Abstract

An estimated 1.6 million breast biopsies are performed in the US each year. In order to provide real-time, in-vivo imaging with sub-cellular resolution for optical biopsies, we have designed an ultra-slim objective to fit inside the 1-mm-diameter hypodermic needles currently used for breast biopsies to image tissue stained by the fluorescent probe proflavine. To ensure high-quality imaging performance, experimental tests were performed to characterize fiber bundle’s light-coupling efficiency and simulations were performed to evaluate the impact of candidate lens materials’ autofluorescence. A prototype of NA = 0.4, 250-µm field of view, ultra-slim objective optics was built and tested, yielding diffraction-limited performance and estimated resolution of 0.9 µm. When used in conjunction with a commercial coherent fiber bundle to relay the image formed by the objective, the measured resolution was 2.5 µm.

© 2010 OSA

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References

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2009 (3)

M. Silverstein, “Where’s the outrage?” J. Am. Coll. Surg. 208(1), 78–79 (2009).
[CrossRef]

W. Zhong, J. P. Celli, I. Rizvi, Z. Mai, B. Q. Spring, S. H. Yun, and T. Hasan, “In vivo high-resolution fluorescence microendoscopy for ovarian cancer detection and treatment monitoring,” Br. J. Cancer 101(12), 2015–2022 (2009).
[CrossRef]

S. Santos, K. K. Chu, D. Lim, N. Bozinovic, T. N. Ford, C. Hourtoule, A. C. Bartoo, S. K. Singh, and J. Mertz, “Optically sectioned fluorescence endomicroscopy with hybrid-illumination imaging through a flexible fiber bundle,” J. Biomed. Opt. 14(3), 030502 (2009).
[CrossRef]

2008 (2)

W. C. Sweatt, D. D. Gill, D. P. Adams, M. J. Vasile, and A. A. Claudet, “Diamond milling of micro-optics,” IEEE Aerosp. Electron. Syst. Mag. 23(1), 13–17 (2008).
[CrossRef]

P. Kim, M. Puoris’haag, D. Côté, C. P. Lin, and S. H. Yun, “In vivo confocal and multiphoton microendoscopy,” J. Biomed. Opt. 13(1), 010501 (2008).
[CrossRef]

2007 (2)

2006 (1)

2004 (1)

2002 (2)

C. Liang, K.-B. Sung, R. R. Richards-Kortum, and M. R. Descour, “Design of a high-numerical-aperture miniature microscope objective for an endoscopic fiber confocal reflectance microscope,” Appl. Opt. 41(22), 4603–4610 (2002).
[CrossRef]

V. Dubaj, A. Mazzolini, A. Wood, and M. Harris, “Optic fibre bundle contact imaging probe employing a laser scanning confocal microscope,” J. Microsc. 207(2), 108–117 (2002).
[CrossRef]

1995 (1)

A. P. Tzannes and J. M. Mooney, “Measurement of the modulation transfer-function of infrared cameras,” Opt. Eng. 34(6), 1808–1817 (1995).
[CrossRef]

1993 (1)

1977 (1)

S. Georghiou, “Interaction of acridine drugs with DNA and nucleotides,” Photochem. Photobiol. 26(1), 59–68 (1977).
[CrossRef]

Adams, D. P.

W. C. Sweatt, D. D. Gill, D. P. Adams, M. J. Vasile, and A. A. Claudet, “Diamond milling of micro-optics,” IEEE Aerosp. Electron. Syst. Mag. 23(1), 13–17 (2008).
[CrossRef]

Aziz, D.

Bartoo, A. C.

S. Santos, K. K. Chu, D. Lim, N. Bozinovic, T. N. Ford, C. Hourtoule, A. C. Bartoo, S. K. Singh, and J. Mertz, “Optically sectioned fluorescence endomicroscopy with hybrid-illumination imaging through a flexible fiber bundle,” J. Biomed. Opt. 14(3), 030502 (2009).
[CrossRef]

Bozinovic, N.

S. Santos, K. K. Chu, D. Lim, N. Bozinovic, T. N. Ford, C. Hourtoule, A. C. Bartoo, S. K. Singh, and J. Mertz, “Optically sectioned fluorescence endomicroscopy with hybrid-illumination imaging through a flexible fiber bundle,” J. Biomed. Opt. 14(3), 030502 (2009).
[CrossRef]

Carlson, K. D.

Celli, J. P.

W. Zhong, J. P. Celli, I. Rizvi, Z. Mai, B. Q. Spring, S. H. Yun, and T. Hasan, “In vivo high-resolution fluorescence microendoscopy for ovarian cancer detection and treatment monitoring,” Br. J. Cancer 101(12), 2015–2022 (2009).
[CrossRef]

Chidley, M. D.

Christenson, T.

Chu, K. K.

S. Santos, K. K. Chu, D. Lim, N. Bozinovic, T. N. Ford, C. Hourtoule, A. C. Bartoo, S. K. Singh, and J. Mertz, “Optically sectioned fluorescence endomicroscopy with hybrid-illumination imaging through a flexible fiber bundle,” J. Biomed. Opt. 14(3), 030502 (2009).
[CrossRef]

Claudet, A. A.

W. C. Sweatt, D. D. Gill, D. P. Adams, M. J. Vasile, and A. A. Claudet, “Diamond milling of micro-optics,” IEEE Aerosp. Electron. Syst. Mag. 23(1), 13–17 (2008).
[CrossRef]

Côté, D.

P. Kim, M. Puoris’haag, D. Côté, C. P. Lin, and S. H. Yun, “In vivo confocal and multiphoton microendoscopy,” J. Biomed. Opt. 13(1), 010501 (2008).
[CrossRef]

Descour, M. R.

Dubaj, V.

V. Dubaj, A. Mazzolini, A. Wood, and M. Harris, “Optic fibre bundle contact imaging probe employing a laser scanning confocal microscope,” J. Microsc. 207(2), 108–117 (2002).
[CrossRef]

Ford, T. N.

S. Santos, K. K. Chu, D. Lim, N. Bozinovic, T. N. Ford, C. Hourtoule, A. C. Bartoo, S. K. Singh, and J. Mertz, “Optically sectioned fluorescence endomicroscopy with hybrid-illumination imaging through a flexible fiber bundle,” J. Biomed. Opt. 14(3), 030502 (2009).
[CrossRef]

Georghiou, S.

S. Georghiou, “Interaction of acridine drugs with DNA and nucleotides,” Photochem. Photobiol. 26(1), 59–68 (1977).
[CrossRef]

Gill, D. D.

W. C. Sweatt, D. D. Gill, D. P. Adams, M. J. Vasile, and A. A. Claudet, “Diamond milling of micro-optics,” IEEE Aerosp. Electron. Syst. Mag. 23(1), 13–17 (2008).
[CrossRef]

Gillenwater, A.

Gmitro, A. F.

Harris, M.

V. Dubaj, A. Mazzolini, A. Wood, and M. Harris, “Optic fibre bundle contact imaging probe employing a laser scanning confocal microscope,” J. Microsc. 207(2), 108–117 (2002).
[CrossRef]

Hasan, T.

W. Zhong, J. P. Celli, I. Rizvi, Z. Mai, B. Q. Spring, S. H. Yun, and T. Hasan, “In vivo high-resolution fluorescence microendoscopy for ovarian cancer detection and treatment monitoring,” Br. J. Cancer 101(12), 2015–2022 (2009).
[CrossRef]

Hourtoule, C.

S. Santos, K. K. Chu, D. Lim, N. Bozinovic, T. N. Ford, C. Hourtoule, A. C. Bartoo, S. K. Singh, and J. Mertz, “Optically sectioned fluorescence endomicroscopy with hybrid-illumination imaging through a flexible fiber bundle,” J. Biomed. Opt. 14(3), 030502 (2009).
[CrossRef]

Kano, A.

Kester, R. T.

Kim, P.

P. Kim, M. Puoris’haag, D. Côté, C. P. Lin, and S. H. Yun, “In vivo confocal and multiphoton microendoscopy,” J. Biomed. Opt. 13(1), 010501 (2008).
[CrossRef]

Kroto, S. M.

Liang, C.

Lim, D.

S. Santos, K. K. Chu, D. Lim, N. Bozinovic, T. N. Ford, C. Hourtoule, A. C. Bartoo, S. K. Singh, and J. Mertz, “Optically sectioned fluorescence endomicroscopy with hybrid-illumination imaging through a flexible fiber bundle,” J. Biomed. Opt. 14(3), 030502 (2009).
[CrossRef]

Lin, C. P.

P. Kim, M. Puoris’haag, D. Côté, C. P. Lin, and S. H. Yun, “In vivo confocal and multiphoton microendoscopy,” J. Biomed. Opt. 13(1), 010501 (2008).
[CrossRef]

Mai, Z.

W. Zhong, J. P. Celli, I. Rizvi, Z. Mai, B. Q. Spring, S. H. Yun, and T. Hasan, “In vivo high-resolution fluorescence microendoscopy for ovarian cancer detection and treatment monitoring,” Br. J. Cancer 101(12), 2015–2022 (2009).
[CrossRef]

Mazzolini, A.

V. Dubaj, A. Mazzolini, A. Wood, and M. Harris, “Optic fibre bundle contact imaging probe employing a laser scanning confocal microscope,” J. Microsc. 207(2), 108–117 (2002).
[CrossRef]

Mertz, J.

S. Santos, K. K. Chu, D. Lim, N. Bozinovic, T. N. Ford, C. Hourtoule, A. C. Bartoo, S. K. Singh, and J. Mertz, “Optically sectioned fluorescence endomicroscopy with hybrid-illumination imaging through a flexible fiber bundle,” J. Biomed. Opt. 14(3), 030502 (2009).
[CrossRef]

Mooney, J. M.

A. P. Tzannes and J. M. Mooney, “Measurement of the modulation transfer-function of infrared cameras,” Opt. Eng. 34(6), 1808–1817 (1995).
[CrossRef]

Muldoon, T. J.

Nida, D. L.

Pierce, M. C.

Puoris’haag, M.

P. Kim, M. Puoris’haag, D. Côté, C. P. Lin, and S. H. Yun, “In vivo confocal and multiphoton microendoscopy,” J. Biomed. Opt. 13(1), 010501 (2008).
[CrossRef]

Richards-Kortum, R.

Richards-Kortum, R. R.

Rizvi, I.

W. Zhong, J. P. Celli, I. Rizvi, Z. Mai, B. Q. Spring, S. H. Yun, and T. Hasan, “In vivo high-resolution fluorescence microendoscopy for ovarian cancer detection and treatment monitoring,” Br. J. Cancer 101(12), 2015–2022 (2009).
[CrossRef]

Rouse, A. R.

Santos, S.

S. Santos, K. K. Chu, D. Lim, N. Bozinovic, T. N. Ford, C. Hourtoule, A. C. Bartoo, S. K. Singh, and J. Mertz, “Optically sectioned fluorescence endomicroscopy with hybrid-illumination imaging through a flexible fiber bundle,” J. Biomed. Opt. 14(3), 030502 (2009).
[CrossRef]

Silverstein, M.

M. Silverstein, “Where’s the outrage?” J. Am. Coll. Surg. 208(1), 78–79 (2009).
[CrossRef]

Singh, S. K.

S. Santos, K. K. Chu, D. Lim, N. Bozinovic, T. N. Ford, C. Hourtoule, A. C. Bartoo, S. K. Singh, and J. Mertz, “Optically sectioned fluorescence endomicroscopy with hybrid-illumination imaging through a flexible fiber bundle,” J. Biomed. Opt. 14(3), 030502 (2009).
[CrossRef]

Spring, B. Q.

W. Zhong, J. P. Celli, I. Rizvi, Z. Mai, B. Q. Spring, S. H. Yun, and T. Hasan, “In vivo high-resolution fluorescence microendoscopy for ovarian cancer detection and treatment monitoring,” Br. J. Cancer 101(12), 2015–2022 (2009).
[CrossRef]

Sung, K.-B.

Sweatt, W. C.

W. C. Sweatt, D. D. Gill, D. P. Adams, M. J. Vasile, and A. A. Claudet, “Diamond milling of micro-optics,” IEEE Aerosp. Electron. Syst. Mag. 23(1), 13–17 (2008).
[CrossRef]

Tkaczyk, T. S.

Tzannes, A. P.

A. P. Tzannes and J. M. Mooney, “Measurement of the modulation transfer-function of infrared cameras,” Opt. Eng. 34(6), 1808–1817 (1995).
[CrossRef]

Udovich, J. A.

Vasile, M. J.

W. C. Sweatt, D. D. Gill, D. P. Adams, M. J. Vasile, and A. A. Claudet, “Diamond milling of micro-optics,” IEEE Aerosp. Electron. Syst. Mag. 23(1), 13–17 (2008).
[CrossRef]

Williams, M. D.

Wood, A.

V. Dubaj, A. Mazzolini, A. Wood, and M. Harris, “Optic fibre bundle contact imaging probe employing a laser scanning confocal microscope,” J. Microsc. 207(2), 108–117 (2002).
[CrossRef]

Yun, S. H.

W. Zhong, J. P. Celli, I. Rizvi, Z. Mai, B. Q. Spring, S. H. Yun, and T. Hasan, “In vivo high-resolution fluorescence microendoscopy for ovarian cancer detection and treatment monitoring,” Br. J. Cancer 101(12), 2015–2022 (2009).
[CrossRef]

P. Kim, M. Puoris’haag, D. Côté, C. P. Lin, and S. H. Yun, “In vivo confocal and multiphoton microendoscopy,” J. Biomed. Opt. 13(1), 010501 (2008).
[CrossRef]

Zhong, W.

W. Zhong, J. P. Celli, I. Rizvi, Z. Mai, B. Q. Spring, S. H. Yun, and T. Hasan, “In vivo high-resolution fluorescence microendoscopy for ovarian cancer detection and treatment monitoring,” Br. J. Cancer 101(12), 2015–2022 (2009).
[CrossRef]

Appl. Opt. (3)

Br. J. Cancer (1)

W. Zhong, J. P. Celli, I. Rizvi, Z. Mai, B. Q. Spring, S. H. Yun, and T. Hasan, “In vivo high-resolution fluorescence microendoscopy for ovarian cancer detection and treatment monitoring,” Br. J. Cancer 101(12), 2015–2022 (2009).
[CrossRef]

IEEE Aerosp. Electron. Syst. Mag. (1)

W. C. Sweatt, D. D. Gill, D. P. Adams, M. J. Vasile, and A. A. Claudet, “Diamond milling of micro-optics,” IEEE Aerosp. Electron. Syst. Mag. 23(1), 13–17 (2008).
[CrossRef]

J. Am. Coll. Surg. (1)

M. Silverstein, “Where’s the outrage?” J. Am. Coll. Surg. 208(1), 78–79 (2009).
[CrossRef]

J. Biomed. Opt. (2)

S. Santos, K. K. Chu, D. Lim, N. Bozinovic, T. N. Ford, C. Hourtoule, A. C. Bartoo, S. K. Singh, and J. Mertz, “Optically sectioned fluorescence endomicroscopy with hybrid-illumination imaging through a flexible fiber bundle,” J. Biomed. Opt. 14(3), 030502 (2009).
[CrossRef]

P. Kim, M. Puoris’haag, D. Côté, C. P. Lin, and S. H. Yun, “In vivo confocal and multiphoton microendoscopy,” J. Biomed. Opt. 13(1), 010501 (2008).
[CrossRef]

J. Microsc. (1)

V. Dubaj, A. Mazzolini, A. Wood, and M. Harris, “Optic fibre bundle contact imaging probe employing a laser scanning confocal microscope,” J. Microsc. 207(2), 108–117 (2002).
[CrossRef]

Opt. Eng. (1)

A. P. Tzannes and J. M. Mooney, “Measurement of the modulation transfer-function of infrared cameras,” Opt. Eng. 34(6), 1808–1817 (1995).
[CrossRef]

Opt. Express (2)

Opt. Lett. (1)

Photochem. Photobiol. (1)

S. Georghiou, “Interaction of acridine drugs with DNA and nucleotides,” Photochem. Photobiol. 26(1), 59–68 (1977).
[CrossRef]

Other (13)

“Normal anatomy of the breast,” Yale University School of Medicine, http://www.med.yale.edu/intmed/cardio/imaging/anatomy/breast_anatomy/index.html.

J. D. Gaskill, Linear Systems, Fourier Transforms, and Optics (John Wiley and Sons, 1978).

E. Hecht, Optics, Fourth Edition (Addison Wesley, 2002).

R. T. Kester, T. Christenson, R. Richards-Kortum, and T. Tkaczyk, “High Performance Self Aligning Miniature Optical Systems for in vivo Diagnostics,” (Optical Society of America, 2008)

B. Saleh, and M. Teich, Fundamentals of Photonics (Wiley-Interscience, 1991).

ISO 12233:2000(E), Photography - electronic still picture cameras - Resolution measurements (2000).

ZEMAX Development Corporation, Bellevue, WA 98004–8017, http://www.zemax.com/.

L. P. Zeon Chemicals, Louisville, KY 40211, http://www.zeonchemicals.com/

R. R. Shannon, The Art and Science of Optical Design (Cambridge University Press, 1997).

D. Toomre, and J. B. Pawley, “Disk-scanning confocal microscopy,” in Handbook of biological confocal microscopy, J. B. Pawley, ed., (Springer, New York, 2006), pp. 28, 985 p.

R. Richards-Kortum, Department of Bioengineering, Rice University, MS 142, 6100 Main St., Houston, TX, 77005, USA (personal communication, 2010).

PENTAX Medical Company, Montvale, NJ 07645, http://www.pentaxmedical.com/brochures/Confocal.pdf.

Optiscan Pty. Ltd., Victoria, Australia, 3168 http://www.optiscan.com/Products/FIVE1_Brochure.pdf.

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