RESUMO
BACKGROUND: The development of a quantifiable and noninvasive method of monitoring disease activity and response to therapy is vital for arthritis management. OBJECTIVE: The purpose of this study was to investigate the utility of quantitative dynamic contrast-enhanced MRI (DCE-MRI) based on pharmacokinetic (PK) modeling to evaluate disease activity in the knee and correlate the results with the clinical assessment in children with juvenile idiopathic arthritis (JIA). MATERIALS AND METHODS: A group of 17 children with JIA underwent longitudinal clinical and laboratory assessment and DCE-MRI of the knee at enrollment, 3 months, and 12 months. A PK model was employed using MRI signal enhancement data to give three parameters, K(trans') (min(-1)), k(ep) (min(-1)), and V(p) (') and to calculate synovial volume. RESULTS: The PK parameters, synovial volumes, and clinical and laboratory assessments in most children were significantly decreased (P < 0.05) at 12 months when compared to the enrollment values. There was excellent correlation between the PK and synovial volume and the clinical and laboratory assessments. Differences in MR and clinical parameter values in individual subjects illustrate persistent synovitis when in clinical remission. CONCLUSION: A decrease in PK parameter values obtained from DCE-MRI in children with JIA likely reflects diminution of disease activity. This technique may be used as an objective follow-up measure of therapeutic efficacy in patients with JIA. MR imaging can detect persistent synovitis in patients considered to be in clinical remission.
Assuntos
Artrite Juvenil/tratamento farmacológico , Artrite Juvenil/patologia , Meios de Contraste/farmacocinética , Gadolínio DTPA/farmacocinética , Articulação do Joelho/patologia , Imageamento por Ressonância Magnética/métodos , Adolescente , Corticosteroides/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Antirreumáticos/uso terapêutico , Criança , Meios de Contraste/administração & dosagem , Progressão da Doença , Feminino , Gadolínio DTPA/administração & dosagem , Humanos , Injeções Intravenosas , Estudos Longitudinais , Masculino , Projetos Piloto , Estatísticas não ParamétricasRESUMO
Improved management of arthritis requires a reliable, quantifiable, noninvasive method to monitor the degree of inflammation and therapeutic response during the early phase of the disease. For this purpose, the uptake of Gd-DTPA in the distal femoral physis and synovium in children with juvenile rheumatoid arthritis (JRA) was evaluated with a two-compartment pharmacokinetic model and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Employing a two-compartment pharmacokinetic model, the theoretical signal enhancement from Gd-DTPA enhanced dynamic 3D gradient-recalled echo (GRE) images was shown to have a simple linear relationship with tissue concentration independent of flip angle. The signal-enhancement patterns for each individual knee were found to be characterized by three pharmacokinetic parameters: k(ep) (min(-1)), the rate constant; k(el) (min(-1)), the elimination rate constant; and E(R) (min(-1)), the initial enhancement rate, which is proportional to the transfer constant K(trans) (min(-1)). Characteristic patterns were observed in the image signal intensity-time course. The initial enhancement rate, E(R), in regions of interest (ROIs) was found to have a wide range of variation: 5 to 38 min(-1) over the distal femoral physis and 1 to 10 min(-1) in the synovium. The E(R) of the synovium was correlated with the E(R) of the distal femoral physis (P<.05). In addition, the E(R) of the synovium was correlated to the clinical outcome measures of knee swelling. Further investigation is needed to determine whether wide variations in the pharmacokinetic parameters reflect the degree of disease activity, and whether there are changes in response to therapy. This method can also be applied in adults with rheumatoid arthritis (RA) and other disorders where T(1)-weighted contrast is used (breast cancer, brain tumors).
Assuntos
Artrite Juvenil/diagnóstico , Meios de Contraste/farmacocinética , Gadolínio DTPA/farmacocinética , Aumento da Imagem/métodos , Articulação do Joelho/patologia , Imageamento por Ressonância Magnética/métodos , Adolescente , Artrite Juvenil/patologia , Compartimentos de Líquidos Corporais , Criança , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Masculino , Modelos Teóricos , Membrana Sinovial , Fatores de TempoRESUMO
The potential benefits of functional magnetic resonance imaging (MRI) for the investigation of normal development have been limited by difficulties in its use with children. We describe the practical aspects, including failure rates, involved in conducting large-scale functional MRI studies with normal children. Two hundred and nine healthy children between the ages of 5 and 18 years participated in a functional MRI study of language development. Reliable activation maps were obtained across the age range. Younger children had significantly higher failure rates than older children and adolescents. It is concluded that it is feasible to conduct large-scale functional MRI studies of children as young as 5 years old. These findings can be used by other research groups to guide study design and plans for recruitment of young subjects.