Predictive Virtual Patient Modelling of Mechanical Ventilation: Impact of Recruitment Function

Mechanical ventilation is a life-support therapy for intensive care patients suffering from respiratory failure. To reduce the current rate of ventilator-induced lung injury requires ventilator settings that are patient-, time-, and disease-specific. A common lung protective strategy is to optimise the level of positive end-expiratory pressure (PEEP) through a recruitment manoeuvre to prevent alveolar collapse at the end of expiration and to improve gas exchange through recruitment of additional alveoli. However, this process can subject parts of the lung to excessively high pressures or volumes. This research significantly extends and more robustly validates a previously developed pulmonary mechanics model to predict lung mechanics throughout recruitment manoeuvres. In particular, the process of recruitment is more thoroughly investigated and the impact of the inclusion of expiratory data when estimating peak inspiratory pressure is assessed. Data from the McREM trial and CURE pilot trial were used to test model predictive capability and assumptions. For PEEP changes of up to and including 14 cmH2O, the parabolic model was shown to improve peak inspiratory pressure prediction resulting in less than 10% absolute error in the CURE cohort and 16% in the McREM cohort. The parabolic model also better captured expiratory mechanics than the exponential model for both cohorts

Methods of system identification, parameter estimation and optimisation applied to problems of modelling and control in engineering and physiology

Mathematical and computer-based models provide the foundation of most methods of engineering design. They are recognised as being especially important in the development of integrated dynamic systems, such as “control-configured” aircraft or in complex robotics applications. These models usually involve combinations of linear or nonlinear ordinary differential equations or difference equations, partial differential equations and algebraic equations. In some cases models may be based on differential algebraic equations. Dynamic models are also important in many other fields of research, including physiology where the highly integrated nature of biological control systems is starting to be more fully understood. Although many models may be developed using physical, chemical, or biological principles in the initial stages, the use of experimentation is important for checking the significance of underlying assumptions or simplifications and also for estimating appropriate sets of parameters. This experimental approach to modelling is also of central importance in establishing the suitability, or otherwise, of a given model for an intended application – the so-called “model validation” problem. System identification, which is the broad term used to describe the processes of experimental modelling, is generally considered to be a mature field and classical methods of identification involve linear discrete-time models within a stochastic framework. The aspects of the research described in this thesis that relate to applications of identification, parameter estimation and optimisation techniques for model development and model validation mainly involve nonlinear continuous time models Experimentally-based models of this kind have been used very successfully in the course of the research described in this thesis very in two areas of physiological research and in a number of different engineering applications. In terms of optimisation problems, the design, experimental tuning and performance evaluation of nonlinear control systems has much in common with the use of optimisation techniques within the model development process and it is therefore helpful to consider these two areas together. The work described in the thesis is strongly applications oriented. Many similarities have been found in applying modelling and control techniques to problems arising in fields that appear very different. For example, the areas of neurophysiology, respiratory gas exchange processes, electro-optic sensor systems, helicopter flight-control, hydro-electric power generation and surface ship or underwater vehicles appear to have little in common. However, closer examination shows that they have many similarities in terms of the types of problem that are presented, both in modelling and in system design. In addition to nonlinear behaviour; most models of these systems involve significant uncertainties or require important simplifications if the model is to be used in a real-time application such as automatic control. One recurring theme, that is important both in the modelling work described and for control applications, is the additional insight that can be gained through the dual use of time-domain and frequency-domain information. One example of this is the importance of coherence information in establishing the existence of linear or nonlinear relationships between variables and this has proved to be valuable in the experimental investigation of neuromuscular systems and in the identification of helicopter models from flight test data. Frequency-domain techniques have also proved useful for the reduction of high-order multi-input multi-output models. Another important theme that has appeared both within the modelling applications and in research on nonlinear control system design methods, relates to the problems of optimisation in cases where the associated response surface has many local optima. Finding the global optimum in practical applications presents major difficulties and much emphasis has been placed on evolutionary methods of optimisation (both genetic algorithms and genetic programming) in providing usable methods for optimisation in design and in complex nonlinear modelling applications that do not involve real-time problems. Another topic, considered both in the context of system modelling and control, is parameter sensitivity analysis and it has been found that insight gained from sensitivity information can be of value not only in the development of system models (e.g. through investigation of model robustness and the design of appropriate test inputs), but also in feedback system design and in controller tuning. A technique has been developed based on sensitivity analysis for the semi-automatic tuning of cascade and feedback controllers for multi-input multi-output feedback control systems. This tuning technique has been applied successfully to several problems. Inverse systems also receive significant attention in the thesis. These systems have provided a basis for theoretical research in the control systems field over the past two decades and some significant applications have been reported, despite the inherent difficulties in the mathematical methods needed for the nonlinear case. Inverse simulation methods, developed initially by others for use in handling-qualities studies for fixed-wing aircraft and helicopters, are shown in the thesis to provide some important potential benefits in control applications compared with classical methods of inversion. New developments in terms of methodology are presented in terms of a novel sensitivity based approach to inverse simulation that has advantages in terms of numerical accuracy and a new search-based optimisation technique based on the Nelder-Mead algorithm that can handle inverse simulation problems involving hard nonlinearities. Engineering applications of inverse simulation are presented, some of which involve helicopter flight control applications while others are concerned with feed-forward controllers for ship steering systems. The methods of search-based optimisation show some important advantages over conventional gradient-based methods, especially in cases where saturation and other nonlinearities are significant. The final discussion section takes the form of a critical evaluation of results obtained using the chosen methods of system identification, parameter estimation and optimisation for the modelling and control applications considered. Areas of success are highlighted and situations are identified where currently available techniques have important limitations. The benefits of an inter-disciplinary and applications-oriented approach to problems of modelling and control are also discussed and the value in terms of cross-fertilisation of ideas resulting from involvement in a wide range of applications is emphasised. Areas for further research are discussed

A forward model-based analysis of cardiovascular system identification methods

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2000.Includes bibliographical references (p. 211-221).Cardiovascular system identification is a potentially powerful approach for intelligent patient monitoring of cardiovascular function. Rather than merely recording hemodynamic signals, the signals are mathematically analyzed so as to provide a dynamical characterization of the physiologic mechanisms responsible for generating them. The fundamental aim of this thesis is to develop and evaluate cardiovascular system identification methods based on a test bed of data generated from a forward model of the cardiovascular system whose dynamical properties are known. To this end, we developed a computer model of the human cardiovascular system which includes a lumped parameter model of the heart and circulation and a model of the short-term cardiovascular regulatory system continuously disturbed by resting physiologic perturbations. The short-term regulatory system consists of arterial and cardiopulmonary baroreflex systems and a direct neural coupling mechanism between respiration and heart rate. The resting physiologic perturbations include respiratory activity and stochastic disturbances to total peripheral resistance (TPR) and heart rate representing, for example, autoregulation of local vascular beds and higher brain center activity. We demonstrated that this model emulates experimental data in terms of steady-state pulsatility, limiting static behavior, and low frequency hemodynamic variability. We first evaluated the performance of a previously developed cardiovascular system identification method against the forward model.(cont.) The method involves the analysis of fluctuations in heart rate, arterial blood pressure (ABP), and instantaneous lung volume in order to characterize quantitatively important physiologic mechanisms including, for example, the heart rate baroreflex. From this analysis, we inferred that the cardiovascular system identification results derived from experimental data are likely to reflect the actual system dynamics of underlying physiologic mechanisms. We then introduced novel identification methods for quantifying TPR baroreflex dynamics from only fluctuations in cardiac output and ABP and for monitoring steady-state changes in TPR from only the ABP waveform. We demonstrated the efficacy f these identification methods with respect to forward model generated data and a preliminary set of experimental data. The results of this forward model-based analysis motivate the experimental validation of the cardiovascular system identification methods considered in this thesis.by Ramakrishna Mukkamala.Ph.D