RESUMO
UNLABELLED: PET radioligand binding to the 18-kD translocator protein (TSPO) in the brains of patients with multiple sclerosis (MS) primarily reflects activated microglia and macrophages. We previously developed genetic stratification for accurate quantitative estimation of TSPO using second-generation PET radioligands. In this study, we used (18)F-PBR111 PET and MR imaging to measure relative binding in the lesional, perilesional, and surrounding normal-appearing white matter of MS patients, as an index of the innate immune response. METHODS: (18)F-PBR111 binding was quantified in 11 MS patients and 11 age-matched healthy volunteers, stratified according to the rs6971 TSPO gene polymorphism. Fluid-attenuated inversion recovery and magnetization transfer ratio (MTR) MR imaging were used to segment the white matter in MS patients as lesions, perilesional volumes, nonlesional white matter with reduced MTR, and nonlesional white matter with normal MTR. RESULTS: (18)F-PBR111 binding was higher in the white matter lesions and perilesional volumes of MS patients than in white matter of healthy controls (P < 0.05). Although there was substantial heterogeneity in binding between different lesions, a within-subject analysis showed higher (18)F-PBR111 binding in MS lesions (P < 0.05) and in perilesional (P < 0.05) and nonlesional white matter with reduced MTR (P < 0.005) than in nonlesional white matter with a normal MTR. A positive correlation was observed between the mean (18)F-PBR111 volume of distribution increase in lesions relative to nonlesional white matter with a normal MTR and the MS severity score (Spearman ρ = 0.62, P < 0.05). CONCLUSION: This study demonstrates that quantitative TSPO PET with a second-generation radioligand can be used to characterize innate immune responses in MS in vivo and provides further evidence supporting an association between the white matter TSPO PET signal in lesions and disease severity. Our approach is practical for extension to studies of the role of the innate immune response in MS for differentiation of antiinflammatory effects of new medicines and their longer term impact on clinical outcome.
Assuntos
Esclerose Múltipla/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Piridinas , Substância Branca/diagnóstico por imagem , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Inflamação/diagnóstico por imagem , Macrófagos/imunologia , Masculino , Microglia/patologia , Pessoa de Meia-Idade , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologia , Reprodutibilidade dos Testes , Substância Branca/imunologia , Substância Branca/patologiaRESUMO
Muscle damage, edema, and fat infiltration are hallmarks of a range of neuromuscular diseases. The T(2) of water, T(2,w) , in muscle lengthens with both myocellular damage and inflammation and is typically measured using multiple spin-echo or Carr-Purcell-Meiboom-Gill acquisitions. However, microscopic fat infiltration in neuromuscular diseases prevents accurate T(2,w) quantitation as the longer T(2) of fat, T(2,f) , masks underlying changes in the water component. Fat saturation can be inconsistent across the imaging volume and removes valuable physiological fat information. A new method is presented that combines iterative decomposition of water and fat with echo asymmetry and least squares estimation with a Carr-Purcell-Meiboom-Gill-sequence. The sequence results in water and fat separated images at each echo time for use in T(2,w) and T(2,f) quantification. With knowledge of the T(2,w) and T(2,f) , a T(2) -corrected fat fraction map can also be calculated. Monte-Carlo simulations and measurements in phantoms, volunteers, and a patient with inclusion body myositis are demonstrated. In healthy volunteers, uniform T(2,w) and T(2) -corrected fat fraction maps are present within all muscle groups. However, muscle-specific patterns of fat infiltration and edema are evident in inclusion body myositis, which demonstrates the power of separating and quantifying the fat and water components.