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Dynamic Metabolic Imaging of Hyperpolarized Substrates

超极化基质的动态代谢成像

基本信息

批准号：
8750998
负责人：
Dirk Mayer
金额：
$ 14.72万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-04-01 至 2014-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8750998
关键词：
Dynamic Metabolic Imaging Hyperpolarized Substrates

项目摘要

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.

描述（由申请人提供）：超极化磁共振成像（MRI）试剂（即磁化强度远高于体内温度下通常达到的磁化强度的MRI可见化合物）的开发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) 增强约 10,000 倍，代谢活性底物的动态核极化 (DNP) 理论上允许对注射剂和下游代谢产物进行高分辨率体内化学位移成像 (CSI)，从而提供评估动态代谢过程的独特方法。最近的研究表明，在推注超极化13C1-丙酮酸后，可以在体内研究无氧和有氧代谢，其应用包括肿瘤诊断和监测、心血管病理学研究以及代谢紊乱的评估。尽管可靠、经过充分验证的方法对于超极化 CSI 成功应用于体内代谢研究至关重要，但优化的数据采集和分析工具尚未开发出来。这个为期 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）并结合稳健的动力学建模算法（目标 2）来显着增强这项新技术，以定量评估体内数据。由此产生的工具将针对动物模型中的超极化基底成像进行优化，并在模拟、体模和体内啮齿动物模型中评估最终的采集方法和数据分析算法（目标 3）。尽管该提案的重点是超极化 13C-丙酮酸及其下游代谢产物的成像，但大部分工作将同样适用于开发的其他药物。这些目标的成功完成将为正常和病理条件下的代谢直接成像、疾病过程的纵向监测以及治疗干预的早期评估提供必要的定量工具。鉴于该技术的非侵入性，这种新的代谢成像功能预计将在未来 3-5 年内从实验室转化为临床，预计将于 2009 年进行首次使用超极化丙酮酸盐评估前列腺癌的人体试验。