OSA's Digital Library

Biomedical Optics Express

Biomedical Optics Express

  • Editor: Joseph A. Izatt
  • Vol. 1, Iss. 1 — Aug. 2, 2010
  • pp: 59–73

Differentiating atherosclerotic plaque burden in arterial tissues using femtosecond CARS-based multimodal nonlinear optical imaging

Leila B. Mostaço-Guidolin, Michael G. Sowa, Andrew Ridsdale, Adrian F. Pegoraro, Michael S. D. Smith, Mark D. Hewko, Elicia K. Kohlenberg, Bernie Schattka, Masashi Shiomi, Albert Stolow, and Alex C.-T. Ko  »View Author Affiliations

Biomedical Optics Express, Vol. 1, Issue 1, pp. 59-73 (2010)

View Full Text Article

Enhanced HTML    Acrobat PDF (2977 KB)

Browse Journals / Lookup Meetings

Browse by Journal and Year


Lookup Conference Papers

Close Browse Journals / Lookup Meetings

Article Tools



A femtosecond CARS-based nonlinear optical microscope was used to simultaneously image extracellular structural proteins and lipid-rich structures within intact aortic tissue obtained from myocardial infarction-prone Watanabe heritable hyperlipidemic rabbits (WHHLMI). Clear differences in the NLO microscopic images were observed between healthy arterial tissue and regions dominated by atherosclerotic lesions. In the current ex-vivo study, we present a single parameter based on intensity changes derived from multi-channel NLO image to classify plaque burden within the vessel. Using this parameter we were able to differentiate between healthy regions of the vessel and regions with plaque, as well as distinguish plaques relative to the age of the WHHLMI rabbit.

© 2010 OSA

OCIS Codes
(170.3880) Medical optics and biotechnology : Medical and biological imaging
(170.4580) Medical optics and biotechnology : Optical diagnostics for medicine
(300.6230) Spectroscopy : Spectroscopy, coherent anti-Stokes Raman scattering
(180.4315) Microscopy : Nonlinear microscopy

ToC Category:
Diagnostic Applications

Original Manuscript: May 5, 2010
Revised Manuscript: June 24, 2010
Manuscript Accepted: June 25, 2010
Published: July 14, 2010

Virtual Issues
Bio-Optics in Clinical Application, Nanotechnology, and Drug Discovery (2010) Biomedical Optics Express

Leila B. Mostaço-Guidolin, Michael G. Sowa, Andrew Ridsdale, Adrian F. Pegoraro, Michael S. D. Smith, Mark D. Hewko, Elicia K. Kohlenberg, Bernie Schattka, Masashi Shiomi, Albert Stolow, and Alex C.-T. Ko, "Differentiating atherosclerotic plaque burden in arterial tissues using femtosecond CARS-based multimodal nonlinear optical imaging," Biomed. Opt. Express 1, 59-73 (2010)

Sort:  Author  |  Year  |  Journal  |  Reset  


  1. P. Libby, “Atherosclerosis: disease biology affecting the coronary vasculature,” Am. J. Cardiol. 98(12), S3–S9 (2006). [CrossRef] [PubMed]
  2. G. K. Hansson, “Inflammation, atherosclerosis, and coronary artery disease,” N. Engl. J. Med. 352(16), 1685–1695 (2005). [CrossRef] [PubMed]
  3. A. J. Lusis, “Atherosclerosis,” Nature 407(6801), 233–241 (2000). [CrossRef] [PubMed]
  4. B. K. Courtney, N. R. Munce, K. J. Anderson, A. S. Thind, G. Leung, P. E. Radau, F. S. Foster, I. A. Vitkin, R. S. Schwartz, A. J. Dick, G. A. Wright, and B. H. Strauss, “Innovations in imaging for chronic total occlusions: a glimpse into the future of angiography’s blind-spot,” Eur. Heart J. 29(5), 583–593 (2008). [CrossRef] [PubMed]
  5. D. A. Bluemke, S. Achenbach, M. Budoff, T. C. Gerber, B. Gersh, L. D. Hillis, W. G. Hundley, W. J. Manning, B. F. Printz, M. Stuber, and P. K. Woodard, “Noninvasive coronary artery imaging: magnetic resonance angiography and multidetector computed tomography angiography: a scientific statement from the american heart association committee on cardiovascular imaging and intervention of the council on cardiovascular radiology and intervention, and the councils on clinical cardiology and cardiovascular disease in the young,” Circulation 118(5), 586–606 (2008). [CrossRef] [PubMed]
  6. Y. Honda and P. J. Fitzgerald, “Frontiers in intravascular imaging technologies,” Circulation 117(15), 2024–2037 (2008). [CrossRef] [PubMed]
  7. P. G. Yock and P. J. Fitzgerald, “Optimal Directional Coronary Atherectomy Final Results of the Optimal Atherectomy Restenosis Study (OARS),” Am. J. Cardiol. 81, 27E–32E (1998). [PubMed]
  8. J. M. Hodgson, K. G. Reddy, R. Suneja, R. N. Nair, E. J. Lesnefsky, and H. M. Sheehan, “Intracoronary ultrasound imaging: correlation of plaque morphology with angiography, clinical syndrome and procedural results in patients undergoing coronary angioplasty,” J. Am. Coll. Cardiol. 21(1), 35–44 (1993). [CrossRef] [PubMed]
  9. J. Sun, Z. Zhang, B. Lu, W. Yu, Y. Yang, Y. Zhou, Y. Wang, and Z. Fan, “Identification and quantification of coronary atherosclerotic plaques: a comparison of 64-MDCT and intravascular ultrasound,” AJR Am. J. Roentgenol. 190(3), 748–754 (2008). [CrossRef] [PubMed]
  10. P. Barlis and J. M. Schmitt, “Current and future developments in intracoronary optical coherence tomography imaging,” EuroIntervention 4(4), 529–533 (2009). [PubMed]
  11. P. Barlis, P. W. Serruys, A. Devries, and E. Regar, “Optical coherence tomography assessment of vulnerable plaque rupture: predilection for the plaque ‘shoulder’,” Eur. Heart J. 29(16), 2023 (2008). [CrossRef] [PubMed]
  12. P. Barlis, G. Ferrante, F. Del Furia, and C. Di Mario, “In-vivo characterisation of coronary atherosclerosis with optical coherence tomography,” Med. J. Aust. 188(12), 728 (2008). [PubMed]
  13. I. K. Jang, G. J. Tearney, B. MacNeill, M. Takano, F. Moselewski, N. Iftima, M. Shishkov, S. Houser, H. T. Aretz, E. F. Halpern, and B. E. Bouma, “In vivo characterization of coronary atherosclerotic plaque by use of optical coherence tomography,” Circulation 111(12), 1551–1555 (2005). [CrossRef] [PubMed]
  14. R. Rocha, L. Silveira, A. B. Villaverde, C. A. Pasqualucci, M. S. Costa, A. Brugnera, and M. T. T. Pacheco, “Use of near-infrared Raman spectroscopy for identification of atherosclerotic plaques in the carotid artery,” Photomed. Laser Surg. 25(6), 482–486 (2007). [CrossRef] [PubMed]
  15. Y. Komachi, H. Sato, and H. Tashiro, “Intravascular Raman spectroscopic catheter for molecular diagnosis of atherosclerotic coronary disease,” Appl. Opt. 45(30), 7938–7943 (2006). [CrossRef] [PubMed]
  16. J. T. Motz, M. Fitzmaurice, A. Miller, S. J. Gandhi, A. S. Haka, L. H. Galindo, R. R. Dasari, J. R. Kramer, and M. S. Feld, “In vivo Raman spectral pathology of human atherosclerosis and vulnerable plaque,” J. Biomed. Opt. 11(2), 021003 (2006). [CrossRef] [PubMed]
  17. G. V. Nogueira, L. Silveira, A. A. Martin, R. A. Zângaro, M. T. Pacheco, M. C. Chavantes, and C. A. Pasqualucci, “Raman spectroscopy study of atherosclerosis in human carotid artery,” J. Biomed. Opt. 10(3), 031117 (2005). [CrossRef] [PubMed]
  18. T. J. Römer, J. F. Brennan, G. J. Puppels, A. H. Zwinderman, S. G. van Duinen, A. van der Laarse, A. F. van der Steen, N. A. Bom, and A. V. Bruschke, “Intravascular ultrasound combined with Raman spectroscopy to localize and quantify cholesterol and calcium salts in atherosclerotic coronary arteries,” Arterioscler. Thromb. Vasc. Biol. 20(2), 478–483 (2000). [PubMed]
  19. W. R. Zipfel, R. M. Williams, and W. W. Webb, “Nonlinear magic: multiphoton microscopy in the biosciences,” Nat. Biotechnol. 21(11), 1369–1377 (2003). [CrossRef] [PubMed]
  20. F. Helmchen and W. Denk, “Deep tissue two-photon microscopy,” Nat. Methods 2(12), 932–940 (2005). [CrossRef] [PubMed]
  21. W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7075–7080 (2003). [CrossRef] [PubMed]
  22. P. J. Campagnola and L. M. Loew, “Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms,” Nat. Biotechnol. 21(11), 1356–1360 (2003). [CrossRef] [PubMed]
  23. R. M. Williams, W. R. Zipfel, and W. W. Webb, “Interpreting second-harmonic generation images of collagen I fibrils,” Biophys. J. 88(2), 1377–1386 (2005). [CrossRef] [PubMed]
  24. A. Zoumi, A. Yeh, and B. J. Tromberg, “Imaging cells and extracellular matrix in vivo by using second-harmonic generation and two-photon excited fluorescence,” Proc. Natl. Acad. Sci. U.S.A. 99(17), 11014–11019 (2002). [CrossRef] [PubMed]
  25. J.-X. Cheng and X. S. Xie, “Coherent Anti-Stokes Raman Scattering Microscopy: Instrumentation, Theory, and Applications,” J. Phys. Chem. B 108(3), 827–840 (2004). [CrossRef]
  26. C. L. Evans, E. O. Potma, M. Puoris’haag, D. Côté, C. P. Lin, and X. S. Xie, “Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy,” Proc. Natl. Acad. Sci. U.S.A. 102(46), 16807–16812 (2005). [CrossRef] [PubMed]
  27. X. Nan, J.-X. Cheng, and X. S. Xie, “Vibrational imaging of lipid droplets in live fibroblast cells with coherent anti-Stokes Raman scattering microscopy,” J. Lipid Res. 44(11), 2202–2208 (2003). [CrossRef] [PubMed]
  28. Y.-M. Wu, H.-C. Chen, W.-T. Chang, J.-W. Jhan, H.-L. Lin, and I. Liau, “Quantitative assessment of hepatic fat of intact liver tissues with coherent anti-stokes Raman scattering microscopy,” Anal. Chem. 81(4), 1496–1504 (2009). [CrossRef] [PubMed]
  29. A. Zoumi, X. Lu, G. S. Kassab, and B. J. Tromberg, “Imaging coronary artery microstructure using second-harmonic and two-photon fluorescence microscopy,” Biophys. J. 87(4), 2778–2786 (2004). [CrossRef] [PubMed]
  30. M. B. Lilledahl, O. A. Haugen, C. de Lange Davies, and L. O. Svaasand, “Characterization of vulnerable plaques by multiphoton microscopy,” J. Biomed. Opt. 12(4), 044005 (2007). [CrossRef] [PubMed]
  31. H.-W. Wang, T. T. Le, and J.-X. Cheng, “Label-free imaging of arterial cells and extracellular matrix using a multimodal CARS microscope,” Opt. Commun. 281(7), 1813–1822 (2008). [CrossRef] [PubMed]
  32. T. T. Le, I. M. Langohr, M. J. Locker, M. Sturek, and J.-X. Cheng, “Label-free molecular imaging of atherosclerotic lesions using multimodal nonlinear optical microscopy,” J. Biomed. Opt. 12(5), 054007 (2007). [CrossRef] [PubMed]
  33. H.-W. Wang, I. M. Langohr, M. Sturek, and J.-X. Cheng, “Imaging and quantitative analysis of atherosclerotic lesions by CARS-based multimodal nonlinear optical microscopy,” Arterioscler. Thromb. Vasc. Biol. 29(9), 1342–1348 (2009). [CrossRef] [PubMed]
  34. A. F. Pegoraro, A. Ridsdale, D. J. Moffatt, Y. Jia, J. P. Pezacki, and A. Stolow, “Optimally chirped multimodal CARS microscopy based on a single Ti:sapphire oscillator,” Opt. Express 17(4), 2984–2996 (2009). [CrossRef] [PubMed]
  35. A. C.-T. Ko, A. Ridsdale, M. S. D. Smith, L. B. Mostaço-Guidolin, M. D. Hewko, A. F. Pegoraro, E. K. Kohlenberg, B. Schattka, M. Shiomi, A. Stolow, and M. G. Sowa, “Multimodal nonlinear optical imaging of atherosclerotic plaque development in myocardial infarction-prone rabbits,” J. Biomed. Opt. 15(2), 020501 (2010). [CrossRef] [PubMed]
  36. S. Tang, W. Jung, D. McCormick, T. Xie, J. Su, Y. C. Ahn, B. J. Tromberg, and Z. Chen, “Design and implementation of fiber-based multiphoton endoscopy with microelectromechanical systems scanning,” J. Biomed. Opt. 14(3), 034005 (2009). [CrossRef] [PubMed]
  37. G. Liu, T. Xie, I. V. Tomov, J. Su, L. Yu, J. Zhang, B. J. Tromberg, and Z. Chen, “Rotational multiphoton endoscopy with a 1 microm fiber laser system,” Opt. Lett. 34(15), 2249–2251 (2009). [CrossRef] [PubMed]
  38. M. Balu, G. Liu, Z. Chen, B. J. Tromberg, and E. O. Potma, “Fiber delivered probe for efficient CARS imaging of tissues,” Opt. Express 18(3), 2380–2388 (2010). [CrossRef] [PubMed]
  39. M. Shiomi, T. Ito, S. Yamada, S. Kawashima, and J. Fan, “Development of an animal model for spontaneous myocardial infarction (WHHLMI rabbit),” Arterioscler. Thromb. Vasc. Biol. 23(7), 1239–1244 (2003). [CrossRef] [PubMed]
  40. M. Shiomi, T. Ito, S. Yamada, S. Kawashima, and J. Fan, “Correlation of vulnerable coronary plaques to sudden cardiac events. Lessons from a myocardial infarction-prone animal model (the WHHLMI rabbit),” J. Atheroscler. Thromb. 11(4), 184–189 (2004). [PubMed]
  41. P. Whittaker, R. A. Kloner, D. R. Boughner, and J. G. Pickering, “Quantitative assessment of myocardial collagen with picrosirius red staining and circularly polarized light,” Basic Res. Cardiol. 89(5), 397–410 (1994). [CrossRef] [PubMed]
  42. T. A. Pologruto, B. L. Sabatini, and K. Svoboda, “ScanImage: flexible software for operating laser scanning microscopes,” Biomed. Eng. Online 2(1), 13 (2003). [CrossRef] [PubMed]
  43. M. Strupler, A. M. Pena, M. Hernest, P. L. Tharaux, J. L. Martin, E. Beaurepaire, and M. C. Schanne-Klein, “Second harmonic imaging and scoring of collagen in fibrotic tissues,” Opt. Express 15(7), 4054–4065 (2007). [CrossRef] [PubMed]
  44. H. C. Stary, A. B. Chandler, R. E. Dinsmore, V. Fuster, S. Glagov, W. Insull, M. E. Rosenfeld, C. J. Schwartz, W. D. Wagner, and R. W. Wissler, “A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association,” Circulation 92(5), 1355–1374 (1995). [PubMed]
  45. L. M. Buja, T. Kita, J. L. Goldstein, Y. Watanabe, and M. S. Brown, “Cellular pathology of progressive atherosclerosis in the WHHL rabbit. An animal model of familial hypercholesterolemia,” Arteriosclerosis 3(1), 87–101 (1983). [PubMed]
  46. A. M. Seddon, N. Woolf, A. La Ville, R. M. Pittilo, P. M. Rowles, P. R. Turner, and B. Lewis, “Hereditary hyperlipidemia and atherosclerosis in the rabbit due to overproduction of lipoproteins. II. Preliminary report of arterial pathology,” Arteriosclerosis 7(2), 113–124 (1987). [PubMed]

Cited By

Alert me when this paper is cited

OSA is able to provide readers links to articles that cite this paper by participating in CrossRef's Cited-By Linking service. CrossRef includes content from more than 3000 publishers and societies. In addition to listing OSA journal articles that cite this paper, citing articles from other participating publishers will also be listed.

« Previous Article  |  Next Article »

OSA is a member of CrossRef.

CrossCheck Deposited