CYBER-PHYSICAL MODELING OF IMPLANTABLE CARDIAC MEDICAL DEVICES

SOL YOON

ICE, DGIST

FEB. 6TH. 2012

OUTLINE

Introduction

Overview of model-based design

Background knowledge

Integrated Heart Model

Heart Model Validation

Pacemaker Model

Closed-loop case study

Conclusion

INTRODUCTION

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

OVERVIEW OF MODEL-BASED DE-SIGN

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 KNOWLEDGE

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

HEART MODEL

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

HEART MODEL VALIDATION

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

VHM SIMULATION VHM is able to generate similar result with extrastimuli

technique

PACEMAKER MODEL

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

CLOSED-LOOP CASE STUDY

ENDLESS LOOP TACHYCARDIA (ELT) The ELT is induced by premature ventricular contraction

(PVC), which is due to abnormal self-depolarization of ventricular tissue

CONCLUSION

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