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Biomedical Optics Express

Biomedical Optics Express

  • Editor: Joseph A. Izatt
  • Vol. 4, Iss. 1 — Jan. 1, 2013
  • pp: 178–186

Virtual optical biopsy of human adipocytes with third harmonic generation microscopy

Cheng-Kun Tsai, Tzung-Dau Wang, Jong-Wei Lin, Ron-Bin Hsu, Lun-Zhang Guo, San-Tai Chen, and Tzu-Ming Liu  »View Author Affiliations

Biomedical Optics Express, Vol. 4, Issue 1, pp. 178-186 (2013)

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Using the sectioning capability of third harmonic generation (THG) microscopy, we assessed the morphologic features of human adipocytes directly without fixation and labeling. At the plane of the largest cross-sectional area, both area-equivalent circular diameters (AECD) and perimeters of adipocytes were measured, and their statistical distributions were examined. We found, in patients with no cardiovascular risk factors, the average AECD of epicardial adipocytes were 70–90 μm with 11–17 μm standard deviations. In contrast, for patients with coronary artery disease, amounts of small-sized (AECD <40 µm) epicardial adipocytes were observed and the corresponding standard deviations of AECD were increased to 20–29 μm. Our results indicate that the THG tomography platform can be used to explore the histopathological features of adipocytes in clinical scenarios based on its superior resolution for virtual optical biopsy.

© 2012 OSA

OCIS Codes
(170.6900) Medical optics and biotechnology : Three-dimensional microscopy
(190.1900) Nonlinear optics : Diagnostic applications of nonlinear optics

ToC Category:

Original Manuscript: October 8, 2012
Revised Manuscript: November 19, 2012
Manuscript Accepted: November 21, 2012
Published: December 20, 2012

Cheng-Kun Tsai, Tzung-Dau Wang, Jong-Wei Lin, Ron-Bin Hsu, Lun-Zhang Guo, San-Tai Chen, and Tzu-Ming Liu, "Virtual optical biopsy of human adipocytes with third harmonic generation microscopy," Biomed. Opt. Express 4, 178-186 (2013)

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  1. P. Wang, E. Mariman, J. Keijer, F. Bouwman, J. P. Noben, J. Robben, and J. Renes, “Profiling of the secreted proteins during 3T3-L1 adipocyte differentiation leads to the identification of novel adipokines,” Cell. Mol. Life Sci.61(18), 2405–2417 (2004). [CrossRef] [PubMed]
  2. H. Hauner, “Secretory factors from human adipose tissue and their functional role,” Proc. Nutr. Soc.64(02), 163–169 (2005). [CrossRef] [PubMed]
  3. G. Fantuzzi, “Adipose tissue, adipokines, and inflammation,” J. Allergy Clin. Immunol.115(5), 911–919, quiz 920 (2005). [CrossRef] [PubMed]
  4. J. P. Bastard, M. Maachi, C. Lagathu, M. J. Kim, M. Caron, H. Vidal, J. Capeau, and B. Feve, “Recent advances in the relationship between obesity, inflammation, and insulin resistance,” Eur. Cytokine Netw.17(1), 4–12 (2006). [PubMed]
  5. M. Dolinková, I. Dostálová, Z. Lacinová, D. Michalský, D. Haluzíková, M. Mráz, M. Kasalický, and M. Haluzík, “The endocrine profile of subcutaneous and visceral adipose tissue of obese patients,” Mol. Cell. Endocrinol.291(1-2), 63–70 (2008). [CrossRef] [PubMed]
  6. G. S. Hotamisligil, P. Arner, J. F. Caro, R. L. Atkinson, and B. M. Spiegelman, “Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance,” J. Clin. Invest.95(5), 2409–2415 (1995). [CrossRef] [PubMed]
  7. P. Mathieu, P. Pibarot, E. Larose, P. Poirier, A. Marette, and J. P. Després, “Visceral obesity and the heart,” Int. J. Biochem. Cell Biol.40(5), 821–836 (2008). [CrossRef] [PubMed]
  8. B. L. Wajchenberg, “Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome,” Endocr. Rev.21(6), 697–738 (2000). [CrossRef] [PubMed]
  9. K. E. Wellen and G. S. Hotamisligil, “Obesity-induced inflammatory changes in adipose tissue,” J. Clin. Invest.112(12), 1785–1788 (2003). [PubMed]
  10. P. Björntorp, ““Portal” adipose tissue as a generator of risk factors for cardiovascular disease and diabetes,” Arteriosclerosis10(4), 493–496 (1990). [CrossRef] [PubMed]
  11. J. N. Fain, A. K. Madan, M. L. Hiler, P. Cheema, and S. W. Bahouth, “Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans,” Endocrinology145(5), 2273–2282 (2004). [CrossRef] [PubMed]
  12. S. P. Weisberg, D. McCann, M. Desai, M. Rosenbaum, R. L. Leibel, and A. W. Ferrante., “Obesity is associated with macrophage accumulation in adipose tissue,” J. Clin. Invest.112(12), 1796–1808 (2003). [PubMed]
  13. S. Eroglu, L. E. Sade, A. Yildirir, U. Bal, S. Ozbicer, A. S. Ozgul, H. Bozbas, A. Aydinalp, and H. Muderrisoglu, “Epicardial adipose tissue thickness by echocardiography is a marker for the presence and severity of coronary artery disease,” Nutr. Metab. Cardiovasc. Dis.19(3), 211–217 (2009). [CrossRef] [PubMed]
  14. T.-D. Wang, W.-J. Lee, F.-Y. Shih, C.-H. Huang, W.-J. Chen, Y.-T. Lee, T. T.-F. Shih, and M.-F. Chen, “Association of epicardial adipose tissue with coronary atherosclerosis is region-specific and independent of conventional risk factors and intra-abdominal adiposity,” Atherosclerosis213(1), 279–287 (2010). [CrossRef] [PubMed]
  15. A. A. Mahabadi, J. M. Massaro, G. A. Rosito, D. Levy, J. M. Murabito, P. A. Wolf, C. J. O’Donnell, C. S. Fox, and U. Hoffmann, “Association of pericardial fat, intrathoracic fat, and visceral abdominal fat with cardiovascular disease burden: the Framingham Heart Study,” Eur. Heart J.30(7), 850–856 (2009). [CrossRef] [PubMed]
  16. G. A. Rosito, J. M. Massaro, U. Hoffmann, F. L. Ruberg, A. A. Mahabadi, R. S. Vasan, C. J. O’Donnell, and C. S. Fox, “Pericardial fat, visceral abdominal fat, cardiovascular disease risk factors, and vascular calcification in a community-based sample: the Framingham Heart Study,” Circulation117(5), 605–613 (2008). [CrossRef] [PubMed]
  17. D. M. Jaworski, O. Sideleva, H. M. Stradecki, G. D. Langlois, A. Habibovic, B. Satish, W. G. Tharp, J. Lausier, K. Larock, T. L. Jetton, M. Peshavaria, and R. E. Pratley, “Sexually dimorphic diet-induced insulin resistance in obese tissue inhibitor of metalloproteinase-2 (TIMP-2)-deficient mice,” Endocrinology152(4), 1300–1313 (2011). [CrossRef] [PubMed]
  18. S. A. Boppart, W. Luo, D. L. Marks, and K. W. Singletary, “Optical coherence tomography: feasibility for basic research and image-guided surgery of breast cancer,” Breast Cancer Res. Treat.84(2), 85–97 (2004). [CrossRef] [PubMed]
  19. C. Zhou, D. W. Cohen, Y. Wang, H.-C. Lee, A. E. Mondelblatt, T.-H. Tsai, A. D. Aguirre, J. G. Fujimoto, and J. L. Connolly, “Integrated optical coherence tomography and microscopy for ex vivo multiscale evaluation of human breast tissues,” Cancer Res.70(24), 10071–10079 (2010). [CrossRef] [PubMed]
  20. R. A. McLaughlin, L. Scolaro, P. Robbins, S. Hamza, C. Saunders, and D. D. Sampson, “Imaging of human lymph nodes using optical coherence tomography: potential for staging cancer,” Cancer Res.70(7), 2579–2584 (2010). [CrossRef] [PubMed]
  21. A. Ahmad, S. G. Adie, M. Wang, and S. A. Boppart, “Sonification of optical coherence tomography data and images,” Opt. Express18(10), 9934–9944 (2010). [CrossRef] [PubMed]
  22. H. Mori, A. D. Borowsky, R. Bhat, C. M. Ghajar, M. Seiki, and M. J. Bissell, “Laser scanning-based tissue autofluorescence/fluorescence imaging (LS-TAFI), a new technique for analysis of microanatomy in whole-mount tissues,” Am. J. Pathol.180(6), 2249–2256 (2012). [CrossRef] [PubMed]
  23. Z. Huang, S. Zhuo, J. Chen, R. Chen, and X. Jiang, “Multiphoton microscopic imaging of adipose tissue based on second-harmonic generation and two-photon excited fluorescence,” Scanning30(6), 452–456 (2008). [CrossRef] [PubMed]
  24. 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]
  25. M.-R. Tsai, S.-Y. Chen, D.-B. Shieh, P.-J. Lou, and C.-K. Sun, “In vivo optical virtual biopsy of human oral mucosa with harmonic generation microscopy,” Biomed. Opt. Express2(8), 2317–2328 (2011). [CrossRef] [PubMed]
  26. S.-W. Chu, S.-Y. Chen, T.-H. Tsai, T.-M. Liu, C.-Y. Lin, H.-J. Tsai, and C.-K. Sun, “In vivo developmental biology study using noninvasive multi-harmonic generation microscopy,” Opt. Express11(23), 3093–3099 (2003). [CrossRef] [PubMed]
  27. C.-S. Hsieh, C.-Y. Ko, S.-Y. Chen, T.-M. Liu, J.-S. Wu, C.-H. Hu, and C.-K. Sun, “In vivo long-term continuous observation of gene expression in zebrafish embryo nerve systems by using harmonic generation microscopy and morphant technology,” J. Biomed. Opt.13(6), 064041 (2008). [CrossRef] [PubMed]
  28. H.-C. Lee, W.-A. Tseng, F.-Y. Lo, T.-M. Liu, and H.-J. Tsai, “FoxD5 mediates anterior-posterior polarity through upstream modulator Fgf signaling during zebrafish somitogenesis,” Dev. Biol.336(2), 232–245 (2009). [CrossRef] [PubMed]
  29. C.-K. Tsai, Y.-S. Chen, P.-C. Wu, T.-Y. Hsieh, H.-W. Liu, C.-Y. Yeh, W.-L. Lin, J.-S. Chia, and T.-M. Liu, “Imaging granularity of leukocytes with third harmonic generation microscopy,” Biomed. Opt. Express3(9), 2234–2243 (2012). [CrossRef] [PubMed]
  30. S.-Y. Chen, H.-Y. Wu, and C.-K. Sun, “In vivo harmonic generation biopsy of human skin,” J. Biomed. Opt.14(6), 060505 (2009). [CrossRef] [PubMed]
  31. S.-Y. Chen, S.-U. Chen, H.-Y. Wu, W.-J. Lee, Y.-H. Liao, and C.-K. Sun, “In vivo virtual biopsy of human skin by using noninvasive higher harmonic generation microscopy,” IEEE J. Sel. Top. Quantum Electron.16(3), 478–492 (2010). [CrossRef]
  32. C.-K. Chen and T.-M. Liu, “Imaging morphodynamics of human blood cells in vivo with video-rate third harmonic generation microscopy,” Biomed. Opt. Express3(11), 2860–2865 (2012). [CrossRef] [PubMed]
  33. T. McLaughlin, A. Sherman, P. Tsao, O. Gonzalez, G. Yee, C. Lamendola, G. M. Reaven, and S. W. Cushman, “Enhanced proportion of small adipose cells in insulin-resistant vs insulin-sensitive obese individuals implicates impaired adipogenesis,” Diabetologia50(8), 1707–1715 (2007). [CrossRef] [PubMed]
  34. A. Liu, A. Sonmez, G. Yee, M. Bazuine, M. Arroyo, A. Sherman, T. McLaughlin, G. Reaven, S. Cushman, and P. Tsao, “Differential adipogenic and inflammatory properties of small adipocytes in Zucker Obese and Lean rats,” Diab. Vasc. Dis. Res.7(4), 311–318 (2010). [CrossRef] [PubMed]

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