Imaging Markers for Monitoring Disease Activity in Multiple Sclerosis
Multiple sclerosis (MS) is an immune-mediated disease affecting the central nervous system (CNS). Magnetic resonance imaging (MRI) has long been recognized as an important tool in the diagnosis of MS. It is increasingly recognized that in addition to its role in diagnosis, MRI can play a key role as a noninvasive tool for prognostication, disease monitoring, assessment of treatment efficacy, and safety monitoring of disease-modifying therapies (DMTs). A confluence of factors, including increased availability of MRI, development of improved MRI techniques, and increased availability of DMTs have contributed to the expanding role of MRI in MS clinical care. As the clinical use of MRI in MS expands, it is important that MRI protocols amongst clinical centers are standardized. Here, we summarize recent evidence supporting the use of MRI in clinical practice, summarize various clinical guidelines and recommendations for the use of MRI in MS disease monitoring, and provide our recommendations for standardized MRI protocols.
KeywordsMRI Multiple sclerosis Standardized protocols Disease monitoring Safety Treatment efficacy
Compliance with Ethical Standards
Conflict of Interest
David Kim declares that he has no conflict of interest.
Suradech Suthiphosuwan has received grants from Sanofi-Genzyme.
Aditya Bharatha has received honorarium for education lectures from Novartis, Biogen, and EMD Serono.
Jiwon Oh has received a grant from the MS Society of Canada, the National MS Society, grants and consultation fees from Biogen-Idec and Sanofi-Genzyme, and consultation fees from EMD Serono, Novartis, Roche, and Teva.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
References and Recommended Reading
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 5.• Rovira A, Wattjes MP, Tintore M, Tur C, Yousry TA, Sormani MP, et al. Evidence-based guidelines: MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis—clinical implementation in the diagnostic process. Nat Rev Neurol. 2015;11(8):471–82. doi: 10.1038/nrneurol.2015.106. These guidelines provide an up-to-date, evidence-based approach on the use of MRI in the diagnosis and management of patients with multiple sclerosis.CrossRefPubMedGoogle Scholar
- 9.•• Traboulsee A, Simon JH, Stone L, Fisher E, Jones DE, Malhotra A, et al. Revised recommendations of the consortium of MS centers task force for a standardized MRI protocol and clinical guidelines for the diagnosis and follow-up of multiple sclerosis. AJNR Am J Neuroradiol. 2016;37(3):394–401. doi: 10.3174/ajnr.A4539. This review provides the latest recommendations on standardized MRI protocols for use in the clincial management of multiple sclerosis.CrossRefPubMedGoogle Scholar
- 13.• Yousry TA, Pelletier D, Cadavid D, Gass A, Richert ND, Radue EW, et al. Magnetic resonance imaging pattern in natalizumab-associated progressive multifocal leukoencephalopathy. Ann Neurol. 2012;72(5):779–87. doi: 10.1002/ana.23676. This study highlights characteristic MRI findings of progressive multifocal leukoencephalopathy in natalizumab-treated patients with multiple sclerosis.CrossRefPubMedGoogle Scholar
- 20.Alcaide-Leon P, Pauranik A, Alshafai L, Rawal S, Oh J, Montanera W, et al. Comparison of sagittal FSE T2, STIR, and T1-weighted phase-sensitive inversion recovery in the detection of spinal cord lesions in MS at 3T. AJNR Am J Neuroradiol. 2016;37(5):970–5. doi: 10.3174/ajnr.A4656.CrossRefPubMedGoogle Scholar
- 21.• Okuda DT, Siva A, Kantarci O, Inglese M, Katz I, Tutuncu M, et al. Radiologically isolated syndrome: 5-year risk for an initial clinical event. PLoS One. 2014;9(3):e90509. doi: 10.1371/journal.pone.0090509. This retrospective study, which includes the largest number of radiologically isolated syndrome subjects reported to date, identified important factors that increase the risk of developing clinically isolated syndrome or multiple sclerosis.CrossRefPubMedPubMedCentralGoogle Scholar
- 33.•• Tintore M, Rovira A, Rio J, Otero-Romero S, Arrambide G, Tur C, et al. Defining high, medium and low impact prognostic factors for developing multiple sclerosis. Brain. 2015;138(Pt 7):1863–74. doi: 10.1093/brain/awv105. This prospective study of over 1000 patients with clinically isolated syndrome assessed a wide range of clinical, radiologic, and biologic prognostic factors and identified low, medium, and high prognostic factors that increase the risk of developing multiple sclerosis and disability accumulation.CrossRefPubMedGoogle Scholar
- 34.Romeo M, Martinelli-Boneschi F, Rodegher M, Esposito F, Martinelli V, Comi G, et al. Clinical and MRI predictors of response to interferon-beta and glatiramer acetate in relapsing-remitting multiple sclerosis patients. Eur J Neurol. 2013;20(7):1060–7. doi: 10.1111/ene.12119.CrossRefPubMedGoogle Scholar
- 37.•• Sormani MP, Bruzzi P. MRI lesions as a surrogate for relapses in multiple sclerosis: a meta-analysis of randomised trials. The Lancet Neurology. 2013;12(7):669–76. doi: 10.1016/s1474-4422(13)70103-0. This meta-analysis of 31 randomized controlled trials in multiple sclerosis confirmed that a disease-modifying therapy’s treatment effect on clinical relapses can be predicted by its effect on MRI lesion activity, supporting the use of MRI measures as primary endpoints in future clinical trials.CrossRefPubMedGoogle Scholar
- 49.Kanda T, Ishii K, Kawaguchi H, Kitajima K, Takenaka D. High signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted MR images: relationship with increasing cumulative dose of a gadolinium-based contrast material. Radiology. 2014;270(3):834–41. doi: 10.1148/radiol.13131669.CrossRefPubMedGoogle Scholar
- 51.Stojanov DA, Aracki-Trenkic A, Vojinovic S, Benedeto-Stojanov D, Ljubisavljevic S. Increasing signal intensity within the dentate nucleus and globus pallidus on unenhanced T1W magnetic resonance images in patients with relapsing-remitting multiple sclerosis: correlation with cumulative dose of a macrocyclic gadolinium-based contrast agent, gadobutrol. Eur Radiol. 2016;26(3):807–15. doi: 10.1007/s00330-015-3879-9.CrossRefPubMedGoogle Scholar
- 52.Kanda T, Osawa M, Oba H, Toyoda K, Kotoku J, Haruyama T, et al. High signal intensity in dentate nucleus on unenhanced T1-weighted MR images: association with linear versus macrocyclic gadolinium chelate administration. Radiology. 2015;275(3):803–9. doi: 10.1148/radiol.14140364.CrossRefPubMedGoogle Scholar
- 54.Robert P, Lehericy S, Grand S, Violas X, Fretellier N, Idee JM, et al. T1-weighted hypersignal in the deep cerebellar nuclei after repeated administrations of gadolinium-based contrast agents in healthy rats: difference between linear and macrocyclic agents. Investig Radiol. 2015;50(8):473–80. doi: 10.1097/RLI.0000000000000181.CrossRefGoogle Scholar
- 58.Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group. Lancet (London, England). 1998;352(9139):1498–504.Google Scholar
- 60.•• Freedman MS, Selchen D, Arnold DL, Prat A, Banwell B, Yeung M, et al. Treatment optimization in MS: Canadian MS Working Group updated recommendations. The Canadian Journal of Neurological Sciences. 2014;40(03):307–23. doi: 10.1017/s0317167100014244. This review provides a practical approach to assessing treatment response in patients with multiple sclerosis and a strategy for switching amongst available disease-modifying treatments.CrossRefGoogle Scholar
- 63.Comi G, Filippi M, Wolinsky JS. European/Canadian multicenter, double-blind, randomized, placebo-controlled study of the effects of glatiramer acetate on magnetic resonance imaging–measured disease activity and burden in patients with relapsing multiple sclerosis. European/Canadian Glatiramer acetate study group Ann Neurol 2001;49(3):290–297.Google Scholar
- 64.Vagberg M, Axelsson M, Birgander R, Burman J, Cananau C, Forslin Y, et al. Guidelines for the use of magnetic resonance imaging in diagnosing and monitoring the treatment of multiple sclerosis: recommendations of the Swedish Multiple Sclerosis Association and the Swedish Neuroradiological Society. Acta Neurol Scand. 2017;135(1):17–24. doi: 10.1111/ane.12667.CrossRefPubMedGoogle Scholar
- 72.McGuigan C, Craner M, Guadagno J, Kapoor R, Mazibrada G, Molyneux P, et al. Stratification and monitoring of natalizumab-associated progressive multifocal leukoencephalopathy risk: recommendations from an expert group. J Neurol Neurosurg Psychiatry. 2016;87(2):117–25. doi: 10.1136/jnnp-2015-311100.PubMedGoogle Scholar