Performance Analysis of Extracted Rule-Base Multivariable Type-2 Self-Organizing Fuzzy Logic Controller Applied to Anesthesia

We compare type-1 and type-2 self-organizing fuzzy logic controller (SOFLC) using expert initialized and pretrained extracted rule-bases applied to automatic control of anaesthesia during surgery. We perform experimental simulations using a nonfixed patient model and signal noise to account for environmental and patient drug interaction uncertainties. The simulations evaluate the performance of the SOFLCs in their ability to control anesthetic delivery rates for maintaining desired physiological set points for muscle relaxation and blood pressure during a multistage surgical procedure. The performances of the SOFLCs are evaluated by measuring the steady state errors and control stabilities which indicate the accuracy and precision of control task. Two sets of comparisons based on using expert derived and extracted rule-bases are implemented as Wilcoxon signed-rank tests. Results indicate that type-2 SOFLCs outperform type-1 SOFLC while handling the various sources of uncertainties. SOFLCs using the extracted rules are also shown to outperform those using expert derived rules in terms of improved control stability

Closed-loop control of anesthesia : survey on actual trends, challenges and perspectives

Automation empowers self-sustainable adaptive processes and personalized services in many industries. The implementation of the integrated healthcare paradigm built on Health 4.0 is expected to transform any area in medicine due to the lightning-speed advances in control, robotics, artificial intelligence, sensors etc. The two objectives of this article, as addressed to different entities, are: i) to raise awareness throughout the anesthesiologists about the usefulness of integrating automation and data exchange in their clinical practice for providing increased attention to alarming situations, ii) to provide the actualized insights of drug-delivery research in order to create an opening horizon towards precision medicine with significantly improved human outcomes. This article presents a concise overview on the recent evolution of closed-loop anesthesia delivery control systems by means of control strategies, depth of anesthesia monitors, patient modelling, safety systems, and validation in clinical trials. For decades, anesthesia control has been in the midst of transformative changes, going from simple controllers to integrative strategies of two or more components, but not achieving yet the breakthrough of an integrated system. However, the scientific advances that happen at high speed need a modern review to identify the current technological gaps, societal implications, and implementation barriers. This article provides a good basis for control research in clinical anesthesia to endorse new challenges for intelligent systems towards individualized patient care. At this connection point of clinical and engineering frameworks through (semi-) automation, the following can be granted: patient safety, economical efficiency, and clinicians' efficacy

Control Strategy for Anaesthetic Drug Dosage with Interaction Among Human Physiological Organs Using Optimal Fractional Order PID Controller

This is the author accepted manuscript. The final version is available from IEEE via the DOI in this record.In this paper, an efficient control strategy for physiological interaction based anaesthetic drug infusion model is explored using the fractional order (FO) proportional integral derivative (PID) controllers. The dynamic model is composed of several human organs by considering the brain response to the anaesthetic drug as output and the drug infusion rate as the control input. Particle Swarm Optimisation (PSO) is employed to obtain the optimal set of parameters for PID/FOPID controller structures. With the proposed FOPID control scheme much less amount of drug-infusion system can be designed to attain a specific anaesthetic target and also shows high robustness for +/-50% parametric uncertainty in the patient's brain model

An open source patient simulator for design and evaluation of computer based multiple drug dosing control for anesthetic and hemodynamic variables

We are witnessing a notable rise in the translational use of information technology and control systems engineering tools in clinical practice. This paper empowers the computer based drug dosing optimization of general anesthesia management by means of multiple variables for patient state stabilization. The patient simulator platform is designed through an interdisciplinary combination of medical, clinical practice and systems engineering expertise gathered in the last decades by our team. The result is an open source patient simulator in Matlab/Simulink from Mathworks(R). Simulator features include complex synergic and antagonistic interaction aspects between general anesthesia and hemodynamic stabilization variables. The anesthetic system includes the hypnosis, analgesia and neuromuscular blockade states, while the hemodynamic system includes the cardiac output and mean arterial pressure. Nociceptor stimulation is also described and acts as a disturbance together with predefined surgery profiles from a translation into signal form of most commonly encountered events in clinical practice. A broad population set of pharmacokinetic and pharmacodynamic (PKPD) variables are available for the user to describe both intra- and inter-patient variability. This simulator has some unique features, such as: i) additional bolus administration from anesthesiologist, ii) variable time-delays introduced by data window averaging when poor signal quality is detected, iii) drug trapping from heterogeneous tissue diffusion in high body mass index patients. We successfully reproduced the clinical expected effects of various drugs interacting among the anesthetic and hemodynamic states. Our work is uniquely defined in current state of the art and first of its kind for this application of dose management problem in anesthesia. This simulator provides the research community with accessible tools to allow a systematic design, evaluation and comparison of various control algorithms for multi-drug dosing optimization objectives in anesthesia

Advanced Signal Processing and Control in Anaesthesia

This thesis comprises three major stages: classification of depth of anaesthesia (DOA); modelling a typical patient’s behaviour during a surgical procedure; and control of DOAwith simultaneous administration of propofol and remifentanil. Clinical data gathered in theoperating theatre was used in this project. Multiresolution wavelet analysis was used to extract meaningful features from the auditory evoked potentials (AEP). These features were classified into different DOA levels using a fuzzy relational classifier (FRC). The FRC uses fuzzy clustering and fuzzy relational composition. The FRC had a good performance and was able to distinguish between the DOA levels. A hybrid patient model was developed for the induction and maintenance phase of anaesthesia. An adaptive network-based fuzzy inference system was used to adapt Takagi-Sugeno-Kang (TSK) fuzzy models relating systolic arterial pressure (SAP), heart rate (HR), and the wavelet extracted AEP features with the effect concentrations of propofol and remifentanil. The effect of surgical stimuli on SAP and HR, and the analgesic properties of remifentanil were described by Mamdani fuzzy models, constructed with anaesthetist cooperation. The model proved to be adequate, reflecting the effect of drugs and surgical stimuli. A multivariable fuzzy controller was developed for the simultaneous administration of propofol and remifentanil. The controller is based on linguistic rules that interact with three decision tables, one of which represents a fuzzy PI controller. The infusion rates of the two drugs are determined according to the DOA level and surgical stimulus. Remifentanil is titrated according to the required analgesia level and its synergistic interaction with propofol. The controller was able to adequately achieve and maintain the target DOA level, under different conditions. Overall, it was possible to model the interaction between propofol and remifentanil, and to successfully use this model to develop a closed-loop system in anaesthesia

Dynamic contrast enhanced (DCE) MRI estimation of vascular parameters using knowledge-based adaptive models

We introduce and validate four adaptive models (AMs) to perform a physiologically based Nested-Model-Selection (NMS) estimation of such microvascular parameters as forward volumetric transfer constant, K(trans), plasma volume fraction, v(p), and extravascular, extracellular space, v(e), directly from Dynamic Contrast-Enhanced (DCE) MRI raw information without the need for an Arterial-Input Function (AIF). In sixty-six immune-compromised-RNU rats implanted with human U-251 cancer cells, DCE-MRI studies estimated pharmacokinetic (PK) parameters using a group-averaged radiological AIF and an extended Patlak-based NMS paradigm. One-hundred-ninety features extracted from raw DCE-MRI information were used to construct and validate (nested-cross-validation, NCV) four AMs for estimation of model-based regions and their three PK parameters. An NMS-based a priori knowledge was used to fine-tune the AMs to improve their performance. Compared to the conventional analysis, AMs produced stable maps of vascular parameters and nested-model regions less impacted by AIF-dispersion. The performance (Correlation coefficient and Adjusted R-squared for NCV test cohorts) of the AMs were: 0.914/0.834, 0.825/0.720, 0.938/0.880, and 0.890/0.792 for predictions of nested model regions, v(p), K(trans), and v(e), respectively. This study demonstrates an application of AMs that quickens and improves DCE-MRI based quantification of microvasculature properties of tumors and normal tissues relative to conventional approaches

Heuristic modeling of macromolecule release from PLGA microspheres

Dissolution of protein macromolecules from poly(lactic-co-glycolic acid) (PLGA) particles is a complex process and still not fully understood. As such, there are difficulties in obtaining a predictive model that could be of fundamental significance in design, development, and optimization for medical applications and toxicity evaluation of PLGA-based multiparticulate dosage form. In the present study, two models with comparable goodness of fit were proposed for the prediction of the macromolecule dissolution profile from PLGA micro- and nanoparticles. In both cases, heuristic techniques, such as artificial neural networks (ANNs), feature selection, and genetic programming were employed. Feature selection provided by fscaret package and sensitivity analysis performed by ANNs reduced the original input vector from a total of 300 input variables to 21, 17, 16, and eleven; to achieve a better insight into generalization error, two cut-off points for every method was proposed. The best ANNs model results were obtained by monotone multi-layer perceptron neural network (MON-MLP) networks with a root-mean-square error (RMSE) of 15.4, and the input vector consisted of eleven inputs. The complicated classical equation derived from a database consisting of 17 inputs was able to yield a better generalization error (RMSE) of 14.3. The equation was characterized by four parameters, thus feasible (applicable) to standard nonlinear regression techniques. Heuristic modeling led to the ANN model describing macromolecules release profiles from PLGA microspheres with good predictive efficiency. Moreover genetic programming technique resulted in classical equation with comparable predictability to the ANN model

Predictive modelling of Loss Of Consciousness under general anaesthesia

Treballs Finals de Grau d'Enginyeria Biomèdica. Facultat de Medicina i Ciències de la Salut. Universitat de Barcelona. Curs: 2021-2022. Director: Pedro L. Gambú