Obesity Effects on Pharyngeal Airway Mechanics by MRI

描述（由申请人提供）：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气道大小的减少和咽气道膨胀性的增加有关，但我们几乎不了解肥胖如何改变咽壁组织的机械特性以影响这些变化。PI开发了一种新的MRI应用，结合组织运动跟踪（磁化空间调制，或SPAMM（）），以检查麻醉大鼠咽气道大小的区域变化与咽壁组织运动之间的关系。使用这种创新技术，我们将通过研究三组具有不同程度体脂的Zucker大鼠来确定肥胖对咽力学的影响：瘦的，肥胖的，甚至更肥胖的高脂肪饮食大鼠。我们的总体假设是，肥胖通过气道狭窄、气道扩张性增加和肌肉力学效果降低而影响咽部气道通畅。目的1是确定1）在年龄匹配的Zucker大鼠中，咽气道顺应性和闭合压力是否按以下顺序逐渐增加：瘦<肥胖<脂肪增加的肥胖大鼠，以及2）这些发现是否与咽脂肪的量直接相关。目的2是确定咽壁组织运动的变化，逐渐增加气道负压直至诱导气道塌陷。在向隔离的密封上气道施加负压期间，使用SPAMM进行MRI，以测试1）气道塌陷是否主要是由于咽前壁移位到气道中，以及2）对于给定的咽部区域，咽壁组织运动和气道压力下降之间的关系是否在年龄匹配的Zucker大鼠中按以下顺序逐渐增加：瘦&lt;肥胖< 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 >肥胖&gt;脂肪增加肥胖。这些研究将为肥胖如何影响咽部力学提供新的信息，并增加我们对肥胖患者在睡眠期间易于发生咽部气道塌陷的原因的理解。

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.