Groundwork for a Synchrotron MicroCT Imaging Resource for Biology (SMIRB)

同步加速器 MicroCT 生物学成像资源 (SMIRB) 的基础

• 批准号: 10169023
• 负责人: Keith Chi Cheng
• 金额: $ 65.55万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-15 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10169023
• 关键词: 3-Dimensional; Adult Respiratory Distress Syndrome; Affect; Alveolar; American; Animal Model; Architecture; Area; Autopsy; Biology; COVID-19; COVID-19 pandemic; Cause of Death; Cell Death; Cell Volumes; Cells; Cellular Structures; Cessation of life; Characteristics; Chemicals; Cicatrix; Clinical; Control Animal; Coronavirus; Data; Development; Diagnosis; Diagnostic; Diagnostic Procedure; Disease; Edema; Epithelial; Epithelial Cells; Epithelium; Equipment; Evaluation; Exudate; Female; Floods; Funding; Future; Genetic; Geometry; Health; Histologic; Histology; Human; Image; Imaging Device; Infection; Inflammatory; Intelligence; Knowledge; Leadership; Liquid substance; Location; Lung; Lung diseases; Lung infections; Lymphocyte; Machine Learning; Mathematics; Measurement; Metals; Microscopy; Middle East Respiratory Syndrome; Middle East Respiratory Syndrome Coronavirus; Modeling; Monoclonal Antibody R24; Morphology; Mus; Negative Staining; Normal tissue morphology; Outcome; Parents; Pathogenesis; Pathologic; Patients; Pattern; Phenotype; Pneumonia; Preclinical Testing; Procedures; Process; Productivity; Radiology Specialty; Readiness; Resolution; Resources; Roentgen Rays; SARS coronavirus; Sampling; Scanning; Science; Scientist; Severe Acute Respiratory Syndrome; Shapes; Slice; Source; Specimen; Stains; Structure of parenchyma of lung; Synchrotrons; Technology; Testing; Thick; Three-Dimensional Imaging; Time; Tissue Model; Tissue Stains; Tissue imaging; Tissues; Toxicology; Training; Transgenic Mice; Translating; Work; Zebrafish; automated segmentation; base; body system; cell type; cellular imaging; computational basis; density; efficacy evaluation; experience; experimental study; human disease; human imaging; human morbidity; human mortality; human tissue; humanized mouse; imaging modality; improved; instrumentation; macrophage; male; mathematical model; microCT; mouse model; neutrophil; novel; pandemic disease; parent project; phenomics; pneumocyte; pre-clinical; reconstruction; submicron; targeted treatment; therapeutic evaluation; vascular inflammation; virtual reality

Project Summary We request a high-flux x-ray source and to acquire new team expertise in segmentation from microCT images, in order to apply a new 3D form of histology developed through our parent R24 to begin to characterize the cellular and tissue geometries of COVID-19-associated Acute Respiratory Distress Syndrome (ARDS) pneumonia, our pandemic’s most common cause of death. Our novel imaging tool, X-ray histotomography, is based on microCT of fixed and metal-stained tissue. It is unique among 3D imaging methods as the only nondestructive way to achieve pan-cellular imaging (allowing characterization of all cell types and tissues) and is potentially practical. Histotomography uniquely allows direct comparison with today’s 2D standard of tissue diagnosis, histology, capable of producing both 3D renderings and undistorted 2D slices at any angle and any slice thickness. Unlike histology, we will also allow us to precisely characterize cellular arrangements into tissues after fixing and staining of samples with metal. The ability to volumetrically characterize cell types and their arrangements in acute respiratory distress syndrome (ARDS) is particularly important because it is what kills most patients in coronavirus-based pandemics, including SARS (severe acute respiratory syndrome coronavirus) in 2003, MERS (Middle East respiratory syndrome coronavirus) in 2012, COVID-19 now. The proposed work will increase our preparedness for future pandemics. ARDS lungs are an ideal human tissue model for mathematically defining human disease because all cell types are affected. The proposed work with COVID-19 lungs will increase the precision with which we understand the different stages of coronavirus lung infection and serve as a model for characterizing the Geometry of Disease across all organ systems. Histotomography in the parent R24 is currently limited to animal models, focusing on the zebrafish. The supplement will allow us to translate our work to human health, which was originally envisioned by the PI, as part of defining the “Geometry of Disease”. Our experience with this technology tells us that we will be able to characterize the numbers of each of the basic inflammatory cell types, including lymphocytes, neutrophils, and macrophages (which are morphologically distinct) in terms of numbers, volumes, shapes, and density in the inflamed tissue, and to also characterize the changes in the lung epithelia (bronchial ciliated epithelial cells and pneumocytes, cell death, and the filling of airways with fluid and fibrinous exudate, and vascular inflammation. In addition to quantitation of tissue changes, we will also be able to visualize pathological change in the tissues using virtual reality. Histotomography will serve as a way to validate a humanized mouse model of COVID-19 infection by comparing the quantitative changes with those in human autopsy samples. We will be comparing both standard histological sections and histotomographic images from adjacent tissue. Machine learning will ultimately allow us to automate recognition of cell types and pathological change. The proposed augmentation of our instrumentation and expertise will facilitate definitions of the “Geometry of Disease” across organ systems.

项目概要 我们需要高通量 X 射线源，并获得新的团队在 microCT 图像分割方面的专业知识， 为了应用通过我们的母体 R24 开发的新的 3D 组织学形式来开始表征 COVID-19 相关急性呼吸窘迫综合征 (ARDS) 的细胞和组织几何结构 肺炎是我们大流行最常见的死因。我们的新型成像工具 X 射线组织断层扫描 基于固定和金属染色组织的 microCT。它在 3D 成像方法中是独一无二的，是唯一的 以非破坏性方式实现全细胞成像（允许表征所有细胞类型和组织）以及 具有潜在实用性。组织断层扫描独特地允许与当今的组织二维标准进行直接比较 诊断、组织学，能够以任何角度和任何角度生成 3D 渲染和不失真的 2D 切片 切片厚度。与组织学不同，我们还可以精确地表征组织中的细胞排列 用金属固定和染色样品后。能够对细胞类型及其体积进行表征 急性呼吸窘迫综合征 (ARDS) 的安排尤为重要，因为它会导致死亡 大多数患者都患有基于冠状病毒的大流行病，包括 SARS（严重急性呼吸道综合症） 2003 年的冠状病毒）、2012 年的 MERS（中东呼吸综合征冠状病毒）、现在的 COVID-19。这 拟议的工作将加强我们对未来流行病的准备。 ARDS肺是理想的人体组织 数学定义人类疾病的模型，因为所有细胞类型都会受到影响。拟议的工作与 COVID-19 肺部将提高我们了解冠状病毒肺部不同阶段的精确度 感染并作为描述所有器官系统疾病几何特征的模型。 亲本 R24 的组织断层扫描目前仅限于动物模型，重点关注斑马鱼。这 补充品将使我们能够将我们的工作转化为人类健康，这也是 PI 最初设想的： 定义“疾病几何”的一部分。我们对这项技术的经验告诉我们，我们将能够 描述每种基本炎症细胞类型的数量，包括淋巴细胞、中性粒细胞和 巨噬细胞（形态上不同）在数量、体积、形状和密度方面 发炎组织，并表征肺上皮细胞（支气管纤毛上皮细胞和 肺细胞、细胞死亡、气道充满液体和纤维蛋白渗出物以及血管炎症。 除了对组织变化进行定量之外，我们还能够可视化组织中的病理变化 使用虚拟现实。组织断层扫描将作为验证 COVID-19 人源化小鼠模型的一种方法 通过与人体尸检样本中的定​​量变化进行比较来确定是否感染。我们将比较 标准组织切片和邻近组织的组织断层图像。机器学习将 最终使我们能够自动识别细胞类型和病理变化。拟议的增强 我们的仪器和专业知识将促进跨器官系统“疾病几何”的定义。