Jiang, Zhihao
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Publication Computer Aided Clinical Trials for Implantable Cardiac Devices(2018-07-12) Jang, Kuk Jin; Weimer, James; Abbas, Houssam; Jiang, Zhihao; Liang, Jackson; Dixit, Sanjay; Mangharam, RahulIn this paper we aim to answer the question, ``How can modeling and simulation of physiological systems be used to evaluate life-critical implantable medical devices?'' Clinical trials for medical devices are becoming increasingly inefficient as they take several years to conduct, at very high cost and suffer from high rates of failure. For example, the Rhythm ID Goes Head-to-head Trial (RIGHT) sought to evaluate the performance of two arrhythmia discriminator algorithms for implantable cardioverter defibrillators, Vitality 2 vs. Medtronic, in terms of time-to-first inappropriate therapy, but concluded with results contrary to the initial hypothesis - after 5 years, 2,000+ patients and at considerable ethical and monetary cost. In this paper, we describe the design and performance of a computer-aided clinical trial (CACT) for Implantable Cardiac Devices where previous trial information, real patient data and closed-loop device models are effectively used to evaluate the trial with high confidence. We formulate the CACT in the context of RIGHT using a Bayesian statistical framework. We define a hierarchical model of the virtual cohort generated from a physiological model which captures the uncertainty in the parameters and allows for the systematic incorporation of information available at the design of the trial. With this formulation, the CACT estimates the inappropriate therapy rate of Vitality 2 compared to Medtronic as 33.22% vs 15.62% (pPublication Automated Closed-Loop Model Checking of Implantable Pacemakers using Abstraction Trees(2016-03-16) Jiang, Zhihao; Abbas, Houssam; Mosterman, Pieter; Mangharam, RahulAutonomous medical devices such as implantable cardiac pacemakers are capable of diagnosing the patient condition and delivering therapy without human intervention. Their ability to autonomously affect the physiological state of the patient makes them safety-critical. Sufficient evidence for the safety and efficacy of the device software, which makes these autonomous decisions, should be provided before these devices can be released on the market. Formal methods like model checking can provide safety evidence that the devices can safely operate under a large variety of physiological conditions. The challenge is to develop physiological models that are general enough to cover the large variability of human physiology, and also expressive enough to provide physiological contexts to counter-examples returned by the model checker. In this paper, the authors develop a set of physiological abstraction rules that introduce physiological constraints to heart models. By applying these abstraction rules to a initial set of heart models, an abstraction tree is created. The root model covers all possible inputs to a pacemaker and derived models cover inputs from different heart conditions. If a counter-example is returned by the model checker, the abstraction tree is traversed so that the most concrete counter-example(s) with physiological contexts can be returned to the domain experts for validity check. The abstraction tree framework replaces the manual abstraction and refinement framework, which reduced the amount of domain knowledge required to perform closed-loop model checking. It encourages the use of model checking during the development of autonomous medical devices, and identifies safety risks earlier in the design process.Publication The Challenges of High-Confidence Medical Device Software(2015-11-12) Jiang, Zhihao; Abbas, Houssam; Jang, Kuk Jin; Mangharam, RahulPublication Towards Model Checking of Implantable Cardioverter Defibrillators(2016-03-03) Abbas, Houssam; Jang, Kuk Jin; Jiang, Zhihao; Mangharam, RahulVentricular Fibrillation is a disorganized electrical excitation of the heart that results in inadequate blood flow to the body. It usually ends in death within a minute. A common way to treat the symptoms of fibrillation is to implant a medical device, known as an Implantable Cardioverter Defibrillator (ICD), in the patient's body. Model-based verification can supply rigorous proofs of safety and efficacy. In this paper, we build a hybrid system model of the human heart+ICD closed loop, and show it to be a STORMED system, a class of o-minimal hybrid systems that admit finite bisimulations. In general, it may not be possible to compute the bisimulation. We show that approximate reachability can yield a finite simulation for STORMED systems, and that certain compositions respect the STORMED property. The results of this paper are theoretical and motivate the creation of concrete model checking procedures for STORMED systems.Publication High-Level Modeling for Computer-Aided Clinical Trials of Medical Devices(2016-08-16) Abbas, Houssam; Jiang, Zhihao; Jang, Kuk Jin; Beccani, Marco; Liang, Jackson; Dixit, Sanjay; Mangharam, RahulPublication Computer Aided Clinical Trials for Implantable Cardiac Devices(2016-08-19) Abbas, Houssam; Jiang, Zhihao; Jang, Kuk Jin; Beccani, Marco; Liang, Jackson; Dixit, Sanjay; Mangharam, RahulIn this effort we investigate the design and use of physiological and device models to conduct pre-clinical trials to provide early insight in the design and execution of the actual clinical trial. Computer models of physiological phenomena like cardiac electrical activity can be extremely complex. However, when the purpose of the model is to interact with a medical device, then it becomes sufficient to model the measurements that the device makes, e.g. the intra-cardiac electrograms (EGMs) that an Implantable Cardioverter Defibrillator (ICD) measures. We present a probabilistic generative model of EGMs, capable of generating exemplars of various arrhythmias. The model uses deformable shape templates, or motifs, to capture the variability in EGM shapes within one EGM channel, and a cycle length parameter to capture the variability in cycle length in one EGM channel. The relation between EGM channels, which is essential for determining whether the current arrhythmia is potentially fatal, is captured by a time-delayed Markov chain, whose states model the various combinations of (learned) motifs. The heart model is minimally parameterized and is learned from real patient data. Thus the statistics of key features reflect the statistics of a real cohort, but the model can also generate rare cases and new combinations from the inferred probabilities. On the device end, algorithms for signal sensing, detection and discrimination for major ICD manufacturers have been implemented both in simulation and on hardware platforms. The generated arrhythmia episodes are used as input to both the modeled ICD algorithms and real ICDs as part of a Computer Aided Clinical Trial (CACT). In a CACT, a computer model simulates the inputs to the device (such as a new, investigational ICD), and the device’s performance is evaluated. By incorporating these results into the appropriate statistical framework, the Computer Aided Clinical Trial results can serve as regulatory evidence when planning and executing an actual clinical trial. We demonstrate this by conducting a mock trial similar to the 2005-2010 RIGHT trial which compared the discrimination algorithms from two major ICD manufacturers. The results of the CACT clearly demonstrate that the failed outcome of the RIGHT trial could have been predicted and provides statistical support for deeper results that could have been captured prior to the trial.Publication Technical Report: Abstraction-Tree For Closed-loop Model Checking of Medical Devices(2015-05-06) Jiang, Zhihao; Abbas, Houssam; Mosterman, Pieter J; Mangharam, Rahul