MYOCARDIAL BLOOD FLOW WITH [15O]H2O

PET:ERROR ESTIMATES

Turku PET CentreVesa Oikonen

http://users.utu.fi/vesoik/

TPC modelling workshop2005-09-14

Model parameters

• MBFmyocardial blood flow in perfusable tissue volume

• αperfusable tissue fraction, PTF

• VA

myocardial blood volume fraction and spill-over from LV cavity

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, CA(t)

2. 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 CentreDate: 2005-09-13 Study: s05851dyData file: S05851\s05851.dftReference region: lv AllData range: 0 - 360 sec (N=20)Beta: 0.85Data was not weighted.

Region flow alpha Va SS AIC lat . All 0.8120 0.6564 0.2671 9.5215e+001 3.8708e+001ant . All 0.8613 0.6391 0.2036 1.2060e+002 4.3434e+001sept . All 0.7151 0.5245 0.4841 1.9348e+002 5.2888e+001whole . All 0.8353 0.6329 0.2863 4.8313e+001 2.5140e+001

Estimates of model parameters Akaike information criteriafor comparison betweenmodels

(Weighted) Sum-of-squaresdescribing goodness-of-fit

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

Measured and fitted TACs

0 60 120 180 240 300 3600

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Co

nce

ntr

atio

n (

kBq

/ml)

Time from injection (s)

LV cavity Whole myocardium Lateral Anterior Septal

Results with error estimatesfitmbf 2.1.3 (c) 1999-2005 by Turku PET Centre

Date: 2005-09-13 Study: s05851dyData file: S05851\s05851.dftReference region: lv AllData range: 0 - 360 sec (N=20)Beta: 0.85Data 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 studyRegion 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 . .

StimulationRegion 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 CentreDate: 2005-09-13 Study: s06003dyData file: S06002\s06003.dftReference region: lv AllData range: 0 - 360 sec (N=20)Beta: 0.85Data 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 CentreDate: 2005-09-13 Study: s06003dyData file: S06002\s06003.dftReference file: results\s06002mbf1.resReference region: lv AllData range: 0 - 360 sec (N=20)Beta: 0.85Data 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 CentreDate: 2005-09-13 Study: s06003dyData file: ..\S06002\s06003.dftReference file: s06002mbf1.resReference region: lv AllData range: 0 - 360 sec (N=20)Beta: 0.85Data 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

References1. 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 15O-water and PET using the basis function method. J. Nucl. Med. 2005; 46: 1219-1224.

More information

• 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