Present and future of the diagnostic work-up of multiple sclerosis: the imaging perspective

Abstract

In recent years, the use of magnetic resonance imaging (MRI) for the diagnostic work-up of multiple sclerosis (MS) has evolved considerably. The 2017 McDonald criteria show high sensitivity and accuracy in predicting a second clinical attack in patients with a typical clinically isolated syndrome and allow an earlier diagnosis of MS. They have been validated, are evidence-based, simplify the clinical use of MRI criteria and improve MS patients' management. However, to limit the risk of misdiagnosis, they should be applied by expert clinicians only after the careful exclusion of alternative diagnoses. Recently, new MRI markers have been proposed to improve diagnostic specificity for MS and reduce the risk of misdiagnosis. The central vein sign and chronic active lesions (i.e., paramagnetic rim lesions) may increase the specificity of MS diagnostic criteria, but further effort is necessary to validate and standardize their assessment before implementing them in the clinical setting. The feasibility of subpial demyelination assessment and the clinical relevance of leptomeningeal enhancement evaluation in the diagnostic work-up of MS appear more limited. Artificial intelligence tools may capture MRI attributes that are beyond the human perception, and, in the future, artificial intelligence may complement human assessment to further ameliorate the diagnostic work-up and patients' classification. However, guidelines that ensure reliability, interpretability, and validity of findings obtained from artificial intelligence approaches are still needed to implement them in the clinical scenario. This review provides a summary of the most recent updates regarding the application of MRI for the diagnosis of MS.

Keywords: Diagnosis; Magnetic resonance imaging; Multiple sclerosis.

Fig. 1

The central vein sign. Representative 3D-EPI T2*-magnitude images in A axial, B sagittal, and C coronal planes acquired at 3T during the injection of gadolinium-based intravenous contrast agent in a 24-years-old relapsing–remitting multiple sclerosis patient. A conspicuous central vein sign is present in the majority of white matter lesions. In the magnified views, a central vein running through the lesion (red arrows) is visible as a hypointense line (axial and coronal planes) or a hypointense dot (sagittal plane). Abbreviations: 3D-EPI three-dimensional echo planar imaging

Fig. 2

Chronic active lesions. Example of chronic active lesion visualization using susceptibility-weighted MRI. A On 3D axial fluid-attenuated inversion recovery sequence in a 48-years-old secondary progressive multiple sclerosis patient (A–B), two confluent periventricular T2-hyperintense white matter lesions and another subcortical T2-hyperintense white matter lesion (white arrows among red-coded lesion mask) show a hypointense rim on phase image derived from a multi echo gradient-echo T2* sequence (C), thus they represent ‘paramagnetic rim lesions’ (PRLs)

Fig. 3

Leptomeningeal enhancement, cortical lesions and subpial demyelination. A, B Example of 7T FLAIR MRI of the brain in a 49-years-old woman with relapsing–remitting multiple sclerosis before (A) and after (B) the administration of gadolinium-based intravenous contrast agent. A focus of post-contrast pial/subarachnoid enhancement highlighted by white arrow. Examples of focal (C) or more extensive (D, E) subpial multiple sclerosis lesions (black arrows) with expansion within white matter/confluence with a juxtacortical lesion (E) in patients with multiple sclerosis as seen on ultrahigh resolution T2* gradient echo images at 7 Tesla. A white matter lesion is also visible in (E) (white arrow). Abbreviations: FLAIR fluid-attenuated inversion recovery, MRI magnetic resonance imaging