A soft X-Ray Phase-Based Microscope for Biomedical Applications

用于生物医学应用的软 X 射线相位显微镜

• 批准号: 10160910
• 负责人: Joseph David Ferrara
• 金额: $ 49.03万
• 依托单位: RIGAKU AMERICAS CORPORATION
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-15 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10160910
• 关键词: 3-Dimensional; Arthritis; Back; Biological; Biomedical Research; Blood; Cancer Center; Cardiovascular Diseases; Cells; Clinical; Clinical Research; Computer software; Databases; Disease; Elements; Evaluation; Generations; Health; Histology; Hour; Hydration status; Image; Image Analysis; Individual; Light; Light Microscope; Malignant Neoplasms; Memorial Sloan-Kettering Cancer Center; Methods; Microscope; Modeling; Multimodal Imaging; Neoplasm Circulating Cells; Optics; Osteoporosis; Outcome; Pathologist; Performance; Phase; Preparation; Procedures; Process; Recommendation; Research; Research Personnel; Resolution; Retrieval; Roentgen Rays; Sampling; Scheme; Slice; Software Tools; Source; Specimen; Stains; Structure; Synchrotrons; System; Testing; Thick; Thinness; Three-Dimensional Image; Three-Dimensional Imaging; Time; Tissue Sample; Tissue imaging; Tissues; Visible Radiation; X ray microscopy; X-Ray Computed Tomography; absorption; attenuation; base; bioimaging; cell type; cellular imaging; contrast imaging; data acquisition; design; flexibility; image processing; imaging modality; imaging system; innovation; macrophage; microscopic imaging; millimeter; multimodality; nano; new technology; optical imaging; preclinical study; prototype; reconstruction; simulation; soft tissue; software development; user-friendly

Abstract Biomedical images are typically obtained utilizing optical light or X-rays. Optical light is suitable for thin tissue slices, but not suitable for obtaining quality 3D images of thick tissue. Tissue specimens up to millimeter in thickness provide information about structure, different cell types and their relationships. One of the problems with optical imaging in thick tissue is the scattering of the optical light. X-rays can penetrate thick tissue, but the currently commercially available X-ray microscope imaging systems, such as the XRadia and Rigaku systems, are not optimal for soft tissue imaging. For the Xradia Versa, the lowest energy X-ray spectrum is 30 kVp, which is too high for soft tissue, while in the Xradia Ultra the field of view is only ~60 µm, and 3D imaging requires several hours. In the case of the Rigaku system, absorption contrast is too low even at low energies. We propose to deliver an intensity-modulation phase-based soft X-ray microscope for non-destructive synchrotron-quality imaging of intact biological samples with the following features:  3D, quantitative and multimodal (phase, attenuation, scatter) images  Acquisition times more than 10 times shorter than in XRadia systems  Resolution of hundreds of nm, same as visible light microscopes  Field of view from 5 mm x 5 mm to 1 mm x 1 mm, resolution from 2 µm to less than 0.5 µm  High-contrast images of cell composition  Imaging tissue/cells in their native hydrated state, with no staining and other disrupting preparation procedures  Implementing two low energy X-ray sources: 5.4 keV and 8 keV. The user can switch back and forth between the two options, as well as adjust the resolution dynamically This will be realized by combining intensity-modulation X-ray phase-based imaging (IM XPBI) method with two innovations such as cycloidal CT acquisition and lab-based ptychography. The microscope will be installed at Memorial Sloan Kettering Cancer Center and validated with a database of existing tissue samples. The 3D histology results from the proposed microscope will be compared to histology results from conventional imaging modalities to determine efficacy. Tests will also be carried out to study cancer- associated cells in blood, such as circulating tumor cells and giant cancer-associated macrophage-like cells discovered by Creatv MicroTech. Possibility to obtain high- resolution high-contrast 3D images of cells in their native state will enhance our biomedical research and clinical utility to cancer. This novel technology will be helpful for basic, pre-clinical and clinical studies related to many health conditions, such as cancer, osteoporosis, arthritis, cardiovascular disease and will assist with understanding of how these diseases progress and how they can be treated.

抽象的 生物医学图像通常利用光学或X射线获得。 适用于薄组织切片，但不适合获得厚组织切片的高质量 3D 图像 厚度达毫米的组织样本可提供有关的信息。 结构、不同细胞类型及其关系是光学问题之一。 厚组织中的成像是X射线可以穿透厚组织的散射。 组织，但目前市售的 X 射线显微镜成像系统，例如 XRadia 和 Rigaku 系统并不是软组织成像的最佳选择。 Xradia Versa，最低能量 X 射线谱为 30 kVp，这对于软射线来说太高 组织，而在 Xradia Ultra 中，视野仅为约 60 µm，并且 3D 成像需要 对于 Rigaku 系统，即使在几个小时内，吸收对比度也太低。 低能量。 我们建议提供一种基于强度调制相位的软 X 射线显微镜 完整生物样本的非破坏性同步加速器质量成像 以下特点：  3D、定量和多模态（相位、衰减、散射）图像  采集时间比 XRadia 系统短 10 倍以上  分辨率达数百纳米，与可见光显微镜相同  视场从 5 mm x 5 mm 到 1 mm x 1 mm，分辨率从 2 µm 到更小 小于0.5微米 细胞组成的高对比度图像  对处于天然水合状态的组织/细胞进行成像，无染色和其他 扰乱准备程序  用户可以使用两个低能量 X 射线源：5.4 keV 和 8 keV。 在两个选项之间来回切换，以及调整分辨率 动态地 这将通过结合强度调制 X 射线相位成像 (IM XPBI）方法具有摆线 CT 采集和基于实验室等两项创新 叠写法。 该显微镜将安装在纪念斯隆凯特琳癌症中心 使用现有组织样本的数据库进行验证。 3D 组织学结果来自 所提出的显微镜将与传统成像的组织学结果进行比较 还将进行确定功效的测试来研究癌症- 血液中的相关细胞，例如循环肿瘤细胞和巨癌相关细胞 Creatv MicroTech 发现的巨噬细胞样细胞有可能获得高- 处于自然状态的细胞的分辨率高对比度 3D 图像将增强我们的能力 癌症的生物医学研究和临床应用。 这项新技术将有助于相关的基础、临床前和临床研究 许多健康问题，例如癌症、骨质疏松症、关节炎、心血管疾病 并将帮助了解这些疾病如何进展以及如何发生 治疗。