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.

项目摘要/摘要阿尔茨海默氏病（AD）是痴呆症的主要原因，其特征是进行性认知能力下降。经过数十年的努力，基本原因仍然很少理解，并且该疾病仍然无法治愈，预防或明显延迟。髓磷脂损伤会破坏轴突运输，完整性和可塑性，导致信号传递的大量减少。鉴于其在开发和维护中的重要作用在较高的认知功能中，髓磷脂的丧失可能在AD的发病机理中起关键作用。非侵入性MR 因此，可以准确评估髓磷脂的成像技术对于精确而言至关重要诊断AD。已提出合成MRI（SYMRI）通过评估大脑间接绘制髓磷脂实质分数（BPF）和髓磷脂实质分数（MYPF）。但是，髓磷脂的T2很短（<< 1 MS），并且与常规序列（例如与Symri一起使用的序列）都是看不见的。结果，仅SYMRI 通过测量水信号来间接评估髓磷脂，无法使用T1和T2*评估髓磷脂质量放松时间。以回波时间（TES）为〜8µs，100-1000 比常规序列的时间短，使直接从髓磷脂中检测信号成为可能质子以及与Symri相关的问题。 UTE方法的主要挑战是同时检测来自各种水分的高信号。 3D短Tr绝热倒转恢复 UTE（楼梯）序列员工的绝热倒转脉冲，用于均匀反转长-T2组织，该脉冲与短的TR和高倾角一起，可以强烈抑制所有宽的水成分 T1值的范围，从而选择性髓磷脂映射。这项研究的第一个目的是验证和比较3D 从没有捐助者的幻影和脑标本中的髓磷脂成像的楼梯和符号序列（n = 20），使用AD（n = 20）使用组织学作为参考标准。第二个目的是评估楼梯间轻度认知障碍（MCI）（n = 40）和AD（n = 40）的患者的髓磷脂映射的SEMRI序列（n = 40）以及健康的对照（n = 40）。参与者是DU博士新资助的R01赠款的一部分。我们将关联 Symri指标（BPF，MYPF）和楼梯量指标（Myelin PD，T1，T2*），包括认知评估小精神国家检查（MMSE），建立痴呆症注册表（CERAD）和临床的财团痴呆评级（CDR）量表。我们的中心假设是3D楼梯序列将稳健地检测到髓磷脂的变化，以及用髓磷脂PD和髓磷脂T1和T2*的髓磷脂数量的映射将提供对髓磷脂损伤的更具体评估，并与残疾和疾病进展更好地相关在AD中，比从Symri方法得出的指标。 Athertya博士和她的心理Du博士设计了详细的培训计划并组建了一个强大的研究团队，以指导Athertya博士在她的奖学金期间进步为她的AD转化研究工作做好准备。