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Advanced MRI and staging of multiple sclerosis lesions

Key Points

  • Recent research efforts have narrowed the gap between in vivo MRI and pathology with respect to multiple sclerosis (MS) lesion development and staging

  • Demyelinated lesions in marmoset experimental autoimmune encephalomyelitis (EAE) resemble their human counterparts far better than do lesions in rodent EAE models

  • Application of parallel MRI methods in MS and marmoset EAE facilitates interpretation of data collected in both conditions

  • The perivenular topography of inflammatory demyelinating lesions might facilitate the diagnostic work-up for MS

  • Smouldering lesions and meningeal inflammation are important features of chronic inflammation that should be targeted for in vivo imaging

Abstract

Over the past few decades, MRI-based visualization of demyelinated CNS lesions has become pivotal to the diagnosis and monitoring of multiple sclerosis (MS). In this Review, we outline current efforts to correlate imaging findings with the pathology of lesion development in MS, and the pitfalls that are being encountered in this research. Multimodal imaging at high and ultra-high magnetic field strengths is yielding biologically relevant insights into the pathophysiology of blood–brain barrier dynamics and both active and chronic inflammation, as well as mechanisms of lesion healing and remyelination. Here, we parallel the results in humans with advances in imaging of a primate model of MS — experimental autoimmune encephalomyelitis (EAE) in the common marmoset — in which demyelinated lesions resemble their human counterparts far more closely than do EAE lesions in the rodent. This approach holds promise for the identification of innovative biological markers, and for next-generation clinical trials that will focus more on tissue protection and repair.

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Figure 1: MRI and histology of the marmoset brain.
Figure 2: Perivenular topography of demyelinated MS lesions in white and grey matter.
Figure 3: MS lesions with paramagnetic rims.
Figure 4: Cortical and leptomeningeal involvement.

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Acknowledgements

The authors acknowledge financial support from the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, USA. D.S.R. has received research support from Vertex Pharmaceuticals and the Myelin Repair Foundation. This funding is not a competing interest in the context of the current article.

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All authors researched data for the article, made substantial contributions to discussions of the content, wrote the article, and reviewed and/or edited the manuscript before submission.

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Correspondence to Daniel S. Reich.

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Supplementary information

Supplementary information S1 (video)

Coronal 3 T FLAIR* images (combination of coregistered T2*-weighted magnitude and T2-weighted fluid-attenuation inversion recovery images) from a 33-year-old woman with relapsing–remitting multiple sclerosis. A prominent central vein can be seen in the majority of lesions. (MP4 12448 kb)

Supplementary information S2 (video)

Dynamic contrast enhancement MRI shows a centripetally enhancing lesion (red arrow) in an untreated 49-year-old woman with progressive multiple sclerosis and radiological relapses. (MP4 2009 kb)

Supplementary information S3 (video)

Dynamic contrast enhancement MRI of a new periventricular centripetally enhancing lesion in a 33-year-old man with relapsing–remitting multiple sclerosis. Over a 20 min period, contrast material progressively and completely fills the lesion. (MP4 5843 kb)

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Absinta, M., Sati, P. & Reich, D. Advanced MRI and staging of multiple sclerosis lesions. Nat Rev Neurol 12, 358–368 (2016). https://doi.org/10.1038/nrneurol.2016.59

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