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.

项目概要/摘要母公司生物工程研究合作伙伴在过去 8 年里在开发用于监测前列腺的定量、超极化 (HP) 稳定同位素 MR 分子成像方法除了标准 mpMRI 检查外，还可在 2 分钟内快速了解癌症代谢重编程和治疗反应。我们的阿尔茨海默病 (AD) 同事现在希望利用独特的 HP MRI 测量脑能量代谢对于大脑功能至关重要，并且已知会随着 AD 的发作而减少。由我们的 AD 多学科团队开发，用于开发 HP 丙酮酸和尿素 MRI 作为定量方法成像方法探测 AD 和相关痴呆症的脑灌注和代谢损伤，这是一种日益增长的公共卫生关注对患者及其家人的有效治疗产生了巨大影响。 AD 的发生和进展的不同假设部分地混淆了 AD，如用于研究 AD 的一系列成像方法，包括正电子发射断层扫描 (PET) 和磁磁共振成像 (MRI) 功能失调的葡萄糖代谢与 AD 密切相关，既是早期的也是关键的。葡萄糖衍生物[18F]氟脱氧葡萄糖（FDG）已被广泛认为是疾病进展的决定因素用于探测 AD 患者的脑代谢虽然这可能反映了葡萄糖需求的减少，但这只是。告知摄取情况，但不提供随 AD 降低的糖酵解代谢的准确信息。此外，FDG-PET 在可及性、成本和准确性方面具有显着的局限性，并且不提供有关葡萄糖摄取和磷酸化下游代谢过程的信息。该补充提案的中心目标是开发和应用测量代谢受损的方法首次在 AD 中使用先进的 HP C-13 MRI HP 丙酮酸 MRI 是一种新兴的分子成像方法。提供母体中 FDG-PET 无法提供的动态和途径特异性代谢信息。 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共极化丙酮酸和尿素的成像和技术，以同时评估代谢和灌注该补充剂旨在扩展这种方法来测量 AD 的代谢损伤。将开发专门技术来使用[2-13C]丙酮酸盐和[13C]尿素获取共极化数据，同时评估人脑的灌注、糖酵解和氧化代谢。然后，技术将应用于最初的一组因 AD 和轻度认知障碍 (MCI) 导致的患者与年龄匹配的对照进行比较，以评估 AD 代谢变化的程度。该项目将为更大规模的研究奠定基础，以评估 HP 13C MRI 作为临床评估和诊断的工具。 AD 的治疗，并将广泛适用于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.