Preclinical Electron Paramagnetic Resonance Tumor Imager

临床前电子顺磁共振肿瘤成像仪

• 批准号: 9131526
• 负责人: Gareth R Eaton
• 金额: $ 54.59万
• 依托单位: UNIVERSITY OF DENVER (COLORADO SEMINARY)
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9131526
• 关键词: Air; Amplifiers; Animals; Arts; Chicago; Computer software; Detection; Development; Dose; Educational workshop; Electron Spin Resonance Spectroscopy; Electrons; Ensure; Experimental Designs; Feedback; Frequencies; Funding; Health; Image; Knowledge; Location; Maryland; Measurement; Measures; Methodology; Methods; Molecular; Monitor; Mus; Oxidation-Reduction; Oxygen; Oxygen saturation measurement; Pattern; Performance; Pharmacologic Substance; Physiologic pulse; Physiological; Physiology; Price; Process; Radiation Oncology; Radiation therapy; Reaction Time; Readiness; Relaxation; Research; Scanning; Series; Source; System; Technology; Test Result; Testing; Time; Tissues; Toxic effect; Translating; Translations; Treatment Efficacy; Treatment outcome; Tumor Oxygenation; Universities; Weight; Work; analog; base; cancer imaging; cancer therapy; commercialization; design; design and construction; detector; digital; flexibility; improved; in vivo; in vivo imaging; innovation; instrument; instrumentation; magnetic field; microwave electromagnetic radiation; new technology; nitroxyl; novel strategies; novel therapeutics; oncology; operation; performance tests; pre-clinical; programs; prototype; research and development; response; software development; technology development; treatment response; tumor; user friendly software

DESCRIPTION (provided by applicant): We propose major improvements in the design, construction, and operation of in vivo electron paramagnetic resonance (EPR) small animal imagers and thereby facilitate quantitative and qualitative enhancements in the translation of EPR to a wide range of physiologic problems, with a focus on tumor imaging. Treatment of cancer requires knowledge of the O2 tension in the tumor, and development of new drugs requires molecular level understanding of tumor physiology. EPR imaging can noninvasively obtain an O2, pH, and redox image of the tumor and surrounding tissue, and correlate images with treatment outcome. No other available in vivo O2 images provide such a combination of accuracy of the O2 tension and lack of confounding biologic variability together with low level of invasiveness and low toxicity. Accurate O2 imaging could be the basis for precise dose painting in radiation oncology. This project is a partnership between the University of Denver (DU) and Bruker BioSpin. Bruker is the largest supplier of EPR instrumentation, worldwide, with expertise in both academic and industrial settings and currently sells a continuous-wave-only L-band small animal EPR imager. Bruker and DU will develop a new imager implementing innovations by Bruker and the DU EPR Center, including low- frequency pulsed EPR, digital EPR at multiple frequencies, rapid-scan EPR methodology, crossed-loop pulse and rapid-scan resonators, rapid-scan driver systems, air-core magnets, current control of magnetic fields during imaging, fast-response RF power amplifiers, low-power pulsed EPR, and new operator-friendly tuning displays. The new pre-commercial prototype in vivo imager will provide capability to measure tumor O2 levels, which are needed for oncology treatment, and will provide capability to measure tumor pH and redox status in addition to O2 tension to understand the physiology of tumors in support of pharmacological developments. The magnetic field will be current-controlled, so the problems with Hall probe location in magnets that use Hall probe feedback control of the field will not occur. The imager will be a very flexible system based on digital EPR concepts in which an arbitrary waveform generator (AWG) and fast digitizer replace much of the current hardware. The prototype will be optimized to exceed current art and be faster, better, and less expensive than existing in vivo EPR imagers, and with user-friendly software to make it easy to operate by people who are not spectroscopists. We will document readiness for manufacturability and commercialization. The new technology developments and sharing of information will result in a prototype small imager that Bruker will then further develop with corporate funds to sell commercially.

描述（由申请人提供）：我们提出了体内电子顺磁共振共鸣（EPR）小动物成像仪的设计，构建和操作的重大改进，从而促进了EPR转化为广泛生理问题的定量和定性增强功能，重点是肿瘤成像。癌症的治疗需要了解肿瘤中的O2张力，而新药的发展需要分子水平对肿瘤生理的理解。 EPR成像可以非侵入性地获得肿瘤和周围组织的O2，pH和氧化还原图像，并将图像与治疗结果相关联。没有其他可用的体内O2图像提供了O2张力的精度和缺乏混杂的生物学变异性以及低侵入性和低毒性水平的结合。准确的O2成像可能是放射肿瘤学中精确剂量绘画的基础。该项目是丹佛大学（DU）和布鲁克·比斯宾（Bruker Biospin）之间的合作伙伴关系。布鲁克（Bruker）是全球EPR仪器的最大供应商，在学术和工业环境中具有专业知识，目前销售仅连续波浪的L波段小动物EPR Imager。布鲁克（Bruker）和杜（DU）将开发一个新的成像仪，该成像师由布鲁克（Bruker）和杜EPR中心（DU EPR中心），包括低频脉冲EPR，多个频率的数字EPR，Rapid-Scan EPR方法，跨环脉冲和快速扫描谐振器，Rapid-Scan can can can驾驶员系统，空中磁铁，成像过程中磁场的当前控制，快速响应RF功率放大器，低功率脉冲EPR以及新的操作员友好型调谐显示器。新的商业前原型体内成像仪将提供测量肿瘤O2水平的能力，这是肿瘤学治疗所需的，并且除了O2张力外，还将提供测量肿瘤pH和氧化还原状态的能力，以了解支持肿瘤的生理学以支持支持药理发展。磁场将是电流控制的，因此不会发生使用Hall Probe反馈控制场中Hall探头位置的问题。成像仪将是一个基于数字EPR的非常灵活的系统 任意波形生成器（AWG）和快速数字化器取代当前许多硬件的概念。该原型将被优化，以超过当前的艺术，并且比现有的体内EPR成像器以及用户友好的软件更快，更好，更便宜，以使其易于由不是光谱学家的人进行操作。我们将记录有关制造性和商业化的准备性。新的技术开发和信息共享将导致一个原型的小型成像仪，然后Bruker将进一步开发公司资金以商业销售。