RESUMO
The purpose of this study was to provide proof of concept for a new three-dimensional (3D) radial dynamic contrast enhanced MRI acquisition technique, called "Radial Entire Tumor with Individual Arterial input function dynamic contrast-enhanced MRI" (RETIA dynamic contrast-enhanced MRI), which allows for the simultaneous measurement of an arterial input function in the mouse heart at 2 s temporal resolution and coverage of the whole tumor. Alternating 2D and 3D projections contribute to the 2D heart image or 3D tumor data with a 3-cm field of view. Sixty-four 2D images of the heart are obtained during acquisition of each 3D tumor dataset. In a pilot study, global K(trans) and ve values were measured in four mice, in a respiratory motion-animated subcutaneously implanted breast tumor model. This technique is expected to be most useful for the characterization of microvasculature in motion-animated orthotopic tumors.
Assuntos
Imagem Cinética por Ressonância Magnética/métodos , Neoplasias Experimentais/irrigação sanguínea , Animais , Artérias , Feminino , Neoplasias Cardíacas/irrigação sanguínea , Neoplasias Mamárias Experimentais/irrigação sanguínea , Camundongos , Projetos PilotoRESUMO
Alzheimer's disease (AD), the most common age-related neurodegenerative disorder, is characterized by the invariant cerebral accumulation of ß-amyloid peptide. This event occurs early in the disease process. In humans, [18F]-fluoro-2-deoxy-D-glucose ([18F]-FDG) positron emission tomography (PET) is largely used to follow-up in vivo cerebral glucose utilization (CGU) and brain metabolism modifications associated with the Alzheimer's disease pathology. Here, [18F]-FDG positron emission tomography was used to study age-related changes of cerebral glucose utilization under resting conditions in 3-, 6-, and 12-month-old APP(SweLon)/PS1(M146L), a mouse model of amyloidosis. We showed an age-dependent increase of glucose uptake in several brain regions of APP/PS1 mice but not in control animals and a higher [18F]-FDG uptake in the cortex and the hippocampus of 12-month-old APP/PS1 mice as compared with age-matched control mice. We then developed a method of 3-D microscopic autoradiography to evaluate glucose uptake at the level of amyloid plaques and showed an increased glucose uptake close to the plaques rather than in amyloid-free cerebral tissues. These data suggest a macroscopic and microscopic reorganization of glucose uptake in relation to cerebral amyloidosis.
Assuntos
Doença de Alzheimer/patologia , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Circulação Cerebrovascular/fisiologia , Glucose/metabolismo , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Análise de Variância , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Córtex Cerebral/diagnóstico por imagem , Circulação Cerebrovascular/genética , Modelos Animais de Doenças , Fluordesoxiglucose F18 , Proteína Glial Fibrilar Ácida/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas dos Microfilamentos/metabolismo , Tomografia por Emissão de Pósitrons , Presenilina-1/genéticaRESUMO
T1 and T2 magnetic resonance relaxation times have the potential to provide biomarkers of amyloid-beta deposition that could be helpful to the development of new therapies for Alzheimer's disease. Here, we measured T1 and T2 times as well as plaques and iron loads in APP/PS1 mice, which model brain amyloidosis, and control PS1 mice. Iron was mostly associated with amyloid deposits in APP/PS1 animals, while it was diffuse in the PS1 mice. T1 was negatively correlated with age in most structures in APP/PS1 animals. This may be related to the age-associated myelin loss described in APP/PS1 mice rather than to amyloid deposition. T2 in the subiculum of adult APP/PS1 animals was lower than in PS1 mice, which may be related to the very high amyloid and iron loads in this region. T2 in the subiculum could thus serve as an early marker of the amyloid pathology.