Skip to main content

Advertisement

SpringerLink
Log in

Longitudinal Molecular Imaging with Single Cell Resolution of Disseminated Ovarian Cancer in Mice with a LED-based Confocal Microendoscope

  • Research Article
  • Published:
Molecular Imaging and Biology Aims and scope Submit manuscript

Abstract

Purpose

We engineered a flexible fiber-optic microendoscope for longitudinal optical imaging studies in a mouse model of disseminated ovarian cancer.

Procedures

The microendoscope delivers 470 nm excitation light from a light-emitting diode through a fiber-optic bundle with outer diameter of 680 μm. Optics were optimized to maximize power and lateral resolution. We used this instrument to repetitively monitor intraperitoneal growth of HeyA8 ovarian cancer cells stably transduced with green fluorescent protein over 4 weeks.

Results

The microendoscope achieves 0.7 mW power and lateral resolution of 4 μm. Initial in vivo imaging studies visualized single cells and small clusters of malignant cells with subsequent studies showing tumor masses and vasculature. We also resolved single cells within intraperitoneal tumor masses.

Conclusions

These studies establish microendoscope technology with single cell resolution for minimally-invasive, longitudinal imaging in living animals. This technology will advance future molecular imaging studies of ovarian cancer and other diseases.

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.
Fig. 5.

Similar content being viewed by others

References

  1. Luker GD, Luker KE (2008) Optical imaging: current applications and future directions. J Nucl Med 49:1–4

    Article  PubMed  Google Scholar 

  2. Choy G, Choyke P, Libutti SK (2003) Current advances in molecular imaging: noninvasive in vivo bioluminescent and fluorescent optical imaging in cancer research. Mol Imaging 2:303–312

    Article  PubMed  CAS  Google Scholar 

  3. Lu S, Lowe AW, Triadafilopoulos G, Hsiung PL, Hao Y, Crawford JM, Wang TD (2009) Endoscopic evaluation of esophago-gastro-jejunostomy in rat model of Barrett's esophagus. Dis Esophagus 22:323–330

    Article  PubMed  CAS  Google Scholar 

  4. Skala MC, Fontanella A, Lan L, Izatt JA, Dewhirst MW (2010) Longitudinal optical imaging of tumor metabolism and hemodynamics. J Biomed Opt 15:011112

    Article  PubMed  Google Scholar 

  5. Sumen C, Mempel TR, Mazo IB, von Andrian UH (2004) Intravital microscopy: visualizing immunity in context. Immunity 21:315–329

    PubMed  CAS  Google Scholar 

  6. Cahalan MD, Parker I (2008) Choreography of cell motility and interaction dynamics imaged by two-photon microscopy in lymphoid organs. Annu Rev Immunol 26:585–626

    Article  PubMed  CAS  Google Scholar 

  7. Muldoon TJ, Pierce MC, Nida DL, Williams MD, Gillenwater A, Richards-Kortum R (2007) Subcellular-resolution molecular imaging within living tissue by fiber microendoscopy. Opt Express 15:16413–16423

    Article  PubMed  CAS  Google Scholar 

  8. Muldoon TJ, Anandasabapathy S, Maru D, Richards-Kortum R (2008) High-resolution imaging in Barrett’s esophagus: a novel, low-cost endoscopic microscope. Gastrointest Endosc 68:737–744

    Article  PubMed  Google Scholar 

  9. Zhong W, Celli JP, Rizvi I et al (2009) In vivo high-resolution fluorescence microendoscopy for ovarian cancer detection and treatment monitoring. Br J Cancer 101:2015–2022

    Article  PubMed  CAS  Google Scholar 

  10. Philips Lumileds Lighting Company. Technical Datasheet DS51. Available at: http://www.philipslumileds.com. Accessed March 19, 2008

  11. Lois C, Hong EJ, Pease S, Brown EJ, Baltimore D (2002) Germline transmission and tissue-specific expression of transgenes delivered by lentiviral vectors. Science 295:868–872

    Article  PubMed  CAS  Google Scholar 

  12. Dittgen T, Nimmerjahn A, Komai S et al (2004) Lentivirus-based genetic manipulations of cortical neurons and their optical and electrophysiological monitoring in vivo. Proc Natl Acad Sci USA 101:18206–18211

    Article  PubMed  CAS  Google Scholar 

  13. Goetz M, Ziebart A, Foersch S et al (2010) In vivo molecular imaging of colorectal cancer with confocal endomicroscopy by targeting epidermal growth factor receptor. Gastroenterology 138:435–446

    Article  PubMed  CAS  Google Scholar 

  14. Hsiung PL, Hardy J, Friedland S et al (2008) Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy. Nat Med 14:454–458

    Article  PubMed  CAS  Google Scholar 

  15. Urano Y, Asanuma D, Hama Y et al (2009) Selective molecular imaging of viable cancer cells with pH-activatable fluorescence probes. Nat Med 15:104–109

    Article  PubMed  CAS  Google Scholar 

  16. Goetz M, Wang TD (2010) Molecular imaging in gastrointestinal endoscopy. Gastroenterology 138:828–833

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Research supported by NIH grants R01 CA136553, R01 CA136829, R01 CA142750, P50 CA93990, and U54 CA136429. We thank Gordon Mills, MD Anderson Cancer Center, for providing the HeyA8 ovarian cancer cells.

Conflict of Interest Statement

The authors state no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Biomedical Engineering, University of Michigan, 109 Zina Pitcher Place, BSRB 1728, Ann Arbor, MI, 48109, USA

    Sakib F. Elahi

  2. Department of Medicine, Division of Gastroenterology, University of Michigan, 109 Zina Pitcher Place, BSRB 1728, Ann Arbor, MI, 48109, USA

    Zhongyao Liu

  3. Center for Molecular Imaging, Department of Radiology, University of Michigan, 109 Zina Pitcher Place, BSRB A526, Ann Arbor, MI, 48109, USA

    Kathryn E. Luker

  4. Department of Medicine, Division of Gastroenterology, University of Michigan, 1500 E. Medical Center Dr. Taubman 3912, Ann Arbor, MI, 48109-5362, USA

    Richard S. Kwon

  5. Center for Molecular Imaging, Departments of Radiology and Microbiology and Immunology, University of Michigan, 109 Zina Pitcher Place, BSRB A526, Ann Arbor, MI, 48109, USA

    Gary D. Luker

  6. Department of Medicine, Division of Gastroenterology, Department of Biomedical Engineering, University of Michigan, 109 Zina Pitcher Pl. BSRB 1522, Ann Arbor, MI, 48109-2200, USA

    Thomas D. Wang

Authors
  1. Sakib F. Elahi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhongyao Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kathryn E. Luker
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Richard S. Kwon
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gary D. Luker
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Thomas D. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sakib F. Elahi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Elahi, S.F., Liu, Z., Luker, K.E. et al. Longitudinal Molecular Imaging with Single Cell Resolution of Disseminated Ovarian Cancer in Mice with a LED-based Confocal Microendoscope. Mol Imaging Biol 13, 1157–1162 (2011). https://doi.org/10.1007/s11307-010-0455-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11307-010-0455-1

Key words

Search

Navigation