Advertisement

Types of advanced optical microscopy techniques for breast cancer research: a review

  • Aparna Dravid U.
  • Nirmal Mazumder
Review Article

Abstract

A cancerous cell is characterized by morphological and metabolic changes which are the key features of carcinogenesis. Adenosine triphosphate (ATP) in cancer cells is primarily produced by aerobic glycolysis rather than oxidative phosphorylation. In normal cellular metabolism, nicotinamide adenine dinucleotide (NADH) is considered as a principle electron donor and flavin adenine dinucleotide (FAD) as an electron acceptor. During metabolism in a cancerous cell, a net increase in NADH is found as the pathway switched from oxidative phosphorylation to aerobic glycolysis. Often during initiation and progression of cancer, the developmental regulation of extracellular matrix (ECM) is restricted and becomes disorganized. Tumor cell behavior is regulated by the ECM in the tumor micro environment. Collagen, which forms the scaffold of tumor micro-environment also influences its behavior. Advanced optical microscopy techniques are useful for determining the metabolic characteristics of cancerous, normal cells and tissues. They can be used to identify the collagen microstructure and the function of NADH, FAD, and lipids in living system. In this review article, various optical microscopy techniques applied for breast cancer research are discussed including fluorescence, confocal, second harmonic generation (SHG), coherent anti-Stokes Raman scattering (CARS), and fluorescence lifetime imaging (FLIM).

Keywords

Breast cancer Confocal fluorescence microscopy Second harmonic generation Coherent anti-Stokes Raman scattering NADH Collagen 

Notes

Acknowledgements

We would like to acknowledge Dr. K. Satyamoorthy, Director, School of Life Sciences for his encouragement and Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, India for providing the infrastructure facilities. We thank Dr. K. K. Mahato, HoD, Department of Biophysics, School of Life Sciences, MAHE, Manipal, India for suggestion in preparing the review.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70Google Scholar
  2. 2.
    Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674CrossRefGoogle Scholar
  3. 3.
    Yokota J (2000) Tumor progression and metastasis. Carcinogenesis 21(3):497–503CrossRefGoogle Scholar
  4. 4.
    Qian B-Z, Pollard JW (2010) Macrophage diversity enhances tumor progression and metastasis. Cell 141(1):39–51CrossRefGoogle Scholar
  5. 5.
    Pike MC, Spicer DV, Dahmoush L, Press MF (1993) Estrogens, progestogens, normal breast cell proliferation, and breast cancer risk. Epidemiol Rev 15(1):17–35CrossRefGoogle Scholar
  6. 6.
    Lloyd-Lewis B, Davis FM, Harris OB, Hitchcock JR, Lourenco FC, Mathias P, Watson CJ (2016) Imaging the mammary gland and mammary tumors in 3D: optical tissue clearing and immunofluorescence methods. BioMed Central 18:1271–12717Google Scholar
  7. 7.
    Jensen EC (2012) Types of imaging, part 2: an overview of fluorescence microscopy. Anat Rec (Hoboken) 295:1621–1627CrossRefGoogle Scholar
  8. 8.
    Wu Y, Fu F, Lian Y et al (2015) Monitoring morphological alterations during invasive ductal breast carcinoma progression using multiphoton microscopy. Lasers Med Sci 30:1109–1115CrossRefGoogle Scholar
  9. 9.
    Campagnola P (2011) Second harmonic generation imaging microscopy: applications to diseases diagnostics. Anal Chem 83(9):3224–3231CrossRefGoogle Scholar
  10. 10.
    Fu L, Gu M (2007) Fibre-optic nonlinear optical microscopy and endoscopy. J Microsc 226:195–206CrossRefGoogle Scholar
  11. 11.
    Baak JPA, Thunnissen FBJM, Oudejans CBM, Schipper NW (1987) Potential clinical uses of laser scan microscopy. Appl Opt 26(16):3413–3416CrossRefGoogle Scholar
  12. 12.
    Dobbs J, Krishnamurthy S, Kyrish M, Benveniste AP, Yang W, Kortum RR (2015) Confocal fluorescence microscopy for rapid evaluation of invasive tumor cellularity of inflammatory breast carcinoma core needle biopsies. Breast Cancer Res Treat 149(1):303–310CrossRefGoogle Scholar
  13. 13.
    Wagnieres GA, Star WM, Wilson BC (1998) In vivo fluorescence spectroscopy and imaging for oncological applications. Photochem Photobiol 68(5):603–632CrossRefGoogle Scholar
  14. 14.
    Burke K, Brown E (2014) The use of second harmonic generation to image the extracellular matrix during tumor progression. Intravital 3(3):e9845091–e9845098CrossRefGoogle Scholar
  15. 15.
    Evans CL, Xie XS (2008) Coherent anti-stokes Raman scattering microscopy: chemical imaging for biology and medicine. Annu Rev Anal Chem 1:833–909CrossRefGoogle Scholar
  16. 16.
    Le TT, Huff TB, Cheng JX (2009) Coherent anti-Stokes Raman scattering imaging of lipids in cancer metastasis. BMC Cancer 9:1471–2407CrossRefGoogle Scholar
  17. 17.
    Bird DK, Yan L, Vrotsos KM, Eliceiri KW, Vaughan EM, Keely PJ, White JG, Ramanujam N (2005) Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH. Cancer Res 65(19):8766–8773CrossRefGoogle Scholar
  18. 18.
    Borst JW, Visser AJWG (2010) Fluorescence lifetime imaging microscopy in life sciences. Meas Sci Technol 21(10):1020021–10200221CrossRefGoogle Scholar
  19. 19.
    Tilli MT, Parrish AR, Cotarla I, Jones LP, Johnson MD, Furth PA (2008) Comparison of mouse mammary gland imaging techniques and applications: reflectance confocal microscopy, GFP imaging, and ultrasound. BMC Cancer 8(21):1–15Google Scholar
  20. 20.
    Georgakoudi I, Quinn PK (2012) Optical imaging using endogenous contrast to assess metabolic state. Annu Rev Biomed Eng 14:351–367CrossRefGoogle Scholar
  21. 21.
    Kortum RR, Muraca ES (1996) Quantitative optical spectroscopy for tissue diagnosis. Annu Rev Phys Chem 47:555–606CrossRefGoogle Scholar
  22. 22.
    Dobbs JL, Mueller JL, Krishnamurthy S, Shin D, Kuerer H, Yang W, Ramanujam N, Kortum RR (2015) Micro-anatomical quantitative optical imaging: toward automated assessment of breast tissues. Breast Cancer Res 17(105):1–14Google Scholar
  23. 23.
    Dobbs J, Ding H, Benveniste AP, Kuerer HM, Krishnamurthy S, Yang W, Kortum RR (2013) Feasibility of confocal fluorescence microscopy for real-time evaluation of neoplasia in fresh human breast tissue. J Biomed Opt 18:1060161–10601610CrossRefGoogle Scholar
  24. 24.
    Dobbs JL, Shin D, Krishnamurthy S, Kuerer H, Yang W, Richards-Kortum R (2016) Confocal fluorescence microscopy to evaluate changes in adipocytes in the tumor microenvironment associated with invasive ductal carcinoma and ductal carcinoma in situ. Int J Cancer 139:1140–1149CrossRefGoogle Scholar
  25. 25.
    Ragazzi M, Piana S, Longo C, Castagnetti F, Foroni M, Ferrari G, Gardini G, Pellacani G (2014) Fluorescence confocal microscopy for pathologists. Mod Pathol 27:460–471CrossRefGoogle Scholar
  26. 26.
    Conklin MW, Eickhoff JC, Riching KM, Pehlke CA, Eliceiri KW, Provenzano PP et al (2011) Aligned collagen is a prognostic signature for survival in human breast carcinoma. Am J Pathol 178(3):1221–1232CrossRefGoogle Scholar
  27. 27.
    Mazumder N, Deka G, Wu WW, Gogoi A, Zhuo GY, Kao FJ (2017) Polarization resolved second harmonic microscopy. Methods 128:105–118CrossRefGoogle Scholar
  28. 28.
    Mazumder N, Qiu J, Foreman MR, Romero CM, Hu CW, Tsai HR, Tӧrӧk P, Kao FJ (2012) Polarization-resolved second harmonic generation microscopy with a four-channel stokes-polarimeter. Opt Express 20(13):14090–14099CrossRefGoogle Scholar
  29. 29.
    Mazumder N, Qiu J, Foreman MR, Romero CM, Török P, Kao FJ (2013) Stokes vector based polarization resolved second harmonic microscopy of starch granules. Biomed Opt Express 4(4):538–547CrossRefGoogle Scholar
  30. 30.
    Tilbury K, Campagnola PJ (2015) Applications of second-harmonic generation imaging microscopy in ovarian and breast cancer. Perspect Medicin Chem 7:21–32CrossRefGoogle Scholar
  31. 31.
    Keikhosravi A, Bredfeldt JS, Sagar AK, Eliceiri KW (2014) Second-harmonic generation imaging of cancer. Methods Cell Biol 123:531–546CrossRefGoogle Scholar
  32. 32.
    Ambekar R, Lau TY, Walsh M, Bhargava R, Toussaint KC Jr (2012) Quantifying collagen structure in breast biopsies using second-harmonic generation imaging. Biomed Opt Express 3(9):2021–2035CrossRefGoogle Scholar
  33. 33.
    Wu PC, Hsieh YT, Tsai UZ, Liu MT (2015) In vivo quantification of the structural changes of collagens in a melanoma microenvironment with second and third harmonic generation microscopy. Sci Rep 5:8879CrossRefGoogle Scholar
  34. 34.
    Golaraei A, Kontenis L, Cisek R, Tokarz D, Done SJ, Wilson BC, Barzda V (2016) Changes of collagen ultrastructure in breast cancer tissue determined by second-harmonic generation double Stokes-Mueller polarimetric microscopy. Biomed Opt Express 7:4058–4068CrossRefGoogle Scholar
  35. 35.
    Chowdary PD, Benalcazar WA, Jiang Z, Chaney EJ, Marks DL, Gruebele M, Boppart SA (2010) Molecular histopathology by spectrally reconstructed nonlinear interferometric vibrational imaging. Cancer Res 70:9562–9569CrossRefGoogle Scholar
  36. 36.
    Tu H, Boppart SA (2014) Coherent anti-Stokes Raman scattering microscopy: overcoming technical barriers for clinical translation. J Biophotonics 7(1–2):9–22CrossRefGoogle Scholar
  37. 37.
    Kong K, Kendall C, Stone N, Notingher I (2015) Raman spectroscopy for medical diagnostics — from in-vitro biofluid assays to in-vivo cancer detection. Adv Drug Deliv Rev 89:121–134CrossRefGoogle Scholar
  38. 38.
    Lee M, Downes A, Chau Y, Serrels B, Hastie N, Elfick A, Brunton V, Frame M, Serrels A (2015) In vivo imaging of the tumor and its associated microenvironment using combined CARS / 2-photon microscopy. Intravital 4:e1055430CrossRefGoogle Scholar
  39. 39.
    Yang Y, Li F, Gao L, Wang Z, Thrall MJ, Shen SS, Wong KK, Wong STC (2011) Differential diagnosis of breast cancer using quantitative, label-free and molecular vibrational imaging. Biomed Opt Express 2(8):2160–2174CrossRefGoogle Scholar
  40. 40.
    Potcoava MC, Futia GL, Aughenbaugh J, Schlaepfer IR, Gibson EA (2014) Raman and coherent anti-Stokes Raman scattering microscopy studies of changes in lipid content and composition in hormone-treated breast and prostate cancer cells. J Biomed Opt 19(11):1116051–11160510CrossRefGoogle Scholar
  41. 41.
    Provenzano PP, Eliceiri KW, Yan L, Nguema NN, Conklin MW, Inman DR, Keely PJ (2008) Nonlinear optical imaging of cellular processes in breast cancer. Microsc Microanal 14(6):532–548CrossRefGoogle Scholar
  42. 42.
    Kao JF, Deka G, Mazumder N (2015) Cellular autofluroscence detection through FLIM/FRET microscopy. The current trends of optics and photonics. Top Appl Phys 129:471–482 (2015) (Springer Netherlands). Online ISBN 978–94–017-9392-6CrossRefGoogle Scholar
  43. 43.
    Periasamy A, Mazumder N, Sun Y, Christopher KG, Day RN (2015) FRET microscopy: basics, issues and advantages of FLIM-FRET imaging. Springer Ser Chem Phys 111:249–276 Advanced Time-Correlated Single Photon Counting Applications, Springer International Publishing Series ISSN 0172–6218CrossRefGoogle Scholar
  44. 44.
    Sud D, Zhong W, Beer DG, Mycek M-A (2006) Time-resolved optical imaging provides a molecular snapshot of altered metabolic function in living human cancer cell models. Opt Express 14(10):4412–4426CrossRefGoogle Scholar
  45. 45.
    Provenzano PP, Eliceiri KW, Keely PJ (2009) Multiphoton microscopy and fluorescence lifetime imaging microscopy (FLIM) to monitor metastasis and the tumor microenvironment. Clin Exp Metastasis 26(4):357–370CrossRefGoogle Scholar
  46. 46.
    Mazumder N, Lyn RK, Singaravelu R, Ridsdale A, Moffatt DJ, Hu CW, Tsai HR, McLauchlan J, Stolow A, Kao FJ, Pezacki JP (2013) Fluorescence lifetime imaging of alterations to cellular metabolism by domain 2 of the hepatitis C virus core protein. PLoS One 8(6):1–10CrossRefGoogle Scholar
  47. 47.
    Tomsia KT, Anwer AG, Cahill MA, Madlum KN, Maki AM, Baker MS, Goldys EM (2014) Multiphoton fluorescence lifetime imaging microscopy reveals free-to-bound NADH ratio changes associated with metabolic inhibition. J Biomed Opt 19(8):086016CrossRefGoogle Scholar
  48. 48.
    Hou J, Wright HJ, Chan N, Tran R, Razorenova OV, Potma EO, Tromberg BJ (2016) Correlating two-photon excited fluorescence imaging of breast cancer cellular redox state with seahorse flux analysis of normalized cellular oxygen consumption. J Biomed Opt 21:0605031–0605033CrossRefGoogle Scholar
  49. 49.
    Xiao A, Gibbons AE, Luker KE, Luker GD (2015) Fluorescence lifetime imaging of apoptosis. Tomography 1(2):115–124CrossRefGoogle Scholar
  50. 50.
    Szulczewski JM, Inman DR, Entenberg D, Ponik SM, Ghiso JA, Castracane J, Condeelis J, Eliceiri KW, Keely PJ (2016) In vivo visualization of stromal macrophages via label-free FLIM-based metabolite imaging. Sci Rep 6:1–9CrossRefGoogle Scholar

Copyright information

© Springer-Verlag London Ltd., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Biophysics, School of Life SciencesManipal Academy of Higher EducationManipalIndia

Personalised recommendations