Seminar on Closed Loop Medical Devices (CSCI 7000-015, Spring 2016)

Week 1 Resources.

Sriram Sankaranarayanan will lead a brief discussion on the following topics.

• Introduction: Discuss motivations for this class.

• Ground rules, grading and other issues.

• Closed Loop Medical Devices: qu'est-ce que c'est?

• What are the key research issues?

  • Clinical performance measures.

  • Engineering: control algorithms.

  • Correctness: Safety/Reliability concerns.

  • Security issues.

  • Regulatory issues.

  • Ethical considerations.

  • Human factors.

• Research: Literature search.

  • Where to look for references?

  • Authoritative vs. Non-authoritative sources.

Week 2 Resources.

• Reading: Claudio Cobelli et al. survey article on the artificial pancreas concept.

• Doyle et al. survey article on AP algorithms.

• Artificial Pancreas: A Race to the Finish, by Robert Neil.

Week 3 Resources

• We will finish the discussion from Week 2

Week 4 Resources

Discussion Lead: Suhas

This week, we will read papers on predictive pump shutoff algorithms for the artificial pancreas.

• Inpatient Studies of a Kalman-Filter-Based Predictive Pump Shutoff Algorithm, Cameron et al., J Diabetes Sci Technol. 2012 Sep; 6(5): 1142–1147.

Here are two other papers that will be good if you can read, but do not worry if you do not have the time.

• Continuous Glucose Monitoring: Real-Time Algorithms for Calibration, Filtering, and Alarms, Wayne Bequette, J Diabetes Sci Technol. 2010 Mar; 4(2): 404–418.

• Prevention of Nocturnal Hypoglycemia Using Predictive Alarm Algorithms and Insulin Pump Suspension, Buckingham et al, Diabetes Care May 2010 vol. 33 no. 5 1013-1017.

Week 5 Resources

Discussion Lead: Ram

We will study PID control algorithms for hybrid and fully automated closed loop insulin delivery.

• Fully Automated Closed-Loop Insulin Delivery Versus Semiautomated Hybrid Control in Pediatric Patients With Type 1 Diabetes Using an Artificial Pancreas, Wenzeimer et al. Diabetes Care May 2008.

• Day and Night Closed-Loop Control Using the Integrated Medtronic Hybrid Closed-Loop System in Type 1 Diabetes at Diabetes Camp, Ly et al., Diabetes Care Volume 38, July 2015.

Basics of Feedback Control

For those who are unfamiliar, the book by Astrom and Murray is an excellent introduction to feedback.

• Feedback Systems: An Introduction for Scientists and Engineers, Karl Astrom and Richard Murray.

Modeling Human Insulin-Glucose Response

Discussion Lead: Taisa

We will now study mathematical models of human insulin-glucose response. We will focus on two ODE-based models.

• Paper on Bergman Minimal Model.

• A nice writeup about that model.

• Meal Simulation Model of the Glucose-Insulin System, C. Dalla Man, R.A. Rizza, and C. Cobelli. IEEE Transactions on Biomedical Engineering (2007) 54(10), 1740-1749.

• A System Model of Oral Glucose Absorption: Validation on Gold Standard Data, C. Dalla Man, M. Camilleri, and C. Cobelli. IEEE Transactions on Biomedical Engineering (2006) 53(12), 2472-2478.

See here for a mathworks simulation demo: Mathworks demo simulation of Dalla Man model.

Week 8 Resources

For weeks 8 and 9, we are looking at model-predictive control.

Model-Predictive Control

Discussion Lead by Suhas A.

Most introductions are rather technical and not easy to understand if you do not know controls already. But the couple of lecture slides below strike a good balance:

• 1 Slides from Oxford University Look at these slides: Lecture 1 slides

• 2 Introduction to MPC from UPenn ESE680

MPC for artificial pancreas

We will review a couple of papers from a large set of papers that look at MPC.

• Model Predictive Control of Type 1 Diabetes: An in Silico Trial, L. Magni et al., J Diabetes Sci Technol. 2007 Nov; 1(6): 804–812.

• Nonlinear model predictive control of glucose concentration in subjects with type 1 diabetes, Hovorka et al., Physiol. Meas. 25 (2004) 905–920.

A notable paper on a clinical trial of Hovorka et al.'s system:

• Manual closed-loop insulin delivery in children and adolescents with type 1 diabetes: a phase 2 randomised crossover trial, Hovorka et al, Lancet Volume 375, No. 9716, p743–751, 27 February 2010.

Week 10 Resources

This week, we will look at Bihormonal control for artificial pancreas that includes insulin and glucagon in the closed loop. Bionic Pancreas Site at Boston University. The page makes it look like the device is already a product on the market.

• El Khatib et al. Science Translational Medicine (2010).

  • Supplementary Material (describes the algorithm used).

• Outpatient study of device in NEJM (2014).

Week 11 Resources

• Blackhat 2011 talk by Jay Radcliffe (Video)

  • Abstract

• Hacking an insulin pump, Li et al.

Week 12 Resources

We will discuss human factors and legal issues for medical devices.

• Improving safety in medical devices and systems, Harold Thimbleby, Keynote lecture at IEEE Intl. Conference on Health Informatics.

• Harold Thimbleby, Is IT a dangerous prescription?. Interesting paper written based on different types of medical devices. Lessons are still applicable to closed loop devices.

• Sandler, K., Ohrstrom, L., Moy, L., McVay, R.: Killed by Code: Software Transparency in Implantable Medical Devices. Software Freedom Law Center (2010)

Week 13 Resources

• Michael Glikson and Paul A Friedman, The implantable cardioverter defibrillator, THE LANCET • Vol 357 • April 7, 2001.

• Holzmeister, Johannes et al., Implantable cardioverter defibrillators and cardiac resynchronisation therapy, The Lancet , Volume 378 , Issue 9792 , 722 - 730, 2011.

Week 14 Resources

• Halperin et al. Pacemakers and Implantable Cardiac Defibrillators: Software Radio Attacks and Zero-Power Defenses, IEEE Security and Privacy 2008.

• Wayne Burleson and Sandro Carrara, Security and Privacy of Implantable Medical Devices (Edited Volume by Springer-Verlag).

Week 15 Resources

• Jiang et al. Modeling and Verification of a Dual Chamber Implantable Pacemaker.

• Jiang et al. Cyber–Physical Modeling of Implantable Cardiac Medical Devices, Proc. IEEE, 100(1), 2012.

• E. Jee et al. Assurance Cases in Model-Driven Development of the Pacemaker Software, Lecture Notes in Computer Science: Leveraging Methods of Formal Methods, Verification, and Validation 6416, 343-356. October 2010.