Multiparameter MRI quantification of microstructural brain alteration in multiple sclerosis

Abstract

Multiple sclerosis (MS) is an inflammatory demyelinating and neurodegenerative disorder of the central nervous system (CNS), which stands as the most common cause of neurological disability in young adults. Traditionally, MS is primarily characterized by the accumulation of focal demyelinated plaques within the white matter (WM). With the advent of highly developed histopathological techniques in the second half of the 20th century, it became clear that focal lesions are also present in grey matter (GM), and that neurodegeneration diffusely affects macroscopically normal-appearing brain tissues (NABT). These observations are particularly evident in the progressive forms of the disease. Nevertheless, in vivo evaluation of MS patients remains unsatisfactory, because conventional MRI is insensitive to many pathological mechanisms underpinning MS. In the present work, we precisely aimed at improving the impact of 3 Tesla MRI on the detection and characterization of these processes, using quantitative MRI (qMRI) parameters sensitive to iron and myelin contents: magnetization transfer (MT) saturation, effective transverse relaxation rate R2* (1/T2*) and longitudinal relaxation rate R1 (1/T1). We designed a prospective cross-sectional study, contrasting 36 MS patients to 36 age-matched healthy controls. Processing and statistical analyses of MRI data were conducted on the basis of two distinct approaches: general analysis looked for differences in qMRI parameters summarized over three different NABT classes (normal appearing cortical and deep grey matters, normal appearing white matter), whereas voxel-based analyses assessed the spatial distribution of qMRI changes within normal appearing cortical and deep grey matters. Consistent with histopathological findings, results suggest a widespread reduction in myelin and/or iron contents within NABT of MS patients, both at the global and loco-regional levels, and beyond the ability of atrophy measurements. Interestingly, these microstructural alterations tend to be more pronounced and diffuse in progressive MS population. Moreover, correlation analyses indicate that they might play a significant role in determining brain volume loss as well as irreversible disability in MS. Our cross-sectional study proves that simultaneous quantification of multiple MRI parameters can sensitively assess NABT microstructure in MS. However, future large-scale studies should evaluate the reproducibility and predictive values of these results