cyber-physical modeling of implantable cardiac medical devices sol yoon ice, dgist feb. 6 th. 2012
TRANSCRIPT
OUTLINE
Introduction
Overview of model-based design
Background knowledge
Integrated Heart Model
Heart Model Validation
Pacemaker Model
Closed-loop case study
Conclusion
THE FDA AND MEDICAL DEVICE SOFTWARE FDA: need for rigorous real-time methodologies to validate
and verify medical device software
The use of artificial implantable heart rhythm devices has grown rapidly over the recent decades
However, there is no formal methodology or platform to validate and verify the correct operation of medical device software
Software is reviewed by the FDA only in the incident of a device re-call.
Implantable medical devices are a primary example of medical cy-ber-physical systems
Safety and efficacy of the device and device software must be eval-uated within a closed-loop context of the patient
CURRENT TESTING, VALIDATION, AND VERIFICATION
The primary approach is unit testing using a playback of pre-recorded electrogram and electrocardiogram signals
April 2010, the FDA began the “Infusion Pump Improvement Initiative”
An effective verification methodology is needed for the risk analysis and certification of medical device software
Pacemaker mediated tachycardia (PMT)
A condition where the pacemaker inappropriately drives the heart rate toward the upper rate limit
Can be used for closed-loop system analysis
METHODOLOGY FOR CLOSED-LOOP MEDICAL DEVICE SAFETY Developed an integrated functional and formal virtual heart
model (VHM)
Clinically relevant Timed automata based
Developed a pacemaker device model for interactive and clin-ically relevant test generation
A set of general and patient condition-specific pacemaker software requirement to ensure the safety
Provide a means to test and verify the closed-loop system
The atrial-ventricle synchrony must be enforced
PREVIOUS HEART MOD-ELING EFFORTS The model of the heart should capture the electrophysiological
(EP) properties of the heart and generate functional signals
Conduction Timing signal
The heart models have been developed to study the heart functions from the electrical and mechanical aspects.
Signal propagation, distortion, and attenuation Cardiac output and valve mechanisms
REQUIREMENTS FOR MODEL-BASED CLOSED-LOOP V&V
1. Model fidelity: must cover the functioning heart
Normal sinus rhythm, sinus bradycardia, pacemaker mediated tachy-cardia, etc.
2. Simplicity
The heart model currently have hundreds of differential equations or millions of finite elements
Simulation of the models are time consuming and do not interact with medical devices
The VHM presents an abstraction of the timing and electrical conduc-tion
3. Physical testbed
Enable to operate the heart on VHDL-based FPGA platform for black-box closed-loop testing
OVERVIEW OF THE VHM APPROACH Platform provide two interface
A formal signal for medical device software A functional electrogram for real device implementation
BACKGROUND KNOWL-EDGE
The heart generates electrical impulses which organize the sequence of muscle contractions during each heart beat
The heart’s electrical timing is fundamental to proper cardiac function
The implantable cardiac pacemaker is a rhythm management device
Such devices have improved the condition of patients with cardiac arrhythmias
CELLULAR-LEVEL ACTION POTENTIAL The heart tissue can be activated by an external voltage ap-
plied to the cell
ELECTRICAL CONDUC-TION SYSTEM The tissue at the sinoatrial node (SA) periodically and
spontaneously self-depolarizes
The activation signal travels through both atria, causing contrac-tion and pushes blood into the ventricles.
Then the activation is delayed at the atrioventricular (AV) node which allows the ventricles to fill fully
CARDIAC ARRHYTHMIAS There are anomalies of the conduction and refractory
properties in heart tissue
Bradycardia: failure of impulse generation with anomalies in the SA node and failure of impulse propagation
Tachycardia: impair hemodynamics caused by anomalies in SA node or reentry circuit
ARRHYTHMIA DIAGNOSIS AND TREATMENT electrophysiology (EP) testing
Catheters with multiple electrodes on the tip are inserted from the groin into the heart
Can locate timing anomalies, using the spatial information from catheter placement and the temporal information from the timing dif-ference between the pulses
Ablation surgery can treat reentry circuit Electrocardiography (ECG)
RHYTHM MANAGEMENT DEVICES
Implantable pacemakers have been developed to deliver timely electrical pulses to the heart to treat bradycardia
The pacemaker has two leads inserted into the heart
One in the right atrium One in the right ventricle
By doing timing analysis of the electrogram (EGM) signals sensed from the two leads
Artificial pacemaker generates electrical pulses when necessary that can maintain ventricular rate
Enforce atrial-ventricular synchronization
A BRIEF OVERVIEW OF EX-TENDED TIMED AUTOMATA VHM uses a timed-automata semantics, which is similar to
the semantic extension used in UPPAAL
The electrical conduction system consists of conduction pathways with different conduction delays and refractory period
The refractory and conduction properties are all timing based, it is natural to model the electrical conduction sys-tem as a network of timed automata
MODELING THE ELECTRICAL CONDUCTION SYSTEM (a) Node automaton that models the refractory properties of heart tissue
and are the minimum and maximum values for of the tissue
MODELING THE ELECTRICAL CONDUCTION SYSTEM (b) Path automaton that models the propagation properties of heart tissue
denote the length of the path and is the conduction velocity
ELECTROPHYSIOLOGY STUDY
1. Catheter Placement
The typical catheter positions used are high right atrium (HRA) His bundle electrogram (HBE), which is placed across the valve be-
tween atrium and ventricle Right ventricle apex (RVA), which is placed at the right ventricle apex
to monitor electrical activity of the ventricle
2. Extrastimuli Technique
HRA catheter deliver external pacing signals faster than the intrinsic heart rate
The interval between two consecutive pacing signals is referred to as basic cycle length (BCL)
The interval between the extrastimulus and the last pacing signal of the pacing sequence is referred to as coupling interval
By decreasing the coupling interval gradually, the extrastimulus will reach the RRP of the tissue, causing changes in conduction delays
CLINICAL CASE STUDY Key interval values when the coupling interval shortens for a
real patient
are the pulse caused by the extrastimulus The interval is equal to the coupling interval indicate conduction delay between the His bundle and the ventricle
Caused by extrastimulus
Coupling interval
PACEMAKER MODEL The artificial pacemaker is designed for patients with brady-
cardia
Two leads, one in the right atrium and one in the right ventricle, are inserted into the heart
Two leads monitor the local activation of the atria and the ventricles, and generate corresponding sensed event (AS, VS) to its software
The software determines the heart condition by measuring time differ-ence between events and delivers pacing events (AP, VP) to analog circuit
Analog circuit delivers pacing signals to the heart to maintain heart rate and A-V synchrony
DDD PACEMAKER TIMING DIA-GRAM Five basic timing cycles which diagnose heart condition
Ventricle pace (LRI), ventricle sense (AVI) Atrial pace (ARP), atrial sense (VRP) Coordinator between the atrium and ventricle leads (URI) Each task was assigned a period of 10 ms
ENDLESS LOOP TACHYCARDIA (ELT) The ELT is induced by premature ventricular contraction
(PVC), which is due to abnormal self-depolarization of ventricular tissue
PHYSICAL IMPLEMENTA-TION Can validate the closed-loop electrical interaction between the
heart (FPGA) and pacemaker (FireFly node)
CONCLUSION AND FU-TURE WORK
A primary challenge in life-critical real-time systems is with the design of bug-free medical device software
Using timed automata
designed an integrated functional and formal model of the heart and pacemaker device
A real-time VHM has been developed to model the electrophys-iological operation of the human heart