Quantitative Magnetization Transfer Imaging for Early Detection of Alzheimer's Disease

用于早期检测阿尔茨海默病的定量磁化转移成像

基本信息

批准号：
10681225
负责人：
Andrew Mao
金额：
$ 5.27万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-01 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10681225
关键词：
Address Alzheimer disease detection Alzheimer&apos s Disease Alzheimer&apos s disease pathology Alzheimer&apos s disease therapeutic American Amyloid Amyloid beta-Protein Binding Biological Markers Biophysics Brain Cessation of life Clinical Clinical Management Clinical Research Cognitive Dementia Demyelinations Diagnostic Disease Disease Progression Early Diagnosis Fellowship HIV Health Care Costs Heart Diseases Hybrids Image Imaging Techniques Impaired cognition Individual Lipids Literature Magnetic Resonance Imaging Maps Measures Methods Modeling Monitor Myelin Nerve Degeneration Network-based Neurobehavioral Manifestations Neurodegenerative Disorders Noise Outcome Pathology Patient Monitoring Patients Pharmacotherapy Physiologic pulse Pilot Projects Population Positron-Emission Tomography Process Proteins Protons Relaxation Reporting Reproducibility Research Resolution Scanning Signal Transduction Stroke Structure Surrogate Markers Technical Expertise Techniques Technology Testing Time Tissues Training United States Water Work abeta accumulation aging population amyloid pathology beta amyloid pathology biophysical properties burden of illness career cerebral atrophy clinical development clinical practice data reduction data space deep learning detection method high resolution imaging image reconstruction image translation imaging modality improved in silico in vivo innovation interest interstitial macromolecule magnetic field mild cognitive impairment mouse model neural network novel therapeutics patient population patient response pre-clinical prisma reconstruction tau Proteins theories tool treatment response

项目摘要

Project Summary Alzheimer's disease (AD) is the most common cause of dementia and, at present, an irreversible neurode- generative disease with an ever-increasing disease burden in the United States. Clinical management and de- velopment of novel therapeutics for AD will beneﬁt from reproducible, robust and non-invasive markers of early in vivo AD pathology, but no such tools are well-established in routine clinical practice. Quantitative magnetization transfer (qMT) is an MRI based technique for detecting microstructural tissue changes such as demyelination and the presence of macromolecules, including amyloid beta protein. This sensitivity to multiple aspects of the amy- loid/tau/neurodegeneration framework offers a promising diagnostic alternative to amyloid PET in a single, rapid and high-resolution imaging exam. My preliminary ﬁndings suggest that, using the theory of hybrid state free precession developed in my research group, qMT images can be acquired in vivo in 12 minutes at 1mm isotropic resolution with good SNR. Additionally, by direct comparison to PET in a cognitively normal but amyloid positive subject, qMT appears to be sensitive to the early accumulation of amyloid beta and conﬁrms previous literature reports of increased qMT exchange rates in AD. My proposal aims to solve the remaining technical challenges surrounding qMT by optimizing the acquisition for improved sensitivity to amyloid beta (Aim 1) and developing a neural network based reconstruction pipeline to substantially reduce the post-processing time and improve its robustness to magnetic ﬁeld inhomogeneities (Aim 2), which create biases in the quantitative parameters. These biases are particularly important to curtail in the deep brain, where the accumulation of amyloid beta is purported to begin in AD. In Aim 3, I will perform a pilot study to compare the proposed qMT method's sensitivity for in vivo amyloid beta in a cognitively normal population directly to amyloid PET. Together, this will establish qMT as a surrogate marker for in vivo amyloid and motivate further clinical studies on its utility in monitoring AD progression and response to therapy.

项目概要阿尔茨海默病（AD）是痴呆症最常见的病因，目前是一种不可逆的神经退行性疾病在美国，遗传性疾病的疾病负担不断增加。 AD 新型疗法的开发将受益于可重复、稳健且非侵入性的早期标志物体内 AD 病理学，但在常规临床实践中还没有成熟的定量磁化工具。转移（qMT）是一种基于 MRI 的技术，用于检测组织的微观结构变化，例如脱髓鞘和大分子的存在，包括淀粉样β蛋白，这种对淀粉的多个方面的敏感性。 loid/tau/神经退行性变框架为淀粉样蛋白 PET 提供了一种有前途的诊断替代方案，可通过单一、快速的方法进行诊断和高分辨率成像检查我的初步发现表明，使用混合态自由理论。我的研究小组开发了进动，可以在 1mm 各向同性下在 12 分钟内获得体内 qMT 图像此外，通过与认知正常但淀粉样蛋白阳性的 PET 直接比较，获得良好的 SNR 分辨率。受试者，qMT 似乎对淀粉样蛋白 β 的早期积累敏感，并证实了先前的文献关于 AD 中 qMT 汇率增加的报道我的建议旨在解决剩余的技术挑战。通过优化采集以提高对淀粉样蛋白 β 的敏感性（目标 1）并开发围绕 qMT 的基于神经网络的重建管道，可大大减少后处理时间并提高其性能对磁场不均匀性的鲁棒性（目标 2），这会造成定量参数的偏差。偏见对于减少大脑深部尤其重要，据称β淀粉样蛋白在大脑深处积累在目标 3 中，我将进行一项试点研究来比较所提出的 qMT 方法的灵敏度。认知正常人群中的体内淀粉样蛋白 PET 直接与淀粉样蛋白 PET 一起，这将建立 qMT 作为一种方法。体内淀粉样蛋白的替代标记并激励进一步的临床研究其在监测 AD 进展方面的效用以及对治疗的反应。