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Advisor(s)
Abstract(s)
A barreira hematoencefálica é uma estrutura cujas funções estão envolvidas na manutenção do normal funcionamento das células neuronais. O interesse na avaliação da sua permeabilidade através de imagem por ressonância magnética (IRM), nomeadamente através de estudos de perfusão, tem vindo a aumentar devido ao facto de permitir identificar in vivo, e de forma minimamente invasiva, a existência de lesões que alterem o seu normal funcionamento. Diversas patologias parecem afectar a permeabilidade da barreira hematoencefálica, sendo premente identificar e quantificar essa alteração para detecção, diferenciação e estadiamento deste tipo de lesões e desenvolvimento de novas metodologias terapêuticas. O objectivo deste estudo foi identificar a existência de alterações da permeabilidade da barreira hematoencefálica na doença de Alzheimer e perceber se esse facto é característico de alguma das regiões anatómicas de interesse analisadas (córtex visual, córtex pré-frontal, córtex estriado e hipocampo). Para tal, foram realizados estudos de perfusão em IRM, com recurso à técnica DCE (Dynamic Contrast Enhancement), em 8 ratinhos transgénicos, portadores e três mutações genéticas, e em 8 ratinhos saudáveis, aos 4, 8, 12 e 16 meses de idade. Posteriormente, foram calculados os parâmetros de perfusão Área Sob a Curva (Area Under the Curve - AUC), Tempo de Pico (Time to Peak - TTP), Amplitude do Pico de perfusão (Peak Amplitude - Pamp), Índice de Permeabilidade da barreira hematoencefálica (Blood-Brain Barrier Permeability Index - BBBi) e Wash-Out (WO). Comparando os parâmetros de perfusão entre os dois grupos de ratinhos, não se identificaram diferenças significativas, independentemente do parâmetro DCE considerado, para as regiões anatómicas do córtex visual nem para o córtex pré-frontal. No entanto, alguns parâmetros apresentaram diferenças significativas entre os grupos de ratinhos, no córtex estriado e no hipocampo, para os estadios mais avançados da doença (12 e 16 meses). Concluiu-se que as diferenças encontradas entre os dois grupos podem efectivamente estar relacionadas com alterações neurovasculares associadas à doença de Alzheimer, no entanto, podem estar apenas relacionadas com o envelhecimento normal dos animais. Por este motivo, propõe-se a realização de estudos complementares a este, que possam permitir um melhor esclarecimento destas situações.
ABSTRACT - The blood-brain barrier is a structure responsible for maintaining the normal functioning of the neuronal cells. The interest in the evaluation of its permeability through magnetic resonance imaging (MRI), namely through perfusion studies, has been increasing because it allows to identify in vivo, and in a less invasive way, the existence of lesions that affect their normal behavior. Several pathologies seem to affect the integrity of the blood-brain barrier, being of crucial importance to identify and quantify this variation to detect, differentiate and staging this type of lesions and allow the development of new therapeutically approaches. The aim of this study was to identify disfunctions of the blood-brain barrier in Alzheimer disease and understand if this variation in her permeability is usual in any of the anatomical regions analyzed (visual cortex, prefrontal cortex, striatum, and hippocampus). Therefore, perfusion studies in MRI, using a dynamic contrast enhancement (DCE) technique, were performed in 8 transgenic mice, with 3 genetical mutations, and in 8 healthy mice, at the ages of 4, 8, 12 and 16 months. Afterward, the perfusion parameters area under the curve (AUC), time to peak (TTP), peak amplitude (Pamp), Blood-Brain Barrier Permeability Index (BBBi) and wash-out (WO) were calculated. Comparing the perfusion parameters between the study groups, no significant differences were found, regardless of the DCE parameter considered, for the visual cortex or prefrontal cortex, however, some parameters showed significant differences between the groups in the striatum and in the Hippocampus, in advanced stages of the disease (12 and 16 months). It was concluded that the differences detected between the groups may effectively be related to neurovascular changes associated with Alzheimer disease, however, can be just related to the normal aging of the animals. For this reason, it is proposed to perform complementary studies to have a better understanding of these situations.
ABSTRACT - The blood-brain barrier is a structure responsible for maintaining the normal functioning of the neuronal cells. The interest in the evaluation of its permeability through magnetic resonance imaging (MRI), namely through perfusion studies, has been increasing because it allows to identify in vivo, and in a less invasive way, the existence of lesions that affect their normal behavior. Several pathologies seem to affect the integrity of the blood-brain barrier, being of crucial importance to identify and quantify this variation to detect, differentiate and staging this type of lesions and allow the development of new therapeutically approaches. The aim of this study was to identify disfunctions of the blood-brain barrier in Alzheimer disease and understand if this variation in her permeability is usual in any of the anatomical regions analyzed (visual cortex, prefrontal cortex, striatum, and hippocampus). Therefore, perfusion studies in MRI, using a dynamic contrast enhancement (DCE) technique, were performed in 8 transgenic mice, with 3 genetical mutations, and in 8 healthy mice, at the ages of 4, 8, 12 and 16 months. Afterward, the perfusion parameters area under the curve (AUC), time to peak (TTP), peak amplitude (Pamp), Blood-Brain Barrier Permeability Index (BBBi) and wash-out (WO) were calculated. Comparing the perfusion parameters between the study groups, no significant differences were found, regardless of the DCE parameter considered, for the visual cortex or prefrontal cortex, however, some parameters showed significant differences between the groups in the striatum and in the Hippocampus, in advanced stages of the disease (12 and 16 months). It was concluded that the differences detected between the groups may effectively be related to neurovascular changes associated with Alzheimer disease, however, can be just related to the normal aging of the animals. For this reason, it is proposed to perform complementary studies to have a better understanding of these situations.
Description
Mestrado em Radiações Aplicadas às Tecnologias da Saúde. Ramo de especialização: Imagem por Ressonância Magnética.
Keywords
Doença de Alzheimer Barreira hematoencefálica Perfusão em ressonância magnética Córtex visual Córtex pré-frontal Córtex estriado Hipocampo Amplitude do pico de perfusão Alzheimer's disease Blood-brain barrier Magnetic resonance perfusion Visual cortex Prefrontal cortex Striatum Hippocampus Peak amplitude Blood-brain Barrier Permeability Index
Citation
Batista MC. Avaliação da permeabilidade da barreira hematoencefálica num modelo animal da doença de Alzheimer: estudos de perfusão em ressonância magnética [dissertation]. Lisboa: Escola Superior de Tecnologia da Saúde de Lisboa/Instituto Politécnico de Lisboa; 2018.
Publisher
Escola Superior de Tecnologia da Saúde de Lisboa/Instituto Politécnico de Lisboa