Spectro-Holographic Instrument for Dynamic Sensing of Cancer Progression

用于动态感知癌症进展的光谱全息仪器

基本信息

批准号：
10000970
负责人：
Lev T Perelman
金额：
$ 69.64万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10000970
关键词：
Adopted Affect Algorithms Area Biochemical Biogenesis Biological Biological Markers Biomedical Engineering Biopsy Breast Cancer Patient Cancer Biology Cell physiology Cells Cellular Precursor of Cancer Cellular Structures Clinical Clinical Data Clinical Oncology Clinical Research Collaborations Data Development Doctor of Philosophy Dysplasia Electron Microscopy Endoscopy Esophagus Fluorescence Fluorescence Microscopy Fluorescent Probes Functional Imaging Gastroenterologist Gastrointestinal tract structure High-Risk Cancer Human Image Imaging Device Imaging Techniques Label Laser Scanning Confocal Microscopy Length Lesion Light Malignant Neoplasms Malignant neoplasm of pancreas Maps Mathematics Measures Medicine Methods MicroRNAs Microscopic Microscopy Modality Modeling Monitor Morphology Nature Neoplasms Nuclear Nuclear Structure Oncogenic Oncology Optical Biopsy Optics Organelles Organism Pancreatic Cyst Pathologist Pharmaceutical Preparations Phosphotransferases Photobleaching Play Predisposition Property Proteins Refractive Indices Research Resolution Role Sampling Scanning Scientist Screening for cancer Serum Signal Pathway Site Spectrum Analysis Stains Statistical Data Interpretation Structure Subcellular structure System Techniques Testing Time Tissues Training Tumor Suppressor Proteins Work absorption base cancer cell cancer genetics carcinogenesis carcinogenicity cell injury decision making algorithm exosome experience experimental study extracellular fluorophore human subject imaging modality improved in vivo instrument instrumentation interest light scattering malignant breast neoplasm mathematical model novel optical imaging optogenetics patient population physical model physical property predictive marker premalignant prevent prognostic programs standard of care tissue preparation tumor progression tumorigenesis

项目摘要

Project Summary In this application we propose to develop a native contrast optical spectroscopic sensing approach that identifies and characterizes subcellular structures and quantifies their properties when cells undergo pre- cancerous alterations, by using light scattering spectra as native optical biomarkers. Such a technique would enable simultaneous labeling of large number of subcellular and subnuclear structures without the use of stains and would be of great value for studying early cancer progression. The absence of stains also makes such methods easy to implement in time-course cancer progression studies and would be amenable for in vivo observations in humans. Although cellular alterations in organelle and nuclear structure are readily observed and studied in cancer, there are fundamental limitations in existing imaging techniques that prevent the study of very early stage pre-cancerous alterations. In contrast to dysplastic cellular alterations such as nuclear enlargement and organization, the earliest stages of carcinogenesis have much more subtle alterations that are not easily discernible with standard microscopy techniques. Perhaps the most often used imaging tool for observing cellular structure is fluorescence microscopy. It can achieve targeted contrast for specific organelles or proteins, however imaging in live cells remains limited to just a few types of fluorophores and therefore structure types. Although recently developed optogenetic methods and new live cell fluorescent probes have significantly improved the utility of fluorescence in living systems, the method is inherently limited to observing a few types of structures at relatively short time scales. An even more substantial limitation of conventional optical imaging is that it is subject to the diffraction limit and cannot discern the properties of cellular structures that are significantly smaller than a wavelength. On the other hand, electron microscopy imaging methods are destructive, involve extensive manipulations with the sample, and cannot be utilized in living systems. In order to overcome the limitations of both methods, a technique that is based on an entirely different physical principle is required. This method should ideally identify all important cellular structures in live cells, while simultaneously dynamically quantifying their properties when cells undergo pre-cancerous alterations.

项目摘要在此应用中，我们建议开发一种天然对比光谱传感方法识别和表征亚细胞结构并量化细胞前的特性通过将光散射光谱作为天然光学生物标志物，癌变改变。这样的技术将同时标记大量的亚细胞和亚核结构，而没有使用污渍，对于研究早期癌症进展将具有很大的价值。没有污渍还使这些方法易于在时期癌症的进展研究中实施，这将是适用于人类体内观察。尽管细胞器和核结构的细胞改变很容易观察和研究在癌症中，现有成像技术存在根本的局限性，可以防止研究非常早期癌前改变。与诸如核的发育不良细胞改变相反扩大和组织，癌变的最早阶段具有更细微的改变标准显微镜技术不容易辨别出来。也许最常使用的观察细胞结构的成像工具是荧光显微镜。它可以实现目标对比对于特定细胞器或蛋白质，但是活细胞中的成像仍然仅限于几种类型的荧光团，因此结构类型。尽管最近开发了光遗传学方法和新方法活细胞荧光探针显着改善了荧光在生物系统中的效用，方法固有地限于在相对较短的时间尺度上观察几种类型的结构。一个偶数常规光学成像的更实质性限制是，它受衍射极限和无法辨别出明显小于波长的细胞结构的特性。在另一方面，电子显微镜成像方法具有破坏性，涉及广泛的操作使用样本，不能在生活系统中使用。为了克服两者的局限方法，一种基于完全不同的物理原理的技术。此方法理想情况下应识别活细胞中的所有重要细胞结构，而同时动态当细胞经过癌前改变时，量化其特性。