Concurrent volumetric imaging with multimodal optical systems

多模态光学系统的并行体积成像

• 批准号: 10727499
• 负责人: Patrice Tankam
• 金额: $ 28.43万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10727499
• 关键词: Acceleration; Acoustics; Address; Adoption; Affect; Animal Model; Biomedical Research; Cell physiology; Cells; Compensation; Detection; Development; Devices; Drug Delivery Systems; Engineering; Environment; Extracellular Matrix; Fluorescence; Fluorescence Microscopy; Frequencies; Genetically Modified Animals; Goals; Image; Imaging technology; Individual; Investigation; Label; Lateral; Light; Measurement; Methods; Microscopy; Microspheres; Multimodal Imaging; Optical Coherence Tomography; Optics; Outcome; Pathogenicity; Performance; Positioning Attribute; Reproducibility; Research; Resolution; Sampling; Scanning; Science; Silicon; Specimen; System; Techniques; Technology; Thick; Time; Tissues; Transgenic Mice; Variant; arm; biomaterial compatibility; cell behavior; confocal imaging; design; flexibility; imaging capabilities; imaging modality; imaging system; in vivo; in vivo fluorescence; in vivo imaging; interest; lens; meter; multimodality; nanoparticle drug; novel; research facility; response to injury; temporal measurement; tool; two photon microscopy

PROJECT SUMMARY The rapid adoption of genetically modified animals and fluorescently labeled biocompatible nanoparticles for drug delivery in biomedical science have increased demand for imaging technologies capable of fast volumetric imaging to enable longitudinal investigations of cell dynamics in their natural environment. The complexity of information required to understand tissue response to injury and treatment has also generated increased interest in multimodal imaging systems that combine complementary performance strengths. In this regard, we have developed an integrated dual-modality imaging system that combines optical coherence microscopy (OCM) and dual-channel confocal fluorescence microscopy (CFM) to enable the simultaneous measurements of fluorescence and reflectance from deep tissue layers. The combined system provides a unique opportunity to inform cells’ behavior in their natural environment by offering complementary information not available with either system alone. CFM interogates the distribution of fluorescently labeled molecules in cells. OCM is a label-free, episcopic method providing information about the cell boundaries, extracellular matrix, and thickness changes in layers of normal and pathogenic tissues. Despite its potential, the integration of these technologies is incomplete without the capability of concurrent volumetric imaging allowing the tracking of cell dynamics progressively in the same specimen. As for scanning- based systems, fast volumetric imaging in OCM and CFM requires dynamic focusing at the level of individual scanning points, which is challenging due to the limited temporal resolution of dynamic focusing devices. This project aims to establish the capability of the tunable acoustic gradient lens, the fastest dynamic focusing technology to date, in OCM and CFM to enable a fast volumetric and concurrent imaging of depth-resolved reflectance and fluorescence from deep tissue layers in vivo. This integration will have a tremendous impact on biomedical research as OCM and CFM technologies remain the most affordable, flexible, and the latter is readily available in many research facilities. We propose the following two specific aims: Aim 1: Enable fast volumetric imaging in confocal fluorescence microscopy. Aim 2: Enable extended depth-of-field in optical coherence microscopy. Significance The ability to concurrently acquire volumetric information such as reflectance and fluorescence rapidly from deep tissue layers will provide a powerful tool for longitudinal investigations into developmental and pathophysiological mechanisms in various research fields and facilitate in vivo cell tracking in the same specimen while increasing the rigor and reproducibility of studies by decreasing the inter-subject variability that can affect the outcomes of cellular processes.

项目总结 转基因动物和荧光标记的生物相容纳米颗粒的快速采用 生物医学中的药物输送增加了对能够快速成像技术的需求 体积成像技术可对自然环境中的细胞动力学进行纵向研究。这个 理解组织对损伤和治疗的反应所需的复杂信息也产生了 对结合互补性能优势的多模式成像系统的兴趣与日俱增。 在这方面，我们开发了一种集成的双模式成像系统，它结合了光学 相干显微镜(OCM)和双通道共聚焦荧光显微镜(CFM)使 同时测量深层组织的荧光和反射率。组合式系统 提供独特的机会来了解细胞在其自然环境中的行为，通过提供补充 这两个系统单独提供的信息都不可用。荧光标记的CFM标记的分布 细胞中的分子。OCM是一种提供关于细胞边界的信息的无标记、可观察的方法， 细胞外基质，正常组织和病变组织各层的厚度变化。 尽管这些技术有潜力，但如果没有并发能力，这些技术的集成是不完整的 体积成像允许在同一样本中逐步跟踪细胞动力学。至于扫描- 基于系统，OCM和CFM中的快速体积成像需要在个体水平上进行动态聚焦 由于动态调焦设备的时间分辨率有限，这是一项具有挑战性的任务。 本项目旨在建立可调谐声学梯度透镜的能力，最快的动态 到目前为止，在OCM和CFM中使用聚焦技术，可以实现快速的体积成像和并发成像 体内深层组织的深度分辨反射和荧光。这一整合将具有 对生物医学研究产生巨大影响，因为OCM和CFM技术仍然是最经济、最灵活、 而后者在许多研究机构中都很容易获得。我们提出以下两个具体目标： 目的1：在共聚焦荧光显微镜中实现快速体积成像。 目标2：在光学相干显微镜中实现扩展景深。 意义 能够同时从以下位置快速获取体积信息，如反射率和荧光 深层组织层将提供一个强大的工具，纵向研究发育和 不同研究领域的病理生理机制并促进体内细胞追踪 样本，同时通过减少研究对象间的可变性来增加研究的严谨性和重复性 会影响细胞过程的结果。