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OBJECTIVES: To investigate whether a treat-to-target strategy based on methotrexate (MTX) and intra-articular (IA) betamethasone suppresses magnetic resonance imaging (MRI)-determined measures of disease activity and reduces joint destruction in early rheumatoid arthritis (eRA) patients, and to investigate whether concomitant cyclosporin A (CyA) provides an additional effect. METHOD: In the 2-year randomized, double-blind, treat-to-target trial CIMESTRA, 160 patients with eRA (< 6 months) were randomized to MTX, intra-articular betamethasone and CyA, or placebo CyA. A total of 129 patients participated in the MRI substudy, and had contrast-enhanced MR images of the non-dominant hand at months 0, 6, 12, and 24. MR images were evaluated for osteitis, synovitis, tenosynovitis, bone erosion, and joint space narrowing (JSN), using validated scoring methods. RESULTS: Significant reductions were seen at 6 months in all inflammatory parameters [synovitis, mean change -1.6 (p < 0.001, Wilcoxon), tenosynovitis, -3.5 (p < 0.001), and osteitis, -1.3 (p < 0.05)] and at 12/24 months in synovitis and tenosynovitis [-1.6/-2.2 and -3.6/-3.8, respectively; all p < 0.001]. MRI signs of inflammation were not fully eliminated, and increases in erosion and JSN scores were observed at 6 months [0.4 (p < 0.01)/0.1 (p < 0.05)], 12 months [0.8 (p < 0.001)/0.3 (p < 0.01)], and 24 months [1.0 (p < 0.001)/0.4 (p < 0.001)]. Clinical measures decreased significantly (p < 0.001) at all time points. There were no consistent statistically significant differences between treatment groups. CONCLUSIONS: In this eRA treat-to-target trial, MTX and intra-articular glucocorticoids markedly reduced, but did not eliminate, MRI osteitis, synovitis, and tenosynovitis. Accordingly, minimal but statistically significant increases in bone erosion and JSN were observed. No additional effect of CyA was demonstrated.
Assuntos
Artrite Reumatoide , Betametasona/administração & dosagem , Doenças Ósseas , Ciclosporina/administração & dosagem , Metotrexato/administração & dosagem , Sinovite , Tendinopatia , Adulto , Idoso , Antirreumáticos/administração & dosagem , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/fisiopatologia , Doenças Ósseas/tratamento farmacológico , Doenças Ósseas/etiologia , Método Duplo-Cego , Vias de Administração de Medicamentos , Sistemas de Liberação de Medicamentos/métodos , Monitoramento de Medicamentos/métodos , Quimioterapia Combinada , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Sinovite/tratamento farmacológico , Sinovite/etiologia , Tendinopatia/tratamento farmacológico , Tendinopatia/etiologia , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the role of hippocampal plasticity in the antidepressant effect of electroconvulsive therapy (ECT). METHOD: We used magnetic resonance (MR) imaging including diffusion tensor imaging (DTI) and proton MR spectroscopy (1 H-MRS) to investigate hippocampal volume, diffusivity, and metabolite changes in 19 patients receiving ECT for severe depression. Other regions of interest included the amygdala, dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex, and hypothalamus. Patients received a 3T MR scan before ECT (TP1), 1 week (TP2), and 4 weeks (TP3) after ECT. RESULTS: Hippocampal and amygdala volume increased significantly at TP2 and continued to be increased at TP3. DLPFC exhibited a transient volume reduction at TP2. DTI revealed a reduced anisotropy and diffusivity of the hippocampus at TP2. We found no significant post-ECT changes in brain metabolite concentrations, and we were unable to identify a spectral signature at ≈1.30 ppm previously suggested to reflect neurogenesis induced by ECT. None of the brain imaging measures correlated to the clinical response. CONCLUSION: Our findings show that ECT causes a remodeling of brain structures involved in affective regulation, but due to their lack of correlation with the antidepressant effect, this remodeling does not appear to be directly underlying the antidepressant action of ECT.
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OBJECTIVES: To investigate the responsiveness to treatment and the reliability of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in rheumatoid arthritis (RA) knee joints. METHODS: DCE-MRI was performed in 12 clinically active RA knee joints before and 1, 7, 30, and 180 days after intra-articular injection with 80 mg methylprednisolone. Using semi-automated image processing software, DCE-MRI parameters, including the initial rate of enhancement (IRE) and maximal enhancement (ME), were generated for three regions of interest (ROIs): 'Whole slice', 'Quick ROI', and 'Precise ROI'. The smallest detectable difference (SDD), the smallest detectable change (SDC), and intra- and inter-reader intraclass correlation coefficients (ICCs) were used to assess the reliability of DCE-MRI. Responsiveness to treatment was assessed by the standardized response mean (SRM). RESULTS: In all patients clinical remission of the knee was achieved at day 7. All DCE-MRI parameters decreased from day 0 to day 7. Using the Quick and Precise ROI methods, respectively, IRE decreased by 63% and 69%, ME decreased by 11% and 11%, N decreased by 55% and 57%, and IRE × N decreased by 84% and 85%. The intra- and inter-reader ICCs were very high (0.96-1.00). The decrease in DCE-MRI parameters was larger than the SDC for all patients. SRM was large for all parameters, ranging from -1.04 to -2.40. When the Whole slice ROI method was used, no parameters were responsive to treatment. CONCLUSIONS: DCE-MRI analysed using semi-automatic software is a reliable and responsive tool for assessing treatment in RA knees joints. Rough manual delineation of the joint to omit enhancement artefacts is necessary.
Assuntos
Artrite Reumatoide/diagnóstico , Glucocorticoides/administração & dosagem , Articulação do Joelho/patologia , Imageamento por Ressonância Magnética/métodos , Metilprednisolona/administração & dosagem , Sinovite/diagnóstico , Adulto , Idoso , Artrite Reumatoide/tratamento farmacológico , Estudos de Coortes , Seguimentos , Gadolínio DTPA , Humanos , Aumento da Imagem , Injeções Intra-Articulares , Articulação do Joelho/efeitos dos fármacos , Estudos Longitudinais , Pessoa de Meia-Idade , Recidiva , Indução de Remissão , Reprodutibilidade dos Testes , Sinovite/tratamento farmacológico , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To determine whether dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) evaluated using semi-automatic image processing software can accurately assess synovial inflammation in rheumatoid arthritis (RA) knee joints. METHODS: In 17 RA patients undergoing knee surgery, the average grade of histological synovial inflammation was determined from four biopsies obtained during surgery. A preoperative series of T(1)-weighted dynamic fast low-angle shot (FLASH) MR images was obtained. Parameters characterizing contrast uptake dynamics, including the initial rate of enhancement (IRE), were generated by the software in three different areas: (I) the entire slice (Whole slice); (II) a manually outlined region of interest (ROI) drawn quickly around the joint, omitting large artefacts such as blood vessels (Quick ROI); and (III) a manually outlined ROI following the synovial capsule of the knee joint (Precise ROI). Intra- and inter-reader agreement was assessed using the intra-class correlation coefficient (ICC). RESULTS: The IRE from the Quick ROI and the Precise ROI revealed high correlations to the grade of histological inflammation (Spearman's correlation coefficient (rho) = 0.70, p = 0.001 and rho = 0.74, p = 0.001, respectively). Intra- and inter-reader ICCs were very high (0.93-1.00). No Whole slice parameters were correlated to histology. CONCLUSION: DCE-MRI provides fast and accurate assessment of synovial inflammation in RA patients. Manual outlining of the joint to omit large artefacts is necessary.
Assuntos
Artrite Reumatoide/diagnóstico , Imageamento por Ressonância Magnética/métodos , Sinovite/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico por imagem , Artroplastia do Joelho , Meios de Contraste , Feminino , Gadolínio , Humanos , Interpretação de Imagem Assistida por Computador , Articulação do Joelho/metabolismo , Articulação do Joelho/patologia , Articulação do Joelho/cirurgia , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Cintilografia , Reprodutibilidade dos Testes , Sinovite/diagnóstico por imagem , Sinovite/etiologia , Adulto JovemRESUMO
Global brain ischemia provoked by transient occlusion of the carotid arteries (2VO) in gerbils results in a severe loss of neurons in the hippocampal CA1 region. We measured the concentration of the neuron specific N-acetyl-aspartate, [NAA], in the gerbil dorsal hippocampus by proton MR spectroscopy (1H-MRS) in situ, and HPLC, 4 days after global ischemia. The [NAA] was correlated with graded hippocampus damage scoring and stereologically determined neuronal density. A basal hippocampal [NAA] of 8.37+/-0.10 and 9.81+/-0.44 mmol/l were found from HPLC and 1H-MRS, respectively. HPLC measurements of [NAA] obtained from hippocampus 4 days after 2VO showed a 20% reduction in the [NAA] following 4 min of ischemia (P<0.001). 1H-MRS measurements on gerbils subjected to 4 or 8 min of ischemia showed a similar 24% decline in the [NAA] (P<0.05). Thus, there was correlation between the HPLC and 1H-MRS determined NAA decline. There was also a significant correlation between 1H-MRS [NAA] and the corresponding reduction in CA1 neuronal density (P<0.004). In summary our findings show that single voxel 1H-MRS can be used as a supplement to histological evaluation of neuronal injury in studies after global brain ischemia. Accordingly, volume selective spectroscopy has a potential for assessment of neuroprotective therapeutic compounds/strategies with respect to neuronal rescue for delayed ischemic brain damage.
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Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Encéfalo/patologia , Ataque Isquêmico Transitório/patologia , Espectroscopia de Ressonância Magnética/métodos , Neurônios/patologia , Animais , Ácido Aspártico/análise , Biomarcadores/análise , Cromatografia Líquida de Alta Pressão , Gerbillinae , Hipocampo/metabolismo , Hipocampo/patologia , Hidrogênio , Masculino , Neurônios/metabolismo , Reprodutibilidade dos Testes , Fatores de TempoRESUMO
BACKGROUND: Late infantile metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disorder that causes severe demyelination of the nervous system. The neuronal metabolite N-acetylaspartate (NAA) serves as a source of acetyl groups for myelin lipid synthesis in oligodendrocytes and is known as a marker for neuronal and axonal loss. NAA and other metabolite levels measured by proton magnetic resonance spectroscopy (MRS) correlate with performance of the brain in normal children. There is a need for sensitive measures of disease progression in patients with MLD to enable development of future treatments. METHODS: A cross-section of 13 children with late infantile MLD were examined by proton MRS. Signals from NAA, total choline, and total creatine in the deep white matter were measured and correlated with the results of cognitive and motor function tests. RESULTS: The NAA signal decreased as the disease process advanced. Motor function, measured by the Gross Motor Function Measure-88, varied from 13 (only head movement in the supine position) to 180 (able to walk) across the study cohort, demonstrating a wide range in functional status. Similarly, varied decreases were observed in cognitive function. We report strong positive correlations between standardized measures of motor and cognitive function and NAA levels in the deep white matter. CONCLUSIONS: We suggest that NAA levels could serve as a sensitive biomarker in children with MLD. Proton MRS may provide a valuable tool for measuring the effects of treatment interventions in this disorder.
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Ácido Aspártico/análogos & derivados , Encéfalo/metabolismo , Leucodistrofia Metacromática/diagnóstico , Leucodistrofia Metacromática/fisiopatologia , Movimento , Ácido Aspártico/metabolismo , Biomarcadores/metabolismo , Pré-Escolar , Colina/metabolismo , Cognição , Creatina/metabolismo , Progressão da Doença , Feminino , Humanos , Leucodistrofia Metacromática/psicologia , Espectroscopia de Ressonância Magnética , Masculino , Sensibilidade e EspecificidadeRESUMO
The most commonly encountered form of echo planar spectroscopy involves oscillating gradients in one spatial dimension during readout. Data are consequently not sampled on a Cartesian grid. A fast gridding algorithm applicable to this particular situation is presented. The method is optimal, i.e., it performs as well as the full discrete Fourier transform for band limited signals while allowing for use of the fast Fourier transform. The method is demonstrated for reconstruction of data that are partially undersampled in the time domain. The advantages of undersampling are lower hardware requirements or fewer interleaves per acquisition. The method is of particular interest when large bandwidths are needed (e.g., for high field scanning) and for scanners with limited gradient performance. The unavoidable artifacts resulting from undersampling are demonstrated to be acceptable for spectroscopy with long echo times.
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Algoritmos , Ácido Aspártico/análogos & derivados , Imagem Ecoplanar/métodos , Processamento de Imagem Assistida por Computador/métodos , Processamento de Sinais Assistido por Computador , Artefatos , Ácido Aspártico/análise , Ácido Aspártico/metabolismo , Encéfalo/anatomia & histologia , Encéfalo/metabolismo , Química Encefálica , Análise de Fourier , Humanos , Fibras Nervosas Mielinizadas/química , Fibras Nervosas Mielinizadas/metabolismo , Imagens de Fantasmas , Água/análise , Água/metabolismoRESUMO
Quantification of gray and white matter levels of spectroscopically visible metabolites can provide important insights into brain development and pathological conditions. Chemical shift imaging offers a gain in efficiency for estimation of global gray and white matter metabolite concentrations compared to single voxel methods. In the present study, the optimal voxel size is calculated from segmented human brain data and accompanying field maps. The optimal voxel size is found to be approximately 8 cc, but a wide range of values, 4-64 cc, can be chosen with little increase in estimated concentration error (<15%). Magn Reson Med 44:10-18, 2000.
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Encéfalo/metabolismo , Processamento de Imagem Assistida por Computador , Espectroscopia de Ressonância Magnética/métodos , Água Corporal/metabolismo , Colina/metabolismo , Creatina/metabolismo , Humanos , Ácido Láctico/metabolismo , Modelos Lineares , Matemática , Prótons , Processamento de Sinais Assistido por ComputadorRESUMO
The quantification of perfusion using dynamic susceptibility contrast MRI (DSC-MRI) requires deconvolution to obtain the residual impulse response function (IRF). In this work, a method using the Gaussian process for deconvolution (GPD) is proposed. The fact that the IRF is smooth is incorporated as a constraint in the method. The GPD method, which automatically estimates the noise level in each voxel, has the advantage that model parameters are optimized automatically. The GPD is compared to singular value decomposition (SVD) using a common threshold for the singular values, and to SVD using a threshold optimized according to the noise level in each voxel. The comparison is carried out using artificial data as well as data from healthy volunteers. It is shown that GPD is comparable to SVD with a variable optimized threshold when determining the maximum of the IRF, which is directly related to the perfusion. GPD provides a better estimate of the entire IRF. As the signal-to-noise ratio (SNR) increases or the time resolution of the measurements increases, GPD is shown to be superior to SVD. This is also found for large distribution volumes.