Implantable Cardiac Defibrillators (ICDs) are at the forefront of preventing sudden death in patients suffering from ventricular arrhythmias. ICDs have evolved into complex Cyber-Physical Systems (CPS)which tightly sensing, hardware, and software to diagnose arrythmias based on electrogram signals and control cardiac excitation. These devices are life-critical, yet the Verification and Validation (V&V) techniques used for establishing their safety have remained somewhat informal, and rely largely on extensive unit testing. There have been a number of exciting developments in formal verification technologies. This proposal introduces these techniques into the ICD verification process, and will demonstrate their suitability for application in other medical devices. The project will develop a model-based framework for ICDs, and will apply formal verification techniques, such as model checking and reachability analysis, to high-fidelity cardiac electrophysiological models that capture the electrical excitation induced by the ICD's control software. Through extensive collaboration with FDA research staff, the proposal will demonstrate the effectiveness of formal verification technology and suitability in medical device applications.

The project investigates a formal verification framework for artificial pancreas (AP) controllers that automate the delivery of insulin to patients with type-1 diabetes (T1D). AP controllers are safety critical: excessive insulin delivery can lead to serious, potentially fatal, consequences. The verification framework under development allows designers of AP controllers to check that their control algorithms will operate safely and reliably against large disturbances that include patient meals, physical activities, and sensor anomalies including noise, delays, and sensor attenuation. The intellectual merits of the project lie in the development of state-of-the-art formal verification tools, that reason over mathematical models of the closed-loop including external disturbances and insulin-glucose response. These tools perform an exhaustive exploration of the closed loop system behaviors, generating potentially adverse situations for the control algorithm under verification. In addition, automatic techniques are being investigated to help AP designers improve the control algorithm by tuning controller parameters to eliminate harmful behaviors and optimize performance. The broader significance and importance of the project are to minimize the manual testing effort for AP controllers, integrate formal tools in the certification process, and ultimately ensure the availability of safe and reliable devices to patients with type-1 diabetes. The framework is made available to researchers who are developing AP controllers to help them verify and iteratively improve their designs. The team is integrating the research into the educational mission by designing hands-on courses to train undergraduate students in the science of Cyber-Physical Systems (CPS) using the design of AP controllers as a motivating example. Furthermore, educational material that explains the basic ideas, current challenges and promises of the AP concept is being made available to a wide audience that includes patients with T1D, their families, interested students, and researchers. The research is being carried out collaboratively by teams of experts in formal verification for Cyber-Physical Systems, control system experts with experience designing AP controllers, mathematical modeling experts, and clinical experts who have clinically evaluated AP controllers. To enable the construction of the verification framework from the current state-of-the-art verification tools, the project is addressing major research challenges, including (a) building plausible mathematical models of disturbances from available clinical datasets characterizing human meals, activity patterns, and continuous glucose sensor anomalies. The resulting models are integrated in a formal verification framework; (b) simplifying existing models of insulin glucose response using smaller but more complex delay differential models; (c) automating the process of abstracting the controller implementation for the purposes of verification; (d) producing verification results that can be interpreted by control engineers and clinical researchers without necessarily understanding formal verification techniques; and (e) partially automating the process of design improvements to potentially eliminate severe faults and improve performance. The framework is evaluated on a set of promising AP controller designs that are currently under various stages of clinical evaluation.

This project aims to achieve key technology, infrastructure, and regulatory science advances for next generation medical systems based on the concept of medical application platforms (MAPs). A MAP is a safety/security-critical real-time computing platform for: (a) integrating heterogeneous devices and medical IT systems, (b) hosting application programs ("apps") that provide medical utility through the ability to both acquire information and update/control integrated devices, IT systems, and displays. The project will develop formal architectural and behavioral specification languages for defining MAPs, with a focus on techniques that enable compositional reasoning about MAP component interoperability and safety. These formal languages will include an extensible property language to enable the specification of real-time, quality-of-service, and attributes specific to medical contexts that can be leveraged by code generation, testing, and verification tools. The project will work closely with a synergistic team of clinicians, device industry partners, regulators, and medical device interoperability and safety standard organizations to develop an open source MAP innovation platform to enable key stakeholders within the nation's health care ecosphere to identify, prototype, and evaluate solutions to key technology and regulatory challenges that must be overcome to develop a commodity market of regulated MAP components. Because MAPs provide pre-built certified infrastructure and building blocks for rapidly developing multi-device medical applications, this research has the potential to usher in a new paradigm of medical system that significantly increases the pace of innovation, lowers development costs, enables new functionality by aggregating multiple devices into a system of systems, and achieves greater system safety.

The objective of this project is to create a focused cyber-physical design environment to accelerate the development of miniature medical devices in general and swallowable systems in particular. The project develops new models and tools including a web-based integrated simulation environment,capturing the interacting dynamics of the computational and physical components of devices designed to work inside the human body, to enable wider design space exploration, and, ultimately, to lower the barriers which have thus far impeded system engineering of miniature medical devices. Currently, a few select individuals with deep domain expertise create these systems. The goal is to open this field to a wider community and at the same time create better designs through advanced tool support. The project defines a component model and corresponding domain-specific modeling language to provide a common framework for design capture, design space exploration, analysis and automated synthesis of all hardware and software artifacts. The project also develops a rich and extensible component and design template library that designers can reuse. The online design environment will provide early feedback and hence, it will lower the cost of experimentation with alternatives. The potential benefit is not just incremental (in time and cost), but can lead to novel ideas by mitigating the risk of trying unconventional solutions. Trends in consumer electronics such as miniaturization, low power operation, and wireless technologies have enabled the design of miniature devices that hold the potential to revolutionize medicine. Transformational societal public health benefits (e.g., early diagnosis of colorectal cancer or prevention of heart failure) are possible through less invasive and more accurate diagnostic and interventional devices. By eliminating large incisions in favor of natural orifices or small ports, these medical devices can increase diagnostic screening effectiveness and reduce pain and recovery time. Furthermore, if successful, the proposed scientific approach can be extended to any other application, wherever size, power efficiency, and high confidence are stringent requirements. The educational plan of the project is centered on the web-based design environment that will also contain an interface for high school students to experiment with medical cyber-physical devices in a virtual environment. Students will be able to build medical devices from a library of components, program them using an intuitive visual programming language and operate them in various simulated environments. A Summer Camp organized in the framework of this project will enhance students learning experience with real hands-on experimentation in a lab.