Accelerated Electron Paramagnetic Resonance Imaging

描述（由申请人提供）：缺氧（缺氧）和周期性缺氧（肿瘤内区域在常氧和缺氧水平之间波动）的肿瘤已被证明对治疗有抵抗力。虽然了解肿瘤的缺氧状态可以改善治疗过程，但通过体内成像定量评估缺氧（静态和循环）是困难的。电子顺磁共振成像（EPRI）已被证明提供小动物组织氧合（pO2）的直接量化。EPRI具有成本低、对肿瘤氧合成像特异性高的优点。虽然使用现有技术可以可视化实体肿瘤内的慢性和间歇性缺氧，但空间和时间分辨率目前尚不理想。该项目的技术目标是为EPRI开发新的图像采集策略，以提高空间分辨率和重建图像帧率。实现这些想法的关键是结合径向数据采样技术。这些技术，当与迭代图像重建相结合时，尽管数据采样要求宽松，但已被证明为动态成像提供了良好的结果，因此与以前的技术相比，提供了显著的加速。这些新方法将提高空间和时间分辨率，并通过对缺氧肿瘤的药代动力学评估，为肿瘤微环境研究提供新的见解，这是目前任何其他成像技术都无法实现的。这些改进将在植入小鼠腿部的SCCVII实体瘤的动态成像中得到证明，通过使用加速EPR成像来表征呼吸不同气体混合物时的慢性和间歇性缺氧。

DESCRIPTION (provided by applicant): Tumors that are oxygen-starved (hypoxic) and exhibit cycling hypoxia (where regions within a tumor fluctuate between normoxic and hypoxic levels) have been shown to be resistant to treatment. While knowledge of the hypoxic status of tumors could inform an improved therapeutic course, quantitative assessment of hypoxia (both static and cycling) via in vivo imaging is difficult. Electron paramagnetic resonance imaging (EPRI) has been shown to provide direct quantification of tissue oxygenation (pO2) in small animals. EPRI is advantageous in being low cost and highly specific to image tumor oxygenation. While both chronic and intermittent hypoxia can be visualized within solid tumors using existing techniques, the spatial and temporal resolution is currently sub-optimal. The technical aim of this project is to develop new image acquisition strategies for EPRI to improve spatial resolution and reconstructed image framerate. Key to the implementation of these ideas will be the incorporation of radial data sampling techniques. These techniques, when combined with iterative image reconstruction, have been shown to provide good results for dynamic imaging in spite of relaxed data sampling requirements, thus providing significant acceleration compared to previous techniques. These new methods will enable improved spatial and temporal resolution and allow novel insights into study of the tumor microenvironment with a pharmcokinetic assessment of hypoxic tumors that is currently not possible with any other imaging technique. These improvements will be demonstrated in dynamic imaging of SCCVII solid tumors implanted in the legs of mice by using accelerated EPR imaging to characterize chronic and intermittent hypoxia in response to breathing different gas mixtures. PUBLIC HEALTH RELEVANCE: Knowledge of oxygen-starved (hypoxic) regions of tumors, which are known to be treatment-resistant, could suggest the selection of optimal therapy, however, quantitative assessments of hypoxia are difficult to obtain non-invasively. Quantification of tissue oxygenation (pO2) with dynamic imaging is possible with electron paramagnetic resonance imaging (EPRI), and this developing modality has been successfully demonstrated in in vivo. Unfortunately, current EPRI techniques are limited in spatial and temporal resolution; thus, this proposal will develop methods to allow substantial improvements in EPR imaging, which has the promise to become a low cost and highly specific modality to spatially and temporally characterize tumor hypoxia.