ABSTRACT
Objective: Positron emission tomography (PET) allows in vivo evaluation of molecular targets in neurodegenerative diseases, such as Alzheimer's disease. Mild cognitive impairment is an intermediate stage between normal cognition and Alzheimer-type dementia. In vivo fibrillar amyloid-beta can be detected in PET using [11C]-labeled Pittsburgh compound B (11C-PiB). In contrast, [18F]fluoro-2-deoxy-d-glucose (18F-FDG) is a neurodegeneration biomarker used to evaluate cerebral glucose metabolism, indicating neuronal injury and synaptic dysfunction. In addition, early cerebral uptake of amyloid-PET tracers can determine regional cerebral blood flow. The present study compared early-phase 11C-PiB and 18F-FDG in older adults without cognitive impairment, amnestic mild cognitive impairment, and clinical diagnosis of probable Alzheimer's disease. Methods: We selected 90 older adults, clinically classified as healthy controls, with amnestic mild cognitive impairment, or with probable Alzheimer's disease, who underwent an 18F-FDG PET, early-phase 11C-PiB PET and magnetic resonance imaging. All participants were also classified as amyloid-positive or -negative in late-phase 11C-PiB. The data were analyzed using statistical parametric mapping. Results: We found that the probable Alzheimer's disease and amnestic mild cognitive impairment group had lower early-phase 11C-PiB uptake in limbic structures than 18F-FDG uptake. The images showed significant interactions between amyloid-beta status (negative or positive). However, early-phase 11C-PiB appears to provide different information from 18F-FDG about neurodegeneration. Conclusions: Our study suggests that early-phase 11C-PiB uptake correlates with 18F-FDG, irrespective of the particular amyloid-beta status. In addition, we observed distinct regional distribution patterns between both biomarkers, reinforcing the need for more robust studies to investigate the real clinical value of early-phase amyloid-PET imaging.
ABSTRACT
OBJECTIVE: To describe a protocol that was based on an integrative neurobiological model of scientific investigation to better understand the pathophysiology of obsessive-compulsive disorder and to present the clinical and demographic characteristics of the sample. METHOD: A standardized research protocol that combines different methods of investigation (genetics, neuropsychology, morphometric magnetic resonance imaging and molecular neuroimaging of the dopamine transporter) obtained before and after treatment of drug-naïve adult obsessive-compulsive disorder patients submitted to a sequentially allocated 12-week clinical trial with a selective serotonin reuptake inhibitor (fluoxetine) and group cognitive-behavioral therapy. RESULTS: Fifty-two treatment-naïve obsessive-compulsive disorder patients entered the clinical trial (27 received fluoxetine and 25 received group cognitive-behavioral therapy). At baseline, 47 blood samples for genetic studies, 50 neuropsychological evaluations, 50 morphometrical magnetic resonance images and 48 TRODAT-1 single-photon emission computed tomography (SPECT) exams were obtained. After 12 weeks, 38 patients completed the protocol (fluoxetine = 20 and GCBT = 18). Thirty-eight neuropsychological evaluations, 31 morphometrical magnetic resonance images and 34 TRODAT-1 SPECT exams were obtained post-treatment. Forty-one healthy controls matched for age, gender, socioeconomic status, level of education and laterality were submitted to the same research procedures at baseline. CONCLUSION: The comprehensive treatment response protocol applied in this project allowing integration on genetic, neuropsychological, morphometrical and molecular imaging of the dopamine transporter data in drug-naïve patients has the potential to generate important original information on the neurobiology of obsessive-compulsive disorder, and at the same time be clinically meaningful.
OBJETIVO: Descrever um protocolo integrativo de investigação neurobiológica para melhor compreender as bases patofisiológicas do transtorno obsessivo-compulsivo e apresentar as características clínicas e demográficas da amostra. MÉTODO: Protocolo padronizado que combina diferentes modalidades de investigação (genética, neuropsicologia, ressonância magnética cerebral e imagem molecular do transportador de dopamina) obtidas antes e depois do tratamento em pacientes com transtorno obsessivo-compulsivo nunca expostos à medicação submetidos a um ensaio clínico comparando um inibidor seletivo da recaptação de serotonina (fluoxetina) e terapia cognitivo-comportamental em grupo. RESULTADOS: Cinquenta e dois pacientes com transtorno obsessivo-compulsivo entraram no ensaio clínico (27 no grupo fluoxetina e 25 no grupo de terapia). No início, foram realizadas 47 coletas de sangue para genética, 50 avaliações neuropsicológicas, 50 ressonâncias magnéticas cerebrais e 48 exames de tomografia computadorizada por emissão de fóton único (SPECT) com TRODAT-1. Depois de 12 semanas, 38 pacientes terminaram o protocolo (20 no grupo de fluoxetina e 18 no grupo de terapia). Trinta e oito reavaliações neuropsicológicas, 31 ressonâncias magnéticas de crânio e 34 exames de SPECT foram obtidos após o tratamento. Quarenta e um controles pareados foram submetidos ao mesmo protocolo inicial. CONCLUSÃO: Os dados genéticos, neuropsicológicos, volumétricos e moleculares do transportador de dopamina aliados à resposta a tratamento podem tanto gerar informações importantes a respeito da neurobiologia do transtorno obsessivo-compulsivo quanto ter uma aplicação clínica.
Subject(s)
Adolescent , Adult , Aged , Humans , Middle Aged , Young Adult , Cognitive Behavioral Therapy , Fluoxetine/therapeutic use , Obsessive-Compulsive Disorder/therapy , Selective Serotonin Reuptake Inhibitors/therapeutic use , Magnetic Resonance Imaging , Molecular Imaging , Obsessive-Compulsive Disorder/physiopathology , Tomography, Emission-Computed, Single-Photon , Treatment OutcomeABSTRACT
INTRODUÇÃO: O processamento de imagens de ressonância magnética (RM) estrutural tem sido amplamente utilizado em pesquisas neuro-psiquiátricas. Os métodos mais usados para este fim são a volumetria manual por regiões de interesse (regions of interest - ROIs) e a morfometria baseada no voxel (Voxel-based morphometry - VBM). Nesta tese, foi usado um banco de imagens de pacientes diagnosticados com transtorno-obsessivo compulsivo (TOC) (n=19) e controles saudáveis (n=15), as quais foram processadas nas duas técnicas de análise morfométrica denominadas VBM padrão e VBM otimizado. Foram comparados os resultados obtidos com tais métodos automatizados de VBM versus método de ROIs, e comparou-se também a incidência de artefatos de normalização espacial e segmentação entre o VBM padrão e o otimizado. MÉTODOS: As imagens foram processadas usando VBM com o programa Statistical Parametric Mapping (SPM), e ROIs foram desenhadas sobre as regiões cerebrais adjacentes aos ventrículos laterais usando o programa MRIcro. O processamento pelo VBM padrão incluiu normalização das imagens para um molde anatômico pré-definido, segmentação em compartimentos de substância cinzenta, branca e líquor, suavização com filtro gaussiano (12mm), e comparações estatísticas usando o modelo linear geral. Para o VBM otimizado, foram construídos moldes customizados para o próprio estudo. Utilizando estes moldes, as imagens foram segmentadas e normalizadas para cada compartimento cerebral, gerando parâmetros para que a imagem original pudesse ser normalizada de forma mais precisa. Após esta segunda normalização as imagens foram segmentadas, moduladas pelo determinante jacobiano, suavizadas com filtro gaussiano (12mm), e comparadas estatisticamente. As ROIs foram desenhadas seguindo padrões estabelecidos na literatura internacional. RESULTADOS: Para as regiões cerebrais nas quais se previa a priori a presença de anormalidades associadas ao TOC, o VBM otimizado mostrou alterações volumétricas de...
INTRODUCTION: Processing methods for magnetic resonance imaging (MRI) brain data have been largely used in research studies of psychiatric disorders. The techniques most widely used for this purpose are manual volumetry using regions of interest (ROIs) and voxel-based morphometry (VBM). In this thesis, images from a databank of patients diagnosed with obsessive-compulsive disorder (OCD) (n=19) and healthy controls (n=15) were processed using the two VBM methods, namely standard and optimized VBM. The results obtained with those two automated methods were compared to the ROI approach, and the presence of artifacts of spatial normalization and image segmentation were also compared between standard and optimized VBM. METHODS: Image processing using VBM was conducted with the Statistical Parametric Mapping (SPM) program, and the ROIs were drawn over the brain regions adjacent to the lateral ventricles using the MRIcro program. The standard VBM processing included normalization of images to a pre-defined template, segmentation in gray matter, white matter and cerebrospinal fluid compartments, gaussian smoothing (12mm), and statistical comparisons using the general linear model. For optimized VBM, customized templates were built specifically for the study. Using these templates, images were segmented and spatially normalized for each brain compartment, generating parameters that allowed spatial normalization of images with greater precision. After such second normalization, images were segmented, modulated using the jacobian determinants, smoothed with a gaussian filter (12mm), and compared statistically. The ROIs were built using guidelines established in the previous international literature. RESULTS: For the brain regions in which abnormalities in association with OCD were predicted a priori, optimized VBM showed gray matter changes in the OCD group relative to controls, including reduced volume of the anterior cingulate gyrus, and increased volume of the...