MR imaging of gray matter involvement in multiple sclerosis: implications for understanding disease pathophysiology and monitoring treatment efficacy

Abstract

Recent pathologic and MR imaging studies have challenged the classic view of MS as a chronic inflammatory-demyelinating condition affecting solely the WM of the central nervous system. Indeed, an involvement of the GM has been shown to occur from the early stages of the disease, to progress with time, and to be only moderately correlated with the extent of WM injury. In this review, we summarize how advances in MR imaging technology and methods of analysis are contributing to ameliorating the detection of focal lesions and to quantifying the extent of "occult" pathology and atrophy, as well as to defining the topographic distribution of such changes in the GM of patients with MS. These advances, combined with the imaging of brain reorganization occurring after tissue injury, should ultimately result in an improved understanding and monitoring of MS clinical manifestations and evolution, either natural or modified by treatment.

Fig 1.

Brain axial DIR images from a patient with RRMS at baseline (A) and after 6 months (B). Multiple cortical lesions are visible. The size of 1 cortical lesion in the right parietal lobe (arrows) is increased after 6 months. Reprinted from Neuroimage, 42, Calabrese M et al, Morphology and evolution of cortical lesions in multiple sclerosis: a longitudinal MRI study, 1324–28, 2008, with permission from Elsevier.

Fig 2.

SPM regions with decreased GM concentration, overlaid on a high-resolution T1-weighted image, contrasting patients with different MS phenotypes. A and B, SPM regions with GM loss in patients with SPMS compared with those with RRMS. C and D, SPM regions with GM loss in patients with SPMS compared with those with PPMS. Reprinted from Neuroimage, 42, Ceccarelli A et al, A voxel-based morphometry study of grey matter loss in MS patients with different clinical phenotypes, 315–22, 2008, with permission from Elsevier.

Fig 3.

SPM regions with anatomic correspondence between GM atrophy (blue) and GM mean diffusivity (red) changes in patients with PPMS compared with controls. A and B, An overlap is visible in the thalami. Reprinted with permission from Ceccarelli et al, 2009.

Fig 4.

A and B, Cortical activations on a rendered brain from healthy controls (A) and patients with MS (B) from 8 European centers during the performance of a simple motor task with the right hand. Compared with controls, patients with MS had more significant activations bilaterally in several regions of the sensorimotor network. C, A dynamic causal model shows the results of the between-group analysis of effective connectivity. Increased strength of the connections in patients versus controls is reported as continuous black lines, whereas reduced strength of the connections in patients versus controls is reported as dotted black lines. Reprinted with permission from Rocca et al, 2009.