Volumetric and morphological analysis of the memory circuit in healthy ageing

健康衰老过程中记忆回路的体积和形态分析

• 批准号: RGPIN-2014-04034
• 负责人: Chakravarty, Mallar
• 金额: $ 2.26万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=587565
• 关键词: Volumetric; morphological; analysis; memory; circuit

The hippocampus is located in the medial temporal of the brain and has long been associated with episodic memory in humans and has long been associated with several neuropsychiatric disorders such as Alzheimer’s disease and schizophrenia. Further, there is a well-known relationship between healthy ageing and the overall decline in volume of the hippocampus. In modern magnetic resonance imaging (MRI) studies, the hippocampus is typically treated as a single homogeneous structure with uniform function. However, the hippocampus is truly the combination of several intricately patterned subfields, with complex three-dimensional geometry and inter-spatial relationships. Further, there are very few analyses of the entire memory network that include the hippocampus, entorhinal cortex, the fornix, and mamillary bodies. Further, although many groups are using these software packages as a means to assess hippocampal subfield volume, there is little to no knowledge in the literature regarding the trajectories of hippocampal subfield volumes or the neuroanatomy of the memory network through the course of healthy ageing. The goal of this research proposal is to map the volumetric and morphometric trajectories of the hippocampus in males and females through the course of healthy ageing using a robust MRI image acquisition and segmentation pipeline. My group has recently published a detailed MRI acquisition and manual segmentation protocol that allows for T1- and T2-weighted high-resolution scanning (300 micron isotropic voxel dimensions) of the entire brain on a 3T MRI scanner (available to most research centres) that we have paired with a detailed manual segmentation protocol. These acquisitions, when paired with a detailed segmentation protocol, allows for the robust and reliable identification of the cornu ammonus (CA1), CA2/3, CA4/Dentate Gyrus, the molecular layers, and the subiculum. Despite it’s robustness, the manual segmentation protocol is time consuming even for the most skilled manual rater. Thus, this proposal will pair our manual segmentations with a sophisticated image processing pipeline, developed in my group, that uses a small number of manually labeled imaged as inputs and then bootstraps the segmentation process using the subject set being analyzed to provide a final set of accurate segmentation level, even at the level of the hippocampal subfields. The study design will be as follows. We will recruit 62 subjects between the ages of 18 and 80. High-resolution T1- and T2-weighted image volumes will be acquired for each study participant and automatically segmented using the image segmentation software developed in my group. Sexually dimorphic and age related tends in overall hippocampal volume and shape will be assessed. Shape analysis will be carried out relative to a surface-based population mean representation. Local vertex-wise inward and outward displacements will be used as the metric of interest for assessing shape using an extension of the segmentation pipeline previously described. The result of this work will be the first comprehensive analysis of the memory network through the course healthy ageing and will provide a baseline for other studies that are interested in the relationship between the subfields and cognitive abilities. As is the ethic of my research team, we propose not only to develop these imaging protocols and automatically generated segmentations, but to also make all our data publicly available (as we have done with our previous atlas work and algorithmic work; see http://imaging-genetics.camh.ca/Hippocampus and https://github.com/pipitone/MAGeTbrain respectively).

海马体位于大脑内侧颞叶，长期以来一直与人类的情景记忆有关，并与阿尔茨海默病和精神分裂症等几种神经精神疾病有关。此外，在健康衰老和海马体体积总体下降之间存在着众所周知的关系。在现代磁共振成像（MRI）研究中，海马体通常被视为具有统一功能的单一均匀结构。然而，海马体实际上是几个复杂模式子区域的组合，具有复杂的三维几何和空间间关系。此外，对包括海马体、内嗅皮质、穹窿和乳状体在内的整个记忆网络的分析很少。此外，尽管许多研究小组正在使用这些软件包作为评估海马体子区体积的一种手段，但在文献中，关于海马体子区体积的轨迹或记忆网络在健康衰老过程中的神经解剖学知识很少或根本没有。本研究计划的目标是利用强大的MRI图像采集和分割管道，绘制男性和女性在健康衰老过程中海马体的体积和形态轨迹。