Dynamic Metabolic Imaging of Hyperpolarized Substrates

超极化基质的动态代谢成像

• 批准号: 7662585
• 负责人: Dirk Mayer
• 金额: $ 39.66万
• 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/7662585
• 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(申请人提供)：超极化磁共振成像(MRI)试剂的发展，即MRI可见的化合物，其磁化强度远远高于在活体温度下通常获得的磁化强度，这既带来了前所未有的机遇，也带来了新的技术挑战。特别是，随着信噪比(SNR)的提高约10,000倍，代谢活性底物的动态核极化(DNP)理论上允许注射试剂和下游代谢产物的高分辨率体内化学位移成像(CSI)，为评估动态代谢过程提供了一种独特的方法。最近的研究表明，注射超极化13Cl-丙酮酸后，无氧代谢和有氧代谢都可以在体内进行研究，应用包括肿瘤诊断和监测、心血管病理学研究和代谢紊乱的评估。虽然，可靠、有效的方法对于成功应用超极化CSI研究体内代谢至关重要，但优化的数据采集和分析工具尚未开发出来。这一为期4年的技术开发项目建议通过实施高速体积CSI技术(目标1)和用于体内数据定量评估的稳健动力学建模算法(目标2)来显著增强这项新技术。最终的采集方法和数据分析算法将在模拟、幻影和活体啮齿动物模型中进行评估，最终的采集方法和数据分析算法将针对动物模型中的超极化底物成像进行优化(目标3)。虽然这项提议的重点是对超极化的13C-丙酮酸及其下游代谢产物进行成像，但大部分工作将同样适用于其他开发的试剂。这些目标的成功完成将提供必要的量化工具，以便能够对正常和病理条件下的代谢进行直接成像，对疾病过程进行纵向监测，并对治疗干预措施进行早期评估。鉴于这项技术的非侵入性，这种新的代谢成像能力预计将在未来3-5年内从实验室转化到临床，第一次使用超极化丙酮酸评估前列腺癌的人体试验定于2009年进行。与公众健康相关：具有动态核极化的超极化磁共振成像将可注射代谢活性底物的信噪比提高约10,000倍，为评估代谢过程提供了一种独特的方法，并为体内询问正常和疾病改变的代谢提供了前所未有的机会。这也带来了新的技术挑战，因为尚未开发优化的数据获取和分析工具。这一技术开发项目的目标是实施和评估一套可靠的敏感技术，用于超极化底物及其代谢产物的活体成像。