Molecular Imaging
Understand fundamental molecular pathways
* specific biomarkers are addressed by tracer or contrast agent or internal signal
Signal via
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
Pharmacokinetics (PK)
The branch of pharmacology concerned with the movement of
drugs within the body
Study of the fate of substances administered
to a living organism
ADME
1) Absorption
2) Distribution
3) Metabolism
4) Excretion
Factors influencing drug distribution:
- Blood flow
- Capillary permeability
- Relative hydrophobicity of the drug/tracer
- (binding to plasma/proteins)
Image Processing methods
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
Pharmacokinetic Modeling
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)
“A compartment is a
chemical species in a physical place”
1-Tissue-Compartmental Model (2-compartment) is used for
substances/drugs that rapidly equilibrate with the tissue compartment (<20 min)
Assumptions 1-Tissue-Compartmental
- Instant homogeneous distribution within entire compartment (blood, tissues)
- Steady-state: constant physiological processes & molecular interactions
- Transport between compartments: pure diffusion
- Linear interconnections among compartments
Radioactive decay
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
First order vs second order kinetics
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)
- [15O]H2O which model
- One compartment
- [18F]FDG
- [18F]FMISO which model
Two compartment
❑ Compartment model:
➢ Non-linear curve fitting
➢ Time consuming
Solution?
Linear Model
* Compartment model => Graphical model
* Irreversible two compartment model => Patlak Plot
* Reversible two compartment model => Logan Plot
Blood Input Function methods
Blood Sampling
Image Based
Blood Sampling adv disadv
Advantages:
* Direct measurement
* Blood analysis possible
Disadvantages:
* Time consuming and labor-intensive
* Invasive
* Limited time resolution
* Error sensitive
* Delay and dispersion in catheter
Image Based adv disadv
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)
Reference Tissue
❑Advantages:
➢Noninvasive
➢System internal
❑Disadvantages:
➢Bias of modeling
➢Suitable reference tissue required
Direct Parametric Image Reconstruction (Direct PIR):
- 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
