Biokinetic Modeling

Question 1

Molecular Imaging

Answer 1

Understand fundamental molecular pathways
* specific biomarkers are addressed by tracer or contrast agent or internal signal

Question 2

Signal via

Answer 2

signal via internal signal
* Bioluminescence

Signal via contrast agent
* Contrast CT
* Contrast MRI
* Ultrasound bubble

Signal via tracer
* Radio activity (PET, SPECT)
* Magnetic wave (Hyperpolarized MRI)
* Optical light (Fluorescence tomography

Question 3

Pharmacokinetics (PK)

Answer 3

The branch of pharmacology concerned with the movement of
drugs within the body

Question 4

Study of the fate of substances administered
to a living organism

Answer 4

ADME
1) Absorption
2) Distribution
3) Metabolism
4) Excretion

Question 5

Factors influencing drug distribution:

Answer 5

• Blood flow
• Capillary permeability
• Relative hydrophobicity of the drug/tracer
• (binding to plasma/proteins)

Question 6

Image Processing methods

Answer 6

Principal component analysis (PCA) and Factor analysis (FA)

Problem in dynamic PET/SPECT:
* tissue heterogeneity
* partial volume effect

Aims of PCA and FA:
* Resolve true TACs
* Tissue segmentation
* Image-derived input functions
* Parametric images

Question 7

Pharmacokinetic Modeling

Answer 7

define mathematical models to describe and quantify drug behavior in
individuals

• Models:
• Non-compartmental models
• Compartmental models (most common: 1-compartment model and 2-compartment model)

Question 8

“A compartment is a

Answer 8

chemical species in a physical place”

Question 9

1-Tissue-Compartmental Model (2-compartment) is used for

Answer 9

substances/drugs that rapidly equilibrate with the tissue compartment (<20 min)

Question 10

Assumptions 1-Tissue-Compartmental

Answer 10

• Instant homogeneous distribution within entire compartment (blood, tissues)
• Steady-state: constant physiological processes & molecular interactions
• Transport between compartments: pure diffusion
• Linear interconnections among compartments

Question 11

Radioactive decay

Answer 11

decay correction of the measured PET data before further analysis
(data are corrected for decay at time 0)
* by implementation of decay into the compartmental model

Question 12

First order vs second order kinetics

Answer 12

Zero order kinetics
Constant amount
Concentration independent
Process is saturable
E.g ethanol

First order kinetics
Constant fraction
Concentration dependent
Most drugs (metabolized in liver)

Question 13

• [15O]H2O which model

Answer 13

• One compartment

Question 14

• [18F]FDG
• [18F]FMISO which model

Answer 14

Two compartment

Question 15

❑ Compartment model:
➢ Non-linear curve fitting
➢ Time consuming
Solution?

Answer 15

Linear Model
* Compartment model => Graphical model
* Irreversible two compartment model => Patlak Plot
* Reversible two compartment model => Logan Plot

Question 16

Blood Input Function methods

Answer 16

Blood Sampling
Image Based

Question 17

Blood Sampling adv disadv

Answer 17

Advantages:
* Direct measurement
* Blood analysis possible

Disadvantages:
* Time consuming and labor-intensive
* Invasive
* Limited time resolution
* Error sensitive
* Delay and dispersion in catheter

Question 18

Image Based adv disadv

Answer 18

Advantages:
* Straightforward
* Noninvasive
* Commonly used in humans

Disadvantages:
* Limited temporal resolution
* Whole blood
* Cardiac and respiratory motion
* Partial volume effect and spillover (e.g. brain)

Question 19

Reference Tissue

Answer 19

❑Advantages:
➢Noninvasive
➢System internal

❑Disadvantages:
➢Bias of modeling
➢Suitable reference tissue required

Question 20

Direct Parametric Image Reconstruction (Direct PIR):

Answer 20

• Low SNR:
  Indirect parametric image generation:

combine tracer kinetic modeling and emission image reconstruction into a single formula to estimate parametric images directly from the raw projection data