Preclinical Electron Paramagnetic Resonance Tumor Imager

描述(由申请人提供)：我们建议在体内电子顺磁共振(EPR)小动物成像仪的设计、构造和操作方面进行重大改进，从而促进EPR在翻译为广泛的生理问题方面的定量和定性增强，重点是肿瘤成像。癌症的治疗需要了解肿瘤中的氧气张力，而新药的开发需要对肿瘤生理学的分子水平的了解。EPR成像可以无创地获得肿瘤及其周围组织的O2、pH和氧化还原图像，并将图像与治疗结果相关联。没有其他可用的活体氧气图像提供这样的组合，氧气张力的准确性和缺乏混杂的生物变异性，以及低水平的侵入性和低毒性。准确的O2成像可能是放射肿瘤学精确绘制剂量图的基础。该项目是丹佛大学(DU)和Bruker BioSpin的合作项目。布鲁克公司是全球最大的EPR仪器供应商，拥有学术和工业领域的专业知识，目前销售仅限L波段的连续波小动物EPR成像仪。Bruker和DU将开发一种新的成像仪，实施Bruker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、交叉环路脉冲和快速扫描谐振器、快速扫描驱动器系统、空芯磁铁、成像过程中的磁场电流控制、快速响应射频功率放大器、低功率脉冲EPR和新型操作员友好型调谐显示器。新的商用前原型活体成像仪将提供测量肿瘤治疗所需的肿瘤氧气水平的能力，并将提供测量肿瘤pH值和氧化还原状态的能力，以及氧气压力，以了解肿瘤的生理，以支持药物开发。磁场将是电流控制的，所以使用霍尔探头反馈控制磁场的磁体中霍尔探头位置的问题不会发生。该成像仪将是一个基于数字EPR的非常灵活的系统 任意波形发生器(AWG)和快速数字转换器取代当前大部分硬件的概念。原型将经过优化，以超过目前的技术，比现有的在体EPR成像仪更快、更好、更便宜，并配备用户友好的软件，使非光谱分析人员可以轻松操作。我们将记录可制造性和商业化的准备情况。新技术的发展和信息的共享将产生一个小型成像器的原型，然后布鲁克将用公司资金进一步开发，以便进行商业销售。

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.