Assessing abnormal iron content in the deep gray matter of patients with multiple sclerosis versus healthy controls

Abstract

Background and purpose: It is well known that patients with MS tend to have abnormal iron deposition in and around the MS plaques, in the basal ganglia and the THA. In this study, we used SWI to quantify iron content in patients with MS and healthy volunteers.

Materials and methods: Fifty-two patients with MS were recruited to assess abnormal iron content in their basal ganglia and THA structures. One hundred twenty-two healthy subjects were recruited to establish a baseline of normal iron content in deep GM structures. Each structure was separated into 2 regions: a low-iron-content region and a high-iron-content region. The average phase, the percentage area, and the total phase of the high-iron-content region were evaluated. A weighting was also assigned to each subject depending on the level of iron content and its deviation from the normal range.

Results: A clear separation between iron content in healthy subjects versus patients with MS was seen. For healthy subjects 13% and for patients with MS 65% showed an iron-weighting factor >3 SDs from the normal mean (P < .05). The results for those patients younger than 40 years are even more impressive. In these cases, only 1% of healthy subjects and 67% of patients with RRMS showed abnormally high iron content.

Conclusions: Iron-weighting factors in the basal ganglia, THA, and the midbrain appeared to be abnormal in roughly two-thirds of patients with MS as measured by SWI.

Fig 1.

SWI filtered-phase images displaying the basal ganglia and the midbrain of an age-matched healthy control (A−C) and patient with MS (D−F), showing abnormal iron deposition in the GP, PUT, and the CN (D); the SN and the RN of the midbrain (E); and the PT (F).

Fig 2.

Average phase, normalized area, and total phase of RII in the CN and PT. Small dots represent healthy subjects. The solid line is the regression line, and the outer dashed lines represent the 95% prediction interval of the regression. Hollow squares and triangles represent patients with RRMS, and the solid squares and triangles represent patients with SPMS. The squares and triangles represent the left and right hemispheres respectively. Many of the patients with MS have brain iron content beyond the 95% prediction intervals.

Fig 3.

Plots showing individual weighting of different parameters (average phase: upper row; normalized area: middle row; and the total phase: lower row) of the PT (A−C) and the RN (D−F). The asterisks represent the patients with RRMS, the triangles represent those with SPMS, and the diamonds represent the healthy subjects. Patients with MS and healthy subjects with weighting higher than 1 are shown in the plots (these results correspond to m = 3; for quantitative evaluation, please refer to Tables 1 and 2).

Fig 4.

Four plots showing the subtotal (A−C) weighting factors and the total weighting factor (D) of the 4 structures with the weighting factor >1 (these results correspond to m = 3): CN, PT, RN, and SN. The asterisks represent the patients with RRMS, the triangles represent the patients with SPMS, and the diamonds represent healthy subjects. For quantitative results of these graphs, please refer to Table 3.