Imaging platform and computational HARDI atlas of the human hippocampus

总结 海马结构是神经影像学中的一个非常感兴趣的结构，这是由于其在广泛的神经成像中的关键作用。 神经系统疾病，包括癫痫、精神分裂症和阿尔茨海默病（AD）。三个... 复杂的海马内组织和子区域连接的三维映射是至关重要的 重要性，因为已知海马的不同亚区表现出选择性和差异性， 易患不同的神经系统疾病，如癫痫和AD。尽管它在主要领域发挥着核心作用， 神经系统疾病，人类海马的内部层状显微结构和亚区连通性 仍然难以用三维成像技术描绘。 该R 01提案的目标是开发第一个三维扩散MRI计算图谱， 完整的人类海马体拟议的地图集将以关键技术发展为基础， 在11.7T下对完整固定的海马进行高空间-角分辨率弥散MRI（dMRI）。的 基于来自多个海马的高角分辨率扩散成像（HARDI）数据的所得图谱 标本将以前所未有的方式描绘人类海马内组织和电路， 微观结构细节此外，目前对海马电路及其在疾病中的破坏的理解是 主要基于二维组织切片。本文建立的成像平台和dMRI图谱 将首次允许调查和三维绘制区域内特定变化， 海马结构在正常老化和AD大脑，提供了更大的海马病理学的细节， 比以前更详细。我们将从四个方面具体实现这些目标：（1）加快发展 用于组合（k，q）空间的有效采样的三维扩散MRI技术，（2）以获取 在11.7T下，将整个海马样本的高空间-角度分辨率3D dMRI数据组合，（3）至 构建一个计算平均的HARDI图谱的整个海马使用一个同构非线性 基于旋转不变HARDI特征和Riemannian平均的配准框架，以及（4） 研究正常衰老和AD海马内结构的区域变化。该项目带来 结合创新的成像技术和计算分析方法，这将使发展的 具有显微结构细节的高场dMRI图谱。完成后，这些目标将建立第一个HARDI 人类海马的图谱，这将是一个宝贵的资源，神经影像学研究，并提供 重要的见解，以促进我们对AD和衰老中海马病理学的理解。

Summary The hippocampal formation is a structure of acute interest in neuroimaging, due to its crucial role in a wide spectrum of neurological disorders, including epilepsy, schizophrenia, and Alzheimer’s disease (AD). Three- dimensional mapping of the complex intra-hippocampal organization and subfield connectivity is of paramount importance, since different subregions of the hippocampus are known to exhibit selective and differential vulnerability to different neurological diseases, such as epilepsy and AD. Despite its central role in major neurological disorders, the internal laminar microstructure and subfield connectivity of the human hippocampus remain difficult to delineate with three-dimensional imaging techniques. The goal of this R01 proposal is to develop the first three-dimensional diffusion MRI computational atlas of the intact whole human hippocampus. The proposed atlas will build on key technical developments enabling combined high spatio-angular resolution diffusion MRI (dMRI) of the intact fixed hippocampus at 11.7T. The resulting atlas based on high angular resolution diffusion imaging (HARDI) data from multiple hippocampus specimens will provide delineation of human intra-hippocampal organization and circuitry in unprecedented microstructural detail. Further, current understanding of hippocampal circuitry and its disruption in disease is largely based on two-dimensional histological sections. The imaging platform and dMRI atlas established here will allow for the first time, investigation and three-dimensional mapping of region-specific changes in intra- hippocampal structure in normal aging and AD brains, providing details of hippocampal pathology in greater detail than previously possible. We will achieve these goals in four specific aims: (1) to develop accelerated three-dimensional diffusion MRI techniques for efficient sampling of the combined (k,q)-space, (2) to acquire combined high spatio-angular resolution 3D dMRI data of whole hippocampal specimens at 11.7T, (3) to construct a computational averaged HARDI atlas of the whole hippocampus using a diffeomorphic non-linear registration framework based on rotation-invariant HARDI features and Riemannian averaging, and (4) to investigate regional changes in intra-hippocampal structure in normal aging and AD. This project brings together innovative imaging techniques and computational analysis methods, that will allow development of the high-field dMRI atlas with microstructural detail. Upon completion, these goals will establish the first HARDI atlas of the human hippocampus, which will be an invaluable resource for neuroimaging studies, and provide significant insights to advance our understanding of hippocampal pathology in AD and aging.