Abstract

A custom built coherent anti-Stokes Raman scattering (CARS) microscope was used to image prostatic glands and nerve structures from 17 patients undergoing radical prostatectomy. Imaging of glandular and nerve structures showed distinctive cellular features that correlated to histological stains. Segmentation of cell nucleus was performed to establish a cell feature-based model to separate normal glands from cancer glands. In this study, we use a single parameter, average cell neighbor distance based on CARS imaging, to characterize normal and cancerous glandular structures. By combining CARS with our novel classification model, we are able to characterize prostate glandular and nerve structures in a manner that potentially enables real-time, intra-operative assessment of surgical margins and neurovascular bundles. As such, this method could potentially improve outcomes following radical prostatectomy.

© 2011 OSA

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    [CrossRef] [PubMed]

2010

L. M. Su, “Robot-assisted radical prostatectomy: advances since 2005,” Curr. Opin. Urol. 20(2), 130–135 (2010).
[CrossRef] [PubMed]

F. Li, X. Zhou, J. Ma, and S. T. Wong, “Multiple nuclei tracking using integer programming for quantitative cancer cell cycle analysis,” IEEE Trans. Med. Imaging 29(1), 96–105 (2010).
[CrossRef] [PubMed]

S. H. Parekh, Y. J. Lee, K. A. Aamer, and M. T. Cicerone, “Label-free cellular imaging by broadband coherent anti-Stokes Raman scattering microscopy,” Biophys. J. 99(8), 2695–2704 (2010).
[CrossRef] [PubMed]

M. Kirsch, G. Schackert, R. Salzer, and C. Krafft, “Raman spectroscopic imaging for in vivo detection of cerebral brain metastases,” Anal. Bioanal. Chem. 398(4), 1707–1713 (2010).
[CrossRef] [PubMed]

T. H. Van der Kwast, A. Evans, G. Lockwood, D. Tkachuk, D. G. Bostwick, J. I. Epstein, P. A. Humphrey, R. Montironi, G. J. Van Leenders, C. G. Pihl, I. Neetens, P. M. Kujala, M. Laurila, C. Mazerolles, L. Bubendorf, A. Finelli, K. Watson, and J. Srigley, “Variability in diagnostic opinion among pathologists for single small atypical foci in prostate biopsies,” Am. J. Surg. Pathol. 34(2), 169–177 (2010).
[CrossRef] [PubMed]

M. Balu, G. Liu, Z. Chen, B. J. Tromberg, and E. O. Potma, “Fiber delivered probe for efficient CARS imaging of tissues,” Opt. Express 18(3), 2380–2388 (2010).
[CrossRef] [PubMed]

Z. Wang, Y. Yang, P. Luo, L. Gao, K. K. Wong, and S. T. C. Wong, “Delivery of picosecond lasers in multimode fibers for coherent anti-Stokes Raman scattering imaging,” Opt. Express 18(12), 13017–13028 (2010).
[CrossRef] [PubMed]

2009

R. Yadav, S. Mukherjee, M. Hermen, G. Tan, F. R. Maxfield, W. W. Webb, and A. K. Tewari, “Multiphoton microscopy of prostate and periprostatic neural tissue: a promising imaging technique for improving nerve-sparing prostatectomy,” J. Endourol. 23(5), 861–867 (2009).
[CrossRef] [PubMed]

2008

S. Rais-Bahrami, A. W. Levinson, N. M. Fried, G. A. Lagoda, A. Hristov, Y. Chuang, A. L. Burnett, and L. M. Su, “Optical coherence tomography of cavernous nerves: a step toward real-time intraoperative imaging during nerve-sparing radical prostatectomy,” Urology 72(1), 198–204 (2008).
[CrossRef] [PubMed]

C. L. Evans and X. S. Xie, “Coherent anti-stokes Raman scattering microscopy: chemical imaging for biology and medicine,” Annu Rev Anal Chem (Palo Alto Calif) 1(1), 883–909 (2008).
[CrossRef] [PubMed]

E. Rodriguez, O. Melamud, and T. E. Ahlering, “Nerve-sparing techniques in open and laparoscopic prostatectomy,” Expert Rev. Anticancer Ther. 8(3), 475–479 (2008).
[CrossRef] [PubMed]

2007

M. Wang, X. Zhou, F. Li, J. Huckins, R. W. King, and S. T. C. Wong, “Novel cell segmentation and online SVM for cell cycle phase identification in automated microscopy,” Bioinformatics 24(1), 94–101 (2007).
[CrossRef] [PubMed]

L. B. Boyette, M. A. Reardon, A. J. Mirelman, T. D. Kirkley, J. J. Lysiak, J. B. Tuttle, and W. D. Steers, “Fiberoptic imaging of cavernous nerves in vivo,” J. Urol. 178(6), 2694–2700 (2007).
[CrossRef] [PubMed]

T. B. Huff and J. X. Cheng, “In vivo coherent anti-Stokes Raman scattering imaging of sciatic nerve tissue,” J. Microsc. 225(2), 175–182 (2007).
[CrossRef] [PubMed]

2006

F. Légaré, C. L. Evans, F. Ganikhanov, and X. S. Xie, “Towards CARS Endoscopy,” Opt. Express 14(10), 4427–4432 (2006).
[CrossRef] [PubMed]

A. Heidenreich, “Intraoperative frozen section analysis to monitor nerve-sparing radical prostatectomy,” Eur. Urol. 49(6), 948–949 (2006).
[CrossRef] [PubMed]

C. Eichelberg, A. Erbersdobler, A. Haese, T. Schlomm, F. K. Chun, E. Currlin, J. Walz, T. Steuber, M. Graefen, and H. Huland, “Frozen section for the management of intraoperatively detected palpable tumor lesions during nerve-sparing scheduled radical prostatectomy,” Eur. Urol. 49(6), 1011–1018 (2006).
[CrossRef] [PubMed]

C. Q. Le and M. T. Gettman, “Laparoscopic and robotic radical prostatectomy,” Expert Rev. Anticancer Ther. 6(7), 1003–1011 (2006).
[CrossRef] [PubMed]

2005

P. Gontero and R. S. Kirby, “Nerve-sparing radical retropubic prostatectomy: techniques and clinical considerations,” Prostate Cancer Prostatic Dis. 8(2), 133–139 (2005).
[CrossRef] [PubMed]

A. L. Burnett, “Erectile dysfunction following radical prostatectomy,” JAMA 293(21), 2648–2653 (2005).
[CrossRef] [PubMed]

C. L. Evans, E. O. Potma, M. Puoris’haag, D. Côté, C. P. Lin, and X. S. Xie, “Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy,” Proc. Natl. Acad. Sci. U.S.A. 102(46), 16807–16812 (2005).
[CrossRef] [PubMed]

2004

2002

R. Z. Goharderakhshan, D. Sudilovsky, L. A. Carroll, G. D. Grossfeld, R. Marn, and P. R. Carroll, “Utility of intraoperative frozen section analysis of surgical margins in region of neurovascular bundles at radical prostatectomy,” Urology 59(5), 709–714 (2002).
[CrossRef] [PubMed]

2000

G. D. Grossfeld, J. J. Chang, J. M. Broering, D. P. Miller, J. Yu, S. C. Flanders, J. M. Henning, D. M. Stier, and P. R. Carroll, “Impact of positive surgical margins on prostate cancer recurrence and the use of secondary cancer treatment: data from the CaPSURE database,” J. Urol. 163(4), 1171–1177, quiz 1295 (2000).
[CrossRef] [PubMed]

1997

D. A. Novis and R. J. Zarbo, “Interinstitutional comparison of frozen section turnaround time. A College of American Pathologists Q-Probes study of 32868 frozen sections in 700 hospitals,” Arch. Pathol. Lab. Med. 121(6), 559–567 (1997).
[PubMed]

1994

W. Gander, G. H. Golub, and R. Strebel, “Least-squares fitting of circles and ellipses,” BIT Numerical Math. 34(4), 558–578 (1994).
[CrossRef]

1991

L. Vincent and P. Soille, “Watersheds in digital spaces: an efficient algorithm based on immersion simulations,” IEEE Trans. Pattern Anal. Mach. Intell. 13(6), 583–598 (1991).
[CrossRef]

Aamer, K. A.

S. H. Parekh, Y. J. Lee, K. A. Aamer, and M. T. Cicerone, “Label-free cellular imaging by broadband coherent anti-Stokes Raman scattering microscopy,” Biophys. J. 99(8), 2695–2704 (2010).
[CrossRef] [PubMed]

Ahlering, T. E.

E. Rodriguez, O. Melamud, and T. E. Ahlering, “Nerve-sparing techniques in open and laparoscopic prostatectomy,” Expert Rev. Anticancer Ther. 8(3), 475–479 (2008).
[CrossRef] [PubMed]

Alexandersson, A.

A. Alexandersson, “Graphing confidence ellipses: An update of ellip for Stata 8,” Stata J. 4, 242–256 (2004).

Balu, M.

Bostwick, D. G.

T. H. Van der Kwast, A. Evans, G. Lockwood, D. Tkachuk, D. G. Bostwick, J. I. Epstein, P. A. Humphrey, R. Montironi, G. J. Van Leenders, C. G. Pihl, I. Neetens, P. M. Kujala, M. Laurila, C. Mazerolles, L. Bubendorf, A. Finelli, K. Watson, and J. Srigley, “Variability in diagnostic opinion among pathologists for single small atypical foci in prostate biopsies,” Am. J. Surg. Pathol. 34(2), 169–177 (2010).
[CrossRef] [PubMed]

Boyette, L. B.

L. B. Boyette, M. A. Reardon, A. J. Mirelman, T. D. Kirkley, J. J. Lysiak, J. B. Tuttle, and W. D. Steers, “Fiberoptic imaging of cavernous nerves in vivo,” J. Urol. 178(6), 2694–2700 (2007).
[CrossRef] [PubMed]

Broering, J. M.

G. D. Grossfeld, J. J. Chang, J. M. Broering, D. P. Miller, J. Yu, S. C. Flanders, J. M. Henning, D. M. Stier, and P. R. Carroll, “Impact of positive surgical margins on prostate cancer recurrence and the use of secondary cancer treatment: data from the CaPSURE database,” J. Urol. 163(4), 1171–1177, quiz 1295 (2000).
[CrossRef] [PubMed]

Bubendorf, L.

T. H. Van der Kwast, A. Evans, G. Lockwood, D. Tkachuk, D. G. Bostwick, J. I. Epstein, P. A. Humphrey, R. Montironi, G. J. Van Leenders, C. G. Pihl, I. Neetens, P. M. Kujala, M. Laurila, C. Mazerolles, L. Bubendorf, A. Finelli, K. Watson, and J. Srigley, “Variability in diagnostic opinion among pathologists for single small atypical foci in prostate biopsies,” Am. J. Surg. Pathol. 34(2), 169–177 (2010).
[CrossRef] [PubMed]

Burnett, A. L.

S. Rais-Bahrami, A. W. Levinson, N. M. Fried, G. A. Lagoda, A. Hristov, Y. Chuang, A. L. Burnett, and L. M. Su, “Optical coherence tomography of cavernous nerves: a step toward real-time intraoperative imaging during nerve-sparing radical prostatectomy,” Urology 72(1), 198–204 (2008).
[CrossRef] [PubMed]

A. L. Burnett, “Erectile dysfunction following radical prostatectomy,” JAMA 293(21), 2648–2653 (2005).
[CrossRef] [PubMed]

Carroll, L. A.

R. Z. Goharderakhshan, D. Sudilovsky, L. A. Carroll, G. D. Grossfeld, R. Marn, and P. R. Carroll, “Utility of intraoperative frozen section analysis of surgical margins in region of neurovascular bundles at radical prostatectomy,” Urology 59(5), 709–714 (2002).
[CrossRef] [PubMed]

Carroll, P. R.

R. Z. Goharderakhshan, D. Sudilovsky, L. A. Carroll, G. D. Grossfeld, R. Marn, and P. R. Carroll, “Utility of intraoperative frozen section analysis of surgical margins in region of neurovascular bundles at radical prostatectomy,” Urology 59(5), 709–714 (2002).
[CrossRef] [PubMed]

G. D. Grossfeld, J. J. Chang, J. M. Broering, D. P. Miller, J. Yu, S. C. Flanders, J. M. Henning, D. M. Stier, and P. R. Carroll, “Impact of positive surgical margins on prostate cancer recurrence and the use of secondary cancer treatment: data from the CaPSURE database,” J. Urol. 163(4), 1171–1177, quiz 1295 (2000).
[CrossRef] [PubMed]

Chang, J. J.

G. D. Grossfeld, J. J. Chang, J. M. Broering, D. P. Miller, J. Yu, S. C. Flanders, J. M. Henning, D. M. Stier, and P. R. Carroll, “Impact of positive surgical margins on prostate cancer recurrence and the use of secondary cancer treatment: data from the CaPSURE database,” J. Urol. 163(4), 1171–1177, quiz 1295 (2000).
[CrossRef] [PubMed]

Chen, Z.

Cheng, J. X.

T. B. Huff and J. X. Cheng, “In vivo coherent anti-Stokes Raman scattering imaging of sciatic nerve tissue,” J. Microsc. 225(2), 175–182 (2007).
[CrossRef] [PubMed]

Chuang, Y.

S. Rais-Bahrami, A. W. Levinson, N. M. Fried, G. A. Lagoda, A. Hristov, Y. Chuang, A. L. Burnett, and L. M. Su, “Optical coherence tomography of cavernous nerves: a step toward real-time intraoperative imaging during nerve-sparing radical prostatectomy,” Urology 72(1), 198–204 (2008).
[CrossRef] [PubMed]

Chun, F. K.

C. Eichelberg, A. Erbersdobler, A. Haese, T. Schlomm, F. K. Chun, E. Currlin, J. Walz, T. Steuber, M. Graefen, and H. Huland, “Frozen section for the management of intraoperatively detected palpable tumor lesions during nerve-sparing scheduled radical prostatectomy,” Eur. Urol. 49(6), 1011–1018 (2006).
[CrossRef] [PubMed]

Cicerone, M. T.

S. H. Parekh, Y. J. Lee, K. A. Aamer, and M. T. Cicerone, “Label-free cellular imaging by broadband coherent anti-Stokes Raman scattering microscopy,” Biophys. J. 99(8), 2695–2704 (2010).
[CrossRef] [PubMed]

Côté, D.

C. L. Evans, E. O. Potma, M. Puoris’haag, D. Côté, C. P. Lin, and X. S. Xie, “Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy,” Proc. Natl. Acad. Sci. U.S.A. 102(46), 16807–16812 (2005).
[CrossRef] [PubMed]

Currlin, E.

C. Eichelberg, A. Erbersdobler, A. Haese, T. Schlomm, F. K. Chun, E. Currlin, J. Walz, T. Steuber, M. Graefen, and H. Huland, “Frozen section for the management of intraoperatively detected palpable tumor lesions during nerve-sparing scheduled radical prostatectomy,” Eur. Urol. 49(6), 1011–1018 (2006).
[CrossRef] [PubMed]

Eichelberg, C.

C. Eichelberg, A. Erbersdobler, A. Haese, T. Schlomm, F. K. Chun, E. Currlin, J. Walz, T. Steuber, M. Graefen, and H. Huland, “Frozen section for the management of intraoperatively detected palpable tumor lesions during nerve-sparing scheduled radical prostatectomy,” Eur. Urol. 49(6), 1011–1018 (2006).
[CrossRef] [PubMed]

Epstein, J. I.

T. H. Van der Kwast, A. Evans, G. Lockwood, D. Tkachuk, D. G. Bostwick, J. I. Epstein, P. A. Humphrey, R. Montironi, G. J. Van Leenders, C. G. Pihl, I. Neetens, P. M. Kujala, M. Laurila, C. Mazerolles, L. Bubendorf, A. Finelli, K. Watson, and J. Srigley, “Variability in diagnostic opinion among pathologists for single small atypical foci in prostate biopsies,” Am. J. Surg. Pathol. 34(2), 169–177 (2010).
[CrossRef] [PubMed]

Erbersdobler, A.

C. Eichelberg, A. Erbersdobler, A. Haese, T. Schlomm, F. K. Chun, E. Currlin, J. Walz, T. Steuber, M. Graefen, and H. Huland, “Frozen section for the management of intraoperatively detected palpable tumor lesions during nerve-sparing scheduled radical prostatectomy,” Eur. Urol. 49(6), 1011–1018 (2006).
[CrossRef] [PubMed]

Evans, A.

T. H. Van der Kwast, A. Evans, G. Lockwood, D. Tkachuk, D. G. Bostwick, J. I. Epstein, P. A. Humphrey, R. Montironi, G. J. Van Leenders, C. G. Pihl, I. Neetens, P. M. Kujala, M. Laurila, C. Mazerolles, L. Bubendorf, A. Finelli, K. Watson, and J. Srigley, “Variability in diagnostic opinion among pathologists for single small atypical foci in prostate biopsies,” Am. J. Surg. Pathol. 34(2), 169–177 (2010).
[CrossRef] [PubMed]

Evans, C. L.

C. L. Evans and X. S. Xie, “Coherent anti-stokes Raman scattering microscopy: chemical imaging for biology and medicine,” Annu Rev Anal Chem (Palo Alto Calif) 1(1), 883–909 (2008).
[CrossRef] [PubMed]

F. Légaré, C. L. Evans, F. Ganikhanov, and X. S. Xie, “Towards CARS Endoscopy,” Opt. Express 14(10), 4427–4432 (2006).
[CrossRef] [PubMed]

C. L. Evans, E. O. Potma, M. Puoris’haag, D. Côté, C. P. Lin, and X. S. Xie, “Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy,” Proc. Natl. Acad. Sci. U.S.A. 102(46), 16807–16812 (2005).
[CrossRef] [PubMed]

C. L. Evans, E. O. Potma, and X. S. Xie, “Coherent anti-stokes raman scattering spectral interferometry: determination of the real and imaginary components of nonlinear susceptibility χ(3) for vibrational microscopy,” Opt. Lett. 29(24), 2923–2925 (2004).
[CrossRef] [PubMed]

Finelli, A.

T. H. Van der Kwast, A. Evans, G. Lockwood, D. Tkachuk, D. G. Bostwick, J. I. Epstein, P. A. Humphrey, R. Montironi, G. J. Van Leenders, C. G. Pihl, I. Neetens, P. M. Kujala, M. Laurila, C. Mazerolles, L. Bubendorf, A. Finelli, K. Watson, and J. Srigley, “Variability in diagnostic opinion among pathologists for single small atypical foci in prostate biopsies,” Am. J. Surg. Pathol. 34(2), 169–177 (2010).
[CrossRef] [PubMed]

Flanders, S. C.

G. D. Grossfeld, J. J. Chang, J. M. Broering, D. P. Miller, J. Yu, S. C. Flanders, J. M. Henning, D. M. Stier, and P. R. Carroll, “Impact of positive surgical margins on prostate cancer recurrence and the use of secondary cancer treatment: data from the CaPSURE database,” J. Urol. 163(4), 1171–1177, quiz 1295 (2000).
[CrossRef] [PubMed]

Fried, N. M.

S. Rais-Bahrami, A. W. Levinson, N. M. Fried, G. A. Lagoda, A. Hristov, Y. Chuang, A. L. Burnett, and L. M. Su, “Optical coherence tomography of cavernous nerves: a step toward real-time intraoperative imaging during nerve-sparing radical prostatectomy,” Urology 72(1), 198–204 (2008).
[CrossRef] [PubMed]

Gander, W.

W. Gander, G. H. Golub, and R. Strebel, “Least-squares fitting of circles and ellipses,” BIT Numerical Math. 34(4), 558–578 (1994).
[CrossRef]

Ganikhanov, F.

Gao, L.

Gettman, M. T.

C. Q. Le and M. T. Gettman, “Laparoscopic and robotic radical prostatectomy,” Expert Rev. Anticancer Ther. 6(7), 1003–1011 (2006).
[CrossRef] [PubMed]

Goharderakhshan, R. Z.

R. Z. Goharderakhshan, D. Sudilovsky, L. A. Carroll, G. D. Grossfeld, R. Marn, and P. R. Carroll, “Utility of intraoperative frozen section analysis of surgical margins in region of neurovascular bundles at radical prostatectomy,” Urology 59(5), 709–714 (2002).
[CrossRef] [PubMed]

Golub, G. H.

W. Gander, G. H. Golub, and R. Strebel, “Least-squares fitting of circles and ellipses,” BIT Numerical Math. 34(4), 558–578 (1994).
[CrossRef]

Gontero, P.

P. Gontero and R. S. Kirby, “Nerve-sparing radical retropubic prostatectomy: techniques and clinical considerations,” Prostate Cancer Prostatic Dis. 8(2), 133–139 (2005).
[CrossRef] [PubMed]

Graefen, M.

C. Eichelberg, A. Erbersdobler, A. Haese, T. Schlomm, F. K. Chun, E. Currlin, J. Walz, T. Steuber, M. Graefen, and H. Huland, “Frozen section for the management of intraoperatively detected palpable tumor lesions during nerve-sparing scheduled radical prostatectomy,” Eur. Urol. 49(6), 1011–1018 (2006).
[CrossRef] [PubMed]

Grossfeld, G. D.

R. Z. Goharderakhshan, D. Sudilovsky, L. A. Carroll, G. D. Grossfeld, R. Marn, and P. R. Carroll, “Utility of intraoperative frozen section analysis of surgical margins in region of neurovascular bundles at radical prostatectomy,” Urology 59(5), 709–714 (2002).
[CrossRef] [PubMed]

G. D. Grossfeld, J. J. Chang, J. M. Broering, D. P. Miller, J. Yu, S. C. Flanders, J. M. Henning, D. M. Stier, and P. R. Carroll, “Impact of positive surgical margins on prostate cancer recurrence and the use of secondary cancer treatment: data from the CaPSURE database,” J. Urol. 163(4), 1171–1177, quiz 1295 (2000).
[CrossRef] [PubMed]

Haese, A.

C. Eichelberg, A. Erbersdobler, A. Haese, T. Schlomm, F. K. Chun, E. Currlin, J. Walz, T. Steuber, M. Graefen, and H. Huland, “Frozen section for the management of intraoperatively detected palpable tumor lesions during nerve-sparing scheduled radical prostatectomy,” Eur. Urol. 49(6), 1011–1018 (2006).
[CrossRef] [PubMed]

Heidenreich, A.

A. Heidenreich, “Intraoperative frozen section analysis to monitor nerve-sparing radical prostatectomy,” Eur. Urol. 49(6), 948–949 (2006).
[CrossRef] [PubMed]

Henning, J. M.

G. D. Grossfeld, J. J. Chang, J. M. Broering, D. P. Miller, J. Yu, S. C. Flanders, J. M. Henning, D. M. Stier, and P. R. Carroll, “Impact of positive surgical margins on prostate cancer recurrence and the use of secondary cancer treatment: data from the CaPSURE database,” J. Urol. 163(4), 1171–1177, quiz 1295 (2000).
[CrossRef] [PubMed]

Hermen, M.

R. Yadav, S. Mukherjee, M. Hermen, G. Tan, F. R. Maxfield, W. W. Webb, and A. K. Tewari, “Multiphoton microscopy of prostate and periprostatic neural tissue: a promising imaging technique for improving nerve-sparing prostatectomy,” J. Endourol. 23(5), 861–867 (2009).
[CrossRef] [PubMed]

Hristov, A.

S. Rais-Bahrami, A. W. Levinson, N. M. Fried, G. A. Lagoda, A. Hristov, Y. Chuang, A. L. Burnett, and L. M. Su, “Optical coherence tomography of cavernous nerves: a step toward real-time intraoperative imaging during nerve-sparing radical prostatectomy,” Urology 72(1), 198–204 (2008).
[CrossRef] [PubMed]

Huckins, J.

M. Wang, X. Zhou, F. Li, J. Huckins, R. W. King, and S. T. C. Wong, “Novel cell segmentation and online SVM for cell cycle phase identification in automated microscopy,” Bioinformatics 24(1), 94–101 (2007).
[CrossRef] [PubMed]

Huff, T. B.

T. B. Huff and J. X. Cheng, “In vivo coherent anti-Stokes Raman scattering imaging of sciatic nerve tissue,” J. Microsc. 225(2), 175–182 (2007).
[CrossRef] [PubMed]

Huland, H.

C. Eichelberg, A. Erbersdobler, A. Haese, T. Schlomm, F. K. Chun, E. Currlin, J. Walz, T. Steuber, M. Graefen, and H. Huland, “Frozen section for the management of intraoperatively detected palpable tumor lesions during nerve-sparing scheduled radical prostatectomy,” Eur. Urol. 49(6), 1011–1018 (2006).
[CrossRef] [PubMed]

Humphrey, P. A.

T. H. Van der Kwast, A. Evans, G. Lockwood, D. Tkachuk, D. G. Bostwick, J. I. Epstein, P. A. Humphrey, R. Montironi, G. J. Van Leenders, C. G. Pihl, I. Neetens, P. M. Kujala, M. Laurila, C. Mazerolles, L. Bubendorf, A. Finelli, K. Watson, and J. Srigley, “Variability in diagnostic opinion among pathologists for single small atypical foci in prostate biopsies,” Am. J. Surg. Pathol. 34(2), 169–177 (2010).
[CrossRef] [PubMed]

King, R. W.

M. Wang, X. Zhou, F. Li, J. Huckins, R. W. King, and S. T. C. Wong, “Novel cell segmentation and online SVM for cell cycle phase identification in automated microscopy,” Bioinformatics 24(1), 94–101 (2007).
[CrossRef] [PubMed]

Kirby, R. S.

P. Gontero and R. S. Kirby, “Nerve-sparing radical retropubic prostatectomy: techniques and clinical considerations,” Prostate Cancer Prostatic Dis. 8(2), 133–139 (2005).
[CrossRef] [PubMed]

Kirkley, T. D.

L. B. Boyette, M. A. Reardon, A. J. Mirelman, T. D. Kirkley, J. J. Lysiak, J. B. Tuttle, and W. D. Steers, “Fiberoptic imaging of cavernous nerves in vivo,” J. Urol. 178(6), 2694–2700 (2007).
[CrossRef] [PubMed]

Kirsch, M.

M. Kirsch, G. Schackert, R. Salzer, and C. Krafft, “Raman spectroscopic imaging for in vivo detection of cerebral brain metastases,” Anal. Bioanal. Chem. 398(4), 1707–1713 (2010).
[CrossRef] [PubMed]

Krafft, C.

M. Kirsch, G. Schackert, R. Salzer, and C. Krafft, “Raman spectroscopic imaging for in vivo detection of cerebral brain metastases,” Anal. Bioanal. Chem. 398(4), 1707–1713 (2010).
[CrossRef] [PubMed]

Kujala, P. M.

T. H. Van der Kwast, A. Evans, G. Lockwood, D. Tkachuk, D. G. Bostwick, J. I. Epstein, P. A. Humphrey, R. Montironi, G. J. Van Leenders, C. G. Pihl, I. Neetens, P. M. Kujala, M. Laurila, C. Mazerolles, L. Bubendorf, A. Finelli, K. Watson, and J. Srigley, “Variability in diagnostic opinion among pathologists for single small atypical foci in prostate biopsies,” Am. J. Surg. Pathol. 34(2), 169–177 (2010).
[CrossRef] [PubMed]

Lagoda, G. A.

S. Rais-Bahrami, A. W. Levinson, N. M. Fried, G. A. Lagoda, A. Hristov, Y. Chuang, A. L. Burnett, and L. M. Su, “Optical coherence tomography of cavernous nerves: a step toward real-time intraoperative imaging during nerve-sparing radical prostatectomy,” Urology 72(1), 198–204 (2008).
[CrossRef] [PubMed]

Laurila, M.

T. H. Van der Kwast, A. Evans, G. Lockwood, D. Tkachuk, D. G. Bostwick, J. I. Epstein, P. A. Humphrey, R. Montironi, G. J. Van Leenders, C. G. Pihl, I. Neetens, P. M. Kujala, M. Laurila, C. Mazerolles, L. Bubendorf, A. Finelli, K. Watson, and J. Srigley, “Variability in diagnostic opinion among pathologists for single small atypical foci in prostate biopsies,” Am. J. Surg. Pathol. 34(2), 169–177 (2010).
[CrossRef] [PubMed]

Le, C. Q.

C. Q. Le and M. T. Gettman, “Laparoscopic and robotic radical prostatectomy,” Expert Rev. Anticancer Ther. 6(7), 1003–1011 (2006).
[CrossRef] [PubMed]

Lee, Y. J.

S. H. Parekh, Y. J. Lee, K. A. Aamer, and M. T. Cicerone, “Label-free cellular imaging by broadband coherent anti-Stokes Raman scattering microscopy,” Biophys. J. 99(8), 2695–2704 (2010).
[CrossRef] [PubMed]

Légaré, F.

Levinson, A. W.

S. Rais-Bahrami, A. W. Levinson, N. M. Fried, G. A. Lagoda, A. Hristov, Y. Chuang, A. L. Burnett, and L. M. Su, “Optical coherence tomography of cavernous nerves: a step toward real-time intraoperative imaging during nerve-sparing radical prostatectomy,” Urology 72(1), 198–204 (2008).
[CrossRef] [PubMed]

Li, F.

F. Li, X. Zhou, J. Ma, and S. T. Wong, “Multiple nuclei tracking using integer programming for quantitative cancer cell cycle analysis,” IEEE Trans. Med. Imaging 29(1), 96–105 (2010).
[CrossRef] [PubMed]

M. Wang, X. Zhou, F. Li, J. Huckins, R. W. King, and S. T. C. Wong, “Novel cell segmentation and online SVM for cell cycle phase identification in automated microscopy,” Bioinformatics 24(1), 94–101 (2007).
[CrossRef] [PubMed]

Lin, C. P.

C. L. Evans, E. O. Potma, M. Puoris’haag, D. Côté, C. P. Lin, and X. S. Xie, “Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy,” Proc. Natl. Acad. Sci. U.S.A. 102(46), 16807–16812 (2005).
[CrossRef] [PubMed]

Liu, G.

Lockwood, G.

T. H. Van der Kwast, A. Evans, G. Lockwood, D. Tkachuk, D. G. Bostwick, J. I. Epstein, P. A. Humphrey, R. Montironi, G. J. Van Leenders, C. G. Pihl, I. Neetens, P. M. Kujala, M. Laurila, C. Mazerolles, L. Bubendorf, A. Finelli, K. Watson, and J. Srigley, “Variability in diagnostic opinion among pathologists for single small atypical foci in prostate biopsies,” Am. J. Surg. Pathol. 34(2), 169–177 (2010).
[CrossRef] [PubMed]

Luo, P.

Lysiak, J. J.

L. B. Boyette, M. A. Reardon, A. J. Mirelman, T. D. Kirkley, J. J. Lysiak, J. B. Tuttle, and W. D. Steers, “Fiberoptic imaging of cavernous nerves in vivo,” J. Urol. 178(6), 2694–2700 (2007).
[CrossRef] [PubMed]

Ma, J.

F. Li, X. Zhou, J. Ma, and S. T. Wong, “Multiple nuclei tracking using integer programming for quantitative cancer cell cycle analysis,” IEEE Trans. Med. Imaging 29(1), 96–105 (2010).
[CrossRef] [PubMed]

Marn, R.

R. Z. Goharderakhshan, D. Sudilovsky, L. A. Carroll, G. D. Grossfeld, R. Marn, and P. R. Carroll, “Utility of intraoperative frozen section analysis of surgical margins in region of neurovascular bundles at radical prostatectomy,” Urology 59(5), 709–714 (2002).
[CrossRef] [PubMed]

Maxfield, F. R.

R. Yadav, S. Mukherjee, M. Hermen, G. Tan, F. R. Maxfield, W. W. Webb, and A. K. Tewari, “Multiphoton microscopy of prostate and periprostatic neural tissue: a promising imaging technique for improving nerve-sparing prostatectomy,” J. Endourol. 23(5), 861–867 (2009).
[CrossRef] [PubMed]

Mazerolles, C.

T. H. Van der Kwast, A. Evans, G. Lockwood, D. Tkachuk, D. G. Bostwick, J. I. Epstein, P. A. Humphrey, R. Montironi, G. J. Van Leenders, C. G. Pihl, I. Neetens, P. M. Kujala, M. Laurila, C. Mazerolles, L. Bubendorf, A. Finelli, K. Watson, and J. Srigley, “Variability in diagnostic opinion among pathologists for single small atypical foci in prostate biopsies,” Am. J. Surg. Pathol. 34(2), 169–177 (2010).
[CrossRef] [PubMed]

Melamud, O.

E. Rodriguez, O. Melamud, and T. E. Ahlering, “Nerve-sparing techniques in open and laparoscopic prostatectomy,” Expert Rev. Anticancer Ther. 8(3), 475–479 (2008).
[CrossRef] [PubMed]

Miller, D. P.

G. D. Grossfeld, J. J. Chang, J. M. Broering, D. P. Miller, J. Yu, S. C. Flanders, J. M. Henning, D. M. Stier, and P. R. Carroll, “Impact of positive surgical margins on prostate cancer recurrence and the use of secondary cancer treatment: data from the CaPSURE database,” J. Urol. 163(4), 1171–1177, quiz 1295 (2000).
[CrossRef] [PubMed]

Mirelman, A. J.

L. B. Boyette, M. A. Reardon, A. J. Mirelman, T. D. Kirkley, J. J. Lysiak, J. B. Tuttle, and W. D. Steers, “Fiberoptic imaging of cavernous nerves in vivo,” J. Urol. 178(6), 2694–2700 (2007).
[CrossRef] [PubMed]

Montironi, R.

T. H. Van der Kwast, A. Evans, G. Lockwood, D. Tkachuk, D. G. Bostwick, J. I. Epstein, P. A. Humphrey, R. Montironi, G. J. Van Leenders, C. G. Pihl, I. Neetens, P. M. Kujala, M. Laurila, C. Mazerolles, L. Bubendorf, A. Finelli, K. Watson, and J. Srigley, “Variability in diagnostic opinion among pathologists for single small atypical foci in prostate biopsies,” Am. J. Surg. Pathol. 34(2), 169–177 (2010).
[CrossRef] [PubMed]

Mukherjee, S.

R. Yadav, S. Mukherjee, M. Hermen, G. Tan, F. R. Maxfield, W. W. Webb, and A. K. Tewari, “Multiphoton microscopy of prostate and periprostatic neural tissue: a promising imaging technique for improving nerve-sparing prostatectomy,” J. Endourol. 23(5), 861–867 (2009).
[CrossRef] [PubMed]

Neetens, I.

T. H. Van der Kwast, A. Evans, G. Lockwood, D. Tkachuk, D. G. Bostwick, J. I. Epstein, P. A. Humphrey, R. Montironi, G. J. Van Leenders, C. G. Pihl, I. Neetens, P. M. Kujala, M. Laurila, C. Mazerolles, L. Bubendorf, A. Finelli, K. Watson, and J. Srigley, “Variability in diagnostic opinion among pathologists for single small atypical foci in prostate biopsies,” Am. J. Surg. Pathol. 34(2), 169–177 (2010).
[CrossRef] [PubMed]

Novis, D. A.

D. A. Novis and R. J. Zarbo, “Interinstitutional comparison of frozen section turnaround time. A College of American Pathologists Q-Probes study of 32868 frozen sections in 700 hospitals,” Arch. Pathol. Lab. Med. 121(6), 559–567 (1997).
[PubMed]

Parekh, S. H.

S. H. Parekh, Y. J. Lee, K. A. Aamer, and M. T. Cicerone, “Label-free cellular imaging by broadband coherent anti-Stokes Raman scattering microscopy,” Biophys. J. 99(8), 2695–2704 (2010).
[CrossRef] [PubMed]

Pihl, C. G.

T. H. Van der Kwast, A. Evans, G. Lockwood, D. Tkachuk, D. G. Bostwick, J. I. Epstein, P. A. Humphrey, R. Montironi, G. J. Van Leenders, C. G. Pihl, I. Neetens, P. M. Kujala, M. Laurila, C. Mazerolles, L. Bubendorf, A. Finelli, K. Watson, and J. Srigley, “Variability in diagnostic opinion among pathologists for single small atypical foci in prostate biopsies,” Am. J. Surg. Pathol. 34(2), 169–177 (2010).
[CrossRef] [PubMed]

Potma, E. O.

Puoris’haag, M.

C. L. Evans, E. O. Potma, M. Puoris’haag, D. Côté, C. P. Lin, and X. S. Xie, “Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy,” Proc. Natl. Acad. Sci. U.S.A. 102(46), 16807–16812 (2005).
[CrossRef] [PubMed]

Rais-Bahrami, S.

S. Rais-Bahrami, A. W. Levinson, N. M. Fried, G. A. Lagoda, A. Hristov, Y. Chuang, A. L. Burnett, and L. M. Su, “Optical coherence tomography of cavernous nerves: a step toward real-time intraoperative imaging during nerve-sparing radical prostatectomy,” Urology 72(1), 198–204 (2008).
[CrossRef] [PubMed]

Reardon, M. A.

L. B. Boyette, M. A. Reardon, A. J. Mirelman, T. D. Kirkley, J. J. Lysiak, J. B. Tuttle, and W. D. Steers, “Fiberoptic imaging of cavernous nerves in vivo,” J. Urol. 178(6), 2694–2700 (2007).
[CrossRef] [PubMed]

Rodriguez, E.

E. Rodriguez, O. Melamud, and T. E. Ahlering, “Nerve-sparing techniques in open and laparoscopic prostatectomy,” Expert Rev. Anticancer Ther. 8(3), 475–479 (2008).
[CrossRef] [PubMed]

Salzer, R.

M. Kirsch, G. Schackert, R. Salzer, and C. Krafft, “Raman spectroscopic imaging for in vivo detection of cerebral brain metastases,” Anal. Bioanal. Chem. 398(4), 1707–1713 (2010).
[CrossRef] [PubMed]

Schackert, G.

M. Kirsch, G. Schackert, R. Salzer, and C. Krafft, “Raman spectroscopic imaging for in vivo detection of cerebral brain metastases,” Anal. Bioanal. Chem. 398(4), 1707–1713 (2010).
[CrossRef] [PubMed]

Schlomm, T.

C. Eichelberg, A. Erbersdobler, A. Haese, T. Schlomm, F. K. Chun, E. Currlin, J. Walz, T. Steuber, M. Graefen, and H. Huland, “Frozen section for the management of intraoperatively detected palpable tumor lesions during nerve-sparing scheduled radical prostatectomy,” Eur. Urol. 49(6), 1011–1018 (2006).
[CrossRef] [PubMed]

Soille, P.

L. Vincent and P. Soille, “Watersheds in digital spaces: an efficient algorithm based on immersion simulations,” IEEE Trans. Pattern Anal. Mach. Intell. 13(6), 583–598 (1991).
[CrossRef]

Srigley, J.

T. H. Van der Kwast, A. Evans, G. Lockwood, D. Tkachuk, D. G. Bostwick, J. I. Epstein, P. A. Humphrey, R. Montironi, G. J. Van Leenders, C. G. Pihl, I. Neetens, P. M. Kujala, M. Laurila, C. Mazerolles, L. Bubendorf, A. Finelli, K. Watson, and J. Srigley, “Variability in diagnostic opinion among pathologists for single small atypical foci in prostate biopsies,” Am. J. Surg. Pathol. 34(2), 169–177 (2010).
[CrossRef] [PubMed]

Steers, W. D.

L. B. Boyette, M. A. Reardon, A. J. Mirelman, T. D. Kirkley, J. J. Lysiak, J. B. Tuttle, and W. D. Steers, “Fiberoptic imaging of cavernous nerves in vivo,” J. Urol. 178(6), 2694–2700 (2007).
[CrossRef] [PubMed]

Steuber, T.

C. Eichelberg, A. Erbersdobler, A. Haese, T. Schlomm, F. K. Chun, E. Currlin, J. Walz, T. Steuber, M. Graefen, and H. Huland, “Frozen section for the management of intraoperatively detected palpable tumor lesions during nerve-sparing scheduled radical prostatectomy,” Eur. Urol. 49(6), 1011–1018 (2006).
[CrossRef] [PubMed]

Stier, D. M.

G. D. Grossfeld, J. J. Chang, J. M. Broering, D. P. Miller, J. Yu, S. C. Flanders, J. M. Henning, D. M. Stier, and P. R. Carroll, “Impact of positive surgical margins on prostate cancer recurrence and the use of secondary cancer treatment: data from the CaPSURE database,” J. Urol. 163(4), 1171–1177, quiz 1295 (2000).
[CrossRef] [PubMed]

Strebel, R.

W. Gander, G. H. Golub, and R. Strebel, “Least-squares fitting of circles and ellipses,” BIT Numerical Math. 34(4), 558–578 (1994).
[CrossRef]

Su, L. M.

L. M. Su, “Robot-assisted radical prostatectomy: advances since 2005,” Curr. Opin. Urol. 20(2), 130–135 (2010).
[CrossRef] [PubMed]

S. Rais-Bahrami, A. W. Levinson, N. M. Fried, G. A. Lagoda, A. Hristov, Y. Chuang, A. L. Burnett, and L. M. Su, “Optical coherence tomography of cavernous nerves: a step toward real-time intraoperative imaging during nerve-sparing radical prostatectomy,” Urology 72(1), 198–204 (2008).
[CrossRef] [PubMed]

Sudilovsky, D.

R. Z. Goharderakhshan, D. Sudilovsky, L. A. Carroll, G. D. Grossfeld, R. Marn, and P. R. Carroll, “Utility of intraoperative frozen section analysis of surgical margins in region of neurovascular bundles at radical prostatectomy,” Urology 59(5), 709–714 (2002).
[CrossRef] [PubMed]

Tan, G.

R. Yadav, S. Mukherjee, M. Hermen, G. Tan, F. R. Maxfield, W. W. Webb, and A. K. Tewari, “Multiphoton microscopy of prostate and periprostatic neural tissue: a promising imaging technique for improving nerve-sparing prostatectomy,” J. Endourol. 23(5), 861–867 (2009).
[CrossRef] [PubMed]

Tewari, A. K.

R. Yadav, S. Mukherjee, M. Hermen, G. Tan, F. R. Maxfield, W. W. Webb, and A. K. Tewari, “Multiphoton microscopy of prostate and periprostatic neural tissue: a promising imaging technique for improving nerve-sparing prostatectomy,” J. Endourol. 23(5), 861–867 (2009).
[CrossRef] [PubMed]

Tkachuk, D.

T. H. Van der Kwast, A. Evans, G. Lockwood, D. Tkachuk, D. G. Bostwick, J. I. Epstein, P. A. Humphrey, R. Montironi, G. J. Van Leenders, C. G. Pihl, I. Neetens, P. M. Kujala, M. Laurila, C. Mazerolles, L. Bubendorf, A. Finelli, K. Watson, and J. Srigley, “Variability in diagnostic opinion among pathologists for single small atypical foci in prostate biopsies,” Am. J. Surg. Pathol. 34(2), 169–177 (2010).
[CrossRef] [PubMed]

Tromberg, B. J.

Tuttle, J. B.

L. B. Boyette, M. A. Reardon, A. J. Mirelman, T. D. Kirkley, J. J. Lysiak, J. B. Tuttle, and W. D. Steers, “Fiberoptic imaging of cavernous nerves in vivo,” J. Urol. 178(6), 2694–2700 (2007).
[CrossRef] [PubMed]

Van der Kwast, T. H.

T. H. Van der Kwast, A. Evans, G. Lockwood, D. Tkachuk, D. G. Bostwick, J. I. Epstein, P. A. Humphrey, R. Montironi, G. J. Van Leenders, C. G. Pihl, I. Neetens, P. M. Kujala, M. Laurila, C. Mazerolles, L. Bubendorf, A. Finelli, K. Watson, and J. Srigley, “Variability in diagnostic opinion among pathologists for single small atypical foci in prostate biopsies,” Am. J. Surg. Pathol. 34(2), 169–177 (2010).
[CrossRef] [PubMed]

Van Leenders, G. J.

T. H. Van der Kwast, A. Evans, G. Lockwood, D. Tkachuk, D. G. Bostwick, J. I. Epstein, P. A. Humphrey, R. Montironi, G. J. Van Leenders, C. G. Pihl, I. Neetens, P. M. Kujala, M. Laurila, C. Mazerolles, L. Bubendorf, A. Finelli, K. Watson, and J. Srigley, “Variability in diagnostic opinion among pathologists for single small atypical foci in prostate biopsies,” Am. J. Surg. Pathol. 34(2), 169–177 (2010).
[CrossRef] [PubMed]

Vincent, L.

L. Vincent and P. Soille, “Watersheds in digital spaces: an efficient algorithm based on immersion simulations,” IEEE Trans. Pattern Anal. Mach. Intell. 13(6), 583–598 (1991).
[CrossRef]

Walz, J.

C. Eichelberg, A. Erbersdobler, A. Haese, T. Schlomm, F. K. Chun, E. Currlin, J. Walz, T. Steuber, M. Graefen, and H. Huland, “Frozen section for the management of intraoperatively detected palpable tumor lesions during nerve-sparing scheduled radical prostatectomy,” Eur. Urol. 49(6), 1011–1018 (2006).
[CrossRef] [PubMed]

Wang, M.

M. Wang, X. Zhou, F. Li, J. Huckins, R. W. King, and S. T. C. Wong, “Novel cell segmentation and online SVM for cell cycle phase identification in automated microscopy,” Bioinformatics 24(1), 94–101 (2007).
[CrossRef] [PubMed]

Wang, Z.

Watson, K.

T. H. Van der Kwast, A. Evans, G. Lockwood, D. Tkachuk, D. G. Bostwick, J. I. Epstein, P. A. Humphrey, R. Montironi, G. J. Van Leenders, C. G. Pihl, I. Neetens, P. M. Kujala, M. Laurila, C. Mazerolles, L. Bubendorf, A. Finelli, K. Watson, and J. Srigley, “Variability in diagnostic opinion among pathologists for single small atypical foci in prostate biopsies,” Am. J. Surg. Pathol. 34(2), 169–177 (2010).
[CrossRef] [PubMed]

Webb, W. W.

R. Yadav, S. Mukherjee, M. Hermen, G. Tan, F. R. Maxfield, W. W. Webb, and A. K. Tewari, “Multiphoton microscopy of prostate and periprostatic neural tissue: a promising imaging technique for improving nerve-sparing prostatectomy,” J. Endourol. 23(5), 861–867 (2009).
[CrossRef] [PubMed]

Wong, K. K.

Wong, S. T.

F. Li, X. Zhou, J. Ma, and S. T. Wong, “Multiple nuclei tracking using integer programming for quantitative cancer cell cycle analysis,” IEEE Trans. Med. Imaging 29(1), 96–105 (2010).
[CrossRef] [PubMed]

Wong, S. T. C.

Z. Wang, Y. Yang, P. Luo, L. Gao, K. K. Wong, and S. T. C. Wong, “Delivery of picosecond lasers in multimode fibers for coherent anti-Stokes Raman scattering imaging,” Opt. Express 18(12), 13017–13028 (2010).
[CrossRef] [PubMed]

M. Wang, X. Zhou, F. Li, J. Huckins, R. W. King, and S. T. C. Wong, “Novel cell segmentation and online SVM for cell cycle phase identification in automated microscopy,” Bioinformatics 24(1), 94–101 (2007).
[CrossRef] [PubMed]

Xie, X. S.

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Supplementary Material (3)

» Media 1: AVI (54532 KB)     
» Media 2: AVI (46852 KB)     
» Media 3: AVI (31491 KB)     

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Figures (7)

Fig. 1
Fig. 1

Schematic of the CARS microscopy system. The pump (816.7 nm) and Stokes (1,064 nm) beams are overlapped, both temporally and spatially, and delivered into a microscopy system. A dichroic mirror is used to separate CARS signals from excitation lasers for detection. D: PMT detector; DM: dichroic mirror; F: filter; L: lens; M: mirror

Fig. 5
Fig. 5

Overview of the nuclear segmentation process and the resulting Delaunay Triangulation graph. (A) Snapshot of graphic user interface of CARS image analysis software; Red ellipses are the delineated cell boundaries. The green star represents one of the user-selected points, while the green square box indicates the image patch which will be processed; intermediate results: (B) targeted nucleus; (C) watershed segmentation algorithm; (D) local thresholding; (E) Ellipse fitting; (F) final result. (G) Delaunay Triangulation on the segmented image.

Fig. 2
Fig. 2

Ex vivo images of human prostate gland and stroma structures using CARS and H&E stain. (A) A low magnification image shows the position of the imaged glandular (Yellow Square) and stroma (Red Square) areas. (B)/(C) high magnification CARS/H&E images of the prostate gland marked in (A). (D)/(E) high magnification CARS/H&E images of the stroma region marked in (A).

Fig. 3
Fig. 3

CARS images of glandular epithelium structures at different depths and H&E images from a similar gland. (A) H&E image of a normal gland showing the appearance of glandular epithelial cells from different imaging planes. (B) Higher magnification image of the highlighted region in (A) showing different appearance of epithelial cells caused by variation in focal planes. Red and yellow arrows point to cells with and without a visible nucleus, respectively. CARS images from a similar gland show epithelial cells as polygons (C) at a shallow plane and with visible nuclei at a deeper plane (D). Cells indicated by the red and yellow arrows in (C) and (D) have structures comparable to those marked in (B).

Fig. 4
Fig. 4

CARS and H&E images of cancerous glands from three patients. (A)(B)(C) Low/ high magnification H&E images and a CARS image from the first patient (Media 1). Red and yellow arrows point to an enlarged epithelial cell and a distinctive cell nucleolus, respectively. (D)(E)(F) Low/ high magnification H&E images and a CARS image from the same patient (Media 2). Red and yellow arrows point to an enlarged epithelial cell containing prominent secretory material in the cytoplasm and a cancerous epithelial cell of relatively normal size. (G)(H)(I) Low/high H&E and CARS results from the third patient, who possesses significant nuclear pleomorphism (Media 3). Yellow arrow points to a distinctive cell nucleolus.

Fig. 6
Fig. 6

Feature extraction and PCA analysis. (A)-(E) Distribution of the five extracted features of the normal (blue) and cancer group (red); (F) Following PCA analysis, the spatial distribution of 23 normal sample sets and 17 cancer sample sets are plotted in the top two principal components space. The eclipses around the data points are 95% confidence intervals for normal (red) and cancer (blue) groups, showing a significant separation between the two groups. (G) Box plot of normal and cancer groups using a single-feature standard deviation of average cell neighbor distance. Blue bars represent samples’ maximum and minimum, while red quadrangles indicate higher and lower quartiles of the samples.

Fig. 7
Fig. 7

Ex vivo images of a human cavernous nerve using CARS and the H&E stained structure of the same nerve. (A) Two-dimensional projection of 45 images from a z-stack with a step size of 1 μm. YZ and XZ cross sections are presented in the right and bottom panels, which were constructed from the depth stack along the purple and yellow lines, respectively. (C) H&E image of the same nerve.

Tables (1)

Tables Icon

Table 1 Coefficients of top two principal components in the 10-feature space. NS: Nuclear Size; NDV: Neighbor Distance Variation; Ave ND: Average Neighbor Distance; Max ND: Maximum Neighbor Distance; Min ND: Minimum Neighbor Distance.

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