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

项目总结 对放射治疗过程中肿瘤分子特征的认识 治疗是评估治疗效果和调整辐射剂量的关键 优化结果。不幸的是，这不能通过当前的诊断常规地实现 由于复杂的后勤和令人望而却步的成本，核成像模式。或者， 切伦科夫辐射是伴随着外束辐射的一种光学现象 来自直线加速器，并已被证明可用于活体剂量测定和光谱 在放射治疗期间。这种方法显示出巨大的潜力，但来自 商业上可用的探测器限制了其在临床放射治疗实践中的影响。这个 高灵敏度、紧凑型硅光电倍增管(SiPM)器件的最新发展使 CE检测器阵列可定制为任何形状，并直接放置在患者身上以 提供更强的信号，从而使CE成为一种新的、常规的临床工具 放射治疗期间的每日分子肿瘤特征。这个第一阶段的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和 密歇根大学应用物理系和Endectra LLC，这是2015年的衍生产品 来自密歇根大学，该大学专门从事新型辐射的开发 采用SiPM技术和切伦科夫光分析的探测器。在这个项目中，Endectra将 领导几个在体SiPM探头/阵列原型制作、纵向扩展和测试周期，同时 合作的放射肿瘤学研究人员提供设备性能反馈，评估 CMSI相对于其他商业方法的优势，并测试改进后的假设 CE检测(低光子计数)可提高实时检测肿瘤分子的实用性 人物刻画。这项工作的具体目标包括评估CMSI-SiPM阵列1) 它们对肿瘤分子微环境的光谱探测能力和校准能力 使用细胞培养试验的体外表现，以及2)它们确定肿瘤的能力 使用异种移植小鼠模型评估体内的侵袭性/反应性和给药剂量。我们 希望证明CMSI可以同时确定递送剂量 每日和真实的肿瘤放射治疗反应的光谱特征 时间到了。如果成功，Endectra可能会进入第二阶段的努力，包括人体试验， 用于多种临床应用的CMSI探针的开发，以及 这一创新在放射治疗设备市场上有巨大的商业机会。 这将导致放射治疗图像指导的范式转变，极大地改善患者 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.