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Ultrahigh-resolution fMRI of age-altered hippocampal subfield-cortical interactions

年龄改变的海马亚场-皮质相互作用的超高分辨率功能磁共振成像

基本信息

批准号：
9980246
负责人：
Wei-Tang Chang
金额：
$ 23.33万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-01 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9980246
关键词：
3-Dimensional Acceleration Address Affect Age Age-Years Aging Alzheimer disease detection Alzheimer&apos s Disease Alzheimer&apos s disease diagnosis Alzheimer’s disease biomarker Area Biological Markers Brain Brain region Cerebrum Clinical Data Deltastab Dependence Development Diffusion Magnetic Resonance Imaging Early Diagnosis Ensure Exhibits Foundations Functional Magnetic Resonance Imaging Future Head Hippocampal Formation Hippocampus (Brain)Human Image Intervention Learning Magnetic Resonance Imaging Maps Medical Memory Methods Morphologic artifacts Motion Names Network-based Neurodegenerative Disorders Noise Parietal Participant Pathology Performance Physiological Play Positioning Attribute Public Health Reporting Research Resolution Rest Role Scanning Seeds Signal Transduction Slice Structural defect Structure System Techniques Technology Testing Thick Thinness Time Visual Width age effect age related association cortex base connectome early detection biomarkers frontal lobe improved insight neocortical novel novel imaging technology novel marker novel strategies prisma temporal measurement

项目摘要

PROJECT SUMMARY The hippocampus plays a major role in learning and memory, and it is the earliest and most severely affected structure in neurodegenerative disorders such as Alzheimer's disease (AD). The hippocampal formation consists of several distinct subfields, which contribute to different aspects of memory function, as well as exhibit different brain network topologies. A better understanding of how aging affects functional cortical-hippocampal subfield networks is an important step towards the development of an early AD biomarker. Resting-state functional connectivity magnetic resonance imaging (rs-fcMRI) has been widely used to study large-scale functional networks noninvasively. However, the brain-wide functional connectivity of hippocampal subfields in human brain remains poorly understood mainly due to the technical limitation. The physical constraint of excitation slice thickness and insufficient acceleration capability has led to compromises of spatial resolution, field-of-view (FOV), or scan time per volume in several early attempts. We developed a new approach capable of mitigating the aforementioned limitations. The novel technique, named Partition-encoded Simultaneous Multi-slab (PRISM) imaging, achieves sub-millimeter isotropic resolution, while maintaining a high temporal resolution and whole-brain coverage, highly critical for interrogating hippocampal-subfield whole-brain functional networks. Our preliminary results of resting-state FC not only were consistent with the findings that the hippocampus is connected with several cortical regions including parietal association, temporal association and frontal cortices, but also suggested that different hippocampal subfields are associated with different sets of cortical regions. Additionally, the task-based functional connectivity (FC) suggested that the visual association cortex connected stronger with CA4/DG rather than with CA1 during the mnemonic similarity task. Given the preliminary results and previous findings, we hypothesize that 1) the age-dependent effects are heterogeneous between cortical-hippocampal subfield networks, and 2) more neocortical regions show stronger connections with CA4/DG than with CA1 as the age increases. To address these hypotheses, we will further refine the PRISM approach by alleviating signal loss resulting from the T1-saturation effect at the slab boundary and by reducing the sensitivity to head motion. In addition, we will implement the PRISM sequence on the Siemens Prisma 3T system to maximize its future clinical impacts. Thereby, we will investigate the dependency of connectivity strength on age across different cortical-hippocampal subfield networks. Successful implementation of this proposal will fill the gap between local and global hippocampal-subfield circuitry and identify a novel biomarker for early diagnosis of AD in the future.

项目摘要海马在学习记忆中起主要作用，而且是最早也是最严重的在神经退行性疾病如阿尔茨海默氏病（AD）中的受影响结构。海马形成由几个不同的子领域组成，这些子领域对记忆功能的不同方面做出贡献，也展示了不同的大脑网络拓扑结构。更好地了解衰老如何影响功能皮质-海马子域网络是开发早期AD生物标志物的重要一步。静息态功能连接磁共振成像（rs-fcMRI）已被广泛用于研究大规模的功能网络。然而，海马神经元的全脑功能连接主要由于技术限制，对人脑中的子场仍然知之甚少。物理激励切片厚度的限制和不足的加速能力导致了空间的妥协分辨率、视场（FOV）或在几次早期尝试中每体积的扫描时间。我们开发了一种能够减轻上述限制的新方法。小说一种称为分区编码同步多板成像（PRISM）的技术，可以实现亚毫米级成像各向同性分辨率，同时保持高的时间分辨率和全脑覆盖，这对于询问全脑功能网络。我们对静息态FC的初步结果不仅与海马体与几个皮层区域相连的发现相一致，包括顶叶联合，颞叶联合和额叶皮质，但也表明，不同的海马子区域与不同组的皮质区域相关。此外，基于任务的功能连接（FC）提示视觉联合皮层与CA 4/DG的连接更强而不是在记忆相似性任务中使用CA 1。鉴于初步结果和以前的发现，我们假设：1）年龄依赖性效应皮质-海马子域网络之间的异质性，2）更多的新皮质区域显示随着年龄的增长，与CA 4/DG的联系比与CA 1的联系更强。为了解决这些问题，我们将通过减轻由平板处的T1饱和效应引起的信号损失，进一步改进PRISM方法边界，并通过降低头部运动的敏感度。此外，我们将实现PRISM序列西门子Prisma 3 T系统，以最大限度地提高其未来的临床影响。因此，我们将调查不同皮质-海马子域网络之间连接强度对年龄的依赖性。该提案的成功实施将填补地方和全球医疗保健领域之间的差距电路，并确定一种新的生物标志物，为早期诊断AD的未来。