Obesity Effects on Pharyngeal Airway Mechanics by MRI

描述(申请人提供)：肥胖是阻塞性睡眠呼吸暂停最重要的预测因素。虽然我们知道肥胖与咽部呼吸道大小的减小和咽部气道塌陷性的增加有关，但我们几乎不了解肥胖如何改变咽壁组织的机械特性来影响这些变化。PI开发了一种具有组织运动跟踪(空间磁化调制，或Spamm())的MRI的新应用，以检查麻醉大鼠咽部呼吸道大小的局部变化和咽壁组织运动之间的关系。利用这项创新技术，我们将通过研究三组不同体脂程度的Zucker大鼠来确定肥胖对咽力学的影响：精瘦、肥胖、甚至更肥胖的大鼠喂食高脂饮食。我们的全球假设是，肥胖通过气道狭窄、增加气道塌陷性和降低有效的肌肉力学来损害咽部呼吸道通畅。目的1)确定1)在年龄匹配的Zucker大鼠中，咽部呼吸道顺应性和关闭压力是否按瘦胖大鼠的顺序逐渐增加，以及2)这些发现是否与咽部脂肪的数量直接相关。目的2是为了确定越来越负的气道压力直到引起的气道塌陷时咽壁组织运动的变化。在对隔离、密封的上呼吸道施加大气压下压力的过程中，将进行SPAMM磁共振成像，以测试1)呼吸道塌陷是否主要是由于咽前壁移位进入呼吸道，以及2)对于给定的咽部区域，咽壁组织运动和气道压力降低之间的关系是否按下列顺序在年龄匹配的Zucker大鼠中逐渐增加：瘦；肥胖和脂肪增加的肥胖大鼠。目的3测定3组Zucker大鼠在电刺激舌前伸肌和伸缩肌时咽壁组织运动。这一结果将决定，在年龄匹配的Zucker大鼠中，在一定刺激强度范围内，壁组织移位与呼吸道大小增加之间的关系是否按以下顺序逐渐降低：瘦身肥胖和脂肪加重肥胖。这些拟议的研究将提供有关肥胖如何影响咽力学的新信息，并增加我们对为什么肥胖患者在睡眠时容易发生咽部呼吸道塌陷的理解。

DESCRIPTION (provided by applicant): Obesity is the most important predictor for obstructive sleep apnea. Although we know that obesity is associated with a decrease in pharyngeal airway size and an increase in pharyngeal airway collapsibility, we have almost no understanding of how obesity alters the mechanical properties of pharyngeal wall tissues to effect these changes. The PI has developed a novel application of MRI with tissue motion tracking (spatial modulation of magnetization, or SPAMM() to examine the relationships between regional changes in pharyngeal airway size and pharyngeal wall tissue motion in anesthetized rats. Using this innovative technique, we will determine the effects of obesity on pharyngeal mechanics by studying three groups of Zucker rats with different degrees of body fat: lean, obese, and even more obese rats fed a high-fat diet. Our global hypothesis is that obesity compromises pharyngeal airway patency through airway narrowing, increased airway collapsibility, and less effective muscle mechanics. Aim 1 is to determine 1) whether pharyngeal airway compliance and closing pressure progressively increase across age-matched Zucker rats in the order: lean < obese < fat-augmented obese rats, and 2) whether these findings are directly related to the amount of pharyngeal fat. Aim 2 is to determine changes in pharyngeal wall tissue motion for increasingly negative airway pressure up to induced airway collapse. MRI with SPAMM will be performed during application of subatmospheric pressure to the isolated, sealed upper airway to test 1) whether airway collapse is primarily due to displacement of the anterior pharyngeal wall into the airway, and 2) whether, for a given pharyngeal region, the relationship between pharyngeal wall tissue motion and airway pressure decrements is progressively increased across age-matched Zucker rats in the order: lean < obese < fat-augmented obese rats. Aim 3 is to determine pharyngeal wall tissue motion in the 3 groups of Zucker rats during electrical activation of tongue protrudor and retractor muscles. The results will determine whether the relationship between wall tissue displacement and increase in airway size over a range of stimulus intensities is progressively reduced across age-matched Zucker rats in the order: lean > obese > fat augmented obese. The proposed studies will provide new information on how obesity affects pharyngeal mechanics and increase our understanding of why obese patients are predisposed to pharyngeal airway collapse during sleep.