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.

项目摘要 迅速采用一般修饰的动物，并将荧光标记为生物相容性纳米颗粒 生物医学科学中的药物输送增加了对成像技术的需求 体积成像能够对其自然环境中的细胞动力学进行纵向研究。这 了解组织对损伤和治疗所需的信息的复杂性也产生了 增加对结合互补性能强度的多模式成像系统的兴趣。 在这方面，我们开发了一个集成的双模式成像系统，该系统结合了光学 相干显微镜（OCM）和双通道共聚焦荧光显微镜（CFM）以实现 简单测量深层组织层的荧光和反射率。组合系统 提供了一个独特的机会，可以通过提供完整性来告知细胞在其自然环境中的行为 仅两个系统都无法提供信息。 CFM互助荧光标记的分布 细胞中的分子。 OCM是一种无标签的主教方法，可提供有关细胞边界的信息， 细胞外基质以及正常组织和致病组织层的厚度变化。 尽管具有潜力，但这些技术的集成是不完整的，没有并发的能力 体积成像允许在同一样品中逐渐跟踪细胞动力学。至于扫描 - 基于系统，OCM和CFM中的快速体积成像需要动态聚焦在个体的水平上 扫描点，由于动态聚焦设备的暂时分辨率有限，因此受到挑战。 该项目旨在建立可调声梯度镜头的能力，即最快的动态 迄今为止，将技术集中在OCM和CFM中，以实现快速的体积和并发成像 深度分辨的反射率和体内深层组织层的荧光。这种整合将有一个 由于OCM和CFM技术仍然是最负担得起，灵活的，对生物医学研究的巨大影响 后者很容易在许多研究设施中获得。我们提出以下两个具体目标： AIM 1：在共聚焦荧光显微镜中启用快速体积成像。 AIM 2：在光学相干显微镜中启用延长的场地。 意义 同时获取体积信息的能力，例如从 深层组织层将为纵向研究发育和 各个研究领域的病理生理机制，并促进同一体内细胞跟踪 标本同时通过降低受试者间的可变性来增加研究的严格性和可重复性 可以影响细胞过程的结果。