Analysis of PET studies

Calculation of parametric images

Turku PET Centre2003-09-22

Vesa Oikonen

Dynamic PET image

• GE Advance: 35 image planes• 128x128 pixels / plane• N time frames: e.g. 0-30 s, 30-60 s,

60-120 s, 120-180 s, 180-300 s, ...• Pixel value =

radioactivity concentration (kBq/mL) during time frame

Parametric image

• Time frame information combined to one parametric image

• Pixel value = Physiological measure– Examples:Perfusion (mL blood)/(min x mL tissue)Glucose uptake rate

(µmol glucose) / (min x mL tissue)Binding potential (B’max/Kd)

Alternative analysis paths

Regional results

SPM

Dynamicimage

Parametricimage

Regionalcurves

Advantages ofparametric image:

• Effects are easy to see• ROI definition is better• Parametric image can be used in

SPM

Disadvantages ofparametric image:

• Calculation in ”black box”• Distribution of regional pixel values

is often skewed• Results can be biased

How to calculate parametic images:

http://pet.utu.fi/staff/vesoik/

•Program downloads•Documentation•Frequently Asked Questions

SUV and FUR

• Standardized Uptake Value = SUV• ROI divided by patient weight• no blood sampling required• simple value for assessing

cumulated radioactivity

• Fractional Uptake Rate = FUR• ROI corrected for plasma AUC

(area under curve)• blood samples necessary

SUV image: demonstration

1. Check time frames2. Sum selected frames,

or extract one (last) frame

3. Use calculator to determine injected dose / body weight or BSA

4. Divide sum image by this result

F:\demo>dir *.img Volume in drive F is PET Volume Serial Number is EC0C-22C8

Directory of F:\demo

2003-09-11 23:03 19,812,352 ua1015dy1.img 1 File(s) 19,812,352 bytes 0 Dir(s) 4,168,876,032 bytes free

F:\demo>ctiframe ua1015dy1.imgFrame Start End Dur (sec) Start End Dur (min) 1 0 30 30 0.00 0.50 0.50 2 30 60 30 0.50 1.00 0.50 3 60 90 30 1.00 1.50 0.50 4 90 120 30 1.50 2.00 0.50 5 120 180 60 2.00 3.00 1.00 6 180 240 60 3.00 4.00 1.00 7 240 300 60 4.00 5.00 1.00 8 300 600 300 5.00 10.00 5.00 9 600 900 300 10.00 15.00 5.00 10 900 1200 300 15.00 20.00 5.00 11 1200 1500 300 20.00 25.00 5.00 12 1500 1800 300 25.00 30.00 5.00 13 1800 2100 300 30.00 35.00 5.00 14 2100 2400 300 35.00 40.00 5.00 15 2400 2700 300 40.00 45.00 5.00 16 2700 3000 300 45.00 50.00 5.00 17 3000 3300 300 50.00 55.00 5.00

F:\demo>ctisum ua1015dy1.img 13 17 ua1015sum.img....................................done.

F:\demo>ecatcalc ua1015sum.img : 14.2 ua1015suv.img

F:\demo>

FUR image: demonstration

1. Check time frames2. Sum last frames or

extract last frame3. Calculate plasma

AUC from 0 to mid PET time

4. Divide sum image by plasma AUC

F:\demo>ctiframe ua1015dy1.imgFrame Start End Dur (sec) Start End Dur (min) 1 0 30 30 0.00 0.50 0.50 2 30 60 30 0.50 1.00 0.50 3 60 90 30 1.00 1.50 0.50 4 90 120 30 1.50 2.00 0.50 5 120 180 60 2.00 3.00 1.00 6 180 240 60 3.00 4.00 1.00 7 240 300 60 4.00 5.00 1.00 8 300 600 300 5.00 10.00 5.00 9 600 900 300 10.00 15.00 5.00 10 900 1200 300 15.00 20.00 5.00 11 1200 1500 300 20.00 25.00 5.00 12 1500 1800 300 25.00 30.00 5.00 13 1800 2100 300 30.00 35.00 5.00 14 2100 2400 300 35.00 40.00 5.00 15 2400 2700 300 40.00 45.00 5.00 16 2700 3000 300 45.00 50.00 5.00 17 3000 3300 300 50.00 55.00 5.00

F:\demo>ctisplit ua1015dy1.img 17 1-35 ua1015last.img

F:\demo>interpol -a -i -x52.5 ua1015vp.kbq 52.50000 7.144e+02# interpol 2.4 (c) 1993-2002 by Turku PET Centre:

ua1015vp.kbq

F:\demo>ecatcalc ua1015last.img : 714.4 ua1015fur.img

Net uptake rate Ki

• Measure of irreversible uptake• Unit (ml plasma)/(min x ml tissue)

Calculated using two methods:1. Graphical analysis

(Gjedde-Patlak plot)2. Compartmental model fit

1. Calculate Ki image2. Calculate correction

factor

3. Multiply Ki image by this factor

4. View image to check success

F:\demo>imgki ua1015vp.kbq ua1015dy1.img 10 ua1015ki.imgreading dynamic image ua1015dy1.imgcomputing MTGA pixel-by-pixel...................................done.Ki image ua1015ki.img saved.

F:\demo>ecatcalc ua1015ki.img x 924.6 ua1015gur.img

F:\demo>ecat2tif ua1015gur.img ua1015gur_20.tif 20 1reading ua1015gur.imgwriting file ua1015gur_20.tifmaximum pixel value in matrix is 50.2228, unit unknown

F:\demo>

Glucose uptake image: demonstration

mlgdensityTissueLC

mMegluPlasma

/,

,cos100

Unit:(µmol glucose)/(min x 100g tissue)

1. Calculate Ki image2. View image to

check success3. Calculate regional

Ki average and SD values

4. Calculate structural averages over image planes

5. List the regional results on screen

F:\demo>imglhki ua1015vp.kbq ua1015dy1.img ua1015ki.imgreading dynamic image ua1015dy1.imgcomputing NNLS pixel-by-pixel...................................done.parametric image ua1015ki.img saved.

F:\demo>ecat2tif ua1015ki.img ua1015ki_20.tif 20 1reading ua1015ki.imgwriting file ua1015ki_20.tifmaximum pixel value in matrix is 0.0531314, unit unknown

F:\demo>

Ki image from compartmental model fit:

demonstration 1(2)

Unit:(ml plasma)/(min x ml tissue)

1. Calculate Ki image2. View image to

check success3. Calculate regional

Ki average and SD values

4. Calculate structural averages over image planes

5. List the regional results on screen

F:\demo>img2dft ua1015ki.img ua1015*.roi -Vsd calculated sfro dx Pl006 calculated sfro sin Pl006…calculated cer sin Pl025290 regional TACs written in ua1015ki.dftVariance data written in ua1015ki.sd

F:\demo>dftavg -rm ua1015ki.dft…290 TAC(s) are deleted; backup is in ua1015ki.dft%

F:\demo>dftlist ua1015ki.dft 1: sfro dx All 1.791e+04 2.861e-02 2: sfro sin All 1.795e+04 2.795e-02 3: rwmdx All 4.552e+03 2.249e-02 4: rwmsin All 4.599e+03 2.017e-02 5: par dx All 5.463e+03 2.717e-02 6: par sin All 5.510e+03 2.771e-02 7: mfro sin All 1.688e+04 3.156e-02 8: mfro dx All 1.702e+04 3.130e-02 9: ifro dx All 1.142e+04 2.969e-02 10: ifro sin All 1.184e+04 2.967e-02 11: occ dx All 1.032e+04 2.633e-02 12: occ sin All 1.079e+04 2.747e-02 13: stem sin All 1.167e+04 2.816e-02 14: stem dx All 1.188e+04 2.901e-02 15: mtem sin All 1.261e+04 2.702e-02 16: mtem dx All 1.170e+04 2.898e-02 17: cing dx All 8.732e+03 2.996e-02 18: cing sin All 9.292e+03 2.797e-02 19: item dx All 9.875e+03 2.723e-02 20: item sin All 1.002e+04 2.598e-02 21: th dx All 5.534e+03 3.018e-02 22: th sin All 5.509e+03 3.060e-02 23: str sin All 9.757e+03 3.113e-02 24: str dx All 9.385e+03 3.038e-02

Ki image from compartmental model fit:

demonstration 2(2)

Distribution volume DV

Measure of reversible uptake

Calculated using two methods:1. Graphical analysis: Logan plot2. Compartmental model fit

1. Calculate DV image2. Calculate regional

average DV values3. Calculate structural

averages over image planes

4. Divide DV image by reference region DV

5. View image to check success

F:\demo>imgdv uf0061ap.pure.kbq uf0061dy1.img 15 uf0061dv.imgreading dynamic image uf0061dy1.imgcomputing logan plot pixel-by-pixel...................................done.DV image uf0061dv.img saved.

F:\demo>img2dft uf0061dv.img uf0061*.roi…48 regional TACs written in uf0061dv.dft

F:\demo>dftavg -rm uf0061dv.dft…48 TAC(s) are deleted; backup is in uf0061dv.dft%

F:\demo>dftlist uf0061dv.dft 1: frad All 4.062e+03 6.174e+00… 23: pons All 1.027e+03 1.040e+00 24: cerd All 1.389e+04 3.995e+00

F:\demo>ecatcalc uf0061dv.img : 1.040 uf0061dvr.imgF:\demo>ecat2tif uf0061dvr.img uf0061dvr_20.tif 20 1reading uf0061dvr.imgwriting file uf0061dvr_20.tifmaximum pixel value in matrix is 9.64954, unit unknown

DV and DVR images using plasma input: demonstration

DVR is unitless

1. Open Notepad (Start>Programs>Accessories>Notepad)

2. Write the commands3. Save file as ”dvr.bat”

in the data directory4. Run the batch file

with study number as argument, e.g. ”dvr uf0061”

5. View image to check success

echo offecho Calculate regional TACsimg2dft %1dy1.img %1*.roiecho Calculate average reference tissue TACdftavg -rm %1dy1.dft ponsecho Extract reference tissue TAC to a separate datafiledel %1pons.dftdftadd %1pons.dft %1dy1.dft ponsecho Calculate parametric Logan plotimgdv %1pons.dft %1dy1.img 15 %1dvr.imgecho Make TIFF format image just for checkingecat2tif %1dvr.img %1dvr_20.tif 20 1echo Calculate regional DVR valuesimg2dft %1dvr.img %1*.roiecho Calculate regional averages over image planesdftavg %1dvr.dftecho List DVR values on screendftlist %1dvr.dft

DVR images using reference region input: demonstration

DVR is unitless

Contents of batch file dvr.bat :

1. Open Notepad (Start>Programs>Accessories>Notepad)

2. Write the commands3. Save file as ”dv.bat”

in the data directory4. Run the batch file

with study number as argument, e.g. ”dv uf0061”

5. View image to check success

echo offecho Fit DV pixel-by-pixelimglhdv %1ap.pure.kbq %1dy1.img %1dv.imgecho Make TIFF format image just for checkingecat2tif %1dv.img %1dv_20.tif 20 1echo Calculate regional DV valuesimg2dft %1dv.img %1*.roiecho Calculate regional averages over image planesdftavg %1dv.dftecho List DV values on screendftlist %1dv.dft

DV image using plasma input and compartmental model fit: demonstration

Unit of DV is(ml plasma)/(ml tissue)

Contents of batch file dv.bat :

Comparison of the analysis methods

Graphical analysis:

+no information needed of model compartments

– restricted to linear portion of data

Compartmental model fit:

+Not restricted to linear portion of data

– requires good-quality input curve and delay correction

Advantages of batch files

• Less writing = less errors• Calculation steps are easy to

check and repeat• Changes are simple to perform

using any text editor(Wordpad, textedit)

• Unix and Linux have scripting languages with even more features

Simplified reference tissue model (SRTM)

Binding potential= receptor density × affinity

Determined with three programs:

1. RPM (Matlab required)2. imgsrtm Linearized model fit3. imgbfbp, substitute for RPM

(Matlab-independent)

1. Open Notepad (Start>Programs>Accessories>Notepad)

2. Write the commands3. Save file as ”srtm.bat”

in the data directory4. Run the batch file with

study number as argument, and direct output to log file, e.g. ”srtm ub0419 > ub0419.log”

5. View images to check success

echo offecho Calculate regional TACsimg2dft %1dy1.img %1*.roiecho Calculate average reference tissue TACdftavg -rm %1dy1.dft cerecho Extract reference tissue TAC to a separate datafiledel %1cer.dftdftadd %1cer.dft %1dy1.dft cerecho Calculate parametric BP, R1 and k2 imagesimgsrtm %1dy1.img %1cer.dft %1bp.img -R1=%1r1.img -k2=

%1k2.imgecho Make TIFF format images just for checkingecat2tif %1bp.img %1bp_20.tif 20 1ecat2tif %1r1.img %1r1_20.tif 20 1ecat2tif %1k2.img %1k2_20.tif 20 1echo Calculate regional BP valuesimg2dft %1bp.img %1*.roiecho Calculate regional averages over image planesdftavg -rm %1bp.dftecho List BP values on screendftlist %1bp.dft

BP image using imgsrtm: demonstration

Contents of batch file srtm.bat :

BP and R1 are unitless. Unit of k2 is min-1

BP R1 k2

Blood flow (perfusion)

Determined by two methods:

1. Autoradiographic (ARG) method

2. Compartmental model fit

1. Calibrate blood TAC and correct for decay and time delay and dispersion

2. Open Notepad (Start>Programs>Accessories>Notepad)

3. Write the commands4. Save file as ”arg.bat” in

the data directory5. Run the batch file with

study number as argument, e.g. ”arg uo0300”

6. View image to check success

echo offecho Calculate look-up tablearlkup %1fit.kbq 1.0 150 0 120 5000 %1.lkupecho Calculate integral image (change if framing is

different)ctisum -i %1dy1.img 1 12 %1int.imgecho Get flow for each pixel from the tablectilkup %1int.img %1.lkup %1flow.imgecho Make TIFF image just for checkingecat2tif %1flow.img %1flow.tif 14 1echo Calculate regional averagesimg2dft %1flow.img %1*.roiecho List regional flow values on screendftlist %1flow.dft

Flow image using ARG: demonstration

Contents of batch file arg.bat :

With this method, unit of flow is(ml blood) / (min × 100 ml tissue)

Flow

1. Calibrate blood TAC and correct for decay and time delay and dispersion

2. Open Notepad (Start>Programs>Accessories>Notepad)

3. Write the commands4. Save file as ”flow.bat”

in the data directory5. Run the batch file with

study number as argument, e.g. ”flow uo0300”

6. View images to check success

echo offecho Calculate parametric flow and partition volume imageimgflow %1fit.kbq %1dy1.img 240 %1f.img -Va=NONE -DV=%1p.imgecho Make TIFF images just for checkingecat2tif %1f.img %1f.tif 14 1ecat2tif %1p.img %1p.tif 14 1echo Calculate regional averagesimg2dft %1f.img %1*.roiimg2dft %1p.img %1*.roiecho List regional flow values on screendftlist %1f.dftecho List regional p values on screendftlist %1p.dft

Flow image using compartmental model fit:

demonstrationContents of batch file flow.bat :

Flow p

With this method, unit of flow is(ml blood) / (min × ml tissue).Unit of p is (ml blood) / (ml tissue)

Supported image file formats

• Currently all programs use ECAT 6.3 (*.img; ECAT 931, GE Advance)

• Now some programs, and in the near future all programs can also use ECAT 7.x (*.v; ECAT HR+)

• Analyze -format will be supported, possibly also Interfile -format