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1.
Proc Natl Acad Sci U S A ; 110(47): E4502-9, 2013 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-24194552

RESUMO

Major imaging biomarkers of Alzheimer's disease include amyloid deposition [imaged with [(11)C]Pittsburgh compound B (PiB) PET], altered glucose metabolism (imaged with [(18)F]fluro-deoxyglucose PET), and structural atrophy (imaged by MRI). Recently we published the initial subset of imaging findings for specific regions in a cohort of individuals with autosomal dominant Alzheimer's disease. We now extend this work to include a larger cohort, whole-brain analyses integrating all three imaging modalities, and longitudinal data to examine regional differences in imaging biomarker dynamics. The anatomical distribution of imaging biomarkers is described in relation to estimated years from symptom onset. Autosomal dominant Alzheimer's disease mutation carrier individuals have elevated PiB levels in nearly every cortical region 15 y before the estimated age of onset. Reduced cortical glucose metabolism and cortical thinning in the medial and lateral parietal lobe appeared 10 and 5 y, respectively, before estimated age of onset. Importantly, however, a divergent pattern was observed subcortically. All subcortical gray-matter regions exhibited elevated PiB uptake, but despite this, only the hippocampus showed reduced glucose metabolism. Similarly, atrophy was not observed in the caudate and pallidum despite marked amyloid accumulation. Finally, before hypometabolism, a hypermetabolic phase was identified for some cortical regions, including the precuneus and posterior cingulate. Additional analyses of individuals in which longitudinal data were available suggested that an accelerated appearance of volumetric declines approximately coincides with the onset of the symptomatic phase of the disease.


Assuntos
Doença de Alzheimer/patologia , Biomarcadores/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Adulto , Idade de Início , Doença de Alzheimer/genética , Compostos de Anilina/metabolismo , Radioisótopos de Carbono/metabolismo , Estudos de Coortes , Feminino , Fluordesoxiglucose F18/metabolismo , Genes Dominantes/genética , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Tomografia por Emissão de Pósitrons/métodos , Análise de Regressão , Tiazóis/metabolismo , Fatores de Tempo
2.
Neuroimage ; 107: 55-64, 2015 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-25485714

RESUMO

Amyloid imaging is a valuable tool for research and diagnosis in dementing disorders. As positron emission tomography (PET) scanners have limited spatial resolution, measured signals are distorted by partial volume effects. Various techniques have been proposed for correcting partial volume effects, but there is no consensus as to whether these techniques are necessary in amyloid imaging, and, if so, how they should be implemented. We evaluated a two-component partial volume correction technique and a regional spread function technique using both simulated and human Pittsburgh compound B (PiB) PET imaging data. Both correction techniques compensated for partial volume effects and yielded improved detection of subtle changes in PiB retention. However, the regional spread function technique was more accurate in application to simulated data. Because PiB retention estimates depend on the correction technique, standardization is necessary to compare results across groups. Partial volume correction has sometimes been avoided because it increases the sensitivity to inaccuracy in image registration and segmentation. However, our results indicate that appropriate PVC may enhance our ability to detect changes in amyloid deposition.


Assuntos
Neuropatias Amiloides/diagnóstico por imagem , Amiloide/metabolismo , Algoritmos , Doença de Alzheimer/diagnóstico por imagem , Compostos de Anilina , Benzotiazóis , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Estudos de Coortes , Simulação por Computador , Estudos Transversais , Humanos , Individualidade , Estudos Longitudinais , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Tiazóis
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