Welcome to

BME 9502/ECE 4455A:

Biomedical Systems Analysis
and
MEDBIO 4455A:
Biological Control Systems
 Biomedical Engineering Is…

Design of medical devices, processes, and systems.

Application of engineering science to solve problems

in medicine and the biomedical sciences.
 Systems Thinking

Input Information Output Information

Action

“Information” will usually refer to dynamic physiological

variables, e.g., pressure, flow rate, volume,
concentration, transmembrane voltage, etc.

“Action” could be transport, store, dampen, sense,

filter, regulate, etc.
Systems thinking is most useful when analyzing
or designing complex systems composed of
combinations of simpler systems:
series

parallel

feedback
“Biology is the only science where feedback control
and protocols play a dominant role, so it should not
be surprising that there would be popular theories,
coming from within science, that did not emphasize
these issues. Biologists and engineers now have
enough examples of complex systems that they
can close the loop and eliminate specious theories.
We should compare notes.”

M.E. Csete and J.C. Doyle, “Reverse engineering of biological complexity,”

Science, vol. 295, pp. 1664-1669, 2002.
 Course Topics
1. Introduction to biomedical modeling

2. Cardiac electrophysiology
Application: Design of implantable defibrillator pulses
3. Cardiovascular mechanics
Application: Control of left ventricular assist devices
4. Respiratory mechanics
Application: Control of mechanical ventilators
5. Respiratory regulation
Application: Prevention of unstable breathing
 Course Topics
2. Cardiac electrophysiology
Linear time-invariant system
3. Cardiovascular mechanics
Time-varying system
4. Respiratory mechanics
Hybrid system with switching control
5. Respiratory regulation
Closed-loop system with feedback delays
Course-Level Learning Objectives
1. Explain the physiological and biophysical basis of
biomedical systems models and analyze those models
using concepts from systems analysis and control
theory.

2. Demonstrate the use of biomedical systems models to

inform the design of medical devices.
3. Employ software tools to investigate the dynamic
behaviour of biomedical systems and devices.
4. Investigate and critique hypotheses and conclusions
presented in primary-source biomedical engineering
literature.
Course-Level Learning Objectives
5. Analyze ethical issues arising from applications of
medical technology and use of biomedical models to
make decisions about public safety concerns.
 Course Case Analysis Process
1. Specify clinical problem. What physiological
processes are involved?

2. Learn basic anatomy and physiology.

3. Develop systems model from basic anatomy

and physiology.
Research alternative models. Which models are
applied in clinical studies?
NB: Uncomplicated model is often sufficient.
 Course Case Analysis Process
4. Specify functions of relevant device. Incorporate
device into systems model.

5. Develop and experiment with computational

realization of systems model.

6. Perform computational studies. Use results to

interpret conclusions of principal journal article.
 Assignment Format
Each lecture unit will include a case study based
on a journal article and two assessments.

OWL “Quiz”
Multiple-choice questions addressing background
knowledge relevant to the case study.

Homework (MATLAB Investigation)

MATLAB scripts posted to OWL will be used to
investigate questions raised in the case study.
Written results to be submitted to OWL at the end
of the lecture unit.
 Assignment Format
Some class sessions will be dedicated to
preparing you for the MATLAB investigations.

MATLAB investigations can be completed in

groups of 2 or 3 students. One written
submission is required from each group.

Note the strict late submission policies in the

course outline.
 Minute Papers
Two in-class discussions of ethical issues:
Wednesday, October 2
Tuesday, November 19

Brief written reflections completed and due at

the end of class. Marked pass/fail.
 Final Projects
Undergrad project: Guided project based on
Case Study 4 to be carried out individually.

Instructions and code provided by November 29.

Due December 16 at 11:59 pm.

First 3 MATLAB investigations are similar to

undergrad project in format and content.
 Final Projects
Grad project: Independent project to study in
depth (preferably by implementing and
experimenting with) a model based on journal
article of your choice.

1-page project proposal due Nov. 4.

Mark based on project report, due Dec. 16.

See Project Guidelines document on OWL.

FAQ: How much programming is required?

MATLAB implementations of computational models

are provided for homework assignments and
undergrad final project. Assignments may require
Simple changes to the models, but will not involve
original programming.

Computational modeling is strongly encouraged

for graduate projects.
Cardiac Electrophysiology Case Study
Design a practical defibrillation waveform for
an implantable cardioverter-defibrillator that
effectively approximates the theoretically
optimum stimulus and minimizes the risk of
electrical damage to the patient’s heart.

Required journal article:

J. Huang et al., “Ascending defibrillation waveform
significantly reduces myocardial morphological
damage and injury current,” JACC: Clinical
Electrophysiology, vol. 5, pp. 854-862, 2019.
 Transvenous Implantable
Cardioverter-Defibrillator (ICD)
Functions:
1. Anti-bradycardia pacing

2. Anti-tachycardia pacing
(a.k.a. cardioversion)

3. Defibrillation

Figure from www.bostonscientific.com

 ICD Engineering Considerations

Consider: Amplitude
Duration }
 Pulse energy
Pulse shape  Hardware complexity

Too little energy  Pacing/defibrillation unsuccessful

BUT
Too much energy  Damage myocardium?
Reduce battery lifetime
Key Result
Case Study 1 Learning Objectives
Demonstrate the use of a biomedical systems
model to inform the design of a medical device.

Understand the electrophysiological mechanism

by which an external stimulus terminates
ventricular fibrillation.

Formulate an engineering design problem as a

constrained linear optimization.
 Case Study 1 Assignments
OWL quiz due Thursday, September 26 at 11:55 pm.

MATLAB investigation due Friday, October 4 at

11:55 pm.

Additional instructions will be posted on OWL.

Preparation for Sept. 13 Class

Read Case Study 1.

Be prepared to suggest
topics we could study
before attempting to
analyze the case.
Biomedical Modeling 1
September 10, 2024
 Lecture Objectives
Students will be able to…
1. Define parametric and nonparametric models and
explain how both model types are applied to biomedical
systems analysis.
2. Define and state relationships between effort and
flow parameters in multiple types of lumped-parameter
physical systems.
3. Write a system of equations for a mass balance in a
compartmental model.
 Starting Questions
1. Are we only interested in externally observable
behavior, or do we need to understand the internal
structure and/or function of a physiological system?

2. Are we interested in describing past behavior,

analyzing present behavior, or predicting future
behavior?

W. van Meurs, Modeling and Simulation in Biomedical Engineering,

McGraw-Hill, 2011, chap. 1.
 Types of System Models
Black-box/nonparametric models:
Transfer function relating input to output signal(s)
determined from experimental data.

Structural/parametric models:
Transfer function derived from physical laws
applied to known anatomy or physiological
processes.
Parametric models often rely on physical system
analogies.
 Transfer Functions
Time domain:
x(t) y(t) = h(t)x(t)
h(t)

Fourier domain:
X(w) Y(w) = H(w)X(w)
H(w)

Laplace domain:
X(s) Y(s) = H(s)X(s)
H(s)
 Transfer Functions
Terminology: h(t) = impulse response
H(w) = frequency response
H(s) = transfer function

Recall: H w   FTht   H s  s  jw
H(s) = LT[h(t)]

Above relationships apply to linear

time-invariant (LTI) systems only.
 Benefits of Physical Analogies
Enhance understanding of one type of system
using knowledge or intuition about a second type
of system.

Provide a more convenient means of diagramming

a system.

Apply analysis or simulation tools that are more

extensively developed for the analogous system.

W. van Meurs, Modeling and Simulation in Biomedical Engineering,

McGraw-Hill, 2011, chap. 4.
 (Complicated) Parametric Model Example
Electrical circuit model of the cardiovascular system

Y. Sun et al., Am. J. Physiol.

Heart Circ. Physiol. 37:H476-
H489, 1995.
 Lumped-Parameter Models
Network of 1-D connections among elements
representing important physical properties of
system.

Elements treated as spatially compact, so spatial

variation of parameters is neglected.

Lead to systems of ordinary differential equations

as functions of time.
 Analogous Lumped Systems

Type of Variable Type

System “Effort” ( ) “Flow” ( )

Electrical Voltage (v) Current (i )

Solid
Net force (F ) Velocity (v)
mechanics
Fluid
Pressure (P) Flow rate (Q)
mechanics
Chemical
Concentration (f) Mass flux (Q)
diffusion
Notation follows M.C.K. Khoo, Physiological Control Systems, chap. 2.
Components of lumped-parameter models can be
combined in series or in parallel.

Analogies between different types of systems are

established by connecting elements so flow
variable behaves identically in both systems.
System Property 1: Resistance to Flow
Ohm’s Law: (t) = R(t)
i
v1 v2
Electrical: Resistor
R
v1(t) – v2(t) = Ri(t)


R
A
Resistivity, 
Units: Wm
System Property 1: Resistance to Flow
Fluid mechanics: Friction in a pipe Rf
Rf 8L
Q P1t   P2 t   4 Q t 
r
P1 P2 Poiseuille’s law

L = length of pipe,  = viscosity of fluid,

r = radius of pipe

Valid for laminar, incompressible flow

System Property 1: Resistance to Flow
Chemical: Diffusion barrier Rc
f1 f2 T
Q f1t   f2 t   Q t 
DA
Rc Fick’s law of diffusion

T = membrane thickness
A = membrane surface area
D = diffusion coefficient
System Property 1: Resistance to Flow

Solid mechanics: Damper or dashpot

F v
F(t) = Rmv(t)
Rm

Rm = damping coefficient, related to viscosity of

fluid inside dashpot
System Property 2: Potential Energy Storage
1 t
 t      d
C  0
i
v1 v2
Electrical: Capacitor
C
1 t
v1t   v 2 t    i  d
C  0
(Assuming capacitor is discharged initially at t = 0.)
System Property 2: Potential Energy Storage
Solid mechanics: Spring
F v

x2 > x1
x1
Hooke’s law: F = k(x2 – x1) k = spring constant

Define mechanical compliance, Cm = 1/k

t
Observe x   v  d
 0
t
 F t   1
 v  d
Cm  0
System Property 2: Potential Energy Storage
Fluid mechanics: Elastic container
Q
1 t
Po Pi t   Po   Q  d
C  0
Pi
C = compliance, units: volume/pressure
(Assuming Pi = Po initially at t = 0.)

Chemical diffusion: Rigid container w/ volume V

Q 1 t
fi fi t   fo   Q d
fo
V  0
(Assuming fi = fo initially at t = 0.)
System Property 3: Kinetic Energy Storage
d
 t   L  t 
dt
i
v1 v2
Electrical: Inductor
d
L v1t   v 2 t   L i t 
dt

F v
Solid mechanics: Inertia m

d
Newton’s 2nd law: F t   m v t 
dt
System Property 3: Kinetic Energy Storage
Fluid mechanics: Inertia
Mass of fluid, m, w/ density  in a pipe w/ length 
and cross-sectional area A:
m  A

Velocity of fluid, v, assuming plug flow: v = Q/A

Substitute for m and v in Newton’s 2nd law:

dv d Q  dQ
F m  A    
dt dt  A  dt
System Property 3: Kinetic Energy Storage
Fluid mechanics: Inertia
dQ
F  
dt
 dQ
Since P = F/A: P
A dt

inertance

Chemical diffusion: No kinetic energy storage

mechanism.
 Compartmental Models
Lumped-parameter model consisting of discrete
volumes that substance(s) of interest flow between.

Mathematical analysis based on system of mass

balances.

Mass flux between compartments depends on

concentration in supplying compartment and rate
constants.
 Two-Compartment Model

Mass balance for Compartment 1:

 Two-Compartment Model

Mass balance for Compartment 2:

 Summary
Biomedical systems can be represented using
parametric or nonparametric models.
Parametric models are often developed by
applying physical analogies to basic anatomy
and physiology.
Lumped-parameter models are defined based
on mathematical relationships among effort
and flow parameters.
Compartmental models are a common lumped-
parameter modeling approach in biology and
chemistry.
Biomedical Modeling 2
September 11, 2024
 Lecture Objectives
Students will be able to…
1. Explain the equivalence between a pair of analogous
physical system models.
2. Propose lumped-parameter models for simple
physiological systems.
What Is a “Model”, Anyway?
i.e., What information is communicated
by this schematic?

Redraw this system

as an electric circuit…
Figure: ctms.engin.umich.edu
 Glass Jar Lung Model

K.C. Lau, Am. Biol. Teacher 82:413-415, 2020.

 Parallel Two-Compartment
Lung Mechanics Model

Redraw as an
electric circuit…

J.H.T. Bates, Lung Mechanics: An Inverse Modeling Approach,

Cambridge Univ. Press, 2009, Fig. 7.2.
 Arterial Windkessel

R. Berne & M. Levy, Cardiovascular Physiology, 8th ed., Fig. 6-1.

 Windkessel Fire Engine

http://www.auroraregionalfiremuseum.org/ N. Westerhof et al., Med. Biol.

handtubexpo/handtubs_&_musters.html Eng. Comp. 47:131-141, 2009,
(web page no longer accessible) Fig. 1.

windkessel (n, German): Air chamber.

 Arterial Windkessel

Represent by an
electric circuit
model…

R. Berne & M. Levy, Cardiovascular Physiology, 8th ed., Fig. 6-1.

Alternative Windkessel Configurations

I. Kokalari et al., J. Biomed. Sci.

Eng. 6:92-99, 2013, Fig. 7.
Circulatory System as Multiple
Windkessel-Like Compartments

I. Kokalari et al., J. Biomed. Sci. Eng. 6:92-99, 2013, Fig. 6.

 Alveoli

Represent CO2
flux by a
compartmental
model…
J. Keener and J. Sneyd, Mathematical Physiology, 2nd ed., 2009, Fig. 14.2.
Preparation for Friday’s Class

Read Case Study 1.

Be prepared to suggest
topics we could study
before attempting to
analyze the case.
 Summary
Analogous electrical and solid mechanics systems
schematics have different visual layouts.
When drawing electric circuit analogies for hydraulic
or pneumatic systems, consider fluid flow pathways
and locations where reference pressure (or voltage)
is observed.
When setting up compartmental models, consider
how the substance of interest enters and exits the
system and where it can accumulate within the
system.