Skip to main content
Top
Published in: Journal of Cardiovascular Magnetic Resonance 1/2017

Open Access 01-12-2016 | Research

A new automatic algorithm for quantification of myocardial infarction imaged by late gadolinium enhancement cardiovascular magnetic resonance: experimental validation and comparison to expert delineations in multi-center, multi-vendor patient data

Authors: Henrik Engblom, Jane Tufvesson, Robert Jablonowski, Marcus Carlsson, Anthony H. Aletras, Pavel Hoffmann, Alexis Jacquier, Frank Kober, Bernhard Metzler, David Erlinge, Dan Atar, Håkan Arheden, Einar Heiberg

Published in: Journal of Cardiovascular Magnetic Resonance | Issue 1/2017

Login to get access

Abstract

Background

Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) using magnitude inversion recovery (IR) or phase sensitive inversion recovery (PSIR) has become clinical standard for assessment of myocardial infarction (MI). However, there is no clinical standard for quantification of MI even though multiple methods have been proposed. Simple thresholds have yielded varying results and advanced algorithms have only been validated in single center studies. Therefore, the aim of this study was to develop an automatic algorithm for MI quantification in IR and PSIR LGE images and to validate the new algorithm experimentally and compare it to expert delineations in multi-center, multi-vendor patient data.

Methods

The new automatic algorithm, EWA (Expectation Maximization, weighted intensity, a priori information), was implemented using an intensity threshold by Expectation Maximization (EM) and a weighted summation to account for partial volume effects.
The EWA algorithm was validated in-vivo against triphenyltetrazolium-chloride (TTC) staining (n = 7 pigs with paired IR and PSIR images) and against ex-vivo high resolution T1-weighted images (n = 23 IR and n = 13 PSIR images). The EWA algorithm was also compared to expert delineation in 124 patients from multi-center, multi-vendor clinical trials 2–6 days following first time ST-elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI) (n = 124 IR and n = 49 PSIR images).

Results

Infarct size by the EWA algorithm in vivo in pigs showed a bias to ex-vivo TTC of −1 ± 4%LVM (R = 0.84) in IR and −2 ± 3%LVM (R = 0.92) in PSIR images and a bias to ex-vivo T1-weighted images of 0 ± 4%LVM (R = 0.94) in IR and 0 ± 5%LVM (R = 0.79) in PSIR images. In multi-center patient studies, infarct size by the EWA algorithm showed a bias to expert delineation of −2 ± 6 %LVM (R = 0.81) in IR images (n = 124) and 0 ± 5%LVM (R = 0.89) in PSIR images (n = 49).

Conclusions

The EWA algorithm was validated experimentally and in patient data with a low bias in both IR and PSIR LGE images. Thus, the use of EM and a weighted intensity as in the EWA algorithm, may serve as a clinical standard for the quantification of myocardial infarction in LGE CMR images.

Clinical trial registration

CHILL-MI: NCT01379261. MITOCARE: NCT01374321.
Literature
1.
go back to reference Kim RJ, Fieno DS, Parrish TB, Harris K, Chen EL, Simonetti O, et al. Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function. Circulation. 1999;100(19):1992–2002.CrossRefPubMed Kim RJ, Fieno DS, Parrish TB, Harris K, Chen EL, Simonetti O, et al. Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function. Circulation. 1999;100(19):1992–2002.CrossRefPubMed
2.
go back to reference Fieno DS, Kim RJ, Chen EL, Lomasney JW, Klocke FJ, Judd RM. Contrast-enhanced magnetic resonance imaging of myocardium at risk: distinction between reversible and irreversible injury throughout infarct healing. J Am Coll Cardiol. 2000;36(6):1985–91.CrossRefPubMed Fieno DS, Kim RJ, Chen EL, Lomasney JW, Klocke FJ, Judd RM. Contrast-enhanced magnetic resonance imaging of myocardium at risk: distinction between reversible and irreversible injury throughout infarct healing. J Am Coll Cardiol. 2000;36(6):1985–91.CrossRefPubMed
3.
go back to reference Wesbey GE, Higgins CB, McNamara MT, Engelstad BL, Lipton MJ, Sievers R, et al. Effect of gadolinium-DTPA on the magnetic relaxation times of normal and infarcted myocardium. Radiology. 1984;153(1):165–9.CrossRefPubMed Wesbey GE, Higgins CB, McNamara MT, Engelstad BL, Lipton MJ, Sievers R, et al. Effect of gadolinium-DTPA on the magnetic relaxation times of normal and infarcted myocardium. Radiology. 1984;153(1):165–9.CrossRefPubMed
4.
go back to reference Simonetti OP, Kim RJ, Fieno DS, Hillenbrand HB, Wu E, Bundy JM, et al. An improved MR imaging technique for the visualization of myocardial infarction. Radiology. 2001;218(1):215–23.CrossRefPubMed Simonetti OP, Kim RJ, Fieno DS, Hillenbrand HB, Wu E, Bundy JM, et al. An improved MR imaging technique for the visualization of myocardial infarction. Radiology. 2001;218(1):215–23.CrossRefPubMed
5.
go back to reference Kellman P, Arai AE, McVeigh ER, Aletras AH. Phase-sensitive inversion recovery for detecting myocardial infarction using gadolinium-delayed hyperenhancement. Magn Reson Med. 2002;47(2):372–83.CrossRefPubMedPubMedCentral Kellman P, Arai AE, McVeigh ER, Aletras AH. Phase-sensitive inversion recovery for detecting myocardial infarction using gadolinium-delayed hyperenhancement. Magn Reson Med. 2002;47(2):372–83.CrossRefPubMedPubMedCentral
6.
go back to reference Schulz-Menger J, Bluemke DA, Bremerich J, Flamm SD, Fogel MA, Friedrich MG, et al. Standardized image interpretation and post processing in cardiovascular magnetic resonance: Society for Cardiovascular Magnetic Resonance (SCMR) board of trustees task force on standardized post processing. J Cardiovasc Magn Reson. 2013;15:35.CrossRefPubMedPubMedCentral Schulz-Menger J, Bluemke DA, Bremerich J, Flamm SD, Fogel MA, Friedrich MG, et al. Standardized image interpretation and post processing in cardiovascular magnetic resonance: Society for Cardiovascular Magnetic Resonance (SCMR) board of trustees task force on standardized post processing. J Cardiovasc Magn Reson. 2013;15:35.CrossRefPubMedPubMedCentral
7.
go back to reference Bondarenko O, Beek AM, Hofman MB, Kuhl HP, Twisk JW, van Dockum WG, et al. Standardizing the definition of hyperenhancement in the quantitative assessment of infarct size and myocardial viability using delayed contrast-enhanced CMR. J Cardiovasc Magn Reson. 2005;7(2):481–5.CrossRefPubMed Bondarenko O, Beek AM, Hofman MB, Kuhl HP, Twisk JW, van Dockum WG, et al. Standardizing the definition of hyperenhancement in the quantitative assessment of infarct size and myocardial viability using delayed contrast-enhanced CMR. J Cardiovasc Magn Reson. 2005;7(2):481–5.CrossRefPubMed
8.
go back to reference Amado LC, Gerber BL, Gupta SN, Rettmann DW, Szarf G, Schock R, et al. Accurate and objective infarct sizing by contrast-enhanced magnetic resonance imaging in a canine myocardial infarction model. J Am Coll Cardiol. 2004;44(12):2383–9.CrossRefPubMed Amado LC, Gerber BL, Gupta SN, Rettmann DW, Szarf G, Schock R, et al. Accurate and objective infarct sizing by contrast-enhanced magnetic resonance imaging in a canine myocardial infarction model. J Am Coll Cardiol. 2004;44(12):2383–9.CrossRefPubMed
9.
go back to reference Flett AS, Hasleton J, Cook C, Hausenloy D, Quarta G, Ariti C, et al. Evaluation of techniques for the quantification of myocardial scar of differing etiology using cardiac magnetic resonance. JACC Cardiovasc Imaging. 2011;4(2):150–6.CrossRefPubMed Flett AS, Hasleton J, Cook C, Hausenloy D, Quarta G, Ariti C, et al. Evaluation of techniques for the quantification of myocardial scar of differing etiology using cardiac magnetic resonance. JACC Cardiovasc Imaging. 2011;4(2):150–6.CrossRefPubMed
10.
go back to reference McAlindon E, Pufulete M, Lawton C, Angelini GD, Bucciarelli-Ducci C. Quantification of infarct size and myocardium at risk: evaluation of different techniques and its implications. Eur Heart J Cardiovasc Imaging. 2015;16(7):738–46.CrossRefPubMedPubMedCentral McAlindon E, Pufulete M, Lawton C, Angelini GD, Bucciarelli-Ducci C. Quantification of infarct size and myocardium at risk: evaluation of different techniques and its implications. Eur Heart J Cardiovasc Imaging. 2015;16(7):738–46.CrossRefPubMedPubMedCentral
11.
go back to reference Stirrat J, Joncas SX, Salerno M, Drangova M, White J. Influence of phase correction of late gadolinium enhancement images on scar signal quantification in patients with ischemic and non-ischemic cardiomyopathy. J Cardiovasc Magn Reson. 2015;17(1):66.CrossRefPubMedPubMedCentral Stirrat J, Joncas SX, Salerno M, Drangova M, White J. Influence of phase correction of late gadolinium enhancement images on scar signal quantification in patients with ischemic and non-ischemic cardiomyopathy. J Cardiovasc Magn Reson. 2015;17(1):66.CrossRefPubMedPubMedCentral
12.
go back to reference Hsu LY, Natanzon A, Kellman P, Hirsch GA, Aletras AH, Arai AE. Quantitative myocardial infarction on delayed enhancement MRI. Part I: Animal validation of an automated feature analysis and combined thresholding infarct sizing algorithm. J Magn Reson Imaging. 2006;23(3):298–308.CrossRefPubMed Hsu LY, Natanzon A, Kellman P, Hirsch GA, Aletras AH, Arai AE. Quantitative myocardial infarction on delayed enhancement MRI. Part I: Animal validation of an automated feature analysis and combined thresholding infarct sizing algorithm. J Magn Reson Imaging. 2006;23(3):298–308.CrossRefPubMed
13.
go back to reference Hsu LY, Ingkanisorn WP, Kellman P, Aletras AH, Arai AE. Quantitative myocardial infarction on delayed enhancement MRI. Part II: Clinical application of an automated feature analysis and combined thresholding infarct sizing algorithm. J Magn Reson Imaging. 2006;23(3):309–14.CrossRefPubMed Hsu LY, Ingkanisorn WP, Kellman P, Aletras AH, Arai AE. Quantitative myocardial infarction on delayed enhancement MRI. Part II: Clinical application of an automated feature analysis and combined thresholding infarct sizing algorithm. J Magn Reson Imaging. 2006;23(3):309–14.CrossRefPubMed
14.
go back to reference Heiberg E, Ugander M, Engblom H, Gotberg M, Olivecrona GK, Erlinge D, et al. Automated quantification of myocardial infarction from MR images by accounting for partial volume effects: animal, phantom, and human study. Radiology. 2008;246(2):581–8.CrossRefPubMed Heiberg E, Ugander M, Engblom H, Gotberg M, Olivecrona GK, Erlinge D, et al. Automated quantification of myocardial infarction from MR images by accounting for partial volume effects: animal, phantom, and human study. Radiology. 2008;246(2):581–8.CrossRefPubMed
15.
go back to reference Dempster AP, Laird NM, Rubin DB. Maximum Likelihood from Incomplete Data Via Em Algorithm. Journal of the Royal Statistical Society Series B-Methodological. 1977;39(1):1–38. Dempster AP, Laird NM, Rubin DB. Maximum Likelihood from Incomplete Data Via Em Algorithm. Journal of the Royal Statistical Society Series B-Methodological. 1977;39(1):1–38.
16.
go back to reference Sjogren J, Ubachs JF, Engblom H, Carlsson M, Arheden H, Heiberg E. Semi-automatic segmentation of myocardium at risk in T2-weighted cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2012;14:10.CrossRefPubMedPubMedCentral Sjogren J, Ubachs JF, Engblom H, Carlsson M, Arheden H, Heiberg E. Semi-automatic segmentation of myocardium at risk in T2-weighted cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2012;14:10.CrossRefPubMedPubMedCentral
17.
go back to reference Wei D, Sun Y, Ong SH, Chai P, Teo LL, Low AF. A comprehensive 3-D framework for automatic quantification of late gadolinium enhanced cardiac magnetic resonance images. IEEE Trans Biomed Eng. 2013;60(6):1499–508.CrossRefPubMed Wei D, Sun Y, Ong SH, Chai P, Teo LL, Low AF. A comprehensive 3-D framework for automatic quantification of late gadolinium enhanced cardiac magnetic resonance images. IEEE Trans Biomed Eng. 2013;60(6):1499–508.CrossRefPubMed
18.
go back to reference Jablonowski R, Engblom H, Kanski M, Nordlund D, Koul S, van der Pals J, et al. Contrast-enhanced CMR overestimates myocardial infarction size on day 1 but not day 7 relative to TTC in a swine model: Mechanistic insights using extracellular volume measurements. JACC Cardiovasc Imaging. 2015;8(12):1379–89.CrossRefPubMed Jablonowski R, Engblom H, Kanski M, Nordlund D, Koul S, van der Pals J, et al. Contrast-enhanced CMR overestimates myocardial infarction size on day 1 but not day 7 relative to TTC in a swine model: Mechanistic insights using extracellular volume measurements. JACC Cardiovasc Imaging. 2015;8(12):1379–89.CrossRefPubMed
19.
go back to reference Hansson MJ, Llwyd O, Morin D, de Paulis D, Arnoux T, Gouarne C, et al. Differences in the profile of protection afforded by TRO40303 and mild hypothermia in models of cardiac ischemia/reperfusion injury. Eur J Pharmacol. 2015;760:7–19.CrossRefPubMed Hansson MJ, Llwyd O, Morin D, de Paulis D, Arnoux T, Gouarne C, et al. Differences in the profile of protection afforded by TRO40303 and mild hypothermia in models of cardiac ischemia/reperfusion injury. Eur J Pharmacol. 2015;760:7–19.CrossRefPubMed
20.
go back to reference Erlinge D, Gotberg M, Lang I, Holzer M, Noc M, Clemmensen P, et al. Rapid endovascular catheter core cooling combined with cold saline as an adjunct to percutaneous coronary intervention for the treatment of acute myocardial infarction. The CHILL-MI trial: a randomized controlled study of the use of central venous catheter core cooling combined with cold saline as an adjunct to percutaneous coronary intervention for the treatment of acute myocardial infarction. J Am Coll Cardiol. 2014;63(18):1857–65.CrossRefPubMed Erlinge D, Gotberg M, Lang I, Holzer M, Noc M, Clemmensen P, et al. Rapid endovascular catheter core cooling combined with cold saline as an adjunct to percutaneous coronary intervention for the treatment of acute myocardial infarction. The CHILL-MI trial: a randomized controlled study of the use of central venous catheter core cooling combined with cold saline as an adjunct to percutaneous coronary intervention for the treatment of acute myocardial infarction. J Am Coll Cardiol. 2014;63(18):1857–65.CrossRefPubMed
21.
go back to reference Atar D, Arheden H, Berdeaux A, Bonnet JL, Carlsson M, Clemmensen P, et al. Effect of intravenous TRO40303 as an adjunct to primary percutaneous coronary intervention for acute ST-elevation myocardial infarction: MITOCARE study results. Eur Heart J. 2015;36(2):112–9.CrossRefPubMed Atar D, Arheden H, Berdeaux A, Bonnet JL, Carlsson M, Clemmensen P, et al. Effect of intravenous TRO40303 as an adjunct to primary percutaneous coronary intervention for acute ST-elevation myocardial infarction: MITOCARE study results. Eur Heart J. 2015;36(2):112–9.CrossRefPubMed
22.
go back to reference MITOCARE’ Study Group. Rationale and design of the ‘MITOCARE’ Study: a phase II, multicenter, randomized, double-blind, placebo-controlled study to assess the safety and efficacy of TRO40303 for the reduction of reperfusion injury in patients undergoing percutaneous coronary intervention for acute myocardial infarction. Cardiology. 2012;123(4):201–7.CrossRef MITOCARE’ Study Group. Rationale and design of the ‘MITOCARE’ Study: a phase II, multicenter, randomized, double-blind, placebo-controlled study to assess the safety and efficacy of TRO40303 for the reduction of reperfusion injury in patients undergoing percutaneous coronary intervention for acute myocardial infarction. Cardiology. 2012;123(4):201–7.CrossRef
23.
go back to reference Heiberg E, Sjogren J, Ugander M, Carlsson M, Engblom H, Arheden H. Design and validation of Segment--freely available software for cardiovascular image analysis. BMC Med Imaging. 2010;10:1.CrossRefPubMedPubMedCentral Heiberg E, Sjogren J, Ugander M, Carlsson M, Engblom H, Arheden H. Design and validation of Segment--freely available software for cardiovascular image analysis. BMC Med Imaging. 2010;10:1.CrossRefPubMedPubMedCentral
24.
go back to reference Beek AM, Nijveldt R, van Rossum AC. Intramyocardial hemorrhage and microvascular obstruction after primary percutaneous coronary intervention. Int J Cardiovasc Imaging. 2010;26(1):49–55.CrossRefPubMedPubMedCentral Beek AM, Nijveldt R, van Rossum AC. Intramyocardial hemorrhage and microvascular obstruction after primary percutaneous coronary intervention. Int J Cardiovasc Imaging. 2010;26(1):49–55.CrossRefPubMedPubMedCentral
25.
go back to reference Nilsson B, Heyden A. A fast algorithm for level set-like active contours. Pattern Recognition Letters. 2003;24(9–10):1331–7.CrossRef Nilsson B, Heyden A. A fast algorithm for level set-like active contours. Pattern Recognition Letters. 2003;24(9–10):1331–7.CrossRef
26.
go back to reference Otsu N. Threshold Selection Method from Gray-Level Histograms. IEEE Transactions on Systems Man and Cybernetics. 1979;9(1):62–6.CrossRef Otsu N. Threshold Selection Method from Gray-Level Histograms. IEEE Transactions on Systems Man and Cybernetics. 1979;9(1):62–6.CrossRef
27.
go back to reference Dice LR. Measures of the Amount of Ecologic Association between Species. Ecology. 1945;26(3):297–302.CrossRef Dice LR. Measures of the Amount of Ecologic Association between Species. Ecology. 1945;26(3):297–302.CrossRef
28.
go back to reference Saeed M, Bremerich J, Wendland MF, Wyttenbach R, Weinmann HJ, Higgins CB. Reperfused myocardial infarction as seen with use of necrosis-specific versus standard extracellular MR contrast media in rats. Radiology. 1999;213(1):247–57.CrossRefPubMed Saeed M, Bremerich J, Wendland MF, Wyttenbach R, Weinmann HJ, Higgins CB. Reperfused myocardial infarction as seen with use of necrosis-specific versus standard extracellular MR contrast media in rats. Radiology. 1999;213(1):247–57.CrossRefPubMed
29.
go back to reference Saeed M, Lund G, Wendland MF, Bremerich J, Weinmann H, Higgins CB. Magnetic resonance characterization of the peri-infarction zone of reperfused myocardial infarction with necrosis-specific and extracellular nonspecific contrast media. Circulation. 2001;103(6):871–6.CrossRefPubMed Saeed M, Lund G, Wendland MF, Bremerich J, Weinmann H, Higgins CB. Magnetic resonance characterization of the peri-infarction zone of reperfused myocardial infarction with necrosis-specific and extracellular nonspecific contrast media. Circulation. 2001;103(6):871–6.CrossRefPubMed
30.
go back to reference Hennemuth A, Seeger A, Friman O, Miller S, Klumpp B, Oeltze S, et al. A comprehensive approach to the analysis of contrast enhanced cardiac MR images. IEEE Trans Med Imaging. 2008;27(11):1592–610.CrossRefPubMed Hennemuth A, Seeger A, Friman O, Miller S, Klumpp B, Oeltze S, et al. A comprehensive approach to the analysis of contrast enhanced cardiac MR images. IEEE Trans Med Imaging. 2008;27(11):1592–610.CrossRefPubMed
Metadata
Title
A new automatic algorithm for quantification of myocardial infarction imaged by late gadolinium enhancement cardiovascular magnetic resonance: experimental validation and comparison to expert delineations in multi-center, multi-vendor patient data
Authors
Henrik Engblom
Jane Tufvesson
Robert Jablonowski
Marcus Carlsson
Anthony H. Aletras
Pavel Hoffmann
Alexis Jacquier
Frank Kober
Bernhard Metzler
David Erlinge
Dan Atar
Håkan Arheden
Einar Heiberg
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Cardiovascular Magnetic Resonance / Issue 1/2017
Electronic ISSN: 1532-429X
DOI
https://doi.org/10.1186/s12968-016-0242-5

Other articles of this Issue 1/2017

Journal of Cardiovascular Magnetic Resonance 1/2017 Go to the issue