High throughput optical coherence tomography (OCT)-based imaging platform for label-free, non-invasive characterization of 3D tumor spheroids.

基于高通量光学相干断层扫描 (OCT) 的成像平台，用于对 3D 肿瘤球体进行无标记、非侵入性表征。

• 批准号: 10225615
• 负责人: Chao Zhou
• 金额: $ 34.73万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-15 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10225615
• 关键词: 3-Dimensional; Animal Model; Antineoplastic Agents; Antitumor Drug Screening Assays; Basement membrane; Biological Assay; Caliber; Cancer Biology; Cellular Assay; Clinic; Clinical Trials; Collaborations; Collection; Custom; Data; Data Storage and Retrieval; Development; Diffusion; Drug Modelings; Drug toxicity; Endothelial Cells; Extracellular Matrix; Failure; Fibroblasts; Fluorescence Microscopy; Growth; Image; Imaging Techniques; Imaging technology; In Vitro; Investments; Kinetics; Label; Laboratories; Longitudinal Studies; Malignant Neoplasms; Measurement; Medicine; Methods; Microscopy; Modeling; Molecular Analysis; Morphology; Necrosis; Neoplasm Metastasis; Nutrient; Oncology; Optical Coherence Tomography; Optics; Oxygen; Patients; Penetration; Pharmaceutical Preparations; Pharmacology; Phase-Contrast Microscopy; Physiological; Physiology; Predictive Value; Reagent; Regenerative Medicine; Resolution; Sampling; Scanning; Shapes; Signal Pathway; Speed; Stains; System; Techniques; Technology; Testing; Three-dimensional analysis; Time; TimeLine; Tissue Model; Toxic effect; Translational Research; Translations; Tumor Angiogenesis; United States National Institutes of Health; angiogenesis; anticancer research; attenuation; automated image analysis; base; cancer therapy; cell type; clinical development; clinical efficacy; clinical predictors; compound 30; cost; design; drug development; drug discovery; drug efficacy; fluorescence imaging; high throughput screening; imaging platform; improved; in vivo; insight; light scattering; longitudinal analysis; necrotic tissue; neoplastic cell; novel; optical imaging; pressure; programs; relating to nervous system; response; sample fixation; screening; standard of care; targeted treatment; three dimensional structure; tool; tumor; tumor growth; validation studies

Project Summary More than 90% of the drugs being developed fail because of lack of efficacy or unexpected toxicity in clinical trials. This failure rate in the late stages of clinical development is in large part due to the use of overly simplistic in vitro cell assays, and in vivo animal models with limited predictive value during the various stages of drug discovery. Three-dimensional (3D) tissue models are expected to provide novel physiological and pharmacological data that will be more predictive of drug efficacy and toxicity in the clinic, and will therefore have a significant immediate and long-lasting impact in shortening of the timelines, reducing the costs, increasing the return on investment of drug discovery, and bringing new medicines to more patients more efficiently. Although high content fluorescence imaging, both confocal and non-confocal, is heavily used for this purpose in high throughput screening (HTS) laboratories, low penetration of fluorescent reagents and light scattering from 3D tumor spheroid models of a size of >50 μm diameter hugely limits the measurements of the morphology and physiology inside the spheroids, and requires significant manipulation of the samples, including fixation, clearing and staining, which limits its practical use for HTS of large collections of compounds. Recently, we have demonstrated that optical coherence tomography (OCT) can image and obtain morphological and physiological information of an entire 3D tumor spheroid over 1 mm in size without presumptions about its shape. Furthermore, we developed a parallel OCT imaging technology and achieved over 10-fold speed improvement compared to state-of-the-art commercial OCT technologies. In this program, in collaboration with Dr. Marc Ferrer’s group at the NIH National Center for Advancing Translational Sciences, we plan to: 1) Develop and optimize a label-free, non-invasive high throughput OCT (HT-OCT) imaging platform capable of performing parallel imaging (16 channels) on a 384-well plate. We expect that the entire plate can be scanned within less than 5 minutes, including time needed for stage translation and data storage; 2) Perform live, longitudinal studies to characterize the morphology and physiology of single- and multi-cell type tumor spheroids (SCTS and MCTS) using the HT- OCT system; and 3) Evaluate the effects of oncology drugs, which encompass a broad range of mechanisms from targeted therapies modulating cellular signaling pathways to standard of care chemotherapeutics, on 3D tumor spheroids. The 3D and longitudinal information about development of various tumor spheroid models will be the first of its kind. Successful completion of these development and validation studies will establish a label- free, non-invasive HT-OCT imaging platform that can be used to accurately and quantitatively analyze 3D morphological and physiological information of various types of tumor spheroids. The techniques developed in this proposal will also be applicable to any other 3D native and/or biofabricated tissue models, such as neural spheroids, being developed for regenerative medicine and drug discovery studies.

项目摘要 由于缺乏效率或临床意外毒性，超过90％的药物失败了 试验。在临床开发的后期，这种失败率在很大程度上是由于使用过度简单 体外细胞分析和在药物各个阶段的预测值有限的体内动物模型 发现。预计三维（3D）组织模型将提供新颖的生理和 药理学数据将更可预测诊所的药物效率和毒性，因此将具有 缩短时间表的重大直接和持久影响，降低成本，增加 药物发现的投资回报率，并将新药物带给更多患者。虽然 高含量荧光成像，既有共聚焦和非对焦点，都大量用于此目的 吞吐量筛选（HTS）实验室，荧光试剂的低渗透和3D的光散射 直径>50μm的肿瘤球体模型极大地限制了形态的测量值 球状素内的生理学，需要对样品进行重大操纵，包括固定，清除 和染色，这限制了其对大量化合物HTS的实际用途。最近，我们有 证明光学相干断层扫描（OCT）可以形象并获得形态学和生理学 整个3D肿瘤球形的信息在1毫米的大小上，而没有假定其形状。此外， 我们开发了一项平行的OCT成像技术，并且与 最先进的商业OCT技术。在此计划中，与马克·费雷尔博士的小组合作 NIH国家推进转化科学中心，我们计划：1）开发和优化无标签， 非侵入性高吞吐量OCT（HT-OCT）成像平台能够执行平行成像（16 通道）在384孔板上。我们希望可以在不到5分钟的时间内扫描整个盘子 包括舞台翻译和数据存储所需的时间； 2）进行现场，纵向研究以表征 使用HT-的单细胞和多细胞型肿瘤球体（SCT和MCT）的形态和生理学 OCT系统； 3）评估肿瘤药的影响，该药物涵盖了广泛的机制 从调节细胞信号通路的靶向疗法到3D的护理化学治疗疗法 肿瘤球状。有关各种肿瘤球形模型开发的3D和纵向信息将 成为同类的第一个。这些开发和验证研究的成功完成将建立标签 - 可以用于准确和定量分析3D的免费，非侵入性HT-OCT成像平台 各种类型肿瘤球体的形态和物理信息。这些技术在 该建议还适用于其他任何3D天然和/或生物制造的组织模型，例如中性 球体，用于再生医学和药物发现研究。

项目成果

Wide-field Ophthalmic Space-Division Multiplexing Optical Coherence Tomography.

• DOI: 10.1364/prj.383034
• 发表时间: 2020-04
• 期刊: Photonics research
• 影响因子: 7.6
• 作者: Jerwick J;Huang Y;Dong Z;Slaudades A;Brucker AJ;Zhou C
• 通讯作者: Zhou C

ELAC2/RNaseZ-linked cardiac hypertrophy in Drosophila melanogaster.

• DOI: 10.1242/dmm.048931
• 发表时间: 2021-08-01
• 期刊: Disease models & mechanisms
• 影响因子: 4.3
• 作者: Migunova E;Theophilopoulos J;Mercadante M;Men J;Zhou C;Dubrovsky EB
• 通讯作者: Dubrovsky EB

A Drosophila heart optical coherence microscopy dataset for automatic video segmentation.

• DOI: 10.1038/s41597-023-02802-y
• 发表时间: 2023-12-09
• 期刊: SCIENTIFIC DATA
• 影响因子: 9.8
• 作者: Fishman, Matthew;Matt, Abigail;Wang, Fei;Gracheva, Elena;Zhu, Jiantao;Ouyang, Xiangping;Komarov, Andrey;Wang, Yuxuan;Liang, Hongwu;Zhou, Chao
• 通讯作者: Zhou, Chao

Developing Drosophila melanogaster Models for Imaging and Optogenetic Control of Cardiac Function.

• DOI: 10.3791/63939
• 发表时间: 2022-08-25
• 期刊: Journal of visualized experiments : JoVE
• 作者: Gracheva E;Wang F;Matt A;Liang H;Fishman M;Zhou C
• 通讯作者: Zhou C

Optical coherence tomography image denoising using a generative adversarial network with speckle modulation.

• DOI: 10.1002/jbio.201960135
• 发表时间: 2020-04
• 期刊: Journal of biophotonics
• 影响因子: 2.8
• 作者: Dong Z;Liu G;Ni G;Jerwick J;Duan L;Zhou C
• 通讯作者: Zhou C