Pharyngeal mechanics by tagged MRI in a Zucker rat model

描述(申请人提供)：拟议研究的目标是发展先进磁共振成像(MRI)的技术、生理和分析技术，以跟踪麻醉大鼠咽壁的组织运动，以建立咽部呼吸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一种在人类中普遍存在的呼吸系统疾病，其特征是睡眠期间咽部呼吸道反复关闭。以往关于咽部呼吸道通畅控制的研究一般局限于对呼吸道大小、形状和塌陷性的测量。因此，我们对影响这些呼吸道改变的咽壁组织的机械特性的了解非常有限。例如，虽然众所周知，体重指数是阻塞性睡眠呼吸暂停最重要的预测因子，肥胖与呼吸道塌陷性的增加有关，但我们还不清楚肥胖如何改变咽壁组织的机械特性来影响这些变化。为了弥补我们知识中的这些空白，PI将在麻醉大鼠身上采用一种名为空间磁化调制(Spamm(R))的新型磁共振成像(MRI)组织标记技术，以量化咽壁组织运动，即组织运动和组织应变，并量化咽壁组织运动如何导致呼吸道大小和形状的变化。我们建议开发新的技术，使我们能够检测麻醉肥胖和非肥胖Zucker大鼠的咽壁组织运动，肥胖基因的咽部气道受损与阻塞性睡眠呼吸暂停综合征患者相似。具体目标1是开发在高氧和低氧条件下使用MRI和Spamm量化麻醉、非肥胖和肥胖Zucker大鼠自主呼吸过程中咽壁组织运动所需的技术。具体目标2是开发使用MRI和Spamm对非肥胖和肥胖Zucker大鼠的咽壁组织运动进行量化所需的技术，在选择性电刺激舌下神经及其为舌前伸肌(内侧支)和牵引肌(外侧支)提供运动输出的分支时。目标1和目标2的全球假设是，肥胖通过减少横截面积和使咽肌处于机械劣势而损害咽部呼吸道通畅。我们开发的跟踪咽壁组织运动的创新方法将揭示对咽部力学的新见解，从而增加我们对肥胖在阻塞性睡眠呼吸暂停综合征病理生理学中的作用的理解。

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.