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: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=610795
• 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).

海马位于大脑的内侧，长期以来与人类的情节记忆有关，长期以来一直与几种神经精神疾病有关，例如阿尔茨海默氏病和精神分裂症。此外，健康衰老与海马体积的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，海马通常被视为具有均匀功能的单个同质结构。但是，海马确实是几个复杂的图案子场的结合，具有复杂的三维几何形状和空间间关系。此外，对整个内存网络的分析很少，包括海马，内嗅皮层，福尼克斯和mamillary身体。此外，尽管许多小组都使用这些软件包作为评估海马子场量的一种手段，但文献中几乎没有关于海马子场量的轨迹或通过健康衰老的记忆网络的轨迹的轨迹。该研究建议的目的是使用强大的MRI图像采集和分段管道来绘制男性和女性海马和女性海马的体积和形态轨迹。 我的小组最近发布了一项详细的MRI采集和手动分割协议，该协议允许在3T MRI扫描仪（可用于大多数研究中心）上的T1-和T2加权高分辨率扫描（300微米各向同性体素维度），该扫描仪可与我们与详细的手动分组协议配对。这些采集与详细的分割协议配对时，可以允许对Cornu Ammonus（CA1），Ca2/3，Ca4/Dentate Gyrus，Molecular Layers和subiculum的稳健且可靠的鉴定。尽管具有鲁棒性，但即使是最熟练的手动分数，手动细分协议也很耗时。该提案将使我们的手动分割与我的小组中开发的复杂图像处理管道相结合，该管道使用少数手动标记为输入的手动标记，然后使用分析的主题集进行分割过程，以提供最终的准确分割水平，即使在海马室子场的水平下也是如此。 研究设计将如下。我们将在18至80岁之间招募62名受试者。每个研究参与者将获得高分辨率T1和T2加权图像量，并使用我小组中开发的图像分割软件自动进行分割。将评估海马体积和形状的性二态和年龄相关的趋势。形状分析将相对于基于表面的种群平均表示。局部顶点的内向和向外位移将用作使用先前描述的分割管道的扩展来评估形状的关注度量。这项工作的结果将是通过健康衰老的课程对记忆网络的首次综合分析，并将为其他研究中的研究提供基准，这些研究在子场与认知能力之间的关系中很有趣。 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).