Complementary ex vivo multimodal optical imaging and in vivo Raman spectroscopy to understand tissue dynamics

补充离体多模态光学成像和体内拉曼光谱以了解组织动力学

• 批准号: 10683232
• 负责人: Anita Mahadevan-Jansen
• 金额: $ 66.79万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10683232
• 关键词: Actins; Affect; Alprostadil; Biochemical; Biochemical Markers; Biochemistry; Biological; Biological Assay; Biological Sciences; Biomechanics; Biomedical Engineering; Blood; Blood Vessels; Carbocyanines; Cardiac; Cervical; Cervical Ripening; Cervix Incompetence; Cervix Uteri; Clinical; Collagen; Complex; Custom; Detection; Development; Dyes; Early Diagnosis; Early treatment; Elasticity; Elastin; Etiology; Extracellular Matrix; Extracellular Matrix Proteins; Fiber Optics; Fingerprint; Freeze Drying; Goals; Health; Heme; Hormonal; Human; Hyaluronic Acid; Hydration status; Image; Imaging Techniques; Immunohistochemistry; Impairment; Infection; Interdisciplinary Study; Label; Length; Light; Lipids; Longitudinal Studies; Maps; Measures; Mechanics; Medical; Microscope; Microscopy; Mifepristone; Modeling; Molecular; Molecular Conformation; Monitor; Multi-modal optical imaging; Mus; Neonatal Mortality; Optics; Outcome; Perfusion; Perinatal; Phase; Phenotype; Physiological; Physiology; Pregnancy; Premature Birth; Preparation; Process; Property; Proteins; Proteoglycan; Raman Spectrum Analysis; Reporting; Reproduction; Research; Research Project Grants; Structural Protein; Syndrome; System; Techniques; Technology; Term Birth; Testing; Time; Tissue imaging; Tissues; United States; Uterus; Vascularization; Visualization; Water; Work; biomechanical test; cervical remodeling; data fusion; decorin; design; ex vivo imaging; improved; in vivo; in vivo monitoring; in vivo optical imaging; infant morbidity; infant morbidity/mortality; innovation; insight; microscopic imaging; morphometry; mouse model; multimodality; neonatal morbidity; novel; optical fiber; physical science; pregnant; premature; prototype; response; tissue mapping

PROJECT SUMMARY Limited approaches exist to examine longitudinal changes in the structural and biochemical properties of tissues under various physiological conditions such as pregnancy. Light and light based technologies offer the potential for non-invasive, real-time, in vivo monitoring of longitudinal shifts in tissue physiology in response to developmental, hormonal, or environmental influences. The objective of the proposed research is to pursue a multi-pronged platform with complementary Raman scattering approaches to study longitudinal changes in tissue physiology in vivo as well as ex vivo and compare the results with conventional assays to validate our approach. In addition, we will combine various forms of in vivo Raman imaging, including (i) dual wavelength, dual region Raman (ii) polarization-sensitive Raman, and (iii) resonance Raman spectroscopy to quantitatively analyze changes in tissue physiology. In response to a lack of detailed understanding of preterm birth and its tissue biochemistry, our group has reported the utility of in vivo RS to detect and extract longitudinal biochemical changes in the mouse as well as human cervix, a tissue that undergoes extensive remodeling over the course of pregnancy. We established the ability of a conventional in vivo RS probe to identify significant spectral changes in collagen, elastin, water, and blood. Moreover, we can correlate these Raman spectra with changes in biomechanical properties of the mouse cervix, including stiffness and distensibility, as the cervical tissue undergoes normal remodeling/maturation in preparation for labor. Building on our prior research, the present proposal will focus multimodal ex vivo and in vivo Raman approaches to gain in-depth, quantitative information during physiologic cervical maturation and in mouse models of premature remodeling. We hypothesize that multimodal Raman approaches will enable detection of key biochemical changes, such as extracellular matrix (ECM) organization, tissue hydration, lipid and protein influx and vascularity that will allow molecular and structural phenotyping of the cervix as a prototype of physiologic tissue remodeling. Results will be correlated with spatial information obtained via ex vivo imaging and biomechanical testing. Our Aims are to: 1) Implement multimodal non-linear imaging to characterize changes in structural proteins in the mouse cervix, 2) Use dual wavelength, dual region Raman Spectroscopy to track changes in tissue hydration and lipid dynamics, and 3) Evaluate spatial and temporal changes in blood and vascularization in the mouse cervix over the course of pregnancy. Ultimately, this project will integrate the results of these aims to provide a more complete picture of the molecular and structural changes that can be used to understand normal as well as compromised pregnancies. The resultant in-depth biomolecular profiles and spatial tissue maps obtained for normal term and preterm pregnancies with the innovative Raman approaches will provide vital information about the mechanism of premature cervical remodeling and for monitoring longitudinal changes in the structural and biochemical properties of other tissues with RS.

项目摘要 存在有限的方法来检查组织结构和生化特性的纵向变化 在各种生理条件下，例如怀孕。基于轻便的技术具有潜力 用于非侵入性的，实时的，体内监测组织生理中纵向转移的响应 发展，荷尔蒙或环境影响。拟议研究的目的是追求 具有互补的拉曼散射方法研究组织纵向变化的多管平台 在体内和体内生理学，并将结果与​​常规测定法进行比较，以验证我们的方法。 此外，我们将结合各种形式的体内拉曼成像，包括（i）双波长，双区域 拉曼（II）偏振敏感的拉曼和（iii）共振拉曼光谱法以定量分析 组织生理的变化。响应缺乏对早产及其组织的详细了解 生物化学，我们的小组报告了体内检测和提取纵向生化的实用性 小鼠和人类子宫颈的变化，这是一种在整个过程中经历大量重塑的组织 怀孕。我们确定了常规体内RS探针识别重大光谱变化的能力 在胶原蛋白，弹性蛋白，水和血液中。此外，我们可以将这些拉曼光谱与变化相关联 小鼠子宫颈的生物力学特性，包括刚度和扩张性，作为颈组织 经过正常的重塑/成熟以准备劳动。基于我们先前的研究，现在 提案将集中于多模式的离体和体内拉曼方法，以获得深入的定量信息 在生理宫颈成熟和过早重塑的小鼠模型中。我们假设这一点 多模式的拉曼方法将能够检测关键的生化变化，例如细胞外基质 （ECM）组织，组织水合，脂质和蛋白质流入和血管，这将允许分子和 子宫颈的结构表型作为生理组织重塑的原型。结果将相关 通过通过体内成像和生物力学测试获得的空间信息。我们的目标是：1）实施 多模式的非线性成像以表征小鼠子宫颈中结构蛋白的变化，2）使用双重 波长，双区域拉曼光谱法，以跟踪组织水合和脂质动力学的变化，3） 评估小鼠子宫颈血液和血管化的空间和时间变化。 怀孕。最终，该项目将整合这些旨在提供更完整的图片的结果 可用于理解正常和受损的分子和结构变化 怀孕。由正常期限获得的最终深入的生物分子轮廓和空间组织图 以创新的拉曼方法的早产将提供有关该机制的重要信息 过早的宫颈重塑，用于监测结构和生化的纵向变化 其他组织的特性。