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.

项目摘要 尽管组织氧水平在诊断，预后和 治疗几种病理，目前显然有未满足的方法来量化组织 氧气水平具有合理程度的准确性，可靠性和鲁棒性 设置。该提案的总体目的是带来电子顺磁的独特能力 共振（EPR）血氧饱和度到临床领域，特别是用于增强癌症治疗的方法。我们有 发现了独特的固态传感器，称为Oxychips和程序，使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，这是无限期的。 但是，这些传感器仅限于涉及小动物的实验室研究。我们有 观察到 - 在一小撮癌症患者中，将这种新技术转换为临床应用 将需要创新的传感器来提供增强的检测能力，安全性，稳定性和鲁棒性 常规临床工具。我们建议通过增强的检测开发一类新型的Oxychip传感器 敏感性，临床成像期间易于识别以及长期的安全性和稳定性 - 特别是 设计和优化，用于在较深的肿瘤中进行测量。拟议的发展与 EPR血氧仪技术的独特功能将是一种有价值的临床工具，能够提供现实 肿瘤氧水平的时间知识，以增强癌症治疗和临床结局。下列 提出了具体目的：（1）氧气的特征以确定其适合临时性和 常规临床成像中的空间定位。带有GNP的氧气将受到谨慎 在临床相关的成像条件下进行评估，以确定其适合临时和空间的适用性 常规临床成像期间的定位。评估将包括区域性明显（即，Oxychip的可见性 关于其局部肿瘤环境），可检测性的定量度量，即信噪比和 对比度比率），以及用于视觉和定量增强的图像处理方法 氧。 （2）评估在临床前兔肿瘤模型中用GNP嵌入的新氧气 在临床环境中建立其安全性，鲁棒性和实用性，以进行成像和氧测量。我们 将使用兔乳腺肿瘤模型确定新传感器在临床适用性方面的能力。这 评估标准将包括使用临床成像方式对肿瘤中传感器的可视化，例如 作为CT，CB-CT，平面X射线和超声波。拟议的研究将进一步提高EPR的能力 用Oxychip进行癌症治疗的血氧仪。