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Biomedical Optics Express

Biomedical Optics Express

  • Editor: Joseph A. Izatt
  • Vol. 5, Iss. 1 — Jan. 1, 2014
  • pp: 69–77

High-resolution visualization of mouse cardiac microvasculature using optical histology

Austin J. Moy, Patrick C. Lo, and Bernard Choi  »View Author Affiliations

Biomedical Optics Express, Vol. 5, Issue 1, pp. 69-77 (2014)

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Cardiovascular disease typically is associated with dysfunction of the coronary vasculature and microvasculature. The study of cardiovascular disease typically involves imaging of the large coronary vessels and quantification of cardiac blood perfusion. These methods, however, are not well suited for imaging of the cardiac microvasculature. We used the optical histology method, which combines chemical optical clearing and optical imaging, to create high-resolution, wide-field maps of the cardiac microvasculature in ventral slices of mouse heart. We have demonstrated the ability of the optical histology method to enable wide-field visualization of the cardiac microvasculature in high-resolution and anticipate that optical histology may have significant impact in studying cardiovascular disease.

© 2013 Optical Society of America

OCIS Codes
(000.1430) General : Biology and medicine
(170.0170) Medical optics and biotechnology : Medical optics and biotechnology
(170.1790) Medical optics and biotechnology : Confocal microscopy
(170.3880) Medical optics and biotechnology : Medical and biological imaging
(170.6930) Medical optics and biotechnology : Tissue

ToC Category:

Original Manuscript: August 2, 2013
Revised Manuscript: October 4, 2013
Manuscript Accepted: November 15, 2013
Published: December 4, 2013

Virtual Issues
Advances in Optics for Biotechnology, Medicine and Surgery (2013) Biomedical Optics Express

Austin J. Moy, Patrick C. Lo, and Bernard Choi, "High-resolution visualization of mouse cardiac microvasculature using optical histology," Biomed. Opt. Express 5, 69-77 (2014)

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  1. A. S. Go, D. Mozaffarian, V. L. Roger, E. J. Benjamin, J. D. Berry, W. B. Borden, D. M. Bravata, S. Dai, E. S. Ford, C. S. Fox, S. Franco, H. J. Fullerton, C. Gillespie, S. M. Hailpern, J. A. Heit, V. J. Howard, M. D. Huffman, B. M. Kissela, S. J. Kittner, D. T. Lackland, J. H. Lichtman, L. D. Lisabeth, D. Magid, G. M. Marcus, A. Marelli, D. B. Matchar, D. K. McGuire, E. R. Mohler, C. S. Moy, M. E. Mussolino, G. Nichol, N. P. Paynter, P. J. Schreiner, P. D. Sorlie, J. Stein, T. N. Turan, S. S. Virani, N. D. Wong, D. Woo, M. B. Turner, and American Heart Association Statistics Committee and Stroke Statistics Subcommittee, “Heart disease and stroke statistics--2013 update: a report from the American Heart Association,” Circulation127(1), e6–e245 (2013). [CrossRef] [PubMed]
  2. A. C. Lardo, M. A. 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. Lima, “Contrast-enhanced multidetector computed tomography viability imaging after myocardial infarction: characterization of myocyte death, microvascular obstruction, and chronic scar,” Circulation113(3), 394–404 (2006). [CrossRef] [PubMed]
  3. T. H. Schindler, H. R. Schelbert, A. Quercioli, and V. Dilsizian, “Cardiac PET imaging for the detection and monitoring of coronary artery disease and microvascular health,” JACC Cardiovasc. Imaging3(6), 623–640 (2010). [CrossRef] [PubMed]
  4. K. Wei, A. R. Jayaweera, S. Firoozan, A. Linka, D. M. Skyba, and S. Kaul, “Quantification of myocardial blood flow with ultrasound-induced destruction of microbubbles administered as a constant venous infusion,” Circulation97(5), 473–483 (1998). [CrossRef] [PubMed]
  5. J. R. Panting, P. D. Gatehouse, G. Z. Yang, F. Grothues, D. N. Firmin, P. Collins, and D. J. Pennell, “Abnormal subendocardial perfusion in cardiac syndrome X detected by cardiovascular magnetic resonance imaging,” N. Engl. J. Med.346(25), 1948–1953 (2002). [CrossRef] [PubMed]
  6. R. Nijveldt, M. B. Hofman, A. Hirsch, A. M. Beek, V. A. Umans, P. R. Algra, J. J. Piek, and A. C. van Rossum, “Assessment of microvascular obstruction and prediction of short-term remodeling after acute myocardial infarction: cardiac MR imaging study,” Radiology250(2), 363–370 (2009). [CrossRef] [PubMed]
  7. W. L. Proudfit, E. K. Shirey, and F. M. Sones., “Selective cine coronary arteriography. Correlation with clinical findings in 1,000 patients,” Circulation33(6), 901–910 (1966). [CrossRef] [PubMed]
  8. D. Eitzman, Z. al-Aouar, H. L. Kanter, J. vom Dahl, M. Kirsh, G. M. Deeb, and M. Schwaiger, “Clinical outcome of patients with advanced coronary artery disease after viability studies with positron emission tomography,” J. Am. Coll. Cardiol.20(3), 559–565 (1992). [CrossRef] [PubMed]
  9. E. M. Geltman, D. Biello, M. J. Welch, M. M. Ter-Pogossian, R. Roberts, and B. E. Sobel, “Characterization of nontransmural myocardial infarction by positron-emission tomography,” Circulation65(4), 747–755 (1982). [CrossRef] [PubMed]
  10. K. L. Gould, R. A. Goldstein, N. A. Mullani, R. L. Kirkeeide, W. H. Wong, T. J. Tewson, M. S. Berridge, L. A. Bolomey, R. K. Hartz, R. W. Smalling, F. Fuentes, and A. Nishikawa, “Noninvasive assessment of coronary stenoses by myocardial perfusion imaging during pharmacologic coronary vasodilation. VIII. Clinical feasibility of positron cardiac imaging without a cyclotron using generator-produced rubidium-82,” J. Am. Coll. Cardiol.7(4), 775–789 (1986). [CrossRef] [PubMed]
  11. S. E. Nissen, J. C. Gurley, C. L. Grines, D. C. Booth, R. McClure, M. Berk, C. Fischer, and A. N. DeMaria, “Intravascular ultrasound assessment of lumen size and wall morphology in normal subjects and patients with coronary artery disease,” Circulation84(3), 1087–1099 (1991). [CrossRef] [PubMed]
  12. B. N. Potkin, A. L. Bartorelli, J. M. Gessert, R. F. Neville, Y. Almagor, W. C. Roberts, and M. B. Leon, “Coronary artery imaging with intravascular high-frequency ultrasound,” Circulation81(5), 1575–1585 (1990). [CrossRef] [PubMed]
  13. J. M. Tobis, J. Mallery, D. Mahon, K. Lehmann, P. Zalesky, J. Griffith, J. Gessert, M. Moriuchi, M. McRae, and M. L. Dwyer, “Intravascular ultrasound imaging of human coronary arteries in vivo. Analysis of tissue characterizations with comparison to in vitro histological specimens,” Circulation83(3), 913–926 (1991). [CrossRef] [PubMed]
  14. E. A. Zerhouni, D. M. Parish, W. J. Rogers, A. Yang, and E. P. Shapiro, “Human heart: tagging with MR imaging--a method for noninvasive assessment of myocardial motion,” Radiology169(1), 59–63 (1988). [PubMed]
  15. P. G. Camici and F. Crea, “Coronary microvascular dysfunction,” N. Engl. J. Med.356(8), 830–840 (2007). [CrossRef] [PubMed]
  16. C. A. Molyneux, M. C. Glyn, and B. J. Ward, “Oxidative stress and cardiac microvascular structure in ischemia and reperfusion: the protective effect of antioxidant vitamins,” Microvasc. Res.64(2), 265–277 (2002). [CrossRef] [PubMed]
  17. G. M. Kazanskaia, A. M. Volkov, T. M. D’iakonitsa, and A. M. Karas’kova, “Ultrastructure of coronary microvessels in conditions of heart reperfusion following prolonged ischemia while applying various methods of artificial hypothermia,” Tsitologiia53(12), 968–977 (2011). [PubMed]
  18. K. Rakusan, N. Cicutti, and F. Kolar, “Cardiac function, microvascular structure, and capillary hematocrit in hearts of polycythemic rats,” Am. J. Physiol. Heart Circ. Physiol.281(6), H2425–H2431 (2001). [PubMed]
  19. J. C. Russell and S. D. Proctor, “Small animal models of cardiovascular disease: tools for the study of the roles of metabolic syndrome, dyslipidemia, and atherosclerosis,” Cardiovasc. Pathol.15(6), 318–330 (2006). [CrossRef] [PubMed]
  20. A. R. Pries, H. Habazettl, G. Ambrosio, P. R. Hansen, J. C. Kaski, V. Schächinger, H. Tillmanns, G. Vassalli, I. Tritto, M. Weis, C. de Wit, and R. Bugiardini, “A review of methods for assessment of coronary microvascular disease in both clinical and experimental settings,” Cardiovasc. Res.80(2), 165–174 (2008). [CrossRef] [PubMed]
  21. S. Lee, C. Vinegoni, P. F. Feruglio, L. Fexon, R. Gorbatov, M. Pivoravov, A. Sbarbati, M. Nahrendorf, and R. Weissleder, “Real-time in vivo imaging of the beating mouse heart at microscopic resolution,” Nat Commun3, 1054 (2012). [CrossRef] [PubMed]
  22. J. Jones, R. Chowdhury, D. Jalloh, B. K. Seo, J. K. Pandya, C. B. Schaffer, and N. Nishimura, “In-Vivo Imaging of Beating Mouse Heart with Multiphoton Microscopy ” in Frontiers in Optics(OSA, Rochester, NY, 2012), p. FM4D.6.
  23. Y. S. Mukouyama, J. James, J. Nam, and Y. Uchida, “Whole-mount confocal microscopy for vascular branching morphogenesis,” Methods Mol. Biol.843, 69–78 (2012). [CrossRef] [PubMed]
  24. J. Nam, I. Onitsuka, J. Hatch, Y. Uchida, S. Ray, S. Huang, W. Li, H. Zang, P. Ruiz-Lozano, and Y. S. Mukouyama, “Coronary veins determine the pattern of sympathetic innervation in the developing heart,” Development140(7), 1475–1485 (2013). [CrossRef] [PubMed]
  25. J. A. Scherschel and M. Rubart, “Cardiovascular imaging using two-photon microscopy,” Microsc. Microanal.14(6), 492–506 (2008). [CrossRef] [PubMed]
  26. V. Caorsi, C. Toepfer, M. B. Sikkel, A. R. Lyon, K. MacLeod, and M. A. Ferenczi, “Non-linear optical microscopy sheds light on cardiovascular disease,” PLoS ONE8(2), e56136 (2013). [CrossRef] [PubMed]
  27. J. W. Verjans, D. Lovhaug, N. Narula, A. D. Petrov, B. Indrevoll, E. Bjurgert, T. B. Krasieva, L. B. Petersen, G. M. Kindberg, M. Solbakken, A. Cuthbertson, M. A. Vannan, C. P. Reutelingsperger, B. J. Tromberg, L. Hofstra, and J. Narula, “Noninvasive imaging of angiotensin receptors after myocardial infarction,” JACC Cardiovasc. Imaging1(3), 354–362 (2008). [CrossRef] [PubMed]
  28. A. J. Moy, M. P. Wiersma, and B. Choi, “Optical histology: a method to visualize microvasculature in thick tissue sections of mouse brain,” PLoS ONE8(1), e53753 (2013). [CrossRef] [PubMed]
  29. Y. Li, Y. Song, L. Zhao, G. Gaidosh, A. M. Laties, and R. Wen, “Direct labeling and visualization of blood vessels with lipophilic carbocyanine dye DiI,” Nat. Protoc.3(11), 1703–1708 (2008). [CrossRef] [PubMed]
  30. D. J. Ravnic, X. Jiang, T. Wolloscheck, J. P. Pratt, H. Huss, S. J. Mentzer, and M. A. Konerding, “Vessel painting of the microcirculation using fluorescent lipophilic tracers,” Microvasc. Res.70(1-2), 90–96 (2005). [CrossRef] [PubMed]
  31. S. M. White, S. C. George, and B. Choi, “Automated computation of functional vascular density using laser speckle imaging in a rodent window chamber model,” Microvasc. Res.82(1), 92–95 (2011). [CrossRef] [PubMed]
  32. R. K. Jain, L. L. Munn, and D. Fukumura, “Measuring angiogenesis and hemodynamics in mice,” Cold Spring Harb Protoc2013(4), 354–358 (2013). [CrossRef] [PubMed]
  33. J. E. Brush, R. O. Cannon, W. H. Schenke, R. O. Bonow, M. B. Leon, B. J. Maron, and S. E. Epstein, “Angina due to coronary microvascular disease in hypertensive patients without left ventricular hypertrophy,” N. Engl. J. Med.319(20), 1302–1307 (1988). [CrossRef] [PubMed]
  34. G. A. Lanza and F. Crea, “Primary coronary microvascular dysfunction: clinical presentation, pathophysiology, and management,” Circulation121(21), 2317–2325 (2010). [CrossRef] [PubMed]
  35. J. Herrmann, J. C. Kaski, and A. Lerman, “Coronary microvascular dysfunction in the clinical setting: from mystery to reality,” Eur. Heart J.33(22), 2771–2782 (2012). [CrossRef] [PubMed]
  36. H. M. Arthur, P. Campbell, P. J. Harvey, M. McGillion, P. Oh, E. Woodburn, and C. Hodgson, “Women, cardiac syndrome X, and microvascular heart disease,” Can. J. Cardiol.28(2Suppl), S42–S49 (2012). [CrossRef] [PubMed]
  37. J. C. Kaski, “Overview of gender aspects of cardiac syndrome X,” Cardiovasc. Res.53(3), 620–626 (2002). [CrossRef] [PubMed]
  38. S. E. Reis, R. Holubkov, A. J. Conrad Smith, S. F. Kelsey, B. L. Sharaf, N. Reichek, W. J. Rogers, C. N. Merz, G. Sopko, C. J. Pepine, and WISE Investigators, “Coronary microvascular dysfunction is highly prevalent in women with chest pain in the absence of coronary artery disease: results from the NHLBI WISE study,” Am. Heart J.141(5), 735–741 (2001). [CrossRef] [PubMed]
  39. F. Leuschner and M. Nahrendorf, “Molecular imaging of coronary atherosclerosis and myocardial infarction: considerations for the bench and perspectives for the clinic,” Circ. Res.108(5), 593–606 (2011). [CrossRef] [PubMed]
  40. I. Y. Chen and J. C. Wu, “Cardiovascular molecular imaging: focus on clinical translation,” Circulation123(4), 425–443 (2011). [CrossRef] [PubMed]

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