Patient specific numerical simulation of flow in the human upper airways for assessing the effect of nasal surgery

The study is looking into the potential of using computational fluid dynamics (CFD) as a tool for predicting the outcome of surgery for alleviation of obstructive sleep apnea syndrome (OSAS). From pre- and post-operative computed tomography (CT) of an OSAS patient, the pre- and post-operative geometries of the patient's upper airways were generated. CFD simulations of laminar flow in the patient's upper airway show that after nasal surgery the mass flow is more evenly distributed between the two nasal cavities and the pressure drop over the nasal cavity has increased. The pressure change is contrary to clinical measurements that the CFD results have been compared with, and this is most likely related to the earlier steps of modelling - CT acquisition and geometry retrieval.Comment: Proceedings of the 12th International Conference on CFD in Oil & Gas, Metallurgical and Process Industries, Trondheim, Norway, May 30th - June 1st, 2017, 11 pages, 13 figure

Effect of Orthognathic Surgery on the Upper Airway System

Sleep apnea is a disease which has not been getting an adequate amount of attention in the research community for a long time. However, the strain on the cardiovascular system and other serious problems, such as daytime sleepiness and even neurocognitive dysfunction, that it causes may be severe in advanced cases of the illness, as such it can significantly affect the heart especially and lead to cardiac arrest. Thus, it has been receiving a lot of attention recently. Tampere University Hospital has a goal of creating a comprehensive upper airway airflow model for surgery outcome prediction. That requires knowledge of available models and analysis of static magnetic resonance images, among other things. This document deals with these two main issues. This thesis has two major parts, one of them being a literature review of sleep apnea and models used in airflow modelling in the upper airways. Modelling of airflow generally includes acquisition of a static upper airway system model (in the case of upper airway modelling) and then adding a dynamic component to it. The second part of this thesis deals with acquisition of the static model, which involves segmentation of MRI image sets from 3 patients (pre- and post-operative sequences). It also answers the question, whether the effect of orhtognathic surgery on the upper airway system can be seen from volumetric analysis of the segmented images and the segmented images themselves. The main methods of adding a dynamic component to the static model turned out to be computational fluid mechanics and finite element modelling, including their sub-methods, such as direct numerical simulation of large eddy simulation. As with the second part of the thesis, the volumetric segmentation data is rather inconclusive and should not be related solely for evaluation of the effect of orthognathic surgery on the upper airway system. It can be said, nonetheless, that the volume of the upper airway itself is rather easily obtainable and reliable. The images themselves, however, provide very visual information about that, and shifting of certain muscles and muscle groups and other structures can be seen

Computational Fluid Dynamics and Its Solicitation in Dentistry and Its Various Divisions – An Update and Review of Literature

  Computational fluid dynamics (CFD) is a part of fluid mechanics that uses numerical means and algorithms to anticipate and resolve problems associated with fluid flow (gas or liquid). Boundary conditions that are set, intends to mimic the clinical condition. Fluid flow dynamics in the various aspects of the biological systems such as blood flow can contribute significantly to the area of research and development. Alteration in the flow dynamics in relation to gas or liquid may have important effects over the biological systems involved. The present review article aims to shed light upon the fundamental aspects of the modelling the digital clinical model or a 3-dimensional model in order to know about the behaviour of the system concerned and to acquire knowledge for carrying out future experimentation which would be beneficial in scientific field for various treatment modalities

Biomechanical Models of Human Upper and Tracheal Airway Functionality

The respiratory tract, in other words, the airway, is the primary airflow path for several physiological activities such as coughing, breathing, and sneezing. Diseases can impact airway functionality through various means including cancer of the head and neck, Neurological disorders such as Parkinson\u27s disease, and sleep disorders and all of which are considered in this study. In this dissertation, numerical modeling techniques were used to simulate three distinct airway diseases: a weak cough leading to aspiration, upper airway patency in obstructive sleep apnea, and tongue cancer in swallow disorders. The work described in this dissertation, therefore, divided into three biomechanical models, of which fluid and particulate dynamics model of cough is the first. Cough is an airway protective mechanism, which results from a coordinated series of respiratory, laryngeal, and pharyngeal muscle activity. Patients with diminished upper airway protection often exhibit cough impairment resulting in aspiration pneumonia. Computational Fluid Dynamics (CFD) technique was used to simulate airflow and penetrant behavior in the airway geometry reconstructed from Computed Tomography (CT) images acquired from participants. The second study describes Obstructive Sleep Apnea (OSA) and the effects of dilator muscular activation on the human retro-lingual airway in OSA. Computations were performed for the inspiration stage of the breathing cycle, utilizing a fluid-structure interaction (FSI) method to couple structural deformation with airflow dynamics. The spatiotemporal deformation of the structures surrounding the airway wall was predicted and found to be in general agreement with observed changes in luminal opening and the distribution of airflow from upright to supine posture. The third study describes the effects of cancer of the tongue base on tongue motion during swallow. A three-dimensional biomechanical model was developed and used to calculate the spatiotemporal deformation of the tongue under a sequence of movements which simulate the oral stage of swallow

疾患鼻気道における空気流と粒子堆積の計算流体力学的研究

Understanding the properties of airflow in the nasal cavity is very important in determining the nasal physiology and in diagnosis of various anomalies associated with the nose. The complex anatomy of the nasal cavity has proven to be a significant obstacle in the understanding of nasal obstructive disorders. Due to their non-invasiveness, Computational Fluid Dynamics (CFD) has now been utilized to assess the effects of surgical interventions on nasal morphological changes as well as local breathing airflow characteristics through the upper airway of individual patients. Furthermore, nasal inhalation is a major route of entry into body for airborne pollutions. Therefore, the function of the upper airway to filter out the inhaled toxic particles is considered important. The determination of the total particle filtering efficiency and the precise location of the induced lesion in the upper airway is the first step in understanding the critical factors involved in the pathogenesis of the upper airway injury. The present work involved development of three-dimensional diseased upper airway models from Computed Tomographic (CT) scan images derived from a nasal airway without any nasal diseased and an upper airway which was diagnosed with chronic nasal obstruction and obstructive sleep apnea. Numerical simulation of airflow and transport and deposition of inhaled pollutant through chronic diseased nasal airway, constricted pharyngeal representing Obstructive Sleep Apnea (OSA) and diseased upper airway with OSA for pre- and post-operative cases have been studied. Detailed flow pattern and characteristics for inspiratory airflow for various breathing rates (7.5-40 L/min) were evaluated. Simulation of the particle transport and deposition of micro-sized particles with particle diameter ranging from 1-40 ?m were also investigated. In the first part of this study, the surgical treatment performed in the nasal cavity which include septoplasty, inferior turbinate reduction and partial concha bullosa resection substantially increased nasal volume, which influenced flow partitioning and decreases the pressure drop and flow resistance of the nasal passage. The removal of the obstruction in the nasal airway significantly improve the breathing quality. However, the nasal airway experienced approximately about a 50 % decrease in total particle filtering efficiency after surgery. Therefore, careful consideration should be given to this matter before nasal operation especially for a patient with breathing allergic history. In the second part of this study, the morphology of the constricted pharyngeal representing OSA was found to significantly affect the airflow pattern and the deposition fraction of microparticles. The morphology of the upper airway, the size of the inhaled particle and breathing rate was found significantly affect the total particle deposition efficiency and local deposition fraction in the upper airway. The presented regional deposition fraction may be used in specifying the site of highest possibility for respiratory lesions according to the breathing rate and the size of the inhaled toxic particles. Results obtained from this study can be also used to estimate the location of airway obstruction in upper airway of patient with sleep apnea symptom. In the third part of this study, the surgical conducted procedure has cleared out the obstructions in the nasal airway hence improve the airflow distribution through the upper airway during inhalation process. This study shows that the nasal surgery alone can help improve the breathing quality in the upper airway with OSA. The reduction of the airflow resistance in the nasal cavity affect the pressure distribution in the lower part of the upper airway. Obstruction in the nasal passage and sudden airway expansion in the upper airway increased number of particles trap, recirculated and finally deposited in the airway. Finally, the experimental data obtained from the experimental study utilizing the developed pharyngeal airway further validate the result obtained from the numerical study.九州工業大学博士学位論文 学位記番号：生工博甲第315号 学位授与年月日：平成30年3月23日1: INTRODUCTION|2: LITERATURE REVIEW|3: MODELLING THE HUMAN UPPER AIRWAY|4: NUMERICAL SIMULATION METHODOLOGY|5: NUMERICAL INVESTIGATION ON AIRFLOW CHARACTERISTICS IN NASAL CAVITY HAVING TURBINATE HYPERTROPHY, CONCHA BULLOSA, AND SEPTUM DEVIATION WITH OSA: PRE- AND POST SURGERY|6: COMPUTATIONAL FLUID DYNAMICS STUDY OF AIRFLOW AND MICROPARTICLE DEPOSITION IN A CONSTRICTED PHARYNGEAL SECTION REPRESENTING OBSTRUCTIVE SLEEP APNEA DISEASE|7: NUMERICAL SIMULATION OF AIRFLOW AND AEROSOL DEPOSITION IN REALISTIC HUMAN UPPER AIRWAY WITH OBSTRUCTIVE SLEEP APNEA AND CHRONIC NASAL OBSTRUCTION: PRE- AND POST-SURGERY|8: EXPERIMENTAL INVESTIGATION|9: CONCLUSIONS AND FUTURE RECOMMENDATIONS九州工業大学平成29年

Feasibility of Individualized Airway Surgery in Horses

This thesis describes a progressive series of studies that was conducted to investigate the use of benchtop and computational models in the investigation of multiple upper airway surgeries for recurrent laryngeal neuropathy (RLN) in horses. Overall, the objective was to build the knowledge of laryngeal conformation and fluid mechanics with various surgical procedures for application in patients as an evaluation for the surgery of best outcome and as a step toward patient-specific diagnosis and treatment of upper airway disorders. The first study built upon a previously reported vacuum-based box setup that was used to compare RLN to four different surgical procedures within twenty-eight different equine larynges. Each larynx underwent these procedures in order and inhalation was simulated while measuring resistance to airflow (translaryngeal impedance). Two of the procedures, the combined laryngoplasty, ipsilateral ventriculocordectomy with arytenoid corniculectomy (LLPCOR) and laryngoplasty with ipsilateral ventriculocordectomy (LLP) were found to be significantly different from the RLN, arytenoid corniculectomy (COR) and partial arytenoidectomy (PA). The adapter used to mount the larynges was found to have a significant effect for the RLN, LLP and LLPCOR procedures. There was also a residual intraclass correlation of 27.6% in the final statistical model from individual laryngeal differences which were observed during the study. The variation of laryngeal features observed during the first study led to questions about the interaction between these geometries and airflow development. To capture the three-dimensional geometry effectively, similar methodology was repeated with concurrent computed tomography (CT) scans. These scans were analyzed focusing on cross-sectional area and changes along the airstream. Each procedural run was analyzed and used to simulate a pipe constriction. Entrance and exit conformations were modeled with respect to the ratio of the inlet cross-sectional area (CSA), constriction CSA and the divergent CSA downstream. The entrance characteristics were found to be significant; specifically, the angle of constriction and the ratio of the larger and smaller areas had a significant effect on laryngeal impedance. A frictional coefficient was measured as a function of energy lost by air passing through the constricted area and was found to be significant. This confirmed the importance of detail in surgically addressing disease affecting the laryngeal entrance. To provide a more thorough analysis of geometry and flow application of computational fluid dynamics (CFD) analysis was next reasonable step. The next study consisted of CFD analysis of the CT scans to determine the accuracy of CFD in reflecting the findings of the vacuum box airflow model. CFD provides a three-dimensional analysis of flow through complex geometries but also reduces the expense and intensive labor of complex flow experiments. Given these potential applications, this study reported the use of CFD to predict the procedure with the lowest impedance for each larynx. CFD results were compared to the measured values. Additionally, qualitative characteristics of the flow within the anatomical paradigm were examined. The CFD models corroborated the procedure of lowest impedance for 7 out of 10 of the larynges; 2 larynges had 2 procedures that were very close in impedance and the last larynx had unique collapse characteristics that may explain the lack of agreement. The measured pressure and impedance values showed a linear trend compared to the calculated values with measured impedance about 0.7 times that of the calculated (CFD) values. Qualitatively, areas of negative pressure and high velocity were noted in the higher impedance procedures and around tissue irregularities. While the CFD model was reasonably successful for the laryngeal study, demonstration of use in a more realistic equine patient application is needed. The final study took an additional step toward the equine patient by incorporating an entire head with measured translaryngeal impedance similar to the previous studies. A cadaver head was used and RLN, LLP, LLPCOR, COR and PA were simulated and subjected to negative airflow. The impedance values measured during this study were higher than expected, but the computational model reported values that were similar to the previous literature. The observed flow characteristics showed some differences to previous studies but the CFD model clarified these differences by highlighting the differences in three-dimensional geometry between the heads used in each study. The PA was the lowest impedance procedure both as measured and as calculated. Thus, CFD continued to demonstrate a predictive capability when it comes to determining the procedure of lowest impedance for the whole equine upper airway. Although there have been a large number of biomechanical models investigating the equine upper airway, they have not kept up with the technological advancements in human respiratory mechanics and CFD. CFD consistently confirmed the procedure of lowest impedance while incorporating individual patient geometry and can be performed much more efficiently than when the first equine application was reported over a decade ago. While more studies are needed, these models unquestionably provide a foundation for individual patient analysis in the future

A computational neuromuscular model of the human upper airway with application to the study of obstructive sleep apnoea

Includes bibliographical references.Numerous challenges are faced in investigations aimed at developing a better understanding of the pathophysiology of obstructive sleep apnoea. The anatomy of the tongue and other upper airway tissues, and the ability to model their behaviour, is central to such investigations. In this thesis, details of the construction and development of a three-dimensional finite element model of soft tissues of the human upper airway, as well as a simplified fluid model of the airway, are provided. The anatomical data was obtained from the Visible Human Project, and its underlying micro-histological data describing tongue musculature were also extracted from the same source and incorporated into the model. An overview of the mathematical models used to describe tissue behaviour, both at a macro- and microscopic level, is given. Hyperelastic constitutive models were used to describe the material behaviour, and material incompressibility was accounted for. An active Hill three-element muscle model was used to represent the muscular tissue of the tongue. The neural stimulus for each muscle group to a priori unknown external forces was determined through the use of a genetic algorithm-based neural control model. The fundamental behaviour of the tongue under gravitational and breathing-induced loading is investigated. The response of the various muscles of the tongue to the complex loading developed during breathing is determined, with a particular focus being placed to that of the genioglossus. It is demonstrated that, when a time-dependent loading is applied to the tongue, the neural model is able to control the position of the tongue and produce a physiologically realistic response for the genioglossus. A comparison is then made to the response determined under quasi-static conditions using the pressure distribution extracted from computational fluid-dynamics results. An analytical model describing the time-dependent response of the components of the tongue musculature most active during oral breathing is developed and validated. It is then modified to simulate the activity of the tongue during sleep and under conditions relating to various possible neural and physiological pathologies. The retroglossal movement of the tongue resulting from the pathologies is quantified and their role in the potential to induce airway collapse is discussed

Functional respiratory imaging : opening the black box

In respiratory medicine, several quantitative measurement tools exist that assist the clinicians in their diagnosis. The main issue with these traditional techniques is that they lack sensitivity to detect changes and that the variation between different measurements is very high. The result is that the development of respiratory drugs is the most expensive of all drug development. This limits innovation, resulting in an unmet need for sensitive quantifiable outcome parameters in pharmacological development and clinical respiratory practice. In this thesis, functional respiratory imaging (FRI) is proposed as a tool to tackle these issues. FRI is a workflow where patient specific medical images are combined with computational fluid dynamics in order to give patient specific local information of anatomy and functionality in the respiratory system. A robust high throughput automation system is designed in order get a workflow that is of a high quality, consistent and fast. This makes it possible to apply this technology on large datasets as typically seen in clinical trials. FRI is performed on 486 unique geometries of patients with various pathologies such as asthma, chronic obstructive lung disease, sleep apnea and cystic fibrosis. This thesis shows that FRI can have an added value in multiple research domains. The high sensitivity and specificity of FRI make it very well suited as a tool to make decisions early in the development process of a device or drug. Furthermore, FRI also seems to be an interesting technology to gain better insight in rare diseases and can possibly be useful in personalized medicine

A novel optogenetics-based therapy for obstructive sleep apnoea

Obstructive sleep apnoea (OSA) is characterised by repeat upper airway narrowing and/or collapse during sleep. Many patients are sub-optimally treated due to poor tolerance or incomplete response to established therapies. We propose a novel, optogenetics-based therapy, that enables light-stimulation induced upper airway dilator muscle contractions to maintain airway patency. The primary aims of this thesis were to determine feasibility in a rodent model of OSA, and identify effective optogenetic constructs for activating upper airway muscles. Chapters 2 and 3 outline the development of a novel construct for the expression of light-sensitive proteins (opsins) in upper airway muscles, comparing two promotors and two recombinant adeno-associated virus capsids (rAAV) for optogenetic gene transfer. Results show that a muscle-specific promotor (tMCK) was superior to a non-specific promotor (CAG). With tMCK, opsin expression in the tongue was 470% greater (p=0.013, RM-ANOVA), brainstem expression was abolished, and light stimulation facilitated a 66% increase in muscle activity from that recorded during unstimulated breaths in an acute model of OSA (p<0.001, linear mixed model) (Chapter 2). Moreover, a novel, highly myotropic rAAV serotype, AAVMYO, was superior to a wild-type serotype, AAV9. The AAVMYO serotype driven by tMCK facilitated a further increase in muscle activity with light stimulation to 194% of that recorded during unstimulated breaths (p<0.001, linear mixed model) (Chapter 3). Finally, ultrasound imaging confirmed that the optimised construct was able to generate effective light-induced muscle contractions and airway dilation (Chapter 4). A secondary aim was to advance preclinical trials for the proposed therapy. To this end, a surgical protocol for chronic implantation of light delivery hardware and recording electrodes in rodents was developed (Chapter 5). The final protocol will allow us to determine the effects of acute and chronic light stimulation on opsin-expressing upper airway muscles during natural sleep. In summary, Chapters 2 to 4 provide proof-of-concept for a non-invasive optogenetics-based OSA therapy. The combination of a muscle-specific promotor and a muscle-specific viral vector presents a novel and highly effective method of inducing light sensitivity into skeletal muscle and facilitating light-evoked airway dilation. Finally, Chapter 5 commences the development of a surgical protocol that will aid ongoing preclinical trials

Three dimensional study to quantify the relationship between facial hard and soft tissue movement as a result of orthognathic surgery

Introduction Prediction of soft tissue changes following orthognathic surgery has been frequently attempted in the past decades. It has gradually progressed from the classic “cut and paste” of photographs to the computer assisted 2D surgical prediction planning; and finally, comprehensive 3D surgical planning was introduced to help surgeons and patients to decide on the magnitude and direction of surgical movements as well as the type of surgery to be considered for the correction of facial dysmorphology. A wealth of experience was gained and numerous published literature is available which has augmented the knowledge of facial soft tissue behaviour and helped to improve the ability to closely simulate facial changes following orthognathic surgery. This was particularly noticed following the introduction of the three dimensional imaging into the medical research and clinical applications. Several approaches have been considered to mathematically predict soft tissue changes in three dimensions, following orthognathic surgery. The most common are the Finite element model and Mass tensor Model. These were developed into software packages which are currently used in clinical practice. In general, these methods produce an acceptable level of prediction accuracy of soft tissue changes following orthognathic surgery. Studies, however, have shown a limited prediction accuracy at specific regions of the face, in particular the areas around the lips. Aims The aim of this project is to conduct a comprehensive assessment of hard and soft tissue changes following orthognathic surgery and introduce a new method for prediction of facial soft tissue changes.   Methodology The study was carried out on the pre- and post-operative CBCT images of 100 patients who received their orthognathic surgery treatment at Glasgow dental hospital and school, Glasgow, UK. Three groups of patients were included in the analysis; patients who underwent Le Fort I maxillary advancement surgery; bilateral sagittal split mandibular advancement surgery or bimaxillary advancement surgery. A generic facial mesh was used to standardise the information obtained from individual patient’s facial image and Principal component analysis (PCA) was applied to interpolate the correlations between the skeletal surgical displacement and the resultant soft tissue changes. The identified relationship between hard tissue and soft tissue was then applied on a new set of preoperative 3D facial images and the predicted results were compared to the actual surgical changes measured from their post-operative 3D facial images. A set of validation studies was conducted. To include: • Comparison between voxel based registration and surface registration to analyse changes following orthognathic surgery. The results showed there was no statistically significant difference between the two methods. Voxel based registration, however, showed more reliability as it preserved the link between the soft tissue and skeletal structures of the face during the image registration process. Accordingly, voxel based registration was the method of choice for superimposition of the pre- and post-operative images. The result of this study was published in a refereed journal. • Direct DICOM slice landmarking; a novel technique to quantify the direction and magnitude of skeletal surgical movements. This method represents a new approach to quantify maxillary and mandibular surgical displacement in three dimensions. The technique includes measuring the distance of corresponding landmarks digitized directly on DICOM image slices in relation to three dimensional reference planes. The accuracy of the measurements was assessed against a set of “gold standard” measurements extracted from simulated model surgery. The results confirmed the accuracy of the method within 0.34mm. Therefore, the method was applied in this study. The results of this validation were published in a peer refereed journal. • The use of a generic mesh to assess soft tissue changes using stereophotogrammetry. The generic facial mesh played a major role in the soft tissue dense correspondence analysis. The conformed generic mesh represented the geometrical information of the individual’s facial mesh on which it was conformed (elastically deformed). Therefore, the accuracy of generic mesh conformation is essential to guarantee an accurate replica of the individual facial characteristics. The results showed an acceptable overall mean error of the conformation of generic mesh 1 mm. The results of this study were accepted for publication in peer refereed scientific journal. Skeletal tissue analysis was performed using the validated “Direct DICOM slices landmarking method” while soft tissue analysis was performed using Dense correspondence analysis. The analysis of soft tissue was novel and produced a comprehensive description of facial changes in response to orthognathic surgery. The results were accepted for publication in a refereed scientific Journal. The main soft tissue changes associated with Le Fort I were advancement at the midface region combined with widening of the paranasal, upper lip and nostrils. Minor changes were noticed at the tip of the nose and oral commissures. The main soft tissue changes associated with mandibular advancement surgery were advancement and downward displacement of the chin and lower lip regions, limited widening of the lower lip and slight reversion of the lower lip vermilion combined with minimal backward displacement of the upper lip were recorded. Minimal changes were observed on the oral commissures. The main soft tissue changes associated with bimaxillary advancement surgery were generalized advancement of the middle and lower thirds of the face combined with widening of the paranasal, upper lip and nostrils regions. In Le Fort I cases, the correlation between the changes of the facial soft tissue and the skeletal surgical movements was assessed using PCA. A statistical method known as ’Leave one out cross validation’ was applied on the 30 cases which had Le Fort I osteotomy surgical procedure to effectively utilize the data for the prediction algorithm. The prediction accuracy of soft tissue changes showed a mean error ranging between (0.0006mm±0.582) at the nose region to (-0.0316mm±2.1996) at the various facial regions