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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

基本信息

批准号：
10504836
负责人：
Anita Mahadevan-Jansen
金额：
$ 64.78万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
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/10504836
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 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 Water Work base biomechanical test cervical remodeling data fusion decorin design ex vivo imaging improved in vivo in vivo monitoring infant morbidity/mortality innovation insight microscopic imaging morphometry mouse model multimodality neonatal morbidity novel physical science pregnant premature prototype response tissue mapping

项目摘要

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.

项目总结