Abstract

We present a portable, multimodal, nonlinear endo-microscopy probe designed for intraoperative oncological imaging. Application of a four-wave mixing noise suppression scheme using dual wavelength wave plates (DWW) and a polarization-maintaining fiber improves tissue signal collection efficiency, allowing for miniaturization. The probe, with a small 14 mm transversal diameter, includes a customized miniaturized two-axis MEMS (micro-electromechanical system) raster scanning mirror and micro-optics with an illumination laser delivered by a polarization-maintaining fiber. The probe can potentially be integrated into the arms of a surgical robot, such as da Vinci robotic surgery system, due to its minimal cross sectional area. It has the ability to incorporate multiple imaging modalities including CARS (coherent anti-Stokes Raman scattering), SHG (second harmonic generation), and TPEF (two-photon excited fluorescence) in order to allow the surgeon to locate tumor cells within the context of normal stromal tissue. The resolution of the endo-microscope is experimentally determined to be 0.78 µm, a high level of accuracy for such a compact probe setup. The expected resolution of the as-built multimodal, nonlinear, endo-microscopy probe is 1 µm based on the calculation tolerance allocation using Monte-Carlo simulation. The reported probe is intended for use in laparoscopic or radical prostatectomy, including detection of tumor margins and avoidance of nerve impairment during surgery.

© 2015 Optical Society of America

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References

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2014 (5)

D. Niemeier, H. Gombachika, and R. Richards-Kortum, “How to transform the practice of engineering to meet global health needs,” Science 345(6202), 1287–1290 (2014).
[Crossref] [PubMed]

C. W. Freudiger, W. Yang, G. R. Holtom, N. Peyghambarian, X. S. Xie, and K. Q. Kieu, “Stimulated Raman scattering microscopy with a robust fibre laser source,” Nat. Photonics 8(2), 153–159 (2014).
[Crossref] [PubMed]

R. Siegel, J. Ma, Z. Zou, and A. Jemal, “Cancer statistics, 2014,” CA Cancer J. Clin. 64(1), 9–29 (2014).
[Crossref] [PubMed]

C. Di Napoli, I. Pope, F. Masia, P. Watson, W. Langbein, and P. Borri, “Hyperspectral and differential CARS microscopy for quantitative chemical imaging in human adipocytes,” Biomed. Opt. Express 5(5), 1378–1390 (2014).
[Crossref] [PubMed]

V. Sharma, E. O. Olweny, P. Kapur, J. A. Cadeddu, C. G. Roehrborn, and H. Liu, “Prostate cancer detection using combined auto-fluorescence and light reflectance spectroscopy: ex vivo study of human prostates,” Biomed. Opt. Express 5(5), 1512–1529 (2014).
[Crossref] [PubMed]

2013 (8)

B. Smith, M. Naji, S. Murugkar, E. Alarcon, C. Brideau, P. Stys, and H. Anis, “Portable, miniaturized, fibre delivered, multimodal CARS exoscope,” Opt. Express 21(14), 17161–17175 (2013).
[Crossref] [PubMed]

D. G. Ouzounov, D. R. Rivera, W. O. Williams, J. A. Stupinski, T. L. Southard, K. H. Hume, J. Bentley, R. S. Weiss, W. W. Webb, and C. Xu, “Dual modality endomicroscope with optical zoom capability,” Biomed. Opt. Express 4(9), 1494–1503 (2013).
[Crossref] [PubMed]

X. Xu, J. Cheng, M. J. Thrall, Z. Liu, X. Wang, and S. T. C. Wong, “Multimodal non-linear optical imaging for label-free differentiation of lung cancerous lesions from normal and desmoplastic tissues,” Biomed. Opt. Express 4(12), 2855–2868 (2013).
[Crossref] [PubMed]

I. I. Patel, C. Steuwe, S. Reichelt, and S. Mahajan, “Coherent anti-Stokes Raman scattering for label-free biomedical imaging,” J. Opt. 15(9), 094006 (2013).
[Crossref]

J. H. Lee, J. C. Kim, G. Tae, M.-K. Oh, and D.-K. Ko, “Rapid diagnosis of liver fibrosis using multimodal multiphoton nonlinear optical microspectroscopy imaging,” J. Biomed. Opt. 18(7), 076009 (2013).
[Crossref] [PubMed]

R. Richards-Kortum and M. Oden, “Engineering. Devices for Low-Resource Health Care,” Science 342(6162), 1055–1057 (2013).
[Crossref] [PubMed]

C. Robertson, A. Close, C. Fraser, T. Gurung, X. Jia, P. Sharma, L. Vale, C. Ramsay, and R. Pickard, “Relative effectiveness of robot-assisted and standard laparoscopic prostatectomy as alternatives to open radical prostatectomy for treatment of localised prostate cancer: a systematic review and mixed treatment comparison meta-analysis,” BJU Int. 112(6), 798–812 (2013).
[Crossref] [PubMed]

N. P. Ghimire, H. C. Bao, and M. Gu, “Broadband excitation and collection in fiber-optic nonlinear endomicroscopy,” Appl. Phys. Lett. 103(7), 073703 (2013).
[Crossref]

2012 (5)

2011 (6)

L. Gao, H. Zhou, M. J. Thrall, F. Li, Y. Yang, Z. Wang, P. Luo, K. K. Wong, G. S. Palapattu, and S. T. C. Wong, “Label-free high-resolution imaging of prostate glands and cavernous nerves using coherent anti-Stokes Raman scattering microscopy,” Biomed. Opt. Express 2(4), 915–926 (2011).
[Crossref] [PubMed]

Z. Wang, L. Gao, P. Luo, Y. Yang, A. A. Hammoudi, K. K. Wong, and S. T. C. Wong, “Coherent anti-Stokes Raman scattering microscopy imaging with suppression of four-wave mixing in optical fibers,” Opt. Express 19(9), 7960–7970 (2011).
[PubMed]

B. G. Saar, R. S. Johnston, C. W. Freudiger, X. S. Xie, and E. J. Seibel, “Coherent Raman scanning fiber endoscopy,” Opt. Lett. 36(13), 2396–2398 (2011).
[Crossref] [PubMed]

L. Gao, F. Li, M. J. Thrall, Y. Yang, J. Xing, A. A. Hammoudi, H. Zhao, Y. Massoud, P. T. Cagle, Y. Fan, K. K. Wong, Z. Wang, and S. T. C. Wong, “On-the-spot lung cancer differential diagnosis by label-free, molecular vibrational imaging and knowledge-based classification,” J. Biomed. Opt. 16(9), 096004 (2011).
[Crossref] [PubMed]

D. R. Rivera, C. M. Brown, D. G. Ouzounov, I. Pavlova, D. Kobat, W. W. Webb, and C. Xu, “Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue,” Proc. Natl. Acad. Sci. U.S.A. 108(43), 17598–17603 (2011).
[Crossref] [PubMed]

J. Chen, S. Zhuo, X. Jiang, X. Zhu, L. Zheng, S. Xie, B. Lin, and H. Zeng, “Multiphoton microscopy study of the morphological and quantity changes of collagen and elastic fiber components in keloid disease,” J. Biomed. Opt. 16(5), 051305 (2011).
[Crossref] [PubMed]

2010 (2)

2009 (4)

T. T. Le, T. B. Huff, and J. X. Cheng, “Coherent anti-Stokes Raman scattering imaging of lipids in cancer metastasis,” BMC Cancer 9(1), 42 (2009).
[Crossref] [PubMed]

O. Yossepowitch, A. Bjartell, J. A. Eastham, M. Graefen, B. D. Guillonneau, P. I. Karakiewicz, R. Montironi, and F. Montorsi, “Positive surgical margins in radical prostatectomy: outlining the problem and its long-term consequences,” Eur. Urol. 55(1), 87–99 (2009).
[Crossref] [PubMed]

Y. Wu, J. Xi, M. J. Cobb, and X. Li, “Scanning fiber-optic nonlinear endomicroscopy with miniature aspherical compound lens and multimode fiber collector,” Opt. Lett. 34(7), 953–955 (2009).
[Crossref] [PubMed]

Y. Wu, Y. Leng, J. Xi, and X. Li, “Scanning all-fiber-optic endomicroscopy system for 3D nonlinear optical imaging of biological tissues,” Opt. Express 17(10), 7907–7915 (2009).
[Crossref] [PubMed]

2008 (2)

2007 (3)

2006 (2)

2005 (1)

A. R. McCullough, “Sexual Dysfunction after Radical Prostatectomy,” Rev. Urol. 7(2), S3–S10 (2005).
[PubMed]

2004 (1)

J. X. Cheng and X. S. Xie, “Coherent anti-Stokes Raman scattering microscopy: instrumentation, theory, and applications,” J. Phys. Chem. B 108(3), 827–840 (2004).
[Crossref]

2003 (1)

X. Nan, J. X. Cheng, and X. S. Xie, “Vibrational imaging of lipid droplets in live fibroblast cells with coherent anti-Stokes Raman scattering microscopy,” J. Lipid Res. 44(11), 2202–2208 (2003).
[Crossref] [PubMed]

1998 (1)

J. A. Wieder and M. S. Soloway, “Incidence, etiology, location, prevention and treatment of positive surgical margins after radical prostatectomy for prostate cancer,” J. Urol. 160(2), 299–315 (1998).
[Crossref] [PubMed]

1995 (1)

F. Di Silverio, G. D’Eramo, M. Buscarini, P. Casale, S. Di Nicola, D. Colella, and A. Sciarra, “Is there always a role for radical prostatectomy in the treatment of localized prostate cancer?” Minerva Urol. Nefrol. 47(3), 117–124 (1995).
[PubMed]

1980 (1)

S. Roth and I. Freund, “Second harmonic-generation in collagen,” J. Chem. Phys. 73(7), 3521 (1980).
[Crossref]

Ahn, Y. C.

Ahn, Y.-C.

Akins, M. L.

Y. Zhang, M. L. Akins, K. Murari, J. F. Xi, M.-J. Li, K. Luby-Phelps, M. Mahendroo, and X. D. Li, “A compact fiber-optic SHG scanning endomicroscope and its application to visualize cervical remodeling during pregnancy,” Proceedings of the National Academy of Sciences109(32):12878–12883 (2012).
[Crossref]

Alarcon, E.

Allen, J.

Anis, H.

Bao, H.

Bao, H. C.

N. P. Ghimire, H. C. Bao, and M. Gu, “Broadband excitation and collection in fiber-optic nonlinear endomicroscopy,” Appl. Phys. Lett. 103(7), 073703 (2013).
[Crossref]

Bentley, J.

Bjartell, A.

O. Yossepowitch, A. Bjartell, J. A. Eastham, M. Graefen, B. D. Guillonneau, P. I. Karakiewicz, R. Montironi, and F. Montorsi, “Positive surgical margins in radical prostatectomy: outlining the problem and its long-term consequences,” Eur. Urol. 55(1), 87–99 (2009).
[Crossref] [PubMed]

Borri, P.

Brenner, M.

Brideau, C.

Brown, C. M.

D. R. Rivera, C. M. Brown, D. G. Ouzounov, W. W. Webb, and C. Xu, “Use of a lensed fiber for a large-field-of-view, high-resolution, fiber-scanning microendoscope,” Opt. Lett. 37(5), 881–883 (2012).
[Crossref] [PubMed]

D. R. Rivera, C. M. Brown, D. G. Ouzounov, I. Pavlova, D. Kobat, W. W. Webb, and C. Xu, “Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue,” Proc. Natl. Acad. Sci. U.S.A. 108(43), 17598–17603 (2011).
[Crossref] [PubMed]

Buscarini, M.

F. Di Silverio, G. D’Eramo, M. Buscarini, P. Casale, S. Di Nicola, D. Colella, and A. Sciarra, “Is there always a role for radical prostatectomy in the treatment of localized prostate cancer?” Minerva Urol. Nefrol. 47(3), 117–124 (1995).
[PubMed]

Cadeddu, J. A.

Cagle, P. T.

L. Gao, F. Li, M. J. Thrall, Y. Yang, J. Xing, A. A. Hammoudi, H. Zhao, Y. Massoud, P. T. Cagle, Y. Fan, K. K. Wong, Z. Wang, and S. T. C. Wong, “On-the-spot lung cancer differential diagnosis by label-free, molecular vibrational imaging and knowledge-based classification,” J. Biomed. Opt. 16(9), 096004 (2011).
[Crossref] [PubMed]

Casale, P.

F. Di Silverio, G. D’Eramo, M. Buscarini, P. Casale, S. Di Nicola, D. Colella, and A. Sciarra, “Is there always a role for radical prostatectomy in the treatment of localized prostate cancer?” Minerva Urol. Nefrol. 47(3), 117–124 (1995).
[PubMed]

Chen, J.

J. Chen, S. Zhuo, X. Jiang, X. Zhu, L. Zheng, S. Xie, B. Lin, and H. Zeng, “Multiphoton microscopy study of the morphological and quantity changes of collagen and elastic fiber components in keloid disease,” J. Biomed. Opt. 16(5), 051305 (2011).
[Crossref] [PubMed]

Chen, Y.

Chen, Z.

Cheng, J.

Cheng, J. X.

T. T. Le, S. Yue, and J. X. Cheng, “Shedding new light on lipid biology with coherent anti-Stokes Raman scattering microscopy,” J. Lipid Res. 51(11), 3091–3102 (2010).
[Crossref] [PubMed]

T. T. Le, T. B. Huff, and J. X. Cheng, “Coherent anti-Stokes Raman scattering imaging of lipids in cancer metastasis,” BMC Cancer 9(1), 42 (2009).
[Crossref] [PubMed]

J. X. Cheng and X. S. Xie, “Coherent anti-Stokes Raman scattering microscopy: instrumentation, theory, and applications,” J. Phys. Chem. B 108(3), 827–840 (2004).
[Crossref]

X. Nan, J. X. Cheng, and X. S. Xie, “Vibrational imaging of lipid droplets in live fibroblast cells with coherent anti-Stokes Raman scattering microscopy,” J. Lipid Res. 44(11), 2202–2208 (2003).
[Crossref] [PubMed]

Close, A.

C. Robertson, A. Close, C. Fraser, T. Gurung, X. Jia, P. Sharma, L. Vale, C. Ramsay, and R. Pickard, “Relative effectiveness of robot-assisted and standard laparoscopic prostatectomy as alternatives to open radical prostatectomy for treatment of localised prostate cancer: a systematic review and mixed treatment comparison meta-analysis,” BJU Int. 112(6), 798–812 (2013).
[Crossref] [PubMed]

Cobb, M. J.

Colella, D.

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J. Xi, Y. Chen, Y. Zhang, K. Murari, M.-J. Li, and X. Li, “Integrated multimodal endomicroscopy platform for simultaneous en face optical coherence and two-photon fluorescence imaging,” Opt. Lett. 37(3), 362–364 (2012).
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J. H. Lee, J. C. Kim, G. Tae, M.-K. Oh, and D.-K. Ko, “Rapid diagnosis of liver fibrosis using multimodal multiphoton nonlinear optical microspectroscopy imaging,” J. Biomed. Opt. 18(7), 076009 (2013).
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C. W. Freudiger, W. Yang, G. R. Holtom, N. Peyghambarian, X. S. Xie, and K. Q. Kieu, “Stimulated Raman scattering microscopy with a robust fibre laser source,” Nat. Photonics 8(2), 153–159 (2014).
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C. Robertson, A. Close, C. Fraser, T. Gurung, X. Jia, P. Sharma, L. Vale, C. Ramsay, and R. Pickard, “Relative effectiveness of robot-assisted and standard laparoscopic prostatectomy as alternatives to open radical prostatectomy for treatment of localised prostate cancer: a systematic review and mixed treatment comparison meta-analysis,” BJU Int. 112(6), 798–812 (2013).
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I. I. Patel, C. Steuwe, S. Reichelt, and S. Mahajan, “Coherent anti-Stokes Raman scattering for label-free biomedical imaging,” J. Opt. 15(9), 094006 (2013).
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Y. Zhang, M. L. Akins, K. Murari, J. F. Xi, M.-J. Li, K. Luby-Phelps, M. Mahendroo, and X. D. Li, “A compact fiber-optic SHG scanning endomicroscope and its application to visualize cervical remodeling during pregnancy,” Proceedings of the National Academy of Sciences109(32):12878–12883 (2012).
[Crossref]

Xie, H.

Xie, S.

J. Chen, S. Zhuo, X. Jiang, X. Zhu, L. Zheng, S. Xie, B. Lin, and H. Zeng, “Multiphoton microscopy study of the morphological and quantity changes of collagen and elastic fiber components in keloid disease,” J. Biomed. Opt. 16(5), 051305 (2011).
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Xie, T.

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C. W. Freudiger, W. Yang, G. R. Holtom, N. Peyghambarian, X. S. Xie, and K. Q. Kieu, “Stimulated Raman scattering microscopy with a robust fibre laser source,” Nat. Photonics 8(2), 153–159 (2014).
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B. G. Saar, R. S. Johnston, C. W. Freudiger, X. S. Xie, and E. J. Seibel, “Coherent Raman scanning fiber endoscopy,” Opt. Lett. 36(13), 2396–2398 (2011).
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J. X. Cheng and X. S. Xie, “Coherent anti-Stokes Raman scattering microscopy: instrumentation, theory, and applications,” J. Phys. Chem. B 108(3), 827–840 (2004).
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X. Nan, J. X. Cheng, and X. S. Xie, “Vibrational imaging of lipid droplets in live fibroblast cells with coherent anti-Stokes Raman scattering microscopy,” J. Lipid Res. 44(11), 2202–2208 (2003).
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C. W. Freudiger, W. Yang, G. R. Holtom, N. Peyghambarian, X. S. Xie, and K. Q. Kieu, “Stimulated Raman scattering microscopy with a robust fibre laser source,” Nat. Photonics 8(2), 153–159 (2014).
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O. Yossepowitch, A. Bjartell, J. A. Eastham, M. Graefen, B. D. Guillonneau, P. I. Karakiewicz, R. Montironi, and F. Montorsi, “Positive surgical margins in radical prostatectomy: outlining the problem and its long-term consequences,” Eur. Urol. 55(1), 87–99 (2009).
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T. T. Le, S. Yue, and J. X. Cheng, “Shedding new light on lipid biology with coherent anti-Stokes Raman scattering microscopy,” J. Lipid Res. 51(11), 3091–3102 (2010).
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J. Chen, S. Zhuo, X. Jiang, X. Zhu, L. Zheng, S. Xie, B. Lin, and H. Zeng, “Multiphoton microscopy study of the morphological and quantity changes of collagen and elastic fiber components in keloid disease,” J. Biomed. Opt. 16(5), 051305 (2011).
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Zhang, Y.

J. Xi, Y. Chen, Y. Zhang, K. Murari, M.-J. Li, and X. Li, “Integrated multimodal endomicroscopy platform for simultaneous en face optical coherence and two-photon fluorescence imaging,” Opt. Lett. 37(3), 362–364 (2012).
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Y. Zhang, M. L. Akins, K. Murari, J. F. Xi, M.-J. Li, K. Luby-Phelps, M. Mahendroo, and X. D. Li, “A compact fiber-optic SHG scanning endomicroscope and its application to visualize cervical remodeling during pregnancy,” Proceedings of the National Academy of Sciences109(32):12878–12883 (2012).
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Zhao, H.

L. Gao, F. Li, M. J. Thrall, Y. Yang, J. Xing, A. A. Hammoudi, H. Zhao, Y. Massoud, P. T. Cagle, Y. Fan, K. K. Wong, Z. Wang, and S. T. C. Wong, “On-the-spot lung cancer differential diagnosis by label-free, molecular vibrational imaging and knowledge-based classification,” J. Biomed. Opt. 16(9), 096004 (2011).
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Zheng, L.

J. Chen, S. Zhuo, X. Jiang, X. Zhu, L. Zheng, S. Xie, B. Lin, and H. Zeng, “Multiphoton microscopy study of the morphological and quantity changes of collagen and elastic fiber components in keloid disease,” J. Biomed. Opt. 16(5), 051305 (2011).
[Crossref] [PubMed]

Zhou, H.

Zhu, X.

J. Chen, S. Zhuo, X. Jiang, X. Zhu, L. Zheng, S. Xie, B. Lin, and H. Zeng, “Multiphoton microscopy study of the morphological and quantity changes of collagen and elastic fiber components in keloid disease,” J. Biomed. Opt. 16(5), 051305 (2011).
[Crossref] [PubMed]

Zhuo, S.

J. Chen, S. Zhuo, X. Jiang, X. Zhu, L. Zheng, S. Xie, B. Lin, and H. Zeng, “Multiphoton microscopy study of the morphological and quantity changes of collagen and elastic fiber components in keloid disease,” J. Biomed. Opt. 16(5), 051305 (2011).
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Appl. Phys. Lett. (1)

N. P. Ghimire, H. C. Bao, and M. Gu, “Broadband excitation and collection in fiber-optic nonlinear endomicroscopy,” Appl. Phys. Lett. 103(7), 073703 (2013).
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Biomed. Opt. Express (5)

BJU Int. (1)

C. Robertson, A. Close, C. Fraser, T. Gurung, X. Jia, P. Sharma, L. Vale, C. Ramsay, and R. Pickard, “Relative effectiveness of robot-assisted and standard laparoscopic prostatectomy as alternatives to open radical prostatectomy for treatment of localised prostate cancer: a systematic review and mixed treatment comparison meta-analysis,” BJU Int. 112(6), 798–812 (2013).
[Crossref] [PubMed]

BMC Cancer (1)

T. T. Le, T. B. Huff, and J. X. Cheng, “Coherent anti-Stokes Raman scattering imaging of lipids in cancer metastasis,” BMC Cancer 9(1), 42 (2009).
[Crossref] [PubMed]

CA Cancer J. Clin. (1)

R. Siegel, J. Ma, Z. Zou, and A. Jemal, “Cancer statistics, 2014,” CA Cancer J. Clin. 64(1), 9–29 (2014).
[Crossref] [PubMed]

Eur. Urol. (1)

O. Yossepowitch, A. Bjartell, J. A. Eastham, M. Graefen, B. D. Guillonneau, P. I. Karakiewicz, R. Montironi, and F. Montorsi, “Positive surgical margins in radical prostatectomy: outlining the problem and its long-term consequences,” Eur. Urol. 55(1), 87–99 (2009).
[Crossref] [PubMed]

Head Neck (1)

T. J. Muldoon, D. Roblyer, M. D. Williams, V. M. Stepanek, R. Richards-Kortum, and A. M. Gillenwater, “Noninvasive imaging of oral neoplasia with a high-resolution fiber-optic microendoscope,” Head Neck 34(3), 305–312 (2012).
[Crossref] [PubMed]

J. Biomed. Opt. (5)

S. J. Miller, C. M. Lee, B. P. Joshi, A. Gaustad, E. J. Seibel, and T. D. Wang, “Targeted detection of murine colonic dysplasia in vivo with flexible multispectral scanning fiber endoscopy,” J. Biomed. Opt. 17(2), 021103 (2012).
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L. Fu, A. Jain, C. Cranfield, H. Xie, and M. Gu, “Three-dimensional nonlinear optical endoscopy,” J. Biomed. Opt. 12(4), 040501 (2007).
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J. H. Lee, J. C. Kim, G. Tae, M.-K. Oh, and D.-K. Ko, “Rapid diagnosis of liver fibrosis using multimodal multiphoton nonlinear optical microspectroscopy imaging,” J. Biomed. Opt. 18(7), 076009 (2013).
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J. Chen, S. Zhuo, X. Jiang, X. Zhu, L. Zheng, S. Xie, B. Lin, and H. Zeng, “Multiphoton microscopy study of the morphological and quantity changes of collagen and elastic fiber components in keloid disease,” J. Biomed. Opt. 16(5), 051305 (2011).
[Crossref] [PubMed]

L. Gao, F. Li, M. J. Thrall, Y. Yang, J. Xing, A. A. Hammoudi, H. Zhao, Y. Massoud, P. T. Cagle, Y. Fan, K. K. Wong, Z. Wang, and S. T. C. Wong, “On-the-spot lung cancer differential diagnosis by label-free, molecular vibrational imaging and knowledge-based classification,” J. Biomed. Opt. 16(9), 096004 (2011).
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J. Chem. Phys. (1)

S. Roth and I. Freund, “Second harmonic-generation in collagen,” J. Chem. Phys. 73(7), 3521 (1980).
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T. T. Le, S. Yue, and J. X. Cheng, “Shedding new light on lipid biology with coherent anti-Stokes Raman scattering microscopy,” J. Lipid Res. 51(11), 3091–3102 (2010).
[Crossref] [PubMed]

X. Nan, J. X. Cheng, and X. S. Xie, “Vibrational imaging of lipid droplets in live fibroblast cells with coherent anti-Stokes Raman scattering microscopy,” J. Lipid Res. 44(11), 2202–2208 (2003).
[Crossref] [PubMed]

J. Opt. (1)

I. I. Patel, C. Steuwe, S. Reichelt, and S. Mahajan, “Coherent anti-Stokes Raman scattering for label-free biomedical imaging,” J. Opt. 15(9), 094006 (2013).
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J. Phys. Chem. B (1)

J. X. Cheng and X. S. Xie, “Coherent anti-Stokes Raman scattering microscopy: instrumentation, theory, and applications,” J. Phys. Chem. B 108(3), 827–840 (2004).
[Crossref]

J. Urol. (1)

J. A. Wieder and M. S. Soloway, “Incidence, etiology, location, prevention and treatment of positive surgical margins after radical prostatectomy for prostate cancer,” J. Urol. 160(2), 299–315 (1998).
[Crossref] [PubMed]

Minerva Urol. Nefrol. (1)

F. Di Silverio, G. D’Eramo, M. Buscarini, P. Casale, S. Di Nicola, D. Colella, and A. Sciarra, “Is there always a role for radical prostatectomy in the treatment of localized prostate cancer?” Minerva Urol. Nefrol. 47(3), 117–124 (1995).
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Nat. Photonics (1)

C. W. Freudiger, W. Yang, G. R. Holtom, N. Peyghambarian, X. S. Xie, and K. Q. Kieu, “Stimulated Raman scattering microscopy with a robust fibre laser source,” Nat. Photonics 8(2), 153–159 (2014).
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Opt. Express (6)

Opt. Lett. (9)

M. T. Myaing, D. J. MacDonald, and X. Li, “Fiber-optic scanning two-photon fluorescence endoscope,” Opt. Lett. 31(8), 1076–1078 (2006).
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J. Xi, Y. Chen, Y. Zhang, K. Murari, M.-J. Li, and X. Li, “Integrated multimodal endomicroscopy platform for simultaneous en face optical coherence and two-photon fluorescence imaging,” Opt. Lett. 37(3), 362–364 (2012).
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D. R. Rivera, C. M. Brown, D. G. Ouzounov, W. W. Webb, and C. Xu, “Use of a lensed fiber for a large-field-of-view, high-resolution, fiber-scanning microendoscope,” Opt. Lett. 37(5), 881–883 (2012).
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H. Bao, J. Allen, R. Pattie, R. Vance, and M. Gu, “Fast handheld two-photon fluorescence microendoscope with a 475 µm x 475 µm field of view for in vivo imaging,” Opt. Lett. 33(12), 1333–1335 (2008).
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B. G. Saar, R. S. Johnston, C. W. Freudiger, X. S. Xie, and E. J. Seibel, “Coherent Raman scanning fiber endoscopy,” Opt. Lett. 36(13), 2396–2398 (2011).
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Proc. Natl. Acad. Sci. U.S.A. (1)

D. R. Rivera, C. M. Brown, D. G. Ouzounov, I. Pavlova, D. Kobat, W. W. Webb, and C. Xu, “Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue,” Proc. Natl. Acad. Sci. U.S.A. 108(43), 17598–17603 (2011).
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A. R. McCullough, “Sexual Dysfunction after Radical Prostatectomy,” Rev. Urol. 7(2), S3–S10 (2005).
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Science (2)

D. Niemeier, H. Gombachika, and R. Richards-Kortum, “How to transform the practice of engineering to meet global health needs,” Science 345(6202), 1287–1290 (2014).
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R. Richards-Kortum and M. Oden, “Engineering. Devices for Low-Resource Health Care,” Science 342(6162), 1055–1057 (2013).
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Other (1)

Y. Zhang, M. L. Akins, K. Murari, J. F. Xi, M.-J. Li, K. Luby-Phelps, M. Mahendroo, and X. D. Li, “A compact fiber-optic SHG scanning endomicroscope and its application to visualize cervical remodeling during pregnancy,” Proceedings of the National Academy of Sciences109(32):12878–12883 (2012).
[Crossref]

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Figures (5)

Fig. 1
Fig. 1 The schematic optical design of the miniaturized endo-microscope of fiber-based, multimodal, nonlinear probe.
Fig. 2
Fig. 2 The optical imaging path schematic of the multimodal, nonlinear endo-microscopy probe.
Fig. 3
Fig. 3 (a) MTF performance of the as-built multimodal, nonlinear endo-microscopy probe; (b) Spot diameters (represent resolutions) at different FOVs of the multimodal nonlinear endo-microscopy probe.
Fig. 4
Fig. 4 (a). Photo shows PM1300 fiber part of the multimodal, nonlinear endo-microscopy probe; (b) Photo shows the collimator part of the multimodal, nonlinear endo-microscopy probe; (c) Photo shows the endo-microscopy part of the multimodal, nonlinear endo-microscopy probe; (d) resolution experiment setup of the endo-microscope; (e), (f), and (g) present the transmission images in 575 nm (e), 660 nm (f), and 850nm (g) from endo-microscopy imaging of USAF resolution target.
Fig. 5
Fig. 5 CARS and SHG images of prostate epithelial cells obtained using an upright microscope. (a) CARS image. Yellow arrow points to a cell nucleus. (b) SHG image of the same region of the prostate cancer tissue, showing a void in the fibers in the region of the epithelial cells.

Tables (2)

Tables Icon

Table 1 Basic system parameters of the multimodal nonlinear endo-microscopy probe

Tables Icon

Table 2 Tolerance budget of multimodal nonlinear endo-microscopy probe.

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