RESUMO
Quantitative susceptibility mapping (QSM) measures bulk susceptibilities in the brain, which can arise from many sources. In iron-rich subcortical gray matter (GM), non-heme iron is a dominant susceptibility source. We evaluated the use of QSM for iron mapping in subcortical GM by direct comparison to tissue iron staining. We performed in situ or in vivo QSM at 4.7 T combined with Perls' ferric iron staining on the corresponding extracted subcortical GM regions. This histochemical process enabled examination of ferric iron in complete slices that could be related to susceptibility measurements. Correlation analyses were performed on an individual-by-individual basis and high linear correlations between susceptibility and Perls' iron stain were found for the three multiple sclerosis (MS) subjects studied (R(2) = 0.75, 0.62, 0.86). In addition, high linear correlations between susceptibility and transverse relaxation rate (R2*) were found (R(2) = 0.88, 0.88, 0.87) which matched in vivo healthy subjects (R(2) = 0.87). This work validates the accuracy of QSM for brain iron mapping and also confirms ferric iron as the dominant susceptibility source in subcortical GM, by demonstrating high linear correlation of QSM to Perls' ferric iron staining.
Assuntos
Química Encefálica , Substância Cinzenta/metabolismo , Ferro/metabolismo , Fenômenos Magnéticos , Imageamento por Ressonância Magnética/métodos , Substância Cinzenta/química , Substância Cinzenta/patologia , Humanos , Ferro/análise , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/metabolismo , Esclerose Múltipla/patologiaRESUMO
PURPOSE: To investigate the relationship between iron staining and magnetic resonance (MR) imaging measurements in postmortem subjects with multiple sclerosis (MS). MATERIALS AND METHODS: Institutional ethical approval was obtained, and informed consent was obtained from the subjects and/or their families. Four MR imaging methods based on transverse relaxation (T2 weighting, R2 mapping, and R2* mapping) and phase imaging were performed by using a 4.7-T system in three in situ postmortem patients with MS less than 28 hours after death and in one in vivo patient 1 year before death. Iron staining with the Perls iron reaction was performed after brain extraction. Region-of-interest measurements from six subcortical gray matter structures were obtained from MR imaging and then correlated with corresponding locations on photographs of iron-stained pathologic slices by using a separate linear least-squares regression in each subject. Iron status of white matter lesions, as determined by staining, was compared with appearance on MR images. RESULTS: R2* mapping had the highest intrasubject correlations with iron in subcortical gray matter (R(2) = 0.857, 0.628, and 0.685; all P < .001), while R2 mapping (R(2) = 0.807, 0.615, 0.628, and 0.489; P < .001 and P = .001, .034, and .001, respectively), phase imaging (R(2) = 0.672, 0.441, 0.596, 0.548; all P ≤ .001), and T2-weighted imaging (R(2) = 0.463, 0.582, 0.650, and 0.551; all P < .001) had lower but still strong correlations. Within lesions, hypointense areas on phase images did not always represent iron. A hyperintense rim surrounding lesions on R2* maps was only present with iron staining, yet not all iron-staining lesions had R2* rim hyperintensity. CONCLUSION: All four MR imaging methods had significant linear correlations with iron and could potentially be used to determine iron status of subcortical gray matter structures in MS, with R2* mapping being preferred. A reliable method of determining iron status within MS lesions was not established.
Assuntos
Encéfalo/metabolismo , Ferro/metabolismo , Imageamento por Ressonância Magnética/métodos , Esclerose Múltipla/metabolismo , Encéfalo/patologia , Cadáver , Causas de Morte , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Análise dos Mínimos Quadrados , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/patologiaRESUMO
Recent studies suggest that increased T-cell and autoantibody reactivity to lipids may be present in the autoimmune demyelinating disease multiple sclerosis. To perform large-scale multiplex analysis of antibody responses to lipids in multiple sclerosis, we developed microarrays composed of lipids present in the myelin sheath, including ganglioside, sulfatide, cerebroside, sphingomyelin and total brain lipid fractions. Lipid-array analysis showed lipid-specific antibodies against sulfatide, sphingomyelin and oxidized lipids in cerebrospinal fluid (CSF) derived from individuals with multiple sclerosis. Sulfatide-specific antibodies were also detected in SJL/J mice with acute experimental autoimmune encephalomyelitis (EAE). Immunization of mice with sulfatide plus myelin peptide resulted in a more severe disease course of EAE, and administration of sulfatide-specific antibody exacerbated EAE. Thus, autoimmune responses to sulfatide and other lipids are present in individuals with multiple sclerosis and in EAE, and may contribute to the pathogenesis of autoimmune demyelination.
Assuntos
Doenças Autoimunes/patologia , Encéfalo/patologia , Encefalite/patologia , Lipídeos/química , Análise em Microsséries/métodos , Esclerose Múltipla/líquido cefalorraquidiano , Esclerose Múltipla/patologia , Animais , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/líquido cefalorraquidiano , Encefalomielite Autoimune Experimental/metabolismo , Ensaio de Imunoadsorção Enzimática , Humanos , Camundongos , Análise em Microsséries/instrumentação , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Sulfoglicoesfingolipídeos/farmacologia , Linfócitos T/metabolismoRESUMO
PURPOSE: To demonstrate 4.7 Tesla (T) imaging methods for visualizing lesions in multiple sclerosis in the human brain using phase susceptibility-weighting and T2 weighting. MATERIALS AND METHODS: Seven patients with relapsing-remitting multiple sclerosis were imaged at 4.7T using three-dimensional (3D) susceptibility-weighted imaging (SWI) with 0.90 mm(3) voxel volumes, and with 2D T2-weighted fast spin echo (T2WFSE) with 0.34 mm(3) voxels and 1.84 mm(3) voxels. The visibility of MS lesions at 4.7T with phase SWI and T2WFSE was assessed by independent lesion counts made by an experienced neuroradiologist, and by quantitative measures. RESULTS: High resolution T2WFSE at 4.7T provided excellent depiction of hyperintense lesions. When combined with phase SWI, 124 total lesions were identified of which 18% were only visible on phase SWI and not on T2WFSE. The phase lesions had a mean phase shift relative to local background of -11.15 +/- 5.97 parts per billion. CONCLUSION: Imaging at 4.7T can provide both high quality, high resolution T2WFSE and SWI for visualization of lesions in multiple sclerosis. Phase susceptibility-weighting can identify additional lesions that are not visible with high resolution T2WFSE.
Assuntos
Encéfalo/patologia , Imageamento por Ressonância Magnética/métodos , Esclerose Múltipla Recidivante-Remitente/patologia , Adulto , Feminino , Humanos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento Tridimensional , Masculino , Pessoa de Meia-IdadeRESUMO
Autoantibodies to myelin oligodendrocyte glycoprotein (MOG) can induce demyelination and oligodendrocyte loss in models of multiple sclerosis (MS). Whether anti-MOG Abs play a similar role in patients with MS or inflammatory CNS diseases by epitope spreading is unclear. We have therefore examined whether autoantibodies that bind properly folded MOG protein are present in the CNS parenchyma of MS patients. IgG was purified from CNS tissue of 14 postmortem cases of MS and 8 control cases, including cases of encephalitis. Binding was assessed using two independent assays, a fluorescence-based solid-phase assay and a solution-phase RIA. MOG autoantibodies were identified in IgG purified from CNS tissue by solid-phase immunoassay in 7 of 14 cases with MS and 1 case of subacute sclerosing panencephalitis, but not in IgG from noninflamed control tissue. This finding was confirmed with a solution-phase RIA, which measures higher affinity autoantibodies. These data demonstrate that autoantibodies recognizing MOG are present in substantially higher concentrations in the CNS parenchyma compared with cerebrospinal fluid and serum in subjects with MS, indicating that local production/accumulation is an important aspect of autoantibody-mediated pathology in demyelinating CNS diseases. Moreover, chronic inflammatory CNS disease may induce autoantibodies by virtue of epitope spreading.