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）：我们提出了在体内电子顺磁共振（EPR）小动物成像仪的设计、构造和操作方面的重大改进，从而促进EPR转化为广泛生理问题的定量和定性增强，重点是肿瘤成像。癌症的治疗需要了解肿瘤中的O2张力，新药的开发需要对肿瘤生理学的分子水平的了解。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O2张力的准确性和缺乏混淆生物学变异性以及低侵入性和低毒性水平的组合。准确的氧成像可能是放射肿瘤学中精确剂量绘制的基础。该项目是丹佛大学（DU）和布鲁克BioSpin之间的合作项目。布鲁克是全球最大的EPR仪器供应商，在学术和工业领域拥有专业知识，目前销售仅连续波的L波段小动物EPR成像仪。布鲁克和DU将开发一种新的成像仪，实现布鲁克和DU EPR中心的创新，包括低频脉冲EPR、多频率数字EPR、快速扫描EPR方法、交叉回路脉冲和快速扫描谐振器、快速扫描驱动器系统、空芯磁体、成像过程中的磁场电流控制、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。新的预商用原型体内成像仪将提供测量肿瘤治疗所需的肿瘤O2水平的能力，并将提供测量肿瘤pH值和氧化还原状态以及O2张力的能力，以了解肿瘤的生理学，支持药理学发展。磁场将是电流控制的，因此使用霍尔探针反馈控制磁场的磁体中的霍尔探针位置的问题将不会发生。成像仪将是一个非常灵活的系统的基础上数字电子顺磁共振 这是一个概念，其中任意波形发生器（AWG）和快速数字转换器取代了目前的硬件。该原型将进行优化，以超过现有技术，比现有的体内EPR成像仪更快，更好，更便宜，并具有用户友好的软件，使其易于操作的人谁不是光谱仪。我们将记录可制造性和商业化的准备情况。新技术的开发和信息共享将产生一个小型成像仪原型，布鲁克将利用公司资金进一步开发，并进行商业销售。