Abstract

Microscopic examination is one of the most common methods for acute lymphoblastic leukemia (ALL) diagnosis. Most traditional methods of automized blood cell identification are based on RGB color or gray images captured by light microscopes. This paper presents an identification method combining both spectral and spatial features to identify lymphoblasts from lymphocytes in hyperspectral images. Normalization and encoding method is applied for spectral feature extraction and the support vector machine-recursive feature elimination (SVM-RFE) algorithm is presented for spatial feature determination. A marker-based learning vector quantization (MLVQ) neural network is proposed to perform identification with the integrated features. Experimental results show that this algorithm yields identification accuracy, sensitivity, and specificity of 92.9%, 93.3%, and 92.5%, respectively. Hyperspectral microscopic blood imaging combined with neural network identification technique has the potential to provide a feasible tool for ALL pre-diagnosis.

© 2017 Optical Society of America

Full Article  |  PDF Article
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2016 (1)

K. J. Bae, Y. Lee, S. A. Kim, and J. Kim, “Plumbagin exerts an immunosuppressive effect on human T-cell acute lymphoblastic leukemia MOLT-4 cells,” Biochem. Biophys. Res. Commun. 473(1), 272–277 (2016).
[Crossref] [PubMed]

2015 (4)

R. L. Siegel, K. D. Miller, and A. Jemal, “Cancer statistics, 2015,” CA Cancer J. Clin. 65(1), 5–29 (2015).
[Crossref] [PubMed]

J. J. van Dongen, V. H. van der Velden, M. Brüggemann, and A. Orfao, “Minimal residual disease diagnostics in acute lymphoblastic leukemia: need for sensitive, fast, and standardized technologies,” Blood 125(26), 3996–4009 (2015).
[Crossref] [PubMed]

S. Chin Neoh, W. Srisukkham, L. Zhang, S. Todryk, B. Greystoke, C. Peng Lim, M. Alamgir Hossain, and N. Aslam, “An Intelligent Decision Support System for Leukaemia Diagnosis using Microscopic Blood Images,” Sci. Rep. 5, 14938 (2015).
[Crossref] [PubMed]

Q. Li, M. Zhou, H. Liu, Y. Wang, and F. Guo, “Red Blood Cell Count Automation Using Microscopic Hyperspectral Imaging Technology,” Appl. Spectrosc. 69(12), 1372–1380 (2015).
[Crossref] [PubMed]

2014 (2)

S. Mohapatra, D. Patra, and S. Satpathy, “An ensemble classifier system for early diagnosis of acute lymphoblastic leukemia in blood microscopic images,” Neural Comput. Appl. 24(7-8), 1887–1904 (2014).
[Crossref]

L. Putzu, G. Caocci, and C. Di Ruberto, “Leucocyte classification for leukaemia detection using image processing techniques,” Artif. Intell. Med. 62(3), 179–191 (2014).
[Crossref] [PubMed]

2013 (3)

Q. Li, X. He, Y. Wang, H. Liu, D. Xu, and F. Guo, “Review of spectral imaging technology in biomedical engineering: achievements and challenges,” J. Biomed. Opt. 18(10), 100901 (2013).
[Crossref] [PubMed]

G. Gulati, J. Song, A. D. Florea, and J. Gong, “Purpose and criteria for blood smear scan, blood smear examination, and blood smear review,” Ann. Lab. Med. 33(1), 1–7 (2013).
[Crossref] [PubMed]

G. S. Verebes, M. Melchiorre, A. Garcia-Leis, C. Ferreri, C. Marzetti, and A. Torreggiani, “Hyperspectral enhanced dark field microscopy for imaging blood cells,” J. Biophotonics 6(11-12), 960–967 (2013).
[Crossref] [PubMed]

2012 (2)

G. X. Yuan, C. H. Ho, and C. J. Lin, “Recent Advances of Large-Scale Linear Classification,” Proc. IEEE 100(9), 2584–2603 (2012).
[Crossref]

F. D. Van der Meer, H. M. Van der Werff, F. J. van Ruitenbeek, C. A. Hecker, W. H. Bakker, M. F. Noomen, M. van der Meijde, E. J. M. Carranza, J. B. de Smeth, and T. Woldai, “Multi-and hyperspectral geologic remote sensing: A review,” IJAEO 14, 112–128 (2012).

2009 (2)

P. Froom, R. Havis, and M. Barak, “The rate of manual peripheral blood smear reviews in outpatients,” Clin. Chem. Lab. Med. 47(11), 1401–1405 (2009).
[Crossref] [PubMed]

C. Briggs, I. Longair, M. Slavik, K. Thwaite, R. Mills, V. Thavaraja, A. Foster, D. Romanin, and S. J. Machin, “Can automated blood film analysis replace the manual differential? An evaluation of the CellaVision DM96 automated image analysis system,” Int. J. Lab. Hematol. 31(1), 48–60 (2009).
[Crossref] [PubMed]

2008 (1)

C.-H. Pui, L. L. Robison, and A. T. Look, “Acute lymphoblastic leukaemia,” Lancet 371(9617), 1030–1043 (2008).
[Crossref] [PubMed]

2007 (1)

C. G. Mullighan, S. Goorha, I. Radtke, C. B. Miller, E. Coustan-Smith, J. D. Dalton, K. Girtman, S. Mathew, J. Ma, S. B. Pounds, X. Su, C. H. Pui, M. V. Relling, W. E. Evans, S. A. Shurtleff, and J. R. Downing, “Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia,” Nature 446(7137), 758–764 (2007).
[Crossref] [PubMed]

2006 (2)

P. S. Rosenberg, B. P. Alter, A. A. Bolyard, M. A. Bonilla, L. A. Boxer, B. Cham, C. Fier, M. Freedman, G. Kannourakis, S. Kinsey, B. Schwinzer, C. Zeidler, K. Welte, and D. C. Dale, “The incidence of leukemia and mortality from sepsis in patients with severe congenital neutropenia receiving long-term G-CSF therapy,” Blood 107(12), 4628–4635 (2006).
[Crossref] [PubMed]

C.-H. Pui and W. E. Evans, “Treatment of acute lymphoblastic leukemia,” N. Engl. J. Med. 354(2), 166–178 (2006).
[Crossref] [PubMed]

2004 (1)

D. M. U. Sabino, L. da Fontoura Costa, E. G. Rizzatti, and M. A. Zago, “A texture approach to leukocyte recognition,” RTI 10, 205–216 (2004).

2002 (3)

R. V. Pierre, “Peripheral blood film review. The demise of the eyecount leukocyte differential,” Clin. Lab. Med. 22(1), 279–297 (2002).
[Crossref] [PubMed]

B. Hammer and T. Villmann, “Generalized relevance learning vector quantization,” NN 15, 1059–1068 (2002).

I. Guyon, J. Weston, S. Barnhill, and V. Vapnik, “Gene Selection for Cancer Classification using Support Vector Machines,” MLear 46, 389–422 (2002).

2000 (1)

R. W. McKenna, “Multifaceted approach to the diagnosis and classification of acute leukemias,” Clin. Chem. 46(8 Pt 2), 1252–1259 (2000).
[PubMed]

1990 (1)

T. Kohonen, “The self-organizing map,” Proc. IEEE 78(9), 1464–1480 (1990).
[Crossref]

1976 (1)

J. M. Bennett, D. Catovsky, M. T. Daniel, G. Flandrin, D. A. Galton, H. R. Gralnick, and C. Sultan, “Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group,” Br. J. Haematol. 33(4), 451–458 (1976).
[Crossref] [PubMed]

Alamgir Hossain, M.

S. Chin Neoh, W. Srisukkham, L. Zhang, S. Todryk, B. Greystoke, C. Peng Lim, M. Alamgir Hossain, and N. Aslam, “An Intelligent Decision Support System for Leukaemia Diagnosis using Microscopic Blood Images,” Sci. Rep. 5, 14938 (2015).
[Crossref] [PubMed]

Alter, B. P.

P. S. Rosenberg, B. P. Alter, A. A. Bolyard, M. A. Bonilla, L. A. Boxer, B. Cham, C. Fier, M. Freedman, G. Kannourakis, S. Kinsey, B. Schwinzer, C. Zeidler, K. Welte, and D. C. Dale, “The incidence of leukemia and mortality from sepsis in patients with severe congenital neutropenia receiving long-term G-CSF therapy,” Blood 107(12), 4628–4635 (2006).
[Crossref] [PubMed]

Aslam, N.

S. Chin Neoh, W. Srisukkham, L. Zhang, S. Todryk, B. Greystoke, C. Peng Lim, M. Alamgir Hossain, and N. Aslam, “An Intelligent Decision Support System for Leukaemia Diagnosis using Microscopic Blood Images,” Sci. Rep. 5, 14938 (2015).
[Crossref] [PubMed]

Bae, K. J.

K. J. Bae, Y. Lee, S. A. Kim, and J. Kim, “Plumbagin exerts an immunosuppressive effect on human T-cell acute lymphoblastic leukemia MOLT-4 cells,” Biochem. Biophys. Res. Commun. 473(1), 272–277 (2016).
[Crossref] [PubMed]

Bakker, W. H.

F. D. Van der Meer, H. M. Van der Werff, F. J. van Ruitenbeek, C. A. Hecker, W. H. Bakker, M. F. Noomen, M. van der Meijde, E. J. M. Carranza, J. B. de Smeth, and T. Woldai, “Multi-and hyperspectral geologic remote sensing: A review,” IJAEO 14, 112–128 (2012).

Barak, M.

P. Froom, R. Havis, and M. Barak, “The rate of manual peripheral blood smear reviews in outpatients,” Clin. Chem. Lab. Med. 47(11), 1401–1405 (2009).
[Crossref] [PubMed]

Barnhill, S.

I. Guyon, J. Weston, S. Barnhill, and V. Vapnik, “Gene Selection for Cancer Classification using Support Vector Machines,” MLear 46, 389–422 (2002).

Bennett, J. M.

J. M. Bennett, D. Catovsky, M. T. Daniel, G. Flandrin, D. A. Galton, H. R. Gralnick, and C. Sultan, “Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group,” Br. J. Haematol. 33(4), 451–458 (1976).
[Crossref] [PubMed]

Bolyard, A. A.

P. S. Rosenberg, B. P. Alter, A. A. Bolyard, M. A. Bonilla, L. A. Boxer, B. Cham, C. Fier, M. Freedman, G. Kannourakis, S. Kinsey, B. Schwinzer, C. Zeidler, K. Welte, and D. C. Dale, “The incidence of leukemia and mortality from sepsis in patients with severe congenital neutropenia receiving long-term G-CSF therapy,” Blood 107(12), 4628–4635 (2006).
[Crossref] [PubMed]

Bonilla, M. A.

P. S. Rosenberg, B. P. Alter, A. A. Bolyard, M. A. Bonilla, L. A. Boxer, B. Cham, C. Fier, M. Freedman, G. Kannourakis, S. Kinsey, B. Schwinzer, C. Zeidler, K. Welte, and D. C. Dale, “The incidence of leukemia and mortality from sepsis in patients with severe congenital neutropenia receiving long-term G-CSF therapy,” Blood 107(12), 4628–4635 (2006).
[Crossref] [PubMed]

Boxer, L. A.

P. S. Rosenberg, B. P. Alter, A. A. Bolyard, M. A. Bonilla, L. A. Boxer, B. Cham, C. Fier, M. Freedman, G. Kannourakis, S. Kinsey, B. Schwinzer, C. Zeidler, K. Welte, and D. C. Dale, “The incidence of leukemia and mortality from sepsis in patients with severe congenital neutropenia receiving long-term G-CSF therapy,” Blood 107(12), 4628–4635 (2006).
[Crossref] [PubMed]

Briggs, C.

C. Briggs, I. Longair, M. Slavik, K. Thwaite, R. Mills, V. Thavaraja, A. Foster, D. Romanin, and S. J. Machin, “Can automated blood film analysis replace the manual differential? An evaluation of the CellaVision DM96 automated image analysis system,” Int. J. Lab. Hematol. 31(1), 48–60 (2009).
[Crossref] [PubMed]

Brüggemann, M.

J. J. van Dongen, V. H. van der Velden, M. Brüggemann, and A. Orfao, “Minimal residual disease diagnostics in acute lymphoblastic leukemia: need for sensitive, fast, and standardized technologies,” Blood 125(26), 3996–4009 (2015).
[Crossref] [PubMed]

Caocci, G.

L. Putzu, G. Caocci, and C. Di Ruberto, “Leucocyte classification for leukaemia detection using image processing techniques,” Artif. Intell. Med. 62(3), 179–191 (2014).
[Crossref] [PubMed]

Carranza, E. J. M.

F. D. Van der Meer, H. M. Van der Werff, F. J. van Ruitenbeek, C. A. Hecker, W. H. Bakker, M. F. Noomen, M. van der Meijde, E. J. M. Carranza, J. B. de Smeth, and T. Woldai, “Multi-and hyperspectral geologic remote sensing: A review,” IJAEO 14, 112–128 (2012).

Catovsky, D.

J. M. Bennett, D. Catovsky, M. T. Daniel, G. Flandrin, D. A. Galton, H. R. Gralnick, and C. Sultan, “Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group,” Br. J. Haematol. 33(4), 451–458 (1976).
[Crossref] [PubMed]

Cham, B.

P. S. Rosenberg, B. P. Alter, A. A. Bolyard, M. A. Bonilla, L. A. Boxer, B. Cham, C. Fier, M. Freedman, G. Kannourakis, S. Kinsey, B. Schwinzer, C. Zeidler, K. Welte, and D. C. Dale, “The incidence of leukemia and mortality from sepsis in patients with severe congenital neutropenia receiving long-term G-CSF therapy,” Blood 107(12), 4628–4635 (2006).
[Crossref] [PubMed]

Chin Neoh, S.

S. Chin Neoh, W. Srisukkham, L. Zhang, S. Todryk, B. Greystoke, C. Peng Lim, M. Alamgir Hossain, and N. Aslam, “An Intelligent Decision Support System for Leukaemia Diagnosis using Microscopic Blood Images,” Sci. Rep. 5, 14938 (2015).
[Crossref] [PubMed]

Coustan-Smith, E.

C. G. Mullighan, S. Goorha, I. Radtke, C. B. Miller, E. Coustan-Smith, J. D. Dalton, K. Girtman, S. Mathew, J. Ma, S. B. Pounds, X. Su, C. H. Pui, M. V. Relling, W. E. Evans, S. A. Shurtleff, and J. R. Downing, “Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia,” Nature 446(7137), 758–764 (2007).
[Crossref] [PubMed]

da Fontoura Costa, L.

D. M. U. Sabino, L. da Fontoura Costa, E. G. Rizzatti, and M. A. Zago, “A texture approach to leukocyte recognition,” RTI 10, 205–216 (2004).

Dale, D. C.

P. S. Rosenberg, B. P. Alter, A. A. Bolyard, M. A. Bonilla, L. A. Boxer, B. Cham, C. Fier, M. Freedman, G. Kannourakis, S. Kinsey, B. Schwinzer, C. Zeidler, K. Welte, and D. C. Dale, “The incidence of leukemia and mortality from sepsis in patients with severe congenital neutropenia receiving long-term G-CSF therapy,” Blood 107(12), 4628–4635 (2006).
[Crossref] [PubMed]

Dalton, J. D.

C. G. Mullighan, S. Goorha, I. Radtke, C. B. Miller, E. Coustan-Smith, J. D. Dalton, K. Girtman, S. Mathew, J. Ma, S. B. Pounds, X. Su, C. H. Pui, M. V. Relling, W. E. Evans, S. A. Shurtleff, and J. R. Downing, “Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia,” Nature 446(7137), 758–764 (2007).
[Crossref] [PubMed]

Daniel, M. T.

J. M. Bennett, D. Catovsky, M. T. Daniel, G. Flandrin, D. A. Galton, H. R. Gralnick, and C. Sultan, “Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group,” Br. J. Haematol. 33(4), 451–458 (1976).
[Crossref] [PubMed]

de Smeth, J. B.

F. D. Van der Meer, H. M. Van der Werff, F. J. van Ruitenbeek, C. A. Hecker, W. H. Bakker, M. F. Noomen, M. van der Meijde, E. J. M. Carranza, J. B. de Smeth, and T. Woldai, “Multi-and hyperspectral geologic remote sensing: A review,” IJAEO 14, 112–128 (2012).

Di Ruberto, C.

L. Putzu, G. Caocci, and C. Di Ruberto, “Leucocyte classification for leukaemia detection using image processing techniques,” Artif. Intell. Med. 62(3), 179–191 (2014).
[Crossref] [PubMed]

Downing, J. R.

C. G. Mullighan, S. Goorha, I. Radtke, C. B. Miller, E. Coustan-Smith, J. D. Dalton, K. Girtman, S. Mathew, J. Ma, S. B. Pounds, X. Su, C. H. Pui, M. V. Relling, W. E. Evans, S. A. Shurtleff, and J. R. Downing, “Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia,” Nature 446(7137), 758–764 (2007).
[Crossref] [PubMed]

Evans, W. E.

C. G. Mullighan, S. Goorha, I. Radtke, C. B. Miller, E. Coustan-Smith, J. D. Dalton, K. Girtman, S. Mathew, J. Ma, S. B. Pounds, X. Su, C. H. Pui, M. V. Relling, W. E. Evans, S. A. Shurtleff, and J. R. Downing, “Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia,” Nature 446(7137), 758–764 (2007).
[Crossref] [PubMed]

C.-H. Pui and W. E. Evans, “Treatment of acute lymphoblastic leukemia,” N. Engl. J. Med. 354(2), 166–178 (2006).
[Crossref] [PubMed]

Ferreri, C.

G. S. Verebes, M. Melchiorre, A. Garcia-Leis, C. Ferreri, C. Marzetti, and A. Torreggiani, “Hyperspectral enhanced dark field microscopy for imaging blood cells,” J. Biophotonics 6(11-12), 960–967 (2013).
[Crossref] [PubMed]

Fier, C.

P. S. Rosenberg, B. P. Alter, A. A. Bolyard, M. A. Bonilla, L. A. Boxer, B. Cham, C. Fier, M. Freedman, G. Kannourakis, S. Kinsey, B. Schwinzer, C. Zeidler, K. Welte, and D. C. Dale, “The incidence of leukemia and mortality from sepsis in patients with severe congenital neutropenia receiving long-term G-CSF therapy,” Blood 107(12), 4628–4635 (2006).
[Crossref] [PubMed]

Flandrin, G.

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G. Gulati, J. Song, A. D. Florea, and J. Gong, “Purpose and criteria for blood smear scan, blood smear examination, and blood smear review,” Ann. Lab. Med. 33(1), 1–7 (2013).
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G. Gulati, J. Song, A. D. Florea, and J. Gong, “Purpose and criteria for blood smear scan, blood smear examination, and blood smear review,” Ann. Lab. Med. 33(1), 1–7 (2013).
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Q. Li, M. Zhou, H. Liu, Y. Wang, and F. Guo, “Red Blood Cell Count Automation Using Microscopic Hyperspectral Imaging Technology,” Appl. Spectrosc. 69(12), 1372–1380 (2015).
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G. X. Yuan, C. H. Ho, and C. J. Lin, “Recent Advances of Large-Scale Linear Classification,” Proc. IEEE 100(9), 2584–2603 (2012).
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Q. Li, M. Zhou, H. Liu, Y. Wang, and F. Guo, “Red Blood Cell Count Automation Using Microscopic Hyperspectral Imaging Technology,” Appl. Spectrosc. 69(12), 1372–1380 (2015).
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Q. Li, X. He, Y. Wang, H. Liu, D. Xu, and F. Guo, “Review of spectral imaging technology in biomedical engineering: achievements and challenges,” J. Biomed. Opt. 18(10), 100901 (2013).
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C. Briggs, I. Longair, M. Slavik, K. Thwaite, R. Mills, V. Thavaraja, A. Foster, D. Romanin, and S. J. Machin, “Can automated blood film analysis replace the manual differential? An evaluation of the CellaVision DM96 automated image analysis system,” Int. J. Lab. Hematol. 31(1), 48–60 (2009).
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C.-H. Pui, L. L. Robison, and A. T. Look, “Acute lymphoblastic leukaemia,” Lancet 371(9617), 1030–1043 (2008).
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C. G. Mullighan, S. Goorha, I. Radtke, C. B. Miller, E. Coustan-Smith, J. D. Dalton, K. Girtman, S. Mathew, J. Ma, S. B. Pounds, X. Su, C. H. Pui, M. V. Relling, W. E. Evans, S. A. Shurtleff, and J. R. Downing, “Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia,” Nature 446(7137), 758–764 (2007).
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Miller, K. D.

R. L. Siegel, K. D. Miller, and A. Jemal, “Cancer statistics, 2015,” CA Cancer J. Clin. 65(1), 5–29 (2015).
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Mills, R.

C. Briggs, I. Longair, M. Slavik, K. Thwaite, R. Mills, V. Thavaraja, A. Foster, D. Romanin, and S. J. Machin, “Can automated blood film analysis replace the manual differential? An evaluation of the CellaVision DM96 automated image analysis system,” Int. J. Lab. Hematol. 31(1), 48–60 (2009).
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C. G. Mullighan, S. Goorha, I. Radtke, C. B. Miller, E. Coustan-Smith, J. D. Dalton, K. Girtman, S. Mathew, J. Ma, S. B. Pounds, X. Su, C. H. Pui, M. V. Relling, W. E. Evans, S. A. Shurtleff, and J. R. Downing, “Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia,” Nature 446(7137), 758–764 (2007).
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J. J. van Dongen, V. H. van der Velden, M. Brüggemann, and A. Orfao, “Minimal residual disease diagnostics in acute lymphoblastic leukemia: need for sensitive, fast, and standardized technologies,” Blood 125(26), 3996–4009 (2015).
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S. Mohapatra, D. Patra, and S. Satpathy, “An ensemble classifier system for early diagnosis of acute lymphoblastic leukemia in blood microscopic images,” Neural Comput. Appl. 24(7-8), 1887–1904 (2014).
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S. Chin Neoh, W. Srisukkham, L. Zhang, S. Todryk, B. Greystoke, C. Peng Lim, M. Alamgir Hossain, and N. Aslam, “An Intelligent Decision Support System for Leukaemia Diagnosis using Microscopic Blood Images,” Sci. Rep. 5, 14938 (2015).
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C. G. Mullighan, S. Goorha, I. Radtke, C. B. Miller, E. Coustan-Smith, J. D. Dalton, K. Girtman, S. Mathew, J. Ma, S. B. Pounds, X. Su, C. H. Pui, M. V. Relling, W. E. Evans, S. A. Shurtleff, and J. R. Downing, “Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia,” Nature 446(7137), 758–764 (2007).
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C. G. Mullighan, S. Goorha, I. Radtke, C. B. Miller, E. Coustan-Smith, J. D. Dalton, K. Girtman, S. Mathew, J. Ma, S. B. Pounds, X. Su, C. H. Pui, M. V. Relling, W. E. Evans, S. A. Shurtleff, and J. R. Downing, “Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia,” Nature 446(7137), 758–764 (2007).
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C.-H. Pui, L. L. Robison, and A. T. Look, “Acute lymphoblastic leukaemia,” Lancet 371(9617), 1030–1043 (2008).
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C. G. Mullighan, S. Goorha, I. Radtke, C. B. Miller, E. Coustan-Smith, J. D. Dalton, K. Girtman, S. Mathew, J. Ma, S. B. Pounds, X. Su, C. H. Pui, M. V. Relling, W. E. Evans, S. A. Shurtleff, and J. R. Downing, “Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia,” Nature 446(7137), 758–764 (2007).
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C.-H. Pui, L. L. Robison, and A. T. Look, “Acute lymphoblastic leukaemia,” Lancet 371(9617), 1030–1043 (2008).
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C. Briggs, I. Longair, M. Slavik, K. Thwaite, R. Mills, V. Thavaraja, A. Foster, D. Romanin, and S. J. Machin, “Can automated blood film analysis replace the manual differential? An evaluation of the CellaVision DM96 automated image analysis system,” Int. J. Lab. Hematol. 31(1), 48–60 (2009).
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D. M. U. Sabino, L. da Fontoura Costa, E. G. Rizzatti, and M. A. Zago, “A texture approach to leukocyte recognition,” RTI 10, 205–216 (2004).

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S. Mohapatra, D. Patra, and S. Satpathy, “An ensemble classifier system for early diagnosis of acute lymphoblastic leukemia in blood microscopic images,” Neural Comput. Appl. 24(7-8), 1887–1904 (2014).
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C. G. Mullighan, S. Goorha, I. Radtke, C. B. Miller, E. Coustan-Smith, J. D. Dalton, K. Girtman, S. Mathew, J. Ma, S. B. Pounds, X. Su, C. H. Pui, M. V. Relling, W. E. Evans, S. A. Shurtleff, and J. R. Downing, “Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia,” Nature 446(7137), 758–764 (2007).
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R. L. Siegel, K. D. Miller, and A. Jemal, “Cancer statistics, 2015,” CA Cancer J. Clin. 65(1), 5–29 (2015).
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C. Briggs, I. Longair, M. Slavik, K. Thwaite, R. Mills, V. Thavaraja, A. Foster, D. Romanin, and S. J. Machin, “Can automated blood film analysis replace the manual differential? An evaluation of the CellaVision DM96 automated image analysis system,” Int. J. Lab. Hematol. 31(1), 48–60 (2009).
[Crossref] [PubMed]

Song, J.

G. Gulati, J. Song, A. D. Florea, and J. Gong, “Purpose and criteria for blood smear scan, blood smear examination, and blood smear review,” Ann. Lab. Med. 33(1), 1–7 (2013).
[Crossref] [PubMed]

Srisukkham, W.

S. Chin Neoh, W. Srisukkham, L. Zhang, S. Todryk, B. Greystoke, C. Peng Lim, M. Alamgir Hossain, and N. Aslam, “An Intelligent Decision Support System for Leukaemia Diagnosis using Microscopic Blood Images,” Sci. Rep. 5, 14938 (2015).
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Su, X.

C. G. Mullighan, S. Goorha, I. Radtke, C. B. Miller, E. Coustan-Smith, J. D. Dalton, K. Girtman, S. Mathew, J. Ma, S. B. Pounds, X. Su, C. H. Pui, M. V. Relling, W. E. Evans, S. A. Shurtleff, and J. R. Downing, “Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia,” Nature 446(7137), 758–764 (2007).
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J. M. Bennett, D. Catovsky, M. T. Daniel, G. Flandrin, D. A. Galton, H. R. Gralnick, and C. Sultan, “Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group,” Br. J. Haematol. 33(4), 451–458 (1976).
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C. Briggs, I. Longair, M. Slavik, K. Thwaite, R. Mills, V. Thavaraja, A. Foster, D. Romanin, and S. J. Machin, “Can automated blood film analysis replace the manual differential? An evaluation of the CellaVision DM96 automated image analysis system,” Int. J. Lab. Hematol. 31(1), 48–60 (2009).
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Thwaite, K.

C. Briggs, I. Longair, M. Slavik, K. Thwaite, R. Mills, V. Thavaraja, A. Foster, D. Romanin, and S. J. Machin, “Can automated blood film analysis replace the manual differential? An evaluation of the CellaVision DM96 automated image analysis system,” Int. J. Lab. Hematol. 31(1), 48–60 (2009).
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Todryk, S.

S. Chin Neoh, W. Srisukkham, L. Zhang, S. Todryk, B. Greystoke, C. Peng Lim, M. Alamgir Hossain, and N. Aslam, “An Intelligent Decision Support System for Leukaemia Diagnosis using Microscopic Blood Images,” Sci. Rep. 5, 14938 (2015).
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Torreggiani, A.

G. S. Verebes, M. Melchiorre, A. Garcia-Leis, C. Ferreri, C. Marzetti, and A. Torreggiani, “Hyperspectral enhanced dark field microscopy for imaging blood cells,” J. Biophotonics 6(11-12), 960–967 (2013).
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F. D. Van der Meer, H. M. Van der Werff, F. J. van Ruitenbeek, C. A. Hecker, W. H. Bakker, M. F. Noomen, M. van der Meijde, E. J. M. Carranza, J. B. de Smeth, and T. Woldai, “Multi-and hyperspectral geologic remote sensing: A review,” IJAEO 14, 112–128 (2012).

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F. D. Van der Meer, H. M. Van der Werff, F. J. van Ruitenbeek, C. A. Hecker, W. H. Bakker, M. F. Noomen, M. van der Meijde, E. J. M. Carranza, J. B. de Smeth, and T. Woldai, “Multi-and hyperspectral geologic remote sensing: A review,” IJAEO 14, 112–128 (2012).

van der Velden, V. H.

J. J. van Dongen, V. H. van der Velden, M. Brüggemann, and A. Orfao, “Minimal residual disease diagnostics in acute lymphoblastic leukemia: need for sensitive, fast, and standardized technologies,” Blood 125(26), 3996–4009 (2015).
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F. D. Van der Meer, H. M. Van der Werff, F. J. van Ruitenbeek, C. A. Hecker, W. H. Bakker, M. F. Noomen, M. van der Meijde, E. J. M. Carranza, J. B. de Smeth, and T. Woldai, “Multi-and hyperspectral geologic remote sensing: A review,” IJAEO 14, 112–128 (2012).

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J. J. van Dongen, V. H. van der Velden, M. Brüggemann, and A. Orfao, “Minimal residual disease diagnostics in acute lymphoblastic leukemia: need for sensitive, fast, and standardized technologies,” Blood 125(26), 3996–4009 (2015).
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Figures (3)

Fig. 1
Fig. 1 Microscopy hyperspectral image cube
Fig. 2
Fig. 2 (a) Mean spectra of lymphoblast, lymphocyte, and RBC with normalization; (b) mean spectra of lymphoblast, lymphocyte, and RBC after BCD coding; (c) collected lymphoblast spectra; (d) collected lymphocyte spectra; (e) collected RBC spectra.
Fig. 3
Fig. 3 (a) (e) (i) (m) Light microscope images, (b) (f) (j) (n) microscope image identification results by K-means, (c) (g) (k) (o) single band images selected from hyperspectral image, (d) (h) (l) (p) identification results by proposed method.

Tables (2)

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Table 1 Confusion matrix for identification performance evaluation

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Table 2 Performance of lymphoblast and lymphocyte identification with different data set input

Equations (9)

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D k,p,n calibration = K n D k,p,n sample = D k,p,n white i=1 N D k,p,n white / L X L Y N D k,p,n sample
X C m = min k ( X W k ) 2 (k=1,2,...M)
h C j ( k ) ={ 1 W k 0 0 otherwise ( j=1,2,...,L )
M( k )={ j| ( SE ) j h C j ( k ) }
W k ( t+1 )= W k ( t )μ( t )[ X W k ( t ) ]
W k ( t+1 )= W k ( t )+μ( t )[ X W k ( t ) ]
Accuary= ( TP+TN ) ( TP+TN+FP+FN )
Specificity= TN ( TN+FP )
Sensitivity= TP ( TP+FN )

Metrics