A Magnetization Transfer Imaging Study of Normal-Appearing White Matter in Multiple Sclerosis

Abstract

We attempted to define the role of subtle changes in the normal-appearing white matter (NAWM) in the development of disability in multiple sclerosis (MS). Twenty-seven clinically definite MS patients with either relapsing-remitting or chronic-progressive courses and 10 sex- and age-matched controls entered the study. For each patient and control, we studied two NAWM areas in the frontal lobe with magnetization transfer imaging (MTI). For patients, we also calculated the MT ratios (MTRs) for three contiguous areas of NAWM progressively further from "isolated" lesions visible on conventional MRI. Frontal NAWM in MS patients had lower mean MTRs than the frontal white matter of the controls (p = 0.02). MTRs in the NAWM adjacent to isolated lesions increased with distance from them to the cortical gray matter (p = 0.04). This pattern was typical for patients with chronic-progressive MS whose MTRs in the first two regions of NAWM adjacent to lesions were lower than those of the same regions of patients with relapsing-remitting MS. This study confirms that there are alterations in the NAWM of MS patients and suggests that such changes might be relevant to the disability in MS.

Whole Brain and Localized Magnetization Transfer Measurements Are Associated with Cognitive Impairment in Patients Infected with Human Immunodeficiency Virus

“…15 MT studies of other CNS disorders also support the utility of MT for detecting brain changes associated with clinical and neuropsychological outcome. 13,14,24,25 For example, global disease burden, as detected by whole brain MTR, is correlated with cognitive function in multiple sclerosis (MS). 26,27 A previous study in cognitively impaired HIV subjects indicates a relationship between whole brain MT measures and overall cognitive decline in HIV-infected subjects.…”

“…This noninvasive strategy has been used to identify injury in various neurologic pathologies, including HIV encephalitis. [11][12][13][14][15][16] An advantage of MT is the possibility of acquiring measurements of the brain at different levels of analysis. This strategy can be used to derive quantitative MTR measurements for the whole brain as well as for localized regions of interest (ROIs).…”

<i>In Vivo</i> Brain MR Imaging at Subnanoliter Resolution: Contrast and Histology

“…For example, an increase in astrocytes and activated microglia appears to outweigh the decrease in oligodendrocytes in plaques, 107 which may offset prolonged relaxation times due to increased free water. In fact, a number of investigations reported a significantly reduced MTR in otherwise normal-appearing WM and GM, 92,106,[108][109][110][111][112][113][114] a close correlation between the MTR and clinical disability, 114 -117 and a potential prognostic value of magnetization transfer MR imaging. 114,118 -120 More recent studies suggest that iron-laden/activated microglia 71,121 and/or aggregates typical of small bleeding 71 cause focally increased T 2 relaxation rates and/or reduced MTR 92 within normal-appearing WM.…”

Lobar Distribution of Changes in Gray Matter and White Matter in Memory Clinic Patients: Detected Using Magnetization Transfer Imaging

“…7,8 Although MTI has been developed to study WM changes, it is also sensitive to changes in tissue structure of the GM. [9][10][11][12] This makes MTI an attractive tool to study the earliest brain changes in both WM and GM in the continuum of cognitive decline in old age.…”