TR&D Project 3: Photoacoustic Detection of Metal Fluxes at the Tissue Level

TR

• 批准号: 10197971
• 负责人: Hao F Zhang
• 金额: $ 18.21万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10197971
• 关键词: 3-Dimensional; Adopted; Animal Model; Animals; Biological; Biological Process; Biological Sciences; Brain; Bypass; Cells; Coupling; Cryopreservation; Cryopreserved Tissue; Deposition; Detection; Development; Ensure; Extinction (Psychology); Fluorescence; Fluorescence Microscopy; Fluorescent Probes; Future; Generations; Goals; Hemoglobin; Image; Investigation; Ions; Kidney; Label; Larva; Lasers; Measurement; Measures; Metals; Microfluidics; Microscopic; Microscopy; Modality; Modernization; Molecular; Molecular Probes; Mus; Optics; Organ; Pathologic Processes; Pathway interactions; Physiological Processes; Preparation; Process; Research; Research Personnel; Resolution; Resources; Roentgen Rays; Sampling; Slice; System; Technology; Testing; Thick; Tissue imaging; Tissues; Ultrasonic wave; Ultrasonography; Zebrafish; absorption; base; contrast imaging; design; detection method; detection sensitivity; detector; fluorescence imaging; hemodynamics; imaging capabilities; imaging platform; improved; iron metabolism; microscopic imaging; multi-photon; nanoimprinting; novel; optical imaging; pressure; quantum; response; second harmonic; technology research and development; tool; vibration

PROJECT SUMMARY – TR&D PROJECT 3 Photoacoustic Detection of Metal Fluxes at the Tissue Level Modern optical microscopic modalities offer the following optical contrasts: optical scattering, autofluorescence (intrinsic fluorescence), molecular probes (extrinsic fluorescence), and nonlinear optical effects. One key contrast, optical absorption, is inaccessible by established microscopic modalities. As a result, bioelement investigation in biological tissue mainly rely on various fluorescence probes. A lasting challenge in designing fluorescence probes is to overcome low quantum yield, where major optical energy deposited to the probes is dissipated via a non-radiative pathway as heat instead of as fluorescent emissions. Measuring nonradiative thermal generation or optical absorption could offer a new way to conduct bioelement imaging and bypass the quantum yield challenge. Imaging optical absorption quantifies ionic concentrations with high accuracy when the molar extinction coefficient is known. Imaging optical absorption permits direct quantitation of certain highly-optically absorbing ions (i.e. Fe in hemoglobin) and will stimulate the development of a new class of molecular probes that focus on high extinction coefficients only, for which the struggle to achieve high fluorescent quantum yield becomes much less critical. In this Technology Research and Development (TR&D) project we will develop a new optical absorption microscopy modality, referred to as optical Micro-Ring Resonator-Based Photoacoustic Microscopy or MRR- PAM, which measures optical absorption using ultrasound. MRR-PAM detects ultrasound waves induced by laser energy absorption and, consequently, heat generation and thermoelastic vibration. Compared with existing photoacoustic microscopy, MRR-PAM improves the ultrasound detection bandwidth and axial resolution by 10-fold and detection sensitivity by 100-fold. MRR-PAM provides a unique tool to enable tissue imaging in all the DBP themes, such as the strongly scattering brain slices, thick tissue slice or whole mouse kidney, whole zebrafish and zebrafish larvae. It will provide a new tool to quantify iron metabolism. MRR-PAM extends the imaging capabilities developed in other TR&D projects to quantify bioelement distributions and fluxes in both fixed and living tissue slices. It offers the possibility to image whole organs and, potentially, living animals. The unique MRR developed in this TR&D project can be broadly disseminated and will likely impact several other biomedical fields beyond bioelement research.

项目摘要 - TR＆D项目3 金属通量在组织水平上的光声检测 现代光学微观方式提供以下光学对比：光学散射，自动荧光 （内在荧光），分子探针（外部荧光）和非线性光学效应。一个钥匙 对比，光学滥用是通过已建立的微观方式无法访问的。结果，生物元素 对生物组织的研究主要依赖于各种荧光问题。设计的持久挑战 荧光问题是要克服低量子产率，其中沉积在问题上的主要光能是 通过非辐射途径消散，而不是荧光排放。 测量非辐射热产生或光学滥用可能会提供一种新的生物元素的方式 成像和绕过量子收益率挑战。成像光滥用量化离子浓度 当已知摩尔延伸系数时，具有很高的精度。成像光学滥用允许直接 定量某些高度吸收的离子（即血红蛋白中的FE），并将刺激发育 仅关注高扩展系数的新一类分子问题，为此而奋斗 达到高荧光量子产量变得不那么关键。 在该技术研究与开发（TR＆D）项目中，我们将开发新的光学滥用 显微镜模态，称为光学微环谐振器的光声显微镜或MRR- PAM，使用超声测量光滥用。 MRR-PAM检测到由 激光吸收能量，因此是热量产生和热弹性振动。与 现有的光声显微镜，MRR-PAM改善了超声检测带宽和轴向 通过10倍和检测灵敏度分辨率为100倍。 MRR-PAM提供了一种独特的工具来启用组织 在所有DBP主题中成像，例如强烈散射的脑切片，厚的组织切片或整个小鼠 肾脏，整个斑马鱼和斑马鱼幼虫。它将提供一种量化铁代谢的新工具。 MRR-PAM 扩展在其他TR＆D项目中开发的成像功能，以量化生物元素分布和 固定组织和活组织切片中的通量。它提供了图像整个器官的可能性，并可能生活 动物。在此TR＆D项目中开发的独特MRR可能会广泛传播，可能会影响 生物元素研究以外的其他几个生物医学领域。