Modeling Systems and Processes

Anthony McGoron, PhD

Associate Professor
Department of Biomedical Engineering
Florida International University
 Mathematical Modeling
A model is any representation of a real system.
– May deal with structure or function
– May involve words, diagrams, mathematical notation,
physical structure
– May have the same meaning as “hypothesis”
– Must always involve simplification of the real system
– A mathematical model may be as simple as a single equation
relating a single dependent variable (y) to another
independent variable (x) such as: y = ax + b
– May be multi-component involving the interaction of many
equations having several mutually dependent variables
dy1
 f1 (t , y1 , y 2 ,..., y n ); y1 (t 0 )  y1, 0
a11 x1  a12 x2  ...a1n xn  b1 dt
dy 2
a21 x1  a22 x2  ...a2 n xn  b2  f 2 (t , y1 , y 2 ,..., y n ); y 2 (t 0 )  y 2, 0
dt
an1 x1  an 2 x2  ...ann xn  bn dy n
 f n (t , y1 , y 2 ,..., y n ); y n (t 0 )  y n , 0
dt
 Building Models
Stepwise replacement of a system component with a model equation.
1. Conceptual model of the real system. Without an understanding
of the real system and the interaction of the system with its
environment, no model can be developed.
2. Design experiments and collect “good” data that accurately
represents the real system.
3. Examine the data to determine the parameter set that defines the
system f(x,y,t,a,b,c…).
4. Define an equation based on the data (empirical) and/or based on
the characteristics of the system (theory based). For example,
y = ax + b. y and x are variables. a and b are parameters.
5. Find the optimal (most correct) values for the parameters a and b.
6. Implement the model to “experiment” with new concepts.
Building Models: An Example
Food Chain/Ecosystem/Photosynthesis
Conceptual components of a hypothetical system are replaced by
equations to form a multi-component model of a system (Keen and
Spain, 1992)
The role of quantitative modeling and simulation within the process
of research (Keen and Spain, 1992)
 Modeling Application - Transport
mass, energy, momentum

Heart Lung
Hemodialysis Bypass Machine
 An Example: Drug Distribution
Mass Transport

Pharmacology – The history, source, physical and chemical

properties, biochemical and physiological effect, mechanisms of
action, absorption, distribution, biotransformation and excretion,
and therapeutic and other uses of drugs.

Pharmacokinetics – Absorption, Distribution, Metabolism

(biotransformation) and Excretion of drugs (ADME).

Pharmacodynamics – Biochemical and physiological effects

and their mechanisms of action
Concentration of drug in the body as a function of time for
two types of drug dosage forms

(Rowland and Beckett, 1964)

 Locus of Tissue
Action Reservoirs
“receptors”
Bound Free Bound Free

Systemic
Circulation

Absorption Free Drug Excretion

Metabolites
Bound Drug

Biotransformation

Physiochemical factors in transfer of drugs across membranes:

absorption, distribution, biotransformation, and excretion of a drug
involve its passage across cell membranes.
General compartment model for the human body (Bischoff and
Brown, 1966)
Numerical details of a specific pharmacokinetic model of the
body. There will be 36 equations (Bischoff and Brown, 1966).
Model for a local tissue region (Bischoff and brown, 1966)
 Simple Compartmental Model (lumped)
Absorption Elimination
Body k1
R or k0
dA dE dB
1st order absorption: dt  k 0 A kB  k Ak B
dt
0 1
dt
1

Solution: A(t )  A exp(k t )

0 0

kA
B(t )  0
 [exp( k t )  exp( k t )]
0

k k
0 1
1 0

    1  
E (t )  A  A(t )  B(t )  A 1   [k exp( k t )  k exp(k t ]
 k k
0 0 1 0 0 1
1 0  
IC’s:A(o)=A0 100
E
B(0)=0 80
E(o)=0 A A E
% of Dose

60

40
B B
20

0
0 5 10 15 20 25 30 35
Time (hrs)
 Simple Compartmental Model (lumped)
k0 k1
Absorption P Elimination

k12 k21
dA/dt=-ko*A
dP/dt=k0*A-k1*P-k12*P+k21*T
T dT/dt=k12*P-k21T
dE/dt=k1P
20
Plasma
15
mg

10
Tissue
5

0
0 5 10 15 20 25 30
t (minutes)
 Medical Application
Nuclear Medicine Imaging

Plasma time activity curve and Tissue time activity curve

© 1994-2000 Crump Institute for Molecular Imaging

UCLA School of Medicine
 Three compartment FDG model

© 1994-2000 Crump Institute for Molecular Imaging

UCLA School of Medicine
Building the TTAC from
the ROI

© 1994-2000 Crump Institute for Molecular Imaging

UCLA School of Medicine
Building the TTAC from
the ROI

© 1994-2000 Crump Institute for Molecular Imaging

UCLA School of Medicine
Building the TTAC from
the ROI

© 1994-2000 Crump Institute for Molecular Imaging

UCLA School of Medicine
Model Simulation
and optimization

© 1994-2000 Crump Institute for Molecular Imaging

UCLA School of Medicine
Model Simulation
and optimization

© 1994-2000 Crump Institute for Molecular Imaging

UCLA School of Medicine
Model Simulation
and optimization

© 1994-2000 Crump Institute for Molecular Imaging

UCLA School of Medicine