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

• 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
• 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' 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

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）：随着寿命的增加，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的体内解剖磁共振成像（MRI）方法，用于评估内侧颞叶（MTL）的微观结构，其中神经元缠结首次出现在早期AD和β-淀粉样蛋白沉积物中，最终导致痴呆和记忆丧失。提出的成像技术可能有助于早期发现和提高对AD的认识。可靠的疾病早期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，这是一个具有技术挑战性的领域，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。具体而言，我们的目标是对嗅周皮质（特别是第II - III层和皮质厚度）、内嗅皮质（第II层中富含细胞的岛的疣）和海马（子场和分子层）内的结构进行成像。从体外成像，我们知道看到这些结构所需的分辨率。我们的目标是实现3003 um 3和1502 x1200 um 3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。我们将使用最大的N阵列，3 T和7 T字段，扫描时间<= 3小时。为了确保窄点扩散函数（PSF），尽管在长扫描期间受试者运动，我们将基于导航器的实时运动、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）。数据将被流式传输到外部存储设备进行离线处理。将使用最佳组合通道、最佳GRAPPA和复杂平均重建图像。可以从较低分辨率的图像添加先前信息以减少扫描时间。 10个离体MTL样本（5个健康样本，5个AD样本）将在1003 μ m 3下成像，以便所有结构可见并经组织学确认。将对10名健康志愿者和20名老年受试者（10名健康受试者和10名轻度认知障碍受试者）的体内体积进行降采样，以确定所需的分辨率。一名神经解剖专家和经过培训的研究助理（对采集参数不知情）将识别所有体内和体外体积中的结构。图像清晰度将从理论和经验上进行评估。将在5003 um 3和2502 x2000 um 3下评价体内运动校正T2成像。 利用由此产生的技术和知识，我们将提出（1）一个实用的AD临床试验3 T方案， mMR（MR-PET）系统，（2）在3 T和7 T下用于AD研究的更密集的MR协议和（3）极高分辨率组织成像协议，每个协议都有一个可见结构列表。