Chronic Multiple Sclerosis Lesions: Characterization with High-Field-Strength MR Imaging

Abstract

Purpose:To elucidate the mechanism of magnetic resonance (MR) imaging contrast in multiple sclerosis (MS) lesion appearance by using susceptibility-weighted imaging and to assess with histologic correlation the role of iron and myelin in generating this MR imaging contrast. Materials and Methods:Each patient provided written consent to a human subject protocol approved by an institutional review board. Highspatial-resolution susceptibility-weighted 7.0-T MR images were obtained in 21 patients with MS. Contrast patterns in quantitative phase and R2* images, derived from 7.0-T data, were investigated in 220 areas defi ned as chronic MS lesions on conventional T2-weighted fl uid-attenuated inversion recovery, T2-weighted, and T1-weighted spin-echo images. The presence of positive or negative phase shifts (ie, decreased or increased MR frequency, respectively) was assessed in each lesion. In addition, postmortem MR imaging was performed at 7.0 T and 11.7 T, and its results were correlated with those of immunohistochemical staining specifi c for myelin, iron, and ferritin. Results:The majority (133 [60.5%] of 220) of the identifi ed lesions had a normal phase and reduced R2*. A substantial fraction of the lesions (84 [38.2%] of 220) had negative phase shift, either uniformly or at their rim, and a variety of appearances on R2* maps. These two lesion contrast patterns were reproduced in the postmortem MR imaging study. Comparison with histologic fi ndings showed that, while R2* reduction corresponded to severe loss of both iron and myelin, negative phase shift corresponded to focal iron deposits with myelin loss. Conclusion:Combined analysis of 7.0-T R2* and phase data may help in characterizing the pathologic features of MS lesions. The observed R2* decreases suggest profound myelin loss, whereas negative phase shifts suggest a focal iron accumulation.q RSNA, 2011Supplemental material : http://radiology.rsna.org/lookup /suppl

Ultra-High-Field MRI Visualization of Cortical Multiple Sclerosis Lesions with T2 and T2*: A Postmortem MRI and Histopathology Study

“…One postmortem study that did look at T2*WI sensitivity showed a 48% prospective sensitivity but made no distinction among lesion types. 12 Another 7T study found that 46% of cortical lesions could be prospectively detected by using T2*WI and a similar 43% could be detected by using a WMattenuated turbo field echo. 13 However, the 2 sequences studied were suboptimally matched in terms of image resolution, which may explain the relative absence of differences between them.…”

Phase White Matter Signal Abnormalities in Patients with Clinically Isolated Syndrome and Other Neurologic Disorders

“…Recent studies have confirmed histologically that WM-SAs visible on MR imaging phase and R 2* correspond to focal iron deposits, whereas T2 and T1 WM-SAs are influenced by water content. 11 A substantial subset of MS WM-SAs has phase shifts 11,12 and morphologic differences. [11][12][13][14][15] However, factors other than nonheme iron may influence the observed WM-SA signal, such as changes in myelin, deoxyhemoglobin, and inflammation.…”

“…11 A substantial subset of MS WM-SAs has phase shifts 11,12 and morphologic differences. [11][12][13][14][15] However, factors other than nonheme iron may influence the observed WM-SA signal, such as changes in myelin, deoxyhemoglobin, and inflammation. 11,[16][17][18][19] Therefore, because there are a multitude of effects, it is not fully known to what extent they each individually influence SWI-filtered phase changes.…”

“…[11][12][13][14][15] However, factors other than nonheme iron may influence the observed WM-SA signal, such as changes in myelin, deoxyhemoglobin, and inflammation. 11,[16][17][18][19] Therefore, because there are a multitude of effects, it is not fully known to what extent they each individually influence SWI-filtered phase changes. Phase changes may signal early WM-SA development 17,20 in that these phase WM-SAs may appear initially but then disappear as the pathology advances.…”

“…17 Considering that the distinct pathologies influencing phase shift (eg, cellular/myelin destruction, iron levels, microstructural changes) in WM-SAs are most likely intricately related and are observed in MS and related disorders, 12,14,15,[21][22][23] the inquiry into pathology visible on SWI-filtered phase remains important regardless of the causative factors. SWI-filtered phase work has mostly focused on patients with MS, 11,[13][14][15]24 high-field-strength imaging, 11,13,24 or histologically validating phase WM-SAs. 11,25 Regardless of what pathology phase WM-SAs represent, it is imperative to identify whether their presence has diagnostic value.…”