CAREER: Quantitative Imaging of Tissue Oxygenation

职业：组织氧合的定量成像

• 批准号: 1351992
• 负责人: Vikram Kodibagkar
• 金额: $ 44万
• 依托单位: Arizona State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-15 至 2019-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1351992&HistoricalAwards=false
• 关键词: CAREER; Quantitative; Imaging; Tissue; Oxygenation

PI: Kodibagkar, Vikram Proposal Number: 1351992Oxygen is the most important nutrient for life and its deficiency can cause loss of cell viability and organ function. Additionally, oxygen is challenging to deliver in vivo due to its low solubility in water. Therefore, the opportunity to assess hypoxia non-invasively may be significant in understanding mechanisms of tissue function and in clinical prognosis of various diseases, such as cancer and stroke. The overall goal of this proposal is to develop and use quantitative methods employing Magnetic Resonance Imaging (MRI) to measure, non-invasively, oxygen levels in vivo. Besides advancing our fundamental understanding of tissue oxygenation under different physiologic conditions, this capability could also directly impact the development, screening and use of novel therapeutic agents that target hypoxia either for promoting it, as would be desirable with cancer, or for alleviating it, as would be the case in myocardial infarction and stroke. Findings could impact future patients by aiding the design and development of personalized therapy for cancer and by improving how radiotherapy is planned and delivered in the clinic. Educational activities integrate research with education at three different levels (high-school, undergraduate, and graduate), and multiple organizations (ASU, local high schools and foreign universities). A Hands-on Summer Program in Imaging Technology (HoSPIT) will increase awareness in the capabilities and limitations of Medical Imaging and will prepare students for the next steps in their educational paths and towards professional employment.Two approaches will be investigated. The first is based on the binding of an MRI contrast agent in regions that are deficient in oxygen; and the second relies on the change in the MRI properties of a nanoprobe depending on the surrounding oxygen levels. In both cases, a comprehensive pharmacokinetic framework will be used to describe the delivery and distribution of the reporter probe and to relate the observed MRI parameters to tissue oxygenation. Three specific objectives will be pursued: the development of a theoretical model for systemic delivery of MRI-based oxygen imaging probes for dynamic measurement of tissue oxygenation and related parameters; the design and construction of an MRI-compatible tissue simulating phantom with tunable oxygenation and metabolic status for in vitro testing of the theoretical model; and the application of theoretical model for measurement of tissue oxygenation and related parameters to in vivo data. The proposed work is expected to advance the capability of developing three-dimensional images of tissue oxygenation in high resolution under both physiological and pathological conditions and under various pharmacological interventions.

PI：Kodibagkar，Vikram 提案编号：1351992 氧气是生命最重要的营养素，缺乏氧气会导致细胞活力和器官功能丧失。 此外，由于氧气在水中的溶解度较低，因此在体内输送氧气具有挑战性。 因此，非侵入性评估缺氧的机会对于理解组织功能机制和各种疾病（例如癌症和中风）的临床预后可能具有重要意义。 该提案的总体目标是开发和使用磁共振成像 (MRI) 的定量方法来非侵入性地测量体内氧气水平。 除了增进我们对不同生理条件下组织氧合的基本了解外，这种能力还可能直接影响针对缺氧的新型治疗剂的开发、筛选和使用，以促进缺氧（如癌症所需）或缓解缺氧（如心肌梗塞和中风就是这种情况。 研究结果可能会通过帮助癌症个性化治疗的设计和开发以及改善临床中放射治疗的规划和实施方式来影响未来的患者。 教育活动将三个不同层次（高中、本科和研究生）和多个组织（亚利桑那州立大学、当地高中和外国大学）的研究与教育结合起来。 成像技术暑期实践项目 (HoSPIT) 将提高人们对医学成像的能力和局限性的认识，并为学生下一步的教育道路和专业就业做好准备。将研究两种方法。 第一个是基于 MRI 造影剂在缺氧区域的结合；第二个依赖于纳米探针的 MRI 特性随周围氧气水平的变化。在这两种情况下，将使用全面的药代动力学框架来描述报告探针的递送和分布，并将观察到的 MRI 参数与组织氧合联系起来。 将追求三个具体目标：开发基于 MRI 的氧成像探针系统传输的理论模型，用于动态测量组织氧合和相关参数；设计和构建具有可调氧合和代谢状态的 MRI 兼容组织模拟体模，用于理论模型的体外测试；以及测量组织氧合和相关参数的理论模型在体内数据中的应用。 拟议的工作预计将提高在生理和病理条件下以及各种药理学干预下开发高分辨率组织氧合三维图像的能力。