Novel Methods for in Vivo Imaging of Tissue Oxygenation

描述（由申请人提供）：有氧生命依靠氧气进行呼吸和生物能量代谢。人体氧浓度异常与癌症、心肌梗死、中风等多种疾病的发病密切相关。尽管氧的重要性，准确测量和绘制组织氧合是困难的。虽然许多成像方式只能提供组织氧合的相对或描述性数据，但电子顺磁共振（EPR）光谱有可能提供体内组织中氧的定量数据。此外，EPR技术还具有测量氧浓度绝对值的独特能力，其分辨率远高于其他任何技术。这可以使用分子或晶体顺磁探针，其EPR线宽对分子氧敏感。这种能力，结合使用光谱-空间（光谱）EPR成像获得空间分辨信息的能力，可以提供准确的氧浓度映射。尽管在过去十年中，高氧敏感自旋探针和低频成像仪器的发展取得了重大进展，但这一重要技术在生物应用中的使用受到了过于长的采集时间（通常为数十分钟）的严重限制。本提案的主要目标是开发新的图像采集和重建策略，以实现快速和高分辨率的组织中氧浓度制图。该提案旨在开发：(1)用于组织中氧浓度空间映射的高分辨率3D/4D光谱成像软件和技术；(2)旋转/扫描磁场梯度快速三维/四维光谱成像；(3)直接单阶段图像重建算法，实现随机模式采集图像的渐进式可视化；(4)采用敏感模式自适应数据（SMAD）采集方法，提高数据采集效率和图像分辨率；(5)用于氧气快速高分辨率成像的恒定时间光谱空间成像（CT-SSI）方法。初步研究表明，与传统方法相比，该方法的图像采集速度可提高30倍。这些创新程序的可用性将增强我们执行快速/高分辨率图像采集的能力。该技术将为自由基和氧的生物医学成像领域提供令人兴奋的新机会。

DESCRIPTION (provided by applicant): Aerobic life relies on oxygen for respiration and bioenergetic metabolism. Abnormality in the concentration of oxygen in human body is strongly implicated in the pathogenesis of a variety of diseases including cancer, myocardial infarction and stroke. Despite the importance of oxygen, accurate measurement and mapping of tissue oxygenation is difficult. Although many imaging modalities provide only relative or descriptive data on tissue oxygenation, the electron paramagnetic resonance (EPR) spectroscopy has the potential of providing quantitative data of oxygen in tissues, in vivo. In addition, the EPR technique has the unique capability of measuring absolute value of oxygen concentration with resolutions far better than any other technique. This is possible using molecular or crystalline paramagnetic probes whose EPR line-width is sensitive to molecular oxygen. This capability, when combined with the ability to obtain spatially resolved information using spectral-spatial (spectroscopic) EPR imaging, can provide accurate mapping of oxygen concentration. Despite significant advances in the development of highly oxygen-sensitive spin probes and low-frequency imaging instrumentation in the past decade, the use of this important technology for biological applications is severely limited by the prohibitively long acquisition times, usually tens of min. The main objective of this proposal is to develop novel image acquisition and reconstruction strategies to enable fast and high-resolution mapping of oxygen concentration in tissues. The proposal seeks to develop: (1) High-resolution 3D/4D spectroscopic imaging software and techniques for spatial mapping of oxygen concentration in tissues; (2) Fast 3D/4D spectroscopic imaging using spinning/sweeping magnetic field gradients; (3) Direct single-stage image reconstruction algorithm for progressive visualization of images from random-mode acquisitions; (4) Sensitive-mode adaptive data (SMAD) acquisition approach for increased data acquisition efficiency and image resolution; (5) Constant-time spectral-spatial imaging (CT-SSI) methods for fast and high-resolution imaging of oxygen. Preliminary studies show that up to 30-fold increase in the speed of image acquisition can be achieved compared to the conventional methods. The availability of these innovative procedures will enhance our ability to perform fast/high-resolution image acquisition. The technology should offer exciting new opportunities in the field of biomedical imaging of free radicals and oxygen.