The Inuence on Airow Characteristics In Upper Airway In Sleep Apnea Hypopnea By The Disturbance of Pharyngeal Muscle Group Based on High Simulation of The Wall Flow Field

Background: To observe the inuence on morphology and internal airow characteristics in upper airway in sleep apnea hypopnea by the disturbance of pharyngeal muscle group based on high simulation of the wall ow eld. Methods: One goat for experimental purpose bought by our hospital in December 2018 was included as the research object. This experimental goat received injection of hardener and submucosal injection edema into pharyngeal muscle group of upper respiratory tract. The goat received CT scan before and after injection. Computational uid dynamics(CFD) model was built on the base of CT scans by 3Dslicer 4.5 and MeshLab and ANSYS ICEM CFD 14.0. The internal ow of upper respiratory tract was simulated by ANSYS-FLUENT 14.0 and the results were analyzed by ANSYS-CFD-POST 14.0. Results: Soft palate and uvula were elongated and thickened and pharyngeal muscle group was disturbed after injection of hardener and submucosal injection edema into the goat. The area that changed the most of upper airway was located in the lower bound of pharyngopalatiae, and it reduced area from 0.3602cm2 to 0.1699cm2; the air velocity was elevated from 3.53009m/s to 7.24478m/s, the negative pressure was elevated from -28.6184 Pa to -66.4510 Pa, while the resistance of cavum pharyngis elevated from 3396.09Pas/L to 3813.65Pas/L. Conclusion: Injection hardener and into muscle group the goat result the disturbance muscle group, narrow the tract, elevate the the the collapsibility the OSAHS at last.


Background
Obstructive sleep apnea hypopnea syndrome(OSAHS) is caused by obstruction of upper airway during sleep [1] . The incidence of this disease is gradually increasing in recent years, which is closely related to the improvement of people's living standards, the development of medical diagnostic technology and people's increasing attention to health. The study on the etiology of OSAHS has been extended to the entire upper respiratory tract, the coordination of pharyngeal muscle group, the in uence of secretion environment and the role of respiratory air ow with shape resistance, all of which are being gradually incorporated into the etiologic research.
With the swift development of information technology, the combination of medicine and engineering has become the future direction, so computer simulation has become one of the important methods for theoretical and experimental research, and the relevant methods of human body test can be replaced by computer simulation in some elds completely [2] . Three-dimensional images of respiratory tract can be well applied in the evaluation of OSAHS surgical e cacy [3] . Computational Flow Dynamics(CFD) [4,5,6] needs to be combined with clinical medicine and clinical statistics effectively to conduct scienti c and reasonable sorting, analysis and calculation for rst-line clinical data, so as to assist clinical research with more accurate data. Through the study of three-dimensional reconstruction and CFD before and after injection of hardener and submucosal injection edema into goats' pharyngeal muscle group of upper respiratory tract, this paper investigates the results of upper respiratory tract morphology, ow velocity, pressure and airway resistance caused by disturbance of pharyngeal muscle group, so as to qualitatively and quantitatively analyze the effect of the functional status of pharyngeal muscle group to OSAHS and explore a new treatment on the basis of pharyngeal muscle group adjustment.

Materials And Methods
2.1 Selection of research objects One male goat aged 2.7 years old with the weight of 30.42kg (from Shanghai Jiagan Biotechnology Co., LTD.) purchased December 2018 by our hospital was selected. It has no a history of acute and chronic disease in upper respiratory tract, trauma and surgery in maxillofacial region and upper respiratory tract within the last 3 months.

Methods
The goat was performed with injection of hardener and submucosal injection edema in the bilateral soft palates in lower bound of uvula in pharynx, pharyngeal muscle groups in the upper, middle and lower ends of left and right pharyngopalatiaes(3ml of 23.4 % sodium chloride solution each). 3D CT scan of the upper respiratory tract was performed 1 week before and after the injection.

CT scan Siemens SomAToM
Emotion 16-layer spiral CT was adopted to scan. After intramuscular injection of Zoletil, under general anesthesia, goats were in supine position and breathed smoothly with head keep in midline by headstock. From 3 cm above the bottom of skull to supraglottic structure were scanned with 1.25mm of scanning layer. Standard DICOM imaging data was collected by the software of Siemens CT machine.
2.2.2 Three-dimensional reconstruction of the upper respiratory tract CT scanned data were used by 3Dslicer 4.5 to conduct three dimensional reconstruction. After treatment such as threshold value setting, image segmentation and region growth, three dimensional surface mathematical models were obtained, and the smooth outer surface was obtained with algorithm of MeshLab( gure 1). The model storage capacity was reduced and stored as STL format.

2.2.3
Meshing and independence analysis of three dimensional model The three dimensional model in STL format after smooth processing in the previous step was imported into the CFD pre-processing software ANSYS ICEM CFD 14.0 to conduct uid mesh division, de ne upper airway inlet and outlet and build tetrahedral unstructured mesh model.
Before the next CFD calculation, the independence of mesh was rstly analyzed to ensure that the calculation data obtained were grid-independent, and then the next CFD calculation was carried out. The same ux ow at inlets could be set with different numbers of mesh such as 600,000, 1.2 million, 1.65 million and 2 million to calculate the upper respiratory tract. With quality and speed considered overall, the comparative results showed that the accuracy of numerical simulation was directly related to the quality of mesh division. The more the meshes, the more accurate the calculated results would be.
However, in the comparison between 1.65 million and 2 million of meshes, the calculated results were basically the same except for the slight difference in local areas. Through the above analysis, it can be concluded that when the mesh density reaches more than 1.65 million, the calculation result is irrelevant to the number of meshes, and accurate calculation can be carried out in the next step. In this paper, the upper respiratory tract model with 1,751,940 of meshes and 303,981 of nodes was selected before and after injection.

Fluid mechanics parameters and boundary conditions
With CFD method to calculate the internal air ow of upper respiratory tract, calculation domain was from the nostril to the bottom of the epiglottis.
Software ANSYS-FLUENT 14.0 was adopted to conduct numerical simulation and SIMPLEC method was used to calculate the coupling of the velocity and pressure. On the basis of given pressure eld, discrete Navier-Stokes momentum equation can be solved so as to obtain velocity eld. Convergent solution can be calculated through repeated iteration. The whole upper respiratory tract is regarded as a rigid body with air as the uid(normal temperature and incompressible). The thermal effect between uid and wall surface was removed. The air owed into the nose at a constant speed and the direction was vertical to the axial plane of inlet. With other conditions unchanged and RNG k-ε turbulent-ow model to stimulate, it can be analyzed that the uid ow in the upper respiratory tract was turbulent ow of low Reynolds number.
Boundary conditions: the upper respiratory tract was considered as a cavity, and the anterior nostril was directly connected with the outside environment, and a standard atmospheric pressure was applied at the nostril, that is, P=101325Pa; No slip with zero velocity was set on the surrounding wall surface, and the lower edge of throat was de ned as the ow boundary condition with 120.7ml/s or 7.242L/min of ow.
Air was adopted as medium with ρ=1.225kg/m 3 of density and μ=1.7894×10 -5 kg/(m·s ) of dynamic coe cient of viscosity. The Kinetic energy k and turbulent dissipation rate ε were calculated by the following formula: k =3/2(vI) 2 [7] : nasopharynx (from the top of nasopharyngeal to horizontal hard palate), palatopharynx (from the horizontal hard palate to the tip of soft palate), glossopharynx (from the tip of soft palate to the tip of epiglottis), laryngopharynx (from the tip of epiglottis to the bottom of epiglottis ). 5 sections were selected as shown in the gure( gure 2) : Section 1 was the beginning and merging area of the two nasal cavity, forming the end of nasal cavity and the beginning of the nasopharynx (nasopharyngeal apex); Section 2 was the lower nasopharyngeal boundary (horizontal hard palate); Section 3 was the subpalatopharyngeal boundary (the tip of soft palate); Section 4 was the bottom boundary of glossopharyngeum (the tip of epiglottis); Section 5 was the lower boundary of epiglottis (the bottom of epiglottis).

Result analysis
The changes of upper respiratory tract morphology and air ow characteristics of goats' pharyngeal muscle group before and 1 week after injection were compared.   Table 2 Change of area of each section (cm 2 ) of pharyngeal muscle group before and after injection of hardener and submucosal injection edema 3.2 Change of ow velocity in upper respiratory tract The change trend of ow velocity in the upper respiratory of the goat before and after injection was shown in gure 3: Before injection, the air ow velocity in their upper respiratory tract was relatively stable but changed dramatically after injection. As shown in table 3, there was no signi cant change in the airway velocity in the nasopharynx after injection, while the ow velocity in pharyngopalatiae and glossopharyngeum increased signi cantly, especially the lower bound of pharyngopalatiae, with an increase of 105.23%. Table 3 Change of ow velocity m/s of each airway section before and after injection of hardener and submucosal injection edema into pharyngeal muscle group

Pressure change in upper respiratory tract
Pressure change trend of upper respiratory tract before and after injection were shown in gure 4 and table 4: the pressure of the upper respiratory tract decreased gradually along the direction of gas ow before injection. The pressure change in the nasopharynx and epiglottic areas was not signi cant after injection, while the negative pressure at the pharyngopalatiae and glossopharyngeum was signi cantly increased, especially the lower bound of pharyngopalatiae, from -28.6184Pa before injection to -66.4510Pa, with a 132.20% increase.(take pressure of nasal cavity's inlet as the reference point: here the pressure is 101325Pa). Table 4 Pressure change of each airway section before and after injection of hardener and submucosal injection edema into pharyngeal muscle group (Pa)

Resistance change in upper respiratory tract
Air ow resistance refers to the pressure required to push the speci c volume of air ow to the unit distance in unit time. The resistance formula: R=△P/Q, △P is pressure drop; Q is ow, 0.1207L/s. The cavum resistance of pharyngeal muscle group increased signi cantly after injection, from 3396.09Pa·s/L before injection to 3813.65Pa·s/L, and the air ow resistance of pharyngeal muscle group increased 12.30% after injection.

Establishment of the high simulation of the wall ow eld in the upper respiratory tract
Under a condition of smooth breathing, Kelly et al. [8] compared the obtained data recorded in continuous time and found that the air ow was stable. Hahn [9] found through experiments that the nasal hair had no effect on the internal air ow in a 20-fold magni cation model of nasal cavity. With the analysis of heat and mass transfers and the veri cation of Prandtl and Grashof numbers, it can be further concluded that under normal breathing conditions, temperature and humidity have no signi cant in uence on the internal air ow. It is reasonable to regard the upper respiratory tract model in this study as instantaneous rigid model and the air ow in it is stable according to previous studies without the in uence of nose hair and the change of temperature and humidity, therefore, these simpli cations are reasonable.
Three-dimensional reconstruction and numerical simulation analysis of the upper respiratory tract on the basis of CT and MRI imaging in recent years has become increasing prevalent for scholars home and abroad [10][11][12] . Based on CT scan and three dimensional reconstruction of upper respiratory tract before and after injection into pharyngeal muscle group, this study reconstructed the simulative structure of goat's respiratory tract with computer. Whereafter commercial software CFD was conducted to systematically calculate and analyze the ow eld parameters of the upper respiratory tract. From the viewpoint of uid mechanics, discussion and analysis of characteristics of upper respiratory air ow was conducted and analyzed from the anatomical structure with the ow characteristics of the upper respiratory tract taken into consideration. In this way, the relationship between anatomical structure, aerodynamic characteristics and physiological function of the upper respiratory tract can be more completely linked. The upper respiratory tract model was not simpli ed geometrically in the modeling process to establish high simulation of the wall ow eld which could re ect the real situation of it.

Discussion on CFD and characteristics of upper airway ow eld
In the eld of biomedical engineering, Computational Flow Dynamics (CFD) is a new area of OSAHS research. The wall ow eld with high simulation of upper respiratory tract was established through the above experimental goats, and some indexes of CFD analysis could re ect the relationship between related upper respiratory tract air ow and structure, which makes up for the difference between animal tissue structure and human's. Compared with the current commonly used detection methods, it can be found that this method can provide more accurate upper airway uid data, and CFD technology has the advantages of fast modeling, high accuracy, no wound and repeatability.
The reference values of CFD study on upper respiratory tract include the normal range of cross sectional area, volume, velocity, pressure and wall resistance of upper respiratory tract. The effective ventilation volume of the upper respiratory tract is directly related to the degree of airway patency, belonging to an important index [13,14] . The respiratory function of the upper respiratory tract will be signi cantly affected when the effective ventilation volume is reduced. For example, the effective ventilation volume will decelerate the air ow speed in the middle of respiration. However, the reduction of this volume [15] will also have a certain impact on the oxygen saturation capacity of the lower airway, and in severe cases, will result in basic diseases as well. From morphology, air ow distribution, velocity and pressure characteristics, it can be concluded that the impact force of air ow is different in different parts of upper respiratory tract when breath It is convenient to identify the characteristic value parameters of ow eld using CFD to simulate the air ow within the upper respiratory tract so as to know air ow situation and analyze different pressure in upper respiratory tract from three-dimensional direction. The blocked plane and its serious degree can be speculated with statistical analysis of mathematical software, which conduces to learning relationship between the function of upper respiratory tract and anatomical structure. Therefore, it provides a brandnew method to study the pathogenesis of OSAHS and explore the OSAHS mechanism caused by the disturbance of pharyngeal muscle group. In this study, CFD simulation was carried out on the three dimensional models of upper respiratory tract before and after injection of hardener and submucosal injection edema in one goat's pharyngeal muscle groups to study the changes of air ow velocity, pressure and wall resistance in upper respiratory tract after injection of hardener caused disturbance of pharyngeal muscle groups, and the morphological changes of upper respiratory tract were analyzed.

Changes of upper respiratory tract after disturbance of pharyngeal muscle group
In this article, according to the test data, we established three dimensional model of goats' and high simulation of the wall ow eld, analyzed the change of upper respiratory tract before and after injection of hardener and submucosal injection edema into pharyngeal muscle group, adopted CFD software to determine each parameter value of ow eld of the upper respiratory tract under smooth breathing. To sum up, without interference factors, this paper systematically expounds the impact on upper respiratory tract, because of the change of anatomical structure, posed by the disturbance of pharyngeal muscle group.
The numerical models of upper respiratory tract of the goat's pharyngeal muscle group before and after injection of hardener and submucosal injection edema were analyzed in detail. A comparative study found that the structure of the upper respiratory tract changed after injection, and the corresponding hydromechanical features changed signi cantly. After injection, there was almost no change in nasal cavity and laryngopharynx, while the area of pharyngopalatiae and glossopharyngeum were signi cantly shrunk; The air ow of the upper respiratory tract was affected due to the reduction of volume, and the velocity of the this area became rapid, especially the lower bound of pharyngopalatiae with velocity increased from 3.53009m/s to 7.24478m/s. It aggravated the impact force of air ow on the pharyngeal wall and the damage to the airway mucosa. At the same time, the impact force of air ow on the wall of the pharynx cavity caused high-frequency vibration to soft tissues and the occurrence of snoring, and the enhancement of this impact force rose the snoring accordingly. After injection of hardener and submucosal injection edema into pharyngeal muscle group, the negative pressure in the lower bound of pharyngopalatiae was signi cantly increased from -28.6184Pa before injection to -66.4510Pa, with a 132.20% increase, which enhanced the airway compliance and would increase the possibility of airway collapse in this area, leading to OSAHS symptoms. After injection of hardener and submucosal injection edema into pharyngeal muscle group, pharyngeal cavity resistance increased signi cantly by 12.30%, which would make air ow through the airway more tough and further increase the possibility of collapse.

Conclusion
Pharyngeal cavity is the portal of the upper respiratory tract and its stable structure is closely related to respiration. Disturbance of pharyngeal muscle group and constriction of upper respiratory tract occurred after injection of hardener and submucosal injection edema into pharyngeal muscle group, which signi cantly changed the hydromechanical characteristics of the airway. The adaptation of the upper respiratory tract function and morphology was the fundamental cause of OSAHS. Therefore, when treating OSAHS patients, doctors need to consider how to solve disturbance of pharyngeal muscle group and alleviate the pressure and resistance of air ow in the upper respiratory tract of OSAHS patients, rather than just morphological changes.
The physical model of the upper respiratory tract ow eld in this study was obtained from the experimental goats. Experimental studies need to be undertaken at the same time to determine the mechanical features of soft tissue in upper respiratory tract of our people. Based on it, the multi-eld coupling analysis, more perfect uid solid coupling numerical model and multi-scale multi-angle analysis can be performed in succession. Micro-structure discussion can be reached on the basis of macro examination to further understand the pathogenesis of OSAHS.