Closed-Loop Quantitative Verification of Rate-Adaptive Pacemakers

Rate-adaptive pacemakers are cardiac devices able to automatically adjust the pacing rate in patients with chronotropic incompetence, i.e. whose heart is unable to provide an adequate rate at increasing levels of physical, mental or emotional activity. These devices work by processing data from physiological sensors in order to detect the patient’s activity and update the pacing rate accordingly. Rate-adaptation parameters depend on many patient-specific factors, and effective personalisation of such treatments can only be achieved through extensive exercise testing, which is normally intolerable for a cardiac patient. In this work, we introduce a data-driven and model-based approach for the automated verification of rate-adaptive pacemakers and formal analysis of personalised treatments. To this purpose, we develop a novel dual-sensor pacemaker model where the adaptive rate is computed by blending information from an accelerometer, and a metabolic sensor based on the QT interval. Our approach enables personalisation through the estimation of heart model parameters from patient data (electrocardiogram), and closed-loop analysis through the online generation of synthetic, model-based QT intervals and acceleration signals. In addition to personalisation, we also support the derivation of models able to account for the varied characteristics of a virtual patient population, thus enabling safety verification of the device. To capture the probabilistic and non-linear dynamics of the heart, we define a probabilistic extension of timed I/O automata with data and employ statistical model checking for quantitative verification of rate modulation. We evaluate our rate-adaptive pacemaker design on three subjects and a pool of virtual patients, demonstrating the potential of our approach to provide rigorous, quantitative insights into the closed-loop behaviour of the device under different exercise levels and heart conditions

European governance challenges in bio-engineering : making perfect life : bio-engineering (in) the 21st century : final report

In the STOA project Making Perfect Life four fields were studied of 21st century bio-engineering: engineering of living artefacts, engineering of the body, engineering of the brain, and engineering of intelligent artefacts. This report describes the main results of the project. It shows how developments in the four fields of bio-engineering are shaped by two megatrends: "biology becoming technology" and "technology becoming biology". These developments result in a broadening of the bio-engineering debate in our society. The report addresses the long term views that are inspiring this debate and discusses a multitude of ethical, legal and social issues that arise from bio-engineering developments in the fields described. Against this background four specific developments are studied in more detail: the rise of human genome sequencing, the market introduction of neurodevices, the capturing by information technology of the psychological and physiological states of users, and the pursuit of standardisation in synthetic biology. These developments are taken in this report as a starting point for an analysis of some of the main European governance challenges in 21st century bio-engineering

European governance challenges in bio-engineering : making perfect life : bio-engineering (in) the 21st century : final report

In the STOA project Making Perfect Life four fields were studied of 21st century bio-engineering: engineering of living artefacts, engineering of the body, engineering of the brain, and engineering of intelligent artefacts. This report describes the main results of the project. It shows how developments in the four fields of bio-engineering are shaped by two megatrends: "biology becoming technology" and "technology becoming biology". These developments result in a broadening of the bio-engineering debate in our society. The report addresses the long term views that are inspiring this debate and discusses a multitude of ethical, legal and social issues that arise from bio-engineering developments in the fields described. Against this background four specific developments are studied in more detail: the rise of human genome sequencing, the market introduction of neurodevices, the capturing by information technology of the psychological and physiological states of users, and the pursuit of standardisation in synthetic biology. These developments are taken in this report as a starting point for an analysis of some of the main European governance challenges in 21st century bio-engineering