Pharyngeal mechanics by tagged MRI in a Zucker rat model

描述（由申请人提供）：本研究旨在发展先进核磁共振成像（MRI）的技术、生理和分析技术，以追踪麻醉大鼠咽壁的组织运动，建立咽气道力学的小动物模型。该模型与阻塞性睡眠呼吸暂停的病理生理学有关，阻塞性睡眠呼吸暂停是人类普遍存在的呼吸系统疾病，其特征是睡眠期间咽气道反复关闭。以往对咽气道通畅控制的研究一般局限于气道大小、形状和可折叠性的测量。因此，我们对影响这些气道变化的咽壁组织的力学特性的理解非常有限。例如，虽然已知体重指数是OSA最重要的预测指标，并且肥胖与气道湿陷性增加有关，但我们尚不了解肥胖如何改变咽壁组织的力学特性来影响这些变化。为了解决这些知识上的空白，PI将在麻醉大鼠中采用一种新的磁共振成像（MRI）组织标记技术，称为空间磁化调制（SPAMM(r)，由宾夕法尼亚大学开发）来量化咽壁组织运动，即组织运动和组织应变，并量化咽壁组织运动如何产生气道大小和形状的变化。我们建议开发一种新的技术，使我们能够检查麻醉的肥胖和非肥胖Zucker大鼠的咽壁组织运动，肥胖基因型的咽气道受损与OSA患者相似。具体目标1是开发在高氧和低氧条件下，麻醉、非肥胖和肥胖Zucker大鼠在自主呼吸时使用MRI与SPAMM量化咽壁组织运动所需的技术。具体目标2是开发所需的技术，使用MRI与SPAMM来量化非肥胖和肥胖Zucker大鼠在选择性电刺激舌下神经及其分支时咽壁组织的运动，这些分支为舌前突（内侧分支）和牵开（外侧分支）肌肉提供运动输出。目标1和目标2的总体假设是肥胖通过减少横截面积和使咽肌处于机械劣势而损害咽气道通畅。我们开发的跟踪咽壁组织运动的创新方法将揭示咽力学的新见解，从而增加我们对肥胖在OSA病理生理中的作用的理解。

DESCRIPTION (provided by applicant): The goal of the proposed research is to develop the technical, physiological and analytical techniques in advanced magnetic resonance imaging (MRI) to track tissue motion in the pharyngeal walls of anesthetized rats in order to establish a small animal model of pharyngeal airway mechanics. The model is relevant to the pathophysiology of obstructive sleep apnea, a prevalent respiratory disorder in humans characterized by the repetitive closure of the pharyngeal airway during sleep. Previous studies on the control of pharyngeal airway patency have been generally limited to measurements of airway size, shape, and collapsibility. Consequently, our understanding of the mechanical properties of the pharyngeal wall tissues that affect these airway changes is very limited. For example, although it is known that body mass index is the most important predictor of OSA, and that obesity is associated with an increase in airway collapsibility, we do not yet understand how obesity alters the mechanical properties of pharyngeal wall tissues to effect these changes. To address these gaps in our knowledge, the PI will adapt a novel magnetic resonance imaging (MRI) tissue tagging technique in anesthetized rats called spatial modulation of magnetization (SPAMM(r), developed at the University of Pennsylvania) to quantify pharyngeal wall tissue motion, i.e., tissue movement and tissue strain, and quantify how pharyngeal wall tissue motion produces changes in airway size and shape. We propose to develop novel technology that will enable us to examine pharyngeal wall tissue motion in anesthetized obese and non-obese Zucker rats, the obese genotype having a compromised pharyngeal airway similar to that in patients with OSA. Specific Aim 1 is to develop the techniques needed to use MRI with SPAMM to quantify pharyngeal wall tissue motion during spontaneous breathing in anesthetized, non-obese and obese Zucker rats under hyperoxic and hypoxic conditions. Specific Aim 2 is to develop the techniques needed to use MRI with SPAMM to quantify pharyngeal wall tissue motion in non-obese and obese Zucker rats during selective electrical stimulation of the hypoglossus nerve, and its branches that supply motor output to tongue protrudor (medial branch) and retractor (lateral branch) muscles. The global hypothesis for Aims 1 and 2 is that obesity compromises pharyngeal airway patency by reducing cross-sectional area and putting the pharyngeal muscles at a mechanical disadvantage. Our development of innovative methods to track tissue motion in the pharyngeal walls will reveal new insights into pharyngeal mechanics that increase our understanding of the role of obesity in the pathophysiology of OSA.