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Nonlinear optical microscopy in decoding arterial diseases

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Abstract

Pathological understanding of arterial diseases is mainly attributable to histological observations based on conventional tissue staining protocols. The emerging development of nonlinear optical microscopy (NLOM), particularly in second-harmonic generation, two-photon excited fluorescence and coherent Raman scattering, provides a new venue to visualize pathological changes in the extracellular matrix caused by atherosclerosis progression. These techniques in general require minimal tissue preparation and offer rapid three-dimensional imaging. The capability of label-free microscopic imaging enables disease impact to be studied directly on the bulk artery tissue, thus minimally perturbing the sample. In this review, we look at recent progress in applications related to arterial disease imaging using various forms of NLOM.

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References

  • Barad Y, Eisenberg H, Horowitz M, Silberberg Y (1997) Nonlinear scanning laser microscopy by third harmonic generation. Appl Phys Lett 70(8):922–924

    Article  CAS  Google Scholar 

  • Barlis P, Schmitt JM (2009) Current and future developments in intracoronary optical coherence tomography imaging. EuroIntervention 4(4):529–533

    Article  PubMed  Google Scholar 

  • Barlis P, Serruys PW, Devries A, Regar E (2008a) Optical coherence tomography assessment of vulnerable plaque rupture: predilection for the plaque ‘shoulder’. Eur Heart J 29(16):2023

    Article  PubMed  Google Scholar 

  • Barlis P, Ferrante G, Del Furia F, Di Mario C (2008b) In-vivo characterisation of coronary atherosclerosis with optical coherence tomography. Med J Aust 188(12):728

    PubMed  Google Scholar 

  • Boulesteix T, Pena AM, Pages N, Godeau G, Sauviat MP, Beaurepaire E, Schanne-Klein MC (2005) Micrometer scale ex vivo multiphoton imaging of unstained arterial wall structure. Cytometry A 69A:20–26

    Google Scholar 

  • Delaney P, Harris M (2006) Fiber-optics in scanning optical microscopy. In: Pawley JB (ed) Handbook of biological confocal microscopy, 3rd edn. Springer, New York, pp 501–515

    Chapter  Google Scholar 

  • Denk W, Strickler JH, Webb WW (1990) Two-photon laser scanning fluorescence microscopy. Science 248(4951):73–76

    Article  PubMed  CAS  Google Scholar 

  • Doras C, Taupier G, Barsella A, Mager L, Boeglin A, Bulou H, Bousquet P, Dorkenoo KD (2011) Polarization state studies in second harmonic generation signals to trace atherosclerosis lesions. Opt Express 19:15062–15068

    Article  PubMed  CAS  Google Scholar 

  • Dudovich N, Oron D, Silberberg Y (2002) Single-pulse coherently controlled nonlinear Raman spectroscopy and microscopy. Nature 418:512–514

    Article  PubMed  CAS  Google Scholar 

  • Duncan MD, Reintjes J, Manuccia TJ (1982) Scanning coherent anti-Stokes Raman microscope. Opt Lett 7(8):350–352

    Article  PubMed  CAS  Google Scholar 

  • Freudiger CW, Min W, Saar BG, Lu S, Holtom GR, He C, Tsai JC, Kang JX, Xie XS (2008) Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy. Science 322:1857–1861

    Article  PubMed  CAS  Google Scholar 

  • Ganikhanov F, Carrasco S, Xie XS, Katz M, Seitz W, Kopf D (2006) Broadly tunable dual-wavelength light source for coherent anti-Stokes Raman scattering microscopy. Opt Lett 31:1292–1294

    Article  PubMed  Google Scholar 

  • Hansson GK (2005) Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352(16):1685–1695

    Article  PubMed  CAS  Google Scholar 

  • Hodgson JM, Reddy KG, Suneja R, Nair RN, Lesnefsky EJ, Sheehan HM (1993) 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

    Article  PubMed  CAS  Google Scholar 

  • Jang IK, Tearney GJ, MacNeill B, Takano M, Moselewski F, Iftima N, Shishkov M, Houser ST, Aretz H, Halpern EF, Bouma BE (2005) In vivo characterization of coronary atherosclerotic plaque by use of optical coherence tomography. Circulation 111(12):1551–1555

    Article  PubMed  Google Scholar 

  • Jo JA, Fang Q, Papaioannou T, Baker JD, Dorafshar AH, Reil T, Qiao JH, Fishbein MC, Freischlag JA, Marcu L (2006) Laguerre-based method for analysis of time-resolved fluorescence data: Application to in-vivo characterization and diagnosis of atherosclerotic lesions. J Biomed Opt 11(2):021004

    Article  PubMed  Google Scholar 

  • Kim S-H, Lee E-S, Lee JY, Lee ES, Lee BS, Park JE, Moon DW (2010) Multiplex coherent anti-stokes raman spectroscopy images intact atheromatous lesions and concomitantly identifies distinct chemical profiles of atherosclerotic lipids. Circ Res 106:1332–1341

    Article  PubMed  CAS  Google Scholar 

  • Ko ACT, Ridsdale A, Smith MSD, Mostaço-Guidolin LB, Hewko MD, Pegoraro AF, Kohlenberg EK, Schattka B, Shiomi M, Stolow A, Sowa MG (2010) Multimodal nonlinear optical imaging of atherosclerotic plaque development in myocardial infarction-prone rabbits. J Biomed Opt 15(2):020501

    Article  PubMed  Google Scholar 

  • Le TT, Langohr IM, Locker MJ, Sturek M, Cheng J-X (2007) Label-free molecular imaging of atherosclerotic lesions using multimodal nonlinear optical microscopy. J Biomed Opt 12(5):054007

    Article  PubMed  Google Scholar 

  • Lee JY, Kim SH, Moon DV, Lee ES (2009) Three-color multiplex CARS for fast imaging and microspectroscopy in the entire CH stretching vibrational region. Opt Express 17(25):22281

    Article  PubMed  CAS  Google Scholar 

  • Libby P (2006) Atherosclerosis: disease biology affecting the coronary vasculature. Am J Cardiol 98(12):S3–S9

    Article  Google Scholar 

  • Lilledahl MB, Haugen OA, Davies de Lange C, Svaasand LO (2007) Characterization of vulnerable plaques by multiphoton microscopy. J Biomed Opt 12(4):044005

    Article  PubMed  Google Scholar 

  • Maffia P, Zinselmeyer BH, Ialenti A, Kennedy S, Baker AH, McInnes IB, Brewer JM, Garside P (2007) Into apolipoprotein-E–deficient mouse carotid artery multiphoton microscopy for 3-dimensional imaging of lymphocyte recruitment. Circulation 115:e326–e328

    Article  PubMed  Google Scholar 

  • Major A, Sandkuijl D, Barzda V (2009) Efficient frequency doubling of a femtosecond Yb:KGW laser in a BiB3O6 crystal. Opt Express 17:12039–12042

    Article  PubMed  CAS  Google Scholar 

  • Marcu L, Jo JA, Fang Q, Papaioannou T, Reil T, Qiao JH, Baker JD, Freischlag JA, Fishbein MC (2009) Detection of rupture-prone atherosclerotic plaques by time-resolved laser-induced fluorescence spectroscopy. Atherosclerosis 204(1):156–164

    Article  PubMed  CAS  Google Scholar 

  • Megens RTA, Reitsma S, Schiffers PHM, Hilgers RHP, De Mey JGR, Slaaf DW, Oude Egbrink MGA, van Zandvoort MAMJ (2007) Two-photon microscopy of vital murine elastic and muscular arteries. J Vasc A 24(5):1337–1348

    Google Scholar 

  • Megens RTA, oude Egbrink MGA et al (2008) Two-photon microscopy on vital carotid arteries: imaging the relationship between collagen and inflammatory cells in atherosclerotic plaques. J Biomed Opt 13(04):044022

    Article  PubMed  Google Scholar 

  • Millard AC, Wiseman PW, Fittinghoff DN, Wilson KR, Squier JA, Müller M (1999) Third-harmonic generation microscopy by use of a compact, femtosecond fiber laser source. Appl Opt 38(36):7393–7397

    Article  PubMed  CAS  Google Scholar 

  • Miyata K, Rotermund F, Petrov V (2009) Efficient frequency doubling of a low-power femtosecond Er-fiber laser in BiB3O6. IEEE Photo Technol Lett 21(19):1417–1419

    Article  CAS  Google Scholar 

  • Mizutani G, Koyama T, Tomizawa S, Sano H (2005) Distinction between some saccharides in scattered optical sum frequency intensity images. Spectrochim Acta A Mol Biomol Spectrosc 62(4–5):845–849

    Article  PubMed  CAS  Google Scholar 

  • Mostaço-Guidolin LB, Sowa MG, Ridsdale A, Pegoraro AF, Smith MSD, Hewko MD, Kohlenberg EK, Schattka B, Shiomi M, Stolow A, Ko ACT (2010) Differentiating atherosclerotic plaque burden in arterial tissues using femtosecond CARS-based multimodal nonlinear optical imaging. Biomed Opt Express 1:59–73

    Article  PubMed  Google Scholar 

  • Mostaço-Guidolin LB, Ko AC-T, Popescu DP, Smith MSD, Kohlenberg EK, Shiomi M, Major A, Sowa MG (2011) Evaluation of texture parameters for the quantitative description of multimodal nonlinear optical images from atherosclerotic rabbit arteries. Phys Med Biol 56:5319. doi:10.1088/0031-9155/56/16/016

    Article  PubMed  Google Scholar 

  • Murugkar S, Brideau C, Ridsdale A, Naji M, Stys PK, Anis H (2007) Coherent anti-Stokes Raman scattering microscopy using photonic crystal fiber with two closely lying zero dispersion wavelengths. Opt Express 15:14028–14037

    Article  PubMed  CAS  Google Scholar 

  • Naghavi M, Libby P, Falk E et al (2003) Review: current perspective: from vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part I. Circulation 108:1664–1672. doi:10.1161/01.CIR.0000087480.94275.97

    Article  PubMed  Google Scholar 

  • Parasassi T, Yu W, Durbin D, Kuriashkina L, Gratton E, Maeda N, Ursini F (2000) Two-photon microscopy of aorta fibers shows proteolysis induced by LDL hydroperoxides. Free Radic Biol Med 28:1589–1597

    Article  PubMed  CAS  Google Scholar 

  • Paulsen HN, Hilligse KM, Thøgersen J, Keiding SR, Larsen JJ (2003) Coherent anti-Stokes Raman scattering microscopy with a photonic crystal fiber based light source. Opt Lett 28:1123–1125

    Article  PubMed  Google Scholar 

  • Pegoraro AF, Ridsdale A, Moffatt DJ, Jia Y, Pezacki JP, Stolow A (2009a) Optimally chirped multimodal CARS microscopy based on a single Ti:sapphire oscillator. Opt Express 17:2984–2996

    Article  PubMed  CAS  Google Scholar 

  • Pegoraro AF, Ridsdale A, Moffatt DJ, Pezacki JP, Thomas BK, Fu L, Dong L, Fermann ME, Stolow A (2009b) All-fiber CARS microscopy of live cells. Opt Express 17(23):20700–20706

    Article  PubMed  CAS  Google Scholar 

  • Phipps J, Sun Y, Saroufeem R, Hatami N, Marcu L (2009) Fluorescence lifetime imaging microscopy for the characterization of atherosclerotic plaques. Proc Soc Photo Opt Instrum Eng 7161:71612G

    Google Scholar 

  • Prent N, Green C, Greenhalgh C, Cisek R, Major A, Stewart B, Barzda V (2008) Inter-myofilament dynamics of myocytes revealed by second harmonic generation microscopy. J Biomed Opt 13(4):041318–1–041318–7

    Article  Google Scholar 

  • Rinia HA, Burger KNJ, Bonn M, Müller M (2008) Quantitative label-free imaging of lipid composition and packing of individual cellular lipid droplets using multiplex CARS microscopy. Biophys J 95(10):4908–4914

    Article  PubMed  CAS  Google Scholar 

  • Schenke-Layland K, König K, Riemann I, Stock UA (2005) Imaging of cardiovascular structures using near-infrared femtosecond multiphoton laser scanning microscopy. J Biomed Opt 10:024017. doi:10.1117/1.1896966

    Article  PubMed  Google Scholar 

  • Schenke-Layland K, Madershahian N, Riemann I, Starcher B, Halbhuber KJ, König K, Stock UA (2006) Impact of cryopreservation on extracellular matrix structures of heart valve leaflets. Ann Thorac Surg 81(3):918–926

    Article  PubMed  Google Scholar 

  • Sheppard CJR, Gannaway JN, Kompfner R, Walsh D (1977) Scanning harmonic optical microscope. IEEE J Q Electron 13(9):100D

    Google Scholar 

  • Smith MSD, Ko ACT, Ridsdale A, Schattka B, Pegoraro A, Hewko MD, Shiomi M, Stolow A, Sowa MG (2009) A single-photon fluorescence and multi-photon spectroscopic study of atherosclerotic lesions. Proc SPIE 7386:73860I

    Article  Google Scholar 

  • Spence DE, Kean PN, Sibbett W (1991) 60-fsec pulse generation from a self-mode-locked Ti:sapphire laser. Opt Lett 16(1):42–44

    Article  PubMed  CAS  Google Scholar 

  • Strupler M, Pena AM, Hernest M, Tharaux PL, Martin JL, Beaurepaire E, Schanne-Klein MC (2007) Second harmonic imaging and scoring of collagen in fibrotic tissues. Opt Express 15(7):4054–4065

    Article  PubMed  CAS  Google Scholar 

  • Strupler M, Hernest M, Fligny C, Martin J-L, Tharaux P-L, Schanne-Klein MC (2008) Second harmonic microscopy to quantify renal interstitial fibrosis and arterial remodeling. J Biomed Opt 13(5):054041

    Article  PubMed  Google Scholar 

  • Sun J, Zhang Z, Lu B, Yu W, Yang Y, Zhou Y, Wang Y, Fan Z (2008) Identification and quantification of coronary atherosclerotic plaques: a comparison of 64-MDCT and intravascular ultrasound. Am J Roentgenol 190(3):748–754

    Article  Google Scholar 

  • Suhling K, French PM, Phillips D (2005) Time-resolved fluorescence microscopy. Photochem Photobiol Sci 4(1):13–22

    Article  PubMed  CAS  Google Scholar 

  • Timmins LH, Wu Q, Yeh AT, Moore JE Jr, Greenwald SE (2010) Structural inhomogeneity and fiber orientation in the inner arterial media. Am J Physiol Heart Circ Physiol 298:H1537–H1545

    Article  PubMed  CAS  Google Scholar 

  • Thomas P, Pande P, Clubb F, Adame J, Jo JA (2010) Biochemical imaging of human atherosclerotic plaques with fluorescence lifetime angioscopy. Photochem Photobiol 86:727–731

    Article  PubMed  CAS  Google Scholar 

  • Van Zandvoort M, Engels W, Douma K, Beckers L, Oude Egbrink M, Daemen M, Slaaf DW (2004) Two-photon microscopy for imaging of the (atherosclerotic) vascular wall: a proof of concept study. J Vasc Res 41(1):54–63

    Article  PubMed  Google Scholar 

  • Yock PG, Fitzgerald PJ (1998) Optimal directional coronary atherectomy final results of the Optimal Atherectomy Restenosis Study (OARS). Am J Cardiol 81:27E–32E

    Article  PubMed  CAS  Google Scholar 

  • Yu W, Braz JC, Dutton AM, Prusakov P, Rekhter M (2007) In vivo imaging of atherosclerotic plaques in apolipoprotein E deficient mice using nonlinear microscopy. J Biomed Opt 12(5):054008

    Article  PubMed  Google Scholar 

  • Wang H-W, Langohr IM, 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(9):1342–1348

    Article  PubMed  CAS  Google Scholar 

  • Wang H-W, Simianu V, Locker MJ, Cheng J-X, Sturek M (2011) Stent-induced coronary artery stenosis characterized by multimodal nonlinear optical microscopy. J Biomed Opt 16(2):021110

    Article  PubMed  Google Scholar 

  • Zoumi A, Lu XA, Kassab GS, Tromberg BJ (2004) Imaging coronary artery microstructure using second-harmonic and two-photon fluorescence microscopy. Biophys J 87:2778–2786

    Article  PubMed  CAS  Google Scholar 

  • Zumbusch A, Holtom GR, Xie XS (1999) Three-dimensional vibrational imaging by coherent anti-Stokes Raman scattering. Phys Rev Lett 82(20):4142–4145

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. National Research Council Canada, Institute for Biodiagnostics, 435 Ellice Avenue, Winnipeg, Manitoba, Canada, R3B 1Y6

    Alex C.-T. Ko & Michael G. Sowa

  2. National Research Council Canada, Steacie Institute for Molecular Sciences, 100 Sussex Drive, Ottawa, Ontario, Canada, K1A 0R6

    Andrew Ridsdale & Albert Stolow

  3. Department of Electrical and Computer Engineering, University of Manitoba, 75A Chancellor’s Circle, Winnipeg, Manitoba, Canada, R3T 5V6

    Leila B. Mostaço-Guidolin & Arkady Major

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  1. Alex C.-T. Ko
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  2. Andrew Ridsdale
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  3. Leila B. Mostaço-Guidolin
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  4. Arkady Major
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  5. Albert Stolow
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  6. Michael G. Sowa
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Correspondence to Alex C.-T. Ko.

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Ko, A.CT., Ridsdale, A., Mostaço-Guidolin, L.B. et al. Nonlinear optical microscopy in decoding arterial diseases. Biophys Rev 4, 323–334 (2012). https://doi.org/10.1007/s12551-012-0077-8

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