1. MYOCARDIAL BLOOD FLOW WITH [ 15 O]H 2 O PET: ERROR ESTIMATES Turku PET Centre Vesa Oikonen http://users.utu.fi/vesoik/ http://users.utu.fi/vesoik/ TPC modelling workshop 2005-09-14

2. Model parameters MBF myocardial blood flow in perfusable tissue volume α perfusable tissue fraction, PTF V A myocardial blood volume fraction and spill-over from LV cavity

3. MBF model is fitted… 1.to ROI curves drawn on LV cavity (“lv”) and on entire myocardial tissue surrounding the cavity (“whole”) to estimate virtual arterial blood concentration, C A (t) 2.To smaller myocardial ROIs using C A (t) as model input.

4. Results of MBF model fit fitmbf 2.1.3 (c) 1999-2005 by Turku PET Centre Date: 2005-09-13 Study: s05851dy Data file: S05851\s05851.dft Reference region: lv All Data range: 0 - 360 sec (N=20) Beta: 0.85 Data was not weighted. Region flow alpha Va SS AIC lat. All 0.8120 0.6564 0.2671 9.5215e+001 3.8708e+001 ant. All 0.8613 0.6391 0.2036 1.2060e+002 4.3434e+001 sept. All 0.7151 0.5245 0.4841 1.9348e+002 5.2888e+001 whole. All 0.8353 0.6329 0.2863 4.8313e+001 2.5140e+001 Estimates of model parametersAkaike information criteria for comparison between models (Weighted) Sum-of-squares describing goodness-of-fit

5. Error estimate for each model parameter 95% confidence limits and/or standard deviations With command-line options -CL and –SD Bootstrap method (Efron and Tibshirani, 1993; Turkheimer et al., 1998) Starting from fitmbf version 2.1.0, 2005-07-15fitmbf

6. Measured and fitted TACs

7. Results with error estimates fitmbf 2.1.3 (c) 1999-2005 by Turku PET Centre Date: 2005-09-13 Study: s05851dy Data file: S05851\s05851.dft Reference region: lv All Data range: 0 - 360 sec (N=20) Beta: 0.85 Data was not weighted. Region flow alpha Va SS AIC lat. All 0.8120 0.6564 0.2671 9.5215e+001 3.8708e+001 SD.. 0.0456 0.0164 0.0163.. CL 95% Lower 0.7241 0.6228 0.2364.. CL 95% Upper 0.9012 0.6849 0.2955.. ant. All 0.8613 0.6391 0.2036 1.2060e+002 4.3434e+001 SD.. 0.0529 0.0193 0.0191.. CL 95% Lower 0.7701 0.6073 0.1674.. CL 95% Upper 0.9690 0.6768 0.2376.. sept. All 0.7151 0.5245 0.4841 1.9348e+002 5.2888e+001 SD.. 0.0758 0.0205 0.0202.. CL 95% Lower 0.5683 0.4827 0.4439.. CL 95% Upper 0.8756 0.5612 0.5236.. whole. All 0.8353 0.6329 0.2863 4.8313e+001 2.5140e+001 SD.. 0.0401 0.0126 0.0123.. CL 95% Lower 0.7561 0.6076 0.2601.. CL 95% Upper 0.9169 0.6594 0.3097..

8. Larger errors with higher MBF BASAL study Region flow alpha Va SS AIC lat. All 0.7259 0.6577 0.1498 6.3335e+001 3.0554e+001 SD.. 0.0493 0.0176 0.0176.. ant. All 0.6751 0.5503 0.2290 7.2341e+001 3.3213e+001 SD.. 0.0596 0.0186 0.0187.. sept. All 0.5756 0.5703 0.4679 3.4841e+002 6.4653e+001 SD.. 0.1109 0.0401 0.0370.. whole. All 0.6823 0.5924 0.2555 7.0570e+001 3.2717e+001 SD.. 0.0627 0.0193 0.0197.. Stimulation Region flow alpha Va SS AIC lat. All 4.1351 0.7403 0.0500 7.1618e+001 3.3012e+001 SD.. 0.4198 0.0486 0.0461.. ant. All 2.8656 0.4734 0.2891 1.3123e+002 4.5125e+001 SD.. 0.8369 0.0922 0.0906.. sept. All 4.9285 0.7674 0.2390 1.6528e+002 4.9738e+001 SD.. 1.0812 0.1251 0.1183.. whole. All 4.0911 0.6560 0.1708 4.9344e+001 2.5562e+001 SD.. 0.7307 0.0717 0.0682..

9. … with confidence limits fitmbf 2.1.3 (c) 1999-2005 by Turku PET Centre Date: 2005-09-13 Study: s06003dy Data file: S06002\s06003.dft Reference region: lv All Data range: 0 - 360 sec (N=20) Beta: 0.85 Data was not weighted. Region flow alpha Va SS AIC lat. All 4.1351 0.7403 0.0500 7.1618e+001 3.3012e+001 CL 95% Lower 3.3282 0.6074 0.0228.. CL 95% Upper 4.9667 0.7831 0.1776.. ant. All 2.8656 0.4734 0.2891 1.3123e+002 4.5125e+001 CL 95% Lower 1.5818 0.3160 0.0794.. CL 95% Upper 4.7635 0.6941 0.4426.. sept. All 4.9285 0.7674 0.2390 1.6528e+002 4.9738e+001 CL 95% Lower 2.9679 0.5418 0.0292.. CL 95% Upper 6.9406 0.9908 0.4528.. whole. All 4.0911 0.6560 0.1708 4.9344e+001 2.5562e+001 CL 95% Lower 2.8782 0.5174 0.0445.. CL 95% Upper 5.7352 0.7852 0.2994..

10. Reduce SD by constraining α α during stimulation study is constrained to the estimate from basal conditions With command-line options -fAlpha and -f=basal.res, when using fitmbf 2.1.0 and later versionsfitmbf Also V A can be constrained with option -fVa.

11. … after constraints for α fitmbf 2.1.3 (c) 1999-2005 by Turku PET Centre Date: 2005-09-13 Study: s06003dy Data file: S06002\s06003.dft Reference file: results\s06002mbf1.res Reference region: lv All Data range: 0 - 360 sec (N=20) Beta: 0.85 Data was not weighted. Region flow alpha Va SS AIC lat. All 3.5534 0.6577 0.1283 7.6282e+001 3.1480e+001 CL 95% Lower 2.8580 0.6577 0.1096.. CL 95% Upper 4.3003 0.6577 0.1494.. ant. All 3.4219 0.5503 0.2140 1.3465e+002 4.2845e+001 CL 95% Lower 2.5938 0.5503 0.1865.. CL 95% Upper 4.6877 0.5503 0.2379.. sept. All 3.2420 0.5703 0.4294 1.7751e+002 4.8372e+001 CL 95% Lower 2.3396 0.5703 0.4071.. CL 95% Upper 4.5089 0.5703 0.4600.. whole. All 3.5087 0.5924 0.2319 5.0833e+001 2.3362e+001 CL 95% Lower 2.9207 0.5924 0.2190.. CL 95% Upper 4.2717 0.5924 0.2447..

12. … constraints for α and V A fitmbf 2.1.3 (c) 1999-2005 by Turku PET Centre Date: 2005-09-13 Study: s06003dy Data file:..\S06002\s06003.dft Reference file: s06002mbf1.res Reference region: lv All Data range: 0 - 360 sec (N=20) Beta: 0.85 Data was not weighted. Region flow alpha Va SS AIC lat. All 3.0499 0.6577 0.1498 9.4997e+001 3.3384e+001 CL 95% Lower 2.6776 0.6577 0.1498.. CL 95% Upper 3.4477 0.6577 0.1498.. ant. All 2.9320 0.5503 0.2290 1.4408e+002 4.1715e+001 CL 95% Lower 2.3330 0.5503 0.2290.. CL 95% Upper 3.6193 0.5503 0.2290.. sept. All 2.3688 0.5703 0.4679 2.2999e+002 5.1068e+001 CL 95% Lower 1.9069 0.5703 0.4679.. CL 95% Upper 2.9013 0.5703 0.4679.. whole. All 2.8962 0.5924 0.2555 7.2143e+001 2.7881e+001 CL 95% Lower 2.4452 0.5924 0.2555.. CL 95% Upper 3.3895 0.5924 0.2555..

13. Constraints or not? Calculate results without and with constraints ( α, α and V A, V A ) Select the method that gives constantly smaller AIC

14. References 1.Araujo LI, Lammertsma AA, Rhodes CG, McFalls EO, Iida H, Rechavia E, Galassi A, De Silva R, Jones T, Maseri A. Noninvasive quantification of regional myocardial blood flow in coronary artery disease with oxygen-15- labeled carbon dioxide inhalation and positron emission tomography. Circulation 1991; 83: 875-885. 2.Efron B, Tibshirani RJ. An introduction to the bootstrap. (1993) Chapman & Hall, New York. 3.Iida H, Rhodes CG, de Silva R, Yamamoto Y, Araujo LI, Maseri A, Jones T. Myocardial tissue fraction – correction for partial volume effects and measure of tissue viability. J. Nucl. Med. 1991; 32:2169-2175. 4.Iida H, Rhodes CG, de Silva R, Araujo LI, Bloomfield P, Lammertsma AA, Jones T. Use of the left ventricular time-activity curve as a noninvasive input function in dynamic oxygen-15-water positron emission tomography. J. Nucl. Med. 1992; 33:1669-1677. 5.Turkheimer F, Sokoloff L, Bertoldo A, Lucignani G, Reivich M, Jaggi JL, Schmidt K. Estimation of component and parameter distributions in spectral analysis. J. Cereb. Blood Flow Metabol. 1998; 18: 1211-1222. 6.Watabe H, Jino H, Kawachi N, Teramoto N, Hayashi T, Ohta Y, Iida H. Parametric imaging of myocardial blood flow with 15 O-water and PET using the basis function method. J. Nucl. Med. 2005; 46: 1219-1224.

15. More information Detailed report TPCMOD0005 http://www.turkupetcentre.net/reports/ http://www.turkupetcentre.net/reports/ Analysis instructions http://www.turkupetcentre.net/analysis/doc/tracer/mbf_h2o. html http://www.turkupetcentre.net/analysis/doc/tracer/mbf_h2o. html Bootstrap method in estimation of variance of model parameters http://www.turkupetcentre.net/modelling/workshop1/bootstr ap.ppt http://www.turkupetcentre.net/modelling/workshop1/bootstr ap.ppt