Hyperpolarized C-13 Diffusion MRI Measures of Cellular Transport and Metabolism

细胞运输和代谢的超极化 C-13 扩散 MRI 测量

• 批准号: 8632695
• 负责人: Peder Eric Zufall Larson
• 金额: $ 50万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-17 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8632695
• 关键词: Adenocarcinoma; Affect; Angiography; Apoptosis; Biological Markers; Biomedical Engineering; Bioreactors; Blood Vessels; Cancer Biology; Cancer Model; Cancer Patient; Cancerous; Carrier Proteins; Cell Proliferation; Cell model; Cells; Cellularity; Clinical; Clinical Protocols; Clinical Trials; Coupled; Data; Dependence; Development; Diagnostic; Diffusion; Diffusion Magnetic Resonance Imaging; Diffusion weighted imaging; Disease; Disease Progression; Dose; Environment; Enzymes; Goals; Healthcare; Histologic; Image; Injection of therapeutic agent; Kidney Failure; Kinetics; Label; Lactate Dehydrogenase; Liver diseases; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Malignant Neoplasms; Malignant neoplasm of prostate; Mass Spectrum Analysis; Measurement; Measures; Mediating; Medical Imaging; Metabolic; Metabolism; Metastatic to; Methods; Modeling; Motivation; Mus; Necrosis; Normal tissue morphology; Nuclear; Outcome; Pathologic; Patients; Perfusion; Prostate; Pyruvate; Reproducibility; Severity of illness; Signal Transduction; Staging; System; Techniques; Testing; Tissues; Transgenic Organisms; Translating; Translations; Tumor Tissue; Warburg Effect; Weight; base; cancer cell; cancer imaging; cancer type; design; imaging modality; improved; in vivo; inhibitor/antagonist; interstitial; non-alcoholic fatty liver; non-invasive imaging; novel; pre-clinical; preclinical study; public health relevance; research study; response; tumor; tumor progression

DESCRIPTION (provided by applicant): This project consists of both (1) the technical development of novel bioengineering methods for non-invasive imaging of metabolite transport and metabolism and (2) the application of these methods to study cancer biology. The non-invasive imaging is based on the emerging field of hyperpolarized MRI, which is providing valuable new metabolic information for cancer imaging applications. Using this technique, we are able to greatly increase the MR signal of injected substrates, facilitating the ability to acqure fast metabolic data in seconds. The translation potential of this technique has been demonstrated by the first clinical trial in prostate cancer patients with hyperpolarized pyruvate recently completed by our group. Unlike previous hyperpolarized imaging methods, which only probe metabolic conversions, the proposed projects use diffusion-weighted imaging in order to additionally characterize transport of pyruvate and its metabolic product, lactate. This is of grea biomedical importance since the transport of lactate out of cells has promise for predicting aggressiveness of cancer, progression to metastatic disease and response to therapy, as this creates an acidic environment. There are currently no non-invasive imaging methods to measure metabolite transport in vivo. The developments in this proposal are designed specifically to provide and test such methods. This proposal includes cell studies to measure the mechanisms of cellular transport-mediated contrast, preclinical studies to evaluate diffusivity as a biomarker for transport and metabolism in vivo, and development of a novel hyperpolarized diffusion-weighted imaging method that can be translated into the clinical setting for improved characterization of tumor aggressiveness. Both the cell and preclinical studies also require development of specialized hyperpolarized 13C diffusion-weighted methods because, unlike conventional MRI, the signal decay is rapid and unrecoverable. These studies will use cancer cells and cancer models to evaluate tumor characterization capabilities, and the results will be used to design an optimized clinical protocol, which will be validated through preclinical studies. The proposed novel techniques have the potential to transform tumor characterization through improved prediction of aggressiveness and progression to metastatic disease.

描述（由申请人提供）：该项目包括（1）新型生物工程方法的技术开发，用于非代谢物运输和代谢的非侵入性成像，以及（2）这些方法在研究癌症生物学上的应用。非侵入性成像基于超极化MRI的新兴领域，该领域为癌症成像应用提供了宝贵的新代谢信息。使用此技术，我们能够大大增加注射底物的MR信号，从而促进了在几秒钟内获得快速代谢数据的能力。该技术的翻译潜力已通过我们组最近完成的前列腺癌患者的第一次临床试验证明。与以前的超极化成像方法（仅探测代谢转化率）不同，所提出的项目使用扩散加权成像，以便额外表征丙酮酸及其代谢产物乳酸的运输。这是GREA生物医学的重要性，因为乳酸向细胞的运输有望预测癌症的侵略性，向转移性疾病的进展和对治疗的反应，因为这会产生酸性环境。目前尚无非侵入性成像方法来测量体内代谢产物的转运。该提案中的发展专门旨在提供和测试此类方法。该建议包括细胞研究，以测量细胞转运介导的对比度，临床前研究的机制，以评估扩散率作为体内转运和代谢的生物标志物，并开发一种新型超极化扩散加权成像方法，该方法可以转化为临床环境，以改善肿瘤侵袭性的临床环境。细胞和临床前研究都需要开发专门的超极化13C扩散加权方法，因为与常规MRI不同，信号衰减是快速且无法恢复的。这些研究将使用癌细胞和癌症模型来评估肿瘤表征能力，结果将用于设计优化的临床方案，该方案将通过临床前研究进行验证。 拟议的新技术具有通过改善侵略性和发展为转移性疾病的预测来改变肿瘤表征的潜力。