Quantitative Magnetic Resonance Imaging Towards Clinical Application in Multiple Sclerosis

Cristina Granziera; Jens Wuerfel; Frederik Barkhof; Massimiliano Calabrese; Nicola De Stefano; Christian Enzinger; Nikos Evangelou; Massimo Filippi; Jeroen J.G. Geurts; Daniel S. Reich; Maria A. Rocca; Stefan Ropele; Àlex Rovira; Pascal Sati; Ahmed T. Toosy; Hugo Vrenken; Claudia A. M. Gandini Wheeler-Kingshott; Ludwig Kappos


Brain. 2021;144(5):1296-1311. 

In This Article

Abstract and Introduction


Quantitative MRI provides biophysical measures of the microstructural integrity of the CNS, which can be compared across CNS regions, patients, and centres. In patients with multiple sclerosis, quantitative MRI techniques such as relaxometry, myelin imaging, magnetization transfer, diffusion MRI, quantitative susceptibility mapping, and perfusion MRI, complement conventional MRI techniques by providing insight into disease mechanisms. These include: (i) presence and extent of diffuse damage in CNS tissue outside lesions (normal-appearing tissue); (ii) heterogeneity of damage and repair in focal lesions; and (iii) specific damage to CNS tissue components. This review summarizes recent technical advances in quantitative MRI, existing pathological validation of quantitative MRI techniques, and emerging applications of quantitative MRI to patients with multiple sclerosis in both research and clinical settings. The current level of clinical maturity of each quantitative MRI technique, especially regarding its integration into clinical routine, is discussed. We aim to provide a better understanding of how quantitative MRI may help clinical practice by improving stratification of patients with multiple sclerosis, and assessment of disease progression, and evaluation of treatment response.


Conventional MRI provides invaluable information for the diagnosis, prognosis, and monitoring of the effectiveness of therapeutics in patients with multiple sclerosis.[1,2] The term conventional MRI encompasses the methods used in clinical practice to describe pathology by relying on contrast changes in weighted images. These are images that predominantly, but not exclusively, reflect a biophysical contrast mechanism (e.g. T1- and T2-weighted scans). Using conventional MRI in the multiple sclerosis clinic, it is generally possible to identify the number, location, and activity of multiple sclerosis lesions, although the sensitivity to those characteristics generally varies depending on several technical factors.[3] On the other end, conventional MRI is largely insensitive to the heterogeneity of focal multiple sclerosis lesions and to the pathology affecting CNS tissue outside multiple sclerosis lesions (normal-appearing white and grey matter). Furthermore, conventional MRI is unable to depict the level of damage within different CNS tissue components, such as myelin, axons, and glia.

Better quantification of the extent, type, spatial distribution, and evolution over time of CNS tissue damage in patients with multiple sclerosis could improve our understanding of disease mechanisms. It may also aid in stratification of disease burden, assessment of therapy response and evaluation of subclinical disease progression.

Quantitative MRI can potentially address these needs by providing more sensitive measures of multiple sclerosis pathology and more specific information regarding which tissue component has been damaged (Figure 1). Unlike conventional MRI, which acquires datasets that have a mixture of weightings and therefore cannot be resolved into a quantitative map, quantitative MRI relies exclusively on acquisitions that can then be used to disentangle the source of signal variations. Moreover, through computational or mathematical modelling, this approach can provide quantitative maps where intensities have physical units.[4] Thus, quantitative MRI techniques are superior to conventional MRI regarding their sensitivity to subtle alterations within lesions and normal-appearing tissue[4] as well as their increased specificity relating to the damage of different tissue components of the CNS (e.g. myelin, axons, glia, iron and blood flow/volume).

Figure 1.

Information provided by quantitative MRI about key features of multiple sclerosis pathology for clinical applications in patients with multiple sclerosis. Quantitative MRI provides information about normal-appearing tissue pathology, multiple sclerosis lesion heterogeneity, remyelination, and blood–brain barrier disruption. dia-mag = diamagnetic; para-mag = paramagnetic.

Nonetheless, quantitative MRI is not currently used in clinical practice, primarily because it has not reached 'clinical maturity'. A method can be considered 'clinically mature' when it can be run on most up-to-date clinical scanners without the need for additional sequence development, there is available and validated software able to process the data and provide the user with the desired quantitative maps, and cut-off values of pathology assessed with that method have been established.

In this review, we summarize: (i) the information that can, and cannot, be provided by conventional MRI; (ii) the contribution of quantitative MRI to our understanding of multiple sclerosis pathology in the brain and spinal cord; (iii) the relationship between quantitative MRI features and clinical outcome and the potential role of quantitative MRI in improving the prediction of disability, especially motor and cognitive deficits; and (iv) the clinical maturation stage of the various quantitative MRI techniques.