Whole-Organism, Real-time Decision-enabled 3D Tissue Imaging and Recovery for Molecular Analysis

用于分子分析的全生物体、实时决策 3D 组织成像和恢复

• 批准号: 10546698
• 负责人: SUSANN M BRADY-KALNAY
• 金额: $ 22.42万
• 依托单位: BIOINVISION, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-05 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10546698
• 关键词: 3-Dimensional; Academia; Address; Adopted; Anatomy; Animal Organ; Area; Australia; Automation; Biological Markers; Biological Process; Biomedical Research; Brain; Breast cancer metastasis; Cancer Biology; Cells; Clinical; Collection; Color; Communities; Computer software; Consumption; Contracts; Data; Detection; Disease; Disseminated Malignant Neoplasm; Drug Delivery Systems; Economics; Environment; Europe; Face; Feasibility Studies; Fee-for-Service Plans; Feedback; Felis catus; Fluorescence; Freezing; Funding; Gene Expression; Gene Expression Profiling; Genes; Glean; Grant; Hand; Histologic; Histology; Human; Human Resources; Image; Imaging technology; Immune; Immunohistochemistry; In Situ; Industry; Institution; Intervention; Label; Lead; Liver; Lung; Maintenance; Malignant Neoplasms; Mammary Neoplasms; Manuals; Metastatic breast cancer; Middle East; Modeling; Molecular; Molecular Analysis; Mus; Neoplasm Metastasis; North America; Organ; Organism; Paraffin Embedding; Phase; Preparation; Process; Recovery; Regenerative Medicine; Reporter; Research; Research Personnel; Resolution; Route; Sampling; Scientist; Sensitivity and Specificity; Service delivery model; Signal Transduction; Speed; Supervision; Technology; Temperature; Testing; Thinness; Time; Tissue imaging; Tissues; Tracer; Training; Validation; Vision; Whole Organism; animal tissue; base; bone; cancer cell; cell type; cost; cost effective; deep learning; experimental study; fluorophore; high resolution imaging; histological slides; histological stains; image guided; imaging agent; imaging software; improved; instrument; interest; microscopic imaging; molecular marker; novel; operation; pandemic disease; pre-clinical; preclinical imaging; repository; research facility; software as a service; software development; stem cells; targeted imaging; tumor microenvironment; ultra high resolution; user-friendly; 3-Dimensional; Academia; Address; Adopted; Anatomy; Animal Organ; Area; Australia; Automation; Biological Markers; Biological Process; Biomedical Research; Brain; Breast cancer metastasis; Cancer Biology; Cells; Clinical; Collection; Color; Communities; Computer software; Consumption; Contracts; Data; Detection; Disease; Disseminated Malignant Neoplasm; Drug Delivery Systems; Economics; Environment; Europe; Face; Feasibility Studies; Fee-for-Service Plans; Feedback; Felis catus; Fluorescence; Freezing; Funding; Gene Expression; Gene Expression Profiling; Genes; Glean; Grant; Hand; Histologic; Histology; Human; Human Resources; Image; Imaging technology; Immune; Immunohistochemistry; In Situ; Industry; Institution; Intervention; Label; Lead; Liver; Lung; Maintenance; Malignant Neoplasms; Mammary Neoplasms; Manuals; Metastatic breast cancer; Middle East; Modeling; Molecular; Molecular Analysis; Mus; Neoplasm Metastasis; North America; Organ; Organism; Paraffin Embedding; Phase; Preparation; Process; Recovery; Regenerative Medicine; Reporter; Research; Research Personnel; Resolution; Route; Sampling; Scientist; Sensitivity and Specificity; Service delivery model; Signal Transduction; Speed; Supervision; Technology; Temperature; Testing; Thinness; Time; Tissue imaging; Tissues; Tracer; Training; Validation; Vision; Whole Organism; animal tissue; base; bone; cancer cell; cell type; cost; cost effective; deep learning; experimental study; fluorophore; high resolution imaging; histological slides; histological stains; image guided; imaging agent; imaging software; improved; instrument; interest; microscopic imaging; molecular marker; novel; operation; pandemic disease; pre-clinical; preclinical imaging; repository; research facility; software as a service; software development; stem cells; targeted imaging; tumor microenvironment; ultra high resolution; user-friendly

Summary. Tissue capture and recovery for molecular analyses such as immunostaining and gene expression analysis is important for gleaning information from tissue blocks relating to disease. The difficulty with existing solutions is that if tissue recovery is envisioned, sectioning and recovering thin tissue sections from target tissues or organs from an entire organism is not possible. Existing solutions provide manual tissue recovery, requiring the operator to be present to determine whether or not to collect a section from a tissue of interest. To address this challenge, BioInVision will bring to market a 3D tissue imaging solution for preclinical applications that em- ploys automatic, deep-learning, on-the-fly target tissue recognition from a whole organism and semi-automated tissue recovery. BioInVision pioneered the CryoVizTM instrument and has successfully commercialized fee-for- service CryoVizTM imaging for over 10 years. Our existing fee-for-service framework is well-adopted and em- braced by 75+ customers and institutions all over the world. High-resolution, broad-fluorescence-support (visible and NIR fluorophores), high-sensitivity block-face CryoVizTM imaging of preclinical frozen tissue blocks creates anatomical brightfield and molecular marker fluorescence 3D microscopic image volumes. AI-based software for deep-learning that will notify the operator in real-time upon encountering tissues of interest in color anatomy, or upon encountering molecular fluorescence such as eGFP cancer cells, enabling further interrogation of these tissues either through ultra-high-resolution tissue imaging (2µm-scale), or semi-automatic tissue capture for his- tological analyses and immunostaining (what we term “image-guided histology”). Semi-automatic tissue capture through speed and temperature control will enable recovery of tissue for molecular analyses. A demonstration project is outlined that involves characterizing whole mice with fluorescent-reporter metastatic cancer cells and fluorophore-tethered cancer targeted imaging agent. Here, we will study distribution of breast cancer metastases throughout the whole mouse and co-localization with immune cells or disease biomarkers. Our solution will also make possible drug delivery studies with fluorescent tracers. It will enable tracking of multiple fluorescently la- beled markers of cell types helping one better understand the tumor micro-environment in cancer biology. It will reduce manual labor and personnel costs and lead to better throughput to enable image-guided histology. This novel solution will cater to a wide variety of application areas including cancer biology, drug delivery, imaging agents and gene expression.

概括。分子分析（例如免疫染色和基因表达）的组织捕获和恢复 分析对于从与疾病有关的组织块中收集信息很重要。现有的困难 解决方案是，如果设想组织恢复，将从目标时间分割和恢复薄组织切片 或整个生物体的器官是不可能的。现有解决方案提供手动组织恢复，需要 要在场的操作员确定是否从感兴趣的组织中收集部分。解决 这一挑战，生物宣传将为临床前应用提供3D组织成像解决方案 在整个生物体和半自动化 组织恢复。生物启示开创了Cryoviztm仪器，并成功地商业化了费用 服务Cryoviztm成像超过10年。我们现有的用于服务费的框架已被装备良好，并且 全世界有75个以上的客户和机构。高分辨率，宽荧光支持（可见） 和NIR荧光团），临床前冷冻组织块的高敏性cryoviztm成像会产生 解剖明亮场和分子标记荧光3D显微图像体积。基于AI的软件 深入学习将在遇到色彩解剖学感兴趣的组织或 遇到分子荧光（例如EGFP癌细胞）后，可以进一步询问这些细胞 通过超高分辨率组织成像（2µm尺度）或半自动组织捕获的组织 动态分析和免疫染色（我们称为“图像引导的组织学”）。半自动组织捕获 通过速度和温度控制将使组织恢复进行分子分析。示范 概述的项目涉及用荧光蛋白转移性癌细胞和 荧光团癌靶向成像剂。在这里，我们将研究乳腺癌转移的分布 通过整个小鼠，并与免疫细胞或疾病生物标志物共定位。我们的解决方案也将 通过荧光示踪剂进行药物输送研究。它将能够跟踪多个荧光的LA- 细胞类型的贝尔德标记有助于人们更好地了解癌症生物学中的肿瘤微环境。会 降低体力劳动和人员成本，并导致更好的吞吐量，以实现图像引导的组织学。这 新颖的解决方案将迎合各种应用领域，包括癌症生物学，药物输送，成像 药物和基因表达。