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
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, 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
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 .
Keywords: Automatic quantification algorithm; Expectation maximization; Experimental validation; LGE CMR; Multi-center patient data.
Figures
References
- 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. doi: 10.1161/01.CIR.100.19.1992.
- 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. doi: 10.1016/S0735-1097(00)00958-X.
- 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. doi: 10.1148/radiology.153.1.6473778.
- 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. doi: 10.1148/radiology.218.1.r01ja50215.
- 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. doi: 10.1002/mrm.10051.
- 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. doi: 10.1186/1532-429X-15-35.
- 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. doi: 10.1081/JCMR-200053623.
- 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. doi: 10.1016/j.jacc.2004.09.020.
- 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. doi: 10.1016/j.jcmg.2010.11.015.
- 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. doi: 10.1093/ehjci/jev001.
- 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. doi: 10.1186/s12968-015-0163-8.
- 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. doi: 10.1002/jmri.20496.
- 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. doi: 10.1002/jmri.20495.
- 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. doi: 10.1148/radiol.2461062164.
- 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.
- 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. doi: 10.1186/1532-429X-14-10.
- 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. doi: 10.1109/TBME.2013.2237907.
- 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. doi: 10.1016/j.jcmg.2015.08.015.
- 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. doi: 10.1016/j.ejphar.2015.04.009.
- 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. doi: 10.1016/j.jacc.2013.12.027.
- 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. doi: 10.1093/eurheartj/ehu331.
- 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. doi: 10.1159/000342981.
- 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. doi: 10.1186/1471-2342-10-1.
- 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. doi: 10.1007/s10554-009-9499-1.
- Nilsson B, Heyden A. A fast algorithm for level set-like active contours. Pattern Recognition Letters. 2003;24(9–10):1331–7. doi: 10.1016/S0167-8655(02)00374-4.
- Otsu N. Threshold Selection Method from Gray-Level Histograms. IEEE Transactions on Systems Man and Cybernetics. 1979;9(1):62–6. doi: 10.1109/TSMC.1979.4310076.
- Dice LR. Measures of the Amount of Ecologic Association between Species. Ecology. 1945;26(3):297–302. doi: 10.2307/1932409.
- 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. doi: 10.1148/radiology.213.1.r99se30247.
- 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. doi: 10.1161/01.CIR.103.6.871.
- 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. doi: 10.1109/TMI.2008.2006512.
Source: PubMed