Advanced Structural and Functional Brain MRI in Multiple Sclerosis

Antonio Giorgio, MD, PhD; Nicola De Stefano, MD, PhD


Semin Neurol. 2016;36(2):163-176. 

In This Article

Abstract and Introduction


Conventional magnetic resonance imaging (MRI) of the central nervous system is crucial for an early and reliable diagnosis and monitoring of patients with multiple sclerosis (MS). Focal white matter (WM) lesions, as detected by MRI, are the pathological hallmark of the disease and show some relation to clinical disability, especially in the long run. Gray matter (GM) involvement is evident from disease onset and includes focal (i.e., cortical lesions) and diffuse pathology (i.e., atrophy). Both accumulate over time and show close relation to physical disability and cognitive impairment. Using advanced quantitative MRI techniques such as magnetization transfer imaging (MTI), diffusion tensor imaging (DTI), proton MR spectroscopy (1H-MRS), and iron imaging, subtle MS pathology has been demonstrated from early stages outside focal WM lesions in the form of widespread abnormalities of the normal appearing WM and GM. In addition, studies using functional MRI have demonstrated that brain plasticity is driven by MS pathology, playing adaptive or maladaptive roles to neurologic and cognitive status and explaining, at least in part, the clinicoradiological paradox of MS.


Given its sensitivity in revealing focal white matter (WM) abnormalities, magnetic resonance imaging (MRI) has become an indispensable tool for the assessment of patients with multiple sclerosis (MS) in the diagnostic workup. It is also extensively used in monitoring of abnormalities over time and elucidating the mechanisms of disease progression and disability.

There are established MRI guidelines that incorporate WM lesions into the diagnosis of patients with a clinically isolated syndrome (CIS) suggestive of MS,[1] and specific MRI acquisition protocols have been suggested for longitudinally monitoring WM lesion changes in patients with established disease.[2] Moreover, in MS research, conventional MRI has been significantly improved by quantitative and advanced MRI techniques, which have shown greater sensitivity and specificity to the heterogeneous pathological substrates of the disease, not only in focal T2-visible WM lesions, but also in normal-appearing white matter (NAWM) and gray matter (GM).[3]

Efficiency or dysfunction of brain cortical reorganization in the different stages of MS might play an important role in explaining heterogeneity of the clinical manifestations across patients, and several studies have used functional MRI (FMRI) to evaluate functions of brain network in patients with MS.[4,5]

More recently, new MRI methods capable of measuring pathological processes that have been overlooked in the past (e.g., iron deposition) and the advent of high- and ultrahigh-field magnets, have provided further insight into the pathophysiology of MS.[2]

This review aims at elucidating and discussing the role of advanced MRI in the central nervous system (CNS) of patients with MS for the appraisal of focal and diffuse tissue damage, abnormalities in the normal-appearing brain and functional brain changes. Future directions and challenges, with an emphasis on high-field MRI, will be also pointed out.