Skip to main content

Advertisement

SpringerLink
Log in

Raman spectroscopic imaging for in vivo detection of cerebral brain metastases

  • Paper in Forefront
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

We report for the first time a proof-of-concept experiment employing Raman spectroscopy to detect intracerebral tumors in vivo by brain surface mapping. Raman spectroscopy is a non-destructive biophotonic method which probes molecular vibrations. It provides a specific fingerprint of the biochemical composition and structure of tissue without using any labels. Here, the Raman system was coupled to a fiber-optic probe. Metastatic brain tumors were induced by injection of murine melanoma cells into the carotid artery of mice, which led to subcortical and cortical tumor growth within 14 days. Before data acquisition, the cortex was exposed by creating a bony window covered by a calcium fluoride window. Spectral contributions were assigned to proteins, lipids, blood, water, bone, and melanin. Based on the spectral information, Raman images enabled the localization of cortical and subcortical tumor cell aggregates with accuracy of roughly 250 μm. This study demonstrates the prospects of Raman spectroscopy as an intravital tool to detect cerebral pathologies and opens the field for biophotonic imaging of the living brain. Future investigations aim to reduce the exposure time from minutes to seconds and improve the lateral resolution.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Krafft C, Sobottka SB, Schackert G, Salzer R (2006) Raman and infrared spectroscopic mapping of human primary intracranial tumors: a comparative study. J Raman Spectrosc 37:367–375

    Article  CAS  Google Scholar 

  2. Krafft C, Sobottka SB, Schackert G, Salzer R (2005) Near infrared Raman spectroscopic mapping of native brain tissue and intracranial tumors. Analyst 130:1070–1077

    Article  CAS  Google Scholar 

  3. Krafft C, Kirsch M, Beleites C, Schackert G, Salzer R (2007) Methodology for fiber-optic Raman mapping and FTIR imaging of metastases in mouse brains. Anal Bioanal Chem 389:1133–1142

    Article  CAS  Google Scholar 

  4. Schackert G, Fidler IJ (1988) Development of in vivo models for studies of brain metastasis. Int J Cancer 41:589–594

    Article  CAS  Google Scholar 

  5. Kirsch M, Weigel P, Pinzer T, Carroll RS, Black PM, Schackert HK, Schackert G (2005) Therapy of hematogenous melanoma brain metastases with endostatin. Clin Cancer Res 11:1259–1267

    CAS  Google Scholar 

  6. Krafft C, Codrich D, Pelizzo G, Sergo V (2008) Raman and FTIR imaging of lung tissue: methodology for control samples. Vib Spectrosc 46:141–149

    Article  CAS  Google Scholar 

  7. Matousek P, Morris MD, Everall N, Clark IP, Towrie M, Draper E, Goodship A, Parker AW (2005) Numerical simulations of subsurface probing in diffusely scattering media using spatially offset Raman spectroscopy. Appl Spectrosc 59:1485–1492

    Article  CAS  Google Scholar 

  8. Schulmerich MV, Cole JH, Dooley KA, Morris MD, Kreider JM, Goldstein SA, Srinivasan S, Pogue BW (2008) Noninvasive Raman tomographic imaging of canine bone tissue. J Biomed Opt 13:020506

    Article  Google Scholar 

  9. Krafft C, Dietzek B, Popp J (2009) Raman and CARS microspectroscopy of cells and tissues. Analyst 134:1046–1057

    Article  CAS  Google Scholar 

  10. Bakker Schut TC, Witjes MJ, Sterenborg HJ, Speelman OC, Roodenburg JL, Marple ET, Bruining HA, Puppels GJ (2000) In vivo detection of dysplastic tissue by Raman spectroscopy. Anal Chem 72:6010–6018

    Article  CAS  Google Scholar 

  11. Huang Z, Bergholt MS, Zheng W, Lin K, Ho KY, The M, Yeoh KG (2010) In vivo early diagnosis of gastric dysplasia using narrow-band image-guided Raman endoscopy. J Biomed Opt 15:037017

    Article  Google Scholar 

  12. Utzinger U, Heintzelmann DL, Mahadevan-Jansen A, Malpica A, Follen M, Richards-Kortum R (2001) Near-infrared Raman spectroscopy for in vivo detection of cervical precancers. Appl Spectrosc 55:955–959

    Article  CAS  Google Scholar 

  13. Motz JT, Gandhi SJ, Scepanovic OR, Haka AS, Kramer JR, Dasari RR, Feld MS (2005) Real-time Raman system for in vivo disease diagnosis. J Biomed Opt 10:031113

    Article  Google Scholar 

  14. Molckovsky A, Song LM, Shim MG, Marcon NE, Wilson BC (2003) Diagnostic potential of near-infrared Raman spectroscopy in the colon: differentiating adenomatous from hyperplastic polyps. Gastrointest Endosc 57:396–402

    Article  Google Scholar 

  15. Buschman HP, Marple ET, Wach ML, Bennett B, Schut TC, Bruining HA, Bruschke AV, van der Laarse A, Puppels GJ (2000) In vivo determination of the molecular composition of artery wall by intravascular Raman spectroscopy. Anal Chem 72:3771–3775

    Article  CAS  Google Scholar 

  16. Beljebbar A, Dukic S, Amharref N, Manfait M (2010) Ex vivo and in vivo diagnosis of C6 glioblastoma development by Raman spectroscopy coupled to microprobe. Anal Bioanal Chem 398:477–487

    Google Scholar 

  17. Amharref N, Beljebbar A, Dukic S, Venteo L, Schneider L, Pluot M, Manfait M (2007) Discriminating healthy from tumor and necrosis tissue in rat brain tissue samples by Raman spectral imaging. Biochim Biophys Acta 1768:2605–2615

    Article  CAS  Google Scholar 

  18. Magee ND, Villaumie JS, Marple ET, Ennis M, Elborn JS, McGarvey JJ (2009) Ex vivo diagnosis of lung cancer using a Raman miniprobe. J Phys Chem B 113:8137–8141

    Article  CAS  Google Scholar 

  19. Santos LF, Wolthuis R, Koljenovic S, Almeida RM, Puppels GJ (2005) Fiber-optic probes for in vivo Raman spectroscopy in the high-wavenumber region. Anal Chem 77:6747–6752

    Article  CAS  Google Scholar 

  20. Koljenovic S, Bakker Schut TC, Wolthuis R, Vincent AJPE, Hendriks-Hagevi G, Santos LF, Kros JM, Puppels GJ (2007) Raman spectroscopic characterization of porcine brain tissue using a single fiber-optic probe. Anal Chem 79:557–564

    Article  CAS  Google Scholar 

  21. Flusberg BA, Nimmerjahn A, Cocker ED, Mukamel EA, Barretto RP, Ko TH, Burns LD, Jung JC, Schnitzer MJ (2008) High-speed, miniaturized fluorescence microscopy in freely moving mice. Nat Methods 5:935–938

    Article  CAS  Google Scholar 

  22. Dreissig I, Machill S, Salzer R, Krafft C (2009) Quantification of brain lipids by FTIR spectroscopy and partial least squares regression. Spectrochim Acta A Mol Biomol Spectrosc 71:2069–2075

    Article  Google Scholar 

  23. Kohler M, Machill S, Salzer R, Krafft C (2009) Characterization of lipid extracts from brain tissue and tumors using Raman spectroscopy and mass spectrometry. Anal Bioanal Chem 393:1513–1520

    Article  Google Scholar 

  24. Chen P, Shen A, Zhao W, Baek SJ, Yuan H, Hu J (2009) Raman signature from brain hippocampus could aid Alzheimer's disease diagnosis. Appl Opt 48:4743–4748

    Article  CAS  Google Scholar 

  25. Evans CL, Xu X, Kesari S, Xie XS, Wong ST, Young GS (2007) Chemically-selective imaging of brain structures with CARS microscopy. Opt Express 15:12076–12087

    Article  CAS  Google Scholar 

  26. 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  CAS  Google Scholar 

  27. Krafft C, Ramoji AA, Bielecki C, Vogler N, Meyer T, Akimov D, Rosch P, Schmitt M, Dietzek B, Petersen I, Stallmach A, Popp J (2009) A comparative Raman and CARS imaging study of colon tissue. J Biophotonics 2:303–312

    Article  Google Scholar 

Download references

Acknowledgments

We would like to thank Dr. Daniel Martin and Dipl. Biol Elke Leipnitz for their help. The research is funded by the German Research Foundation (DFG) within the project “Real time diagnosis of brain metastasis in animal models using Raman imaging” and by the MedDrive Start-up funds of the Medical Faculty, Dresden University of Technology.

Author information

Author notes

  1. Christoph Krafft

    Present address: Institute of Photonic Technology, Albert-Einstein-Str. 9, 07745, Jena, Germany

Authors and Affiliations

  1. Department of Neurosurgery, Carl Gustav Carus University Hospital, Dresden University of Technology, Fetscherstr. 74, 01307, Dresden, Germany

    Matthias Kirsch & Gabriele Schackert

  2. Institute of Bioanalytical Chemistry, Dresden University of Technology, 01069, Dresden, Germany

    Reiner Salzer & Christoph Krafft

Authors
  1. Matthias Kirsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gabriele Schackert
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Reiner Salzer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christoph Krafft
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Christoph Krafft.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kirsch, M., Schackert, G., Salzer, R. et al. Raman spectroscopic imaging for in vivo detection of cerebral brain metastases. Anal Bioanal Chem 398, 1707–1713 (2010). https://doi.org/10.1007/s00216-010-4116-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-010-4116-7

Keywords

Search

Navigation