Time Domian Electron Paramagnetic Resonance Imaging

时域电子顺磁共振成像

• 批准号: 8552702
• 负责人: murali cherukuri
• 金额: $ 102.41万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8552702
• 关键词: 3-Dimensional; Algorithms; Amplifiers; Anatomy; Angiogenesis Inhibitors; Animals; Blood Vessels; Blood Volume; Blood flow; Bolus Infusion; Chronic; Cytotoxin; Data; Data Set; Dimensions; Dose; Drug-sensitive; Electron Spin Resonance Spectroscopy; Glioblastoma; Goals; Hour; Human; Hypoxia; Image; Injection of therapeutic agent; Ionizing radiation; Magnetic Resonance Imaging; Maps; Metabolic; Methods; Microcirculation; Modality; Modeling; Monitor; Mus; Neoplasms in Vascular Tissue; Oxygen; Pathway interactions; Pharmaceutical Preparations; Pharmacotherapy; Phase; Physics; Physiological; Physiology; Property; Pyruvate; Pyruvic Acid; Radiation therapy; Resolution; Sirolimus; Time; Tissues; Tracer; Tumor Oxygenation; chemotherapeutic agent; chemotherapy; data acquisition; density; human FRAP1 protein; image reconstruction; imaging modality; improved; in vivo; instrumentation; research study; response; scale up; tumor; tumor growth

a) Determining and intrinsic spatial, spectral (physiologic) and temporal resolution of EPRI and co-registration with images from MRI. Improving the temporal resolution using ?partial k-space? image data acquisition strategiesThe fundamental spectrometer dependent factors governing the spatial, spectral and temporal resolutions have been studied to understand the practically realizable resolutions in vivo experiments. This is an important factor which when analyzed will permit conducting in vivo experiments to ask fundamental questions pertaining to the dynamics of physiology and physiological fluctuations in tumors, which has not been possible till now. We have critically examined factors involved in determining the intrinsic resolution in EPRI and developed image formation strategies to optimize the EPRI data sets for optimal spatial, temporal and spectral (physiologic) resolutions. With an understanding of the factors governing the spatial, spectral and temporal resolutions, we have been able to optimize and improve the same. Additionally, we have borrowed concepts from MRI such as compressed sensing and partial k-space imaging strategies and have been able to collect images in as little as 1 minute for a full 3-dimensional image data without sacrificing the spatial and spectral dimensions. With this capability, we have been able to probe the subtle temporal fluctuations in tumor pO2 and also distinguish chronic and cycling hypoxia. We have also implemented imaging of pO2 in glioblastoma models in mice where for the first time we have been able to demonstrate the feasibility of pO2 maps.b) Strategies for imaging larger sized objects:We have redesigned a low field MRI scanner to operate as an EPRI pO2 imager by integrating the EPR RF chain and controlling the gradient amplifiers. The magnet has an 80 cm bore and permits the study of larger objects. We have developed imaging gantries where it is possible to collect pO2 images and move the object to an adjacent MRI scanner operating at 1.0 T to collect anatomical images which can be co-registered with pO2 maps. This has made it possible to increase the number of studies which can be performed. c) Temporal profile of tumor physiology when treated with drugs which impact microcirculation. Using the capability of EPR to monitor changes in tumor pO2 and blood volume when treated with rapamycin, we found that there is a period after initiating treatment where there is a transient increase in tumor pO2 with an accompanying decrease in blood vessel density consistent with the hypothesis of vascular re-normalization in addition to inhibiting mTOR pathways.d) Identification of strategies to induce temporary hypoxia to enhance the efficacy of hypoxic cytotoxins:We have been conducting metabolic MRI using hyperpolarized pyruvic acid as the tracer. We examined the effect of bolus pyruvate injection on tumor pO2 profiles and demonstrated that pyruvate induces hypoxia immediately after a bolus dose which is sustained for 4 hours. This is an important finding in using hypoxia sensitive drugs. We found that in hypoxic tumors, the efficacy of hypoxic cytotoxins such as TH-302 is enhanced by prior treatment with pyruvate which induces hypoxia transiently. The enhanced efficacy of TH-302 is explained as bring the tumor hypoxia into radiobiologic hypoxia.

a）确定EPRI的固有空间、光谱（生理）和时间分辨率，并与来自MRI的图像配准。提高时间分辨率使用？部分k空间图像数据获取策略已经研究了决定空间、光谱和时间分辨率的基本光谱仪依赖因素，以理解在活体实验中实际可实现的分辨率。这是一个重要因素，分析后将允许进行体内实验，以提出与肿瘤生理动力学和生理波动有关的基本问题，而这到目前为止还不可能。我们已经严格审查的因素参与确定内在的分辨率在EPRI和开发的图像形成策略，以优化EPRI数据集的最佳空间，时间和光谱（生理）的分辨率。通过了解空间、光谱和时间分辨率的影响因素，我们能够优化和改进这些因素。 此外，我们还借鉴了MRI的概念，如压缩感知和部分k空间成像策略，并且能够在短短1分钟内收集完整的三维图像数据，而不会牺牲空间和光谱维度。有了这种能力，我们已经能够探测肿瘤pO 2的微妙的时间波动，也区分慢性和循环缺氧。我们还在小鼠胶质母细胞瘤模型中实现了pO 2成像，其中我们第一次能够证明pO 2图的可行性。B）对较大尺寸物体成像的策略：我们重新设计了低场MRI扫描仪，通过集成EPR RF链和控制梯度放大器，作为EPRI pO 2成像仪操作。磁铁有一个80厘米的孔，并允许研究较大的物体。我们开发了成像机架，可以收集pO 2图像并将对象移动到相邻的1.0 T MRI扫描仪，以收集可以与pO 2图配准的解剖图像。这使得能够增加可以进行的研究的数量。c）当用影响微循环的药物治疗时肿瘤生理学的时间曲线。利用EPR监测雷帕霉素治疗时肿瘤pO 2和血容量变化的能力，我们发现，在开始治疗后的一段时间内，除了抑制mTOR途径外，肿瘤pO 2会短暂增加，同时伴随血管密度下降，这与血管重新正常化的假设一致。d）鉴定诱导暂时缺氧以增强缺氧细胞毒素功效的策略：我们一直在使用超极化的甘草酸作为示踪剂进行代谢MRI。我们研究了推注丙酮酸对肿瘤pO 2分布的影响，并证明丙酮酸在推注剂量持续4小时后立即诱导缺氧。这是使用缺氧敏感药物的重要发现。我们发现，在缺氧肿瘤中，缺氧细胞毒素如TH-302的功效通过预先用丙酮酸治疗而增强，丙酮酸诱导短暂缺氧。TH-302的增效作用是将肿瘤缺氧转化为放射生物学缺氧。