Biological Soft X-ray Tomography at the Advanced Light Source

先进光源下的生物软 X 射线断层扫描

• 批准号: 10037804
• 负责人: Carolyn A Larabell
• 金额: $ 58.9万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2021-09-20
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10037804
• 关键词: 3-Dimensional; Algorithmic Software; Biological; Biomedical Research; Calibration; California; Cell Size; Cells; Cellular Structures; Characteristics; Clinical; Collection; Communities; Computer software; Contrast Media; Data; Development; Diabetes Mellitus; Disease; Disseminated Malignant Neoplasm; Educational workshop; Ensure; Feedback; Funding; Goals; Hydration status; Image; Imaging technology; Individual; Internet; Laboratories; Light; Lighting; Maintenance; Mammalian Cell; Methods; Microscope; Modeling; Neurodegenerative Disorders; Organism; Parasites; Peer Review; Preparation; Procedures; Productivity; Research; Research Personnel; Resources; Roentgen Rays; Shapes; Site; Source; Specialist; Specimen; Stains; Synchrotrons; Technology; Training; Training Programs; Work; X-Ray Computed Tomography; X-Ray Tomography; beamline; cellular imaging; computing resources; contrast imaging; cryogenics; data acquisition; design; end of life; experience; human disease; human imaging; improved; insight; instrument; novel therapeutics; operation; outreach; reconstruction; symposium; tomography; tool; user-friendly

Project Summary/Abstract The National Center for X-ray Tomography (NCXT) provides biomedical researchers with access to unique technologies for visualizing and quantifying intact, fully hydrated cells in 3D. The NCXT designed, built, and now operates a soft x-ray microscope (XM-2) at the Advanced Light Source, Berkeley. XM-2 is currently the only microscope of its kind in the Nation. The unique characteristics of soft x-rays make them an excellent illumination source in a microscope designed to images cells. Soft x-rays penetrate large cells easily, allowing researchers to image mammalian cells in great detail. Moreover, soft x-rays produce image contrast without the need to use stains or other contrast agents; procedures that could damage the delicate sub-cellular structures and organization. XM-2 is equipped with a cryogenic specimen stage that can rotate freely through 360 degrees, allowing the specimen to be imaged from different perspectives. The specimen stage allows researchers to image cells by tomographic methods. In tomography 2D images are taken from many different perspectives. The resultant `stack' of projection images is used to calculate a 3D reconstruction of the specimen. In effect, we following the same principles as used in clinical Computed Tomography (CT), but on individual cells rather than a whole body. This funding will support the day-to-day maintenance, upgrades, and user operation of XM-2, together with associated specimen preparation laboratories and ongoing upgrades to our software/computing resources. This support will ensure biomedical researchers have access to a unique cell imaging technology. During the funding cycle, we will achieve the following specific aims: Aim 1: Enable user access to biological soft x-ray tomography (SXT) at the ALS. The work of this aim will ensure users can bring cells to NCXT and leave with soft x-ray tomographic reconstructions of their specimens. Significant consideration will be striving to make the Resource as user-friendly as possible, and therefore accessible to the broadest possible research community as possible, not just to imaging specialists. Aim 2: Maintain and calibrate XM-2, the NCXT operated soft x-ray microscope at the ALS. As with all synchrotron beamlines, XM-2 is a sophisticated instrument that requires regular maintenance and calibration. We will take a programmatic approach to ensure XM-2 is robust, reliable, and operates with minimum unscheduled downtime. Aim 3: Implement upgrades and enhancements to ensure the NCXT remains `state-of-the-art.' Over the timescale of the funding cycles, new hardware, software, and algorithms will become available, and some existing components will reach their end-of-life. We will, therefore, carry out upgrades and enhancements to maintain the NCXT at the `state-of-the-art.'

项目总结/摘要 国家X射线断层扫描中心（NCXT）为生物医学研究人员提供了独特的 用于在3D中可视化和量化完整的、完全水合的细胞的技术。NCXT设计、建造和 现在在伯克利的高级光源公司操作软X射线显微镜（XM-2）。XM-2目前是 国内唯一的显微镜 软X射线的独特特性使其成为设计的显微镜中的出色照明源 to images图像cells细胞.软X射线很容易穿透大细胞，使研究人员能够对哺乳动物细胞进行大范围成像。 详细此外，软X射线产生图像对比，而无需使用染色剂或其他造影剂; 可能破坏脆弱的亚细胞结构和组织的程序。XM-2配备了一个 低温样品台可以自由旋转360度，允许样品从 不同的视角。标本台允许研究人员通过断层扫描方法对细胞进行成像。在 断层摄影2D图像是从许多不同的视角拍摄的。投影图像的合成“堆栈” 用于计算样本的3D重建。实际上，我们遵循的原则与 临床计算机断层扫描（CT），但对单个细胞，而不是整个身体。 这笔资金将用于XM-2的日常维护、升级和用户操作， 相关的标本制备实验室和不断升级我们的软件/计算资源。 这项支持将确保生物医学研究人员能够获得独特的细胞成像技术。期间 我们会在未来的融资周期内，达致以下具体目标： 目标1：使用户能够访问ALS的生物软X射线断层扫描（SXT）。这一目标的工作将 确保用户可以将细胞带到NCXT，并带着标本的软X射线断层扫描重建离开。 重要的考虑因素将是努力使资源尽可能方便用户，因此， 让尽可能广泛的研究团体都能接触到，而不仅仅是成像专家。 目的2：维护和校准XM-2，NCXT操作的软X射线显微镜在ALS。如同所有 XM-2同步加速器光束线是一种需要定期维护和校准的精密仪器。 我们将采取一种程序化的方法，以确保XM-2是强大的，可靠的， 计划外停机时间。 目标3：进行升级和改进，以确保NCXT保持“最先进水平”。在 在资金周期的时间尺度内，新的硬件、软件和算法将可用， 现有的部件将达到其使用寿命。因此，我们将进行升级和改进， 将NCXT保持在最先进的水平。'