Abstract

Fluorescence microscopy can be used to acquire real-time images of tissue morphology and with appropriate algorithms can rapidly quantify features associated with disease. The objective of this study was to assess the ability of various segmentation algorithms to isolate fluorescent positive features (FPFs) in heterogeneous images and identify an approach that can be used across multiple fluorescence microscopes with minimal tuning between systems. Specifically, we show a variety of image segmentation algorithms applied to images of stained tumor and muscle tissue acquired with 3 different fluorescence microscopes. Results indicate that a technique called maximally stable extremal regions followed by thresholding (MSER + Binary) yielded the greatest contrast in FPF density between tumor and muscle images across multiple microscopy systems.

© 2016 Optical Society of America

Full Article  |  PDF Article
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References

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  31. (!!! INVALID CITATION !!!).
  32. M. J. Whitley, D. M. Cardona, A. L. Lazarides, I. Spasojevic, J. M. Ferrer, J. Cahill, C. L. Lee, M. Snuderl, D. G. Blazer, E. S. Hwang, R. A. Greenup, P. J. Mosca, J. K. Mito, K. C. Cuneo, N. A. Larrier, E. K. O’Reilly, R. F. Riedel, W. C. Eward, D. B. Strasfeld, D. Fukumura, R. K. Jain, W. D. Lee, L. G. Griffith, M. G. Bawendi, D. G. Kirsch, and B. E. Brigman, “A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer,” Sci. Transl. Med. 8(320), 320ra4 (2016).
    [Crossref] [PubMed]

2016 (1)

M. J. Whitley, D. M. Cardona, A. L. Lazarides, I. Spasojevic, J. M. Ferrer, J. Cahill, C. L. Lee, M. Snuderl, D. G. Blazer, E. S. Hwang, R. A. Greenup, P. J. Mosca, J. K. Mito, K. C. Cuneo, N. A. Larrier, E. K. O’Reilly, R. F. Riedel, W. C. Eward, D. B. Strasfeld, D. Fukumura, R. K. Jain, W. D. Lee, L. G. Griffith, M. G. Bawendi, D. G. Kirsch, and B. E. Brigman, “A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer,” Sci. Transl. Med. 8(320), 320ra4 (2016).
[Crossref] [PubMed]

2015 (3)

J. L. Mueller, H. L. Fu, J. K. Mito, M. J. Whitley, R. Chitalia, A. Erkanli, L. Dodd, D. M. Cardona, J. Geradts, R. M. Willett, D. G. Kirsch, and N. Ramanujam, “A quantitative microscopic approach to predict local recurrence based on in vivo intraoperative imaging of sarcoma tumor margins,” Int. J. Cancer 137(10), 2403–2412 (2015).
[Crossref] [PubMed]

H. Fu, J. Mueller, M. Whitley, D. Cardona, R. Willet, D. Kirsch, Q. Brown, and N. Ramanujam, “Structured illumination microscopy and a quantitative image analysis for the detection of positive margins in a pre-clinical genetically engineered mouse model of sarcoma,” PLoS One 11(1), e0147006 (2015).
[PubMed]

J. L. Dobbs, J. L. Mueller, S. Krishnamurthy, D. Shin, H. Kuerer, W. Yang, N. Ramanujam, and R. Richards-Kortum, “Micro-anatomical quantitative optical imaging: toward automated assessment of breast tissues,” Breast Cancer Res. 17(1), 105 (2015).
[Crossref] [PubMed]

2013 (4)

J. L. Mueller, Z. T. Harmany, J. K. Mito, S. A. Kennedy, Y. Kim, L. Dodd, J. Geradts, D. G. Kirsch, R. M. Willett, J. Q. Brown, and N. Ramanujam, “Quantitative Segmentation of Fluorescence Microscopy Images of Heterogeneous Tissue: Application to the Detection of Residual Disease in Tumor Margins,” PLoS One 8(6), e66198 (2013).
[Crossref] [PubMed]

H. L. Fu, J. L. Mueller, M. P. Javid, J. K. Mito, D. G. Kirsch, N. Ramanujam, and J. Q. Brown, “Optimization of a widefield structured illumination microscope for non-destructive assessment and quantification of nuclear features in tumor margins of a primary mouse model of sarcoma,” PLoS One 8(7), e68868 (2013).
[Crossref] [PubMed]

J. K. Mito, H. D. Min, Y. Ma, J. E. Carter, B. E. Brigman, L. Dodd, D. Dankort, M. McMahon, and D. G. Kirsch, “Oncogene-dependent control of miRNA biogenesis and metastatic progression in a model of undifferentiated pleomorphic sarcoma,” J. Pathol. 229(1), 132–140 (2013).
[Crossref] [PubMed]

M. Kyrish, J. Dobbs, S. Jain, X. Wang, D. Yu, R. Richards-Kortum, and T. S. Tkaczyk, “Needle-based fluorescence endomicroscopy via structured illumination with a plastic, achromatic objective,” J. Biomed. Opt. 18(9), 096003 (2013).
[Crossref] [PubMed]

2012 (1)

J. K. Mito, J. M. Ferrer, B. E. Brigman, C. L. Lee, R. D. Dodd, W. C. Eward, L. F. Marshall, K. C. Cuneo, J. E. Carter, S. Ramasunder, Y. Kim, W. D. Lee, L. G. Griffith, M. G. Bawendi, and D. G. Kirsch, “Intraoperative detection and removal of microscopic residual sarcoma using wide-field imaging,” Cancer 118(21), 5320–5330 (2012).
[Crossref] [PubMed]

2011 (1)

N. Nyirenda, D. L. Farkas, and V. K. Ramanujan, “Preclinical evaluation of nuclear morphometry and tissue topology for breast carcinoma detection and margin assessment,” Breast Cancer Res. Treat. 126(2), 345–354 (2011).
[Crossref] [PubMed]

2010 (2)

T. J. Muldoon, N. Thekkek, D. Roblyer, D. Maru, N. Harpaz, J. Potack, S. Anandasabapathy, and R. Richards-Kortum, “Evaluation of quantitative image analysis criteria for the high-resolution microendoscopic detection of neoplasia in Barrett’s esophagus,” J. Biomed. Opt. 15(2), 026027 (2010).
[Crossref] [PubMed]

V. J. Tuominen, S. Ruotoistenmäki, A. Viitanen, M. Jumppanen, and J. Isola, “ImmunoRatio: a publicly available web application for quantitative image analysis of estrogen receptor (ER), progesterone receptor (PR), and Ki-67,” Breast Cancer Res. 12(4), R56 (2010).
[Crossref] [PubMed]

2009 (6)

J. K. Karen, D. S. Gareau, S. W. Dusza, M. Tudisco, M. Rajadhyaksha, and K. S. Nehal, “Detection of basal cell carcinomas in Mohs excisions with fluorescence confocal mosaicing microscopy,” Br. J. Dermatol. 160(6), 1242–1250 (2009).
[Crossref] [PubMed]

D. S. Gareau, “Feasibility of digitally stained multimodal confocal mosaics to simulate histopathology,” J. Biomed. Opt. 14(3), 034050 (2009).
[Crossref] [PubMed]

A. A. Tanbakuchi, A. R. Rouse, J. A. Udovich, K. D. Hatch, and A. F. Gmitro, “Clinical confocal microlaparoscope for real-time in vivo optical biopsies,” J. Biomed. Opt. 14(4), 044030 (2009).
[Crossref] [PubMed]

V. R. Korde, H. Bartels, J. Barton, and J. Ranger-Moore, “Automatic segmentation of cell nuclei in bladder and skin tissue for karyometric analysis,” Analytical and quantitative cytology and histology / the International Academy of Cytology, American Society of Cytology 31, 83–89 (2009).

B. Ko, M. Seo, and J. Y. Nam, “Microscopic cell nuclei segmentation based on adaptive attention window,” J. Digit. Imaging 22(3), 259–274 (2009).
[Crossref] [PubMed]

J. A. Udovich, D. G. Besselsen, and A. F. Gmitro, “Assessment of acridine orange and SYTO 16 for in vivo imaging of the peritoneal tissues in mice,” J. Microsc. 234(2), 124–129 (2009).
[Crossref] [PubMed]

2008 (1)

S. Srivastava, J. J. Rodríguez, A. R. Rouse, M. A. Brewer, and A. F. Gmitro, “Computer-aided identification of ovarian cancer in confocal microendoscope images,” J. Biomed. Opt. 13(2), 024021 (2008).
[Crossref] [PubMed]

2007 (2)

T. J. Muldoon, M. C. Pierce, D. L. Nida, M. D. Williams, A. Gillenwater, and R. Richards-Kortum, “Subcellular-resolution molecular imaging within living tissue by fiber microendoscopy,” Opt. Express 15(25), 16413–16423 (2007).
[Crossref] [PubMed]

D. G. Kirsch, D. M. Dinulescu, J. B. Miller, J. Grimm, P. M. Santiago, N. P. Young, G. P. Nielsen, B. J. Quade, C. J. Chaber, C. P. Schultz, O. Takeuchi, R. T. Bronson, D. Crowley, S. J. Korsmeyer, S. S. Yoon, F. J. Hornicek, R. Weissleder, and T. Jacks, “A spatially and temporally restricted mouse model of soft tissue sarcoma,” Nat. Med. 13(8), 992–997 (2007).
[Crossref] [PubMed]

2006 (2)

S. A. Krolenko, S. Y. Adamyan, T. N. Belyaeva, and T. P. Mozhenok, “Acridine orange accumulation in acid organelles of normal and vacuolated frog skeletal muscle fibres,” Cell Biol. Int. 30(11), 933–939 (2006).
[Crossref] [PubMed]

X. Chen, X. Zhou, and S. T. Wong, “Automated segmentation, classification, and tracking of cancer cell nuclei in time-lapse microscopy,” IEEE Trans. Biomed. Eng. 53(4), 762–766 (2006).
[Crossref] [PubMed]

2005 (1)

J. L. Starck, M. Elad, and D. L. Donoho, “Image decomposition via the combination of sparse representations and a variational approach,” IEEE Trans. Image Process. 14(10), 1570–1582 (2005).
[Crossref] [PubMed]

2004 (1)

C. Wählby, I. M. Sintorn, F. Erlandsson, G. Borgefors, and E. Bengtsson, “Combining intensity, edge and shape information for 2D and 3D segmentation of cell nuclei in tissue sections,” J. Microsc. 215(1), 67–76 (2004).
[Crossref] [PubMed]

2002 (1)

J. Matas, “Robust wide baseline stereo from maximally stable extremal regions,” BMVC 1, 384–393 (2002).

2000 (1)

C. Millot and J. Dufer, “Clinical applications of image cytometry to human tumour analysis,” Histol. Histopathol. 15(4), 1185–1200 (2000).
[PubMed]

1997 (1)

1996 (1)

C. Cohen, “Image cytometric analysis in pathology,” Hum. Pathol. 27(5), 482–493 (1996).
[Crossref] [PubMed]

1981 (1)

D. Ballard, “Generalizing the Hough Transform to Detect Arbitrary Shapes,” Pattern Recognit. 13(2), 111–122 (1981).
[Crossref]

Adamyan, S. Y.

S. A. Krolenko, S. Y. Adamyan, T. N. Belyaeva, and T. P. Mozhenok, “Acridine orange accumulation in acid organelles of normal and vacuolated frog skeletal muscle fibres,” Cell Biol. Int. 30(11), 933–939 (2006).
[Crossref] [PubMed]

Anandasabapathy, S.

T. J. Muldoon, N. Thekkek, D. Roblyer, D. Maru, N. Harpaz, J. Potack, S. Anandasabapathy, and R. Richards-Kortum, “Evaluation of quantitative image analysis criteria for the high-resolution microendoscopic detection of neoplasia in Barrett’s esophagus,” J. Biomed. Opt. 15(2), 026027 (2010).
[Crossref] [PubMed]

Ballard, D.

D. Ballard, “Generalizing the Hough Transform to Detect Arbitrary Shapes,” Pattern Recognit. 13(2), 111–122 (1981).
[Crossref]

Bartels, H.

V. R. Korde, H. Bartels, J. Barton, and J. Ranger-Moore, “Automatic segmentation of cell nuclei in bladder and skin tissue for karyometric analysis,” Analytical and quantitative cytology and histology / the International Academy of Cytology, American Society of Cytology 31, 83–89 (2009).

Barton, J.

V. R. Korde, H. Bartels, J. Barton, and J. Ranger-Moore, “Automatic segmentation of cell nuclei in bladder and skin tissue for karyometric analysis,” Analytical and quantitative cytology and histology / the International Academy of Cytology, American Society of Cytology 31, 83–89 (2009).

Bawendi, M. G.

M. J. Whitley, D. M. Cardona, A. L. Lazarides, I. Spasojevic, J. M. Ferrer, J. Cahill, C. L. Lee, M. Snuderl, D. G. Blazer, E. S. Hwang, R. A. Greenup, P. J. Mosca, J. K. Mito, K. C. Cuneo, N. A. Larrier, E. K. O’Reilly, R. F. Riedel, W. C. Eward, D. B. Strasfeld, D. Fukumura, R. K. Jain, W. D. Lee, L. G. Griffith, M. G. Bawendi, D. G. Kirsch, and B. E. Brigman, “A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer,” Sci. Transl. Med. 8(320), 320ra4 (2016).
[Crossref] [PubMed]

J. K. Mito, J. M. Ferrer, B. E. Brigman, C. L. Lee, R. D. Dodd, W. C. Eward, L. F. Marshall, K. C. Cuneo, J. E. Carter, S. Ramasunder, Y. Kim, W. D. Lee, L. G. Griffith, M. G. Bawendi, and D. G. Kirsch, “Intraoperative detection and removal of microscopic residual sarcoma using wide-field imaging,” Cancer 118(21), 5320–5330 (2012).
[Crossref] [PubMed]

Belyaeva, T. N.

S. A. Krolenko, S. Y. Adamyan, T. N. Belyaeva, and T. P. Mozhenok, “Acridine orange accumulation in acid organelles of normal and vacuolated frog skeletal muscle fibres,” Cell Biol. Int. 30(11), 933–939 (2006).
[Crossref] [PubMed]

Bengtsson, E.

C. Wählby, I. M. Sintorn, F. Erlandsson, G. Borgefors, and E. Bengtsson, “Combining intensity, edge and shape information for 2D and 3D segmentation of cell nuclei in tissue sections,” J. Microsc. 215(1), 67–76 (2004).
[Crossref] [PubMed]

Besselsen, D. G.

J. A. Udovich, D. G. Besselsen, and A. F. Gmitro, “Assessment of acridine orange and SYTO 16 for in vivo imaging of the peritoneal tissues in mice,” J. Microsc. 234(2), 124–129 (2009).
[Crossref] [PubMed]

Blazer, D. G.

M. J. Whitley, D. M. Cardona, A. L. Lazarides, I. Spasojevic, J. M. Ferrer, J. Cahill, C. L. Lee, M. Snuderl, D. G. Blazer, E. S. Hwang, R. A. Greenup, P. J. Mosca, J. K. Mito, K. C. Cuneo, N. A. Larrier, E. K. O’Reilly, R. F. Riedel, W. C. Eward, D. B. Strasfeld, D. Fukumura, R. K. Jain, W. D. Lee, L. G. Griffith, M. G. Bawendi, D. G. Kirsch, and B. E. Brigman, “A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer,” Sci. Transl. Med. 8(320), 320ra4 (2016).
[Crossref] [PubMed]

Borgefors, G.

C. Wählby, I. M. Sintorn, F. Erlandsson, G. Borgefors, and E. Bengtsson, “Combining intensity, edge and shape information for 2D and 3D segmentation of cell nuclei in tissue sections,” J. Microsc. 215(1), 67–76 (2004).
[Crossref] [PubMed]

Brewer, M. A.

S. Srivastava, J. J. Rodríguez, A. R. Rouse, M. A. Brewer, and A. F. Gmitro, “Computer-aided identification of ovarian cancer in confocal microendoscope images,” J. Biomed. Opt. 13(2), 024021 (2008).
[Crossref] [PubMed]

Brigman, B. E.

M. J. Whitley, D. M. Cardona, A. L. Lazarides, I. Spasojevic, J. M. Ferrer, J. Cahill, C. L. Lee, M. Snuderl, D. G. Blazer, E. S. Hwang, R. A. Greenup, P. J. Mosca, J. K. Mito, K. C. Cuneo, N. A. Larrier, E. K. O’Reilly, R. F. Riedel, W. C. Eward, D. B. Strasfeld, D. Fukumura, R. K. Jain, W. D. Lee, L. G. Griffith, M. G. Bawendi, D. G. Kirsch, and B. E. Brigman, “A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer,” Sci. Transl. Med. 8(320), 320ra4 (2016).
[Crossref] [PubMed]

J. K. Mito, H. D. Min, Y. Ma, J. E. Carter, B. E. Brigman, L. Dodd, D. Dankort, M. McMahon, and D. G. Kirsch, “Oncogene-dependent control of miRNA biogenesis and metastatic progression in a model of undifferentiated pleomorphic sarcoma,” J. Pathol. 229(1), 132–140 (2013).
[Crossref] [PubMed]

J. K. Mito, J. M. Ferrer, B. E. Brigman, C. L. Lee, R. D. Dodd, W. C. Eward, L. F. Marshall, K. C. Cuneo, J. E. Carter, S. Ramasunder, Y. Kim, W. D. Lee, L. G. Griffith, M. G. Bawendi, and D. G. Kirsch, “Intraoperative detection and removal of microscopic residual sarcoma using wide-field imaging,” Cancer 118(21), 5320–5330 (2012).
[Crossref] [PubMed]

Bronson, R. T.

D. G. Kirsch, D. M. Dinulescu, J. B. Miller, J. Grimm, P. M. Santiago, N. P. Young, G. P. Nielsen, B. J. Quade, C. J. Chaber, C. P. Schultz, O. Takeuchi, R. T. Bronson, D. Crowley, S. J. Korsmeyer, S. S. Yoon, F. J. Hornicek, R. Weissleder, and T. Jacks, “A spatially and temporally restricted mouse model of soft tissue sarcoma,” Nat. Med. 13(8), 992–997 (2007).
[Crossref] [PubMed]

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J. L. Mueller, Z. T. Harmany, J. K. Mito, S. A. Kennedy, Y. Kim, L. Dodd, J. Geradts, D. G. Kirsch, R. M. Willett, J. Q. Brown, and N. Ramanujam, “Quantitative Segmentation of Fluorescence Microscopy Images of Heterogeneous Tissue: Application to the Detection of Residual Disease in Tumor Margins,” PLoS One 8(6), e66198 (2013).
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H. Fu, J. Mueller, M. Whitley, D. Cardona, R. Willet, D. Kirsch, Q. Brown, and N. Ramanujam, “Structured illumination microscopy and a quantitative image analysis for the detection of positive margins in a pre-clinical genetically engineered mouse model of sarcoma,” PLoS One 11(1), e0147006 (2015).
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J. K. Mito, J. M. Ferrer, B. E. Brigman, C. L. Lee, R. D. Dodd, W. C. Eward, L. F. Marshall, K. C. Cuneo, J. E. Carter, S. Ramasunder, Y. Kim, W. D. Lee, L. G. Griffith, M. G. Bawendi, and D. G. Kirsch, “Intraoperative detection and removal of microscopic residual sarcoma using wide-field imaging,” Cancer 118(21), 5320–5330 (2012).
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J. K. Mito, H. D. Min, Y. Ma, J. E. Carter, B. E. Brigman, L. Dodd, D. Dankort, M. McMahon, and D. G. Kirsch, “Oncogene-dependent control of miRNA biogenesis and metastatic progression in a model of undifferentiated pleomorphic sarcoma,” J. Pathol. 229(1), 132–140 (2013).
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J. K. Mito, H. D. Min, Y. Ma, J. E. Carter, B. E. Brigman, L. Dodd, D. Dankort, M. McMahon, and D. G. Kirsch, “Oncogene-dependent control of miRNA biogenesis and metastatic progression in a model of undifferentiated pleomorphic sarcoma,” J. Pathol. 229(1), 132–140 (2013).
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J. K. Mito, J. M. Ferrer, B. E. Brigman, C. L. Lee, R. D. Dodd, W. C. Eward, L. F. Marshall, K. C. Cuneo, J. E. Carter, S. Ramasunder, Y. Kim, W. D. Lee, L. G. Griffith, M. G. Bawendi, and D. G. Kirsch, “Intraoperative detection and removal of microscopic residual sarcoma using wide-field imaging,” Cancer 118(21), 5320–5330 (2012).
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H. L. Fu, J. L. Mueller, M. P. Javid, J. K. Mito, D. G. Kirsch, N. Ramanujam, and J. Q. Brown, “Optimization of a widefield structured illumination microscope for non-destructive assessment and quantification of nuclear features in tumor margins of a primary mouse model of sarcoma,” PLoS One 8(7), e68868 (2013).
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J. K. Mito, J. M. Ferrer, B. E. Brigman, C. L. Lee, R. D. Dodd, W. C. Eward, L. F. Marshall, K. C. Cuneo, J. E. Carter, S. Ramasunder, Y. Kim, W. D. Lee, L. G. Griffith, M. G. Bawendi, and D. G. Kirsch, “Intraoperative detection and removal of microscopic residual sarcoma using wide-field imaging,” Cancer 118(21), 5320–5330 (2012).
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D. G. Kirsch, D. M. Dinulescu, J. B. Miller, J. Grimm, P. M. Santiago, N. P. Young, G. P. Nielsen, B. J. Quade, C. J. Chaber, C. P. Schultz, O. Takeuchi, R. T. Bronson, D. Crowley, S. J. Korsmeyer, S. S. Yoon, F. J. Hornicek, R. Weissleder, and T. Jacks, “A spatially and temporally restricted mouse model of soft tissue sarcoma,” Nat. Med. 13(8), 992–997 (2007).
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J. L. Mueller, Z. T. Harmany, J. K. Mito, S. A. Kennedy, Y. Kim, L. Dodd, J. Geradts, D. G. Kirsch, R. M. Willett, J. Q. Brown, and N. Ramanujam, “Quantitative Segmentation of Fluorescence Microscopy Images of Heterogeneous Tissue: Application to the Detection of Residual Disease in Tumor Margins,” PLoS One 8(6), e66198 (2013).
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M. J. Whitley, D. M. Cardona, A. L. Lazarides, I. Spasojevic, J. M. Ferrer, J. Cahill, C. L. Lee, M. Snuderl, D. G. Blazer, E. S. Hwang, R. A. Greenup, P. J. Mosca, J. K. Mito, K. C. Cuneo, N. A. Larrier, E. K. O’Reilly, R. F. Riedel, W. C. Eward, D. B. Strasfeld, D. Fukumura, R. K. Jain, W. D. Lee, L. G. Griffith, M. G. Bawendi, D. G. Kirsch, and B. E. Brigman, “A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer,” Sci. Transl. Med. 8(320), 320ra4 (2016).
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D. G. Kirsch, D. M. Dinulescu, J. B. Miller, J. Grimm, P. M. Santiago, N. P. Young, G. P. Nielsen, B. J. Quade, C. J. Chaber, C. P. Schultz, O. Takeuchi, R. T. Bronson, D. Crowley, S. J. Korsmeyer, S. S. Yoon, F. J. Hornicek, R. Weissleder, and T. Jacks, “A spatially and temporally restricted mouse model of soft tissue sarcoma,” Nat. Med. 13(8), 992–997 (2007).
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Jain, R. K.

M. J. Whitley, D. M. Cardona, A. L. Lazarides, I. Spasojevic, J. M. Ferrer, J. Cahill, C. L. Lee, M. Snuderl, D. G. Blazer, E. S. Hwang, R. A. Greenup, P. J. Mosca, J. K. Mito, K. C. Cuneo, N. A. Larrier, E. K. O’Reilly, R. F. Riedel, W. C. Eward, D. B. Strasfeld, D. Fukumura, R. K. Jain, W. D. Lee, L. G. Griffith, M. G. Bawendi, D. G. Kirsch, and B. E. Brigman, “A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer,” Sci. Transl. Med. 8(320), 320ra4 (2016).
[Crossref] [PubMed]

Jain, S.

M. Kyrish, J. Dobbs, S. Jain, X. Wang, D. Yu, R. Richards-Kortum, and T. S. Tkaczyk, “Needle-based fluorescence endomicroscopy via structured illumination with a plastic, achromatic objective,” J. Biomed. Opt. 18(9), 096003 (2013).
[Crossref] [PubMed]

Javid, M. P.

H. L. Fu, J. L. Mueller, M. P. Javid, J. K. Mito, D. G. Kirsch, N. Ramanujam, and J. Q. Brown, “Optimization of a widefield structured illumination microscope for non-destructive assessment and quantification of nuclear features in tumor margins of a primary mouse model of sarcoma,” PLoS One 8(7), e68868 (2013).
[Crossref] [PubMed]

Jumppanen, M.

V. J. Tuominen, S. Ruotoistenmäki, A. Viitanen, M. Jumppanen, and J. Isola, “ImmunoRatio: a publicly available web application for quantitative image analysis of estrogen receptor (ER), progesterone receptor (PR), and Ki-67,” Breast Cancer Res. 12(4), R56 (2010).
[Crossref] [PubMed]

Juskaitis, R.

Karen, J. K.

J. K. Karen, D. S. Gareau, S. W. Dusza, M. Tudisco, M. Rajadhyaksha, and K. S. Nehal, “Detection of basal cell carcinomas in Mohs excisions with fluorescence confocal mosaicing microscopy,” Br. J. Dermatol. 160(6), 1242–1250 (2009).
[Crossref] [PubMed]

Kennedy, S. A.

J. L. Mueller, Z. T. Harmany, J. K. Mito, S. A. Kennedy, Y. Kim, L. Dodd, J. Geradts, D. G. Kirsch, R. M. Willett, J. Q. Brown, and N. Ramanujam, “Quantitative Segmentation of Fluorescence Microscopy Images of Heterogeneous Tissue: Application to the Detection of Residual Disease in Tumor Margins,” PLoS One 8(6), e66198 (2013).
[Crossref] [PubMed]

Kim, Y.

J. L. Mueller, Z. T. Harmany, J. K. Mito, S. A. Kennedy, Y. Kim, L. Dodd, J. Geradts, D. G. Kirsch, R. M. Willett, J. Q. Brown, and N. Ramanujam, “Quantitative Segmentation of Fluorescence Microscopy Images of Heterogeneous Tissue: Application to the Detection of Residual Disease in Tumor Margins,” PLoS One 8(6), e66198 (2013).
[Crossref] [PubMed]

J. K. Mito, J. M. Ferrer, B. E. Brigman, C. L. Lee, R. D. Dodd, W. C. Eward, L. F. Marshall, K. C. Cuneo, J. E. Carter, S. Ramasunder, Y. Kim, W. D. Lee, L. G. Griffith, M. G. Bawendi, and D. G. Kirsch, “Intraoperative detection and removal of microscopic residual sarcoma using wide-field imaging,” Cancer 118(21), 5320–5330 (2012).
[Crossref] [PubMed]

Kirsch, D.

H. Fu, J. Mueller, M. Whitley, D. Cardona, R. Willet, D. Kirsch, Q. Brown, and N. Ramanujam, “Structured illumination microscopy and a quantitative image analysis for the detection of positive margins in a pre-clinical genetically engineered mouse model of sarcoma,” PLoS One 11(1), e0147006 (2015).
[PubMed]

Kirsch, D. G.

M. J. Whitley, D. M. Cardona, A. L. Lazarides, I. Spasojevic, J. M. Ferrer, J. Cahill, C. L. Lee, M. Snuderl, D. G. Blazer, E. S. Hwang, R. A. Greenup, P. J. Mosca, J. K. Mito, K. C. Cuneo, N. A. Larrier, E. K. O’Reilly, R. F. Riedel, W. C. Eward, D. B. Strasfeld, D. Fukumura, R. K. Jain, W. D. Lee, L. G. Griffith, M. G. Bawendi, D. G. Kirsch, and B. E. Brigman, “A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer,” Sci. Transl. Med. 8(320), 320ra4 (2016).
[Crossref] [PubMed]

J. L. Mueller, H. L. Fu, J. K. Mito, M. J. Whitley, R. Chitalia, A. Erkanli, L. Dodd, D. M. Cardona, J. Geradts, R. M. Willett, D. G. Kirsch, and N. Ramanujam, “A quantitative microscopic approach to predict local recurrence based on in vivo intraoperative imaging of sarcoma tumor margins,” Int. J. Cancer 137(10), 2403–2412 (2015).
[Crossref] [PubMed]

J. K. Mito, H. D. Min, Y. Ma, J. E. Carter, B. E. Brigman, L. Dodd, D. Dankort, M. McMahon, and D. G. Kirsch, “Oncogene-dependent control of miRNA biogenesis and metastatic progression in a model of undifferentiated pleomorphic sarcoma,” J. Pathol. 229(1), 132–140 (2013).
[Crossref] [PubMed]

H. L. Fu, J. L. Mueller, M. P. Javid, J. K. Mito, D. G. Kirsch, N. Ramanujam, and J. Q. Brown, “Optimization of a widefield structured illumination microscope for non-destructive assessment and quantification of nuclear features in tumor margins of a primary mouse model of sarcoma,” PLoS One 8(7), e68868 (2013).
[Crossref] [PubMed]

J. L. Mueller, Z. T. Harmany, J. K. Mito, S. A. Kennedy, Y. Kim, L. Dodd, J. Geradts, D. G. Kirsch, R. M. Willett, J. Q. Brown, and N. Ramanujam, “Quantitative Segmentation of Fluorescence Microscopy Images of Heterogeneous Tissue: Application to the Detection of Residual Disease in Tumor Margins,” PLoS One 8(6), e66198 (2013).
[Crossref] [PubMed]

J. K. Mito, J. M. Ferrer, B. E. Brigman, C. L. Lee, R. D. Dodd, W. C. Eward, L. F. Marshall, K. C. Cuneo, J. E. Carter, S. Ramasunder, Y. Kim, W. D. Lee, L. G. Griffith, M. G. Bawendi, and D. G. Kirsch, “Intraoperative detection and removal of microscopic residual sarcoma using wide-field imaging,” Cancer 118(21), 5320–5330 (2012).
[Crossref] [PubMed]

D. G. Kirsch, D. M. Dinulescu, J. B. Miller, J. Grimm, P. M. Santiago, N. P. Young, G. P. Nielsen, B. J. Quade, C. J. Chaber, C. P. Schultz, O. Takeuchi, R. T. Bronson, D. Crowley, S. J. Korsmeyer, S. S. Yoon, F. J. Hornicek, R. Weissleder, and T. Jacks, “A spatially and temporally restricted mouse model of soft tissue sarcoma,” Nat. Med. 13(8), 992–997 (2007).
[Crossref] [PubMed]

Ko, B.

B. Ko, M. Seo, and J. Y. Nam, “Microscopic cell nuclei segmentation based on adaptive attention window,” J. Digit. Imaging 22(3), 259–274 (2009).
[Crossref] [PubMed]

Korde, V. R.

V. R. Korde, H. Bartels, J. Barton, and J. Ranger-Moore, “Automatic segmentation of cell nuclei in bladder and skin tissue for karyometric analysis,” Analytical and quantitative cytology and histology / the International Academy of Cytology, American Society of Cytology 31, 83–89 (2009).

Korsmeyer, S. J.

D. G. Kirsch, D. M. Dinulescu, J. B. Miller, J. Grimm, P. M. Santiago, N. P. Young, G. P. Nielsen, B. J. Quade, C. J. Chaber, C. P. Schultz, O. Takeuchi, R. T. Bronson, D. Crowley, S. J. Korsmeyer, S. S. Yoon, F. J. Hornicek, R. Weissleder, and T. Jacks, “A spatially and temporally restricted mouse model of soft tissue sarcoma,” Nat. Med. 13(8), 992–997 (2007).
[Crossref] [PubMed]

Krishnamurthy, S.

J. L. Dobbs, J. L. Mueller, S. Krishnamurthy, D. Shin, H. Kuerer, W. Yang, N. Ramanujam, and R. Richards-Kortum, “Micro-anatomical quantitative optical imaging: toward automated assessment of breast tissues,” Breast Cancer Res. 17(1), 105 (2015).
[Crossref] [PubMed]

Krolenko, S. A.

S. A. Krolenko, S. Y. Adamyan, T. N. Belyaeva, and T. P. Mozhenok, “Acridine orange accumulation in acid organelles of normal and vacuolated frog skeletal muscle fibres,” Cell Biol. Int. 30(11), 933–939 (2006).
[Crossref] [PubMed]

Kuerer, H.

J. L. Dobbs, J. L. Mueller, S. Krishnamurthy, D. Shin, H. Kuerer, W. Yang, N. Ramanujam, and R. Richards-Kortum, “Micro-anatomical quantitative optical imaging: toward automated assessment of breast tissues,” Breast Cancer Res. 17(1), 105 (2015).
[Crossref] [PubMed]

Kyrish, M.

M. Kyrish, J. Dobbs, S. Jain, X. Wang, D. Yu, R. Richards-Kortum, and T. S. Tkaczyk, “Needle-based fluorescence endomicroscopy via structured illumination with a plastic, achromatic objective,” J. Biomed. Opt. 18(9), 096003 (2013).
[Crossref] [PubMed]

Larrier, N. A.

M. J. Whitley, D. M. Cardona, A. L. Lazarides, I. Spasojevic, J. M. Ferrer, J. Cahill, C. L. Lee, M. Snuderl, D. G. Blazer, E. S. Hwang, R. A. Greenup, P. J. Mosca, J. K. Mito, K. C. Cuneo, N. A. Larrier, E. K. O’Reilly, R. F. Riedel, W. C. Eward, D. B. Strasfeld, D. Fukumura, R. K. Jain, W. D. Lee, L. G. Griffith, M. G. Bawendi, D. G. Kirsch, and B. E. Brigman, “A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer,” Sci. Transl. Med. 8(320), 320ra4 (2016).
[Crossref] [PubMed]

Lazarides, A. L.

M. J. Whitley, D. M. Cardona, A. L. Lazarides, I. Spasojevic, J. M. Ferrer, J. Cahill, C. L. Lee, M. Snuderl, D. G. Blazer, E. S. Hwang, R. A. Greenup, P. J. Mosca, J. K. Mito, K. C. Cuneo, N. A. Larrier, E. K. O’Reilly, R. F. Riedel, W. C. Eward, D. B. Strasfeld, D. Fukumura, R. K. Jain, W. D. Lee, L. G. Griffith, M. G. Bawendi, D. G. Kirsch, and B. E. Brigman, “A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer,” Sci. Transl. Med. 8(320), 320ra4 (2016).
[Crossref] [PubMed]

Lee, C. L.

M. J. Whitley, D. M. Cardona, A. L. Lazarides, I. Spasojevic, J. M. Ferrer, J. Cahill, C. L. Lee, M. Snuderl, D. G. Blazer, E. S. Hwang, R. A. Greenup, P. J. Mosca, J. K. Mito, K. C. Cuneo, N. A. Larrier, E. K. O’Reilly, R. F. Riedel, W. C. Eward, D. B. Strasfeld, D. Fukumura, R. K. Jain, W. D. Lee, L. G. Griffith, M. G. Bawendi, D. G. Kirsch, and B. E. Brigman, “A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer,” Sci. Transl. Med. 8(320), 320ra4 (2016).
[Crossref] [PubMed]

J. K. Mito, J. M. Ferrer, B. E. Brigman, C. L. Lee, R. D. Dodd, W. C. Eward, L. F. Marshall, K. C. Cuneo, J. E. Carter, S. Ramasunder, Y. Kim, W. D. Lee, L. G. Griffith, M. G. Bawendi, and D. G. Kirsch, “Intraoperative detection and removal of microscopic residual sarcoma using wide-field imaging,” Cancer 118(21), 5320–5330 (2012).
[Crossref] [PubMed]

Lee, W. D.

M. J. Whitley, D. M. Cardona, A. L. Lazarides, I. Spasojevic, J. M. Ferrer, J. Cahill, C. L. Lee, M. Snuderl, D. G. Blazer, E. S. Hwang, R. A. Greenup, P. J. Mosca, J. K. Mito, K. C. Cuneo, N. A. Larrier, E. K. O’Reilly, R. F. Riedel, W. C. Eward, D. B. Strasfeld, D. Fukumura, R. K. Jain, W. D. Lee, L. G. Griffith, M. G. Bawendi, D. G. Kirsch, and B. E. Brigman, “A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer,” Sci. Transl. Med. 8(320), 320ra4 (2016).
[Crossref] [PubMed]

J. K. Mito, J. M. Ferrer, B. E. Brigman, C. L. Lee, R. D. Dodd, W. C. Eward, L. F. Marshall, K. C. Cuneo, J. E. Carter, S. Ramasunder, Y. Kim, W. D. Lee, L. G. Griffith, M. G. Bawendi, and D. G. Kirsch, “Intraoperative detection and removal of microscopic residual sarcoma using wide-field imaging,” Cancer 118(21), 5320–5330 (2012).
[Crossref] [PubMed]

Ma, Y.

J. K. Mito, H. D. Min, Y. Ma, J. E. Carter, B. E. Brigman, L. Dodd, D. Dankort, M. McMahon, and D. G. Kirsch, “Oncogene-dependent control of miRNA biogenesis and metastatic progression in a model of undifferentiated pleomorphic sarcoma,” J. Pathol. 229(1), 132–140 (2013).
[Crossref] [PubMed]

Marshall, L. F.

J. K. Mito, J. M. Ferrer, B. E. Brigman, C. L. Lee, R. D. Dodd, W. C. Eward, L. F. Marshall, K. C. Cuneo, J. E. Carter, S. Ramasunder, Y. Kim, W. D. Lee, L. G. Griffith, M. G. Bawendi, and D. G. Kirsch, “Intraoperative detection and removal of microscopic residual sarcoma using wide-field imaging,” Cancer 118(21), 5320–5330 (2012).
[Crossref] [PubMed]

Maru, D.

T. J. Muldoon, N. Thekkek, D. Roblyer, D. Maru, N. Harpaz, J. Potack, S. Anandasabapathy, and R. Richards-Kortum, “Evaluation of quantitative image analysis criteria for the high-resolution microendoscopic detection of neoplasia in Barrett’s esophagus,” J. Biomed. Opt. 15(2), 026027 (2010).
[Crossref] [PubMed]

Matas, J.

J. Matas, “Robust wide baseline stereo from maximally stable extremal regions,” BMVC 1, 384–393 (2002).

McMahon, M.

J. K. Mito, H. D. Min, Y. Ma, J. E. Carter, B. E. Brigman, L. Dodd, D. Dankort, M. McMahon, and D. G. Kirsch, “Oncogene-dependent control of miRNA biogenesis and metastatic progression in a model of undifferentiated pleomorphic sarcoma,” J. Pathol. 229(1), 132–140 (2013).
[Crossref] [PubMed]

Miller, J. B.

D. G. Kirsch, D. M. Dinulescu, J. B. Miller, J. Grimm, P. M. Santiago, N. P. Young, G. P. Nielsen, B. J. Quade, C. J. Chaber, C. P. Schultz, O. Takeuchi, R. T. Bronson, D. Crowley, S. J. Korsmeyer, S. S. Yoon, F. J. Hornicek, R. Weissleder, and T. Jacks, “A spatially and temporally restricted mouse model of soft tissue sarcoma,” Nat. Med. 13(8), 992–997 (2007).
[Crossref] [PubMed]

Millot, C.

C. Millot and J. Dufer, “Clinical applications of image cytometry to human tumour analysis,” Histol. Histopathol. 15(4), 1185–1200 (2000).
[PubMed]

Min, H. D.

J. K. Mito, H. D. Min, Y. Ma, J. E. Carter, B. E. Brigman, L. Dodd, D. Dankort, M. McMahon, and D. G. Kirsch, “Oncogene-dependent control of miRNA biogenesis and metastatic progression in a model of undifferentiated pleomorphic sarcoma,” J. Pathol. 229(1), 132–140 (2013).
[Crossref] [PubMed]

Mito, J. K.

M. J. Whitley, D. M. Cardona, A. L. Lazarides, I. Spasojevic, J. M. Ferrer, J. Cahill, C. L. Lee, M. Snuderl, D. G. Blazer, E. S. Hwang, R. A. Greenup, P. J. Mosca, J. K. Mito, K. C. Cuneo, N. A. Larrier, E. K. O’Reilly, R. F. Riedel, W. C. Eward, D. B. Strasfeld, D. Fukumura, R. K. Jain, W. D. Lee, L. G. Griffith, M. G. Bawendi, D. G. Kirsch, and B. E. Brigman, “A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer,” Sci. Transl. Med. 8(320), 320ra4 (2016).
[Crossref] [PubMed]

J. L. Mueller, H. L. Fu, J. K. Mito, M. J. Whitley, R. Chitalia, A. Erkanli, L. Dodd, D. M. Cardona, J. Geradts, R. M. Willett, D. G. Kirsch, and N. Ramanujam, “A quantitative microscopic approach to predict local recurrence based on in vivo intraoperative imaging of sarcoma tumor margins,” Int. J. Cancer 137(10), 2403–2412 (2015).
[Crossref] [PubMed]

J. K. Mito, H. D. Min, Y. Ma, J. E. Carter, B. E. Brigman, L. Dodd, D. Dankort, M. McMahon, and D. G. Kirsch, “Oncogene-dependent control of miRNA biogenesis and metastatic progression in a model of undifferentiated pleomorphic sarcoma,” J. Pathol. 229(1), 132–140 (2013).
[Crossref] [PubMed]

H. L. Fu, J. L. Mueller, M. P. Javid, J. K. Mito, D. G. Kirsch, N. Ramanujam, and J. Q. Brown, “Optimization of a widefield structured illumination microscope for non-destructive assessment and quantification of nuclear features in tumor margins of a primary mouse model of sarcoma,” PLoS One 8(7), e68868 (2013).
[Crossref] [PubMed]

J. L. Mueller, Z. T. Harmany, J. K. Mito, S. A. Kennedy, Y. Kim, L. Dodd, J. Geradts, D. G. Kirsch, R. M. Willett, J. Q. Brown, and N. Ramanujam, “Quantitative Segmentation of Fluorescence Microscopy Images of Heterogeneous Tissue: Application to the Detection of Residual Disease in Tumor Margins,” PLoS One 8(6), e66198 (2013).
[Crossref] [PubMed]

J. K. Mito, J. M. Ferrer, B. E. Brigman, C. L. Lee, R. D. Dodd, W. C. Eward, L. F. Marshall, K. C. Cuneo, J. E. Carter, S. Ramasunder, Y. Kim, W. D. Lee, L. G. Griffith, M. G. Bawendi, and D. G. Kirsch, “Intraoperative detection and removal of microscopic residual sarcoma using wide-field imaging,” Cancer 118(21), 5320–5330 (2012).
[Crossref] [PubMed]

Mosca, P. J.

M. J. Whitley, D. M. Cardona, A. L. Lazarides, I. Spasojevic, J. M. Ferrer, J. Cahill, C. L. Lee, M. Snuderl, D. G. Blazer, E. S. Hwang, R. A. Greenup, P. J. Mosca, J. K. Mito, K. C. Cuneo, N. A. Larrier, E. K. O’Reilly, R. F. Riedel, W. C. Eward, D. B. Strasfeld, D. Fukumura, R. K. Jain, W. D. Lee, L. G. Griffith, M. G. Bawendi, D. G. Kirsch, and B. E. Brigman, “A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer,” Sci. Transl. Med. 8(320), 320ra4 (2016).
[Crossref] [PubMed]

Mozhenok, T. P.

S. A. Krolenko, S. Y. Adamyan, T. N. Belyaeva, and T. P. Mozhenok, “Acridine orange accumulation in acid organelles of normal and vacuolated frog skeletal muscle fibres,” Cell Biol. Int. 30(11), 933–939 (2006).
[Crossref] [PubMed]

Mueller, J.

H. Fu, J. Mueller, M. Whitley, D. Cardona, R. Willet, D. Kirsch, Q. Brown, and N. Ramanujam, “Structured illumination microscopy and a quantitative image analysis for the detection of positive margins in a pre-clinical genetically engineered mouse model of sarcoma,” PLoS One 11(1), e0147006 (2015).
[PubMed]

Mueller, J. L.

J. L. Mueller, H. L. Fu, J. K. Mito, M. J. Whitley, R. Chitalia, A. Erkanli, L. Dodd, D. M. Cardona, J. Geradts, R. M. Willett, D. G. Kirsch, and N. Ramanujam, “A quantitative microscopic approach to predict local recurrence based on in vivo intraoperative imaging of sarcoma tumor margins,” Int. J. Cancer 137(10), 2403–2412 (2015).
[Crossref] [PubMed]

J. L. Dobbs, J. L. Mueller, S. Krishnamurthy, D. Shin, H. Kuerer, W. Yang, N. Ramanujam, and R. Richards-Kortum, “Micro-anatomical quantitative optical imaging: toward automated assessment of breast tissues,” Breast Cancer Res. 17(1), 105 (2015).
[Crossref] [PubMed]

J. L. Mueller, Z. T. Harmany, J. K. Mito, S. A. Kennedy, Y. Kim, L. Dodd, J. Geradts, D. G. Kirsch, R. M. Willett, J. Q. Brown, and N. Ramanujam, “Quantitative Segmentation of Fluorescence Microscopy Images of Heterogeneous Tissue: Application to the Detection of Residual Disease in Tumor Margins,” PLoS One 8(6), e66198 (2013).
[Crossref] [PubMed]

H. L. Fu, J. L. Mueller, M. P. Javid, J. K. Mito, D. G. Kirsch, N. Ramanujam, and J. Q. Brown, “Optimization of a widefield structured illumination microscope for non-destructive assessment and quantification of nuclear features in tumor margins of a primary mouse model of sarcoma,” PLoS One 8(7), e68868 (2013).
[Crossref] [PubMed]

Muldoon, T. J.

T. J. Muldoon, N. Thekkek, D. Roblyer, D. Maru, N. Harpaz, J. Potack, S. Anandasabapathy, and R. Richards-Kortum, “Evaluation of quantitative image analysis criteria for the high-resolution microendoscopic detection of neoplasia in Barrett’s esophagus,” J. Biomed. Opt. 15(2), 026027 (2010).
[Crossref] [PubMed]

T. J. Muldoon, M. C. Pierce, D. L. Nida, M. D. Williams, A. Gillenwater, and R. Richards-Kortum, “Subcellular-resolution molecular imaging within living tissue by fiber microendoscopy,” Opt. Express 15(25), 16413–16423 (2007).
[Crossref] [PubMed]

Nam, J. Y.

B. Ko, M. Seo, and J. Y. Nam, “Microscopic cell nuclei segmentation based on adaptive attention window,” J. Digit. Imaging 22(3), 259–274 (2009).
[Crossref] [PubMed]

Nehal, K. S.

J. K. Karen, D. S. Gareau, S. W. Dusza, M. Tudisco, M. Rajadhyaksha, and K. S. Nehal, “Detection of basal cell carcinomas in Mohs excisions with fluorescence confocal mosaicing microscopy,” Br. J. Dermatol. 160(6), 1242–1250 (2009).
[Crossref] [PubMed]

Neil, M. A.

Nida, D. L.

Nielsen, G. P.

D. G. Kirsch, D. M. Dinulescu, J. B. Miller, J. Grimm, P. M. Santiago, N. P. Young, G. P. Nielsen, B. J. Quade, C. J. Chaber, C. P. Schultz, O. Takeuchi, R. T. Bronson, D. Crowley, S. J. Korsmeyer, S. S. Yoon, F. J. Hornicek, R. Weissleder, and T. Jacks, “A spatially and temporally restricted mouse model of soft tissue sarcoma,” Nat. Med. 13(8), 992–997 (2007).
[Crossref] [PubMed]

Nyirenda, N.

N. Nyirenda, D. L. Farkas, and V. K. Ramanujan, “Preclinical evaluation of nuclear morphometry and tissue topology for breast carcinoma detection and margin assessment,” Breast Cancer Res. Treat. 126(2), 345–354 (2011).
[Crossref] [PubMed]

O’Reilly, E. K.

M. J. Whitley, D. M. Cardona, A. L. Lazarides, I. Spasojevic, J. M. Ferrer, J. Cahill, C. L. Lee, M. Snuderl, D. G. Blazer, E. S. Hwang, R. A. Greenup, P. J. Mosca, J. K. Mito, K. C. Cuneo, N. A. Larrier, E. K. O’Reilly, R. F. Riedel, W. C. Eward, D. B. Strasfeld, D. Fukumura, R. K. Jain, W. D. Lee, L. G. Griffith, M. G. Bawendi, D. G. Kirsch, and B. E. Brigman, “A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer,” Sci. Transl. Med. 8(320), 320ra4 (2016).
[Crossref] [PubMed]

Pierce, M. C.

Potack, J.

T. J. Muldoon, N. Thekkek, D. Roblyer, D. Maru, N. Harpaz, J. Potack, S. Anandasabapathy, and R. Richards-Kortum, “Evaluation of quantitative image analysis criteria for the high-resolution microendoscopic detection of neoplasia in Barrett’s esophagus,” J. Biomed. Opt. 15(2), 026027 (2010).
[Crossref] [PubMed]

Quade, B. J.

D. G. Kirsch, D. M. Dinulescu, J. B. Miller, J. Grimm, P. M. Santiago, N. P. Young, G. P. Nielsen, B. J. Quade, C. J. Chaber, C. P. Schultz, O. Takeuchi, R. T. Bronson, D. Crowley, S. J. Korsmeyer, S. S. Yoon, F. J. Hornicek, R. Weissleder, and T. Jacks, “A spatially and temporally restricted mouse model of soft tissue sarcoma,” Nat. Med. 13(8), 992–997 (2007).
[Crossref] [PubMed]

Rajadhyaksha, M.

J. K. Karen, D. S. Gareau, S. W. Dusza, M. Tudisco, M. Rajadhyaksha, and K. S. Nehal, “Detection of basal cell carcinomas in Mohs excisions with fluorescence confocal mosaicing microscopy,” Br. J. Dermatol. 160(6), 1242–1250 (2009).
[Crossref] [PubMed]

Ramanujam, N.

H. Fu, J. Mueller, M. Whitley, D. Cardona, R. Willet, D. Kirsch, Q. Brown, and N. Ramanujam, “Structured illumination microscopy and a quantitative image analysis for the detection of positive margins in a pre-clinical genetically engineered mouse model of sarcoma,” PLoS One 11(1), e0147006 (2015).
[PubMed]

J. L. Mueller, H. L. Fu, J. K. Mito, M. J. Whitley, R. Chitalia, A. Erkanli, L. Dodd, D. M. Cardona, J. Geradts, R. M. Willett, D. G. Kirsch, and N. Ramanujam, “A quantitative microscopic approach to predict local recurrence based on in vivo intraoperative imaging of sarcoma tumor margins,” Int. J. Cancer 137(10), 2403–2412 (2015).
[Crossref] [PubMed]

J. L. Dobbs, J. L. Mueller, S. Krishnamurthy, D. Shin, H. Kuerer, W. Yang, N. Ramanujam, and R. Richards-Kortum, “Micro-anatomical quantitative optical imaging: toward automated assessment of breast tissues,” Breast Cancer Res. 17(1), 105 (2015).
[Crossref] [PubMed]

H. L. Fu, J. L. Mueller, M. P. Javid, J. K. Mito, D. G. Kirsch, N. Ramanujam, and J. Q. Brown, “Optimization of a widefield structured illumination microscope for non-destructive assessment and quantification of nuclear features in tumor margins of a primary mouse model of sarcoma,” PLoS One 8(7), e68868 (2013).
[Crossref] [PubMed]

J. L. Mueller, Z. T. Harmany, J. K. Mito, S. A. Kennedy, Y. Kim, L. Dodd, J. Geradts, D. G. Kirsch, R. M. Willett, J. Q. Brown, and N. Ramanujam, “Quantitative Segmentation of Fluorescence Microscopy Images of Heterogeneous Tissue: Application to the Detection of Residual Disease in Tumor Margins,” PLoS One 8(6), e66198 (2013).
[Crossref] [PubMed]

Ramanujan, V. K.

N. Nyirenda, D. L. Farkas, and V. K. Ramanujan, “Preclinical evaluation of nuclear morphometry and tissue topology for breast carcinoma detection and margin assessment,” Breast Cancer Res. Treat. 126(2), 345–354 (2011).
[Crossref] [PubMed]

Ramasunder, S.

J. K. Mito, J. M. Ferrer, B. E. Brigman, C. L. Lee, R. D. Dodd, W. C. Eward, L. F. Marshall, K. C. Cuneo, J. E. Carter, S. Ramasunder, Y. Kim, W. D. Lee, L. G. Griffith, M. G. Bawendi, and D. G. Kirsch, “Intraoperative detection and removal of microscopic residual sarcoma using wide-field imaging,” Cancer 118(21), 5320–5330 (2012).
[Crossref] [PubMed]

Ranger-Moore, J.

V. R. Korde, H. Bartels, J. Barton, and J. Ranger-Moore, “Automatic segmentation of cell nuclei in bladder and skin tissue for karyometric analysis,” Analytical and quantitative cytology and histology / the International Academy of Cytology, American Society of Cytology 31, 83–89 (2009).

Richards-Kortum, R.

J. L. Dobbs, J. L. Mueller, S. Krishnamurthy, D. Shin, H. Kuerer, W. Yang, N. Ramanujam, and R. Richards-Kortum, “Micro-anatomical quantitative optical imaging: toward automated assessment of breast tissues,” Breast Cancer Res. 17(1), 105 (2015).
[Crossref] [PubMed]

M. Kyrish, J. Dobbs, S. Jain, X. Wang, D. Yu, R. Richards-Kortum, and T. S. Tkaczyk, “Needle-based fluorescence endomicroscopy via structured illumination with a plastic, achromatic objective,” J. Biomed. Opt. 18(9), 096003 (2013).
[Crossref] [PubMed]

T. J. Muldoon, N. Thekkek, D. Roblyer, D. Maru, N. Harpaz, J. Potack, S. Anandasabapathy, and R. Richards-Kortum, “Evaluation of quantitative image analysis criteria for the high-resolution microendoscopic detection of neoplasia in Barrett’s esophagus,” J. Biomed. Opt. 15(2), 026027 (2010).
[Crossref] [PubMed]

T. J. Muldoon, M. C. Pierce, D. L. Nida, M. D. Williams, A. Gillenwater, and R. Richards-Kortum, “Subcellular-resolution molecular imaging within living tissue by fiber microendoscopy,” Opt. Express 15(25), 16413–16423 (2007).
[Crossref] [PubMed]

Riedel, R. F.

M. J. Whitley, D. M. Cardona, A. L. Lazarides, I. Spasojevic, J. M. Ferrer, J. Cahill, C. L. Lee, M. Snuderl, D. G. Blazer, E. S. Hwang, R. A. Greenup, P. J. Mosca, J. K. Mito, K. C. Cuneo, N. A. Larrier, E. K. O’Reilly, R. F. Riedel, W. C. Eward, D. B. Strasfeld, D. Fukumura, R. K. Jain, W. D. Lee, L. G. Griffith, M. G. Bawendi, D. G. Kirsch, and B. E. Brigman, “A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer,” Sci. Transl. Med. 8(320), 320ra4 (2016).
[Crossref] [PubMed]

Roblyer, D.

T. J. Muldoon, N. Thekkek, D. Roblyer, D. Maru, N. Harpaz, J. Potack, S. Anandasabapathy, and R. Richards-Kortum, “Evaluation of quantitative image analysis criteria for the high-resolution microendoscopic detection of neoplasia in Barrett’s esophagus,” J. Biomed. Opt. 15(2), 026027 (2010).
[Crossref] [PubMed]

Rodríguez, J. J.

S. Srivastava, J. J. Rodríguez, A. R. Rouse, M. A. Brewer, and A. F. Gmitro, “Computer-aided identification of ovarian cancer in confocal microendoscope images,” J. Biomed. Opt. 13(2), 024021 (2008).
[Crossref] [PubMed]

Rouse, A. R.

A. A. Tanbakuchi, A. R. Rouse, J. A. Udovich, K. D. Hatch, and A. F. Gmitro, “Clinical confocal microlaparoscope for real-time in vivo optical biopsies,” J. Biomed. Opt. 14(4), 044030 (2009).
[Crossref] [PubMed]

S. Srivastava, J. J. Rodríguez, A. R. Rouse, M. A. Brewer, and A. F. Gmitro, “Computer-aided identification of ovarian cancer in confocal microendoscope images,” J. Biomed. Opt. 13(2), 024021 (2008).
[Crossref] [PubMed]

Ruotoistenmäki, S.

V. J. Tuominen, S. Ruotoistenmäki, A. Viitanen, M. Jumppanen, and J. Isola, “ImmunoRatio: a publicly available web application for quantitative image analysis of estrogen receptor (ER), progesterone receptor (PR), and Ki-67,” Breast Cancer Res. 12(4), R56 (2010).
[Crossref] [PubMed]

Santiago, P. M.

D. G. Kirsch, D. M. Dinulescu, J. B. Miller, J. Grimm, P. M. Santiago, N. P. Young, G. P. Nielsen, B. J. Quade, C. J. Chaber, C. P. Schultz, O. Takeuchi, R. T. Bronson, D. Crowley, S. J. Korsmeyer, S. S. Yoon, F. J. Hornicek, R. Weissleder, and T. Jacks, “A spatially and temporally restricted mouse model of soft tissue sarcoma,” Nat. Med. 13(8), 992–997 (2007).
[Crossref] [PubMed]

Schultz, C. P.

D. G. Kirsch, D. M. Dinulescu, J. B. Miller, J. Grimm, P. M. Santiago, N. P. Young, G. P. Nielsen, B. J. Quade, C. J. Chaber, C. P. Schultz, O. Takeuchi, R. T. Bronson, D. Crowley, S. J. Korsmeyer, S. S. Yoon, F. J. Hornicek, R. Weissleder, and T. Jacks, “A spatially and temporally restricted mouse model of soft tissue sarcoma,” Nat. Med. 13(8), 992–997 (2007).
[Crossref] [PubMed]

Seo, M.

B. Ko, M. Seo, and J. Y. Nam, “Microscopic cell nuclei segmentation based on adaptive attention window,” J. Digit. Imaging 22(3), 259–274 (2009).
[Crossref] [PubMed]

Shin, D.

J. L. Dobbs, J. L. Mueller, S. Krishnamurthy, D. Shin, H. Kuerer, W. Yang, N. Ramanujam, and R. Richards-Kortum, “Micro-anatomical quantitative optical imaging: toward automated assessment of breast tissues,” Breast Cancer Res. 17(1), 105 (2015).
[Crossref] [PubMed]

Sintorn, I. M.

C. Wählby, I. M. Sintorn, F. Erlandsson, G. Borgefors, and E. Bengtsson, “Combining intensity, edge and shape information for 2D and 3D segmentation of cell nuclei in tissue sections,” J. Microsc. 215(1), 67–76 (2004).
[Crossref] [PubMed]

Snuderl, M.

M. J. Whitley, D. M. Cardona, A. L. Lazarides, I. Spasojevic, J. M. Ferrer, J. Cahill, C. L. Lee, M. Snuderl, D. G. Blazer, E. S. Hwang, R. A. Greenup, P. J. Mosca, J. K. Mito, K. C. Cuneo, N. A. Larrier, E. K. O’Reilly, R. F. Riedel, W. C. Eward, D. B. Strasfeld, D. Fukumura, R. K. Jain, W. D. Lee, L. G. Griffith, M. G. Bawendi, D. G. Kirsch, and B. E. Brigman, “A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer,” Sci. Transl. Med. 8(320), 320ra4 (2016).
[Crossref] [PubMed]

Spasojevic, I.

M. J. Whitley, D. M. Cardona, A. L. Lazarides, I. Spasojevic, J. M. Ferrer, J. Cahill, C. L. Lee, M. Snuderl, D. G. Blazer, E. S. Hwang, R. A. Greenup, P. J. Mosca, J. K. Mito, K. C. Cuneo, N. A. Larrier, E. K. O’Reilly, R. F. Riedel, W. C. Eward, D. B. Strasfeld, D. Fukumura, R. K. Jain, W. D. Lee, L. G. Griffith, M. G. Bawendi, D. G. Kirsch, and B. E. Brigman, “A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer,” Sci. Transl. Med. 8(320), 320ra4 (2016).
[Crossref] [PubMed]

Srivastava, S.

S. Srivastava, J. J. Rodríguez, A. R. Rouse, M. A. Brewer, and A. F. Gmitro, “Computer-aided identification of ovarian cancer in confocal microendoscope images,” J. Biomed. Opt. 13(2), 024021 (2008).
[Crossref] [PubMed]

Starck, J. L.

J. L. Starck, M. Elad, and D. L. Donoho, “Image decomposition via the combination of sparse representations and a variational approach,” IEEE Trans. Image Process. 14(10), 1570–1582 (2005).
[Crossref] [PubMed]

Strasfeld, D. B.

M. J. Whitley, D. M. Cardona, A. L. Lazarides, I. Spasojevic, J. M. Ferrer, J. Cahill, C. L. Lee, M. Snuderl, D. G. Blazer, E. S. Hwang, R. A. Greenup, P. J. Mosca, J. K. Mito, K. C. Cuneo, N. A. Larrier, E. K. O’Reilly, R. F. Riedel, W. C. Eward, D. B. Strasfeld, D. Fukumura, R. K. Jain, W. D. Lee, L. G. Griffith, M. G. Bawendi, D. G. Kirsch, and B. E. Brigman, “A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer,” Sci. Transl. Med. 8(320), 320ra4 (2016).
[Crossref] [PubMed]

Takeuchi, O.

D. G. Kirsch, D. M. Dinulescu, J. B. Miller, J. Grimm, P. M. Santiago, N. P. Young, G. P. Nielsen, B. J. Quade, C. J. Chaber, C. P. Schultz, O. Takeuchi, R. T. Bronson, D. Crowley, S. J. Korsmeyer, S. S. Yoon, F. J. Hornicek, R. Weissleder, and T. Jacks, “A spatially and temporally restricted mouse model of soft tissue sarcoma,” Nat. Med. 13(8), 992–997 (2007).
[Crossref] [PubMed]

Tanbakuchi, A. A.

A. A. Tanbakuchi, A. R. Rouse, J. A. Udovich, K. D. Hatch, and A. F. Gmitro, “Clinical confocal microlaparoscope for real-time in vivo optical biopsies,” J. Biomed. Opt. 14(4), 044030 (2009).
[Crossref] [PubMed]

Thekkek, N.

T. J. Muldoon, N. Thekkek, D. Roblyer, D. Maru, N. Harpaz, J. Potack, S. Anandasabapathy, and R. Richards-Kortum, “Evaluation of quantitative image analysis criteria for the high-resolution microendoscopic detection of neoplasia in Barrett’s esophagus,” J. Biomed. Opt. 15(2), 026027 (2010).
[Crossref] [PubMed]

Tkaczyk, T. S.

M. Kyrish, J. Dobbs, S. Jain, X. Wang, D. Yu, R. Richards-Kortum, and T. S. Tkaczyk, “Needle-based fluorescence endomicroscopy via structured illumination with a plastic, achromatic objective,” J. Biomed. Opt. 18(9), 096003 (2013).
[Crossref] [PubMed]

Tudisco, M.

J. K. Karen, D. S. Gareau, S. W. Dusza, M. Tudisco, M. Rajadhyaksha, and K. S. Nehal, “Detection of basal cell carcinomas in Mohs excisions with fluorescence confocal mosaicing microscopy,” Br. J. Dermatol. 160(6), 1242–1250 (2009).
[Crossref] [PubMed]

Tuominen, V. J.

V. J. Tuominen, S. Ruotoistenmäki, A. Viitanen, M. Jumppanen, and J. Isola, “ImmunoRatio: a publicly available web application for quantitative image analysis of estrogen receptor (ER), progesterone receptor (PR), and Ki-67,” Breast Cancer Res. 12(4), R56 (2010).
[Crossref] [PubMed]

Udovich, J. A.

A. A. Tanbakuchi, A. R. Rouse, J. A. Udovich, K. D. Hatch, and A. F. Gmitro, “Clinical confocal microlaparoscope for real-time in vivo optical biopsies,” J. Biomed. Opt. 14(4), 044030 (2009).
[Crossref] [PubMed]

J. A. Udovich, D. G. Besselsen, and A. F. Gmitro, “Assessment of acridine orange and SYTO 16 for in vivo imaging of the peritoneal tissues in mice,” J. Microsc. 234(2), 124–129 (2009).
[Crossref] [PubMed]

Viitanen, A.

V. J. Tuominen, S. Ruotoistenmäki, A. Viitanen, M. Jumppanen, and J. Isola, “ImmunoRatio: a publicly available web application for quantitative image analysis of estrogen receptor (ER), progesterone receptor (PR), and Ki-67,” Breast Cancer Res. 12(4), R56 (2010).
[Crossref] [PubMed]

Wählby, C.

C. Wählby, I. M. Sintorn, F. Erlandsson, G. Borgefors, and E. Bengtsson, “Combining intensity, edge and shape information for 2D and 3D segmentation of cell nuclei in tissue sections,” J. Microsc. 215(1), 67–76 (2004).
[Crossref] [PubMed]

Wang, X.

M. Kyrish, J. Dobbs, S. Jain, X. Wang, D. Yu, R. Richards-Kortum, and T. S. Tkaczyk, “Needle-based fluorescence endomicroscopy via structured illumination with a plastic, achromatic objective,” J. Biomed. Opt. 18(9), 096003 (2013).
[Crossref] [PubMed]

Weissleder, R.

D. G. Kirsch, D. M. Dinulescu, J. B. Miller, J. Grimm, P. M. Santiago, N. P. Young, G. P. Nielsen, B. J. Quade, C. J. Chaber, C. P. Schultz, O. Takeuchi, R. T. Bronson, D. Crowley, S. J. Korsmeyer, S. S. Yoon, F. J. Hornicek, R. Weissleder, and T. Jacks, “A spatially and temporally restricted mouse model of soft tissue sarcoma,” Nat. Med. 13(8), 992–997 (2007).
[Crossref] [PubMed]

Whitley, M.

H. Fu, J. Mueller, M. Whitley, D. Cardona, R. Willet, D. Kirsch, Q. Brown, and N. Ramanujam, “Structured illumination microscopy and a quantitative image analysis for the detection of positive margins in a pre-clinical genetically engineered mouse model of sarcoma,” PLoS One 11(1), e0147006 (2015).
[PubMed]

Whitley, M. J.

M. J. Whitley, D. M. Cardona, A. L. Lazarides, I. Spasojevic, J. M. Ferrer, J. Cahill, C. L. Lee, M. Snuderl, D. G. Blazer, E. S. Hwang, R. A. Greenup, P. J. Mosca, J. K. Mito, K. C. Cuneo, N. A. Larrier, E. K. O’Reilly, R. F. Riedel, W. C. Eward, D. B. Strasfeld, D. Fukumura, R. K. Jain, W. D. Lee, L. G. Griffith, M. G. Bawendi, D. G. Kirsch, and B. E. Brigman, “A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer,” Sci. Transl. Med. 8(320), 320ra4 (2016).
[Crossref] [PubMed]

J. L. Mueller, H. L. Fu, J. K. Mito, M. J. Whitley, R. Chitalia, A. Erkanli, L. Dodd, D. M. Cardona, J. Geradts, R. M. Willett, D. G. Kirsch, and N. Ramanujam, “A quantitative microscopic approach to predict local recurrence based on in vivo intraoperative imaging of sarcoma tumor margins,” Int. J. Cancer 137(10), 2403–2412 (2015).
[Crossref] [PubMed]

Willet, R.

H. Fu, J. Mueller, M. Whitley, D. Cardona, R. Willet, D. Kirsch, Q. Brown, and N. Ramanujam, “Structured illumination microscopy and a quantitative image analysis for the detection of positive margins in a pre-clinical genetically engineered mouse model of sarcoma,” PLoS One 11(1), e0147006 (2015).
[PubMed]

Willett, R. M.

J. L. Mueller, H. L. Fu, J. K. Mito, M. J. Whitley, R. Chitalia, A. Erkanli, L. Dodd, D. M. Cardona, J. Geradts, R. M. Willett, D. G. Kirsch, and N. Ramanujam, “A quantitative microscopic approach to predict local recurrence based on in vivo intraoperative imaging of sarcoma tumor margins,” Int. J. Cancer 137(10), 2403–2412 (2015).
[Crossref] [PubMed]

J. L. Mueller, Z. T. Harmany, J. K. Mito, S. A. Kennedy, Y. Kim, L. Dodd, J. Geradts, D. G. Kirsch, R. M. Willett, J. Q. Brown, and N. Ramanujam, “Quantitative Segmentation of Fluorescence Microscopy Images of Heterogeneous Tissue: Application to the Detection of Residual Disease in Tumor Margins,” PLoS One 8(6), e66198 (2013).
[Crossref] [PubMed]

Williams, M. D.

Wilson, T.

Wong, S. T.

X. Chen, X. Zhou, and S. T. Wong, “Automated segmentation, classification, and tracking of cancer cell nuclei in time-lapse microscopy,” IEEE Trans. Biomed. Eng. 53(4), 762–766 (2006).
[Crossref] [PubMed]

Yang, W.

J. L. Dobbs, J. L. Mueller, S. Krishnamurthy, D. Shin, H. Kuerer, W. Yang, N. Ramanujam, and R. Richards-Kortum, “Micro-anatomical quantitative optical imaging: toward automated assessment of breast tissues,” Breast Cancer Res. 17(1), 105 (2015).
[Crossref] [PubMed]

Yoon, S. S.

D. G. Kirsch, D. M. Dinulescu, J. B. Miller, J. Grimm, P. M. Santiago, N. P. Young, G. P. Nielsen, B. J. Quade, C. J. Chaber, C. P. Schultz, O. Takeuchi, R. T. Bronson, D. Crowley, S. J. Korsmeyer, S. S. Yoon, F. J. Hornicek, R. Weissleder, and T. Jacks, “A spatially and temporally restricted mouse model of soft tissue sarcoma,” Nat. Med. 13(8), 992–997 (2007).
[Crossref] [PubMed]

Young, N. P.

D. G. Kirsch, D. M. Dinulescu, J. B. Miller, J. Grimm, P. M. Santiago, N. P. Young, G. P. Nielsen, B. J. Quade, C. J. Chaber, C. P. Schultz, O. Takeuchi, R. T. Bronson, D. Crowley, S. J. Korsmeyer, S. S. Yoon, F. J. Hornicek, R. Weissleder, and T. Jacks, “A spatially and temporally restricted mouse model of soft tissue sarcoma,” Nat. Med. 13(8), 992–997 (2007).
[Crossref] [PubMed]

Yu, D.

M. Kyrish, J. Dobbs, S. Jain, X. Wang, D. Yu, R. Richards-Kortum, and T. S. Tkaczyk, “Needle-based fluorescence endomicroscopy via structured illumination with a plastic, achromatic objective,” J. Biomed. Opt. 18(9), 096003 (2013).
[Crossref] [PubMed]

Zhou, X.

X. Chen, X. Zhou, and S. T. Wong, “Automated segmentation, classification, and tracking of cancer cell nuclei in time-lapse microscopy,” IEEE Trans. Biomed. Eng. 53(4), 762–766 (2006).
[Crossref] [PubMed]

Analytical and quantitative cytology and histology / the International Academy of Cytology, American Society of Cytology (1)

V. R. Korde, H. Bartels, J. Barton, and J. Ranger-Moore, “Automatic segmentation of cell nuclei in bladder and skin tissue for karyometric analysis,” Analytical and quantitative cytology and histology / the International Academy of Cytology, American Society of Cytology 31, 83–89 (2009).

BMVC (1)

J. Matas, “Robust wide baseline stereo from maximally stable extremal regions,” BMVC 1, 384–393 (2002).

Br. J. Dermatol. (1)

J. K. Karen, D. S. Gareau, S. W. Dusza, M. Tudisco, M. Rajadhyaksha, and K. S. Nehal, “Detection of basal cell carcinomas in Mohs excisions with fluorescence confocal mosaicing microscopy,” Br. J. Dermatol. 160(6), 1242–1250 (2009).
[Crossref] [PubMed]

Breast Cancer Res. (2)

V. J. Tuominen, S. Ruotoistenmäki, A. Viitanen, M. Jumppanen, and J. Isola, “ImmunoRatio: a publicly available web application for quantitative image analysis of estrogen receptor (ER), progesterone receptor (PR), and Ki-67,” Breast Cancer Res. 12(4), R56 (2010).
[Crossref] [PubMed]

J. L. Dobbs, J. L. Mueller, S. Krishnamurthy, D. Shin, H. Kuerer, W. Yang, N. Ramanujam, and R. Richards-Kortum, “Micro-anatomical quantitative optical imaging: toward automated assessment of breast tissues,” Breast Cancer Res. 17(1), 105 (2015).
[Crossref] [PubMed]

Breast Cancer Res. Treat. (1)

N. Nyirenda, D. L. Farkas, and V. K. Ramanujan, “Preclinical evaluation of nuclear morphometry and tissue topology for breast carcinoma detection and margin assessment,” Breast Cancer Res. Treat. 126(2), 345–354 (2011).
[Crossref] [PubMed]

Cancer (1)

J. K. Mito, J. M. Ferrer, B. E. Brigman, C. L. Lee, R. D. Dodd, W. C. Eward, L. F. Marshall, K. C. Cuneo, J. E. Carter, S. Ramasunder, Y. Kim, W. D. Lee, L. G. Griffith, M. G. Bawendi, and D. G. Kirsch, “Intraoperative detection and removal of microscopic residual sarcoma using wide-field imaging,” Cancer 118(21), 5320–5330 (2012).
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Cell Biol. Int. (1)

S. A. Krolenko, S. Y. Adamyan, T. N. Belyaeva, and T. P. Mozhenok, “Acridine orange accumulation in acid organelles of normal and vacuolated frog skeletal muscle fibres,” Cell Biol. Int. 30(11), 933–939 (2006).
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C. Millot and J. Dufer, “Clinical applications of image cytometry to human tumour analysis,” Histol. Histopathol. 15(4), 1185–1200 (2000).
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IEEE Trans. Biomed. Eng. (1)

X. Chen, X. Zhou, and S. T. Wong, “Automated segmentation, classification, and tracking of cancer cell nuclei in time-lapse microscopy,” IEEE Trans. Biomed. Eng. 53(4), 762–766 (2006).
[Crossref] [PubMed]

IEEE Trans. Image Process. (1)

J. L. Starck, M. Elad, and D. L. Donoho, “Image decomposition via the combination of sparse representations and a variational approach,” IEEE Trans. Image Process. 14(10), 1570–1582 (2005).
[Crossref] [PubMed]

Int. J. Cancer (1)

J. L. Mueller, H. L. Fu, J. K. Mito, M. J. Whitley, R. Chitalia, A. Erkanli, L. Dodd, D. M. Cardona, J. Geradts, R. M. Willett, D. G. Kirsch, and N. Ramanujam, “A quantitative microscopic approach to predict local recurrence based on in vivo intraoperative imaging of sarcoma tumor margins,” Int. J. Cancer 137(10), 2403–2412 (2015).
[Crossref] [PubMed]

J. Biomed. Opt. (5)

S. Srivastava, J. J. Rodríguez, A. R. Rouse, M. A. Brewer, and A. F. Gmitro, “Computer-aided identification of ovarian cancer in confocal microendoscope images,” J. Biomed. Opt. 13(2), 024021 (2008).
[Crossref] [PubMed]

M. Kyrish, J. Dobbs, S. Jain, X. Wang, D. Yu, R. Richards-Kortum, and T. S. Tkaczyk, “Needle-based fluorescence endomicroscopy via structured illumination with a plastic, achromatic objective,” J. Biomed. Opt. 18(9), 096003 (2013).
[Crossref] [PubMed]

T. J. Muldoon, N. Thekkek, D. Roblyer, D. Maru, N. Harpaz, J. Potack, S. Anandasabapathy, and R. Richards-Kortum, “Evaluation of quantitative image analysis criteria for the high-resolution microendoscopic detection of neoplasia in Barrett’s esophagus,” J. Biomed. Opt. 15(2), 026027 (2010).
[Crossref] [PubMed]

D. S. Gareau, “Feasibility of digitally stained multimodal confocal mosaics to simulate histopathology,” J. Biomed. Opt. 14(3), 034050 (2009).
[Crossref] [PubMed]

A. A. Tanbakuchi, A. R. Rouse, J. A. Udovich, K. D. Hatch, and A. F. Gmitro, “Clinical confocal microlaparoscope for real-time in vivo optical biopsies,” J. Biomed. Opt. 14(4), 044030 (2009).
[Crossref] [PubMed]

J. Digit. Imaging (1)

B. Ko, M. Seo, and J. Y. Nam, “Microscopic cell nuclei segmentation based on adaptive attention window,” J. Digit. Imaging 22(3), 259–274 (2009).
[Crossref] [PubMed]

J. Microsc. (2)

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Figures (4)

Fig. 1
Fig. 1 All algorithms achieve low errors when applied to a homogeneous simulation. An image simulation with various sizes and densities of FPFs was segmented with the following algorithms: HPF, Global Thresholding, Otsu, SCA + Binary, SCA + CT, MSER + Binary, and MSER + CT. The areas that were segmented with each method were false colored green and overlaid onto the original image. Overlays for each method can be seen in (A). The percent error associated with calculating the density of FPFs was determined for each method and is shown as a contour plot in (B). The colorbar indicates the percent error (%).
Fig. 2
Fig. 2 Complex algorithms achieve low errors when applied to a heterogeneous simulation. An image simulation with various sizes and densities of FPFs was added to a muscle simulation to create a heterogeneous image. The simulation was segmented with the following algorithms: HPF, Global Thresholding, Otsu, SCA + Binary, SCA + CT, MSER + Binary, and MSER + CT. The areas that were segmented with each method were false colored green and overlaid onto the original image. Overlays for each method can be seen in (A). The percent error associated with calculating the density of FPFs was determined for each method and is shown as a contour plot in (B). The colorbar indicates the percent error (%).
Fig. 3
Fig. 3 MSER + Binary leads to the largest observed difference between the density of FPFs in tumor images compared to muscle images Representative images of acridine orange stained tumor and muscle acquired with the confocal, HRME, and SIM systems are shown in A-C, respectively. Images of the corresponding H&E sections are shown in column 1. The original images of tumor and muscle acquired with the different fluorescent microscopes are shown in column 2. The outputs from SCA + Binary, SCA + CT, MSER + Binary, and MSER + CT were false colored green and overlaid onto the original images. Scale bar 200µm.
Fig. 4
Fig. 4 Average FPF density for tumor and muscle images analyzed using SCA + Binary, SCA + CT, MSER + Binary, and MSER + CT. Density values obtained from manually counting nuclei in H&E images of tumor and muscle is shown in A. Densities seen in the confocal, HRME, and SIM systems are shown in B-D respectively. Asterisks indicate significance (*p<0.05). The p values associated with each algorithm and microscopy system are shown in E.

Tables (2)

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Table 1 Summary of image segmentation algorithms

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Table 2 Microscopy system characteristics

Equations (1)

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% error = (True density estimated density) True density

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