This project represents a cross-disciplinary collaborative research effort on developing rigorous, closed-loop approaches for designing, simulating, and verifying medical devices. The work will open fundamental new approaches for radically accelerating the pace of medical device innovation, especially in the sphere of cardiac-device design. Specific attention will be devoted to developing advanced formal methods-based approaches for analyzing controller designs for safety and effectiveness; and devising methods for expediting regulatory and other third-party reviews of device designs. The project team includes members with research backgrounds in computer science, electrical engineering, biophysics, and cardiology; the PIs will use a coordinated approach that balances theoretical, experimental and practical concerns to yield results that are intended to transform the practice of device design while also facilitating the translation of new cardiac therapies into practice. The proposed effort will lead to significant advances in the state of the art for system verification and cardiac therapies based on the use of formal methods and closed-loop control and verification. The animating vision for the work is to enable the development of a true in silico design methodology for medical devices that can be used to speed the development of new devices and to provide greater assurance that their behaviors match designers' intentions, and to pass regulatory muster more quickly so that they can be used on patients needing their care. The scientific work being proposed will serve this vision by providing mathematically robust techniques for analyzing and verifying the behavior of medical devices, for modeling and simulating heart dynamics, and for conducting closed-loop verification of proposed therapeutic approaches. The acceleration in medical device innovation achievable as a result of the proposed research will also have long-term and sustained societal benefits, as better diagnostic and therapeutic technologies enter into the practice of medicine more quickly. It will also yield a collection of tools and techniques that will be applicable in the design of other types of devices. Finally, it will contribute to the development of human resources and the further inclusion of under-represented groups via its extensive education and outreach programs, including intensive workshop experiences for undergraduates.

Modern medical devices increasingly incorporate connectivity mechanisms that offer the potential to integrate devices via network/middleware technology into larger systems of cooperating devices. Initial integration efforts in the industry are focused on streaming device data into electronic health records and integrating information from multiple devices into single customizable displays. This proposal provides a research foundation for engineering and verification of these safety critical systems through creating an open source Medical Device Coordination Framework (MDCF) which includes: 1)middleware for integrating medical devices and electronic health records, and 2) a model-based development environment that implements medical device coordination applications (apps for short), enabling a systems of systems paradigm for medical devices. The project has substantial broader impact via tools and techniques for verifying the integration of medical systems that are compatible with the Integrated Clinical Environment standard. In addition, the proposer includes extensive interaction with FDA specialists who are looking to transition these methods into their validation and verification processes for their regulatory mission.

Advances in technology mean that computer-controlled physical devices that currently still require human operators, such as automobiles, trains, airplanes, and medical treatment systems, could operate entirely autonomously and make rational decisions on their own. Autonomous cars and drones are a concrete and highly publicized face of this dream. Before this dream can be realized we must address the need for safety - the guaranteed absence of undesirable behaviors emerging from autonomy. Highly publicized technology accidents such as rocket launch failures, uncontrolled exposure to radiation during treatment, aircraft automation failures and unintended automotive accelerations serve as warnings of what can happen if safety is not adequately addressed in the design of such cyber-physical systems. One approach for safety analysis is the use of software tools that apply formal logic to prove the absence of undesired behavior in the control software of a system. In prior work, this approach this been proven to work for simple controller software that is generated automatically by tools from abstract models like Simulink diagrams. However, autonomous decision making requires more complex software that is able to solve optimization problems in real time. Formal verification of control software that includes such optimization algorithms remains an unmet challenge. The project SORTIES (Semantics of Optimization for Real Time Intelligent Embedded Systems) draws upon expertise in optimization theory, control theory, and computer science to address this challenge. Beginning with the convergence properties of convex optimization algorithms, SORTIES examines how these properties can be automatically expressed as inductive invariants for the software implementation of the algorithms, and then incorporates these properties inside the source code itself as formal annotations which convey the underlying reasoning to the software engineer and to existing computer-aided verification tools. The SORTIES goal is an open-source-semantics-carrying autocoder, which takes an optimization algorithm and its convergence properties as input, and produces annotated, verifiable code as output. The demonstration of the tool on several examples, such as a Mars lander, an aircraft avionics system, and a jet engine controller, shows that the evidence of quality produced by annotations is fully compatible with its application to truly functional products. Project research is integrated with education through training of "tri-lingual" professionals, who are equally conversant in system operation, program analysis, and the theory of control and optimization.

Stroke is the leading cause of long-term disability in the US with approximately 7 million stroke survivors living in the US today and for patients with neurological disorders, it has been shown that limited gait velocity commonly results in walking that is predominantly restricted to the household. Unlike traditional exoskeletons which contain rigid linkage elements, the vision for this work is for exosuits that use soft materials such as textiles to provide a more conformal, unobtrusive and compliant means to interface to the human body. This represents a fundamental change in the paradigm of how people have viewed and designed wearable robots for the last half a century. Such a solution would have broad impact beyond the stroke patient population and could provide benefit to children with Cerebral Palsy or elderly individuals with muscle weakness. In addition there are plans to create a set of novel instructional educational toolkits for patient-in-the-loop cyber-physical systems that will be shared via an online portal and the CPS Virtual Organization (CPS-VO). With a patient-in-the-loop CPS, the patient, the physical suit, the computational control algorithms and the task/environment form a system in which all of the elements need to seamlessly interact. Through a modeling and experimental approach involving extensive human subjects studies, the team aims to create a unified engineering, biomechanical and physiological framework for designing and evaluating patient-in-the-loop CPS that include co-operative controllers that adapt in real-time to the patient to ensure safety and reliability an integrated system. Specifically the project will seek to gain a fundamental understanding of how to (1) analytically and experimentally characterize how forces are transmitted from these soft systems to the patient through the underlying soft tissue so as to generate assistance, (2) apply the optimal magnitude and timing of assistance to the patient to promote a more symmetric and natural gait by monitoring biomechanical, physiological and suit sensor data and (3) fuse information from different sensors monitoring patient motion and interaction forces to create an integrated CPS with a co-operative controller than can adapt to non-periodic movements of the patient.

This project represents a cross-disciplinary collaborative research effort on developing rigorous, closed-loop approaches for designing, simulating, and verifying medical devices. The work will open fundamental new approaches for radically accelerating the pace of medical device innovation, especially in the sphere of cardiac-device design. Specific attention will be devoted to developing advanced formal methods-based approaches for analyzing controller designs for safety and effectiveness; and devising methods for expediting regulatory and other third-party reviews of device designs. The project team includes members with research backgrounds in computer science, electrical engineering, biophysics, and cardiology; the PIs will use a coordinated approach that balances theoretical, experimental and practical concerns to yield results that are intended to transform the practice of device design while also facilitating the translation of new cardiac therapies into practice. The proposed effort will lead to significant advances in the state of the art for system verification and cardiac therapies based on the use of formal methods and closed-loop control and verification. The animating vision for the work is to enable the development of a true in silico design methodology for medical devices that can be used to speed the development of new devices and to provide greater assurance that their behaviors match designers' intentions, and to pass regulatory muster more quickly so that they can be used on patients needing their care. The scientific work being proposed will serve this vision by providing mathematically robust techniques for analyzing and verifying the behavior of medical devices, for modeling and simulating heart dynamics, and for conducting closed-loop verification of proposed therapeutic approaches. The acceleration in medical device innovation achievable as a result of the proposed research will also have long-term and sustained societal benefits, as better diagnostic and therapeutic technologies enter into the practice of medicine more quickly. It will also yield a collection of tools and techniques that will be applicable in the design of other types of devices. Finally, it will contribute to the development of human resources and the further inclusion of under-represented groups via its extensive education and outreach programs, including intensive workshop experiences for undergraduates

This project represents a cross-disciplinary collaborative research effort on developing rigorous, closed-loop approaches for designing, simulating, and verifying medical devices. The work will open fundamental new approaches for radically accelerating the pace of medical device innovation, especially in the sphere of cardiac-device design. Specific attention will be devoted to developing advanced formal methods-based approaches for analyzing controller designs for safety and effectiveness; and devising methods for expediting regulatory and other third-party reviews of device designs. The project team includes members with research backgrounds in computer science, electrical engineering, biophysics, and cardiology; the PIs will use a coordinated approach that balances theoretical, experimental and practical concerns to yield results that are intended to transform the practice of device design while also facilitating the translation of new cardiac therapies into practice. The proposed effort will lead to significant advances in the state of the art for system verification and cardiac therapies based on the use of formal methods and closed-loop control and verification. The animating vision for the work is to enable the development of a true in silico design methodology for medical devices that can be used to speed the development of new devices and to provide greater assurance that their behaviors match designers' intentions, and to pass regulatory muster more quickly so that they can be used on patients needing their care. The scientific work being proposed will serve this vision by providing mathematically robust techniques for analyzing and verifying the behavior of medical devices, for modeling and simulating heart dynamics, and for conducting closed-loop verification of proposed therapeutic approaches. The acceleration in medical device innovation achievable as a result of the proposed research will also have long-term and sustained societal benefits, as better diagnostic and therapeutic technologies enter into the practice of medicine more quickly. It will also yield a collection of tools and techniques that will be applicable in the design of other types of devices. Finally, it will contribute to the development of human resources and the further inclusion of under-represented groups via its extensive education and outreach programs, including intensive workshop experiences for undergraduates.

This NSF-FDA Scholar-In-Residence award supports translational research in modeling to inform future medical device design and approval processes. It is supported by the NSF Cyber-Physical Systems program in the Division of Computer and Network Systems in the Directorate for Computer and Information Science and Engineering. Sudden cardiac death is the leading cause of fatalities in the industrialized world. One in five people in the United States is affected by some sort of heart disease and one third of all deaths are due to cardiac diseases with an economic impact of about $200 billion a year. Most of these deaths result from arrhythmias, particularly fibrillation, which is rapid, disorganized electrical activity. The classification of arrhythmias as either reentrant or focal is of clinical significance, yet is difficult to assess. The FDA is responsible for regulating the systems and algorithms that aim to make this important differentiation. Such differentiation is a complex task involving the analysis of complex spatio-temporal patterns of electrical activity. The objectives of this project are to identify the key features of fibrillation that models should represent, to compare how well (or poorly) existing models correspond to measured values of these features, and to develop models that better represent fibrillation. The project develops and extends cell and tissue models and explores the analysis of clinical, experimental and simulation data from the perspective of regulatory science at the FDA, including verification, validation, and uncertainty quantification (VVUQ). The project seeks to 1) validate and create new models that reproduce not only single-cell dynamics, but also experimental and clinically relevant physiological dynamics in tissue and 2) initiate a new developmental framework that the FDA can use not only to test cardiac electrophysiology devices but also to characterize and verify massive submissions of therapeutic compounds obtained by computer-aided drug design methods. The research is conducted in collaboration with the Center for Devices and Radiological Health at FDA, and is aimed at developing tools that can characterize and evaluate real-world performance of devices. This will help the FDA to better regulate and verify the safety and effectiveness of devices that are developed to treat and terminate cardiac arrhythmias. All results from this project will be made freely available to the research community and to the general public.

This project will develop architecture and supporting enabling technologies to avert imminent loss of life or property in fast changing environments. The selected application is resuscitation in an intensive care unit (ICU) because it is life critical, time critical, human-centric and includes complex devices and software. For example, heart attack can be obscured in a trauma patient hemorrhaging from a broken leg in the presence of a collapsed lung. The challenge lies in solving the overarching difficulties of safe execution while maintaining complex and dynamic workflows. The availability and skill levels of medical staff, patient conditions, and medical device configurations all change rapidly. The core contribution is design and verification of reduced complexity situation awareness architecture for Emergency Cyber Physical Human systems (ECPH), supported by enabling technologies such as workflow adaptation protocols, managing data uncertainty and safe device plug and play. The ECPH workflow adaptation protocols are not only a function of the tasks and environment at hand, but must also be aware of the capabilities and training of the medical staff. In addition, risk mitigation driven safety interlock protocols will keep the actions of medical staff and CPS in synchrony with dynamically selected workflows. This is a cooperative effort of UIUC engineering and the ICU department of Carle Foundation Hospital. An ECPH team operates to accomplish a mission under rapidly changing circumstances. The stressful, rushed, and often unfriendly environment of an ECPH system means that errors, uncertainty, and failures will arise. This research will offer safety and resilience in the face of such disruptions. Effective and immediate intervention enabled by an optimized ECPH system will dramatically reduce preventable errors. The societal impact of effective collaboration under high stress will be enormous in terms of human lives and health care costs. According to CDC in 2010, the estimated direct & indirect costs of heart attacks and strokes alone in the U.S. were $503.2 billion; a significant percent of such patients during emergency care suffer complications and harm which are preventable. This project will develop educational material for training the next generation of researchers and engineers. The technology to be developed will also be adapted to other similar ECPH environments such as fighting a raging building fire.

The problem of controlling biomechatronic systems, such as multiarticulating prosthetic hands, involves unique challenges in the science and engineering of Cyber Physical Systems (CPS), requiring integration between computational systems for recognizing human functional activity and intent and controlling prosthetic devices to interact with the physical world. Research on this problem has been limited by the difficulties in noninvasively acquiring robust biosignals that allow intuitive and reliable control of multiple degrees of freedom (DoF). The objective of this research is to investigate a new sensing paradigm based on ultrasonic imaging of dynamic muscle activity. The synergistic research plan will integrate novel imaging technologies, new computational methods for activity recognition and learning, and high-performance embedded computing to enable robust and intuitive control of dexterous prosthetic hands with multiple DoF. The interdisciplinary research team involves collaboration between biomedical engineers, electrical engineers and computer scientists. The specific aims are to: (1) research and develop spatio-temporal image analysis and pattern recognition algorithms to learn and predict different dexterous tasks based on sonographic patterns of muscle activity (2) develop a wearable image-based biosignal sensing system by integrating multiple ultrasound imaging sensors with a low-power heterogeneous multicore embedded processor and (3) perform experiments to evaluate the real-time control of a prosthetic hand. The proposed research methods are broadly applicable to assistive technologies where physical systems, computational frameworks and low-power embedded computing serve to augment human activities or to replace lost functionality. The research will advance CPS science and engineering through integration of portable sensors for image-based sensing of complex adaptive physical phenomena such as dynamic neuromuscular activity, and real-time sophisticated image understanding algorithms to interpret such phenomena running on low-power high performance embedded systems. The technological advances would enable practical wearable image-based biosensing, with applications in healthcare, and the computational methods would be broadly applicable to problems involving activity recognition from spatiotemporal image data, such as surveillance. This research will have societal impacts as well as train students in interdisciplinary methods relevant to CPS. About 1.6 million Americans live with amputations that significantly affect activities of daily living. The proposed project has the long-term potential to significantly improve functionality of upper extremity prostheses, improve quality of life of amputees, and increase the acceptance of prosthetic limbs. This research could also facilitate intelligent assistive devices for more targeted neurorehabilitation of stroke victims. This project will provide immersive interdisciplinary CPS-relevant training for graduate and undergraduate students to integrate computational methods with imaging, processor architectures, human functional activity and artificial devices for solving challenging public health problems. A strong emphasis will be placed on involving undergraduate students in research as part of structured programs at our institution. The research team will involve students with disabilities in research activities by leveraging an ongoing NSF-funded project. Bioengineering training activities will be part of a newly developed undergraduate curriculum and a graduate curriculum under development. The synergistic research plan has been designed to advance CPS science and engineering through the development of new computational methods for dynamic activity recognition and learning from image sequences, development of novel wearable imaging technologies including high-performance embedded computing, and real-time control of a physical system. The specific aims are to: (1) Research and develop spatio-temporal image analysis and pattern recognition algorithms to learn and predict different dexterous tasks based on sonographic patterns of muscle activity. The first aim has three subtasks designed to collect, analyze and understand image sequences associated with functional tasks. (2) Develop a wearable image-based biosignal sensing system by integrating multiple ultrasound imaging sensors with a low-power heterogeneous multicore embedded processor. The second aim has two subtasks designed to integrate wearable imaging sensors with a real-time computational platform. (3) Perform experiments to evaluate the real-time control of a prosthetic hand. The third aim will integrate the wearable image acquisition system developed in Aim 2, and the image understanding algorithms developed in Aim 1, for real-time evaluation of the control of a prosthetic hand interacting with a virtual reality environment. Successful completion of these aims will result in a real-time system that acquires image data from complex neuromuscular activity, decodes activity intent from spatiotemporal image data using computational algorithms, and controls a prosthetic limb in a virtual reality environment in real time. Once developed and validated, this system can be the starting point for developing a new class of sophisticated control algorithms for intuitive control of advanced prosthetic limbs, new assistive technologies for neurorehabilitation, and wearable real-time imaging systems for smart health applications.

In telerobotic applications, human operators interact with robots through a computer network. This project is developing tools to prevent security threats in telerobotics, by monitoring and detecting malicious activities and correcting for them. To develop tools to prevent and mitigate security threats against telerobotic systems, this project adapts cybersecurity methods and extends them to cyber-physical systems. Knowledge about physical constraints and interactions between the cyber and physical components of the system are leveraged for security. A monitoring system is developed which collects operator commands and robot feedback information to perform real-time verification of the operator. Timely and reliable detection of any discrepancy between real and spoofed operator movements enables quick detection of adversarial activities. The results are evaluated on the UW-developed RAVEN surgical robot. This project brings together research in robotics, computer and network security, control theory and machine learning, in order to gain better understanding of complex teleoperated robotic systems and to engineer telerobotic systems that provide strict safety, security and privacy guarantees. The results are relevant and applicable to a wide range of applications, including telerobotic surgery, search and rescue missions, military operations, underwater infrastructure and repair, cleanup and repair in hazardous environments, mining, as well as manipulation/inspections of objects in low earth orbit. The project algorithms, software and hardware are being made available to the non-profit cyber-physical research community. Graduate and undergraduate students are being trained in cyber-physical systems security topics, and K-12, community college students and under-represented minority students are being engaged.