Abstract
Light sheet microscopy (LSM) is an evolving optical imaging technique with a plane illumination for optical sectioning and volumetric imaging spanning cell biology, embryology, and in vivo live imaging. Here, we focus on emerging biomedical applications of LSM for tissue samples. Decoupling of the light sheet illumination from detection enables high-speed and large field-of-view imaging with minimal photobleaching and phototoxicity. These unique characteristics of the LSM technique can be easily adapted and potentially replace conventional histopathological procedures. In this review, we cover LSM technology from its inception to its most advanced technology; in particular, we highlight the human histopathological imaging applications to demonstrate LSM’s rapid diagnostic ability in comparison with conventional histopathological procedures. We anticipate that the LSM technique can become a useful three-dimensional imaging tool for assessing human biopsies in the near future.
Similar content being viewed by others
References
Eichler K, Hempel S, Wilby J, Myers L, Bachmann LM, Kleijnen J. Diagnostic value of systematic biopsy methods in the investigation of prostate cancer: a systematic review. J Urol. 2006;175:1605–12.
Hunninghake GW, Zimmerman MB, Schwartz DA, King TE Jr, Lynch J, Hegele R, Waldron J, Colby T, Müller N, Lynch D, Galvin J, Gross B, Hogg J, Toews G, Helmers R, Cooper JAD Jr, Baughman R, Strange C, Millard M. Utility of a lung biopsy for the diagnosis of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2001;164:193–6.
Gillett CE, Springall RJ, Barnes DM, Hanby AM. Multiple tissue core arrays in histopathology research: a validation study. J Pathol. 2000;192:549–53.
Pasyk KA, Argenta LC, Austad ED. Histopathology of human expanded tissue. Clin Plast Surg. 1987;14:435–45.
Tryka AF, Brooks JR. Histopathology in the evaluation of total pancreatectomy for ductal carcinoma. Ann Surg. 1979;190:373.
Berlin L. Accuracy of diagnostic procedures: Has it improved over the past five decades? AJR Am J Roentgenol. 2007;188:1173–8.
Hodel S, Laux C, Farei-Campagna J, Götschi T, Bode-Lesniewska B, Müller DA. The impact of biopsy sampling errors and the quality of surgical margins on local recurrence and survival in chondrosarcoma. Cancer Manag Res. 2018;10:3765.
Elmore JG, Longton GM, Carney PA, Geller BM, Onega T, Tosteson AN, Nelson HD, Pepe MS, Allison KH, Schnitt SJ, O’malley FP, Weaver DL. Diagnostic concordance among pathologists interpreting breast biopsy specimens. JAMA. 2015;313:1122–32.
Hewitt SM, Lewis FA, Cao Y, Conrad RC, Cronin M, Danenberg KD, Goralski TJ, Langmore JP, Raja RG, Williams PM, Palma JF, Warrington JA. Tissue handling and specimen preparation in surgical pathology: issues concerning the recovery of nucleic acids from formalin-fixed, paraffin-embedded tissue. Arch Pathol Lab Med. 2008;132:1929–35.
Srinivasan M, Sedmak D, Jewell S. Effect of fixatives and tissue processing on the content and integrity of nucleic acids. Am J Pathol. 2002;161:1961–71.
Xie R, Chung JY, Ylaya K, Williams RL, Guerrero N, Nakatsuka N, Badie C, Hewitt SM. Factors influencing the degradation of archival formalin-fixed paraffin-embedded tissue sections. J Histochem Cytochem. 2011;59:356–65.
Ohori M, Wheeler TM, Kattan MW, Goto Y, Scardino PT. Prognostic significance of positive surgical margins in radical prostatectomy specimens. J Urol. 1995;154:1818–24.
Eastham JA, Kattan MW, Riedel E, Begg CB, Wheeler TM, Gerigk C, Gonen M, Reuter V, Scardino PT. Variations among individual surgeons in the rate of positive surgical margins in radical prostatectomy specimens. J Urol. 2003;170:2292–5.
Masters BR, So PT, Gratton E. Multiphoton excitation microscopy of in vivo human skin: functional and morphological optical biopsy based on three-dimensional imaging, lifetime measurements and fluorescence spectroscopya. Ann N Y Acad Sci. 1998;838:58–67.
Rajadhyaksha M, Anderson RR, Webb RH. Video-rate confocal scanning laser microscope for imaging human tissues in vivo. Appl Opt. 1999;38:2105–15.
Masters BR, So PT. Confocal microscopy and multi-photon excitation microscopy of human skin in vivo. Opt Express. 2001;8:2–10.
Masters BR, So PT, Gratton E. Multiphoton excitation fluorescence microscopy and spectroscopy of in vivo human skin. Biophys J. 1997;72:2405–12.
Adur JF, Pelegati VB, Costa LF, de Thomaz AA, Almeida DB, Cesar CL, Pietro L, Andrade LA, Bottcher-Luiz F. Recognition of serous ovarian tumors in human samples by multimodal nonlinear optical microscopy. J Biomed Opt. 2011;16:096017.
Jain M, Robinson BD, Scherr DS, Sterling J, Lee MM, Wysock J, Rubin MA, Maxfield FR, Zipfel WR, Webb WW, Mukherjee S. Multiphoton microscopy in the evaluation of human bladder biopsies. Arch Pathol Lab Med. 2012;136:517–26.
Dodt HU, Leischner U, Schierloh A, Jährling N, Mauch CP, Deininger K, Deussing JM, Eder M, Zieglgänsberger W, Becker K. Ultramicroscopy: three-dimensional visualization of neuronal networks in the whole mouse brain. Nat Methods. 2007;4:331.
Keller PJ, Schmidt AD, Wittbrodt J, Stelzer EH. Reconstruction of zebrafish early embryonic development by scanned light sheet microscopy. Science. 2008;322:1065–9.
Olarte OE, Andilla J, Gualda EJ, Loza-Alvarez P. Light-sheet microscopy: a tutorial. Adv Opt Photonics. 2018;10:111–79.
Schmid B, Shah G, Scherf N, Weber M, Thierbach K, Campos CP, Roeder I, Aanstad P, Huisken J. High-speed panoramic light-sheet microscopy reveals global endodermal cell dynamics. Nat Commun. 2013;4:2207.
Weber M, Huisken J. Light sheet microscopy for real-time developmental biology. Curr Opin Genet Dev. 2011;21:566–72.
Stelzer EH. Light-sheet fluorescence microscopy for quantitative biology. Nat Methods. 2015;12:23–6.
Keller PJ, Dodt HU. Light sheet microscopy of living or cleared specimens. Curr Opin Neurobiol. 2012;22:138–43.
Verveer PJ, Swoger J, Pampaloni F, Greger K, Marcello M, Stelzer EH. High-resolution three-dimensional imaging of large specimens with light sheet-based microscopy. Nat Methods. 2007;4:311.
Maizel A, von Wangenheim D, Federici F, Haseloff J, Stelzer EH. High-resolution live imaging of plant growth in near physiological bright conditions using light sheet fluorescence microscopy. Plant J. 2011;68:377–85.
Fuchs E, Jaffe JS, Long RA, Azam F. Thin laser light sheet microscope for microbial oceanography. Opt Express. 2002;10:145–54.
Zsigmondy R. Colloids and the ultramicroscope: a manual of colloid chemistry and ultramicroscopy. New York: Wiley; 1909.
Voie AH, Burns DH, Spelman FA. Orthogonal-plane fluorescence optical sectioning: three-dimensional imaging of macroscopic biological specimens. J Microsc. 1993;170:229–36.
Huisken J, Swoger J, Del Bene F, Wittbrodt J, Stelzer EH. Optical sectioning deep inside live embryos by selective plane illumination microscopy. Science. 2004;305:1007–9.
Wan P, Zhu J, Xu J, Li Y, Yu T, Zhu D. Evaluation of seven optical clearing methods in mouse brain. Neurophotonics. 2018;5:035007.
Power RM, Huisken J. A guide to light-sheet fluorescence microscopy for multiscale imaging. Nat Methods. 2017;14:360.
Planchon TA, Gao L, Milkie DE, Davidson MW, Galbraith JA, Galbraith CG, Betzig E. Rapid three-dimensional isotropic imaging of living cells using Bessel beam plane illumination. Nat Methods. 2011;8:417.
Fahrbach FO, Gurchenkov V, Alessandri K, Nassoy P, Rohrbach A. Light-sheet microscopy in thick media using scanned Bessel beams and two-photon fluorescence excitation. Opt Express. 2013;21:13824–39.
Vettenburg T, Dalgarno HI, Nylk J, Coll-Lladó C, Ferrier DE, Čižmár T, Gunn-Moore FJ, Dholakia K. Light-sheet microscopy using an Airy beam. Nat Methods. 2014;11:541.
Fahrbach FO, Rohrbach A. Propagation stability of self-reconstructing Bessel beams enables contrast-enhanced imaging in thick media. Nat commun. 2012;3:632.
Truong TV, Supatto W, Koos DS, Choi JM, Fraser SE. Deep and fast live imaging with two-photon scanned light-sheet microscopy. Nat Methods. 2011;8:757.
Fahrbach FO, Voigt FF, Schmid B, Helmchen F, Huisken J. Rapid 3D light-sheet microscopy with a tunable lens. Opt Express. 2013;21:21010–26.
Tomer R, Lovett-Barron M, Kauvar I, Andalman A, Burns VM, Sankaran S, Grosenick L, Broxton M, Yang S, Deisseroth K. SPED light sheet microscopy: fast mapping of biological system structure and function. Cell. 2015;163:1796–806.
Chen BC, Legant WR, Wang K, Shao L, Milkie DE, Davidson MW, Janetopoulos C, Wu XS, Hammer JA III, Liu Z, English BP, Kiyosue YM, Romero DP, Ritter AT, Schwartz JL, Laylin LF, Mullins RD, Mitchell DM, Bembenek JN, Reymann AC, Böhme R, Grill SW, Wang JT, Seydoux G, Tulu US, Kiehart DP, Betzig E. Lattice light-sheet microscopy: imaging molecules to embryos at high spatiotemporal resolution. Science. 2014;346:1257998.
Tomer R, Khairy K, Amat F, Keller PJ. Quantitative high-speed imaging of entire developing embryos with simultaneous multiview light-sheet microscopy. Nat Methods. 2012;9:755.
Krzic U, Gunther S, Saunders TE, Streichan SJ, Hufnagel L. Multiview light-sheet microscope for rapid in toto imaging. Nat Methods. 2012;9:730.
Ahrens MB, Orger MB, Robson DN, Li JM, Keller PJ. Whole-brain functional imaging at cellular resolution using light-sheet microscopy. Nat Methods. 2013;10:413.
Wu Y, Wawrzusin P, Senseney J, Fischer RS, Christensen R, Santella A, York AG, Winter PW, Waterman CM, Bao Z, Colón-Ramos DA, McAuliffe M, Shroff H. Spatially isotropic four-dimensional imaging with dual-view plane illumination microscopy. Nat Biotechnol. 2013;31:1032.
Krzic U, Gunther S, Saunders TE, Streichan SJ, Hufnagel L. Multiview light-sheet microscope for rapid in toto imaging. Nat Methods. 2012;9:730.
Keller PJ, Ahrens MB. Visualizing whole-brain activity and development at the single-cell level using light-sheet microscopy. Neuron. 2015;85:462–83.
Royer LA, Lemon WC, Chhetri RK, Wan Y, Coleman M, Myers EW, Keller PJ. Adaptive light-sheet microscopy for long-term, high-resolution imaging in living organisms. Nat Biotechnol. 2016;34:1267.
Amat F, Höckendorf B, Wan Y, Lemon WC, McDole K, Keller PJ. Efficient processing and analysis of large-scale light-sheet microscopy data. Nat Protoc. 2015;10:1679.
Wu Y, Ghitani A, Christensen R, Santella A, Du Z, Rondeau G, Bao Z, Ramos DC, Shroff H. Inverted selective plane illumination microscopy (iSPIM) enables coupled cell identity lineaging and neurodevelopmental imaging in Caenorhabditis elegans. Proc Natl Acad Sci. 2011;108(43):17708.
Kumar A, Wu Y, Christensen R, Chandris P, Gandler W, McCreedy E, Bokinsky A, Colón-Ramos DA, Bao Z, McAuliffe M, Rondeau G, Shroff H. Dual-view plane illumination microscopy for rapid and spatially isotropic imaging. Nat Protoc. 2014;9:2555.
Bouchard MB, Voleti V, Mendes CS, Lacefield C, Grueber WB, Mann RS, Bruno RM, Hillman EM. Swept confocally-aligned planar excitation (SCAPE) microscopy for high-speed volumetric imaging of behaving organisms. Nat Photonics. 2015;9:113.
Migliori M, Datta MS, Dupre C, Apak MC, Asano S, Gao R, Boyden ES, Hermanson O, Yuste R, Tomer R. Light sheet theta microscopy for rapid high-resolution imaging of large biological samples. BMC Biol. 2018;16:57.
Chang BJ, Meza VDP, Stelzer EH. csiLSFM combines light-sheet fluorescence microscopy and coherent structured illumination for a lateral resolution below 100 nm. Proc Natl Acad Sci. 2017;114(9):4869–74.
Pitrone PG, Schindelin J, Stuyvenberg L, Preibisch S, Weber M, Eliceiri KW, Huisken J, Tomancak P. OpenSPIM: an open-access light-sheet microscopy platform. Nat Methods. 2013;10:598.
Glaser AK, Reder NP, Chen Y, McCarty EF, Yin C, Wei L, Wang Y, True LD, Liu JT. Light-sheet microscopy for slide-free non-destructive pathology of large clinical specimens. Nat Biomed Eng. 2017;1:0084.
Azaripour A, Lagerweij T, Scharfbillig C, Jadczak AE, van der Swaan B, Molenaar M, van der Waal R, Kielbassa K, Tigchelaar W, Picavet DI, Jonker A, Hendrikx EML, Hira VVV, Khurshed M, Van Noorden CJF. Three-dimensional histochemistry and imaging of human gingiva. Sci Rep. 2018;8:1647.
Sangha GS, Hu B, Bolus D, Wang M, Skidmore SJ, Sholl AB, Brown JQ, Goergen CJ. Multi-modality photoacoustic tomography, ultrasound, and light sheet microscopy for volumetric tumor margin detection. In: Proceedings of SPIE, Multimodal Biomedical Imaging XIII 2018, vol 10487, p 104870D.
Johnson SB, Cureoglu S, O’Malley JT, Santi PA. Comparison of traditional histology and TSLIM optical sectioning of human temporal bones. Otol Neurotol. 2014;35(7):1145–9.
Abadie S, Jardet C, Colombelli J, Chaput B, David A, Grolleau JL, Bedos P, Lobjois V, Descargues P, Rouquette J. 3D imaging of cleared human skin biopsies using light-sheet microscopy: a new way to visualize in-depth skin structure. Skin Res Technol. 2018;24(2):294–303.
Richardson DS, Lichtman JW. Clarifying tissue clearing. Cell. 2015;162(2):246–57.
Silvestri L, Costantini I, Sacconi L, Pavone FS. Clearing of fixed tissue: a review from a microscopist’s perspective. J. Biomed. Optics. 2016;21(8):081205.
Acknowledgements
This research was supported by a GIST Research Institute grant funded by GIST in 2019 and grants from the National Research Foundation of Korea (NRF) funded by the Korean government (MEST) (NRF-2016R1A2B4015381), by the Brain Research Program through the NRF funded by the Ministry of Science, ICT & Future Planning (NRF-2017M3C7A1044964), and also by the Bio & Medical Technology Development Program of NRF funded by the Korean government (MSIT) (NRF-2015M3A9E2030125). The authors thank Mr. Ripon Kumar Saha for preparing schematic drawings.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
All authors declare that they have no conflicts of interest.
Ethical approval
This work did not involve any studies with human participants or animals performed by any of the authors.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Poola, P.K., Afzal, M.I., Yoo, Y. et al. Light sheet microscopy for histopathology applications. Biomed. Eng. Lett. 9, 279–291 (2019). https://doi.org/10.1007/s13534-019-00122-y
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13534-019-00122-y