Physiological magnetic resonance imaging methods for cancer applications

癌症是加拿大的主要死因。大约一半的癌症患者接受适形图像引导放射治疗，将放射线输送到肿瘤并保留健康组织。在计算机断层扫描（CT）图像上，通过手动勾画轮廓并结合基于图谱的分割来定义目标结构。尽管取得了这些进展，但治疗的成功率参差不齐。癌症肿瘤的特征是异常的血液供应（异常灌注）和氧合不良（缺氧），这两种侵袭性肿瘤的标志物也会影响治疗效果。缺氧有不同的形式，也是其他疾病的特征。疾病也可以分离组织和血液氧合。 生理成像将为治疗靶向提供一种全新的方法。我们寻求实用的非侵入性成像方法，使用磁共振成像（MRI）（1）MR血氧测定，以映射体内肿瘤氧合，和（2）灌注映射。现有的血氧测定方法，如光学和近红外方法（仅限于浅层组织），极谱（Eppendorf）电极（侵入性太强），正电子发射断层扫描（缺乏解剖软组织成像），氟-19 MRI（不易用于人体成像）和电子自旋共振（在人体中不可行）不能提供我们所寻求的。相反，我们探索质子R1弛豫组织氧合，和R2* 血液氧合。对于灌注成像，动态对比增强（DCE）MRI技术提供最高的信号效率，并可与各种分析技术配对。我们将研究组织中NMR信号行为的基本原理，并开发新技术来满足这些需求。将通过同时脂肪和水质子弛豫标测实现快速、体积体内MR血氧测定。在此过程中，我们将研究脂肪-水混合物的松弛机制，以寻求校准的血氧测定技术。我们将主要使用自参考定量方法推进灌注成像，并结合最新的多室模型来解释血流和渗透性。我们还将研究模式识别，以从DCE-MRI中提取灌注信息，作为数据分析的精益替代方案。除了我们在生理成像方面的工作外，我们还将继续我们的工作，从MRI数据集生成用于辐射剂量计算的X射线吸收图。这项研究将为我们提供更深入的了解核磁共振弛豫动力学在人体组织中，氧对弛豫的影响。这将导致一种新的，快速的3D MR血氧测定技术，同时映射在组织和血液。我们将了解更多关于使用MRI来估计体内X射线吸收的信息。通过这项研究的动机是癌症，MR血氧定量无疑将转化为各种应用，如代谢疾病的研究和表征，如糖尿病，并在运动科学，有一个远远超出本计划的范围的影响。

Cancer is the leading cause of death in Canada. About half of cancer patients receive conformal image-guided radiation therapy, delivering radiation to the tumour and sparing healthy tissues. Target structures are defined by manual contouring combined with atlas-based segmentation, on computed tomography (CT) images. Despite these advances, treatment has variable success. Cancer tumors feature abnormal blood supply (abnormal perfusion) and poor oxygenation (hypoxia), both markers of aggressive tumours that also affect treatment efficacy. Hypoxia takes different forms and is also a feature of other disease conditions. Disease can also decouple tissue and blood oxygenation. Physiological imaging would enable an entirely new approach to treatment targeting. We seek practical non-invasive imaging methods using magnetic resonance imaging (MRI) for (1) MR-oximetry, to map tumour oxygenation in vivo, and (2) perfusion mapping. Existing methods for oximetry, such as optical and near-infrared methods (limited to shallow tissue), polarographic (Eppendorf) electrodes (too invasive), positron emission tomography (lack of anatomical soft tissue imaging), fluorine-19 MRI (not easily accessible for human imaging), and electron spin resonance (not feasible in humans) do not provide what we seek. Instead, we explore proton R1 relaxation for tissue oxygenation, and R2* for blood oxygenation. For perfusion imaging, dynamic contrast enhanced (DCE) MRI techniques provide the highest signal efficiency and can be paired with a variety of analysis techniques. We will study fundamentals of NMR signal behaviour in tissue and develop novel techniques to address these needs. Fast, volumetric in vivo MR-oximetry will be achieved via simultaneous fat and water proton relaxation mapping. In doing so, we will investigate the relaxation mechanisms of fat-water mixtures to pursue a calibrated oximetry technique. We will advance perfusion imaging primarily using self-referenced quantitative methods, integrated with the latest multi-compartment models to account for blood flow and permeability. We will also investigate pattern recognition to draw out perfusion information from DCE-MRI, as a lean alternative for data analysis. In addition to our work in physiological imaging, we will carry on our work to generate X-ray absorption maps for radiation dose calculations from MRI data sets. This research will provide us with deeper knowledge of NMR relaxation dynamics in human tissue, and the influence of oxygen on relaxation. It will result in a novel, fast 3D MR-oximetry technique for simultaneous mapping in tissue and blood. We will know more about using MRI to estimate X-ray absorption in the body. Through this research is motivated by cancer, MR-oximetry would undoubtedly translate to a variety of applications, such as the study and characterization of metabolic diseases such as diabetes, and in exercise science, to have an impact well beyond the scope of this program.