Scientific foundation

The scientists associated with Imacor AB, all work as senior researchers in the Lund cardiac MR group, at Lund University. For almost 20 years, a central theme for the research pursued by the research group has been the pathophysiological mechanisms associated with acute and chronic ischemic heart disease, but also myocardial function, pumping mechanics and ECG.

The research has included quantitative assessments of infarct size, myocardium at risk and, consequently, myocardial salvage as well as myocardial function and ECG changes. A close collaboration between physicians, technicians, engineers, physicists and mathematicians has enabled creation of a research platform well suited for both experimental 1-8 and clinical studies 9-16 of ischemic heart disease and cardioprotection using cardiac magnetic resonance (CMR) and myocardial perfusion SPECT (MPS).

Imacor AB has been consulted in the design and execution of several multi-centre, multi-national cardioprotection trials9, 10, 16. When studying the efficacy of cardioprotective therapies in the situation of acute myocardial infarction it is important to be able to relate final infarct size to myocardium at risk. To ensure accurate and comparable quantitative assessment of infarct size and myocardium at risk using CMR it is of central importance to consider the basic mechanisms of contrast kinetics utilized in late gadolinium enhancement (LGE) CMR, but also the natural course of infarct resorption in humans.

The Lund cardiac MR group has developed and/or validated CMR methods for quantification of both infarct size using LGE 5, 17-18 and myocardium at risk using T2-weighted imaging 7, 19-21 and contrast-enhanced SSFP imaging8, 22. For use in multicenter, multivendor trials, contrast-enhanced SSFP imaging has been shown to be superior to T2-weighted imaging for assessment of MaR23 and is therefore recommended by Imacor AB when designing cardioprotection trials. Utilizing these quantitative techniques, the Lund CMR group was the first to directly describe infarct evolution in relation to duration of ischemia in humans23. Furthermore, the group was also first to show the natural course of infarct resorption in man over the first year after acute infarction, including the early (first week) resorption of hyperenhanced myocardium13. This paper elucidates the importance of considering the initial dynamic phase of infarct involution when determining the timing of the initial LGE examination in clinical trials of cardio-protective therapies. Also, the Lund CMR group has shown the mechanisms for change of hyperenhanced myocardium early after infarction in a more recent experimental study6.

Thus, the knowledge about the basic pathophysiology and contrast kinetics in combination with accurate implementation of the techniques described above can significantly affect the design of clinical cardioprotection trials. This is supported by a recent study by the Lund cardiac MR group showing that myocardial salvage index used as a surrogate endpoint derived from a single CMR examination will enable a significant decrease in sample size needed to reach sufficient statistical power compared to infarct size alone or biochemical markers25.

 

 

 

References

  1. 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;211:698-708.
    DOI: 10.1148/radiology.211.3.r99jn41698
  2. 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;215:520-8. DOI: 10.1148/radiology.215.2.r00ma38520
  3. Gotberg M, Olivecrona GK, Engblom H, et al. Rapid short-duration hypothermia with cold saline and endovascular cooling before reperfusion reduces microvascular obstruction and myocardial infarct size. BMC Cardiovasc Disord 2008;8:7. DOI: 10.1186/1471-2261-8-7
  4. 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;24:77-83. DOI: 10.1002/jmri.20604
  5. Heiberg E, Ugander M, Engblom H, et al. Automated quantification of myocardial infarction from MR images by accounting for partial volume effects: animal, phantom, and human study. Radiology 2008;246:581-8. DOI: 10.1148/radiol.2461062164
  6. Jablonowski R, Engblom H, Kanski M, et al. Contrast-Enhanced CMR Overestimates Early Myocardial Infarct Size: Mechanistic Insights Using ECV Measurements on Day 1 and Day 7. JACC Cardiovasc Imaging 2015;8:1379-89. DOI: 10.1016/j.jcmg.2015.08.015
  7. Ubachs JF, Engblom H, Koul S, et al. Myocardium at risk can be determined by ex vivo T2-weighted magnetic resonance imaging even in the presence of gadolinium: comparison to myocardial perfusion single photon emission computed tomography. Eur Heart J Cardiovasc Imaging 2013;14:261-8. DOI: 10.1093/ehjci/jes142
  8. Nordlund D, Kanski M, Jablonowski R, et al. Experimental validation of contrast-enhanced SSFP cine CMR for quantification of myocardium at risk in acute myocardial infarction. J Cardiovasc Magn Reson 2017;19:12. DOI: 10.1186/s12968-017-0325-y
  9. Atar D, Arheden H, Berdeaux A, 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;36:112-9. DOI: 10.1093/eurheartj/ehu331
  10. Erlinge D, Gotberg M, Lang I, 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;63:1857-65. DOI: 10.1016/j.jacc.2013.12.027
  11. Gotberg M, Olivecrona GK, Koul S, et al. A pilot study of rapid cooling by cold saline and endovascular cooling before reperfusion in patients with ST-elevation myocardial infarction. Circ Cardiovasc Interv 2010;3:400-7. DOI: 10.1161/CIRCINTERVENTIONS.110.957902
  12. 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 Heart J 2005;150:920. DOI: 10.1016/j.ahj.2005.07.022
  13. Engblom H, Hedstrom E, Heiberg E, Wagner GS, Pahlm O, Arheden H. Rapid initial reduction of hyperenhanced myocardium after reperfused first myocardial infarction suggests recovery of the peri-infarction zone: one-year follow-up by MRI. Circ Cardiovasc Imaging 2009;2:47-55.
    DOI: 10.1161/CIRCIMAGING.108.802199
  14. 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 Heart J 2003;146:359-66. DOI: 10.1016/S0002-8703(03)00187-X
  15. Nordlund D, Heiberg E, Carlsson M, et al. Extent of Myocardium at Risk for Left Anterior Descending Artery, Right Coronary Artery, and Left Circumflex Artery Occlusion Depicted by Contrast-Enhanced Steady State Free Precession and T2-Weighted Short Tau Inversion Recovery Magnetic Resonance Imaging. Circ Cardiovasc Imaging 2016;9. DOI: 10.1161/CIRCIMAGING.115.004376
  16. Erlinge D, Gotberg M, Noc M, et al. Therapeutic hypothermia for the treatment of acute myocardial infarction-combined analysis of the RAPID MI-ICE and the CHILL-MI trials. Ther Hypothermia Temp Manag 2015;5:77-84. DOI: 10.1089/ther.2015.0009
  17. Engblom H, Tufvesson J, Jablonowski R, et al. 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. J Cardiovasc Magn Reson 2016;18:27. DOI: 10.1186/s12968-016-0242-5
  18. 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 Cardiovasc J 2005;39:267-75. DOI: 10.1080/14017430500340543
  19. Ubachs JF, Sorensson P, Engblom H, et al. Myocardium at risk by magnetic resonance imaging: head-to-head comparison of T2-weighted imaging and contrast-enhanced steady-state free precession. Eur Heart J Cardiovasc Imaging 2012;13:1008-15. DOI: 10.1093/ehjci/jes091
  20. Carlsson M, Ubachs JF, Hedstrom E, Heiberg E, Jovinge S, Arheden H. Myocardium at risk after acute infarction in humans on cardiac magnetic resonance: quantitative assessment during follow-up and validation with single-photon emission computed tomography. JACC Cardiovasc Imaging 2009;2:569-76. DOI: 10.1016/j.jcmg.2008.11.018
  21. Tufvesson J, Carlsson M, Aletras AH, et al. Automatic segmentation of myocardium at risk from contrast enhanced SSFP CMR: validation against expert readers and SPECT. BMC Med Imaging 2016;16:19. DOI: 10.1186/s12880-016-0124-1
  22. Sorensson P, Heiberg E, Saleh N, et al. Assessment of myocardium at risk with contrast enhanced steady-state free precession cine cardiovascular magnetic resonance compared to single-photon emission computed tomography. J Cardiovasc Magn Reson 2010;12:25.
    DOI: 10.1186/1532-429X-12-25
  23. Nordlund D, Klug G, Heiberg E, et al. Multi-vendor, multicentre comparison of contrast-enhanced SSFP and T2-STIR CMR for determining myocardium at risk in ST-elevation myocardial infarction. Eur Heart J Cardiovasc Imaging 2016;17:744-53. DOI: 10.1093/ehjci/jew027
  24. Hedstrom E, Engblom H, Frogner F, et al. Infarct evolution in man studied in patients with first-time coronary occlusion in comparison to different species - implications for assessment of myocardial salvage. J Cardiovasc Magn Reson 2009;11:38. DOI: 10.1186/1532-429X-11-38
  25. Engblom H, Heiberg E, Erlinge D, et al. Sample Size in Clinical Cardioprotection Trials Using Myocardial Salvage Index, Infarct Size, or Biochemical Markers as Endpoint. J Am Heart Assoc 2016;5:e002708. DOI: 10.1161/JAHA.115.002708
 

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