国人上呼吸道系统生物力学模型研究与临床应用
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摘要
睡眠呼吸障碍性疾病与上呼吸道结构性狭窄密切相关,由于发病率高、危害严重,已成为一个突出的医疗与公共卫生问题,其中以阻塞性睡眠呼吸暂停低通气综合征(Obstructive sleep apnea/hypopnea syndrome, OSAHS)的危害最大。要深刻认知这类与上呼吸道结构异常相关的疾患,需对气道解剖结构与功能之间的交互关系进行定量分析。然而,由于患者的个体差异性和上呼吸道结构形态异常的多样性,给这方面的研究带来了困难。本文针对OSAHS的发病机制和个性化诊疗等临床研究中急需解决的问题,基于计算流体动力学(Computational fluid dynamics, CFD)和流固耦合(Fluid structure interaction, FSI)方法,开展上呼吸道系统生物力学模型的研究,并采集临床观测数据来验证分析方法的可行性和结果的可信性,为深入了解与疾病相关的气道结构与功能的关系,提供了数值量化分析的平台。主要内容包括：
1.根据健康志愿者多层螺旋CT影像学资料,构造较大样本的上呼吸道三维模型。研究四种湍流模型对上呼吸道气流特性的影响,并将得到的计算结果与文献报道的实验和数值模拟数据进行比较,验证本文分析方法的可行性和计算结果的可信性。通过16例健康志愿者上呼吸道气体动力学特性的分析,总结正常气道内气流分布的规律,为进行结构异常的上呼吸道生物力学特性研究奠定基础。
2.针对成人和儿童患者几种典型的手术治疗方案,对手术前后上呼吸道内气流的速度、压强和气道阻力的变化进行定量分析。通过与临床诊断OSAHS的金标准一多导睡眠监测仪(Polysomnograph, PSG)和儿童常规的鼻咽声反射(Acoustic rhinometryAR)的结果进行对比,验证了数值模拟的结果对疗效评估的可靠性。上呼吸道生物力学特性的数值模拟研究能获得常规临床检查无法测得的量化参数,为术式的优选和疗效的评估提供参考依据。
3.对3例伴有鼻阻塞的OSAHS患者行鼻腔结构矫正手术前后上呼吸道的气流特性与软腭的运动姿态进行对比分析,为研究鼻腔结构在OSAHS发病机制中的作用,以及鼻部手术对OSAHS的治疗效果提供定量的依据。数值模拟结果发现,鼻腔结构的矫正与容积的扩大缓解了两例轻度患者上呼吸道的阻塞情况。但对另一例重度患者,尽管术后鼻阻塞的情况得以缓解,但整个上呼吸道气流的速度、压强降和软腭的位移均高于术前,尤其是腭咽区负压的增大对病情的缓解不利。根据获得的力学参数对上呼吸道通气功能进行评估,与PSG的判定和患者的主诉相一致。由于人上呼吸道结构的个体差异性,以及气道结构与气流环境之间复杂的自适应关系,对于不同的上呼吸道结构,鼻阻塞的减轻对整个上呼吸道阻塞情况的影响各不相同。提示临床医生在制定手术方案时,务必对上呼吸道上(鼻腔)、下部分(咽和喉)的一致性和复杂的相关性进行个性化的综合考量。
4.为全面了解OSAHS的发病机理及其与呼吸系统疾病的内在联系,进行异常气道结构对上呼吸道、气管和各级支气管内气流特性影响的研究。由于OSAHS患者腭咽腔的狭窄,使得气管和各级支气管内气流的速度和压强降均高于正常气道。受支气管结构异常的影响,除气管和各级支气管的气流结构发生明显变化之外,上呼吸道的压强降有所升高,尤其在呼气相。此外,分析不同呼吸路线(鼻腔呼吸、鼻腔与口腔共同呼吸作用)对气流结构的影响,揭示张口呼吸加重气道塌陷和阻塞的原因。大量气流经由口腔吸入和呼出时,会导致气道阻力的重新分配,鼻腔阻力大幅降低,而口腔及其以下气道的阻力反而增大。
Sleep-disordered breathing, which is closely related to narrow upper airway, has been a prominent and important clinical and public health issues concerning high prevalence and serious perniciousness. The most potentially dangerous sleep-disordered breathing is obstructive sleep apnea/hypopnea syndrome (OSAHS). It is necessary to perform quantitative analysis on the airway structure-function interaction in order to understand thoroughly these upper respiratory tract diseases associated with structural abnormalities. In this paper, biomechanical model of upper respiratory system, which focus on the pathogenesis and individual care planning problems of OSAHS, are researched based on the computational fluid dynamics (CFD) and fluid structure interaction (FSI) methods to conquer the difficulties of individual differences and structure complexity of the upper respiratory tract. The numerical simulation model is reconstructed on the basis of the feasibility of analytical methods and computational results by comparing with the clinical and experimental data. The simulation results provide a platform of numerical and quantitative analysis for the interrelation between airway structure and function. The main contents are as follows:
1. Based on the multidetector computed tomogram (MDCT) images of volunteers without any respiratory diseases, accurate anatomical models of the upper airway are developed. After comparing the numerical results of four different turbulence models with the experimental data of recent documents, a rational and reliable calculating method is determined for predictions of the flow field distribution of upper airway. The characteristics of flow structures within the normal upper respiratory tract based on sixteen healthy volunteers are summarized as solid groundwork for subsequent biomechanical characteristics investigation on abnormal upper airway.
2. Upper airway models of adults and children are reconstructed aiming at simulating typical surgery schedules. The particular quantitative analysis of velocity, pressure, and airway resistance in preoperative and postoperative upper airway models are performed. The comparison of simulation results and the clinical measurements by polysomnograph (PSG) and acoustic rhinometry (AR) indicates that the ventilation condition evaluated by computational simulation is consistent with the results of clinical measurements. The biomechanical quantitative parameter of the upper respiratory tract, which is not accessible by routine clinical measurements, can provide quantitative reference basis for preferred surgical option and treatment evaluation.
3. The airflow characteristics of the upper respiratory tract and movement of the soft palates in the pre-and post-nasal surgery models in three patients with nasal airway obstruction and OSAHS, provide quantitative basis for the investigation of the exact role of the nasal airway in the pathogenesis of OSAHS and the effect of nasal surgery alone on OSAHS. Numerical simulation results show that two models of mild OSAHS patients demonstrated significant ventilation improved phenomenon after the correction of nasal structure and expansion of nasal volume. Although the nasal obstruction relief after the nasal surgery for the patient with severe OSAHS, the airflow characteristics, such as velocity and pressure, the displacements of soft palates, especially the negative pressure of velopharynx are higher than those in preoperative model. The assessment of respiratory function according to available indicators by numerical simulation is consistent with that of the PSG results. Because of the individual differences in human upper airway and the complex adaptive relationship between the airway structure and air environment, distinct effects of the relief of nasal airway obstruction on airway ventilation for different upper respiratory tract, the surgical program should be established according to individual and comprehensive consideration of the consistency and complex relativity between the upper part and the lower part of the upper respiratory tract.
4. The investigation on the effect of abnormal airway structure on the airflow characteristics can provide quantitative basis for comprehensive understanding of the pathogenesis of OSAHS and the inherent relationship between OSAHS with respiratory diseases. As a result of velopharyngeal stenosis, the airflow velocity and pressure drop in respiratory tract of OSAHS patients are much higher than that in normal model. For the structural abnormalities of the bronchial, in addition to the airflow characteristics of the the trachea and bronchi change significantly, the pressure drop of the upper airway increases mainly in the expiratory phase. Besides, the influences of different breathing modes (nasal breathing and combined oral-nasal breathing) on the flow characteristics are investigated to reveal the reason of increased risk of upper airway collapse and obstruction brought by mouth breathing. A dramatical increase of oral airflow leads to the redistribution of airway resistance, the significantly reduced nasal resistance and also the increased airway resistance in the airway below the oral cavity.
1.根据健康志愿者多层螺旋CT影像学资料,构造较大样本的上呼吸道三维模型。研究四种湍流模型对上呼吸道气流特性的影响,并将得到的计算结果与文献报道的实验和数值模拟数据进行比较,验证本文分析方法的可行性和计算结果的可信性。通过16例健康志愿者上呼吸道气体动力学特性的分析,总结正常气道内气流分布的规律,为进行结构异常的上呼吸道生物力学特性研究奠定基础。
2.针对成人和儿童患者几种典型的手术治疗方案,对手术前后上呼吸道内气流的速度、压强和气道阻力的变化进行定量分析。通过与临床诊断OSAHS的金标准一多导睡眠监测仪(Polysomnograph, PSG)和儿童常规的鼻咽声反射(Acoustic rhinometryAR)的结果进行对比,验证了数值模拟的结果对疗效评估的可靠性。上呼吸道生物力学特性的数值模拟研究能获得常规临床检查无法测得的量化参数,为术式的优选和疗效的评估提供参考依据。
3.对3例伴有鼻阻塞的OSAHS患者行鼻腔结构矫正手术前后上呼吸道的气流特性与软腭的运动姿态进行对比分析,为研究鼻腔结构在OSAHS发病机制中的作用,以及鼻部手术对OSAHS的治疗效果提供定量的依据。数值模拟结果发现,鼻腔结构的矫正与容积的扩大缓解了两例轻度患者上呼吸道的阻塞情况。但对另一例重度患者,尽管术后鼻阻塞的情况得以缓解,但整个上呼吸道气流的速度、压强降和软腭的位移均高于术前,尤其是腭咽区负压的增大对病情的缓解不利。根据获得的力学参数对上呼吸道通气功能进行评估,与PSG的判定和患者的主诉相一致。由于人上呼吸道结构的个体差异性,以及气道结构与气流环境之间复杂的自适应关系,对于不同的上呼吸道结构,鼻阻塞的减轻对整个上呼吸道阻塞情况的影响各不相同。提示临床医生在制定手术方案时,务必对上呼吸道上(鼻腔)、下部分(咽和喉)的一致性和复杂的相关性进行个性化的综合考量。
4.为全面了解OSAHS的发病机理及其与呼吸系统疾病的内在联系,进行异常气道结构对上呼吸道、气管和各级支气管内气流特性影响的研究。由于OSAHS患者腭咽腔的狭窄,使得气管和各级支气管内气流的速度和压强降均高于正常气道。受支气管结构异常的影响,除气管和各级支气管的气流结构发生明显变化之外,上呼吸道的压强降有所升高,尤其在呼气相。此外,分析不同呼吸路线(鼻腔呼吸、鼻腔与口腔共同呼吸作用)对气流结构的影响,揭示张口呼吸加重气道塌陷和阻塞的原因。大量气流经由口腔吸入和呼出时,会导致气道阻力的重新分配,鼻腔阻力大幅降低,而口腔及其以下气道的阻力反而增大。
Sleep-disordered breathing, which is closely related to narrow upper airway, has been a prominent and important clinical and public health issues concerning high prevalence and serious perniciousness. The most potentially dangerous sleep-disordered breathing is obstructive sleep apnea/hypopnea syndrome (OSAHS). It is necessary to perform quantitative analysis on the airway structure-function interaction in order to understand thoroughly these upper respiratory tract diseases associated with structural abnormalities. In this paper, biomechanical model of upper respiratory system, which focus on the pathogenesis and individual care planning problems of OSAHS, are researched based on the computational fluid dynamics (CFD) and fluid structure interaction (FSI) methods to conquer the difficulties of individual differences and structure complexity of the upper respiratory tract. The numerical simulation model is reconstructed on the basis of the feasibility of analytical methods and computational results by comparing with the clinical and experimental data. The simulation results provide a platform of numerical and quantitative analysis for the interrelation between airway structure and function. The main contents are as follows:
1. Based on the multidetector computed tomogram (MDCT) images of volunteers without any respiratory diseases, accurate anatomical models of the upper airway are developed. After comparing the numerical results of four different turbulence models with the experimental data of recent documents, a rational and reliable calculating method is determined for predictions of the flow field distribution of upper airway. The characteristics of flow structures within the normal upper respiratory tract based on sixteen healthy volunteers are summarized as solid groundwork for subsequent biomechanical characteristics investigation on abnormal upper airway.
2. Upper airway models of adults and children are reconstructed aiming at simulating typical surgery schedules. The particular quantitative analysis of velocity, pressure, and airway resistance in preoperative and postoperative upper airway models are performed. The comparison of simulation results and the clinical measurements by polysomnograph (PSG) and acoustic rhinometry (AR) indicates that the ventilation condition evaluated by computational simulation is consistent with the results of clinical measurements. The biomechanical quantitative parameter of the upper respiratory tract, which is not accessible by routine clinical measurements, can provide quantitative reference basis for preferred surgical option and treatment evaluation.
3. The airflow characteristics of the upper respiratory tract and movement of the soft palates in the pre-and post-nasal surgery models in three patients with nasal airway obstruction and OSAHS, provide quantitative basis for the investigation of the exact role of the nasal airway in the pathogenesis of OSAHS and the effect of nasal surgery alone on OSAHS. Numerical simulation results show that two models of mild OSAHS patients demonstrated significant ventilation improved phenomenon after the correction of nasal structure and expansion of nasal volume. Although the nasal obstruction relief after the nasal surgery for the patient with severe OSAHS, the airflow characteristics, such as velocity and pressure, the displacements of soft palates, especially the negative pressure of velopharynx are higher than those in preoperative model. The assessment of respiratory function according to available indicators by numerical simulation is consistent with that of the PSG results. Because of the individual differences in human upper airway and the complex adaptive relationship between the airway structure and air environment, distinct effects of the relief of nasal airway obstruction on airway ventilation for different upper respiratory tract, the surgical program should be established according to individual and comprehensive consideration of the consistency and complex relativity between the upper part and the lower part of the upper respiratory tract.
4. The investigation on the effect of abnormal airway structure on the airflow characteristics can provide quantitative basis for comprehensive understanding of the pathogenesis of OSAHS and the inherent relationship between OSAHS with respiratory diseases. As a result of velopharyngeal stenosis, the airflow velocity and pressure drop in respiratory tract of OSAHS patients are much higher than that in normal model. For the structural abnormalities of the bronchial, in addition to the airflow characteristics of the the trachea and bronchi change significantly, the pressure drop of the upper airway increases mainly in the expiratory phase. Besides, the influences of different breathing modes (nasal breathing and combined oral-nasal breathing) on the flow characteristics are investigated to reveal the reason of increased risk of upper airway collapse and obstruction brought by mouth breathing. A dramatical increase of oral airflow leads to the redistribution of airway resistance, the significantly reduced nasal resistance and also the increased airway resistance in the airway below the oral cavity.
引文
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