Over the past few years, we demonstrated that T2-weighted MRI can detect the ischemic area at risk associated with a myocardial infarction. This means that a single MRI examination is capable of determining how much myocardium was jeopardized during the coronary occlusion based on T2-weighted images and how much was permanently infarcted using conventional delayed enhancement images. The beauty of this paradigm is that both determinations can be made 1-7 days after the myocardial infarction - something much more feasible than emergency room based SPECT methods that might interfere with acute stabilization of the patient (Aletras et al. Circulation 2006; 113: 1865). This methodology opens up the possibilities of studying treatments that might modulate the size of acute myocardial infarction. Determining what myocardium was ischemic during an acute coronary occlusion is potentially valuable clinically and for research purposes (Arai AE et al. J Cardiovasc Pharmacol Ther. 2011;16(3-4):313-20 and Schwartz Longacre Let al. Circulation. 2011;124(10):1172-9). While manganese contrast agents can determine area at risk (Natanzon A et al. Radiology. 2005 Sep;236(3):859-66), preliminary experience with a manganese based contrast agent in humans suggested this agent may have too many side effects to be clinically useful. Next, we found that T2-weighted MRI can determine the area at risk in acute MI and is thus complementary to delayed enhancement imaging in acute reperfused MI (Aletras et al. Circulation 2006; 113: 1865) and in non-reperfused myocardial infarction (Tilak et al. Investigative Radiology 2008; 43: 7-15). We developed 2 new methods for imaging myocardial edema associated with acute coronary syndrome (Kellman et al Magn Resonance Med 2007; 57: 891) and a second method that may offer better signal to noise ratio but is more difficult to implement (Aletras AH et al Magn Reson Med 2008; 59: 229). The T2-prep SSFP method markedly improved the diagnostic accuracy of determining the coronary territory associated with an acute myocardial infarction (Kellman et al Magn Resonance Med 2007; 57: 891). The T2-prep SSFP method also works well in humans and correlates with coronary angiographic measures of area at risk (Berry C et al. Circ Cardiovasc Imaging. 2010;3:527-535). More recently, we found that T2-weighted imaging can also detect intramyocardial hemorrhage with excellent sensitivity and specificity (Payne AR et al. Circ Cardiovasc Imaging. 2011 Sep 19). We extended the pathophysiological understanding of MRI abnormalities associated with the area at risk. Consistent with myocardial edema, the T1 of the area at risk is also abnormal (Ugander M et al. JACC Cardiovasc Imaging. 2012; 5(6): 596-603). This study used quantitative images of T1 and T2 and compared with pathology and microspheres for reference standard measurements of infarction and area at risk. The boundaries of perfusion defects associated with the area at risk have been explored with high resolution MRI, CT, and direct visualization of fluorescent perticles (van der Pals et al. Eur Heart J Cardiovasc Imaging 2015). These studies show a perfusion gradient at the borders of the area at risk and a less severe transmural extent of infarction. The kinetics of gadolinium wash-in and wash-out of salvaged myocardium, acutely infarcted myocardium, and in remote myocardium were studied in humans (Hammer-Hansen et al. Eur Heart Cardiovascular Imaging 2015). This study provides a mechanism for why gadolinium can over-estimate infarct size in acute myocardial infarction. This work led to a successful PhD dissertation (Hammer-Hansen 2018).

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8
Fiscal Year
2018
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U.S. National Heart Lung and Blood Inst
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Fan, H; Li, S; Lu, M et al. (2018) Myocardial late gadolinium enhancement: a head-to-head comparison of motion-corrected balanced steady-state free precession with segmented turbo fast low angle shot. Clin Radiol 73:593.e1-593.e9
Cui, Chen; Wang, Shuli; Lu, Minjie et al. (2018) Detection of Recent Myocardial Infarction Using Native T1 Mapping in a Swine Model: A Validation Study. Sci Rep 8:7391
Bulluck, Heerajnarain; Dharmakumar, Rohan; Arai, Andrew E et al. (2018) Cardiovascular Magnetic Resonance in Acute ST-Segment-Elevation Myocardial Infarction: Recent Advances, Controversies, and Future Directions. Circulation 137:1949-1964
Arai, Andrew E; Leifer, Eric S; Sachdev, Vandana (2017) The Authors Reply. JACC Cardiovasc Imaging 10:606
Arai, Andrew E (2017) Time-Varying Edema Requires Cautious Interpretation of Myocardium at Risk and Infarct Size by All Imaging Methods. Circulation 136:1301-1303
Hammer-Hansen, Sophia; Leung, Steve W; Hsu, Li-Yueh et al. (2017) Early Gadolinium Enhancement for Determination of Area at Risk: A Preclinical Validation Study. JACC Cardiovasc Imaging 10:130-139
Greulich, Simon; Arai, Andrew E; Sechtem, Udo et al. (2016) Recent advances in cardiac magnetic resonance. F1000Res 5:
Hammer-Hansen, Sophia; Bandettini, W Patricia; Hsu, Li-Yueh et al. (2016) Mechanisms for overestimating acute myocardial infarct size with gadolinium-enhanced cardiovascular magnetic resonance imaging in humans: a quantitative and kinetic study. Eur Heart J Cardiovasc Imaging 17:76-84
van der Pals, Jesper; Hammer-Hansen, Sophia; Nielles-Vallespin, Sonia et al. (2015) Temporal and spatial characteristics of the area at risk investigated using computed tomography and T1-weighted magnetic resonance imaging. Eur Heart J Cardiovasc Imaging 16:1232-40
Beliveau, Pascale; Cheriet, Farida; Anderson, Stasia A et al. (2015) Quantitative assessment of myocardial fibrosis in an age-related rat model by ex vivo late gadolinium enhancement magnetic resonance imaging with histopathological correlation. Comput Biol Med 65:103-13

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