High Resolution Hippocampal Magnetic Resonance Imaging for Alzheimer's Research

用于阿尔茨海默病研究的高分辨率海马磁共振成像

基本信息

批准号：
8916534
负责人：
Andre Jan Willem van der Kouwe
金额：
$ 21.1万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-01 至 2018-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8916534
关键词：
Affect Alzheimer&apos s Disease American Amyloid beta-Protein Area Atlases Atrophic Blinded Brain Brain imaging Cells Clinical Trials Common wart Complex Data Dementia Deposition Devices Diagnosis Disease Early Diagnosis Ensure Frequencies Goals Health Hippocampal Formation Hippocampus (Brain)Histology Hour Human Volunteers Image Imaging Techniques Intervention Island Knowledge Label Life Location Longevity Magnetic Resonance Imaging Magnetism Medial Memory Loss Methods Microscopic Motion Neurodegenerative Disorders Neurofibrillary Tangles Noise Onset of illness Output Parietal Lobe Participant Patients Phase Positron-Emission Tomography Predisposition Process Protocols documentation Recruitment Activity Research Research Training Resolution Running Sampling Scanning Societies Staging Staining method Stains Stream Structure Structure of molecular layer of cerebellar cortex Symptoms System Techniques Technology Temporal Lobe Testing Thick Time Tissues Training Vaccines Weight Work alveus base cerebral atrophy cost design entorhinal cortex follow-up healthy volunteer image reconstruction imaging biomarker imaging modality improved in vivo in vivo imaging innovation interest mild cognitive impairment neocortical neuroimaging reconstruction simulation tool ultra high resolution volunteer

项目摘要

DESCRIPTION (provided by applicant): As longevity increases, Alzheimer's disease (AD) is becoming more prevalent, with 5.4 million Americans living with AD in 2012, costing society more than $100 billion per year. In this study we will develop high resolution in vivo anatomical magnetic resonance imaging (MRI) methods for evaluating microstructures of the medial temporal lobe (MTL), where neurofibrillary tangles first appear in early AD and beta-amyloid deposits accumulate, leading eventually to dementia and memory loss. The proposed imaging techniques may contribute to early detection and improved understanding of AD. Reliable early-disease-stage imaging biomarkers are critically important in trials evaluating targeted interventions like anti-beta-amyloid vaccines. Although our methods apply to whole brain imaging, we will optimize and validate using anatomical targets in the MTL. This is a technically challenging area for MRI due to its location relatively deep in the brain and near to areas of differing magnetic susceptibility. Specifically, we aim to image structures within the perirhinal cortex (specifically layers II - III and cortical thickness), entorhinal cortex (verrucae that contin cell rich islands in layer II) and hippocampus (subfields and molecular layer). From ex vivo imaging, we know the resolutions required to see these structures. We aim to achieve in vivo resolutions of 3003 um3 and 1502x1200 um3. We will integrate well-developed methods with experimental approaches to enable robust, efficient, high resolution T1-weighted imaging. Receive coil design, field strength and acquisition time contributes substantially to SNR (therefore resolution). We will use the largest-N arrays, 3 T and 7 T fields, and scan times <= 3 hours. To ensure a narrow point spread function (PSF) despite subject motion during long scans, we will integrate real-time navigator-based motion, frequency drift and first order shim tracking into a low distortion MEMPRAGE with inner-loop GRAPPA (for better contrast and PSF). Data will be streamed to an external storage device for offline processing. Images will be reconstructed with optimally combined channels, optimal GRAPPA and complex averaging. Prior information may be added from lower-resolution images to decrease scan time. Ten ex vivo MTL samples (5 healthy, 5 AD) will be imaged at 1003 um3 so that all structures are visible and confirmed with histology. Volumes will be down-sampled to determine required resolution for in vivo volumes in 10 healthy volunteers and 20 older participants (10 healthy and 10 with mild cognitive impairment). An expert neuroanatomist and trained research assistant, blinded to acquisition parameters, will identify structures in all in vivo and ex vivo volumes. Image sharpness will be evaluated theoretically and empirically. In vivo motion corrected T2 imaging will be evaluated at 5003 um3 and 2502x2000 um3. With the resulting technology and knowledge, we will propose (1) a practical 3 T protocol for AD clinical trials, compatible with the mMR (MR-PET) system, (2) more intensive MR protocols for AD research at 3 T and 7 T and (3) a protocol for extremely high resolution tissue imaging, with a list of visible structures for each.

描述（由申请人提供）：随着寿命的延长，阿尔茨海默病 (AD) 变得越来越普遍，2012 年有 540 万美国人患有 AD，每年给社会造成的损失超过 1000 亿美元。在这项研究中，我们将开发高分辨率体内解剖磁共振成像 (MRI) 方法来评估内侧颞叶 (MTL) 的微观结构，其中神经原纤维缠结首先出现在 AD 早期，β-淀粉样蛋白沉积物积累，最终导致痴呆和记忆丧失。所提出的成像技术可能有助于早期检测和提高对 AD 的理解。可靠的早期疾病阶段成像生物标志物在评估抗β淀粉样蛋白疫苗等靶向干预措施的试验中至关重要。虽然我们的方法适用于全脑成像，但我们将使用 MTL 中的解剖目标进行优化和验证。对于 MRI 来说，这是一个技术上具有挑战性的领域，因为它位于大脑相对较深的位置，并且靠近不同磁化率的区域。具体来说，我们的目标是对鼻周皮质（特别是 II - III 层和皮质厚度）、内嗅皮质（在 II 层中延续细胞丰富岛的疣）和海马体（子区域和分子层）内的结构进行成像。通过离体成像，我们知道观察这些结构所需的分辨率。我们的目标是实现 3003 um3 和 1502x1200 um3 的体内分辨率。我们将把成熟的方法与实验方法相结合，以实现稳健、高效、高分辨率的 T1 加权成像。接收线圈设计、场强和采集时间对 SNR（因此分辨率）有很大影响。我们将使用最大 N 阵列、3 T 和 7 T 场，扫描时间 <= 3 小时。为了确保在长扫描过程中即使对象运动也能实现窄点扩散函数 (PSF)，我们将把基于实时导航器的运动、频率漂移和一阶匀场跟踪集成到具有内环 GRAPPA 的低失真 MEMPRAGE 中（以获得更好的对比度和PSF）。数据将传输到外部存储设备以进行离线处理。图像将通过最佳组合通道、最佳 GRAPPA 和复杂平均来重建。可以从较低分辨率的图像中添加先验信息以减少扫描时间。十个离体 MTL 样本（5 个健康样本，5 个 AD）将以 1003 um3 成像，以便所有结构可见并通过组织学确认。对体积进行下采样，以确定 10 名健康志愿者和 20 名老年参与者（10 名健康志愿者和 10 名患有轻度认知障碍）体内体积所需的分辨率。专家神经解剖学家和训练有素的研究助理，在不了解采集参数的情况下，将识别所有体内和离体体积中的结构。图像清晰度将从理论上和经验上进行评估。体内运动校正 T2 成像将在 5003 um3 和 2502x2000 um3 下进行评估。凭借由此产生的技术和知识，我们将提出（1）一种实用的 AD 临床试验 3T 方案，与 mMR (MR-PET) 系统，(2) 用于 3 T 和 7 T 的 AD 研究的更密集 MR 协议，以及 (3) 用于极高分辨率组织成像的协议，每个协议都有可见结构列表。