least one typical short-segment lesion is sufficient to contribute to DIS(and DIT in case of an enhancing lesion). In individuals with a progressive onset, DIS can be met without lesions in other anatomical locations when at least two spinal cord lesions are present.' Not finding spinal cord lesions should trigger consideration of alternative diagnoses,especially in older patients and individuals with cardiovascular risk factors.

MRI diagnostic considerations in specific situations

The use of MRI findings in the diagnosis of multiple sclerosis requires special consideration in late-onset multiple sclerosis(defined as clinical onset at age>50 years),67 people with vascular and other comorbidities(eg, hypertension, hypercholesterolemia,diabetes, and obesity), people with migraine, in paediatric-onset multiple sclerosis(POMS), and in individuals living outside Europe or North America.

Late-onset multiple sclerosis, vascular comorbidities,and migraine

Deep and some periventricular white matter lesions are frequent with normal ageing, vascular comorbidities,and migraine.68-71 Thus, detecting at least three periventricular lesions in patients with CIS aged 45 years or older improves specificity of multiple sclerosis diagnosis, preserving accuracy and slightly reducing sensitivity, compared with a single peri-ventricular lesion.72,73 Cortical lesions, common in multiple sclerosis, have not been observed in migraine.71,74 In older individuals with vascular risk factors, peripheral pontine lesions make multiple sclerosis more likely than central pontine lesions.75 Incidental T2-hyperintense lesions are exceedingly rare in the spinal cord.

The proportion of CVS-positive lesions in people with multiple sclerosis decreases with age and vascular comorbidities, particularly hypertension. However, the presence of more than 40% of lesions that are CVS positive correctly identifies nearly all people with multiple sclerosis, and the Select 6 rule remains valid even in older individuals.7% Additional studies evaluating the diagnostic performance of PRL in older people with multiple sclerosis, migraine, and vascular comorbidities

are needed, and PRL have not been reported in healthy ageing.56

POMS

Based on the good performance of previous McDonald diagnostic criteria for multiple sclerosis in POMS,the 2024 criteria adopt a common framework for adult and paediatric multiple sclerosis. Early studies of CVS PRL in small POMS cohorts have reported variable results,43,52,77 indicating the need for additional research.No study has evaluated the performance of the Select 6 rule in POMS, hence a conservative threshold of at least 50% of lesions positive for the CVS is recommended when CVS is assessed for diagnosis. Having at least 40% CVS lesions was associated with a greater likelihood to develop disability progression over the subsequent 5 years and a higher relapse rate.78 Few studies have evaluated the presence of PRL in POMS.52,79,80 Based on these studies, the majority of POMS have at least one PRL, which is 100% specific for POMS versus other immune-mediated acquired demyelinating syndromes.

Populations outside North America and Europe

In Latin America and Asia, AQP4+NMOSD is more prevalent than multiple sclerosis, compared with prevalences in Europe and North America, so atypical radiological features should prompt antibody testing.There are few studies evaluating the performance of the CVS and PRL outside Europe and North America.However, scarce data suggest that the CVS has similar diagnostic performance to what has been observed in Europe and North America.82,83

Prognostic relevance of MRI findings in multiple sclerosis beyond diagnostic purposes

Although the focus of our recommendations is on multiple sclerosis diagnosis, initial MRI examinations can also guide prognosis and serve as a reference for monitoring future disease activity. Several features on the initial brain MRI provide prognostic indicators of long-term disability. Unfavourable findings include:a large number(>20) and volume of T2-weighted lesions;the presence of brainstem, cortical, or spinal cord lesions; multiple gadolinium-based contrast agents-enhancing lesions; reduced whole brain volume or ventricular expansion; and regional brain atrophy(eg, corpus callosum, thalamus, or brainstem).73,85-87 Lesion features that portend a poor prognosis include hypointensity on mildly T1-weighted images,88 presence of PRL, and a high proportion of lesions with the CVS.Several studies show that the presence of at least four PRL is associated with greater disability.89,90 The presence of spinal cord lesions and tissue loss are strong predictors of long-term disability accrual89,91,92 and can occur in the absence of clinical manifestations.

Short-term follow-up MRI also carries major prognostic value. The occurrence of new lesions, specifically in

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some anatomical locations(ie, spinal cord and brainstem)strongly predicts long-term disability.93 These data are supported by the finding that early new lesion development in the spinal cord and brainstem is associated with increased risk of worse disease course 15 years after the diagnosis in people with CIS.32 The presence of gadolinium-based contrast agents-enhancing lesions early in the disease is associated with increased relapse rates over time but only weakly with disability accrual over the short term. However, the presence of new enhancing lesions in the first years after CIS presentation is a strong predictor of long-term disability accrual at 15 years.92 Brain volume loss early in the disease course is associated with long-term accumulation of disability in people with relapsing-remitting multiple sclerosis.95.76 Even in RIS, brain atrophy can be present and might serve as a prognostic marker; however, larger studies to document the association of brain volume loss and clinical outcomes in RIS are needed. Finally, MRI is also a useful tool for disease monitoring of treatment,and the initial diagnostic brain and spinal cord imaging can be used as a reference to monitor the development of active lesions and possibly also brain volume.98-100

Recommendations for a standardised and structured radiological diagnostic reporting and for the communication of MRI findings

The use of template-driven structured MRI reports for multiple sclerosis can streamline the radiological reporting process, ensure consistency, and enhance communication between radiologists and referring physicians. ${}^{101,102}$ A good communication between referring practitioners and reporting radiologists is crucial for accurate diagnosis.

We recommend that key information is included in the MRI requisition form completed by the referring practitioner and incorporated in the radiology reported completely by the radiologist(appendix pp 7,8). To aid in the radiological interpretation and diagnostic reporting,the clinical question and the purpose of the MRI requested by the referring practitioner should be clearly stated on the request form. Gadolinium-basedcontrast agents should be requested for the initial MRI, whereas follow-up scans for diagnostic purposes can be done without gadolinium-based contrast agents(as new T2-FLAIR lesions suffice to show DIT).

The radiology report(appendix pp 7,8) should describe lesions with respect to number, location, size, and morphology. Universal nomenclature should be used, for example lesions are best described as periventricular or deep white matter rather than subcortical. The conclusion of the radiology report should define whether the MRI findings fulfil radiological aspects of the diagnostic criteria.The report should also include a recommendation regarding possible follow-up brain MRI imaging to establish DIT or assess additional MRI features not assessed at initial imaging. Finally, the report should

Search strategy and selection criteria

References for this Personal View were identified by reviewing our personal files and through searches of PubMed for articles published in English between Sept 1,2021 and Feb 1,2025,with the terms“multiple sclerosis OR MS”,“guidelines”,diagnosis", and“magnetic resonance imaging OR MRI".We reviewed reference lists of relevant articles and the articles for additional references.The final reference list was generated based on originality,reency, and relevance to the scope of this Personal View.

include a general interpretation of the MRI findings as being typical or atypical for multiple sclerosis.

Automated quantitative tools that provide the location,volume and number of(new) lesions, and global and regional brain volume quantification contextualised relative to normative reference populations can potentially improve the accuracy and objectivity of MRI assessments.These tools are now commercially available;however, their usefulness and benefit will require more extensive real world clinical validation and in-use evaluation.

Conclusions and future directions

In the 2024 McDonald criteria for the diagnosis of multiple sclerosis, MRI plays an increasingly important role, allowing for an earlier and more specific diagnosis of multiple sclerosis than former diagnostic criteria.Optic nerve imaging plays a crucial role, serving as a fifth anatomical location for DIS. Multiple sclerosis can now be diagnosed without further evidence when DIS is shown in at least four anatomical locations and in people with RIS, making it even more important to appropriately interpret MRI scans and recognise atypical features.With the addition of new imaging criteria, such as CVS and PRL-although not necessary in many cases-radiologists, neuroradiologists, and neurologists will need to familiarise themselves with their definitions and characteristic imaging features. The diagnostic value of CVS and PRL in paediatric populations and outside North America and Europe remains to be fully established through further study. We expect that sequences and postprocessing optimised for the detection of the CVS will soon be more widely available.Further work is needed to understand the value of ultra-high field(eg, 7 T) as well as ultra-low field(eg, 0·064 T)in the diagnosis of multiple sclerosis.104 With the great number of MRI features contributing to a diagnosis of multiple sclerosis in the 2024 revisions, it will be important to concisely report and communicate MRI results, allowing their integration with clinical and other paraclinical findings.

#

FBar,DSR,JO,ATr,DO,and AR participated in meetings for discussions and reaching consensus, all prepared the initial draft of

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manuscript, reviewed the draft manuscript, and approved the manuscript.MAR,DKBL,PS,CJA,FBag,PAC,OC,MDG,DA,NDS,CE,MF,CG,JH,RGH,CG,SG,LK,CL,SDN,XM,SM,NS,ATo,JW,TY,JS-G,and AIT participated in in meetings for discussion and reaching consensus, reviewed the draft manuscript, and approved the manuscript.

Declaration of interests

FBar is supported by European Commission, Medical Research Council,NIHR Biomedical Research Centre at University College London Hospitals,GE Healthcare, Roche,and Alzheimer's Disease Data Initiative(paid to institution); is a consultant for Combinostics, IXICO,and Roche; and participates in Steering Committees or Data safety Monitoring Boards for EISAI, Biogen, Prothena, and Merck. DSR is supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, US National Institutes of Health(NIH); and he has received research support from Abata Therapeutics and Sanofi. JO holds the Waugh Family Chair in MS Research at St Michael's Hospital, University of Toronto; has received funding grant from MS Canada, Brain Canada, the National MS Society, Biogen-Delec, Roche,and EMD-Serono; and has received personal compensation for consulting or speaking from Biogen-Idec, BMS, EMD-Serono, Lilly,Horizon Therapeutics, Novartis, Roche, and Sanofi-Genzyme.MAR received consulting fees from Biogen, Bristol Myers Squibb,Eli Lilly,Janssen, and Roche; received speaker honoraria from Astra-Zeneca, Biogen, Bristol Myers Squibb, Bromatche, Celgene, Genzyme,Horizon Therapeutics Italy, Merck Serono SpA, Novartis, Roche, Sanofi,and Teva; and declares research support from the MS Society of Canada,the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosio Multipla. DKBLI is Emeritus Director of the UBC MS/MRI Research Group, which has received grant support for investigator-initiated studies from Genzyme and Roche; and has given lectures, supported by non-restricted education grants from Academy of Health Care Learning, Biogen, Novartis, Consortium of MS Centers, and Sanofi-Genzyme. PS receives research support from the National Institutes of Health, the National Multiple Sclerosis Society,the Department of Defense, and the Irwin Rautenberg Foundation.CJA receives grant support from the National MS Society, the National Institutes of Health, and the Keck School of Medicine; has received consulting honoraria for participation in advisory boards, data safety monitoring committee from MRI Adjudication Committee for Horizon Therapeutics,TG Therapeutics,EDM Serono,Genogenet, and Zenas Biopharma; and for participation in educational events for Sanofi Genzyme,MJH Life Sciences, Efficient, and Spire Learning.FBag is supported by the National Institute of Health, The VA Healthcare Administration, the National MS Society and the Voros Innovation and Impact Funds; is a consultant for Sanofi; and participates in Steering Committee and Advisory Boards for Merck-Serono and Sanofi. PAC has received funding from the NIH, National Multiple Stereosis Society, US Department of Defense, Genentech, and the Myelin Repair Foundation; and has received consulting honoraria for serving on scientific advisory boards for Novartis, Isordia, and Ellis Lilly. OC has received grant funding from Nanof., Isordia, and Elli LLC. OC has received funding from Novartis, Roche, and Biogen. MGD received grant Trust and has received personal compensation for consulting or speaking from Novartis, Roche, and Biogen. MGD received grant support from Novartis, Bristol Myers Squibb, Mapi Pharma, and Merck Serono; and declares consulting from Bristol Myers Squibb and Mapi Pharma.GCD has received research funding from the Oxford Biomedical Research Centre, Medical Research Council(UK), National Health and Medical Research Council, UK MS Society, Department of Defense, Oxford-Quinniac-Trity Health Of New England Partnership, Rosetoresets, and the Multiple Sclerosis Research,Treatment, and Education; and has received honoraria for consulting or speaking for Novartis, Merck, the MS Academy, American Academy of Neurology, and the Wellcome Trust. NDS has received honoraria from Biogen, Celgen,(Bristo Myers Squibb, EMD SERon, Genzyme,Imunic, Novartis, Roche, and Teva for consulting services, speaking and travel support serves on advisory boards for Biogen, Genzyme,Imunic(the healthcare business of Merck), Darmstadt, Germany,Novartis, and Roche; has received research grant support from the Italian MS Society; and is co-founder of Sena Isingroon, CE has received

funding for travel and speaker honoraria from Biogen, Bayer, Celgene,Merck, Novartie, Roche, Shire, Genzyme and Teva Pharmaceutical Industries/Sanofi-Avantis; received research support from Merck Serono,Biogen,and Teva Pharmaceutical Industries/Aanofi-Avantis; and has served on scientific advisory boards for Bayer, Biogen, Celgene,Celmer,Novartis, Roche, and Teva Pharmaceutical Industries/Sanofi-Avantis. MF received compensation for consulting services from Alexion, Almiral, Biogen, Merck, Novartis, Roche, and Sanofi; Deares speaking activities from Bayer, Biogen, Celgene, Chiesi Italia SpA,Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili,Novartis, Novo Jrod, Roche, Sanofi, Takeda, and TEVA; participation in Advisory Boards for Alexion, Biogen, Bristol-Myers Squibb, Merck,Novartis, Sanofi,Aunents,Sanofi,Sanofi-Genzyme,and Takeda;scientific direction of educational events for Biogen, Merck, Roche,Celgene, Bristol-Myers Squibb, Lilly, Novartis, and Sanofi-Genzyme; and the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla. CGo is supported by the Swiss National Science Foundationgrantport(PP00P3_176984), the Stifung zur Forderung der gastroenterologischen und allgemeinen Klinischen Forschung, University Hospital Basel, and the Research Center for Clinical neuroimmunology and Neuroscience; the employers of Cristina Granziera have received the fees(used exclusively for research support) from Siemens, GeNeuro, Genzeu, Genzyme-Siofi, Biogen, and Hoffmann La Roche, the employers of Cristina Granzia advice board and consultancy fees from Actelion,Genzyme-Sanofi, GeNeuro, McNeuro, Merck, Biogen, and Hoffmann La Roche, Biogen, and Hoffmann La Roche, as well as speaker fees from Genzyme-Sanofi, Novartis, GeNeuro, Marke, Biogen, and Hoffmann La Roche, Roche, and Benofra, Roche, Genentech, and Data Frung, Roche, Boine, and and Furthermore from Roche, Genentech, and Atara, GaGe has received fees as a speaker or as an advisory board member from Almiral, Biogen, Merck, Roche, Novartis, Sandoz,AstraZeneca, Viatrias,Sanofi, Jansen, and Bristol Myers Squibb, SG has received grant funding from the National Institutes of Health, National Multiple Stereosis Society, and Genentech; and has received consulting fees from Continuum Therapeutics and Kiniksa Pharmaceuticals. LK received research support to the institution(University Hospital Basel, Basel,Switzerland) including steering committee, advisory board, and consultancy fees from Actelion(Janssen), Bayer, Biogen, Bristol Myers Squibb, GSK, Jansen, Japan Tobacco, Merck, Novartis, Roche, Sanofi, and Tong Therapeutics; speaker fees from Bayer,Biogen, Merck, Norwartis, Roche, and Sanofi; support of educational activities from Allegor, Bayer, Biogen,CSL Behring, Desitin, Merck,Nenurostis, Pfizer, Roche, Sanofi, Shirea, and Teva; license fees for Neurostatus platform access; and grants from Bayer, Biogen, EU,Innowiss, Mcer, Novartis, Roche, Swiss Multiple Sclerosis Society, and Swiss National Research Foundation. CL reports funding support from the Natural Sciences and Engineering Research Council of Canada, the Craig H. Nielsen Foundation, the International Collaboration on Repair Discoveries, and the University of British Columbia. SDN reports grants or contracts from Biogen, Roche, Genentech, Lunbeck, Sanofi, National Multiple Sclerosis Society, Department of Defense, and Patient Centered Outcomes Research Institute; personal compensation for consulting from Biogen, Roche, Genentech, Bristol Myers Squibb, Novartis, and TG Therapeutics; is study lead PI for a Roche clinical trial program;and reports research support from the Stiff Person Syndrome Research Foundation.XM's institution has received compensation for lecture honoraria and travel expenses, participation in scientific meetings,clinical trial steering committee membership, or clinical advisory board participation in recent years from Abbv, Actelion, Alexion, Bial PD,Biogen, Bristol-Myers Squibb/Celgene,EMD Serono, Genzyme,Hoffmann-La Roch, Immunic Therapeutics, Janssen Pharmaceuticals,Medday, Merck, Mlyman, Nervgen, Neuraxpharm, Novartis, Peervoice,Samsung-Bioys,Sandoz,Sanofi-Genzyme,Teva Pharmaceutical, TG Therapeutics, Exmeded, Medscape, European Committee for Treatment and Research Multiple Stereosis, Multiple Sclerosis International Federation, and National Multiple Sclerosis Society or any of their affiliates. In the last 3 years, SAM has served as an advisory board member or receiving consulting fees from Biogen Idec, BMS/Celgene,EMD Serano, Novartis, Roche, and Sanofi Genzyme; participated in a

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speaker's bureau for Biogen Idec, BMS/Celgene, EM Serono, Novartis,Roche, and Sanofi; has received research support from Biogen Idec. EMD Serono, Novartis,Roche, Sanofi Genzyme, MS Canada, Canadian Institute of Health Research, and National Multiple Stereosis Society, has participated as a site investigator in clinical trials sponsored by BMS/Celgene, EMDE, Serono, Novartis, Roche, and Sanofi; Roche, and Sanofi; and has acted as site PI for multi-center trials funded by BMS/Celgene,EMD Serono, Roche, and Sanofi; Roche, and Sanofi; and has acted as site PI for multi-center trials funded by BMS/Celgene,EMD Serono, Roche, and Sanofi; Newurology, Multiple Stereosis Journal, and Frontiers in Neurology;receives research support from the Dutch MS Research Foundation,Eurostars-EUREKA, Association pur la Recherche sur la Scherose en Plaque,Amsterdam Neuroscience,MAGNIMS, and ZonMW(Vidi grant,project number 09150172010056); and has served as a consultant for or received research support from Atara Biotherapeutics, Biogen, Celgene/Bristol Meyers Squibb,EIP,Sanofi,Sanofi,Meday,and Merck.NS receives research funding from the NIH, National MS Society, and Patient Centered Outcomes Research Institute. ATo has been supported by recent grants from the Medical Research Council(MR/S026088/1National Institute for Health and Care Research Biomedical Research Centre(541/CAP/OC/818837), and RoseTrees Trust(A1332 and PGL21/10079);speaker honoraria from Merck, Biomedia, Sereno Symposia International Foundation, Bayer, and At the Limits; was reimbursed for meeting expenses from Merck, Biogen Idec, and Novartis; and was the UK PI for two clinical trials sponsored by MEDDAY pharmaceutical company(MD1003 in optic neuroplassy(MS-ON-NTC22024) and progressive MS[MS-SPI2- NCT02936037]). JW has research support from Biogen; is a consultant for BMS; and has been a speaker for Biogen, EMD Serono,and Sanofi; S-G received compensation in the last 24 months for consulting services and speaking honoraria from BMS, Sanofi, Merck, and Roche; is scientific director of Revista de Neurologia and member of the editorial committee of Multiple Stereosis Journal, for which he receives an honoraria; and he has received research Committee from Fondo de Innovation on Salvo DINO for Seidenal in Salvo P119/00590 and P112/00750) from Institute de Salvo Carlos III, Spain, AT is the MS Canada Research Chair,has received honoraria from Sanofi for membership data in monitoring committee and clinical trial steering committee and from Roche for clinical trial steering committee membership; and declares research funding from Roche, NIH, and MS Society of Canada. has received research support from the National Institutes of Health, National Multiple Stereosis Society, Patient Centered Outcomes Research Institute, Race to Erase MS Foundation, Genentech, Zymegen, Bysteins, Martoys Squibb, and Novartis; and declares consulting from Bristol Myers Squibb,Genentech/Roche, and Continuum Therapeutics,AR serves on scientific boards for Nowartis, Sanofi, Softin, Synthetic MR, Roche, and Biogen; has received honoraria from Bayer, Sanofi-Gezyme.Rermer-Sceroa,Teva Pharmaceutical Industries, Novartis, Roche, Bristol-Myers and Biogen; is the CMO and co-founder of TensorMD; and receives research support from Fondo de Investigacion en Salud(P1019/95090 and P1215/01283). In formut de Salud Carlos III, Spain.All other authors declare no competing interests.

Acknowledgments

Daniel S Reich's contributions were made as part of his official duties as an NIH federal employee, are in compliance with agency policy requirements, and are considered Works of the US Government.However, the findings and conclusions presented in this paper are those of the author and do not necessarily reflect the views of the NIH or the US Department of Health and Human Services.

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