Physiological magnetic resonance imaging methods for cancer applications

癌症是加拿大人死亡的主要原因。大约一半的癌症患者接受适形图像引导放射治疗，向肿瘤提供辐射，同时保留健康组织。在计算机断层扫描（CT）图像上，通过人工轮廓和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。肿瘤以血供异常（灌注异常）和氧合不良（缺氧）为特征，两者都是侵袭性肿瘤的标志，也会影响治疗效果。缺氧有不同的形式，也是其他疾病的一个特征。疾病还能使组织和血液的氧合分离。生理成像将为靶向治疗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）进行(1)磁共振血氧测定，绘制体内肿瘤氧合图，以及(2)灌注图。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（埃彭多夫）电极（侵入性太强）、正电子发射断层扫描（缺乏解剖性软组织成像）、氟-19核磁共振成像（不容易用于人体成像）和电子自旋共振（不可用于人体），都不能提供我们所寻求的东西。相反，我们探索质子R1弛豫用于组织氧合，R2*用于血液氧合。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，可以与各种分析技术配对。我们将研究组织中核磁共振信号行为的基础知识，并开发新的技术来满足这些需求。通过同时进行脂肪和水质子弛豫测绘，可以实现快速、体积的体内磁共振血氧测定。在此过程中，我们将研究脂肪-水混合物的松弛机制，以追求校准的血氧测定技术。我们将主要使用自我参考的定量方法来推进灌注成像，并结合最新的多室模型来解释血流和通透性。我们还将研究从DCE-MRI中提取灌注信息的模式识别，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，我们还将继续从MRI数据集生成用于计算辐射剂量的x射线吸收图。本研究将使我们更深入地了解人体组织的核磁共振弛豫动力学，以及氧对弛豫的影响。它将产生一种新的、快速的3D磁共振血氧测定技术，用于同时绘制组织和血液中的地图。我们将更多地了解如何使用核磁共振成像来估计人体对x射线的吸收。由于这项研究的动机是癌症，磁共振血氧仪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，以及运动科学，其影响远远超出了这个项目的范围。

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.