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Virtual Journal for Biomedical Optics

Virtual Journal for Biomedical Optics


  • Editors: Andrew Dunn and Anthony Durkin
  • Vol. 7, Iss. 7 — Jun. 25, 2012

Visualizing the complex 3D geometry of the perfusion border zone in isolated rabbit heart

Rebecca M. Smith, Adam J. Black, Saalini S. Velamakanni, Taner Akkin, and Elena G. Tolkacheva  »View Author Affiliations

Applied Optics, Vol. 51, Issue 14, pp. 2713-2721 (2012)

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Myocardial infarction, caused by a major blockage of a coronary artery, creates a border zone (BZ) between perfused and nonperfused tissue, which is believed to be the origin of fatal cardiac arrhythmias. We used a combination of optical clearing and polarization-sensitive optical coherence tomography to visualize a three-dimensional organization of the BZ in isolated rabbit hearts (n=5) at the microscopic level with a high spatial resolution. We found that the BZ has a complex three-dimensional structure with nonperfused areas penetrating into perfused tissue with finger-like projections. These “fingers” may play an important role in the initiation and maintenance of ventricular arrhythmias.

© 2012 Optical Society of America

OCIS Codes
(110.4500) Imaging systems : Optical coherence tomography
(170.5380) Medical optics and biotechnology : Physiology

ToC Category:
Imaging Systems

Original Manuscript: October 27, 2011
Revised Manuscript: January 24, 2012
Manuscript Accepted: March 14, 2012
Published: May 10, 2012

Virtual Issues
Vol. 7, Iss. 7 Virtual Journal for Biomedical Optics

Rebecca M. Smith, Adam J. Black, Saalini S. Velamakanni, Taner Akkin, and Elena G. Tolkacheva, "Visualizing the complex 3D geometry of the perfusion border zone in isolated rabbit heart," Appl. Opt. 51, 2713-2721 (2012)

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  1. WRITING GROUP MEMBERS, D. Lloyd-Jones, R. J. Adams, T. M. Brown, M. Carnethon, S. Dai, G. De Simone, T. B. Ferguson, E. Ford, K. Furie, C. Gillespie, A. Go, K. Greenlund, N. Haase, S. Hailpern, P. M. Ho, V. Howard, B. Kissela, S. Kittner, D. Lackland, L. Lisabeth, A. Marelli, M. M. McDermott, J. Meigs, D. Mozaffarian, M. Mussolino, G. Nichol, V. L. Roger, W. Rosamond, R. Sacco, P. Sorlie, R. Stafford, T. Thom, S. Wasserthiel-Smoller, N. D. Wong, and J. Wylie-Rosett, and on behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee, “Heart disease and stroke statistics—2010 update: a report from the American Heart Association,” Circulation 121, e46–e215 (2010). [CrossRef]
  2. R. Coronel, F. J. Wilms-Schopman, T. Opthof, J. Cinca, J. W. Fiolet, and M. J. Janse, “Reperfusion arrhythmias in isolated perfused pig hearts. Inhomogeneities in extracellular potassium, ST and TQ potentials, and transmembrane action potentials,” Circ. Res. 71, 1131–1142 (1992).
  3. M. J. Janse, F. J. van Capelle, H. Morsink, A. G. Kléber, F. Wilms-Schopman, R. Cardinal, C. N. d’Alnoncourt, and D. Durrer, “Flow of ‘injury’ current and patterns of excitation during early ventricular arrhythmias in acute regional myocardial ischemia in isolated porcine and canine hearts. Evidence for two different arrhythmogenic mechanisms,” Circ. Res. 47, 151–165 (1980).
  4. R. M. Shaw and Y. Rudy, “Electrophysiologic effects of acute myocardial ischemia. A mechanistic investigation of action potential conduction and conduction failure,” Circ. Res. 80, 124–138 (1997).
  5. S. G. Dilly and M. J. Lab, “Electrophysiological alternans and restitution during acute regional ischaemia in myocardium of anaesthetized pig,” J. Physiol. (Lond.) 402, 315–333 (1988).
  6. R. M. Shaw and Y. Rudy, “The vulnerable window for unidirectional block in cardiac tissue: characterization and dependence on membrane excitability and intercellular coupling,” J. Cardiovasc. Electrophysiol. 6, 115–131 (1995). [CrossRef]
  7. A. T. Yan, A. J. Shayne, K. A. Brown, S. N. Gupta, C. W. Chan, T. M. Luu, M. F. Di Carli, H. G. Reynolds, W. G. Stevenson, and R. Y. Kwong, “Characterization of the peri-infarct zone by contrast-enhanced cardiac magnetic resonance imaging is a powerful predictor of post-myocardial infarction mortality,” Circulation 114, 32–39 (2006). [CrossRef]
  8. B. M. Jackson, L. M. Parish, J. H. Gorman, Y. Enomoto, H. Sakamoto, T. Plappert, M. G. St John Sutton, I. Salgo, and R. C. Gorman, “Borderzone geometry after acute myocardial infarction: a three-dimensional contrast enhanced echocardiographic study,” Ann. Thorac. Surg 80, 2250–2255 (2005). [CrossRef]
  9. A. N. Lieberman, J. L. Weiss, B. I. Jugdutt, L. C. Becker, B. H. Bulkley, J. G. Garrison, G. M. Hutchins, C. A. Kallman, and M. L. Weisfeldt, “Two-dimensional echocardiography and infarct size: relationship of regional wall motion and thickening to the extent of myocardial infarction in the dog,” Circulation 63, 739–746 (1981). [CrossRef]
  10. J. L. Weiss, B. H. Bulkley, G. M. Hutchins, and S. J. Mason, “Two-dimensional echocardiographic recognition of myocardial injury in man: comparison with postmortem studies,” Circulation 63, 401–408 (1981). [CrossRef]
  11. N. S. Anavekar, “Cardiovascular magnetic resonance imaging,” Heart Lung Circ. 14, Suppl 2, S39–S45 (2005). [CrossRef]
  12. H. Ashikaga, T. Sasano, J. Dong, M. M. Zviman, R. Evers, B. Hopenfeld, V. Castro, R. H. Helm, T. Dickfeld, S. Nazarian, J. K. Donahue, R. D. Berger, H. Calkins, M. R. Abraham, E. Marbán, A. C. Lardo, E. R. McVeigh, and H. R. Halperin, “Magnetic resonance-based anatomical analysis of scar-related ventricular tachycardia: implications for catheter ablation,” Circ. Res. 101, 939–947 (2007). [CrossRef]
  13. T. C.-C. Hu, W. Bao, S. C. Lenhard, T. R. Schaeffer, T.-L. Yue, R. N. Willette, and B. M. Jucker, “Simultaneous assessment of left-ventricular infarction size, function and tissue viability in a murine model of myocardial infarction by cardiac manganese-enhanced magnetic resonance imaging (MEMRI),” NMR Biomed. 17, 620–626 (2004). [CrossRef]
  14. S. Nazarian, D. A. Bluemke, A. C. Lardo, M. M. Zviman, S. P. Watkins, T. L. Dickfeld, G. R. Meininger, A. Roguin, H. Calkins, G. F. Tomaselli, R. G. Weiss, R. D. Berger, J. A. C. Lima, and H. R. Halperin, “Magnetic resonance assessment of the substrate for inducible ventricular tachycardia in nonischemic cardiomyopathy,” Circulation 112, 2821–2825 (2005). [CrossRef]
  15. N. M. Szeverenyi, B. Searles, and A. Pertsov, “Contrast enhanced MRI characterization of the perfusion territories fed by individual coronary arteries in ex-vivo porcine heart,” Proc. SPIE 6916, 69161W (2008).
  16. A. C. Lardo, M. A. S. Cordeiro, C. Silva, L. C. Amado, R. T. George, A. P. Saliaris, K. H. Schuleri, V. R. Fernandes, M. Zviman, S. Nazarian, H. R. Halperin, K. C. Wu, J. M. Hare, and J. A. C. Lima, “Contrast-enhanced multidetector computed tomography viability imaging after myocardial infarction: characterization of myocyte death, microvascular obstruction, and chronic scar,” Circulation 113, 394–404 (2006). [CrossRef]
  17. Z. Liu, G. A. Kastis, G. D. Stevenson, H. H. Barrett, L. R. Furenlid, M. A. Kupinski, D. D. Patton, and D. W. Wilson, “Quantitative analysis of acute myocardial infarct in rat hearts with ischemia-reperfusion using a high-resolution stationary SPECT system,” J. Nucl. Med. 43, 933–939 (2002).
  18. P. Panse, C. Klassen, N. Panse, A. Siuciak, C. Rickers, M. Jerosch-Herold, and N. M. Wilke, “Magnetic resonance quantitative myocardial perfusion reserve demonstrates improved myocardial blood flow after angiogenic implant therapy,” Int. J. Cardiovasc. Imaging 23, 217–224 (2007). [CrossRef]
  19. M. T. Vivaldi, R. A. Kloner, and F. J. Schoen, “Triphenyltetrazolium staining of irreversible ischemic injury following coronary artery occlusion in rats,” Am. J. Pathol. 121, 522–530 (1985).
  20. N. L. Walker, F. L. Burton, S. Kettlewell, G. L. Smith, and S. M. Cobbe, “Mapping of epicardial activation in a rabbit model of chronic myocardial infarction,” J. Cardiovasc. Electrophysiol. 18, 862–868 (2007). [CrossRef]
  21. C. Bucciarelli-Ducci, E. Wu, D. C. Lee, T. A. Holly, F. J. Klocke, and R. O. Bonow, “Contrast-enhanced cardiac magnetic resonance in the evaluation of myocardial infarction and myocardial viability in patients with ischemic heart disease,” Curr. Probl. Cardiol. 31, 128–168 (2006). [CrossRef]
  22. Y. Jiang, K. Pandya, O. Smithies, and E. W. Hsu, “Three-dimensional diffusion tensor microscopy of fixed mouse hearts,” Magn. Reson. Med. 52, 453–460 (2004). [CrossRef]
  23. O. Bernus, R. M. Smith, N. M. Szeverenyi, M. Qin, and A. M. Pertsov, “The geometry of the ischemic region as an arrhythmogenic factor: insights from an MRI-based modeling study,” Heart Rhythm5, S310 PO5–8 (2008).
  24. D. J. Hearse and D. M. Yellon, “The ‘border zone’ in evolving myocardial infarction: controversy or confusion?,” Am. J. Cardiol. 47, 1321–1334 (1981). [CrossRef]
  25. R. M. Smith, A. Matiukas, C. W. Zemlin, and A. M. Pertsov, “Nondestructive optical determination of fiber organization in intact myocardial wall,” Microsc. Res. Tech. 71, 510–516 (2008). [CrossRef]
  26. X. Xu and R. K. Wang, “The role of water desorption on optical clearing of biotissue: studied with near infrared reflectance spectroscopy,” Med. Phys. 30, 1246–1253 (2003). [CrossRef]
  27. D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, and C. A. Puliafito, “Optical coherence tomography,” Science 254, 1178–1181 (1991). [CrossRef]
  28. M. K. Al-Qaisi and T. Akkin, “Swept-source polarization-sensitive optical coherence tomography based on polarization-maintaining fiber,” Opt. Express 18, 3392–3403 (2010). [CrossRef]
  29. W. T. Baxter, S. F. Mironov, A. V. Zaitsev, J. Jalife, and A. M. Pertsov, “Visualizing excitation waves inside cardiac muscle using transillumination,” Biophys. J. 80, 516–530 (2001). [CrossRef]
  30. H. Mahrholdt, A. Wagner, T. A. Holly, M. D. Elliott, R. O. Bonow, R. J. Kim, and R. M. Judd, “Reproducibility of chronic infarct size measurement by contrast-enhanced magnetic resonance imaging,” Circulation 106, 2322–2327 (2002). [CrossRef]
  31. A. Wagner, H. Mahrholdt, T. A. Holly, M. D. Elliott, M. Regenfus, M. Parker, F. J. Klocke, R. O. Bonow, R. J. Kim, and R. M. Judd, “Contrast-enhanced MRI and routine single photon emission computed tomography (SPECT) perfusion imaging for detection of subendocardial myocardial infarcts: an imaging study,” Lancet 361, 374–379 (2003). [CrossRef]
  32. W. W. Lee, B. Marinelli, A. M. van der Laan, B. F. Sena, R. Gorbatov, F. Leuschner, P. Dutta, Y. Iwamoto, T. Ueno, M. P. V. Begieneman, H. W. M. Niessen, J. J. Piek, C. Vinegoni, M. J. Pittet, F. K. Swirski, A. Tawakol, M. Di Carli, R. Weissleder, and M. Nahrendorf, “PET/MRI of inflammation in myocardial infarction,” J. Am. Coll. Cardiol. 59, 153–163 (2012). [CrossRef]
  33. E. Dall Armellina and R. P. Choudhury, “The role of cardiovascular magnetic resonance in patients with acute coronary syndromes,” Prog. Cardiovasc. Dis. 54, 230–239 (2011). [CrossRef]
  34. S. Desch, I. Eitel, S. de Waha, G. Fuernau, P. Lurz, M. Gutberlet, G. Schuler, and H. Thiele, “Cardiac magnetic resonance imaging parameters as surrogate endpoints in clinical trials of acute myocardial infarction,” Trials 12, 204 (2011). [CrossRef]
  35. G. D. Aquaro, A. Pingitore, E. Strata, G. Di Bella, C. Palmieri, D. Rovai, A. S. Petronio, A. L’Abbate, and M. Lombardi, “Relation of pain-to-balloon time and myocardial infarct size in patients transferred for primary percutaneous coronary intervention,” Am. J. Cardiol. 100, 28–34 (2007). [CrossRef]
  36. P. J. Slomka, D. Fieno, L. Thomson, J. D. Friedman, S. W. Hayes, G. Germano, and D. S. Berman, “Automatic detection and size quantification of infarcts by myocardial perfusion SPECT: clinical validation by delayed-enhancement MRI,” J. Nucl. Med. 46, 728–735 (2005).
  37. H. Peng, Z. Ruan, F. Long, J. H. Simpson, and E. W. Myers, “V3D enables real-time 3D visualization and quantitative analysis of large-scale biological image data sets,” Nat. Biotechnol. 28, 348–353 (2010). [CrossRef]
  38. J. W. Villard, M. D. Feldman, J. Kim, T. E. Milner, and G. L. Freeman, “Use of a blood substitute to determine instantaneous murine right ventricular thickening with optical coherence tomography,” Circulation 105, 1843–1849 (2002). [CrossRef]
  39. J. G. Fujimoto, “Optical coherence tomography for ultrahigh resolution in vivo imaging,” Nat. Biotechnol. 21, 1361–1367 (2003). [CrossRef]
  40. C. P. Fleming, C. M. Ripplinger, B. Webb, I. R. Efimov, and A. M. Rollins, “Quantification of cardiac fiber orientation using optical coherence tomography,” J. Biomed. Opt. 13, 030505 (2008). [CrossRef]
  41. W. J. Hucker, C. M. Ripplinger, C. P. Fleming, V. V. Fedorov, A. M. Rollins, and I. R. Efimov, “Bimodal biophotonic imaging of the structure-function relationship in cardiac tissue,” J. Biomed. Opt. 13, 054012 (2008). [CrossRef]
  42. M. W. Jenkins, O. Q. Chughtai, A. N. Basavanhally, M. Watanabe, and A. M. Rollins, “In vivo gated 4D imaging of the embryonic heart using optical coherence tomography,” J. Biomed. Opt. 12, 030505 (2007). [CrossRef]
  43. C.-W. Sun, Y.-M. Wang, L.-S. Lu, C.-W. Lu, I.-J. Hsu, M.-T. Tsai, C. C. Yang, Y.-W. Kiang, and C.-C. Wu, “Myocardial tissue characterization based on a polarization-sensitive optical coherence tomography system with an ultrashort pulsed laser,” J. Biomed. Opt. 11, 054016 (2006). [CrossRef]
  44. A. Kanai and G. Salama, “Optical mapping reveals that repolarization spreads anisotropically and is guided by fiber orientation in guinea pig hearts,” Circ. Res. 77, 784–802 (1995).
  45. D. D. Streeter, H. M. Spotnitz, D. P. Patel, J. Ross, and E. H. Sonnenblick, “Fiber orientation in the canine left ventricle during diastole and systole,” Circ. Res. 24, 339–347 (1969).

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