Multimodal Marker for imaging oximetry in radiotherapy

项目总结 尽管组织氧水平在诊断、预后和治疗中的临床意义和重要性 几种病理的治疗，目前显然对量化组织的方法的需求还没有得到满足 具有临床使用所需的合理程度的准确性、可靠性和健壮性的氧气水平 设置。这一提议的总体目标是带来电子顺磁的独特能力 共振(EPR)血氧仪应用于临床领域，特别是用于加强癌症治疗。我们有 发现了独特的固态传感器，称为OxyChips和程序，可实现无与伦比的可靠性和 在一段时间内重复询问特定组织部位的组织氧水平--可能是无限期的。 然而，这些传感器主要局限于涉及小动物的实验室研究。我们有 在一小群癌症患者中观察到，这项新技术转化为临床应用 将需要创新的传感器来提供增强的检测能力、安全性、稳定性和健壮性 一种常规的临床工具。我们建议开发一种新型的具有增强检测功能的氧芯片传感器 敏感度、在临床成像过程中易于识别以及长期安全性和稳定性--所有这些都是 专为更深层肿瘤的测量而设计和优化。建议的发展项目，连同 EPR血氧仪技术的独特功能，将是一种有价值的临床工具，能够提供真正的 肿瘤氧气水平的时间知识，以加强癌症治疗和临床结果。以下是 提出了具体的目标：(1)OxyChips的特征，以建立其在时间和 常规临床影像中的空间定位。嵌入了GNP的OxyChips将受到谨慎的对待 临床相关成像条件下的评估以确定其在时间和空间上的适宜性 常规临床影像定位。评估将包括区域显着性(即氧芯片的可见度 关于其局部肿瘤环境)、可检测性的定量测量(即，信噪比和 对比度噪声比)，以及用于视觉和定量增强的图像处理方法 OxyChips。(2)在临床前兔肿瘤模型中评价新的嵌入GNP的OxyChips 确定它们在临床环境中用于成像和氧气测量的安全性、稳健性和实用性。我们 将利用兔乳腺肿瘤模型来确定新传感器的临床适用性。这个 评估标准将包括使用临床成像方式对肿瘤中的传感器进行可视化，例如 如CT、CB-CT、平面X光和超声。建议的研究将进一步提高电子病历的能力。 氧芯片血氧测定法在癌症治疗中的应用

PROJECT SUMMARY Despite the clinical significance and importance of tissue oxygen levels in the diagnosis, prognosis, and treatment of several pathologies, currently there is clearly an unmet need for methods to quantify tissue oxygen levels with a reasonable degree of accuracy, reliability, and robustness required for use in the clinical settings. The overall objective of this proposal is to bring the unique capability of electron paramagnetic resonance (EPR) oximetry to the clinical realm, particularly for enhancement of cancer treatment. We have discovered unique solid-state sensors, called OxyChips and procedures that enable unsurpassed reliability and repeated interrogation of tissue oxygen levels at specific tissue sites over a period—possibly indefinitely. However, these sensors are limited primarily to laboratory research involving small animals. We have observed—in a small cohort of cancer patients—that translation of this novel technology to clinical applications would require innovative sensors to provide enhanced detection capability, safety, stability, and robustness as a routine clinical tool. We propose to develop a novel class of the OxyChip sensor with enhanced detection sensitivity, easy identification during clinical imaging, and long-term safety and stability—all specifically designed and optimized for measurement in deeper tumors. The proposed developments, combined with the unique capabilities of the EPR oximetry technology, will be a valuable clinical tool capable of providing real- time knowledge of tumor oxygen levels for enhanced cancer treatments and clinical outcomes. The following specific aims are proposed: (1) Characterization of OxyChips to establish their suitability for temporal and spatial localization in routine clinical imaging. The OxyChips embedded with GNP will be subjected to careful evaluation under clinically relevant imaging conditions to determine its suitability for temporal and spatial localization during routine clinical imaging. Evaluation will include regional conspicuity (i.e., visibility of OxyChip with respect to its local tumor environment), quantitative measure of detectability, (i.e., signal-to-noise ratio and contrast-to-noise ratio), and image processing methods for visual and quantitative enhancement of the OxyChips. (2) Evaluation of the new OxyChips embedded with GNP in a pre-clinical rabbit tumor model to establish their safety, robustness, and utility for imaging and oxygen measurements in the clinical settings. We will determine the capability of the new sensors for clinical applicability using rabbit breast tumor model. The evaluation criteria will include visualization of the sensors in the tumor using clinical imaging modalities, such as CT, CB-CT, planar X-ray, and ultrasound. The proposed research will further advance the capability of EPR oximetry with OxyChip for cancer treatment.