Tomographic X-Ray Microscope System

描述（由申请人提供）：本提案的目标是获得资金，为分子和基因组成像中心增加X射线“显微镜”，该中心是加州大学戴维斯分校的核心设施，提供集中的基础设施和专业知识，以在动物模型和生物标本中进行成像研究。我们建议购买Xradia microXCT-200高分辨率X射线断层扫描显微镜系统，该系统包括90 kV微焦点X射线源、4 M像素CCD传感器、放大倍数范围为4 X至40 X的可选探测器光学器件以及用于重建和显示大型CT数据集的工作站。该系统将用于对来自3D细胞培养物、动物模型组织和患者活检样本的一系列生物样本进行高分辨率成像，其应用范围包括肿瘤和动脉粥样硬化斑块中钙化的成像、骨和关节病理学和再生疗法的成像、生物材料和支架的3D结构和机械性能的评估，以及高密度（例如金）纳米颗粒和纳米棒的分布的成像，仅举几例。所提出的系统可以实现空间分辨率（10%MTF）< 1？m使用40 X光学器件，可以成像尺寸达50 mm的样品（40 X探测器为20 mm）。该系统将被放置在我们的核心设施中，用于支持和帮助NIH资助的不同领域的研究，如肌肉骨骼疾病，动脉粥样硬化，癌症，再生医学，生物材料，纳米诊断和纳米治疗。该系统将通过对患者动物模型的手术或活检标本进行高分辨率、高对比度成像，对工程植入物、结构和组织进行表征，以及一系列治疗策略的效果，直接支持对疾病的更好理解。 公共卫生相关性：成像是一种强大的技术，用于可视化复杂的3-D生物组织和这些组织在疾病中发生的变化。拟议的X射线断层扫描显微镜系统利用先进的光学和相位对比方法，以实现前所未有的分辨率（~ 1 μ m）和高对比度的图像，在大量的生物组织，而无需染色或切片，提供不失真和高度定量的组织形态图像。这允许对整个活检标本或来自动物模型的器官/组织进行成像，并在整个标本上评估各种形态学参数（例如细胞结构、密度、血管分布、微结构），这是由于生物组织内的高度光散射而无法用光学技术完成的。拟议的X射线显微镜将与现有的2D和3D体内成像系统集成在我们的成像中心，为NIH资助的研究人员提供全面的资源，以使用成像技术研究疾病的动物模型。

DESCRIPTION (provided by applicant): The goal of this proposal is to secure funding to add an X-ray "microscope" to the Center for Molecular and Genomic Imaging, a core facility at UC Davis that provides centralized infrastructure and expertise to conduct imaging studies in animal models and biospecimens. We propose to purchase an Xradia microXCT-200 high- resolution X-ray tomography microscope system that includes a 90kV microfocus X-ray source, a 4 M pixel CCD sensor, selectable detector optics with magnifications ranging from 4X to 40X, and a workstation for reconstruction and display of the large CT datasets. The system will be used for high resolution imaging of a range of biospecimens from 3-D cell culture, animal model tissues and patient biopsy samples in applications that span imaging of calcifications in tumors and atherosclerotic plaques, imaging of bone and joint pathologies and regenerative therapies, evaluation of the 3-D structure and mechanical properties of biomaterials and scaffolds, and imaging of the distribution of high-density (e.g. gold) nanoparticles and nanorods, to name just a few. The proposed system can achieve a spatial resolution (10% MTF) of < 1 ?m using the 40X optics and can image specimens up to 50 mm in size (20 mm with 40X detector). The system will be placed in our core facility and used to support and aid NIH-funded research in diverse areas such as musculoskeletal disease, atherosclerosis, cancer, regenerative medicine, biomaterials, nanodiagnostics and nanotherapeutics. The system will directly support improved understanding of disease through high-resolution, high contrast imaging of surgical or biopsy specimens from animal models of patients, the characterization of engineered implants, constructs and tissues, and the effects of a range of therapeutic strategies. PUBLIC HEALTH RELEVANECE: Imaging is a powerful technology for visualizing complex 3-D biological tissues and changes in these tissues that occur through disease. The proposed X-ray tomography microscope system utilizes advanced optics and phase contrast methods to achieve unprecedented resolution (~ 1 ¿m) and high contrast images across large volumes of biological tissue without staining or sectioning, providing undistorted and highly quantitative images of tissue morphology. This allows entire biopsy specimens, or organs/tissues from animal models to be imaged, and a wide range of morphological parameters (e.g. cellularity, density, vascularity, microarchitecture) to be assessed across the entire specimen, something that cannot be done with optical techniques due to the high degree of light scatter within biological tissues. The proposed X-ray microscope will be integrated in our imaging center with existing 2D and 3D in vivo imaging systems to provide a comprehensive resource for NIH funded researchers to study animal models of disease using imaging techniques.