Multimodal Marker for imaging oximetry in radiotherapy

用于放射治疗中成像血氧测定的多模态标记物

• 批准号: 10818101
• 负责人: PERIANNAN KUPPUSAMY
• 金额: $ 9.92万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10818101
• 关键词: Aftercare; Algorithms; Animal Model; Animals; Automation; Breast Cancer Model; Cancer Patient; Clinic; Clinical; Clinical Research; Computer software; Data; Detection; Development; Devices; Diagnosis; Disease; Electron Spin Resonance Spectroscopy; Engineering; Environment; Evaluation; Funding; Goals; Health; Human; Hypoxia; Image; Implant; In Vitro; Knowledge; Laboratory Research; Location; Malignant Neoplasms; Measurement; Measures; Medical center; Methods; Modeling; Modification; Monitor; Myocardial Infarction; Noise; Oryctolagus cuniculus; Outcome; Oxygen; Oxygen saturation measurement; Parents; Partial Pressure; Pathology; Patients; Performance; Physiologic pulse; Pre-Clinical Model; Procedures; Prognosis; Radiation therapy; Research; Roentgen Rays; Safety; Signal Transduction; Site; Technology; Testing; Time; Tissues; Translations; Visual; Visualization; anatomic imaging; cancer therapy; clinical application; clinical imaging; clinical practice; clinically relevant; clinically significant; cohort; contrast imaging; design; detection sensitivity; first-in-human; human subject; image processing; imaging biomarker; imaging modality; in vivo; innovation; multimodality; nanoGold; new technology; novel; operation; parent project; phantom model; pre-clinical; response; sensor; solid state; therapy outcome; tissue phantom; tool; treatment planning; tumor; ultrasound; usability; user-friendly; wound healing

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.

项目概要 尽管组织氧水平在诊断、预后和治疗中具有临床意义和重要性， 治疗多种病理，目前显然对量化组织的方法的需求未得到满足 具有临床使用所需的合理程度的准确性、可靠性和稳健性的氧气水平 该提案的总体目标是带来电子顺磁的独特能力。 共振（EPR）血氧测定法应用于临床领域，特别是用于增强癌症治疗。 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（可能无限期）重复询问特定组织部位的组织氧水平。 然而，这些传感器主要仅限于涉及小动物的实验室研究。 在一小群癌症患者中观察到这项新技术转化为临床应用 需要创新的传感器来提供增强的检测能力、安全性、稳定性和鲁棒性 我们建议开发一种具有增强检测功能的新型 OxyChip 传感器。 灵敏度、临床成像过程中易于识别以及长期安全性和稳定性——所有这些都特别 为测量更深层次的肿瘤而设计和优化。 EPR 血氧测定技术的独特功能将成为一种有价值的临床工具，能够提供真实的 肿瘤氧水平的时间知识用于增强癌症治疗和临床结果。 提出了具体目标： (1) 表征 OxyChips 以确定其对于时间和时间的适用性 嵌入 GNP 的 OxyChips 会受到仔细的空间定位。 在临床相关成像条件下进行评估，以确定其对时间和空间的适用性 常规临床成像期间的定位评估将包括区域显着性（即 OxyChip 的可见性） 相对于其局部肿瘤环境），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 (2) 嵌入 GNP 的新型 OxyChips 在临床前兔肿瘤模型中的评价 确定其在临床环境中成像和氧气测量的安全性、稳健性和实用性。 将使用兔乳腺肿瘤模型确定新传感器的临床适用性。 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 CT、CB-CT、平面 X 射线和超声等研究将进一步提高 EPR 的能力。 使用 OxyChip 进行血氧测定，用于癌症治疗。