1. Analysis of PET studies Calculation of parametric images Turku PET Centre 2003-09-22 Vesa Oikonen

2. 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

3. 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 /K d )

4. Alternative analysis paths Regional results SPM Dynamic image Parametric image Regional curves

5. Advantages of parametric image: Effects are easy to see ROI definition is better Parametric image can be used in SPM

6. Disadvantages of parametric image: Calculation in ”black box” Distribution of regional pixel values is often skewed Results can be biased

7. How to calculate parametic images: http://pet.utu.fi/staff/vesoik/ Program downloads Documentation Frequently Asked Questions

8. 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

9. SUV image: demonstration 1.Check time frames 2.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.img Frame 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>

10. FUR image: demonstration 1.Check time frames 2.Sum last frames or extract last frame 3.Calculate plasma AUC from 0 to mid PET time 4.Divide sum image by plasma AUC F:\demo>ctiframe ua1015dy1.img Frame 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

11. Net uptake rate K i 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

12. 1.Calculate K i image 2.Calculate correction factor 3.Multiply K i image by this factor 4.View image to check success F:\demo>imgki ua1015vp.kbq ua1015dy1.img 10 ua1015ki.img reading dynamic image ua1015dy1.img computing 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 1 reading ua1015gur.img writing file ua1015gur_20.tif maximum pixel value in matrix is 50.2228, unit unknown F:\demo> Glucose uptake image: demonstration Unit: (µmol glucose)/ (min x 100g tissue)

13. 1.Calculate K i image 2.View image to check success 3.Calculate regional K i 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.img reading dynamic image ua1015dy1.img computing NNLS pixel-by-pixel...................................done. parametric image ua1015ki.img saved. F:\demo>ecat2tif ua1015ki.img ua1015ki_20.tif 20 1 reading ua1015ki.img writing file ua1015ki_20.tif maximum pixel value in matrix is 0.0531314, unit unknown F:\demo> K i image from compartmental model fit: demonstration 1(2) Unit: (ml plasma)/ (min x ml tissue)

14. 1.Calculate K i image 2.View image to check success 3.Calculate regional K i 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 Pl025 290 regional TACs written in ua1015ki.dft Variance 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 K i image from compartmental model fit: demonstration 2(2)

15. Distribution volume DV Measure of reversible uptake Calculated using two methods: 1.Graphical analysis: Logan plot 2.Compartmental model fit

16. 1.Calculate DV image 2.Calculate regional average DV values 3.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.img reading dynamic image uf0061dy1.img computing 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.img F:\demo>ecat2tif uf0061dvr.img uf0061dvr_20.tif 20 1 reading uf0061dvr.img writing file uf0061dvr_20.tif maximum pixel value in matrix is 9.64954, unit unknown DV and DVR images using plasma input: demonstration DVR is unitless

17. 1.Open Notepad (Start>Programs> Accessories>Notepad) 2.Write the commands 3.Save file as ”dvr.bat” in the data directory 4.Run the batch file with study number as argument, e.g. ”dvr uf0061” 5.View image to check success echo off echo Calculate regional TACs img2dft %1dy1.img %1*.roi echo Calculate average reference tissue TAC dftavg -rm %1dy1.dft pons echo Extract reference tissue TAC to a separate datafile del %1pons.dft dftadd %1pons.dft %1dy1.dft pons echo Calculate parametric Logan plot imgdv %1pons.dft %1dy1.img 15 %1dvr.img echo Make TIFF format image just for checking ecat2tif %1dvr.img %1dvr_20.tif 20 1 echo Calculate regional DVR values img2dft %1dvr.img %1*.roi echo Calculate regional averages over image planes dftavg %1dvr.dft echo List DVR values on screen dftlist %1dvr.dft DVR images using reference region input: demonstration DVR is unitless Contents of batch file dvr.bat :

18. 1.Open Notepad (Start>Programs> Accessories>Notepad) 2.Write the commands 3.Save file as ”dv.bat” in the data directory 4.Run the batch file with study number as argument, e.g. ”dv uf0061” 5.View image to check success echo off echo Fit DV pixel-by-pixel imglhdv %1ap.pure.kbq %1dy1.img %1dv.img echo Make TIFF format image just for checking ecat2tif %1dv.img %1dv_20.tif 20 1 echo Calculate regional DV values img2dft %1dv.img %1*.roi echo Calculate regional averages over image planes dftavg %1dv.dft echo List DV values on screen dftlist %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 :

19. 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

20. 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

21. Simplified reference tissue model (SRTM) Binding potential = receptor density × affinity Determined with three programs: 1.RPM (Matlab required) 2.imgsrtm Linearized model fit 3.imgbfbp, substitute for RPM (Matlab-independent)

22. 1.Open Notepad (Start>Programs> Accessories>Notepad) 2.Write the commands 3.Save file as ”srtm.bat” in the data directory 4.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 off echo Calculate regional TACs img2dft %1dy1.img %1*.roi echo Calculate average reference tissue TAC dftavg -rm %1dy1.dft cer echo Extract reference tissue TAC to a separate datafile del %1cer.dft dftadd %1cer.dft %1dy1.dft cer echo Calculate parametric BP, R1 and k2 images imgsrtm %1dy1.img %1cer.dft %1bp.img -R1=%1r1.img -k2=%1k2.img echo Make TIFF format images just for checking ecat2tif %1bp.img %1bp_20.tif 20 1 ecat2tif %1r1.img %1r1_20.tif 20 1 ecat2tif %1k2.img %1k2_20.tif 20 1 echo Calculate regional BP values img2dft %1bp.img %1*.roi echo Calculate regional averages over image planes dftavg -rm %1bp.dft echo List BP values on screen dftlist %1bp.dft BP image using imgsrtm: demonstration Contents of batch file srtm.bat : BP and R 1 are unitless. Unit of k 2 is min -1 BPR1R1 k2k2

23. Blood flow (perfusion) Determined by two methods: 1.Autoradiographic (ARG) method 2.Compartmental model fit

24. 1.Calibrate blood TAC and correct for decay and time delay and dispersion 2.Open Notepad (Start>Programs> Accessories>Notepad) 3.Write the commands 4.Save file as ”arg.bat” in the data directory 5.Run the batch file with study number as argument, e.g. ”arg uo0300” 6.View image to check success echo off echo Calculate look-up table arlkup %1fit.kbq 1.0 150 0 120 5000 %1.lkup echo Calculate integral image (change if framing is different) ctisum -i %1dy1.img 1 12 %1int.img echo Get flow for each pixel from the table ctilkup %1int.img %1.lkup %1flow.img echo Make TIFF image just for checking ecat2tif %1flow.img %1flow.tif 14 1 echo Calculate regional averages img2dft %1flow.img %1*.roi echo List regional flow values on screen dftlist %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

25. 1.Calibrate blood TAC and correct for decay and time delay and dispersion 2.Open Notepad (Start>Programs> Accessories>Notepad) 3.Write the commands 4.Save file as ”flow.bat” in the data directory 5.Run the batch file with study number as argument, e.g. ”flow uo0300” 6.View images to check success echo off echo Calculate parametric flow and partition volume image imgflow %1fit.kbq %1dy1.img 240 %1f.img -Va=NONE -DV=%1p.img echo Make TIFF images just for checking ecat2tif %1f.img %1f.tif 14 1 ecat2tif %1p.img %1p.tif 14 1 echo Calculate regional averages img2dft %1f.img %1*.roi img2dft %1p.img %1*.roi echo List regional flow values on screen dftlist %1f.dft echo List regional p values on screen dftlist %1p.dft Flow image using compartmental model fit: demonstration Contents of batch file flow.bat : Flowp With this method, unit of flow is (ml blood) / (min × ml tissue). Unit of p is (ml blood) / (ml tissue)

26. 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