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

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.
项目总结/摘要 在过去的8年里,母公司生物工程研究伙伴关系在开发 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 癌症代谢重编程和对治疗的反应,在标准mpMRI检查的基础上增加2分钟。 我们的阿尔茨海默病(AD)同事现在想利用独特的HP MRI测量, 脑能量代谢,这对脑功能至关重要,并且已知随着AD发作而降低。这个项目 已由我们的AD多学科团队开发,以开发HP丙酮酸盐和尿素MRI作为定量 成像方法探测AD和相关痴呆的脑灌注和代谢损伤, 公众对健康的关注日益增加,对病人及其家属产生巨大影响。努力有效治疗 AD部分被关于其发生和进展的不同假设所混淆,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)和磁共振成像(MRI)。 磁共振成像(MRI)。葡萄糖代谢功能障碍与AD密切相关,是AD的早期和关键因素。 疾病进展的决定因素,葡萄糖衍生物[18F]氟脱氧葡萄糖(FDG)已被广泛应用于 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,但它只是 提供了摄取的信息,并且没有提供关于随着AD而减少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著的限制,并且不能提供 关于葡萄糖摄取和磷酸化下游代谢过程的信息。 本补充提案的中心目标是开发和应用测量代谢受损的方法 在AD中首次使用先进的HP C-13 MRI。HP丙酮酸盐MRI是一种新兴的分子影像学方法 它提供了FDG-PET无法提供的动态和特定途径的代谢信息。在母 BRP,我们已经开发出的方法,大大提高了覆盖面,速度和可靠性的HP代谢 成像和技术,以共同代谢丙酮酸和尿素,同时评估代谢和灌注, 前列腺这种补充旨在扩展这种方法来测量AD的代谢障碍。 将开发专门的技术,使用[2- 13 C]丙酮酸盐和[13 C]尿素获取共极化数据, 提供了对人脑中灌注、糖酵解和氧化代谢的同时评估。这些 然后将这些技术应用于患有AD所致轻度认知障碍(MCI)的初始队列患者, 与年龄匹配的对照组进行比较,以评估AD中代谢变化的幅度。这个试验的数据 该项目将为更大规模的研究奠定基础,以评估HP 13 C MRI作为临床评估工具, 治疗AD,并将具有广泛的适用性,为其他神经退行性疾病的代谢评估。

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:
  • 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。
Hyperpolarized Metabolic MRI-Acquisition, Reconstruction, and Analysis Methods.
  • DOI:
    10.3390/metabo11060386
  • 发表时间:
    2021-06-14
  • 期刊:
  • 影响因子:
    4.1
  • 作者:
    Larson PEZ;Gordon JW
  • 通讯作者:
    Gordon JW
Di-chromatic interpolation of magnetic resonance metabolic images.
  • DOI:
    10.1007/s10334-020-00903-y
  • 发表时间:
    2021-03
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Dwork N;Gordon JW;Tang S;O'Connor D;Hansen ESS;Laustsen C;Larson PEZ
  • 通讯作者:
    Larson PEZ
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Jeremy William Gordon其他文献

Jeremy William Gordon的其他文献

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{{ truncateString('Jeremy William Gordon', 18)}}的其他基金

Multimodality Neuroimaging Evaluation of Cognitive Functioning in Lower Grade Astrocytoma
低级别星形细胞瘤认知功能的多模态神经影像评估
  • 批准号:
    10701775
  • 财政年份:
    2022
  • 资助金额:
    $ 40.38万
  • 项目类别:
Development and Translation of Hyperpolarized C-13 Prostate Cancer MRI Methods
超极化 C-13 前列腺癌 MRI 方法的开发和转化
  • 批准号:
    10588591
  • 财政年份:
    2019
  • 资助金额:
    $ 40.38万
  • 项目类别:
Development and Translation of Hyperpolarized C-13 Prostate Cancer MRI Methods
超极化 C-13 前列腺癌 MRI 方法的开发和转化
  • 批准号:
    10393570
  • 财政年份:
    2019
  • 资助金额:
    $ 40.38万
  • 项目类别:
Development and Translation of Hyperpolarized C-13 Prostate Cancer MRI Methods
超极化 C-13 前列腺癌 MRI 方法的开发和转化
  • 批准号:
    10455772
  • 财政年份:
    2019
  • 资助金额:
    $ 40.38万
  • 项目类别:
Development and Translation of Hyperpolarized C-13 Prostate Cancer MRI Methods
超极化 C-13 前列腺癌 MRI 方法的开发和转化
  • 批准号:
    10591571
  • 财政年份:
    2019
  • 资助金额:
    $ 40.38万
  • 项目类别:
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