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Turku PET Centre Vesa Oikonen http://users.utu.fi/vesoik/. MYOCARDIAL BLOOD FLOW WITH [ 15 O]H 2 O PET: ERROR ESTIMATES. TPC modelling workshop 2005-09-14. Model parameters. MBF myocardial blood flow in perfusable tissue volume α perfusable tissue fraction, PTF
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Turku PET Centre Vesa Oikonenhttp://users.utu.fi/vesoik/ MYOCARDIAL BLOOD FLOW WITH [15O]H2O PET:ERROR ESTIMATES TPC modelling workshop 2005-09-14
Model parameters • MBFmyocardial blood flow in perfusable tissue volume • αperfusable tissue fraction, PTF • VAmyocardial blood volume fraction and spill-over from LV cavity
MBF model is fitted… • to ROI curves drawn on LV cavity (“lv”) and on entire myocardial tissue surrounding the cavity (“whole”) to estimate virtual arterial blood concentration, CA(t) • To smaller myocardial ROIs using CA(t) as model input.
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 (Weighted) Sum-of-squaresdescribing goodness-of-fit Estimates of model parameters Akaike information criteriafor comparison betweenmodels
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 2.1.0,2005-07-15
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 . .
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 . .
… 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 . .
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 versions • Also VA can be constrained with option-fVa.
… 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 . .
… constraints for α and VA 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 . .
Constraints or not? • Calculate results without and with constraints (α, α and VA, VA) • Select the method that gives constantly smaller AIC
References • 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. • Efron B, Tibshirani RJ. An introduction to the bootstrap. (1993) Chapman & Hall, New York. • 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. • 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. • 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. • Watabe H, Jino H, Kawachi N, Teramoto N, Hayashi T, Ohta Y, Iida H. Parametric imaging of myocardial blood flow with 15O-water and PET using the basis function method. J. Nucl. Med. 2005; 46: 1219-1224.
Moreinformation • Detailed report TPCMOD0005http://www.turkupetcentre.net/reports/ • Analysis instructionshttp://www.turkupetcentre.net/analysis/doc/tracer/mbf_h2o.html • Bootstrap method in estimation of variance of model parametershttp://www.turkupetcentre.net/modelling/workshop1/bootstrap.ppt