Structured Illumination Computational Microscopy with UV Surface Excitation (MUSE) for Multispectral Super-Resolution Histology

用于多光谱超分辨率组织学的紫外表面激发 (MUSE) 结构照明计算显微镜

基本信息

  • 批准号:
    10213544
  • 负责人:
  • 金额:
    $ 2.31万
  • 依托单位:
  • 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 2020-12-31
  • 项目状态:
    已结题

项目摘要

Project Summary/Abstract Current clinical practices for the diagnosis and management of diseases often rely on histopathological exami- nation of tissue via optical microscopy. Brightfield imaging of hematoxylin-eosin (H&E)-stained samples repre- sents the predominant approach for accurate and comprehensive evaluation and diagnosis in clinical histopathol- ogy [1, 2]. Additional techniques for disease characterization involve molecularly specific labeling, and use im- munohistochemical or immunofluorescence techniques for brightfield and fluorescence microscopy, respec- tively. Using the latter, multiple analytes can be examined simultaneously [3, 4]. Unfortunately, the complexity of a fluorescent microscope’s optical design scales with the number of multiplexed fluorescent reporters to visual- ize, thus limiting its clinical utility [5]. Another area of interest is to explore clinically relevant information that may exist at spatial resolutions beyond what can be achieved with conventional microscopes. Typical fluorescence microscopy is generally limited by diffraction to an optical resolution of ~200 nm. Though this resolution enables visualization of large cellular structures, it does not support examination of organelle- and suborganelle-level ultrastructure whose morphological changes can correlate with disease, as seen in neurodegeneration, age, and cancer [6-10]. Recently, optical super-resolution technologies have been introduced that achieve imaging reso- lutions better than 50 nm. However, such technologies depend on complex hardware and are currently too costly to be incorporated into typical clinical pathology budgets. Electron microscopy (EM) systems are also an availa- ble option, and routinely image at resolutions of ~1 nm – however, these are not widely available and are not well suited for molecular specific imaging [11-14]. Additional issues, including size, cost, limited field-of-view, and complexity of sample-prep protocols have prevented EM from being incorporated into standard clinical work- flow. This project will develop a robust, comparatively simple, and low-cost optical system for molecularly-specific multispectral fluorescence imaging at spatial resolutions of ~70 nm, well beneath the classical 200 nm optical resolution limit. To do so, a framework for computational structured illumination (SI) microscopy will be developed to enable super-resolution using uncalibrated illumination patterns. This framework will be deployed using single- wavelength ultraviolet (UV) excitation, which has demonstrated capabilities for simultaneous excitation of multi- ple fluorescent reporters. Specific innovations in this work include a novel reformulation of SI microscopy that uses computational optimization to robustly increase imaging resolution in the presence of system unknowns and imperfections. Furthermore, because UV-based excitation has wavelengths more than a factor of 2 shorter than the fluorophores’ visible emission wavelengths, resolution gains by factors greater than 2 are expected, hence enabling sub-100-nm spatial resolutions. If successful, the aims of this project will combine the benefits of multispectral optical imaging with the advantages of sub-100-nm spatial resolution to create a more informative and less demanding alternative to electron microscopy, with applications across biology and histopathology.
项目摘要/摘要 目前诊断和治疗疾病的临床实践通常依赖于组织病理学检查。 通过光学显微镜观察组织的国度。苏木精-伊红(H&E)染色样品的明场成像 为临床组织病理学准确、全面的评价和诊断提供了主要途径。 OGY[1,2]。疾病表征的其他技术包括分子特异性标记,并使用免疫组化。 Brightfield和荧光显微镜的免疫组织化学或免疫荧光技术,分别为 分别。使用后者,可以同时检测多个分析物[3,4]。不幸的是,它的复杂性 荧光显微镜的光学设计与多路荧光记者的数量成比例- 因此限制了它的临床应用[5]。另一个感兴趣的领域是探索临床相关信息,这些信息可能 存在的空间分辨率超过了传统显微镜所能达到的水平。典型荧光 显微镜通常被限制在光学分辨率为~200纳米的衍射。尽管这项决议使 大型细胞结构的可视化,不支持细胞器和亚细胞器级别的检查 超微结构,其形态变化可与疾病相关,如神经退行性变、年龄和 癌症[6-10]。近年来,光学超分辨率技术被引入,以实现成像分辨率。 优于50 nm的乳剂。然而,这些技术依赖于复杂的硬件,目前成本太高 纳入典型的临床病理学预算。电子显微镜(EM)系统也是一种有效的- Bble选项,通常以~1 nm的分辨率成像-但是,这些选项并不广泛使用,也不是 非常适合于分子特定成像[11-14]。其他问题,包括大小、成本、有限的视野、 而样本准备方案的复杂性阻碍了EM被纳入标准的临床工作- 流。该项目将开发一种强大的、相对简单的、低成本的分子专用光学系统 空间分辨率为~70 nm的多光谱荧光成像,远低于经典的200 nm光学 分辨率限制。为此,将开发一个用于计算结构照明(SI)显微镜的框架 以使用未校准的照明图案实现超分辨率。该框架将使用单一- 波长紫外(UV)激发,已显示出同时激发多个原子的能力。 大量的荧光记者。这项工作的具体创新包括SI显微镜的新配方, 在存在系统未知的情况下,使用计算优化来稳健地提高成像分辨率 和不完美的地方。此外,由于基于紫外线的激发的波长短了2倍以上 与荧光团的可见发射波长相比,分辨率增益有望达到2倍以上, 因此可以实现低于100纳米的空间分辨率。如果成功,该项目的目标将结合 利用多光谱光学成像的优势,以低于100纳米的空间分辨率来创建更丰富的信息 要求较低的电子显微镜替代品,可应用于生物学和组织病理学。

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Computational structured illumination for high-content fluorescence and phase microscopy.
  • DOI:
    10.1364/boe.10.001978
  • 发表时间:
    2018-12
  • 期刊:
  • 影响因子:
    3.4
  • 作者:
    Li-Hao Yeh;Shwetadwip Chowdhury;L. Waller
  • 通讯作者:
    Li-Hao Yeh;Shwetadwip Chowdhury;L. Waller
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Shwetadwip Chowdhury其他文献

Shwetadwip Chowdhury的其他文献

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{{ truncateString('Shwetadwip Chowdhury', 18)}}的其他基金

Computational Framework to Enhance Antenna-based Electromagnetic Imaging
增强基于天线的电磁成像的计算框架
  • 批准号:
    10667975
  • 财政年份:
    2023
  • 资助金额:
    $ 2.31万
  • 项目类别:
Structured Illumination Computational Microscopy with UV Surface Excitation (MUSE) for Multispectral Super-Resolution Histology
用于多光谱超分辨率组织学的紫外表面激发 (MUSE) 结构照明计算显微镜
  • 批准号:
    9788760
  • 财政年份:
    2018
  • 资助金额:
    $ 2.31万
  • 项目类别:

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