- Email: [email protected]
Myocardial infarct quantification: Is magnetic resonance imaging ready to serve as a gold standard for electrocardiography?
Journal of Electrocardiology 40 (2007) 243 – 245 www.jecgonline.com
Editorial
Myocardial infarct quantification: Is magnetic resonance imaging ready to serve as a gold standard for electrocardiography?
The determination of myocardial viability in patients with ischemic heart disease has been a clinical challenge for decades. Viable myocardium has the potential for functional recovery after reperfusion therapy, whereas infarcted myocardium has not, whether it is acutely necrotic or chronically scarred. Thus, it is of great clinical importance to be able to distinguish viable from nonviable myocardium in order not to expose patients to unnecessary risks associated with revascularization procedures in the non-acute situation. The 12-lead electrocardiogram (ECG) has been used to detect and estimate myocardial infarction (MI) size for many decades.1 The validation of the accuracy of different ECG indices has, however, been limited by deficiencies in the gold standards used to delineate the regions of acute myocardial necrosis and/or chronic myocardial scar. Proof of concept has, until recently, relied on comparisons with indirect measurements of MI extent in vivo2-4 or direct histopathologic assessment of MI postmortem.5-7 However, for further clinical evaluation and optimization of ECG indices of MI, comparisons with direct measurements of MI size and location in vivo are needed. Thus, historically, it has been difficult to visualize infarcted myocardium in vivo. Recently, however, delayed contrast-enhanced magnetic resonance imaging (DE-MRI) has emerged as a new reference method for infarct characterization in vivo.8 By acquiring DE–magnetic resonance (MR) images 20 to 40 minutes after injection of a gadolinium-based extracellular contrast agent, infarcted myocardium can be visualized. The mechanism for the delayed enhancement of infarcted myocardium is an increased distribution volume caused by loss of myocyte integrity, edema, and scar tissue replacement in the area of infarction. Therefore, the extracellular contrast agent has a larger distribution volume in the infarcted myocardium compared with that which is noninfarcted.9-12 Different wash-in/wash-out profiles have also been proposed to explain parts of the difference in the amount of contrast agent in infarcted and viable myocardium.10,13-15 Infarct sizing using DE-MRI has been shown to accurately depict areas of infarction in animal models by comparing regions of hyperenhancement with triphenyltetrazolium chloride– stained gross histologic slices of the heart.16,17 Furthermore, human studies have revealed that the transmural extent of 0022-0736/$ – see front matter D 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.jelectrocard.2007.02.009
hyperenhanced myocardium correlates well with the probability, magnitude, and timing of functional recovery after both reperfused acute MI18,19 and elective reperfusion therapy in chronic ischemic heart disease.20,21 The high accuracy of the DE-MRI technique for depicting areas of infarction shown in previous animal studies, however, relies on infarct quantification of hyperenhanced areas in high-spatial-resolution (0.5 0.5 0.5 mm) ex vivo images. This high spatial resolution is not obtained when acquiring standard DE-MR images in clinical routine. The typical spatial resolution of a clinically acquired DE-MR image is 1.5 1.5 8 mm. Thus, the thickness of standard infarct MR images is 16 times that of the high-spatial-resolution MR image acquired ex vivo. Consequently, the problem of partial volume arises in the clinical setting.16,22 Within the 8-mm-thick image slice the infarcted myocardium can be irregular within the image slice, resulting in unsharp infarct borders. Hence, there is a need for a standardization of how to delineate the region of hyperenhancement for accurate MI sizing.23 There is a variety of commercially available postprocessing software used to measure infarct size from in vivo images acquired with the DE-MRI technique. Often, the simple choice of whether whole pixels enclosed by the perimeter, inclusion of half pixels enclosed, or even including pixels on the perimeter still varies between different software. Another important issue is that of relative contrast and brightness used with different image display systems. The relative contrast and brightness can be altered in order to optimize visualization of the infarcted myocardium. By doing so, visible image contrast in the periphery of the hyperenhanced region is manipulated subjectively, which can affect the assessment of MI size in an unpredictable manner. It has recently been shown that manual delineation of hyperenhanced regions can overestimate both MI size and transmurality.17,24 Thus, a means of standardizing the range of grey scale levels and account for partial volume effects when delineating the infarcted myocardium is paramount.22 Other factors, such as contrast dose,25,26 time between injection of the contrast agent and image acquisition,25-27 and myocardial perfusion28 are also of importance for accurate MI visualization. Furthermore, the timing of image
244
Editorial / Journal of Electrocardiology 40 (2007) 243 – 245
acquisition in relation to the acute infarction needs to be considered when interpreting findings with DE-MRI. It has previously been shown that the penumbra of an infarcted region differs from both infarcted and normal myocardium.11,29-31 By using the DE-MRI technique early after acute MI, the region of hyperenhancement might overestimate the actual MI size, possibly because of an increased distribution volume due to the acute edema and inflammation in this peri-infarction zone.18,29,31-33 Optimization of the MRI acquisition parameter inversion time (TI) has to be considered as well, since TI affects the relative signal intensities in infarcted and non-infarcted myocardium as well as in blood. Consequently, TI affects the assessment of infarct size by DE-MRI.25,26 In order to decrease the dependence on optimal TI when acquiring DE-MRI images, a so-called phase sensitive acquisition technique has been developed.34 If the above discussed issues can be taken into consideration, DE-MRI has an excellent potential for depicting MI in vivo, being associated with a low interobserver variability.35,36 Hence, the DE-MRI technique can potentially be used to further develop and validate ECG indices of MI as well as reveal the pathologic basis of infarct-related ECG changes.37-41 Furthermore, since MRI does not require ionizing radiation, this imaging modality is suitable for serial examinations, enabling studies on MI evolution and ECG changes during the MI healing phase.18 However, in order to further develop established ECG indices of MI, large patient populations are needed. Thus, multicenter studies are desirable. To enable comparison of results from different sites, it is fundamental to have a standardized image acquisition protocol and standardized post-processing methods for MI quantification. Thus, we believe that there is a need for a broad consensus regarding how MI characterization should be performed using DEMRI. This is important for DE-MRI to serve not only as a reference method for MI quantification by ECG, but also for MI size assessed by DE-MRI to be used as a reliable outcome variable in ongoing and future clinical trials. Henrik Engblom, MD, PhD H3kan Arheden, MD, PhD Department of Clinical Physiology Lund University Hospital, Lund, Sweden E-mail address: [email protected] John E. Foster, PhD Thomas N. Martin, MD Glasgow Cardiac Magnetic Resonance Unit Glasgow, Lanarkshire, UK
References 1. Barnes AR. Electrocardiogram in myocardial infarction: review of one hundred and seven clinical cases and one hundred and eight proved cases at necropsy. Arch Intern Med 1935;55:457. 2. Palmeri ST, Harrison DG, Cobb FR, et al. A QRS scoring system for assessing left ventricular function after myocardial infarction. N Engl J Med 1982;306:4.
3. De Sutter J, Van de Wiele C, Gheeraert P, et al. The Selvester 32-point QRS score for evaluation of myocardial infarct size after primary coronary angioplasty. Am J Cardiol 1999;83:255-7, A5. 4. Clemmensen P, Grande P, Saunamaki K, Wagner NB, Selvester RH, Wagner GS. Evolution of electrocardiographic and echocardiographic abnormalities during the 4 years following first acute myocardial infarction. Eur J Heart 1995;16:1063. 5. Ideker RE, Wagner GS, Ruth WK, et al. Evaluation of a QRS scoring system for estimating myocardial infarct size. II. Correlation with quantitative anatomic findings for anterior infarcts. Am J Cardiol 1982;49:1604. 6. Ward RM, White RD, Ideker RE, et al. Evaluation of a QRS scoring system for estimating myocardial infarct size. IV. Correlation with quantitative anatomic findings for posterolateral infarcts. Am J Cardiol 1984;53:706. 7. Roark SF, Ideker RE, Wagner GS, et al. Evaluation of a QRS scoring system for estimating myocardial infarct size. III. Correlation with quantitative anatomic findings for inferior infarcts. Am J Cardiol 1983;51:382. 8. Pennell DJ, Sechtem UP, Higgins CB, et al. Clinical indications for cardiovascular magnetic resonance (CMR): Consensus Panel report. Eur J Heart 2004;25:1940. 9. Flacke SJ, Fischer SE, Lorenz CH. Measurement of the gadopentetate dimeglumine partition coefficient in human myocardium in vivo: normal distribution and elevation in acute and chronic infarction. Radiology 2001;218:703. 10. Tong CY, Prato FS, Wisenberg G, et al. Measurement of the extraction efficiency and distribution volume for Gd-DTPA in normal and diseased canine myocardium. Magn Reson Med 1993;30:337. 11. Arheden H, Saeed M, Higgins CB, et al. Measurement of the distribution volume of gadopentetate dimeglumine at echo-planar MR imaging to quantify myocardial infarction: comparison with 99mTc-DTPA autoradiography in rats. Radiology 1999;211:698. 12. Saeed M, Wendland MF, Masui T, Higgins CB. Reperfused myocardial infarctions on T1- and susceptibility-enhanced MRI: evidence for loss of compartmentalization of contrast media. Magn Reson Med 1994;31:31. 13. Diesbourg LD, Prato FS, Wisenberg G, et al. Quantification of myocardial blood flow and extracellular volumes using a bolus injection of Gd-DTPA: kinetic modeling in canine ischemic disease. Magn Reson Med 1992;23:239. 14. Klein C, Nekolla SG, Balbach T, et al. The influence of myocardial blood flow and volume of distribution on late Gd-DTPA kinetics in ischemic heart failure. J Magn Reson Imaging 2004;20:588. 15. Judd RM, Lugo-Olivieri CH, Arai M, et al. Physiological basis of myocardial contrast enhancement in fast magnetic resonance images of 2-day-old reperfused canine infarcts. Circulation 1995;92:1902. 16. Kim RJ, Fieno DS, Parrish TB, et al. Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function. Circulation 1999;100:1992. 17. 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;23:298. 18. Engblom H, Hedstrom E, Heiberg E, Wagner GS, Pahlm O, Arheden H. Time course and magnitude of infarct involution, functional recovery, and electrocardiographic changes in patients with reperfused first myocardial infarction [submitted for publication]. 19. Choi CJ, Haji-Momenian S, Dimaria JM, et al. Infarct involution and improved function during healing of acute myocardial infarction: the role of microvascular obstruction. J Cardiovasc Magn Reson 2004;6:917. 20. Kim RJ, Wu E, Rafael A, et al. The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction. N Engl J Med 2000;343:1445. 21. Ugander M, Cain P, Johnsson P, Arheden H. Time dependence of segmental functional improvement after bypass surgery: the interacting effects of stress perfusion by SPECT and scar by delayed enhancement MRI at baseline and 1 and 6 months post CABG. Circulation 2003;108(1857 Suppl):401.
Editorial / Journal of Electrocardiology 40 (2007) 243 – 245 22. Heiberg E, Ugander M, Engblom H, et al. Accounting for partial volume effects in the automated quantification of myocardial infarction from delayed enhancement MRI. Radiology [in press]. 23. Gibbons RJ, Valeti US, Araoz PA, Jaffe AS. The quantification of infarct size. J Am Coll Cardiol 2004;44:1533. 24. 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;23:309. 25. Petersen SE, Mohrs OK, Horstick G, et al. Influence of contrast agent dose and image acquisition timing on the quantitative determination of nonviable myocardial tissue using delayed contrast-enhanced magnetic resonance imaging. J Cardiovasc Magn Reson 2004;6:541. 26. Wagner A, Mahrholdt H, Thomson L, et al. Effects of time, dose, and inversion time for acute myocardial infarct size measurements based on magnetic resonance imaging–delayed contrast enhancement. J Am Coll Cardiol 2006;47:2027. 27. Oshinski JN, Yang Z, Jones JR, Mata JF, French BA. Imaging time after Gd-DTPA injection is critical in using delayed enhancement to determine infarct size accurately with magnetic resonance imaging. Circulation 2001;104:2838. 28. Hedstrom E, Arheden H, Eriksson R, Johansson L, Ahlstrom H, Bjerner T. Importance of perfusion in myocardial viability studies using delayed contrast-enhanced magnetic resonance imaging. J Magn Reson Imaging 2006;24:77. 29. 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;103:871. 30. Reimer KA, Jennings RB. The changing anatomic reference base of evolving myocardial infarction. Underestimation of myocardial collateral blood flow and overestimation of experimental anatomic infarct size due to tissue edema, hemorrhage and acute inflammation. Circulation 1979;60:866. 31. Arheden H, Saeed M, Higgins CB, et al. Reperfused rat myocardium subjected to various durations of ischemia: estimation of the distribution volume of contrast material with echo-planar MR imaging. Radiology 2000;215:520.
245
32. Schaefer S, Malloy CR, Katz J, et al. Gadolinium-DTPA–enhanced nuclear magnetic resonance imaging of reperfused myocardium: identification of the myocardial bed at risk. J Am Coll Cardiol 1988;12:1064. 33. Nishimura T, Yamada Y, Hayashi M, et al. Determination of infarct size of acute myocardial infarction in dogs by magnetic resonance imaging and gadolinium-DTPA: comparison with indium-111 antimyosin imaging. Am J Physiol Imaging 1989;4:83. 34. Kellman P, Arai AE, McVeigh ER, Aletras AH. Phase-sensitive inversion recovery for detecting myocardial infarction using gadolinium-delayed hyperenhancement. Magn Reson Med 2002; 47:372. 35. Bondarenko O, Beek AM, Hofman MB, 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;7:481. 36. Heiberg E, Engblom H, Engvall J, Hedstrom E, Ugander M, Arheden H. Semi-automatic quantification of myocardial infarction from delayed contrast enhanced magnetic resonance imaging. Scand J Cardiovasc 2005;39:267. 37. Engblom H, Wagner GS, Setser RM, et al. Quantitative clinical assessment of chronic anterior myocardial infarction with delayed enhancement magnetic resonance imaging and QRS scoring. Am J Heart 2003;146:359. 38. Moon JC, De Arenaza DP, Elkington AG, et al. The pathologic basis of Q-wave and non–Q-wave myocardial infarction: a cardiovascular magnetic resonance study. J Am Coll Cardiol 2004;44:554. 39. Engblom H, Hedstrom E, Heiberg E, Wagner GS, Pahlm O, Arheden H. Size and transmural extent of first-time reperfused myocardial infarction assessed by cardiac magnetic resonance can be estimated by 12-lead electrocardiogram. Am J Heart 2005;150:920. 40. Kaandorp TA, Bax JJ, Lamb HJ, et al. Which parameters on magnetic resonance imaging determine Q waves on the electrocardiogram? Am J Cardiol 2005;95:925. 41. Engblom H, Carlsson MB, Hedstrfm E, et al. The endocardial extent of reperfused myocardial infarction is a stronger determinant of pathological Q waves than is infarct transmurality. Clin Physiol Funct Imaging 2007;27:101.
Editorial
Myocardial infarct quantification: Is magnetic resonance imaging ready to serve as a gold standard for electrocardiography?
The determination of myocardial viability in patients with ischemic heart disease has been a clinical challenge for decades. Viable myocardium has the potential for functional recovery after reperfusion therapy, whereas infarcted myocardium has not, whether it is acutely necrotic or chronically scarred. Thus, it is of great clinical importance to be able to distinguish viable from nonviable myocardium in order not to expose patients to unnecessary risks associated with revascularization procedures in the non-acute situation. The 12-lead electrocardiogram (ECG) has been used to detect and estimate myocardial infarction (MI) size for many decades.1 The validation of the accuracy of different ECG indices has, however, been limited by deficiencies in the gold standards used to delineate the regions of acute myocardial necrosis and/or chronic myocardial scar. Proof of concept has, until recently, relied on comparisons with indirect measurements of MI extent in vivo2-4 or direct histopathologic assessment of MI postmortem.5-7 However, for further clinical evaluation and optimization of ECG indices of MI, comparisons with direct measurements of MI size and location in vivo are needed. Thus, historically, it has been difficult to visualize infarcted myocardium in vivo. Recently, however, delayed contrast-enhanced magnetic resonance imaging (DE-MRI) has emerged as a new reference method for infarct characterization in vivo.8 By acquiring DE–magnetic resonance (MR) images 20 to 40 minutes after injection of a gadolinium-based extracellular contrast agent, infarcted myocardium can be visualized. The mechanism for the delayed enhancement of infarcted myocardium is an increased distribution volume caused by loss of myocyte integrity, edema, and scar tissue replacement in the area of infarction. Therefore, the extracellular contrast agent has a larger distribution volume in the infarcted myocardium compared with that which is noninfarcted.9-12 Different wash-in/wash-out profiles have also been proposed to explain parts of the difference in the amount of contrast agent in infarcted and viable myocardium.10,13-15 Infarct sizing using DE-MRI has been shown to accurately depict areas of infarction in animal models by comparing regions of hyperenhancement with triphenyltetrazolium chloride– stained gross histologic slices of the heart.16,17 Furthermore, human studies have revealed that the transmural extent of 0022-0736/$ – see front matter D 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.jelectrocard.2007.02.009
hyperenhanced myocardium correlates well with the probability, magnitude, and timing of functional recovery after both reperfused acute MI18,19 and elective reperfusion therapy in chronic ischemic heart disease.20,21 The high accuracy of the DE-MRI technique for depicting areas of infarction shown in previous animal studies, however, relies on infarct quantification of hyperenhanced areas in high-spatial-resolution (0.5 0.5 0.5 mm) ex vivo images. This high spatial resolution is not obtained when acquiring standard DE-MR images in clinical routine. The typical spatial resolution of a clinically acquired DE-MR image is 1.5 1.5 8 mm. Thus, the thickness of standard infarct MR images is 16 times that of the high-spatial-resolution MR image acquired ex vivo. Consequently, the problem of partial volume arises in the clinical setting.16,22 Within the 8-mm-thick image slice the infarcted myocardium can be irregular within the image slice, resulting in unsharp infarct borders. Hence, there is a need for a standardization of how to delineate the region of hyperenhancement for accurate MI sizing.23 There is a variety of commercially available postprocessing software used to measure infarct size from in vivo images acquired with the DE-MRI technique. Often, the simple choice of whether whole pixels enclosed by the perimeter, inclusion of half pixels enclosed, or even including pixels on the perimeter still varies between different software. Another important issue is that of relative contrast and brightness used with different image display systems. The relative contrast and brightness can be altered in order to optimize visualization of the infarcted myocardium. By doing so, visible image contrast in the periphery of the hyperenhanced region is manipulated subjectively, which can affect the assessment of MI size in an unpredictable manner. It has recently been shown that manual delineation of hyperenhanced regions can overestimate both MI size and transmurality.17,24 Thus, a means of standardizing the range of grey scale levels and account for partial volume effects when delineating the infarcted myocardium is paramount.22 Other factors, such as contrast dose,25,26 time between injection of the contrast agent and image acquisition,25-27 and myocardial perfusion28 are also of importance for accurate MI visualization. Furthermore, the timing of image
244
Editorial / Journal of Electrocardiology 40 (2007) 243 – 245
acquisition in relation to the acute infarction needs to be considered when interpreting findings with DE-MRI. It has previously been shown that the penumbra of an infarcted region differs from both infarcted and normal myocardium.11,29-31 By using the DE-MRI technique early after acute MI, the region of hyperenhancement might overestimate the actual MI size, possibly because of an increased distribution volume due to the acute edema and inflammation in this peri-infarction zone.18,29,31-33 Optimization of the MRI acquisition parameter inversion time (TI) has to be considered as well, since TI affects the relative signal intensities in infarcted and non-infarcted myocardium as well as in blood. Consequently, TI affects the assessment of infarct size by DE-MRI.25,26 In order to decrease the dependence on optimal TI when acquiring DE-MRI images, a so-called phase sensitive acquisition technique has been developed.34 If the above discussed issues can be taken into consideration, DE-MRI has an excellent potential for depicting MI in vivo, being associated with a low interobserver variability.35,36 Hence, the DE-MRI technique can potentially be used to further develop and validate ECG indices of MI as well as reveal the pathologic basis of infarct-related ECG changes.37-41 Furthermore, since MRI does not require ionizing radiation, this imaging modality is suitable for serial examinations, enabling studies on MI evolution and ECG changes during the MI healing phase.18 However, in order to further develop established ECG indices of MI, large patient populations are needed. Thus, multicenter studies are desirable. To enable comparison of results from different sites, it is fundamental to have a standardized image acquisition protocol and standardized post-processing methods for MI quantification. Thus, we believe that there is a need for a broad consensus regarding how MI characterization should be performed using DEMRI. This is important for DE-MRI to serve not only as a reference method for MI quantification by ECG, but also for MI size assessed by DE-MRI to be used as a reliable outcome variable in ongoing and future clinical trials. Henrik Engblom, MD, PhD H3kan Arheden, MD, PhD Department of Clinical Physiology Lund University Hospital, Lund, Sweden E-mail address: [email protected] John E. Foster, PhD Thomas N. Martin, MD Glasgow Cardiac Magnetic Resonance Unit Glasgow, Lanarkshire, UK
References 1. Barnes AR. Electrocardiogram in myocardial infarction: review of one hundred and seven clinical cases and one hundred and eight proved cases at necropsy. Arch Intern Med 1935;55:457. 2. Palmeri ST, Harrison DG, Cobb FR, et al. A QRS scoring system for assessing left ventricular function after myocardial infarction. N Engl J Med 1982;306:4.
3. De Sutter J, Van de Wiele C, Gheeraert P, et al. The Selvester 32-point QRS score for evaluation of myocardial infarct size after primary coronary angioplasty. Am J Cardiol 1999;83:255-7, A5. 4. Clemmensen P, Grande P, Saunamaki K, Wagner NB, Selvester RH, Wagner GS. Evolution of electrocardiographic and echocardiographic abnormalities during the 4 years following first acute myocardial infarction. Eur J Heart 1995;16:1063. 5. Ideker RE, Wagner GS, Ruth WK, et al. Evaluation of a QRS scoring system for estimating myocardial infarct size. II. Correlation with quantitative anatomic findings for anterior infarcts. Am J Cardiol 1982;49:1604. 6. Ward RM, White RD, Ideker RE, et al. Evaluation of a QRS scoring system for estimating myocardial infarct size. IV. Correlation with quantitative anatomic findings for posterolateral infarcts. Am J Cardiol 1984;53:706. 7. Roark SF, Ideker RE, Wagner GS, et al. Evaluation of a QRS scoring system for estimating myocardial infarct size. III. Correlation with quantitative anatomic findings for inferior infarcts. Am J Cardiol 1983;51:382. 8. Pennell DJ, Sechtem UP, Higgins CB, et al. Clinical indications for cardiovascular magnetic resonance (CMR): Consensus Panel report. Eur J Heart 2004;25:1940. 9. Flacke SJ, Fischer SE, Lorenz CH. Measurement of the gadopentetate dimeglumine partition coefficient in human myocardium in vivo: normal distribution and elevation in acute and chronic infarction. Radiology 2001;218:703. 10. Tong CY, Prato FS, Wisenberg G, et al. Measurement of the extraction efficiency and distribution volume for Gd-DTPA in normal and diseased canine myocardium. Magn Reson Med 1993;30:337. 11. Arheden H, Saeed M, Higgins CB, et al. Measurement of the distribution volume of gadopentetate dimeglumine at echo-planar MR imaging to quantify myocardial infarction: comparison with 99mTc-DTPA autoradiography in rats. Radiology 1999;211:698. 12. Saeed M, Wendland MF, Masui T, Higgins CB. Reperfused myocardial infarctions on T1- and susceptibility-enhanced MRI: evidence for loss of compartmentalization of contrast media. Magn Reson Med 1994;31:31. 13. Diesbourg LD, Prato FS, Wisenberg G, et al. Quantification of myocardial blood flow and extracellular volumes using a bolus injection of Gd-DTPA: kinetic modeling in canine ischemic disease. Magn Reson Med 1992;23:239. 14. Klein C, Nekolla SG, Balbach T, et al. The influence of myocardial blood flow and volume of distribution on late Gd-DTPA kinetics in ischemic heart failure. J Magn Reson Imaging 2004;20:588. 15. Judd RM, Lugo-Olivieri CH, Arai M, et al. Physiological basis of myocardial contrast enhancement in fast magnetic resonance images of 2-day-old reperfused canine infarcts. Circulation 1995;92:1902. 16. Kim RJ, Fieno DS, Parrish TB, et al. Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function. Circulation 1999;100:1992. 17. 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;23:298. 18. Engblom H, Hedstrom E, Heiberg E, Wagner GS, Pahlm O, Arheden H. Time course and magnitude of infarct involution, functional recovery, and electrocardiographic changes in patients with reperfused first myocardial infarction [submitted for publication]. 19. Choi CJ, Haji-Momenian S, Dimaria JM, et al. Infarct involution and improved function during healing of acute myocardial infarction: the role of microvascular obstruction. J Cardiovasc Magn Reson 2004;6:917. 20. Kim RJ, Wu E, Rafael A, et al. The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction. N Engl J Med 2000;343:1445. 21. Ugander M, Cain P, Johnsson P, Arheden H. Time dependence of segmental functional improvement after bypass surgery: the interacting effects of stress perfusion by SPECT and scar by delayed enhancement MRI at baseline and 1 and 6 months post CABG. Circulation 2003;108(1857 Suppl):401.
Editorial / Journal of Electrocardiology 40 (2007) 243 – 245 22. Heiberg E, Ugander M, Engblom H, et al. Accounting for partial volume effects in the automated quantification of myocardial infarction from delayed enhancement MRI. Radiology [in press]. 23. Gibbons RJ, Valeti US, Araoz PA, Jaffe AS. The quantification of infarct size. J Am Coll Cardiol 2004;44:1533. 24. 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;23:309. 25. Petersen SE, Mohrs OK, Horstick G, et al. Influence of contrast agent dose and image acquisition timing on the quantitative determination of nonviable myocardial tissue using delayed contrast-enhanced magnetic resonance imaging. J Cardiovasc Magn Reson 2004;6:541. 26. Wagner A, Mahrholdt H, Thomson L, et al. Effects of time, dose, and inversion time for acute myocardial infarct size measurements based on magnetic resonance imaging–delayed contrast enhancement. J Am Coll Cardiol 2006;47:2027. 27. Oshinski JN, Yang Z, Jones JR, Mata JF, French BA. Imaging time after Gd-DTPA injection is critical in using delayed enhancement to determine infarct size accurately with magnetic resonance imaging. Circulation 2001;104:2838. 28. Hedstrom E, Arheden H, Eriksson R, Johansson L, Ahlstrom H, Bjerner T. Importance of perfusion in myocardial viability studies using delayed contrast-enhanced magnetic resonance imaging. J Magn Reson Imaging 2006;24:77. 29. 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;103:871. 30. Reimer KA, Jennings RB. The changing anatomic reference base of evolving myocardial infarction. Underestimation of myocardial collateral blood flow and overestimation of experimental anatomic infarct size due to tissue edema, hemorrhage and acute inflammation. Circulation 1979;60:866. 31. Arheden H, Saeed M, Higgins CB, et al. Reperfused rat myocardium subjected to various durations of ischemia: estimation of the distribution volume of contrast material with echo-planar MR imaging. Radiology 2000;215:520.
245
32. Schaefer S, Malloy CR, Katz J, et al. Gadolinium-DTPA–enhanced nuclear magnetic resonance imaging of reperfused myocardium: identification of the myocardial bed at risk. J Am Coll Cardiol 1988;12:1064. 33. Nishimura T, Yamada Y, Hayashi M, et al. Determination of infarct size of acute myocardial infarction in dogs by magnetic resonance imaging and gadolinium-DTPA: comparison with indium-111 antimyosin imaging. Am J Physiol Imaging 1989;4:83. 34. Kellman P, Arai AE, McVeigh ER, Aletras AH. Phase-sensitive inversion recovery for detecting myocardial infarction using gadolinium-delayed hyperenhancement. Magn Reson Med 2002; 47:372. 35. Bondarenko O, Beek AM, Hofman MB, 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;7:481. 36. Heiberg E, Engblom H, Engvall J, Hedstrom E, Ugander M, Arheden H. Semi-automatic quantification of myocardial infarction from delayed contrast enhanced magnetic resonance imaging. Scand J Cardiovasc 2005;39:267. 37. Engblom H, Wagner GS, Setser RM, et al. Quantitative clinical assessment of chronic anterior myocardial infarction with delayed enhancement magnetic resonance imaging and QRS scoring. Am J Heart 2003;146:359. 38. Moon JC, De Arenaza DP, Elkington AG, et al. The pathologic basis of Q-wave and non–Q-wave myocardial infarction: a cardiovascular magnetic resonance study. J Am Coll Cardiol 2004;44:554. 39. Engblom H, Hedstrom E, Heiberg E, Wagner GS, Pahlm O, Arheden H. Size and transmural extent of first-time reperfused myocardial infarction assessed by cardiac magnetic resonance can be estimated by 12-lead electrocardiogram. Am J Heart 2005;150:920. 40. Kaandorp TA, Bax JJ, Lamb HJ, et al. Which parameters on magnetic resonance imaging determine Q waves on the electrocardiogram? Am J Cardiol 2005;95:925. 41. Engblom H, Carlsson MB, Hedstrfm E, et al. The endocardial extent of reperfused myocardial infarction is a stronger determinant of pathological Q waves than is infarct transmurality. Clin Physiol Funct Imaging 2007;27:101.