One of the most important issues in clinical cardiology is the detection of injured but salvageable myocardium. Despite extensive study, the potential role of contrast MRI in detecting salvageable myocardium is not fully understood perhaps secondary to the complexity of myocardial injury and healing. In addition, new contrast enhancement patterns are observed with advances in MRI technology. We recognized that resolution of three key issues would provide important guidance for future investigations: 1) Do regions subjected to severe but reversible ischemic injury hyperenhance? 2) Does the spatial extent of hyperenhancement overestimate that of acute myocyte necrosis? 3) Do chronic infarcts (collagenous scar) hyperenhance? Over the past year we have studied these issues in chronically instrumented dogs (Appendix 1). We found that delayed hyperenhancement (images acquired >5 min after Gd-DTPA) does not occur following severe but reversible ischemic injury despite a persistent wall motion abnormality (Part 1 of Preliminary Studies). We found that at a spatial resolution of 500x500x500 mu m the size and shape of MRI hyperenhanced regions appear to be identical to those of acute myocyte necrosis at 2 hours (with reperfusion), l day (without reperfusion), and 3 days post- infarct (Part 2 of Preliminary Studies). We also found that collagenous scars hyperenhance and that scar size matches the size of hyperenhancement (Part 3 of Preliminary Studies). In the pathophysiologies investigated to date, the data suggest a potentially important hypothesis: to the limit of the spatial resolution of contrast MRI, myocardium that does not hyperenhance is viable irrespective of contractile function and infarct age. To investigate this further, we propose to determine the relation between the spatial extent of MRI hyperenhancement to that of myocyte necrosis and scar throughout the processes of injury and healing (Aim l), to determine the mechanisms which underlie contrast enhancement (Aim 2), and to understand how longitudinal changes in contrast enhancement patterns within individuals relate to the evolution of injury (Aim 3). This will be achieved by combining in vivo and ex vivo MRI with established techniques such as histochemical staining, light and electron microscopy, electron probe X-ray microanalysis and inductively-coupled plasma emission spectroscopy. Our proposed five-year plan will allow us to establish the relationship of MRI contrast enhancement patterns to the presence and extent of viable myocardium.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL063268-02
Application #
6185065
Study Section
Diagnostic Radiology Study Section (RNM)
Project Start
1999-07-01
Project End
2003-06-30
Budget Start
2000-07-01
Budget End
2001-06-30
Support Year
2
Fiscal Year
2000
Total Cost
$331,215
Indirect Cost
Name
Northwestern University at Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Mendoza, Dorinna D; Kochar, Minisha; Devereux, Richard B et al. (2011) Impact of image analysis methodology on diagnostic and surgical classification of patients with thoracic aortic aneurysms. Ann Thorac Surg 92:904-12
Weinsaft, Jonathan W; Kim, Han W; Crowley, Anna Lisa et al. (2011) LV thrombus detection by routine echocardiography: insights into performance characteristics using delayed enhancement CMR. JACC Cardiovasc Imaging 4:702-12
Patel, Manesh R; Cawley, Peter J; Heitner, John F et al. (2009) Detection of myocardial damage in patients with sarcoidosis. Circulation 120:1969-77
Kim, Han W; Klem, Igor; Shah, Dipan J et al. (2009) Unrecognized non-Q-wave myocardial infarction: prevalence and prognostic significance in patients with suspected coronary disease. PLoS Med 6:e1000057
Thomson, Louise E J; Crowley, Anna Lisa; Heitner, John F et al. (2008) Direct en face imaging of secundum atrial septal defects by velocity-encoded cardiovascular magnetic resonance in patients evaluated for possible transcatheter closure. Circ Cardiovasc Imaging 1:31-40
Klem, Igor; Greulich, Simon; Heitner, John F et al. (2008) Value of cardiovascular magnetic resonance stress perfusion testing for the detection of coronary artery disease in women. JACC Cardiovasc Imaging 1:436-45
Weinsaft, Jonathan W; Kim, Han W; Shah, Dipan J et al. (2008) Detection of left ventricular thrombus by delayed-enhancement cardiovascular magnetic resonance prevalence and markers in patients with systolic dysfunction. J Am Coll Cardiol 52:148-57
Sievers, Burkhard; Elliott, Michael D; Hurwitz, Lynne M et al. (2007) Rapid detection of myocardial infarction by subsecond, free-breathing delayed contrast-enhancement cardiovascular magnetic resonance. Circulation 115:236-44
Wagner, Anja; Mahrholdt, Heiko; Thomson, Louise et al. (2006) 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 47:2027-33
Klem, Igor; Heitner, John F; Shah, Dipan J et al. (2006) Improved detection of coronary artery disease by stress perfusion cardiovascular magnetic resonance with the use of delayed enhancement infarction imaging. J Am Coll Cardiol 47:1630-8

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