Correlative Imaging with Multi-energy X-ray Tomography

简介：Ford博士的研究实验室在肺的临床前微型计算机断层扫描(Micro-CT)成像方面建立了强大的背景，开发了使用碘和氙气作为造影剂分别显示血管和呼吸道的多能量对比度增强Micro-CT成像方案。我们还在加拿大光源同步加速器设施(CLS)的生物医学光束线(BMIT)上开发了新的成像技术，包括第一次对氙气进行K边缘减影(KES)成像，以及第一次使用啮齿动物的呼吸信号在指定的呼吸期触发图像采集。我们的微型CT和BMIT光束线技术将能够对啮齿动物器官和组织的结构、生理和功能进行活体定量分析。 计划目标：比较来自微CT和同步辐射研究的3D X射线图像与光学技术，包括2D共焦显微镜和3D光学投影断层扫描(OPT)。在微型CT和同步加速器图像中进行的测量提供了关于活动物体内器官结构和功能的信息。对于光学技术，对器官进行切片，以提供关于器官或组织内细胞的结构和功能的信息。 方法：我们将引入造影剂或染色，在不同的成像技术下显示相同的器官特征。对于活体成像，我们使用碘和氙气分别显示血管和空气空间；这两种材料都可以在Micro-CT和KES同步成像中看到。为了将X射线和光学技术联系起来，可能的造影剂候选包括金和银纳米颗粒以及硫化镉/硫化锌量子点。我们预计所有这些材料都将在同步加速器和微型计算机断层扫描图像中可见。银纳米粒子和量子点都已被确定为光学标记。 同步加速器成像将在CLS同步加速器设施中使用一种新的光谱KES技术进行。UBC高通量表观基因组学中心(CHTP)有两台微型CT扫描仪，适用于对活体啮齿动物和切除的器官和组织进行成像。CHTP还配备了一台光学投影断层扫描仪，可以生成荧光标记组织的3D光学图像或自动荧光图像，以及一台带有多个激光源的白光激光共聚焦显微镜。 影响：该计划的新颖性包括将图像采集与BMIT光束线上的生理信号同步，并使用世界范围内独特的光谱KES技术。使用同步加速器将能够进行非常准确的测量，这些测量将与体内Micro-CT、体外Micro-CT、OPT和显微镜进行比较。总而言之，这些测量提供了器官如何运作的更完整的图景，或识别器官中没有正常运作的区域。

INTRODUCTION: Dr. Ford’s research lab has built upon a strong background in preclinical micro-computed tomography (micro-CT) imaging of the lung to develop multi-energy contrast-enhanced micro-CT imaging protocols using iodine and xenon as contrast agents to visualize the blood vessels and airways respectively. We have also developed new imaging techniques on the biomedical beam line (BMIT) of the Canadian Light Source Synchrotron facility (CLS), including the first K-edge subtraction (KES) imaging of xenon and the first images using the respiratory signal from the rodent to trigger image acquisition during a specified respiratory phase. Our techniques for micro-CT and on the BMIT beam line will enable in vivo quantitative analysis of structure, physiology and function in rodent organs and tissues. PROGRAM GOAL: To compare 3D x-ray images from micro-CT and synchrotron studies with optical techniques, including 2D confocal microscopy and 3D optical projection tomography (OPT). The measurements performed in the micro-CT and synchrotron images provide information about the organ structure and function within a living animal. For the optical techniques, the organs are sectioned to give information about the structure and function of the cells within the organ or tissue. METHODS: We will introduce contrast media or staining to visualize the same organ features under different imaging techniques. For in vivo imaging, we are using iodine and xenon to visualize the blood vessels and air spaces respectively; both of these materials are visible in the micro-CT and in KES synchrotron imaging. To correlate x-ray and optical techniques, possible contrast agent candidates include gold and silver nanoparticles and CdSe/ZnS quantum dots. We expect all of these materials will be visible in the synchrotron and micro-computed tomography images. Both the silver nanoparticles and quantum dots have been established as optical markers. Synchrotron imaging will be performed at the CLS synchrotron facility using a novel spectral KES technique. The UBC Centre for High-Throughput Phenogenomics (CHTP) has two micro-CT scanners suitable for imaging live rodents and excised organs and tissues. The CHTP also houses an optical projection tomography machine that produces 3D optical images of fluorescently labeled tissues or auto fluorescence images and a white light laser confocal microscope with multiple laser sources. IMPACT: The novelty of this program includes synchronizing the image acquisition with physiological signals at the BMIT beam line and using a world-wide unique spectral KES technique. Using the synchrotron will enable very accurate measurements that will be compared with in vivo micro-CT, ex vivo micro-CT, OPT and microscopy. Together, these measurements provide a more complete picture of how the organ functions or identify regions of the organ that are not functioning properly.