3D Fourier Imaging System for High Throughput Analyses of Cancer Organoids
用于癌症类器官高通量分析的 3D 傅里叶成像系统
基本信息
- 批准号:10577796
- 负责人:
- 金额:$ 19.24万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-03-01 至 2025-02-28
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalAccountingAdoptedAlgorithmsAntineoplastic AgentsAntitumor Drug Screening AssaysApoptoticBedsBrightfield MicroscopyCellsCellularityClassificationClinicalCodeColorComputer softwareDataData SetDetectionDrug resistanceDrug usageEnvironmentEpitheliumExtracellular MatrixGoalsHeterogeneityImageIndividualInfusion proceduresLateralLightLightingMachine LearningMalignant NeoplasmsMechanicsMesenchymalMethodsMicrofluidicsMicroscopeMicroscopyModelingMolecularMonitorOpticsOrganoidsOutcomePatientsPharmaceutical PreparationsPharmacotherapyPhenotypePhysiologicalPositioning AttributeProliferatingRadiationResearch PersonnelResistanceResolutionScanningSourceSpecimenSpeedStimulusStructureSystemSystems DevelopmentTechniquesTestingTrainingTreatment outcomeVisualadvanced analyticsanticancer researchcancer imagingcellular imagingchemotherapycomputational pipelinescomputerized data processingdata acquisitiondeep learningdeep learning algorithmdesigndrug developmentdrug resistance developmentempowermentexperimental studyfeature extractionhigh resolution imaginghigh throughput analysisimaging platformimaging systemimprovedin vivoinnovationmetermicroscopic imagingmultidimensional datapredicting responseprospectivereconstructionresistance mechanismresponseself organizationsingle cell analysisstatisticstemozolomidethree dimensional cell culturetomographytooltraittumortumor heterogeneity
项目摘要
Challenges. Tumor spheroids (and organoids) have become an instrumental tool in cancer research. These
self-organized, three-dimensional (3D) systems can recapitulate phenotypic and functional traits of patient
tumors in vivo, thereby serving as a powerful testing bed to study tumor heterogeneity, interactions with the
environment (e.g., extracellular matrix), and responses to external stimuli (e.g., chemotherapy, radiation). Fully
harnessing spheroids' utility, however, is stymied by lack of high-throughput analysis methods. Conventional
bright-field microscopy, although widely used to monitor spheroids in culture, fails to capture detailed cellular
organizations; advanced fluorescent microscopy can resolve individual cells, but its imaging throughput is
restricted by the small field-of-view (FOV) and the scanning mechanisms involved. Innovations. We aim to
advance a new volumetric imaging microscope (VIM) for single cell analyses in tumor spheroids. Specifically,
we will explore integrating Fourier ptychographic microscopy (FPM) with diffraction tomography. FPM is based
on a spatially coded-illumination technique, collecting low resolution image sequences while changing the
position of a point-light source. These images are then numerically combined in the Fourier space, which
allows FPM to achieve both wide field-of-view and high spatial resolution in 2D images. We reason that full 3D
microscopic images can be recovered by accounting for optical diffraction during the numerical reconstruction.
Approaches. Aim 1. System development. We will build a VIM system featuring: i) a new numerical algorithm
to reconstruct 3D volumetric images; ii) a new light-illumination strategy to speed up the data acquisition; iii)
microfluidic cartridges optimized for spheroid culture and drug treatment; and iv) multicolor imaging capacity for
molecular detection. The complete VIM will resolve individual cells constituting a spheroid at high resolution
(lateral, 0.4 µm; axial, 1 µm) in a large imaging volume. Aim 2. Treatment monitoring with tumor spheroids. We
will test VIM's practical utility: VIM-enabled spheroid imaging will reveal earlier than bulk imaging whether a
spheroid is responsive or resistance to drug treatment. To generate a tumor model, we will use primary GBM
cells from patients. GBM spheroids will be grown and treated with drug (temozolomide) inside microfluidic
cartridges. We will use the VIM to monitor how single cells change their phenotypes under treatment, and
correlate these changes with treatment outcomes. Impact. The VIM will be a transformative tool for cancer
research, empowering researchers with rich data sets and substantially advanced analytics. Immediate
applications include better monitoring of anticancer drug responses in 3D cell culture, analyzing cellular
heterogeneity, and prospectively detecting cellular fate under various physiological conditions. These
outcomes will strengthen the clinical and scientific utility of tumor spheroids in cancer research.
挑战。肿瘤球体(和类器官)已成为癌症研究的重要工具。这些
自组织的三维 (3D) 系统可以概括患者的表型和功能特征
体内肿瘤,从而作为研究肿瘤异质性、与肿瘤的相互作用的强大测试平台
环境(例如细胞外基质)和对外部刺激(例如化疗、放疗)的反应。完全
然而,由于缺乏高通量分析方法,利用球体的实用性受到阻碍。传统的
明场显微镜虽然广泛用于监测培养中的球体,但无法捕获详细的细胞
组织;先进的荧光显微镜可以分辨单个细胞,但其成像通量
受到小视场(FOV)和所涉及的扫描机制的限制。创新。我们的目标是
开发一种新的体积成像显微镜(VIM),用于肿瘤球体中的单细胞分析。具体来说,
我们将探索将傅立叶叠层显微术 (FPM) 与衍射断层扫描相结合。 FPM基于
基于空间编码照明技术,收集低分辨率图像序列,同时改变
点光源的位置。然后这些图像在傅里叶空间中进行数字组合,
允许 FPM 在 2D 图像中实现宽视场和高空间分辨率。我们认为全 3D
显微图像可以通过在数值重建过程中考虑光学衍射来恢复。
方法。目标1.系统开发。我们将构建一个 VIM 系统,其特点是:i) 一种新的数值算法
重建 3D 体积图像; ii) 一种新的光照策略来加速数据采集;三)
针对球体培养和药物治疗进行了优化的微流体盒; iv) 多色成像能力
分子检测。完整的 VIM 将以高分辨率解析构成球体的单个细胞
(横向,0.4 µm;轴向,1 µm)在大成像体积中。目标 2. 使用肿瘤球体进行治疗监测。我们
将测试 VIM 的实用性:支持 VIM 的球体成像将比批量成像更早地揭示是否
球体对药物治疗有反应或耐药。为了生成肿瘤模型,我们将使用原发性 GBM
来自患者的细胞。 GBM 球体将在微流体内生长并用药物(替莫唑胺)进行处理
墨盒。我们将使用 VIM 监测单细胞在治疗下如何改变其表型,以及
将这些变化与治疗结果相关联。影响。 VIM 将成为癌症治疗的变革性工具
研究,为研究人员提供丰富的数据集和先进的分析。即时
应用包括更好地监测 3D 细胞培养中的抗癌药物反应、分析细胞
异质性,并前瞻性地检测各种生理条件下的细胞命运。这些
结果将加强肿瘤球体在癌症研究中的临床和科学实用性。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Hakho Lee其他文献
Hakho Lee的其他文献
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- 批准号:
10659397 - 财政年份:2023
- 资助金额:
$ 19.24万 - 项目类别:
3D Fourier Imaging System for High Throughput Analyses of Cancer Organoids
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