Accelerated Electron Paramagnetic Resonance Imaging

描述(申请人提供)：肿瘤缺氧(低氧)和表现出循环低氧(肿瘤内的区域在常氧和低氧水平之间波动)已被证明对治疗具有抵抗力。虽然了解肿瘤的低氧状态可以改善治疗过程，但通过体内成像对低氧(静态和循环)进行定量评估是困难的。电子顺磁共振成像(EPRI)已被证明可以提供对小动物组织氧合(PO2)的直接定量。EPRI具有成本低、对肿瘤氧合的成像特异性高等优点。虽然使用现有技术可以在实体肿瘤内显示慢性和间歇性缺氧，但空间和时间分辨率目前还不是最理想的。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的帧速率。实施这些想法的关键将是纳入径向数据抽样技术。这些技术与迭代图像重建相结合，已被证明在数据采样要求较低的情况下仍能为动态成像提供良好的结果，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，并允许对肿瘤微环境的研究提供新的见解，对缺氧肿瘤进行药代动力学评估，这是目前任何其他成像技术都不可能做到的。这些改进将在植入小鼠腿部的SCCVII实体肿瘤的动态成像中得到证明，方法是使用加速的EPR成像来表征呼吸不同混合气体时的慢性和间歇性低氧。 与公共卫生相关：已知耐药的肿瘤缺氧(缺氧)区域的知识可以建议选择最佳治疗方法，然而，很难非侵入性地获得对缺氧的定量评估。通过电子顺磁共振成像(EPRI)可以用动态成像来定量组织氧合(PO2)，这一发展模式已经在活体中得到了成功的验证。不幸的是，目前的EPRI技术在空间和时间分辨率上是有限的；因此，这项提议将开发方法来允许EPR成像的实质性改进，这有望成为一种低成本和高度特异性的方法来表征肿瘤缺氧的空间和时间特征。

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.