Supplement for Development and Translation of Specialized Hyperpolarized C-13 MRI Methods for Alzheimer's Disease

阿尔茨海默病专用超极化 C-13 MRI 方法开发和转化的补充

基本信息

批准号：
10715712
负责人：
Jeremy William Gordon
金额：
$ 40.38万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-06-01 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10715712
关键词：
Age Alzheimer&apos s Disease Alzheimer&apos s disease patient Alzheimer&apos s disease related dementia Bicarbonates Biological Markers Biomedical Engineering Brain Cell Respiration Cerebrum Chemicals Clinical Assessment Tool Clinical Management Clinical Treatment Data Development Disease Disease Progression Energy Metabolism Evaluation Family Foundations Functional disorder Glucose Glutamates Glycolysis Goals Human Image Imaging Device Impairment Injections Investigation Label Link Magnetic Resonance Imaging Malignant neoplasm of prostate Measurement Measures Metabolic Metabolism Methodology Methods Monitor Onset of illness Parents Participant Pathway interactions Patients Perfusion Persons Phosphorylation Pilot Projects Positron-Emission Tomography Production Prostate Public Health Pyruvate Research Running Signal Transduction Specificity Speed Sterility Stratification Techniques Time Translations Treatment Efficacy United States National Institutes of Health Universities Urea brain metabolism cohort cost cost effective design disorder subtype fluorodeoxyglucose fluorodeoxyglucose positron emission tomography glucose metabolism glucose uptake healthy volunteer imaging approach imaging modality improved insight metabolic imaging mild cognitive impairment molecular imaging multidisciplinary neurotransmitter biosynthesis parent grant quantitative imaging spectroscopic imaging stable isotope success time use tool treatment response uptake

项目摘要

Project Summary/Abstract The parent Bioengineering Research Partnership has been highly successful over the past 8 years in developing quantitative, hyperpolarized (HP) stable-isotope MR molecular imaging approaches for monitoring prostate cancer metabolic reprogramming and response to therapy in a fast 2-minute addition to standard mpMRI exams. Our Alzheimer’s Disease (AD) colleagues now want to take advantage of the unique HP MRI measurements of cerebral energy metabolism that is critical for brain function and known to decrease with AD onset. This project has been developed by our AD multidisciplinary team to develop HP pyruvate and urea MRI as a quantitative imaging approach to probe cerebral perfusion and metabolic impairment in AD and related dementias that are a growing public health concern with tremendous impact on patients and their families. Efforts to effectively treat AD are partially confounded by different hypotheses regarding its initiation and progression, as reflected by the range of imaging methods used to study AD, including positron emission tomography (PET) and magnetic resonance imaging (MRI). Dysfunctional glucose metabolism is strongly linked to AD as both an early and critical determinant of disease progression, and the glucose derivative [18F]Fluorodeoxyglucose (FDG) has been widely used to probe cerebral metabolism in AD patients. While this may reflect a decrease in glucose demand, it only informs on uptake and does not provide accurate information on glycolytic metabolism that decreases with AD. Furthermore, FDG-PET has significant limitations in accessibility, cost, and accuracy, and provides no information on metabolic processes downstream of glucose uptake and phosphorylation. The central goal of this supplement proposal is to develop and apply methods of measuring impaired metabolism in AD for the first time using advanced HP C-13 MRI. HP pyruvate MRI is an emerging molecular imaging method that provides dynamic and pathway-specific metabolic information not available with FDG-PET. In the parent BRP, we have developed methods to greatly improve the coverage, speed, and reliability of HP metabolic imaging and techniques to co-polarize pyruvate and urea to simultaneously assess metabolism and perfusion in the prostate. This supplement is designed to extend this approach to measure metabolic impairment in AD. Specialized techniques will be developed to acquire co-polarized data using [2-13C]pyruvate and [13C]urea, providing simultaneous assessment of perfusion, glycolysis, and oxidative metabolism in the human brain. These techniques will then be applied to an initial cohort of patients with mild cognitive impairment (MCI) due to AD and compared to age-matched controls to assess the magnitude of metabolic changes in AD. The data from this pilot project will form the foundation for larger studies to evaluate HP 13C MRI as a tool for clinical assessment and treatment of AD and will have broad applicability for metabolic assessment of other neurogenerative diseases.

项目摘要/摘要在过去的8年中定量，超极化（HP）稳定 - 同位素MR分子成像方法监测前列腺癌症代谢重编程和对治疗的反应在标准MPMRI检查的快速添加中。我们的阿尔茨海默氏病（AD）同事现在想利用独特的HP MRI测量对大脑功能至关重要的脑能量代谢，并且随着AD发作而降低。这个项目我们的AD多学科团队已经开发了用于开发HP丙酮酸和尿素MRI作为定量的探测AD和相关痴呆症中脑灌注和代谢障碍的成像方法公共卫生对患者及其家人的巨大影响不断增加。有效治疗的效果广告对其主动性和进步的不同假设部分混淆，如用于研究AD的成像方法范围，包括极性发射断层扫描（PET）和磁性共振成像（MRI）。功能障碍的葡萄糖代谢与AD密切相关，既是早期又关键的疾病进展的决定因素和葡萄糖衍生物[18F]氟脱氧葡萄糖（FDG）已被广泛广泛用于探测AD患者的大脑代谢。虽然这可能反映了葡萄糖需求的减少有关摄取的信息，并且没有提供有关AD降低的糖酵解代谢的准确信息。此外，FDG-PET在可访问性，成本和准确性方面有重大限制，并且没有提供有关葡萄糖摄取和磷酸化下游代谢过程的信息。该补充建议的核心目标是开发和应用测量新陈代谢受损的方法在AD中首次使用高级HP C-13 MRI。 HP丙酮酸MRI是一种新兴的分子成像法这提供了FDG-PET无法获得动态和途径特异性的代谢信息。在父母中 BRP，我们开发了大大提高HP代谢的覆盖范围，速度和可靠性的方法对丙酮酸和尿素共可偏振的成像和技术，以同时评估代谢和灌注前列腺。该补充旨在扩展这种方法以测量AD中的代谢损害。将开发专门的技术，以使用[2-13C]丙酮酸和[13C]尿素，获取共偏数据，提供人脑中灌注，糖酵解和氧化代谢的同时评估。这些然后，技术将应用于初始的患有轻度认知障碍患者（MCI）的队列与年龄匹配的对照相比，以评估AD代谢变化的幅度。该飞行员的数据项目将构成大型研究的基础，以评估HP 13C MRI作为临床评估的工具和 AD的治疗将具有广泛的适用性，可用于对其他神经生成疾病的代谢评估。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Optimization in the space domain for density compensation with the nonuniform FFT.

DOI：
10.1016/j.mri.2023.03.003
发表时间：
2023-03
期刊：
Magnetic resonance imaging
影响因子：
2.5
作者：
Nicholas Dwork;Daniel O’Connor;Ethan M. I. Johnson;C. Baron;J. Gordon;J. Pauly;P. Larson
通讯作者：
Nicholas Dwork;Daniel O’Connor;Ethan M. I. Johnson;C. Baron;J. Gordon;J. Pauly;P. Larson

Using a local low rank plus sparse reconstruction to accelerate dynamic hyperpolarized 13C imaging using the bSSFP sequence.

使用局部低秩加稀疏重建来加速使用 bSSFP 序列的动态超极化 13C 成像。

DOI：
10.1016/j.jmr.2018.03.006
发表时间：
2018
期刊：
Journal of magnetic resonance (San Diego, Calif. : 1997)
影响因子：
0
作者：
Milshteyn,Eugene;vonMorze,Cornelius;Reed,GalenD;Shang,Hong;Shin,PeterJ;Larson,PederEZ;Vigneron,DanielB
通讯作者：
Vigneron,DanielB

Di-chromatic interpolation of magnetic resonance metabolic images.