Dynamic Metabolic Imaging of Hyperpolarized Substrates

超极化基质的动态代谢成像

• 批准号: 7783802
• 负责人: Dirk Mayer
• 金额: $ 39.57万
• 依托单位: SRI INTERNATIONAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7783802
• 关键词: Affect; Alanine; Alcohol dehydrogenase; Algorithms; Animal Model; Animals; Bicarbonates; Bolus Infusion; Cardiovascular Pathology; Cell Respiration; Chemical Shift Imaging; Clinic; Clinical; Data; Data Analyses; Development; Diagnosis; Disease; Ethanol; Evaluation; Goals; Human; Image; Imaging Techniques; Injectable; Injection of therapeutic agent; Kidney; Kinetics; Laboratories; Lactate Dehydrogenase; Liver; Magnetic Resonance Imaging; Malignant neoplasm of prostate; Measurement; Measures; Metabolic; Metabolic Diseases; Metabolism; Methods; Metric; Modeling; Monitor; Morphologic artifacts; Mus; NADH; Nature; Noise; Nuclear; Nuclear Magnetic Resonance; Organ; Pathologic; Performance; Process; Production; Pyruvate; Pyruvate Metabolism Pathway; Pyruvates; Quantitative Evaluations; Rattus; Relaxation; Research; Resolution; Rodent; Rodent Model; Schedule; Signal Transduction; Speed; System; Techniques; Technology; Temperature; Testing; Therapeutic Intervention; Time; Toxic effect; Translations; Work; data acquisition; in vivo; mouse model; nervous system disorder; new technology; public health relevance; simulation; tool; tumor

DESCRIPTION (provided by applicant): The development of hyperpolarized magnetic resonance imaging (MRI) agents, i.e., MRI-visible compounds whose magnetization is much higher than that normally achieved at in vivo temperatures, presents both unprecedented opportunities as well as new technical challenges. In particular, with signal-to-noise ratio (SNR) enhancements on the order of the 10,000-fold, dynamic nuclear polarization (DNP) of metabolically active substrates theoretically permits high-resolution in vivo chemical shift imaging (CSI) of both the injected agent and downstream metabolic products, providing a unique method to assess dynamic metabolic processes. Recent studies have demonstrated that both anaerobic and aerobic metabolism can be studied in vivo following the bolus injection of hyperpolarized 13C1-pyruvate, and applications include tumor diagnosis and monitoring, the study of cardiovascular pathologies, and the evaluation of metabolic disorders. Although, reliable, well-validated methods are critical for the successful application of hyperpolarized CSI to the study of in vivo metabolism, optimized data acquisition and analysis tools have yet to be developed. This 4- year technical development project proposes to significantly enhance this new technology through the implementation of high-speed volumetric CSI techniques (Aim 1) in conjunction with robust kinetic modeling algorithms (Aim 2) for the quantitative evaluation of in vivo data. The resulting tools will be optimized for imaging hyperpolarized substrates in animal models with the final acquisition methods and data analysis algorithms evaluated in simulations, phantoms, and in vivo rodent models (Aim 3). Although this proposal is focused on imaging hyperpolarized 13C-pyruvate and its downstream metabolic products, much of the work will be equally applicable to other agents as they are developed. The successful completion of these goals will provide the quantitative tools necessary to allow the direct imaging of metabolism in normal and pathologic conditions, the longitudinal monitoring of disease processes, and the early evaluation of therapeutic interventions. Given the noninvasive nature of the technology, translation of this new metabolic imaging capability from the laboratory to the clinic is anticipated occur within the next 3-5 years, with the first human trial using hyperpolarized pyruvate for the evaluation of prostate cancer scheduled for 2009. PUBLIC HEALTH RELEVANCE: Hyperpolarized magnetic resonance imaging with Dynamic Nuclear Polarization, that enhances signal-to-noise ratio on the order of the 10,000-fold, of injectable metabolically active substrates provides a unique method to assess metabolic processes and presents unprecedented opportunities for in vivo interrogation of normal and disease altered metabolism. It also poses new technical challenges as optimized data acquisition and analysis tools have yet to be developed. The goal of this technical development project is to implement and evaluate a robust set of sensitive techniques for the in vivo imaging of hyperpolarized substrates and their metabolic products.

描述（由申请人提供）：超极化磁共振成像（MRI）剂的发展，即MRI-Visible化合物，其磁化强度远高于在体内温度下通常所实现的磁化化合物，这既提出了前所未有的机会，也提出了新的技术挑战。特别是，随着信噪比（SNR）的增强，即代谢活性底物的10,000倍动态核极化（DNP）理论上允许在体内化学移位成像（CSI）中进行高分辨率的注射剂和下游代谢产品，从而提供了一种用于评估动力代谢方法的动力学方法。最近的研究表明，在注射超极化13C1-丙酮酸后，可以在体内研究厌氧和有氧代谢，并且应用包括肿瘤诊断和监测，心血管病理学的研究，以及代谢性疾病的评估。尽管可靠，验证的方法可靠，对于成功应用超极化CSI在体内代谢，优化的数据获取和分析工具的研究中至关重要。这项为期4年的技术开发项目建议通过实施高速体积CSI技术（AIM 1）与强大的动力学建模算法（AIM 2）来显着增强这项新技术，以对体内数据进行定量评估。最终的采集方法和数据分析算法在模拟，幻影和体内啮齿动物模型中评估的最终采集方法和数据分析算法（AIM 3），将优化所得工具，用于对动物模型中的超极化底物进行成像（AIM 3）。尽管该建议集中于成像超极化的13C-丙酮酸及其下游代谢产物，但大部分工作将同样适用于其他代理。这些目标的成功完成将提供必要的定量工具，以直接在正常和病理条件下直接对代谢，疾病过程的纵向监测以及治疗干预措施的早期评估。鉴于该技术的无创性，预计这种新的代谢成像能力从实验室到诊所的翻译发生在未来3 - 5年内，首次使用超极化的丙酮酸来评估计划于2009年预定的前列腺癌。可注射的代谢活性底物提供了一种评估代谢过程的独特方法，并为正常和疾病改变代谢的体内询问提供了前所未有的机会。由于尚未开发出优化的数据采集和分析工具，因此它也带来了新的技术挑战。该技术开发项目的目的是实施和评估一组强大的敏感技术，用于对超极化底物及其代谢产物的体内成像。