High Resolution Hippocampal Magnetic Resonance Imaging for Alzheimer's Research

描述(申请人提供)：随着寿命的延长，阿尔茨海默病(AD)正变得越来越普遍，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在体解剖磁共振成像(MRI)方法来评估内侧颞叶(MTL)的微结构，内侧颞叶(MTL)在AD早期首次出现神经原纤维缠结，并积聚β-淀粉样蛋白，最终导致痴呆和记忆丧失。所提出的成像技术可能有助于AD的早期发现和更好的理解。可靠的疾病早期成像生物标记物在评估抗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。这对核磁共振来说是一个具有技术挑战性的领域，因为它在大脑中的位置相对较深，而且靠近不同磁化率的区域。具体地说，我们的目标是成像周围皮质(特别是第II-III层和皮质厚度)、内嗅皮层(包含富含细胞的第二层的疣)和海马体(亚场和分子层)内的结构。从体外成像中，我们知道了观察这些结构所需的分辨率。我们的目标是在体内达到3003um3和1502x1200um3的分辨率。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个阵列，3T和7T场，扫描时间=3小时。为了确保在长扫描过程中主体运动时仍能获得窄点扩展函数(PSF)，我们将基于导航仪的实时运动、频率漂移和一阶填补跟踪集成到一个带有内环GRAPPA的低失真MEMPRAGE中(以获得更好的对比度和PSF)。数据将被传输到外部存储设备进行离线处理。图像将通过最佳组合通道、最佳GRAPPA和复数平均进行重建。可以从较低分辨率的图像添加先验信息以减少扫描时间。10个体外MTL样本(5个健康的，5个AD的)将在1003um3进行成像，以便所有结构都可见并经组织学证实。将对10名健康志愿者和20名老年参与者(10名健康志愿者和10名轻度认知障碍患者)进行体积下采样，以确定体内体积所需的分辨率。一位神经解剖学家和训练有素的研究助理，在不了解获取参数的情况下，将识别所有体内和体外卷的结构。图像清晰度将从理论和经验两方面进行评估。活体运动校正T2成像将评估为5003um3和2502x2000um3。在所获得的技术和知识的基础上，我们将提出(1)适用于AD临床试验的实用3T方案，与 MMR(MR-PET)系统，(2)用于3T和7T AD研究的更密集的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的列表。

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.