Analog Computer Simulation of Maximum Expiratory Flow Limitation

This paper extends previous modeling work in our laboratory on the simulation of the panting maneuver executed in a body plethysmograph [8] to the simulation of a wider range of pulmonary function tests and, in particular, the maximum expiratory flow-volume (MEFV) curve. The simulation is implemented on an analog computer for ease of parameter manipulation; the effects of changes in several model parameters (such as large and small airway resistance, and airway and lung compliance) on the MEFV curve are discussed. The model structure presented here is much simpler than the ventilatory system models of Fry [6] and Pardaens et al. [18], and yet yields the same information in a diagnostic sense.     

Estimating lung mechanics of dogs with unilateral lung injury

Extended least-squares algorithms using transpulmonary pressure and airway flow data from ventilatory waveforms were studied for their ability to track parameters of one- and two-compartment models of lung mechanics. A recursive extended least-squares algorithm with discounted measures estimated parameters of discrete-time models during synchronized intermittent mandatory ventilation. In tests on seven dogs developing oleic acid-induced unilateral hemorrhagic pulmonary edema, the one-compartment estimator responded rapidly and appropriately to changes in mechanics: compliance fell to 0.55 +/- 0.15 of its initial value and resistance rose by a factor of 1.8 +/- 0.5 in 3 h following injection of oleic acid. One-compartment parameter estimates revealed a difference between the airway resistance of inspiration and expiration. Two-compartment estimates were seldom physiologically plausible. The difference between inspiratory and expiratory resistance may have caused the two-compartment estimator to fail when applied to data from the entire respiratory cycle; when only expiratory data were used for estimation, the two-compartment estimates were meaningful. These estimates demonstrated increasing lung inhomogeneity after oleic acid was injected; at the end of 3 h, the ratio of the time constants of the two compartments ranged from 5 to 20 in six of the seven dogs. We conclude that the one- and two-compartment estimates may be combined to provide a meaningful assessment of lung mechanics.     

Automated Spectral Characterization of Wheezing in Asthmatic Children

Breath sounds were recorded in normal and asthmatic children over the chest and trachea. The power spectra of the sounds were analyzed for peaks of high amplitude and high frequency as indications of wheezing. The percent of inspiration and expiration spent wheezing was used as an indication of the severity of bronchial obstruction. Wheezing was found to be strongly dependent upon air flow, and generally followed the changes in pulmonary function as indicated by the forced expiratory volume at 1 s (FEV1). The trachea was found to be a better location for analyzing wheezes than the lung.     

An Instrument for the Accurate Measurement of MEFV Parameters

An instrument which measures maximally forced expiratory airflow directly, computes its integral (lung volume decrement ), and interrupts the storage oscilloscope display of this flow-volume trajectory at fixed but adjustable intervals of time is described. This new device is portable and does not involve bellows or a water-filled canister.     

The change in initial lung volume during exercise

The lung volumes from which inhalation and exhalation proceed change during exercise. There have been previous attempts to predict these lung volumes but none have been completely successful. Prediction of initial lung volume is important in the accurate calculation of respiratory power during exercise, especially when the subject is encumbered with respiratory protective apparatus and exercising above the anaerobic threshold. Although there is no direct work advantage to varying lung volumes at the beginning of inspiration or expiration, such changes appear to be dictated by the asymmetry of lung recoil pressure about the lung relaxation volume. Equalizing inspiratory and expiratory elastic pressures has been found to match available data on lung initial volume     

Mathematical Modeling of Pulmonary Airway Dynamics

A mathematical model has been derived that describes the pressure-flow relationship in the ventilatory system under conditions of constant lung volume. The parameters of the model include small airway resistance, large airway resistance, and lung elastic recoil. A collapsible airway segment is included to model compression of the airways during expiration.     

Sensitivity of Breath-to-Breath Gas Exchange Measurements to Expiratory Flow Errors

During expiration, fluctuations in gas composition, water vapor, and temperature result in flowmeter errors when the flowmeter is calibrated for a given ambient inspiratory gas. In this paper, we indicate that alternative analytical methods of caleulating breath-to-breath gas exchange exhibit differing sensitivities to this error. A theoretical sensitivity analysis is verified by O2 consumption records from rest to exhausting exercise. We conclude that an error sensitivity of less than one is achieved by a method that incorporates measurements of nitrogen flow into and out of the lung, and includes the analysis of breath-to-breath changes in lung volume.     

Equivalent Circuit Analysis of High-Frequency Ventilators Including a New High-Impedance Flow-Interrupting Ventilator

The small tidal volumes (VT) delivered to the lungs by highfrequency ventilators can be very sensitive to changes in the patient's respiratory mechanics. Analysis of a Thevenin equivalent circuit, consisting of a ventilator internal oscillatory pressure source in series with a ventilator internal impedance and a patient's respiratory impedance, reveals the need of a high-internal-impedance ventilator to minimize this VT sensitivity problem. We present a general methodology to estimate the internal impedance of any type of ventilator. The internal impedance, at a given frequency and flow setting, is calculated from the slope of the relationship between the generated peak-to-peak pressure and the VT delivered into a calibrated rigid tank through a varying constriction. We tested a typical high-frequency jet (HFJ) ventilator and a new high-impedance flow-interrupting (HIFI) ventilator consisting of a flow source, a rotary valve, a high-impedance expiratory tube, and a servocontrolled mean proximal airway pressure (MPAP) regulator. We found that the VT delivered by the HIFI ventilator was independent of MPAP and decreased by 12 percent after a fivefold increase in the constriction-tank system impedance. In contrast, the VT delivered by the HFJ ventilator decreased by 80 percent after a similar change in load. We therefore conclude that the VT delivered by the HIFI ventilator should be significantly less sensitive to changes in patient's respiratory impedance than the VT delivered by an HFJ ventilator.     

Development of a time-cycled volume-controlled pressure-limited respirator and lung mechanics system for total liquid ventilation

Total liquid ventilation can support gas exchange in animal models of lung injury. Clinical application awaits further technical improvements and performance verification. Our aim was to develop a liquid ventilator, able to deliver accurate tidal volumes, and a computerized system for measuring lung mechanics. The computer-assisted, piston-driven respirator controlled ventilatory parameters that were displayed and modified on a real-time basis. Pressure and temperature transducers along with a lineal displacement controller provided the necessary signals to calculate lung mechanics. Ten newborn lambs (<6 days old) with respiratory failure induced by lung lavage, were monitored using the system. Electromechanical, hydraulic, and data acquisition/analysis components of the ventilator were developed and tested in animals with respiratory failure. All pulmonary signals were collected synchronized in time, displayed in real-time, and archived on digital media. The total mean error (due to transducers, analog-to-digital conversion, amplifiers, etc.) was less than 5% compared with calibrated signals. Components (tubing, pistons, etc.) in contact with exchange fluids were developed so that they could be readily switched, a feature that will be important in clinical settings. Improvements in gas exchange and lung mechanics were observed during liquid ventilation, without impairment of cardiovascular profiles. The total liquid ventilator maintained accurate control of tidal volumes and the sequencing of inspiration/expiration. The computerized system demonstrated its ability to monitor in vivo lung mechanics, providing valuable data for early decision making.     

Cerebrospinal fluid flow in the normal and hydrocephalic human brain

Advances in magnetic resonance (MR) imaging techniques enable the accurate measurements of cerebrospinal fluid (CSF) flow in the human brain. In addition, image reconstruction tools facilitate the collection of patient-specific brain geometry data such as the exact dimensions of the ventricular and subarachnoidal spaces (SAS) as well as the computer-aided reconstruction of the CSF-filled spaces. The solution of the conservation of CSF mass and momentum balances over a finite computational mesh obtained from the MR images predict the patients' CSF flow and pressure field. Advanced image reconstruction tools used in conjunction with first principles of fluid mechanics allow an accurate verification of the CSF flow patters for individual patients. This paper presents a detailed analysis of pulsatile CSF flow and pressure dynamics in a normal and hydrocephalic patient. Experimental CSF flow measurements and computational results of flow and pressure fields in the ventricular system, the SAS and brain parenchyma are presented. The pulsating CSF motion is explored in normal and pathological conditions of communicating hydrocephalus. This paper predicts small transmantle pressure differences between lateral ventricles and SASs (approximately 10 Pa). The transmantle pressure between ventricles and SAS remains small even in the hydrocephalic patient (approximately 30 Pa), but the ICP pulsatility increases by a factor of four. The computational fluid dynamics (CFD) results of the predicted CSF flow velocities are in good agreement with Cine MRI measurements. Differences between the predicted and observed CSF flow velocities in the prepontine area point towards complex brain-CSF interactions. The paper presents the complete computational model to predict the pulsatile CSF flow in the cranial cavity.     

基于隐含模式的异常检测算法

如何检测系统中的临界变化,一直是一个难题。该文提供了一种新的基于隐含模式的异常检测算法。机是一种新的计算力学理论,它能从时间序列中发掘系统的隐含模式。因果态分割重建算法(CSSR)是目前重构机的最成熟算法,它可以推理出一个因果态集合,所有的因果态构成一个隐马尔可夫模型。在因果态集合的基础上,建立一个表达系统特征的向量,不同向量间的距离可以定义成系统异常的测度。把时间序列分段,分别计算每部分的异常度,就可以得到系统的异常演变曲线。在Duffing振子的例子中,该算法不仅有效检测,还提前预测到系统分叉的发生,说明该算法具有很好的应用潜力。     

Assessment of Changes in Upper Airway Obstruction by Automatic Identification of Inspiratory Flow Limitation During Sleep

New techniques for automatic invasive and noninvasive identification of inspiratory flow limitation (IFL) are presented. Data were collected from 11 patients with full nocturnal polysomnography and gold-standard esophageal pressure (Pes) measurement. A total of 38,782 breaths were extracted and automatically analyzed. An exponential model is proposed to reproduce the relationship between Pes and airflow of an inspiration and achieve an objective assessment of changes in upper airway obstruction. The characterization performance of the model is appraised with three evaluation parameters: mean-squared error when estimating resistance at peak pressure, coefficient of determination, and assessment of IFL episodes. The model's results are compared to the two best-performing models in the literature. The obtained gold-standard IFL annotations were then employed to train, test, and validate a new noninvasive automatic IFL classification system. Discriminant analysis, support vector machines, and Adaboost algorithms were employed to objectively classify breaths noninvasively with features extracted from the time and frequency domains of the breathspsila flow patterns. The results indicated that the exponential model characterizes IFL and subtle relative changes in upper airway obstruction with the highest accuracy and objectivity. The new noninvasive automatic classification system also succeeded in identifying IFL episodes, achieving a sensitivity of 0.87 and a specificity of 0.85.     

Active MEMS-based flow control using artificial neural network

These last years several research works have studied the application of Micro-Electro-Mechanical Systems (MEMS) for aerodynamic active flow control. Controlling such MEMS-based systems remains a challenge. Among the several existing control approaches for time varying systems, many of them use a process model representing the dynamic behavior of the process to be controlled. The purpose of this paper is to study the suitability of an artificial neural network first to predict the flow evolution induced by MEMS, and next to optimize the flow w.r.t. a numerical criterion. To achieve this objective, we focus on a dynamic flow over a backward facing step where MEMS actuators velocities are adjusted to maximize the pressure over the step surface. The first effort has been to establish a baseline database provided by computational fluid dynamics simulations for training the neural network. Then we investigate the possibility to control the flow through MEMS configuration changes. Results are promising, despite slightly high computational times for real time application.     

新的功能有机薄膜中的分子识别研究

本文应用AFM及力曲线的统计方法并结合分子力学计算方法研究了具有不同官能团的两种酞菁分子的LB膜及聚丙烯基梯形高分子、它的有机纳米管及其超分子系列薄膜的分子识别。力曲线的统计方法提供了有价值的信息,理论计算结果能够成为识别功能有机分子的重要依据。     

A computer controller for vest cardiopulmonary resuscitation (CPR)

The authors recently developed a cardiopulmonary resuscitation (CPR) technique in which the airways are obstructed automatically during each chest wall compression. Energy loss accompanying air convection from the lungs during chest wall compression is limited so lung volume and intrathoracic pressures are increased. This technique required the development of a simple controller device to govern the pressure applied to ribcage and abdominal vests together with controller airflow at the airway opening. Experiments with the controller device on eight mongrel dogs showed that cardiac output increased obstructed expiratory cardiopulmonary resuscitation (OECPR) by 19% relative to the cardiac output during standard vest CPR (61% of the prearrest cardiac output relative to 24%, respectively). Furthermore, the OECPR technique without adjunct ventilation resolved the hypocapnic respiratory alkalosis that developed during the standard vest CPR with no ventilatory support. The authors give background information on the obstructed expiratory vest CPR and describe the controller device for delivering this CPR method     

On-Line Measurement of Airway Closing Volume

An on-line real-time program for measurement of airway closing volume has been developed, using the Lab-8/e (PDP-8/e) computer. The paper describes the procedure for measurement of airway closing volume and the program which was developed. The program in addition to measuring airway closing volume also measures the alveolar plateau volume, and the slopes of the alveolar plateau and the closing volume excursion. The program operates in conjunction with the Digital Equipment Corporation Pulmonary Test System.     

Rule-based detection of intrathoracic airway trees

New sensitive and reliable methods for assessing alterations in regional lung structure and function are critically important for the investigation and treatment of pulmonary diseases. Accurate identification of the airway tree will provide an assessment of airway structure and will provide a means by which multiple volumetric images of the lung at the same lung volume over time can be used to assess regional parenchymal changes. The authors describe a novel rule-based method for the segmentation of airway trees from three-dimensional (3-D) sets of computed tomography (CT) images, and its validation. The presented method takes advantage of a priori anatomical knowledge about pulmonary airway and vascular trees and their interrelationships. The method is based on a combination of 3-D seeded region growing that is used to identify large airways, rule-based two-dimensional (2-D) segmentation of individual CT slices to identify probable locations of smaller diameter airways, and merging of airway regions across the 3-D set of slices resulting in a tree-like airway structure. The method was validated in 40 3-mm-thick CT sections from five data sets of canine lungs scanned via electron beam CT in vivo with lung volume held at a constant pressure. The method's performance was compared with that of the conventional 3-D region growing method. The method substantially outperformed an existing conventional approach to airway tree detection.     

Estimation of Mechanical Parameters in Multicompartment Models Applied to Normal and Obstructed Lungs During Tidal Breathing

A technique is presented which allows quantitative assessment of the use of parallel compartment models for characterizing pulmonary mechanical function during tidal breathing. A model consisting of a conducting airway leading to two parallel parenchymal regions is used. Numerical simulation and sensitivity analysis indicated that a) the compliance of the conducting airway was not significant under the experimental conditions of interest and that b) estimates of the distribution of central and peripheral resistances would not be precise. The techniques were demonstrated using measurements of transpulmonary pressure, flow, and volume changes during tidal breathing obtained from a human subject with normal lungs and a human subject with obstructed lungs. Optimal estimates of the parameters were obtained by minimizing the difference between the model output and experimental data combined from two breathing frequencies. In the estimation procedure, the sum of the peripheral compliances was constrained to equal the independently measured static lung compliance. This constraint was critical for correct evaluation of nonuniform mechanical lung function. From the parameter estimates, the ratio of parenchymal time constants was about five in the subject with normal lungs and 60 in the subject with obstructed lungs. These results suggest that a full study with several normal and obstructed lung subjects is warranted.     

Relations Between Fractional-Order Model Parameters and Lung Pathology in Chronic Obstructive Pulmonary Disease

In this study, changes in respiratory mechanics from healthy and chronic obstructive pulmonary disease (COPD) diagnosed patients are observed from identified fractional-order (FO) model parameters. The noninvasive forced oscillation technique is employed for lung function testing. Parameters on tissue damping and elastance are analyzed with respect to lung pathology and additional indexes developed from the identified model. The observations show that the proposed model may be used to detect changes in respiratory mechanics and offers a clear-cut separation between the healthy and COPD subject groups. Our conclusion is that an FO model is able to capture changes in viscoelasticity of the soft tissue in lungs with disease. Apart from this, nonlinear effects present in the measured signals were observed and analyzed via signal processing techniques and led to supporting evidence in relation to the expected phenomena from lung pathology in healthy and COPD patients.      

Programmable Melt Electrowriting to Engineer Soft Connective Tissues with Prescribed,Biomimetic, Biaxial Mechanical Properties

Appropriate load-bearing function of soft connective tissues is provided by their nonlinear and often anisotropic mechanics. Recapitulating such complex mechanical behavior in tissue-engineered structures is particularly crucial, as deviation from native tissue mechanics can trigger pathological biomechanical pathways, causing adverse tissue remodeling and dysfunction. Here, a novel method combining computational modeling, melt electrowriting (MEW), and design of experiments (DOE) is reported to generate scaffolds composed of sinusoidal fibers with prescribed biaxial mechanical properties, recapitulating the distinct nonlinear, anisotropic stress–strain behavior of three model tissues: adult aortic valve, pediatric pulmonary valve, and pediatric pericardium. Finite element analysis is used to efficiently optimize scaffold architecture over a broad parameter space, representing up to 65 conditions, to define MEW print parameters to achieve polycaprolactone scaffolds with target mechanical properties. Architectural parameters are further optimized experimentally using DOE and regression to account for uncertainties involved in the simulation, yielding functional scaffolds with accurate, prescribed mechanics. The prescribed architecture also primarily governs the mechanics of hybrid structures generated by casting cell-laden fibrin hydrogel within the scaffolds. This high-fidelity approach recapitulates biaxial mechanical properties over a broad range of mechanical nonlinearity and anisotropy and is generalizable for programmed biofabrication in a variety of tissue engineering applications.