Comparison of direct and indirect magnetic resonance imaging of myelin in Alzheimer's disease

阿尔茨海默病髓磷脂直接和间接磁共振成像的比较

基本信息

批准号：
10680319
负责人：
Jiyo S Athertya
金额：
$ 7.86万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-04-01 至 2026-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10680319
关键词：
3-Dimensional Action Potentials Affect Alzheimer&apos s Disease Alzheimer&apos s disease diagnosis Alzheimer&apos s disease patient Axonal Transport Biological Brain Brain imaging Cadaver Child Child Development Clinical Clinical dementia rating scale Complex Cross-Sectional Studies Dementia Demyelinations Deposition Detection Development Diagnosis Disease Disease Progression Edema Evaluation Event Fellowship Funding Generations Goals Grant Histology Human Image Imaging Techniques Impaired cognition Impairment Inflammation Iron Learning Magnetic Resonance Imaging Maintenance Maps Measures Mechanics Mentors Monitor Motor Skills Myelin Nerve Degeneration Neurofibrillary Tangles Oligodendroglia Participant Pathogenesis Patients Physiologic pulse Play Powder dose form Pregnant Women Productivity Protocols documentation Protons Recovery Reference Standards Refractory Registries Relaxation Research Role Sampling Senile Plaques Sensitivity and Specificity Signal Transduction Specimen Speed Suspensions Techniques Time Tissues Training Translational Research Vendor Vesicle Water absorption career cognitive function cognitive testing cohort commercialization data acquisition design detection method diagnostic strategy disability extracellular gray matter healthy volunteer improved in vivo in vivo imaging mental state mild cognitive impairment non-invasive imaging novel novel diagnostics prevent simulation transmission process white matter

项目摘要

PROJECT SUMMARY/ABSTRACT Alzheimer’s Disease (AD) is the leading cause of dementia characterized by progressive cognitive decline. The underlying causes remain poorly understood after decades of efforts, and the disease still cannot be cured, prevented, or significantly delayed. Myelin impairment can disrupt axonal transport, integrity, and plasticity, leading to a massive reduction in signal transduction. Given its essential role in development and maintenance of higher cognitive functions, loss of myelin could play a key role in the pathogenesis of AD. A non-invasive MR imaging technique that can accurately evaluate myelin could therefore be of critical importance for precise diagnosis of AD. Synthetic MRI (SyMRI) has been proposed to indirectly map myelin by assessing brain parenchymal fraction (BPF) and myelin parenchymal fraction (MyPF). However, myelin has a very short T2 (<<1 ms) and is invisible with conventional sequences such as those used with SyMRI. As a result, SyMRI only indirectly evaluates myelin via measuring water signals, and cannot evaluate myelin quality using the T1 and T2* relaxation times. Ultrashort echo time (UTE) sequences with echo times (TEs) of ~8µs, which are 100-1000 times shorter than the TEs of conventional sequences, make it possible to directly detect signal from myelin protons and so circumvent problems associated with SyMRI. The major challenge with UTE approach is the concurrent detection of high signal from various water components. The 3D short TR adiabatic inversion recovery UTE (STAIR-UTE) sequence employs an adiabatic inversion pulse for uniform inversion of long-T2 tissues, which together with a short TR and a high flip angle allow robust suppression of all water components with a wide range of T1 values, thereby selective myelin mapping. The first aim of this study is to validate and compare 3D STAIR-UTE and SyMRI sequences for myelin imaging in phantoms and brain specimens from donors without (n=20), and with AD (n=20) using histology as reference standard. The second aim is to evaluate STAIR-UTE and SyMRI sequences for myelin mapping in patients with mild cognitive impairment (MCI) (n=40) and AD (n=40) as well as healthy controls (n=40). The participants are part of Dr. Du’s newly funded R01 grant. We will correlate SyMRI metrics (BPF, MyPF) and STAIR-UTE metrics (myelin PD, T1, T2*) with cognitive assessments including Mini-Mental State Examination (MMSE), Consortium to Establish a Registry of Dementia (CERAD), and Clinical Dementia Rating (CDR) scales. Our central hypothesis is that 3D STAIR-UTE sequence will robustly detect changes in myelin, and that mapping of myelin quantity with myelin PD and quality with myelin T1 and T2* will provide more specific evaluation of myelin damage and correlate better with disability and disease progression in AD than metrics derived from the SyMRI approach. Dr. Athertya and her mentor, Dr Du, have designed a detailed training plan and assembled a strong research team to guide Dr. Athertya through her fellowship period towards preparing her for a productive career in translational research for AD.

项目概要/摘要阿尔茨海默病 (AD) 是导致痴呆症的主要原因，其特征是进行性认知能力下降。经过数十年的努力，其根本原因仍然知之甚少，而且这种疾病仍然无法治愈，髓磷脂损伤会破坏轴突运输、完整性和可塑性，鉴于其在发育和维护中的重要作用，导致信号转导大量减少。髓鞘质的丧失可能在 AD 的发病机制中发挥关键作用。因此，能够准确评估髓磷脂的成像技术对于精确评估髓磷脂至关重要。综合 MRI (SyMRI) 已被提议通过评估大脑来间接绘制髓磷脂图。实质分数 (BPF) 和髓磷脂实质分数 (MyPF) 然而，髓磷脂的 T2 非常短 (<<1)。 ms)，并且对于传统序列（例如与 SyMRI 一起使用的序列）来说是不可见的。因此，仅 SyMRI。通过测量水信号间接评估髓磷脂，无法使用 T1 和 T2 评估髓磷脂质量* 回波时间 (TE) 约为 8μs（100-1000）的超短回波时间 (UTE) 序列。比传统序列的 TE 短一倍，使得直接检测髓磷脂信号成为可能 UTE 方法的主要挑战是质子，从而规避与 SyMRI 相关的问题。同时检测来自各种水成分的高信号。 3D 短 TR 绝热反演恢复。 UTE (STAIR-UTE) 序列采用绝热反转脉冲来均匀反转长 T2 组织，这结合短 TR 和高翻转角，可以在较宽的范围内强力抑制所有水成分。 T1 值范围，选择性髓磷脂图谱因此，本研究的首要目的是验证和比较 3D。 STAIR-UTE 和 SyMRI 序列，用于对来自无脑捐献者的模型和脑标本进行髓磷脂成像 (n=20)，以及使用组织学作为参考标准的 AD (n=20) 第二个目标是评估 STAIR-UTE。和 SyMRI 序列，用于轻度认知障碍 (MCI) (n=40) 和 AD (n=40) 患者的髓磷脂定位以及健康对照（n=40）。参与者是杜博士新资助的 R01 资助的一部分。我们将关联起来。 SyMRI 指标（BPF、MyPF）和 STAIR-UTE 指标（髓磷脂 PD、T1、T2*）以及认知评估，包括简易精神状态检查 (MMSE)、建立痴呆症登记联盟 (CERAD) 和临床我们的中心假设是 3D STAIR-UTE 序列能够稳健地检测痴呆症评级 (CDR) 量表。髓磷脂的变化，并且用髓磷脂 PD 绘制髓磷脂数量，用髓磷脂 T1 和 T2* 绘制髓磷脂质量，将提供对髓磷脂损伤更具体的评估，并与残疾和疾病进展更好地关联在 AD 领域，Athertya 博士和她的导师 Du 博士设计了一种基于 SyMRI 方法的指标。详细的培训计划并组建了强大的研究团队来指导Athertya博士度过她的奖学金期间为她在 AD 转化研究领域的富有成效的职业生涯做好准备。