ANALYSIS OF PET STUDIES PET Basics Course 2006 Turku PET Centre 2006-04-24 Vesa Oikonen

ANALYSIS OF PET STUDIES

PET Basics Course 2006

Turku PET Centre2006-04-24

Vesa Oikonenhttp://users.utu.fi/vesoik/

Analysis of PET studies

1. Instructions in quality system2. Retrieving data for analysis3. Steps of analysis4. Quantification in PET analysis5. Models6. Analysis tools in intranet and WWW7. Imaging, modelling and IT in

intranet

Quality documents:SOP, MET, DAN

• MET: analysis methods in general terms

• DAN: more detailed data analysis instructions

• http://petintra/

Quality data analysis

• Check when starting new study project:– the current analysis method– most recent software releases– never follow old ”recipes”!

• Even SOP and MET can be outdated!

Quality data analysis

• Follow a certain analysis chain (SOP, MET, DAN)

• If new software version is released during the study, recalculate all (or nothing)

• Record what documents you follow and software versions you use in electronic format

• Document all exceptions• Record final versions of documents and

analysis results in database (PETO)

PETO

• Requesting and scheduling studies• Retrieving data for analysis• Recording documentation• Storing final analysis results

PETO

http://petintra/Instructions/PETO_manual.pdf

Steps of analysis

Resu

lts

Para

metr

icIm

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e

+ Blood Data

Model calculations

Model calculations

Drawing ROI

SPM

Dyn

am

ic P

ET Im

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e

Reg

ion

al

TA

Cs

+ MRI

+ MRI

+ Blood Data

Drawing ROI

Collection of data and the specific method of analysis

depends on the studied question

• Sometimes the visual inspection of single image (static imaging) is sufficient, e.g. in tumour detection

• Detailed analysis requires dynamic imaging, often blood sampling, and elaborate modelling

• The more advanced statistical methods require parametric images

Static image

• One scan

• Resulting image planes (example):

Dynamic image

0 1 2 3 4 5 6 7

02468

1012141618202224

12

3

4

56

7

8

9

10

11

12 13

1415

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1718

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20

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B

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D

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H

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K L

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Con

cent

ratio

n (k

Bq/

ml)

Time from injection (min)Femoral region[15O]O2 bolus

Example of TACs

TACs tell us about the tissueTAC = time-activity (concentration) curve

0 15 30 45 60 75 900

10

20

30

40

50

60

70

80

90

Co

nce

ntr

atio

n o

f au

then

tic

trac

er (

kBq

/mL

)

Time (min)

0 15 30 45 60 75 900

10

20

30

40

50

60

70

80

90

Co

nce

ntr

atio

n in

tis

sue

(kB

q/m

L)

Time (min)

TAC of tracer concentration

in arterial blood

TAC of concentration

in tissue measured byPET scanner

Tissue characteristics:Perfusion

Endothelial permeabilityVascular volume fraction

Transport across cell membranes

Specific binding to receptorsNon-specific binding

Enzyme activity

Parametric image• Dynamic information is converted to

functional information with dedicated software– Not a series of scans (smaller file size)– image voxel value = the value of the

studied physiological parameter (perfusion, glucose consumption, receptor density)

• More sophisticated analyses possible– requires careful evaluation of alternative

models before choosing the right model

Regions of interest = ROI

• Anatomical regions – detection requires MRI– drawn into the MR image by

hand– also automatic software are

developed• Aim: calculate the average

of the studied physiological parameter in a specific anatomical region

• E. g. quantification of dopamine receptor densities in frontal cortex of brain

www.imadeus.com

PET is a quantitative tool• Radioactivity concentration (tissue or

plasma) can be easily converted to drug concentration:

drug concentration =

• Drug concentration is used to measure tissue function in vivo: perfusion, glucose consumption, receptor density, enzyme activity, etc.

]/[]/[ 3

molGBqityradioactivspecificcmkBqionconcentratityradioactiv

Calibration

• Tissue and reference radioactivity must be comparable

• PET, well counter for plasma samples, and dose calibratorare all cross-calibrated

• Calibration is done by PET physicist

Physical decay

• In PET, drugs are labelled with positron emitting isotopes with very short half-lives

• During the PET study, isotope label is decaying substantially, compared to the drug; specific radioactivity is decreasing

• To correct this, all measured radioactivity are corrected to the time of injection

)2ln(21)()0(

T

t

etCC

How to study the characteristics of tissue?

• Alternatives for model calculation:– Compartment models– Spectral analysis– Ratio– MTGA (Logan or Gjedde-Patlak plot)– FUR– SUV

• Comparison table http://www.turkupetcentre.net/modelling/methods/pet_analysis_method_table.html

Arterial FDG

Venous FDG

Interstitial FDG

Intracellular FDG

Intracellular FDG-6-P

Compartmental model for [18F]FDG in muscle

Multiple-time graphical analysis (MTGA)

• Independent of compartments• Data is transformed to a linear plot• Macro-parameter estimated directly

as the slope of linear phase of plot• Reversible models:

Logan analysis (DV, DVR)• Irreversible models:

Gjedde-Patlak analysis (Ki)

Logan analysiswith plasma input

0 5 10 15 20 25 300

20

40

60

80

100

120

140

160

CR

OI i

nte

gra

l / C

RO

I

CPLASMA

integral / CROI

Distribution volume=

Slope of the Logan plot

Distribution volumeratio =Ratio of slopes of theROI and referenceregionLogan J. Graphical analysis of PET data applied to reversible

and irreversible tracers. Nucl Med Biol 2000;27:661-670

Gjedde-Patlak analysiswith plasma input

0 20 40 60 80 1000.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

CR

OI/C

PL

AS

MA (

mL

/mL

)

CPLASMA

integral/CPLASMA

(min)

Net influx rate Ki=

Slope of the Patlak plot

Unit of Ki =ml plasma * min-1 * ml tissue-1

Patlak CS, Blasberg RG. Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. Generalizations. J Cereb Blood Flow Metab 1985;5:584-590.

Standardized uptake value SUV

• Simple, semi-quantitative measure (g/ml) • Regional radioactivity concentration

(kBq/ml) normalized by injected dose (GBq) and subject weight (kg)

• Average SUV in entire body = body density• Blood sampling not needed• Example: measuring amino acid

methionine uptake in tumour studies

Using analysis software

• Can be used on any PCwith Windows XP inhospital network and/orPET intranet

• Downloadable in WWW• Analysis instructions in

WWW

• http://www.turkupetcentre.net/• P:\bin\windows

www.turkupetcentre.net

www.turkupetcentre.net

Requesting software

• New software• Feature requests• Bug reports• Project follow-up• Software documents

• http://petintra/softaryhma/

• or ask IT or modelling group members

Imaging and modellingmethod development and

validation• Instrumentation• Image processing• Modelling• Project follow-up• Documentation

• http://petintra/imaging/• or ask imaging group

members