Laryngeal Blood Flow Measurement via micro Particle Image Velocimetry

描述（由申请人提供）：喉负责保护下呼吸道，允许通气，并用于发声。这些关键的喉功能因年龄而改变，并且可能由与肌肉减少症相关的机制引起（即，骨骼肌质量、组织和强度的损失）。然而，可能导致喉肌减少症的潜在生物学机制尚不清楚。衰老个体在血管系统内表现出结构和功能适应的模式，这可能导致肌肉减少症，例如骨骼肌血流量减少和毛细血管密度降低。在我们的实验室中，我们发现了与年龄相关的变化，在大鼠喉在体模型中的微循环几何形状。然而，我们在喉微血管系统内的工作一直受到繁琐的，也许是不准确的，测量技术的阻碍。在拟议的探索性/发展性研究项目中，我们计划开发创新方法，使用微尺度粒子图像测速仪（5 PIV）研究活体动物喉部的血流。我们的假设是，血流的变化有一个因果关系的影响喉肌少肌症。我们计划在未来的R 01应用中使用肌肉生理学、微血管生理学、生物化学和分子生物学方法来测试这一假设。然而，为了进行这项未来的工作，必须首先进行探索性/发展性研究，以开发研究活体动物喉部血流的创新方法。本研究有三个具体目标。目标1和2是里程碑驱动的，而目标3是假设驱动的。我们的目标是：（1）开发和实施5 PIV技术来测量肌肉中的血流量，（2）操纵红细胞速度和加速度，以确定5 PIV测量是否对治疗相关变化敏感，以及（3）通过5 PIV定量确定衰老是否影响毛细血管喉肌血流量，并确定氧交换的影响。这项工作是创新和重要的，因为衰老影响喉肌功能的机制在很大程度上尚未探索。我们的探索性研究将允许开发一种尖端技术，以在未来的研究中研究这种机制，包括治疗干预的效果，如电神经/肌肉刺激和锻炼。因此，这项工作将奠定基础，为未来的研究，旨在了解机制背后的颅肌肌少症。公共卫生相关性：喉部肌肉的血流变化可能对与年龄相关的肌肉衰退产生因果影响，肌肉衰退是声音和吞咽功能减退的基础。这项工作将使用最先进的成像技术（微粒子图像测速法），以开发一种测量喉肌中红细胞（RBC）速度的方法，并测试微血管血流动力学在衰老肌肉中改变的假设。这个探索性/发展性研究项目将开发新的方法，以允许准确，机械和假设驱动的未来研究集中在一个重要的临床问题。

DESCRIPTION (provided by applicant): The larynx is responsible for protecting the lower airway, permitting ventilation, and for the production of voice. These critical laryngeal functions are altered by aging, and may be caused by mechanisms related to sarcopenia (i.e., the loss of skeletal muscle mass, organization, and strength). However, the underlying biological mechanisms that may cause laryngeal sarcopenia are unclear. Senescent individuals exhibit a pattern of structural and functional adaptations within the vascular system that may contribute to sarcopenia, such as a reduction in skeletal muscle blood flow, and decreased capillary density. In our laboratory, we have found age-related changes in microcirculatory geometry in a rat larynx in vivo model. However, our work within the laryngeal microvascular system has been hampered by cumbersome, and perhaps inaccurate, measurement techniques. In the proposed exploratory/developmental research project, we plan to develop innovative methods for studying blood flow in the larynx of living animals, using microscale Particle Image Velocimetry (5PIV). Our hypothesis is that alterations in blood flow have a causal influence on sarcopenia of laryngeal muscles. We plan to test this hypothesis in a future R01 application using muscle physiology, microvascular physiology, biochemistry, and molecular biology methods. In order to perform this future work, however, exploratory/developmental research first must be performed to develop innovative methods for studying blood flow in the larynx of living animals. The proposed research has 3 specific aims. Aims 1 and 2 are milestone-driven, while Aim 3 is hypothesis-driven. Our aims are: (1) To develop and implement the 5PIV technique to measure blood flow in muscles, (2) To manipulate red blood cell velocity and acceleration to determine if 5PIV measures are sensitive to treatment-related changes, and (3) To determine whether aging effects capillary laryngeal muscle blood flow via 5PIV quantification and to determine the implications for oxygen exchange. This work is innovative and important because the mechanisms whereby aging impacts laryngeal muscle function are largely unexplored. Our exploratory study will allow the development of a cutting-edge technique to investigate such mechanisms in future studies, including the effects of therapeutic interventions, such as electrical nerve/muscle stimulation and exercise. Accordingly, this work will lay the groundwork for future studies aimed at understanding mechanisms underlying cranial muscle sarcopenia. PUBLIC HEALTH RELEVANCE: Alterations in blood flow to muscles in the larynx may have a causal influence on the age- related muscular decline that underlies functional decrements in voice and swallowing. This work will use state of the art imaging techniques (micro Particle Image Velocimetry) to develop a method of measuring the velocity of red blood cells (RBCs) in a laryngeal muscle and to test the hypothesis that microvascular hemodynamics are altered in aging muscles. This exploratory/developmental research project will develop new methodology to allow accurate, mechanistic, and hypothesis-driven future research focused on an important clinical problem.