Jiang, Zhihao

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Now showing 1 - 10 of 25
  • 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, Rahul
    In 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% (p
  • Publication
    Heart-on-a-Chip: A Closed-loop Testing Platform for Implantable Pacemakers
    (2014-07-02) Jiang, Zhihao; Radhakrishnan, Sriram; Sampath, Varun; Sarode, Shilpa; Mangharam, Rahul
    Implantable cardiac pacemakers restore normal heart rhythm by delivering external electrical pacing to the heart. The pacemaker software is life-critical as the timing of the pulses determine its ability to control the heart rate. Recalls due to software issues have been on the rise with the increasing complexity of pacing algorithms. Open-loop testing remains the primary approach to evaluate the safety of pacemaker software. While this tests how the pacemaker responds to stimulus, it cannot reveal pacemaker malfunctions which drive the heart into an unsafe state over multiple cycles. To evaluate the safety and efficacy of pacemaker software we have developed a heart model to generate different heart conditions and interact with real pacemakers. In this paper, we introduce the closed-loop testing platform which consists of a programmable hardware implementation of the heart that can interact with a commercial pacemaker in closed-loop. The heart-on-a-chip implementation is automatically generated from the Virtual Heart Model in Simulink which models different heart conditions. We describe a case study of Endless Loop Tachycardia to demonstrate potential closed-loop pacemaker malfunctions which inappropriately increase the heart rate. The test platform is part of our model-based design framework for verification and testing of medical devices with the patient--in-the-loop.
  • Publication
    Model-Based Conformance Testing for Implantable Pacemakers
    (2013-07-31) Chen, George; Jiang, Zhihao; Mangharam, Rahul
  • Publication
    Cyber-Physical Modeling of Implantable Cardiac Medical Devices
    (2011-12-29) Jiang, Zhihao; Pajic, Miroslav; Mangharam, Rahul
    The design of bug-free and safe medical device software is challenging, especially in complex implantable devices that control and actuate organs in unanticipated contexts. Safety recalls of pacemakers and implantable cardioverter defibrillators between 1990 and 2000 affected over 600,000 devices. Of these, 200,000 or 41%, were due to firmware issues and their effect continues to increase in frequency. There is currently no formal methodology or open experimental platform to test and verify the correct operation of medical device software within the closed-loop context of the patient. To this effect, a real-time Virtual Heart Model (VHM) has been developed to model the electrophysiological operation of the functioning and malfunctioning (i.e., during arrhythmia) heart. By extracting the timing properties of the heart and pacemaker device, we present a methodology to construct a timed-automata model for functional and formal testing and verification of the closed-loop system. The VHM's capability of generating clinically-relevant response has been validated for a variety of common arrhythmias. Based on a set of requirements, we describe a closed-loop testing environment that allows for interactive and physiologically relevant model-based test generation for basic pacemaker device operations such as maintaining the heart rate, atrial-ventricle synchrony and complex conditions such as pacemaker-mediated tachycardia. This system is a step toward a testing and verification approach for medical cyber-physical systems with the patient-in-the-loop.
  • Publication
    Real-time Heart Model for Implantable Cardiac Device Validation and Verification
    (2010-01-20) Jiang, Zhihao; Pajic, Miroslav; Connolly, Allison T; Dixit, Sanjay; Mangharam, Rahul
    Designing bug-free medical device software is dif- ficult, especially in complex implantable devices that may be used in unanticipated contexts. Safety recalls of pacemakers and implantable cardioverter defibrillators due to firmware problems between 1990 and 2000 affected over 200,000 devices, comprising 41% of the devices recalled and are increasing in frequency. There is currently no formal methodology or open experimental platform to validate and verify the correct operation of medical device software. To this effect, a real-time Virtual Heart Model (VHM) has been developed to model the electrophysiological operation of the functioning (i.e. during normal sinus rhythm) and malfunctioning (i.e. during arrhythmia) heart. We present a methodology to extract timing properties of the heart to construct a timed-automata model. The platform exposes functional and formal interfaces for validation and verification of implantable cardiac devices. We demonstrate the VHM is capable of generating clinically-relevant response to intrinsic (i.e. premature stimuli) and external (i.e. artificial pacemaker) signals for a variety of common arrhythmias. By connecting the VHM with a pacemaker model, we are able to pace and synchronize the heart during the onset of irregular heart rhythms. The VHM has also been implemented on a hardware platform for closed-loop experimentation with existing and virtual medical devices. The VHM allows for exploratory electrophysiology studies for physicians to evaluate their diagnosis and determine the appropriate device therapy. This integrated functional and formal device design approach will potentially help expedite medical device certification for safer operation.
  • Publication
    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, Rahul
    In 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
  • Publication
    Requirement-Guided Model Refinement
    (2014-12-02) Jiang, Zhihao; Mosterman, Pieter; Mangharam, Rahul
    Medical device is a typical Cyber-Physical System and ensuring the safety and efficacy of the device requires closed-loop verification. Currently closed-loop verifications of medical devices are performed in the form of clinical trials in which the devices are tested on the patients.
  • Publication
    The Challenges of High-Confidence Medical Device Software
    (2015-11-12) Jiang, Zhihao; Abbas, Houssam; Jang, Kuk Jin; Mangharam, Rahul
  • Publication
    Towards Model Checking of Implantable Cardioverter Defibrillators
    (2016-03-03) Abbas, Houssam; Jang, Kuk Jin; Jiang, Zhihao; Mangharam, Rahul
    Ventricular 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.