Cerenkov Multi-Spectral Imaging (CMSI) for Adaptation and Real-Time Imaging in Radiotherapy

项目摘要 了解放疗过程中的肿瘤分子特征（RT） 治疗是至关重要的，以评估治疗的疗效和适应辐射剂量， 优化结果。不幸的是，目前的诊断方法无法常规实现这一点。 由于复杂的后勤和高昂的成本，核成像模式。可选择地， 切伦科夫发射（CE）是一种伴随着外部光束辐射的光学现象 并已被证明用于体内剂量测定和光谱学 在放疗期间。这种方法显示出巨大的潜力，但是来自 商业上可获得的探测器限制了其在临床放射治疗实践中的影响。的 高灵敏度、紧凑型硅光电倍增管（SiPM）器件的最新发展使得 CE探测器阵列可定制为任何形状并直接放置在患者身体上， 提供更强的信号，从而使CE成为一种新的常规临床工具， 放射治疗期间的每日分子肿瘤表征。第一阶段STTR将 评估这一革命性的切伦科夫多光谱成像（CMSI）创新的可行性， 这是放射肿瘤学研究人员合作的产物， 密歇根大学应用物理系和2015年分拆的Endectra LLC 密歇根大学专门研究新型辐射 探测器采用SiPM技术和切伦科夫光分析。在这个项目中，Endectra将 领导了几个体上SiPM探针/阵列原型设计、放大和测试周期， 合作放射肿瘤学研究人员提供设备性能反馈，评估 CMSI优于其他商业方法的优势，并测试改进的假设 CE的检测（在低光子计数下）可以在实时肿瘤分子生物学中产生改进的效用。 特征化这项工作的具体目标包括评估CMSI-SiPM阵列1） 他们的能力，光谱探测肿瘤分子微环境和校准他们的 使用细胞培养测定的体外性能，和2）它们测定肿瘤的能力， 攻击性/反应并使用异种移植小鼠模型评估体内递送剂量。我们 预计将证明CMSI可以同时确定输送剂量， 每天和真实的光谱表征肿瘤对放射治疗的反应 时间如果成功的话，Endectra可以进入第二阶段的工作，包括人体试验， 开发用于多种临床应用的CMSI探针， 这一创新在放射治疗设备市场上具有巨大的商业机会。 这将导致放射治疗图像引导的范式转变，大大改善患者的 安全性和治疗效果，以及对公共卫生的重大改善。

PROJECT SUMMARY Understanding of tumor molecular characteristics during a course of radiotherapy (RT) treatment is crucial to assess the efficacy of the treatment and adapt radiation dosage to optimize outcomes. Unfortunately, this cannot be routinely achieved by current diagnostic nuclear imaging modalities due to complex logistics and prohibitive costs. Alternatively, Cerenkov Emission (CE) is an optical phenomenon that accompanies external beam radiation from a linear accelerator and has been demonstrated for in vivo dosimetry and spectroscopy during radiotherapy. This approach shows great potential, but the low photon response from commercially available detectors has limited its impact in clinical radiotherapy practice. The recent development of highly sensitive, compact silicon photomultiplier (SiPM) devices enables arrays of CE detectors to be customized in any shape and placed directly on a patient’s body to provide a much enhanced signal, thus enabling CE to become a new, routine clinical tool for daily molecular tumor characterization during radiation treatment. This Phase I STTR will assess the feasibility of this revolutionary Cerenkov Multi-Spectral Imaging (CMSI) innovation, which is the product of collaboration between researchers in the Radiation Oncology and Applied Physics Departments at the University of Michigan, and Endectra LLC, a 2015 spinout from the University of Michigan which specializes in the development of novel radiation detectors utilizing SiPM technology and Cerenkov light analytics. In this project, Endectra will lead several on-body SiPM probe/array prototyping, scale-up, and testing cycles, while collaborating radiation oncology researchers provide device performance feedback, assess the advantages of CMSI over other commercial approaches, and test the hypothesis that improved detection of CE (at low photon counts) can yield improved utility in real-time tumor molecular characterization. Specific aims of this effort include the evaluation of CMSI-SiPM arrays for 1) their capacity to spectrally probe tumor molecular microenvironment and calibrate their performance in vitro using cell culture assays, and 2) their capacity to determine tumor aggressiveness/response and assess delivered dose in vivo using xenograft mouse models. We expect to demonstrate that CMSI can simultaneously determine delivered dose while spectroscopically characterizing tumor response to radiotherapy on a daily basis and in real time. If successful, Endectra could proceed to a Phase II effort including human trials, development of CMSI probes for multiple clinical applications, and development of the substantial commercial opportunity for this innovation in the radiotherapy equipment market. This would result in a paradigm shift in radiotherapy image-guidance, greatly improved patient safety and therapeutic impact, and a major improvement to public health.