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.

项目总结

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

High dynamic range 3D motion tracking using circular scans with optical coherence tomography.

• DOI: 10.1364/boe.493725
• 发表时间: 2023-07
• 期刊: Biomedical optics express
• 影响因子: 3.4
• 作者: Senyue Hao;M. Amaral;Chao Zhou