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Biomedical Engineering / Biomedizinische Technik

Joint Journal of the German Society for Biomedical Engineering in VDE and the Austrian and Swiss Societies for Biomedical Engineering and the German Society of Biomaterials

Editor-in-Chief: Dössel, Olaf

Editorial Board: Augat, Peter / Habibović, Pamela / Haueisen, Jens / Jahnen-Dechent, Wilhelm / Jockenhoevel, Stefan / Knaup-Gregori, Petra / Lenarz, Thomas / Leonhardt, Steffen / Plank, Gernot / Radermacher, Klaus M. / Schkommodau, Erik / Stieglitz, Thomas / Boenick, Ulrich / Jaramaz, Branislav / Kraft, Marc / Lenthe, Harry / Lo, Benny / Mainardi, Luca / Micera, Silvestro / Penzel, Thomas / Robitzki, Andrea A. / Schaeffter, Tobias / Snedeker, Jess G. / Sörnmo, Leif / Sugano, Nobuhiko / Werner, Jürgen /

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Volume 63, Issue 5


Volume 57 (2012)

Optical molecular imaging of corpora amylacea in human brain tissue

Roberta Galli
  • Clinical Sensoring and Monitoring, Clinic of Anesthesiology and Intensive Care Therapy, Medical Faculty, TU Dresden, 01307 Dresden, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Matthias Meinhardt / Edmund Koch
  • Clinical Sensoring and Monitoring, Clinic of Anesthesiology and Intensive Care Therapy, Medical Faculty, TU Dresden, 01307 Dresden, Germany
  • Center for Regenerative Therapies, TU Dresden, 01307 Dresden, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Gabriele Schackert / Gerald Steiner
  • Clinical Sensoring and Monitoring, Clinic of Anesthesiology and Intensive Care Therapy, Medical Faculty, TU Dresden, 01307 Dresden, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Matthias Kirsch
  • Center for Regenerative Therapies, TU Dresden, 01307 Dresden, Germany
  • Neurosurgery, University Hospital Carl Gustav Carus, TU Dresden, 01307 Dresden, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Ortrud Uckermann
  • Corresponding author
  • Neurosurgery, University Hospital Carl Gustav Carus, TU Dresden, Fetscherstr. 74, 01307 Dresden, Germany, Phone: +49 351 4583114, Fax: +49 351 4584304
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2018-02-28 | DOI: https://doi.org/10.1515/bmt-2017-0073


Label-free multiphoton imaging constitutes a promising technique for clinical diagnosis and therapeutic monitoring. Corpora amylacea (CoA) are starch-like structures often found in the diseased brain, whose origin and role in nervous pathologies are still a matter of debate. Recently, CoA in the diseased human hippocampus were found to be second harmonic generation (SHG) active. Here, we show that CoA formed in other parts of the diseased brain and in brain neoplasms display a similar SHG activity. The SHG pattern of CoA depended on laser polarization, indicating that a radial structure is responsible for their nonlinear activity. Vibrational spectroscopy was used to study the biochemistry underlying the SHG activity. Infrared (IR) and Raman spectroscopy showed that CoA contain polyglucosans that are biochemically similar to glycogen, but with an unusual structure that is similar to amylopectin, which justifies the nonlinear activity of CoA. Our findings explain the SHG activity of CoA and demonstrate that CoA in the pathological brain are amenable to label-free multiphoton imaging. Further research will clarify whether intraoperative assessment of CoA can be diagnostically exploited.

Keywords: label-free imaging; multiphoton microscopy; nervous system; pathology; second harmonic generation; vibrational spectroscopy


  • [1]

    Ahn T-B, Langston JW, Aachi VR, Dickson DW. Relationship of neighboring tissue and gliosis to α-synuclein pathology in a fetal transplant for Parkinson’s disease. Am J Neurodegener Dis 2012; 1: 49–59.Google Scholar

  • [2]

    Augé E, Cabezón I, Pelegrí C, Vilaplana J. New perspectives on corpora amylacea in the human brain. Sci Rep 2017; 7: 41807.Google Scholar

  • [3]

    Bélanger E, Crépeau J, Laffray S, Vallée R, De Koninck Y, Côté D. Live animal myelin histomorphometry of the spinal cord with video-rate multimodal nonlinear microendoscopy. J Biomed Opt 2012; 17: 021107.Google Scholar

  • [4]

    Bilbao JM, Schmidt RE. The axon: normal structure and pathological alterations. In: Biopsy Diagnosis of Peripheral Neuropathy. Switzerland: Springer International Publishing 2015: 51–84.Google Scholar

  • [5]

    Bocklitz TW, Salah FS, Vogler N, et al. Pseudo-HE images derived from CARS/TPEF/SHG multimodal imaging in combination with Raman-spectroscopy as a pathological screening tool. BMC Cancer 2016; 16: 534.Google Scholar

  • [6]

    Bourhill G, Mansour K, Perry KJ, et al. Powder second harmonic generation efficiencies of saccharide materials. Chem Mater 1993; 5: 802–808.Google Scholar

  • [7]

    Bulkin BJ, Kwak Y, Dea ICM. Retrogradation kinetics of waxy-corn and potato starches; a rapid, Raman-spectroscopic study. Carbohydr Res 1987; 160: 95–112.Google Scholar

  • [8]

    Cael JJ, Koenig JL, Blackwell J. Infrared and Raman spectroscopy of carbohydrates. 3. Raman spectra of the polymorphic forms of amylose. Carbohydr Res 1973; 29: 123–134.Google Scholar

  • [9]

    Campagnola P. Second harmonic generation imaging microscopy: applications to diseases diagnostics. Anal Chem 2011; 83: 3224–3231.Google Scholar

  • [10]

    Campagnola PJ, Millard AC, Terasaki M, Hoppe PE, Malone CJ, Mohler WA. Three-dimensional high-resolution second-harmonic generation imaging of endogenous structural proteins in biological tissues. Biophys J 2002; 82: 493–508.Google Scholar

  • [11]

    Cavanagh JB. Corpora-amylacea and the family of polyglucosan diseases. Brain Res Brain Res Rev 1999; 29: 265–295.Google Scholar

  • [12]

    Cox G. Biological applications of second harmonic imaging. Biophys Rev 2011; 3: 131.Google Scholar

  • [13]

    De Gelder J, De Gussem K, Vandenabeele P, Moens L. Reference database of Raman spectra of biological molecules. J Raman Spectrosc 2007; 38: 1133–1347.Google Scholar

  • [14]

    Dombeck DA, Kasischke KA, Vishwasrao HD, Ingelsson M, Hyman BT, Webb WW. Uniform polarity microtubule assemblies imaged in native brain tissue by second-harmonic generation microscopy. Proc Natl Acad Sci USA 2003; 100: 7081–7086.Google Scholar

  • [15]

    Freund I, Deutsch M. Second-harmonic microscopy of biological tissue. Opt Lett 1986; 11: 94–96.Google Scholar

  • [16]

    Galli R, Uckermann O, Winterhalder MJ, et al. Vibrational spectroscopic imaging and multiphoton microscopy of spinal cord injury. Anal Chem 2012; 84: 8707–8714.Google Scholar

  • [17]

    Galli R, Uckermann O, Koch E, Schackert G, Kirsch M, Steiner G. Effects of tissue fixation on coherent anti-Stokes Raman scattering images of brain. J Biomed Opt 2014; 19: 071402.Google Scholar

  • [18]

    Galli R, Uckermann O, Temme A, et al. Assessing the efficacy of coherent anti-Stokes Raman scattering microscopy for the detection of infiltrating glioblastoma in fresh brain samples. J Biophotonics 2016. doi: 10.1002/jbio.201500323. [Epub ahead of print].Google Scholar

  • [19]

    Goodfellow BJ, Wilson RH. A Fourier transform IR study of the gelation of amylose and amylopectin. Biopolymers 1990; 30: 1183–1189.Google Scholar

  • [20]

    Imitola J, Côté D, Rasmussen S, et al. Multimodal coherent anti-Stokes Raman scattering microscopy reveals microglia-associated myelin and axonal dysfunction in multiple sclerosis-like lesions in mice. J Biomed Opt 2011; 16: 021109.Google Scholar

  • [21]

    Lee JH, Kim DH, Song WK, Oh M-K, Ko D-K. Label-free imaging and quantitative chemical analysis of Alzheimer’s disease brain samples with multimodal multiphoton nonlinear optical microspectroscopy. J Biomed Opt 2015; 20: 56013.Google Scholar

  • [22]

    Leel-Ossy L. Corpora amylacea in hippocampal sclerosis. J Neurol Neurosurg Psychiatry 1998; 65: 614.Google Scholar

  • [23]

    Leel-Ossy L. New data on the ultrastructure of the corpus amylaceum (polyglucosan body). Pathol Oncol Res POR 2001; 7: 145–150.Google Scholar

  • [24]

    Légaré F, Evans CL, Ganikhanov F, Xie XS. Towards CARS endoscopy. Opt Express 2006; 14: 4427–4432.Google Scholar

  • [25]

    Mazumder N, Qiu J, Foreman MR, Romero CM, Török P, Kao F-J. Stokes vector based polarization resolved second harmonic microscopy of starch granules. Biomed Opt Express 2013; 4: 538–547.Google Scholar

  • [26]

    Meyer T, Schmitt M, Dietzek B, Popp J. Accumulating advantages, reducing limitations: multimodal nonlinear imaging in biomedical sciences – the synergy of multiple contrast mechanisms. J Biophotonics 2013; 6: 887–904.Google Scholar

  • [27]

    Movasaghi Z, Rehman S, Rehman DIU. Raman spectroscopy of biological tissues. Appl Spectrosc Rev 2007; 42: 493–541.Google Scholar

  • [28]

    Movasaghi Z, Rehman S, Rehman DIU. Fourier transform infrared (FTIR) spectroscopy of biological tissues. Appl Spectrosc Rev 2008; 43: 134–179.Google Scholar

  • [29]

    Mrak RE, Griffin ST, Graham DI. Aging-associated changes in human brain. J Neuropathol Exp Neurol 1997; 56: 1269–1275.Google Scholar

  • [30]

    Nishio S, Morioka T, Kawamura T, Fukui K, Nonaka H, Matsushima M. Corpora amylacea replace the hippocampal pyramidal cell layer in a patient with temporal lobe epilepsy. Epilepsia 2001; 42: 960–962.Google Scholar

  • [31]

    Orringer DA, Pandian B, Niknafs YS, et al. Rapid intraoperative histology of unprocessed surgical specimens via fibre-laser-based stimulated Raman scattering microscopy. Nat Biomed Eng 2017; 1. doi: 10.1038/s41551-016-0027. [Epub ahead of print].Google Scholar

  • [32]

    Plotnikov SV, Millard AC, Campagnola PJ, Mohler WA. Characterization of the myosin-based source for second-harmonic generation from muscle sarcomeres. Biophys J 2006; 90: 693–703.Google Scholar

  • [33]

    Psilodimitrakopoulos S, Amat-Roldan I, Loza-Alvarez P, Artigas D. Estimating the helical pitch angle of amylopectin in starch using polarization second harmonic generation microscopy. J Opt 2010; 12: 084007.Google Scholar

  • [34]

    Schindelin J, Arganda-Carreras I, Frise E, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods 2012; 9: 676–682.Google Scholar

  • [35]

    Suhalim JL, Chung C-Y, Lilledahl MB, et al. Characterization of cholesterol crystals in atherosclerotic plaques using stimulated Raman scattering and second-harmonic generation microscopy. Biophys J 2012; 102: 1988–1995.Google Scholar

  • [36]

    Tamosaityte S, Galli R, Uckermann O, et al. Biochemical monitoring of spinal cord injury by FT-IR spectroscopy – effects of therapeutic alginate implant in rat models. PLoS One 2015; 10: e0142660.Google Scholar

  • [37]

    Uckermann O, Galli R, Tamosaityte S, et al. Label-free delineation of brain tumors by coherent anti-Stokes Raman scattering microscopy in an orthotopic mouse model and human glioblastoma. PLoS One 2014; 9: e107115.Google Scholar

  • [38]

    Uckermann O, Galli R, Leupold S, et al. Label-free multiphoton microscopy reveals altered tissue architecture in hippocampal sclerosis. Epilepsia 2017; 58: e1–e5.Google Scholar

  • [39]

    Van Paesschen W, Revesz T, Duncan JS. Corpora amylacea in hippocampal sclerosis. J Neurol Neurosurg Psychiatry 1997; 63: 513–515.Google Scholar

  • [40]

    Yano K, Sakamoto Y, Hirosawa N, et al. Applications of Fourier transform infrared spectroscopy, Fourier transform infrared microscopy and near-infrared spectroscopy to cancer research. J Spectrosc 2003; 17: 315–321.Google Scholar

  • [41]

    Zhuo Z-Y, Liao C-S, Huang C-H, et al. Second harmonic generation imaging – a new method for unraveling molecular information of starch. J Struct Biol 2010; 171: 88–94.Google Scholar

  • [42]

    Zipfel WR, Williams RM, Christie R, Nikitin AY, Hyman BT, Webb WW. Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation. Proc Natl Acad Sci USA 2003; 100: 7075–7080.Google Scholar

  • [43]

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

About the article

Received: 2017-05-16

Accepted: 2017-07-31

Published Online: 2018-02-28

Published in Print: 2018-10-25

Author Statement

Research funding: The research was partly funded by the Bundesministerium für Bildung und Forschung (German Federal Ministry of Education and Research) project EndoCARS (Funder ID: 10.13039/501100002347, AZ: 13N13807).

Conflict of interest: Authors state no conflict of interest.

Informed consent: Human tissue was obtained from surgery for the treatment of pharmacoresistant epilepsy or brain tumor surgery. All patients gave their written consent.

Ethical approval: The research related to human use complied with all the relevant national regulations and institutional policies and was performed in accordance with the tenets of the Helsinki Declaration and has been approved by the Ethics Committee at Dresden University Hospital (EK 323122008).

Citation Information: Biomedical Engineering / Biomedizinische Technik, Volume 63, Issue 5, Pages 579–585, ISSN (Online) 1862-278X, ISSN (Print) 0013-5585, DOI: https://doi.org/10.1515/bmt-2017-0073.

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