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.
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