CYBERMED PNRR I9 Grant No. 760018/27.01.2023

CYBERMED- Cyber-medical solution for drug delivery systems using fractional calculus

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Research grant awarded by the Romanian Ministry of Research, Innovation and Digitization, PNRR-III-C9-2022 – I9, grant number 760018/27.01.2023

SUMMARY

A patient’s well-being during/after surgery is drastically affected by the application of general anaesthesia and maintenance of anesthetic and hemodynamic variables within safe ranges. Closed loop control of the anesthesia-hemodynamic system has been shown to decrease the risks for over/underdosing, but a complete multivariable control has not yet been fully considered. The proposal attempts to offer such a solution. To account for the challenges brought by modeling uncertainties, patient intra and intervariability, a novel approach that consists in the design of a multivariable fractional order robust control strategy for the entire anesthesia-hemodynamic system will be developed. The aim of the proposal consists then in: develop specific fractional order models for anesthesia components, integrate these with a personalized multivariable hemodynamic model, design a robust multivariable control algorithm to tackle model uncertainties, efficiently reject disturbances and decrease subsystem interactions. The overall objective consists in developing a standalone user-friendly software cyber-medical system for open/closed loop tests/ analysis for drug deliveryto raise awareness and acceptance among clinicians.

Potential impact of the cyber-medical system (open/closed-loop patient simulator) for combined AHS control during surgery is both direct (open/closed loop testing in anaesthesia-hemodynamic drug delivery issues), offers improved understanding of the anaesthesia-hemodynamic paradigm in closed loop control and indirect (leads to improved patient safety, better-trained clinical staff, reduced costs for drug dosing). The most significant result is the development of a model for analgesia. The quantification of pain using a pain index is novel and was modelled in correlation with the dose of the opioid drug administered to a patient. The development of such a pain index and its correlation to the opioid drug dosage is possible thanks to dedicated devices that measure skin impedance or conductance. This pain index represents an element of novelty in relation to the current state, ensuring the possibility of approaching automatic control in anesthesia from a multivariable perspective. From this perspective, the impact of the obtained results can be significant, opening the way to new approaches and solutions in the automatic control of anesthesia.

PROJECT OBJECTIVES

1) The development of a simplified, but suitable model of analgesic drug diffusion into the human body based on novel ideas of fractional order impedance models (FOIM); 2)  The integration of the analgesia model with models of hypnosis and neuromuscular blockade in order to obtain a fully interactive anaesthesia environment;3)  The integration of anaesthesia with the hemodynamic system and surgical stimulus, acting as a disturbance; 4)  The development of novel robust fractional order control (FOC) methodologies to tackle the interactions of this complex environment.

EXPECTED RESULT INDICATORS AND DELIVERABLES

  • Minimum of 3 Q1 journal papers (i.e. ISA Transactions, Fractal and Fractional, IEEE Trans. Control Systems Technology, Journal of Advanced Research, etc.) 4 Web of Science conference papers (IEEE Int. Conf. on Systems, Man, and Cybernetics 2023, 2024; IEEE Conf. on Control Technology and Applications 2023, 2024; European Control Conference 2023, 2024; American Control Conference 2024, etc).
  • 1 researcher C. Muresan working in research centers receiving support (full-time equivalent)
  • 1 proposal as a follow-up to be submitted to European Union Horizon research programs

CURRENT RESULT INDICATORS AND DELIVERABLES

  • 1 researcher C. Muresan working in research centers receiving support (full-time equivalent)
  • 1 grant proposal submitted in the 2023 call for HORIZON-MSCA-2023-DN-01 (MSCA Doctoral Networks 2023), Proposal Number: 101168471, Proposal acronym: moTIVAte, Proposal Title: Multi drug Optimisation Total IntraVenous Anesthesia with Tangible Exposition
  • 2 Q1 journal papers (published), 1 Q2 journal paper (published), 3 Q1 journal papers (under review), 1 book chapter, 3 Web of Science conference papers (Published), 4 Web of Science conference papers (accepted, 2024). For more details, see below.
  • 2 Q1 journal papers (Published)

M. Ghita, I.R. Birs, D. Copot, C.I. Muresan, M. Neckebroek, C.M. Ionescu (2023) Parametric modeling and deep learning for enhancing pain assessment in postanesthesia, IEEE Transactions on Biomedical Engineering, vol. 70(10), pp. 2991-3002, doi: 10.1109/TBME.2023.3274541 (revistă ISI Q1, factor de impact 4.6)

C.I. Muresan, I.R. Birs (2023), Fractional order control for unstable first order processes with time delays, Fractional Calculus and Applied Analytics, doi: 10.1007/s13540-024-00301-4 (revistă ISI Q1, factor de impact 3)

  • 3 Q1 journal papers (under review, major revisions)

C.I. Muresan, E. Hegedus, M. Mihai, I. R. Birs, D. Copot, E.H. Dulf, R. De Keyser, C. M. Ionescu, M. Neckebroek (2024), Fractional Order Modeling of the Depth of Analgesia for Control Purposes, Fractal and Fractional,  în recenzie (revistă ISI Q1, factor de impact 5.4)

Erwin T. Hegedüs, Isabela R. Birs, Clara M. Ionescu, Cristina I. Muresan (2024), An optimal decentralized-decoupled fractional order control strategy for complete anesthesia-hemodynamic stabilization in patients undergoing surgical procedures, Fractal and Fractional,  în recenzie (revistă ISI Q1, factor de impact 5.4)

R. De Keyser, I.R. Birs, C.I. Muresan, C.M. Ionescu (2023), Process information extraction for controller tuning from minimal datasets with low excitatory content, ISA Transactions, în recenzie major revisions (revistă ISI Q1, factor de impact 7.3)

  • 1 Q2 journal paper (Published)

C.M. Ionescu, D. Copot, E. Yumuk, R. De Keyser, C.I. Muresan, I.R. Birs, G. Ben Otham, H. Farbakhsh, A.R. Ynineb, M. Neckebroek(2023), Development, validation and comparison of a novel nociception/anti-nociception monitor against two commercial monitors in general anesthesia, Sensors, (revistă ISI Q2, factor de impact 3.9)

  • 1 book chapter (Springer)

Muresan, C.I., Hegedus, E.T., Mihai, M., Birs, I.R. (2023). Analysis of a Robust Fractional Order Multivariable Controller for Combined Anesthesia and Hemodynamic Stabilization. In: Pinto, C.M., Ionescu, C.M. (eds) Computational and Mathematical Models in Biology. Nonlinear Systems and Complexity, vol 38. Springer, Cham. https://doi.org/10.1007/978-3-031-42689-6_11

  • 3 Web of Science conference papers (Published)

M. Ghita, D. Copot, I. Birs, C. Muresan, M. Neckebroek, C. Ionescu (2023), Modelling of Blood Loss Influence on Propofol Concentrations and Anesthetic States in Critical Response, 2023 American Control Conference (ACC), San Diego, CA, USA, 2023, pp. 2216-2221, doi: 10.23919/ACC55779.2023.10156356 (conferință indexată ISI proceedings)

I. Birs, C. Muresan, M. Ghita, M. Ghita, I. Nascu, C. Ionescu (2023), Event-based fractional order MIMO control for hemodynamic stabilization during general anesthesia, 2023 IEEE Conference on Systems, Man, and Cybernetics, October 1-4, 2023, Honolulu, Oahu, Hawaii, USA (conferință indexată ISI proceedings)

E. Hegedus, M. Ghita, I.R. Birs, D. Copot, C.I. Muresan (2023), Robustness analysis of a multivariable fractional order controller for the hemodynamic variables in anesthetized patients, 2023 European Control Conference (ECC), Bucharest, Romania, 2023, pp. 1-6, doi: 10.23919/ECC57647.2023.10178146 (conferință indexată ISI proceedings)

  • 4 Web of Science conference papers (Accepted, 2024)

T. Popescu, I.R. Birs, G. Ben Othman, E. Yumuk, M. Mihai, E. Hegedus, D. Copot, R. De Keyser, C.M. Ionescu, C.I. Muresan, Uncertainty and Its Effect On Optimal Multidrug Control of Hemodynamic Variables, 2024 American Control Conference, July 8-12, 2024, Toronto, Canada, acceptata (conferință indexată ISI proceedings)

E. Hegedus, M.D. Mihai, I.R. Birs, H. Farbakhsh, E. Yumuk, D. Copot, R. De Keyser, C.M. Ionescu, C.I. Muresan, A Decoupled Fractional Order Control Strategy to increase patient safety during Anesthesia-Hemodynamic Interactions, 2024 European Control Conference, 25-28 June 2024, Stockholm, Sweden, acceptata (conferință indexată ISI proceedings)

M. Mihai, I. Birs, H. Erwin, D. Copot, M. Neckebroek, R. De Keyser, C.M. Ionescu, C.I. Muresan, A compact fractional-order model for hypnosis in general anesthesia, 12th IFAC Conference on Fractional Differentiation and its Applications, Bordeaux, France, July 9-12, 2024, acceptata (conferință indexată ISI proceedings)

A. R. Ynineb, H. Farbakhsh, G. Ben Othman, Y. Wahlquist, I. R. Birs, E. Yumuk, C. I. Muresan, R. De Keyser, D. Copot, C. M. Ionescu and M. Neckebroek (2024), Comparative Analysis of Pharmacokinetic-Pharmacodynamic Models for Propofol and Remifentanil Using Model Predictive Control, 2024 European Control Conference, 25-28 June 2024, Stockholm, Sweden, acceptat (conferință indexată ISI proceedings)