PLEASE TYPE THE UNIVERSITY OF NEW SOUTH WALES Thesis/Dissertation Sheet Surname or Family name: Kwan First name: Benjamin Other name/s: Chi Hin Abbreviation for degree as given in the University calendar: PhD School: Prince of Wales Hospital Clinical School Faculty: Medicine Title: Breathing movements of the human tongue and genioglossus measured with ultrasound imaging Abstract 350 words maximum: (PLEASE TYPE) Genioglossus muscle is the largest extrinsic tongue muscle and upper airway dilator. To maintain pharyngeal patency within and between breaths, delicate moment-to-moment coordination of pharyngeal muscles activity and drive is required. Dynamic pharyngeal muscle movement in response to the neural input during sleep/wake states is not clearly understood. This thesis reports a novel ultrasound method to visualise and measure dynamic genioglossus motion in healthy and OSA subjects. In Chapter 2, the method revealed ~1 mm predominantly anterior peak displacement within a 50 mm2 area in the infero-posterior genioglossus in healthy awake subjects during quiet breathing. Motion within this area was non-uniform. The method has good reliability, intraclass correlation coefficient (ICC) of 0.85 across separate imaging sessions. Chapter 3 reported good agreement between ultrasound and tagged MRI in measuring regional tongue motion in healthy and OSA subjects, with an ICC of 0.79. Compared to MRI, ultrasound revealed greater anterior displacement in the posterior tongue (mean difference of 0.24 ± 0.64 mm, 95% limits of agreement: 1.03 to -1.49). Chapter 4 examined influence of respiratory mechanics and drive on genioglossus movement. Inspiration against a resistive load increased posterior genioglossus motion, but it had less anterior and more inferior displacement at the highest inspiratory resistance. An increase in voluntary respiratory drive resulted in increased motion and a more uniform motion within the infero-posterior genioglossus. No significant change in genioglossus motion was observed with alteration of end-expiratory lung volumes. Chapter 5 examined the patterns of posterior tongue motion in awake healthy and OSA subjects. More uniform peak inspiratory motion was recorded within the posterior genioglossus in OSA subjects. Three types of inspiratory posterior tongue motion were observed, with breath-to-breath variability within and across subjects. There may be an association between tongue motion pattern with BMI and tongue-base angle. Likely effect of the motion is to counterbalance the negative pharyngeal collapsing forces. Variation between breaths and individual is possibly due to local anatomical, neural and biomechanical factors. Future research to investigate the biomechanical behaviour of the tongue in OSA subjects during sleep with concurrent neural drive measures may further our understanding into OSA pathogenesis. Declaration relating to disposition of project thesis/dissertation I hereby grant to the University of New South Wales or its agents the right to archive and to make available my thesis or dissertation in whole or in part in the University libraries in all forms of media, now or here after known, subject to the provisions of the Copyright Act 1968. I retain all property rights, such as patent rights. I also retain the right to use in future works (such as articles or books) all or part of this thesis or dissertation. I also authorise University Microfilms to use the 350 word abstract of my thesis in Dissertation Abstracts International (this is applicable to doctoral theses only). 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Breathing movements of the human tongue and genioglossus measured with ultrasound imaging Benjamin Chi Hin Kwan A thesis in fulfilment of the requirements for the degree of Doctor of Philosophy Neuroscience Research Australia Faculty of Medicine, Prince of Wales Hospital Clinical School University of New South Wales August 2018 Abstract Genioglossus muscle is the largest extrinsic tongue muscle and upper airway dilator. To maintain pharyngeal patency within and between breaths, delicate moment-to-moment coordination of pharyngeal muscles activity and drive is required. Dynamic pharyngeal muscle movement in response to the neural input during sleep/wake states is not clearly understood. This thesis reports a novel ultrasound method to visualise and measure dynamic genioglossus motion in healthy and OSA subjects. In Chapter 2, the method revealed ~1 mm predominantly anterior peak displacement within a 50 mm2 area in the infero-posterior genioglossus in healthy awake subjects during quiet breathing. Motion within this area was non-uniform. The method has good reliability, intraclass correlation coefficient (ICC) of 0.85 across separate imaging sessions. Chapter 3 reported good agreement between ultrasound and tagged MRI in measuring regional tongue motion in healthy and OSA subjects, with an ICC of 0.79. Compared to MRI, ultrasound revealed greater anterior displacement in the posterior tongue (mean difference of 0.24 ± 0.64 mm, 95% limits of agreement: 1.03 to -1.49). Chapter 4 examined influence of respiratory mechanics and drive on genioglossus movement. Inspiration against a resistive load increased posterior genioglossus motion, but it had less anterior and more inferior displacement at the highest inspiratory resistance. An increase in voluntary respiratory drive resulted in increased motion and a more uniform motion within the infero-posterior genioglossus. No significant change in genioglossus motion was observed with alteration of end-expiratory lung volumes. Chapter 5 examined the patterns of posterior tongue motion in awake healthy and OSA subjects. More uniform peak inspiratory motion was recorded within the posterior genioglossus in OSA subjects. Three types of inspiratory posterior tongue motion were observed, with breath-to-breath variability within and across subjects. There may be an association between tongue motion pattern with BMI and tongue-base angle. Likely effect of the motion is to counterbalance the negative pharyngeal collapsing forces. Variation between breaths and individual is possibly due to local anatomical, neural and biomechanical factors. Future research to investigate the biomechanical behaviour of the tongue in OSA subjects during sleep with concurrent neural drive measures may further our understanding into OSA pathogenesis. ii Acknowledgements First and foremost, I would like to express my sincere gratitude to Prof. Simon Gandevia for the continuous support of my PhD study, for his tremendous patience, motivation, guidance, understanding and immense knowledge. His mentorship and guidance helped me in all the time of research and writing of this thesis. His selfless time and care encourages me to become a better mentor and teacher to my own students and junior team members. I could not have imagined