Hostname: page-component-848d4c4894-ndmmz Total loading time: 0 Render date: 2024-05-22T00:28:18.462Z Has data issue: false hasContentIssue false
  • English
  • Français

(Second) Harmonic Disharmony: Nonlinear Microscopy Shines New Light on the Pathology of Atherosclerosis

Published online by Cambridge University Press:  22 June 2016

Shana R. Watson  and
Susan M. Lessner
Shana R. Watson
Affiliation:
Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC, USA
Susan M. Lessner*
Affiliation:
Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC, USA
*
*Corresponding author. Susan.Lessner@uscmed.sc.edu
Get access

Abstract

There has been increasing interest in second harmonic generation (SHG) imaging approaches for the investigation of atherosclerosis due to the deep penetration and three-dimensional sectioning capabilities of the nonlinear optical microscope. Atherosclerosis involves remodeling or alteration of the collagenous framework in affected vessels. The disease is often characterized by excessive collagen deposition and altered collagen organization. SHG has the capability to accurately characterize collagen structure, which is an essential component in understanding atherosclerotic lesion development and progression. As a structure-based imaging modality, SHG is most impactful in atherosclerosis evaluation in conjunction with other, chemically specific nonlinear optics (NLO) techniques to identify additional components of the lesion. These include the use of coherent anti-Stokes Raman scattering and two-photon excitation fluorescence for studying atherosclerosis burden, and application of stimulated Raman scattering to image cholesterol crystals. However, very few NLO studies have attempted to quantitate differences in control versus atherosclerotic states or to correlate the application to clinical situations. This review highlights the potential of SHG imaging to directly and indirectly describe atherosclerosis as a pathological condition.

Keywords

atherosclerosisarterial tissuesecond harmonic generation microscopynonlinear microscopy
Type
Biological Applications
Information
Microscopy and Microanalysis , Volume 22 , Issue 3 , June 2016 , pp. 589 - 598
Copyright
Copyright © Microscopy Society of America 2016

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abela, G.S. (2010). Cholesterol crystals piercing the arterial plaque and intima trigger local and systemic inflammation. J Clin Lipidol 4, 156–164.Google Scholar
American Cancer Society (2006). Cancer Facts and Figures. Atlanta: Amercan Cancer Society.Google Scholar
Badimon, L., Padró, T. & Vilahur, G. (2012). Atherosclerosis, platelets and thrombosis in acute ischaemic heart disease. Eur Heart J Acute Cardiovasc Care 1, 60–74.Google Scholar
Benvenuti, L.A., Onishi, R.Y., Gutierrez, P.S. & Higuchi, M. de L. (2005). Different patterns of atherosclerotic remodeling in the thoracic and abdominal aorta. Clinics 60, 355–360.Google Scholar
Bode, M.K., Mosorin, M., Satta, J., Risteli, L., Juvonen, T. & Risteli, J. (1999). Complete processing of type III collagen in atherosclerotic plaques. Arterioscler Thromb Vasc Biol 19, 1506–1511.Google Scholar
Brown, E., McKee, T., diTomaso, E., Pluen, A., Seed, B., Boucher, Y. & Jain, R.K. (2003). Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation. Nat Med 9, 796–800.Google Scholar
Buck, R.C. (1958). The fine structure of the aortic endothelial lesions in experimental cholesterol atherosclerosis of rabbits. Am J Pathol 34, 897–909.Google Scholar
Campagnola, P.J., Clark, H.A., Mohler, W.A., Lewis, A. & Loew, L.M. (2001). Second-harmonic imaging microscopy of living cells. J Biomed Opt 6, 277–286.Google Scholar
Campagnola, P.J., Millard, A.C., Terasaki, M., Hoppe, P.E., Malone, C.J. & Mohler, W.A. (2002). Three-dimensional high-resolution second-harmonic generation imaging of endogenous structural proteins in biological tissues. Biophys J 82, 493–508.Google Scholar
Caro, C.G., Fitz-Gerald, J.M. & Schroter, R.C. (1971). Atheroma and arterial wall shear. Observation, correlation and proposal of a shear dependent mass transfer mechanism for atherogenesis. Proc R Soc Lond B Biol Sci 177, 109–133.Google Scholar
Chen, S.-Y., Hsu, C.-Y.S. & Sun, C.-K. (2008). Epi-third and second harmonic generation microscopic imaging of abnormal enamel. Opt Express 16, 11670–11679.Google Scholar
Chen, W.-L., Li, T.-H., Su, P.-J., Chou, C.-K., Fwu, P.T., Lin, S.-J., Kim, D., So, P.T.C. & Dong, C.-Y. (2010). Second-order susceptibility imaging with polarization-resolved second harmonic generation microscopy. In Multiphoton Microscopy in the Biomedical Sciences X. Proc. SPIE Vol. 7569, Periasamy, A, So, P.T.C. & König, K. (Eds.), pp. 75691P–7569P7. San Francisco: SPIE.Google Scholar
Chu, S.-W., Chen, S.-Y., Chern, G.-W., Tsai, T.-H., Chen, Y.-C., Lin, B.-L. & Sun, C.-K. (2004). Studies of chi(2)/chi(3) tensors in submicron-scaled bio-tissues by polarization harmonics optical microscopy. Biophys J 86, 3914–3922.Google Scholar
Chu, S.-W., Tai, S.-P., Chan, M.-C., Sun, C.-K., Hsiao, I.-C., Lin, C.-H., Chen, Y.-C. & Lin, B.-L. (2007). Thickness dependence of optical second harmonic generation in collagen fibrils. Opt Express 15, 12005.Google Scholar
Cox, G. & Kable, E. (2006). Second-harmonic imaging of collagen. Methods Mol Biol 319, 15–35.Google Scholar
Cox, G., Kable, E., Jones, A., Fraser, I., Manconi, F. & Gorrell, M.D. (2003). 3-Dimensional imaging of collagen using second harmonic generation. J Struct Biol 141, 53–62.Google Scholar
Davies, M.J., Richardson, P.D., Woolf, N., Katz, D.R. & Mann, J. (1993). Risk of thrombosis in human atherosclerotic plaques: Role of extracellular lipid, macrophage, and smooth muscle cell content. Heart 69, 377–381.Google Scholar
Doras, C., Taupier, G., Barsella, A., Mager, L., Boeglin, A., Bulou, H., Bousquet, P. & Dorkenoo, K.D. (2011 a). Polarization state studies in second harmonic generation signals to trace atherosclerosis lesions. Opt Express 19, 15062–15068.Google Scholar
Erikson, A., Ortegren, J., Hompland, T., de Lange Davies, C. & Lindgren, M. (2007). Quantification of the second-order nonlinear susceptibility of collagen I using a laser scanning microscope. J Biomed Opt 12, 044002.Google Scholar
Finn, A.V., Nakano, M., Narula, J., Kolodgie, F.D. & Virmani, R. (2010). Concept of vulnerable/unstable plaque. Arterioscler Thromb Vasc Biol 30, 1282–1292.Google Scholar
Franken, P., Hill, A., Peters, C. & Weinreich, G. (1961). Generation of optical harmonics. Phys Rev Lett 7, 118–119.Google Scholar
Gannaway, J.N. & Sheppard, C.J.R. (1978). Second-harmonic imaging in the scanning optical microscope. Opt Quant Electron 10, 435–439.Google Scholar
Gauderon, R., Lukins, P.B. & Sheppard, C.J. (2001). Simultaneous multichannel nonlinear imaging: Combined two-photon excited fluorescence and second-harmonic generation microscopy. Micron 32, 685–689.Google Scholar
George, M.H., Morgan, J.B., Glock, R.D., Tatum, J.D., Schmidt, G.R., Sofos, J.N., Cowman, G.L. & Smith, G.C. (1995). Injection-site lesions: Incidence, tissue histology, collagen concentration, and muscle tenderness in beef rounds. J Anim Sci 73, 3510–3518.Google Scholar
Georgiou, E., Theodossiou, T., Hovhannisyan, V., Politopoulos, K., Rapti, G. & Yova, D. (2000). Second and third optical harmonic generation in type I collagen, by nanosecond laser irradiation, over a broad spectral region. Opt Commun 176, 253–260.Google Scholar
Halloran, B.G., Davis, V.A., McManus, B.M., Lynch, T.G. & Baxter, B.T. (1995). Localization of aortic disease is associated with intrinsic differences in aortic structure. J Surg Res 59, 17–22.Google Scholar
Hamamdzic, D. & Wilensky, R.L. (2013). Porcine models of accelerated coronary atherosclerosis: Role of diabetes mellitus and hypercholesterolemia. J Diabetes Res 2013, 761415.Google Scholar
Isselbacher, E.M. (2005). Thoracic and abdominal aortic aneurysms. Circulation 111, 816–828.Google Scholar
Jawien, J., Toton-Zuranska, J., Gajda, M., Niepsuj, A., Gebska, A., Kus, K., Suski, M., Pyka-Fosciak, G., Nowak, B., Guzik, T.J., Marcinkiewicz, J., Olszanecki, R. & Korbut, R. (2012). Angiotensin-(1-7) receptor Mas agonist ameliorates progress of atherosclerosis in apoE-knockout mice. J Physiol Pharmacol 63, 77–85.Google Scholar
Jemal, A., Siegel, R., Ward, E., Murray, T., Xu, J., Smigal, C. & Thun, M.J. (2006). Cancer statistics. CA Cancer J Clin 56, 106–130.Google Scholar
Katsuda, S., Okada, Y., Minamoto, T., Oda, Y., Matsui, Y. & Nakanishi, I. (1992). Collagens in human atherosclerosis. Immunohistochemical analysis using collagen type-specific antibodies. Arterioscler Thromb Vasc Biol 12, 494–502.Google Scholar
Kim, B.M., Eichler, J., Reiser, K.M., Rubenchik, A.M. & Da Silva, L.B. (2000). Collagen structure and nonlinear susceptibility: Effects of heat, glycation, and enzymatic cleavage on second harmonic signal intensity. Lasers Surg Med 27, 329–335.Google Scholar
Knowles, J.W. & Maeda, N. (2000). Genetic modifiers of atherosclerosis in mice. Arterioscler Thromb Vas Biol 20, 2336–2345.Google Scholar
Kolodgie, F.D., Katocs, A.S., Largis, E.E., Wrenn, S.M., Cornhill, J.F., Herderick, E.E., Lee, S.J. & Virmani, R. (1996). Hypercholesterolemia in the rabbit induced by feeding graded amounts of low-level cholesterol: Methodological considerations regarding individual variability in response to dietary cholesterol and development of lesion type. Arterioscler Thromb Vasc Biol 16, 1454–1464.Google Scholar
Ku, D.N., Giddens, D.P., Zarins, C.K. & Glagov, S. (1985). Pulsatile flow and atherosclerosis in the human carotid bifurcation. Positive correlation between plaque location and low oscillating shear stress. Arterioscler Thromb Vasc Biol 5, 293–302.Google Scholar
Le, T.T., Langohr, I.M., Locker, M.J., Sturek, M. & Cheng, J.-X. (2007). Label-free molecular imaging of atherosclerotic lesions using multimodal nonlinear optical microscopy. J Biomed Opt 12, 054007.Google Scholar
Lee, R.T., Schoen, F.J., Loree, H.M., Lark, M.W. & Libby, P. (1996). Circumferential stress and matrix metalloproteinase 1 in human coronary atherosclerosis: Implications for plaque rupture. Arterioscler Thromb Vasc Biol 16, 1070–1073.Google Scholar
Libby, P. (2002). Inflammation in atherosclerosis. Nature 420, 868–874.Google Scholar
Libby, P., DiCarli, M. & Weissleder, R. (2010). The vascular biology of atherosclerosis and imaging targets. J Nucl Med 51(Suppl 1), 33S–37S.Google Scholar
Libby, P. & Hansson, G.K. (2015). Inflammation and immunity in diseases of the arterial tree: Players and layers. Circ Res 116, 307–311.Google Scholar
Lim, R.S., Kratzer, A., Barry, N.P., Miyazaki-Anzai, S., Miyazaki, M., Mantulin, W.W., Levi, M., Potma, E.O. & Tromberg, B.J. (2010). Multimodal CARS microscopy determination of the impact of diet on macrophage infiltration and lipid accumulation on plaque formation in ApoE-deficient mice. J Lipid Res 51, 1729–1737.Google Scholar
Liu, H., Qin, W., Shao, Y., Ma, Z., Ye, T., Borg, T. & Gao, B.Z. (2011). Myofibrillogenesis in live neonatal cardiomyocytes observed with hybrid two-photon excitation fluorescence-second harmonic generation microscopy. J Biomed Opt 16, 126012.Google Scholar
Ma, Y., Wang, W., Zhang, J., Lu, Y., Wu, W., Yan, H. & Wang, Y. (2012). Hyperlipidemia and atherosclerotic lesion development in Ldlr-deficient mice on a long-term high-fat diet. PLoS One 7, e35835.Google Scholar
Malek, A.M. (1999). Hemodynamic shear stress and its role in atherosclerosis. JAMA 282, 2035.Google Scholar
Meir, K.S. & Leitersdorf, E. (2004). Atherosclerosis in the apolipoprotein-E-deficient mouse: A decade of progress. Arterioscler Thromb Vasc Biol 24, 1006–1014.Google Scholar
Meyer, T., Baumgartl, M., Gottschall, T., Pascher, T., Wuttig, A., Matthäus, C., Romeike, B.F.M., Brehm, B.R., Limpert, J., Tünnermann, A., Guntinas-Lichius, O., Dietzek, B., Schmitt, M. & Popp, J. (2013). A compact microscope setup for multimodal nonlinear imaging in clinics and its application to disease diagnostics. Analyst 138, 4048–4057.Google Scholar
Mostaço-Guidolin, L.B., Sowa, M.G., Risdale, A., Pegoraro, A., Smith, M.S.D., Hewko, M.D., Kohlenberg, E.K., Schatta, B., Shiomi, M., Stolow, A. & Ko, A.C.-T. (2010). Differentiating atherosclerotic plaque burden in arterial tissues using femtosecond CARS-based multimodal nonlinear optical imaging. Biomedical Optics Express 1, 59–73.Google Scholar
Mostaço-Guidolin, L.B., Ko, A.C-T., Popescu, D.P., Smith, M.S.D., Kohlenberg, E.K., Shiomi, M., Major, A. & Sowa, M.G. (2011). Evaluation of texture parameters for the quantitative description of multimodal nonlinear optical images from atherosclerotic rabbit arteries. Physics in Medicine and Biology 56, 5319.Google Scholar
Mostaço-Guidolin, L.B., Ko, A.C.-T., Wang, F., Xiang, B., Hewko, M., Tian, G., Major, A., Shiomi, M. & Sowa, M.G. (2013). Collagen morphology and texture analysis: From statistics to classification. Sci Rep 3, 2190.Google Scholar
Mozaffarian, D., Benjamin, E.J., Go, A.S., Arnett, D.K., Blaha, M.J., Cushman, M., Das, S.R., de Ferranti, S., Després, J.-P., Fullerton, H.J., Howard, V.J., Huffman, M.D., Isasi, C.R., Jiménez, M.C., Judd, S.E., Kissela, B.M., Lichtman, J.H., Lisabeth, L.D., Liu, S., Mackey, R.H., Magid, D.J., McGuire, D.K., Mohler, E.R., Moy, C.S., Muntner, P., Mussolino, M.E., Nasir, K., Neumar, R.W., Nichol, G., Palaniappan, L., Pandey, D.K., Reeves, M.J., Rodriguez, C.J., Rosamond, W., Sorlie, P.D., Stein, J., Towfighi, A., Turan, T.N., Virani, S.S., Woo, D., Yeh, R.W. & Turner, M.B. (2016). American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2016 Update: A Report from the American Heart Association. Circulation 133, e38–e360.Google Scholar
Mueller, M.M. & Fusenig, N.E. (2002). Tumor-stroma interactions directing phenotype and progression of epithelial skin tumor cells. Differentiation 70, 486–497.Google Scholar
Nakashima, Y., Plump, A.S., Raines, E.W., Breslow, J.L. & Ross, R. (1994). ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree. Arterioscler Thromb Vasc Biol 14, 133–140.Google Scholar
Osborn, E.A. & Jaffer, F.A. (2013). Imaging atherosclerosis and risk of plaque rupture. Curr Atheroscler Rep 15, 359.Google Scholar
Palero, J.A., de Bruijn, H.S., van der Ploeg van den Heuvel, A., Sterenborg, H.J.C.M. & Gerritsen, H.C. (2007). Spectrally resolved multiphoton imaging of in vivo and excised mouse skin tissues. Biophys J 93, 992–1007.Google Scholar
Plotnikov, S.V., Millard, A.C., Campagnola, P.J. & Mohler, W.A. (2006). Characterization of the myosin-based source for second-harmonic generation from muscle sarcomeres. Biophys J 90, 693–703.Google Scholar
Psilodimitrakopoulos, S., Petegnief, V., de Vera, N., Hernandez, O., Artigas, D., Planas, A.M. & Loza-Alvarez, P. (2013). Quantitative imaging of microtubule alteration as an early marker of axonal degeneration after ischemia in neurons. Biophys J 104, 968–975.Google Scholar
Rawlins, J.M., Lam, W.L., Karoo, R.O., Naylor, I.L. & Sharpe, D.T. (2006). Quantifying collagen type in mature burn scars: A novel approach using histology and digital image analysis. J Burn Care Res 27, 60–65.Google Scholar
Rekhter, M. (1999). Collagen synthesis in atherosclerosis: Too much and not enough. Cardiovasc Res 41, 376–384.Google Scholar
Roth, S. & Freund, I. (1981). Optical second-harmonic scattering in rat-tail tendon. Biopolymers 20, 1271–1290.Google Scholar
Sánchez, S.A., Méndez-Barbero, N., Santos-Beneit, A.M., Esteban, V., Jiménez-Borreguero, L.J., Campanero, M.R. & Redondo, J.M. (2014). Nonlinear optical 3-dimensional method for quantifying atherosclerosis burden. Circ Cardiovasc Imaging 7, 566–569.Google Scholar
Schenke-Layland, K., Riemann, I., Stock, U.A. & König, K. (2005). Imaging of cardiovascular structures using near-infrared femtosecond multiphoton laser scanning microscopy. J Biomed Opt 10, 024017.Google Scholar
Stoletov, K., Fang, L., Choi, S.-H., Hartvigsen, K., Hansen, L.F., Hall, C., Pattison, J., Juliano, J., Miller, E.R., Almazan, F., Crosier, P., Witztum, J.L., Klemke, R.L. & Miller, Y.I. (2009). Vascular lipid accumulation, lipoprotein oxidation, and macrophage lipid uptake in hypercholesterolemic zebrafish. Circ Res 104, 952–960.Google Scholar
Stoller, P., Kim, B.-M., Rubenchik, A.M., Reiser, K.M. & Da Silva, L.B. (2002). Polarization-dependent optical second-harmonic imaging of a rat-tail tendon. J Biomed Opt 7, 205–214.Google Scholar
Suhalim, J.L., Chung, C.-Y., Lilledahl, M.B., Lim, R.S., Levi, M., Tromberg, B.J. & Potma, E.O. (2012). Characterization of cholesterol crystals in atherosclerotic plaques using stimulated Raman scattering and second-harmonic generation microscopy. Biophys J 102, 1988–1995.Google Scholar
Ushiki, T. (2002). Collagen fibers, reticular fibers and elastic fibers. A comprehensive understanding from a morphological viewpoint. Archives of Histology and Cytology 65, 109–125.Google Scholar
Virmani, R., Burke, A.P., Farb, A. & Kolodgie, F.D. (2006). Pathology of the vulnerable plaque. J Am Coll Cardiol 47, C13–C18.Google Scholar
Wang, H.-W., Langohr, I.M., Sturek, M. & Cheng, J.-X. (2009). Imaging and quantitative analysis of atherosclerotic lesions by CARS-based multimodal nonlinear optical microscopy. Arterioscler Thromb Vasc Biol 29, 1342–1348.Google Scholar
Watson, S.R., Liu, P., Peña, E.A., Sutton, M.A., Eberth, J.F. & Lessner, S.M. (2016). Comparison of aortic collagen fiber angle distribution in mouse models of atherosclerosis using second-harmonic generation (SHG) microscopy. Microsc Microanal 22, 55–62.Google Scholar
Whitman, S.C. (2004). A practical approach to using mice in atherosclerosis research. Clin Biochem Rev 25, 81–93.Google Scholar
Williams, R.M., Zipfel, W.R. & Webb, W.W. (2005). Interpreting second-harmonic generation images of collagen I fibrils. Biophys J 88, 1377–1386.Google Scholar
Yu, W., Braz, J.C., Dutton, A.M., Prusakov, P. & Rekhter, M. (2007). In vivo imaging of atherosclerotic plaques in apolipoprotein E deficient mice using nonlinear microscopy. J Biomed Opt 12, 054008.Google Scholar
Zipfel, W.R., Williams, R.M., Christie, R., Nikitin, A.Y., Hyman, B.T. & Webb, W.W. (2003). Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation. Proc Nat Acad Sci USA 100, 7075–7080.Google Scholar
Zoumi, A., Lu, X., Kassab, G.S. & Tromberg, B.J. (2004). Imaging coronary artery microstructure using second-harmonic and two-photon fluorescence microscopy. Biophys J 87, 2778–2786.Google Scholar