Abstract

Hyperspectral imaging (HSI) and multispectral imaging (MSI) technologies have the potential to transform the fields of digital and computational pathology. Traditional digitized histopathological slides are imaged with RGB imaging. Utilizing HSI/MSI, spectral information across wavelengths within and beyond the visual range can complement spatial information for the creation of computer-aided diagnostic tools for both stained and unstained histological specimens. In this systematic review, we summarize the methods and uses of HSI/MSI for staining and color correction, immunohistochemistry, autofluorescence, and histopathological diagnostic research. Studies include hematology, breast cancer, head and neck cancer, skin cancer, and diseases of central nervous, gastrointestinal, and genitourinary systems. The use of HSI/MSI suggest an improvement in the detection of diseases and clinical practice compared with traditional RGB analysis, and brings new opportunities in histological analysis of samples, such as digital staining or alleviating the inter-laboratory variability of digitized samples. Nevertheless, the number of studies in this field is currently limited, and more research is needed to confirm the advantages of this technology compared to conventional imagery.

© 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

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2019 (22)

S. Gioux, A. Mazhar, and D. J. Cuccia, “Spatial frequency domain imaging in 2019: principles, applications, and perspectives,” J. Biomed. Opt. 24(07), 1 (2019).
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M. Halicek, H. Fabelo, S. Ortega, G. M. Callico, and B. Fei, “In-vivo and ex-vivo tissue analysis through hyperspectral imaging techniques: revealing the invisible features of cancer,” Cancers 11(6), 756 (2019).
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S. Ortega, H. Fabelo, D. K. Iakovidis, A. Koulaouzidis, and G. M. Callico, “Use of Hyperspectral/Multispectral Imaging in Gastroenterology. Shedding Some–Different–Light into the Dark,” J. Clin. Med. 8(1), 36 (2019).
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N. Audebert, B. Le Saux, and S. Lefevre, “Deep learning for classification of hyperspectral data: A comparative review,” IEEE Geosci. Remote Sens. Mag. 7(2), 159–173 (2019).
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S. Li, W. Song, L. Fang, Y. Chen, P. Ghamisi, and J. A. Benediktsson, “Deep learning for hyperspectral image classification: An overview,” IEEE Trans. Geosci. Electron. 57(9), 6690–6709 (2019).
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F. Fereidouni, A. Todd, Y. Li, C.-W. Chang, K. Luong, A. Rosenberg, Y.-J. Lee, J. W. Chan, A. Borowsky, K. Matsukuma, K.-Y. Jen, and R. Levenson, “Dual-mode emission and transmission microscopy for virtual histochemistry using hematoxylin- and eosin-stained tissue sections,” Biomed. Opt. Express 10(12), 6516 (2019).
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L. Guo, J. Stormmesand, Z. Fang, Q. Zhu, R. Balesar, J. van Heerikhuize, A. Sluiter, D. Swaab, and A.-M. Bao, “Quantification of tyrosine hydroxylase and erbb4 in the locus coeruleus of mood disorder patients using a multispectral method to prevent interference with immunocytochemical signals by neuromelanin,” Neurosci. Bull. 35(2), 205–215 (2019).
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M. E. Ijsselsteijn, T. P. Brouwer, Z. Abdulrahman, E. Reidy, A. Ramalheiro, A. M. Heeren, A. Vahrmeijer, E. S. Jordanova, and N. F. de Miranda, “Cancer immunophenotyping by seven-colour multispectral imaging without tyramide signal amplification,” J. Pathol.: Clin. Res. 5(1), 3–11 (2019).
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C. Mascaux, M. Angelova, A. Vasaturo, J. Beane, K. Hijazi, G. Anthoine, B. Buttard, F. Rothe, K. Willard-Gallo, A. Haller, V. Ninane, A. Burny, J.-P. Sculier, A. Spira, and J. Galon, “Immune evasion before tumour invasion in early lung squamous carcinogenesis,” Nature 571(7766), 570–575 (2019).
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G. Hong, S. Fan, T. Phyu, P. Maheshwari, M. M. Hoppe, H. M. Phuong, S. De Mel, M. Poon, S.-B. Ng, and A. D. Jeyasekharan, “Multiplexed fluorescent immunohistochemical staining, imaging, and analysis in histological samples of lymphoma,” J. Visualized Exp. 143, 58711 (2019).
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P. D. Sehgal, T. M. Bauman, T. M. Nicholson, J. E. Vellky, E. A. Ricke, W. Tang, W. Xu, W. Huang, and W. A. Ricke, “Tissue-specific quantification and localization of androgen and estrogen receptors in prostate cancer,” Hum. Pathol. 89, 99–108 (2019).
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N. Dey, S. Hong, T. Ach, Y. Koutalos, C. A. Curcio, R. T. Smith, and G. Gerig, “Tensor decomposition of hyperspectral images to study autofluorescence in age-related macular degeneration,” Med. Image Anal. 56, 96–109 (2019).
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A. Habibalahi, C. Bala, A. Allende, A. G. Anwer, and E. M. Goldys, “Novel automated non invasive detection of ocular surface squamous neoplasia using multispectral autofluorescence imaging,” The Ocul. Surf. 17(3), 540–550 (2019).
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L. Septiana, H. Suzuki, M. Ishikawa, T. Obi, N. Kobayashi, N. Ohyama, T. Ichimura, A. Sasaki, E. Wihardjo, and D. Andiani, “Elastic and collagen fibers discriminant analysis using H&E stained hyperspectral images,” Opt. Rev. 26(4), 369–379 (2019).
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J. L. Xu, K. V. Thomas, Z. Luo, and A. A. Gowen, “FTIR and Raman imaging for microplastics analysis: State of the art, challenges and prospects,” TrAC, Trends Anal. Chem. 119, 115629 (2019).
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2018 (20)

I. J. Maybury, D. Howell, M. Terras, and H. Viles, “Comparing the effectiveness of hyperspectral imaging and Raman spectroscopy: a case study on Armenian manuscripts,” Heritage Sci. 6(1), 42 (2018).
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Q. Wang, Q. Li, M. Zhou, L. Sun, S. Qiu, and Y. Wang, “Melanoma and melanocyte identification from hyperspectral pathology images using object-based multiscale analysis,” Appl. Spectrosc. 72(10), 1538–1547 (2018).
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J. Wang and Q. Li, “Quantitative analysis of liver tumors at different stages using microscopic hyperspectral imaging technology,” J. Biomed. Opt. 23(10), 1–14 (2018).
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R. Awan, S. Al-Maadeed, and R. Al-Saady, “Using spectral imaging for the analysis of abnormalities for colorectal cancer: When is it helpful?” PLoS One 13(6), e0197431 (2018).
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Y. Khouj, J. Dawson, J. Coad, and L. Vona-Davis, “Hyperspectral imaging and K-means classification for histologic evaluation of ductal carcinoma in situ,” Front. Oncol. 8(FEB), 17 (2018).
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A. Chaddad, P. Daniel, and T. Niazi, “Radiomics evaluation of histological heterogeneity using multiscale textures derived from 3D wavelet transformation of multispectral images,” Front. Oncol. 8(APR), 96 (2018).
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R. Peyret, A. Bouridane, F. Khelifi, M. A. Tahir, and S. Al-Maadeed, “Automatic classification of colorectal and prostatic histologic tumor images using multiscale multispectral local binary pattern texture features and stacked generalization,” Neurocomputing 275, 83–93 (2018).
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J. Deal, B. Harris, W. Martin, M. Lall, C. Lopez, C. Boudreaux, T. Rich, S. Leavesley, and P. Rider, “Demystifying autofluorescence with excitation scanning hyperspectral imaging,” in Imaging, Manipulation, and Analysis of Biomolecules,” Proc. SPIE 10497, 40 (2018).
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J. Deal, S. Mayes, C. Browning, S. Hill, P. Rider, C. Boudreaux, T. C. Rich, and S. J. Leavesley, “Identifying molecular contributors to autofluorescence of neoplastic and normal colon sections using excitation-scanning hyperspectral imaging,” J. Biomed. Opt. 24(02), 1–11 (2018).
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S. Ortega, H. Fabelo, R. Camacho, M. L. Plaza, G. M. Callicó, R. Sarmiento, M. de la Luz Plaza, G. M. Callico, and R. Sarmiento, “Detecting brain tumor in pathological slides using hyperspectral imaging,” Biomed. Opt. Express 9(2), 818–831 (2018).
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M. A. J. Gorris, A. Halilovic, K. Rabold, A. van Duffelen, I. N. Wickramasinghe, D. Verweij, I. M. N. Wortel, J. C. Textor, I. J. M. de Vries, and C. G. Figdor, “Eight-color multiplex immunohistochemistry for simultaneous detection of multiple immune checkpoint molecules within the tumor microenvironment,” J. Immunol. 200(1), 347–354 (2018).
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K. Silina, A. Soltermann, F. M. Attar, R. Casanova, Z. M. Uckeley, H. Thut, M. Wandres, S. Isajevs, P. Cheng, A. Curioni-Fontecedro, P. Foukas, M. P. Levesque, H. Moch, A. Line, and M. Van Den Broek, “Germinal centers determine the prognostic relevance of tertiary lymphoid structures and are impaired by corticosteroids in lung squamous cell carcinoma,” Cancer Res. 78(5), 1308–1320 (2018).
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A. Mezheyeuski, C. H. Bergsland, M. Backman, D. Djureinovic, T. Sjoblom, J. Bruun, P. Micke, T. Sjöblom, J. Bruun, and P. Micke, “Multispectral imaging for quantitative and compartment-specific immune infiltrates reveals distinct immune profiles that classify lung cancer patients,” J. Pathol. 244(4), 421–431 (2018).
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C. J. Cho, H. J. Kang, Y.-M. Ryu, Y. S. Park, H. J. Jeong, Y.-M. Park, H. Lim, J. H. Lee, H. J. Song, H.-Y. Jung, S.-Y. Kim, and S.-J. Myung, “Poor prognosis in Epstein-Barr virus-negative gastric cancer with lymphoid stroma is associated with immune phenotype,” Gastric Cancer 21(6), 925–935 (2018).
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D. Takahashi, M. Kojima, T. Suzuki, M. Sugimoto, S. Kobayashi, S. Takahashi, M. Konishi, N. Gotohda, M. Ikeda, T. Nakatsura, A. Ochiai, and M. Nagino, “Profiling the tumour immune microenvironment in pancreatic neuroendocrine neoplasms with multispectral imaging indicates distinct subpopulation characteristics concordant with WHO 2017 classification,” Sci. Rep. 8(1), 13166 (2018).
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C. Jiang, Y.-H. Huang, J.-B. Lu, Y.-Z. Yang, H.-L. Rao, B. Zhang, W.-Z. He, and L.-P. Xia, “Perivascular cell coverage of intratumoral vasculature is a predictor for bevacizumab efficacy in metastatic colorectal cancer,” Cancer Manage. Res. 10, 3589–3597 (2018).
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M. Fang, J. Yuan, M. M. Chen, Z. Sun, L. Liu, G. Cheng, H. Ying, S. Yang, and M. M. Chen, “The heterogenic tumor microenvironment of hepatocellular carcinoma and prognostic analysis based on tumor neo-vessels, macrophages and α-SMA,” Oncol. Lett. 15(4), 4805–4812 (2018).
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J. Liao, S. Jiang, Z. Zhang, K. Guo, Z. Bian, Y. Jiang, J. Zhong, and G. Zheng, “Terapixel hyperspectral whole-slide imaging via slit-array detection and projection,” J. Biomed. Opt. 23(06), 1–7 (2018).
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M. Hermes, R. B. Morrish, L. Huot, L. Meng, S. Junaid, J. Tomko, G. R. Lloyd, W. T. Masselink, P. Tidemand-Lichtenberg, C. Pedersen, F. Palombo, and N. Stone, “Mid-IR hyperspectral imaging for label-free histopathology and cytology,” J. Opt. 20(2), 023002 (2018).
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A. C. S. Talari, M. A. G. Martinez, Z. Movasaghi, S. Rehman, and I. U. Rehman, “Advances in Fourier transform infrared (FTIR) spectroscopy of biological tissues,” Appl. Spectrosc. Rev. 52(5), 456–506 (2017).
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D. W. Shipp, F. Sinjab, and I. Notingher, “Raman spectroscopy: techniques and applications in the life sciences,” Adv. Opt. Photonics 9(2), 315 (2017).
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K. A. Salva, M. J. Reeder, R. Lloyd, and G. S. Wood, “c-CBL E3 ubiquitin ligase expression increases across the spectrum of benign and malignant T-cell skin diseases,” Am. J. Dermatopathol. 39(10), 731–737 (2017).
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M. J. Campbell, F. Baehner, T. O’Meara, E. Ojukwu, B. Han, R. Mukhtar, V. Tandon, M. Endicott, Z. Zhu, J. Wong, G. Krings, A. Au, J. W. Gray, L. Esserman, T. O’Meara, E. Ojukwu, B. Han, R. Mukhtar, V. Tandon, M. Endicott, Z. Zhu, J. Wong, G. Krings, A. Au, J. W. Gray, and L. Esserman, “Characterizing the immune microenvironment in high-risk ductal carcinoma in situ of the breast,” Breast Cancer Res. Treat. 161(1), 17–28 (2017).
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Y. Rivenson, Z. Göröcs, H. Günaydin, Y. Zhang, H. Wang, and A. Ozcan, “Deep learning microscopy,” Optica 4(11), 1437 (2017).
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L. Ying, F. Yan, Q. Meng, X. Yuan, L. Yu, B. R. G. Williams, D. W. Chan, L. Shi, Y. Tu, P. Ni, X. Wang, D. Xu, and Y. Hu, “Understanding immune phenotypes in human gastric disease tissues by multiplexed immunohistochemistry,” J. Transl. Med. 15(1), 206 (2017).
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A. M. Mahmoud, V. Macias, U. Al-Alem, R. J. Deaton, A. Kadjaksy-Balla, P. H. Gann, and G. H. Rauscher, “BRCA1 protein expression and subcellular localization in primary breast cancer: Automated digital microscopy analysis of tissue microarrays,” PLoS One 12(9), e0184385 (2017).
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Z. Feng, D. Bethmann, M. Kappler, C. Ballesteros-Merino, A. Eckert, R. B. Bell, A. Cheng, T. Bui, R. Leidner, W. J. Urba, K. Johnson, C. Hoyt, C. B. Bifulco, J. Bukur, C. Wickenhauser, B. Seliger, and B. A. Fox, “Multiparametric immune profiling in HPV- oral squamous cell cancer,” JCI Insight 2(14), 93652 (2017).
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A. Vasaturo, S. Di Blasio, D. Verweij, W. A. M. Blokx, J. H. van Krieken, I. J. M. de Vries, and C. G. Figdor, “Multispectral imaging for highly accurate analysis of tumour-infiltrating lymphocytes in primary melanoma,” Histopathology 70(4), 643–649 (2017).
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M. Dobosz, U. Haupt, and W. Scheuer, “Improved decision making for prioritizing tumor targeting antibodies in human xenografts: Utility of fluorescence imaging to verify tumor target expression, antibody binding and optimization of dosage and application schedule,” mAbs 9(1), 140–153 (2017).
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I. J. Park, S. An, S.-Y. Kim, H. M. Lim, S.-M. Hong, M.-J. Kim, Y. J. Kim, and C. S. Yu, “Prediction of radio-responsiveness with immune-profiling in patients with rectal cancer,” Oncotarget 8(45), 79793–79802 (2017).
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E. R. Parra, N. Uraoka, M. Jiang, P. Cook, D. Gibbons, M.-A. Forget, C. Bernatchez, C. Haymaker, I. I. Wistuba, and J. Rodriguez-Canales, “Validation of multiplex immunofluorescence panels using multispectral microscopy for immune-profiling of formalin-fixed and paraffin-embedded human tumor tissues,” Sci. Rep. 7(1), 13380 (2017).
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H. Haj-Hassan, A. Chaddad, Y. Harkouss, C. Desrosiers, M. Toews, and C. Tanougast, “Classifications of multispectral colorectal cancer tissues using convolution neural network,” J Pathol Inform 8(1), 1 (2017).
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Q. Wang, J. Wang, M. Zhou, Q. Li, and Y. Wang, “Spectral-spatial feature-based neural network method for acute lymphoblastic leukemia cell identification via microscopic hyperspectral imaging technology,” Biomed. Opt. Express 8(6), 3017 (2017).
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J. W. Wilson, F. E. Robles, S. Deb, W. S. Warren, and M. C. Fischer, “Comparison of pump-probe and hyperspectral imaging in unstained histology sections of pigmented lesions,” Biomed. Opt. Express 8(8), 3882–3890 (2017).
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2016 (15)

A. Chaddad, C. Desrosiers, A. Bouridane, M. Toews, L. Hassan, and C. Tanougast, “Multi texture analysis of colorectal cancer continuum using multispectral imagery,” PLoS One 11(2), e0149893 (2016).
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T. M. Bauman, C. M. Vezina, E. A. Ricke, R. B. Halberg, W. Huang, R. E. Peterson, and W. A. Ricke, “Expression and colocalization of beta-catenin and lymphoid enhancing factor-1 in prostate cancer progression,” Hum. Pathol. 51, 124–133 (2016).
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J. Kim, P. C. de Sampaio, D. M. Lundy, Q. Peng, K. W. Evans, H. Sugimoto, M. Gagea, Y. Kienast, N. S. do Amaral, R. M. Rocha, H. P. Eikesdal, P. E. Lonning, F. Meric-Bernstam, and V. S. LeBleu, “Heterogeneous perivascular cell coverage affects breast cancer metastasis and response to chemotherapy,” JCI insight 1(21), e90733 (2016).
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T. M. Bauman, W. Huang, M. H. Lee, and E. J. Abel, “Neovascularity as a prognostic marker in renal cell carcinoma,” Hum. Pathol. 57, 98–105 (2016).
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T. M. Bauman, E. A. Ricke, S. A. Drew, W. Huang, and W. A. Ricke, “Quantitation of Protein expression and Co-localization using multiplexed Immuno-Histochemical staining and multispectral imaging,” J. Visualized Exp. 110, 53837 (2016).
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S. W. Kim, J. Roh, and C. S. Park, “Immunohistochemistry for pathologists: Protocols, pitfalls, and tips,” J. Pathol. Transl. Med. 50(6), 411–418 (2016).
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E. Vazgiouraki, V. M. Papadakis, P. Efstathopoulos, I. Lazaridis, I. Charalampopoulos, C. Fotakis, and A. Gravanis, “Application of multispectral imaging detects areas with neuronal myelin loss, without tissue labelling,” Microscopy 65(2), 109–118 (2016).
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P. F. Favreau, J. A. Deal, D. S. Weber, T. C. Rich, and S. J. Leavesley, “Feasibility for detection of autofluorescent signatures in rat organs using a novel excitation-scanning hyperspectral imaging system,” Proc. SPIE 9711, 971113 (2016).
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S. J. Leavesley, M. Walters, C. Lopez, T. Baker, P. F. Favreau, T. C. Rich, P. F. Rider, and C. W. Boudreaux, “Hyperspectral imaging fluorescence excitation scanning for colon cancer detection,” J. Biomed. Opt. 21(10), 104003 (2016).
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W. Liu, L. Wang, J. Liu, J. Yuan, J. Chen, H. Wu, Q. Xiang, G. Yang, and Y. Li, “A comparative performance analysis of multispectral and rgb imaging on her2 status evaluation for the prediction of breast cancer prognosis,” Transl. Oncol. 9(6), 521–530 (2016).
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W.-L. Liu, L.-W. Wang, J.-M. Chen, J.-P. Yuan, Q.-M. Xiang, G.-F. Yang, A.-P. Qu, J. Liu, and Y. Li, “Application of multispectral imaging in quantitative immunohistochemistry study of breast cancer: a comparative study,” Tumor Biol. 37(4), 5013–5024 (2016).
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D. H. Hepp, D. L. E. Vergoossen, E. Huisman, A. W. Lemstra, N. B. Bank, H. W. Berendse, A. J. Rozemuller, E. M. J. Foncke, and W. D. J. Van De Berg, “Distribution and load of amyloid-b pathology in Parkinson disease and dementia with lewy bodies,” J. Neuropathol. Exp. Neurol. 75(10), 936–945 (2016).
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H. L. M. Tucker, C. L. M. Parsons, S. Ellis, M. L. Rhoads, and R. M. Akers, “Tamoxifen impairs prepubertal mammary development and alters expression of estrogen receptor alpha (ESR1) and progesterone receptors (PGR),” Domest. Anim. Endocrinol. 54, 95–105 (2016).
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H. J. Butler, L. Ashton, B. Bird, G. Cinque, K. Curtis, J. Dorney, K. Esmonde-White, N. J. Fullwood, B. Gardner, P. L. Martin-Hirsch, M. J. Walsh, M. R. McAinsh, N. Stone, and F. L. Martin, “Using Raman spectroscopy to characterize biological materials,” Nat. Protoc. 11(4), 664–687 (2016).
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D. N. Louis, M. Feldman, A. B. Carter, A. S. Dighe, J. D. Pfeifer, L. Bry, J. S. Almeida, J. Saltz, J. Braun, J. E. Tomaszewski, J. R. Gilbertson, J. H. Sinard, G. K. Gerber, S. J. Galli, J. A. Golden, and M. J. Becich, “Computational Pathology: A Path Ahead,” Arch. Pathol. Lab. Med. 140(1), 41–50 (2016).
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2015 (17)

B. Zhu and E. M. Sevick-Muraca, “A review of performance of near-infrared fluorescence imaging devices used in clinical studies,” Br. J. Radiol. 88(1045), 20140547 (2015).
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L. Gao and R. T. Smith, “Optical hyperspectral imaging in microscopy and spectroscopy - a review of data acquisition,” J. Biophotonics 8(6), 441–456 (2015).
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H. Yoshimura, Y. Matsuda, A. Matsushita, Y. Nakamura, E. Uchida, and T. Ishiwata, “Multispectral imaging of pancreatic mixed acinar-neuroendocrine-ductal carcinoma with triple-immunoenzyme staining,” J. Nippon Med. Sch. 82(3), 122–123 (2015).
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B. T. Velayudhan, B. P. Huderson, S. E. Ellis, C. L. Parsons, R. C. Hovey, A. R. Rowson, and R. M. Akers, “Ovariectomy in young prepubertal dairy heifers causes complete suppression of mammary progesterone receptors,” Domest. Anim. Endocrinol. 51, 8–18 (2015).
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S. S. More and R. Vince, “Hyperspectral imaging signatures detect amyloidopathy in Alzheimer’s mouse retina well before onset of cognitive decline,” ACS Chem. Neurosci. 6(2), 306–315 (2015).
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L. S. Nelson, J. R. Mansfield, R. Lloyd, K. Oguejiofor, Z. Salih, L. P. Menasce, K. M. Linton, C. J. Rose, and R. J. Byers, “Automated prognostic pattern detection shows favourable diffuse pattern of FOXP3(+) Tregs in follicular lymphoma,” Br. J. Cancer 113(8), 1197–1205 (2015).
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M. Ou-Yang, Y.-F. Hsieh, and C.-C. Lee, “Biopsy diagnosis of oral carcinoma by the combination of morphological and spectral methods based on embedded relay lens microscopic hyperspectral imaging system,” J. Med. Biol. Eng. 35(4), 437–447 (2015).
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C. He, H. He, J. Chang, Y. Dong, S. Liu, N. Zeng, Y. He, and H. Ma, “Characterizing microstructures of cancerous tissues using multispectral transformed Mueller matrix polarization parameters,” Biomed. Opt. Express 6(8), 2934–2945 (2015).
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E. Ansong, Q. Ying, D. N. Ekoue, R. Deaton, A. R. Hall, A. Kajdacsy-Balla, W. Yang, P. H. Gann, and A. M. Diamond, “Evidence that selenium binding protein 1 is a tumor suppressor in prostate cancer,” PLoS One 10(5), e0127295 (2015).
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C. M. de Winde, M. Zuidscherwoude, A. Vasaturo, A. van der Schaaf, C. G. Figdor, and A. B. van Spriel, “Multispectral imaging reveals the tissue distribution of tetraspanins in human lymphoid organs,” Histochem. Cell Biol. 144(2), 133–146 (2015).
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T. M. Bauman, A. J. Becka, P. D. Sehgal, W. Huang, and W. A. Ricke, “SIGIRR/TIR8, an important regulator of TLR4 and IL-1R-mediated NF-κB activation, predicts biochemical recurrence after prostatectomy in low-grade prostate carcinomas,” Hum. Pathol. 46(11), 1744–1751 (2015).
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K. Oguejiofor, J. Hall, C. Slater, G. Betts, G. Hall, N. Slevin, S. Dovedi, P. L. Stern, and C. M. L. West, “Stromal infiltration of CD8 T cells is associated with improved clinical outcome in HPV-positive oropharyngeal squamous carcinoma,” Br. J. Cancer 113(6), 886–893 (2015).
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K. A. Salva, D. Bennett, J. Longley, J. Guitart, and G. S. Wood, “Multispectral imaging approach to the diagnosis of a CD20+ cutaneous T-cell lymphoproliferative disorder: A case report,” Am. J. Dermatopathol. 37(10), e116–e121 (2015).
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I. W. Lao, F. Cui, and H. Zhu, “Quantitation of microRNA-92a in colorectal adenocarcinoma and its precancerous lesions: Co-utilization of in situ hybridization and spectral imaging,” Oncol. Lett. 9(3), 1109–1115 (2015).
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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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P. Haub and T. Meckel, “A model based survey of colour deconvolution in diagnostic brightfield microscopy: error estimation and spectral consideration,” Sci. Rep. 5(1), 12096 (2015).
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K. Kalleberg, J. Nip, and K. Gossage, “Multispectral imaging as a tool for melanin detection,” J. Histotechnol. 38(1), 14–21 (2015).
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2014 (15)

Q. Li, Y. Wang, H. Liu, X. He, D. Xu, J. Wang, and F. Guo, “Leukocyte cells identification and quantitative morphometry based on molecular hyperspectral imaging technology,” Comput. Med. Imaging Graph. 38(3), 171–178 (2014).
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S. Gaudi, R. Meyer, J. Ranka, J. C. Granahan, S. A. Israel, T. R. Yachik, and D. M. Jukic, “Hyperspectral imaging of melanocytic lesions,” Am. J. Dermatopathol. 36(2), 131–136 (2014).
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Q. Li, Z. Sun, Y. Wang, H. Liu, F. Guo, and J. Zhu, “Histological skin morphology enhancement base on molecular hyperspectral imaging technology,” Skin Res. Technol. 20(3), 332–340 (2014).
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D. L. Omucheni, K. A. Kaduki, W. D. Bulimo, and H. K. Angeyo, “Application of principal component analysis to multispectral-multimodal optical image analysis for malaria diagnostics,” Malar. J. 13(1), 485 (2014).
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H. Irshad, A. Gouaillard, L. Roux, and D. Racoceanu, “Multispectral band selection and spatial characterization: Application to mitosis detection in breast cancer histopathology,” Comput. Med. Imaging Graph. 38(5), 390–402 (2014).
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C. Lu and M. Mandal, “Toward automatic mitotic cell detection and segmentation in multispectral histopathological images,” IEEE J. Biomed. Health Inform. 18(2), 594–605 (2014).
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T. M. Bauman, C. M. Vezina, W. Huang, P. C. Marker, R. E. Peterson, and W. A. Ricke, “Beta-catenin is elevated in human benign prostatic hyperplasia specimens compared to histologically normal prostate tissue,” Am. J. Clin. Exp. Urol. 2(4), 313–322 (2014).

J. Rosenbaum, S. Drew, and W. Huang, “Significantly higher expression levels of androgen receptor are associated with erythroblastosis virus E26 oncogene related gene positive prostate cancer,” Am. J. Clin. Exp. Urol. 2(3), 249–257 (2014).

N. Vigneswaran and M. D. Williams, “Epidemiologic trends in head and neck cancer and aids in diagnosis,” Oral Maxillofac. Surg. Clin. North Am. 26(2), 123–141 (2014).
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R. Scott, F. M. Khan, J. Zeineh, M. Donovan, and G. Fernandez, “Gland ring morphometry for prostate cancer prognosis in multispectral immunofluorescence images,” Med. Image Comput. Comput. Assist. Interv. 17(PART 1), 585–592 (2014).
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P. Bautista, N. Hashimoto, and Y. Yagi, “Color standardization in whole slide imaging using a color calibration slide,” J Pathol Inform 5(1), 4 (2014).
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T. M. Bauman, P. D. Sehgal, K. A. Johnson, T. Pier, R. C. Bruskewitz, W. A. Ricke, and W. Huang, “Finasteride treatment alters tissue specific androgen receptor expression in prostate tissues,” Prostate 74(9), 923–932 (2014).
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J. R. Mansfield, “Multispectral imaging: a review of its technical aspects and applications in anatomic pathology,” Vet. Pathol. 51(1), 185–210 (2014).
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G. Lu and B. Fei, “Medical hyperspectral imaging: a review,” J. Biomed. Opt. 19(1), 010901 (2014).
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E. S. Wachman, S. J. Geyer, J. M. Recht, J. Ward, B. Zhang, M. Reed, and C. Pannell, “Simultaneous imaging of cellular morphology and multiple biomarkers using an acousto-optic tunable filter-based bright field microscope,” J. Biomed. Opt. 19(5), 056006 (2014).
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2013 (23)

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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P. Favreau, C. Hernandez, A. S. Lindsey, D. F. Alvarez, T. Rich, P. Prabhat, and S. J. Leavesley, “Thin-film tunable filters for hyperspectral fluorescence microscopy,” J. Biomed. Opt. 19(1), 011017 (2013).
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R. Levenson, J. Beechem, and G. McNamara, “Spectral imaging in preclinical research and clinical pathology,” Biophotonics Pathol. Pathol. Crossroads 35(5-6), 43–75 (2013).
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S. L. Jacques, “Optical properties of biological tissues: a review,” Phys. Med. Biol. 58(11), R37–R61 (2013).
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C. M. van der Loos, O. J. de Boer, C. Mackaaij, L. T. Hoekstra, T. M. van Gulik, and J. Verheij, “Accurate quantitation of Ki67-positive proliferating hepatocytes in rabbit liver by a multicolor immunohistochemical (IHC) approach analyzed with automated tissue and cell segmentation software,” J. Histochem. Cytochem. 61(1), 11–18 (2013).
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J. M. Kruger, M. Thomas, R. Korn, G. Dietmann, C. Rutz, G. Brockhoff, K. Specht, M. Hasmann, and F. Feuerhake, “Detection of truncated HER2 forms in formalin-fixed, paraffin-embedded breast cancer tissue captures heterogeneity and is not affected by HER2-targeted therapy,” Am. J. Pathol. 183(2), 336–343 (2013).
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R. M. Abraham, G. Karakousis, G. Acs, A. F. Ziober, L. Cerroni, M. C. J. Mihm, D. E. Elder, X. Xu, and M. C. Mihm Jr., D. E. Elder and X. Xu, “Lymphatic invasion predicts aggressive behavior in melanocytic tumors of uncertain malignant potential (MELTUMP),” Am. J. Surg. Pathol. 37(5), 669–675 (2013).
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R. M. Abraham, G. Karakousis, G. Acs, A. F. Ziober, L. Cerroni, M. C. J. Mihm, D. E. Elder, X. Xu, and M. C. Mihm Jr., D. E. Elder and X. Xu, “Lymphatic invasion predicts aggressive behavior in melanocytic tumors of uncertain malignant potential (MELTUMP),” Am. J. Surg. Pathol. 37(5), 669–675 (2013).
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C. H. Ussakli, A. Ebaee, J. Binkley, T. A. Brentnall, M. J. Emond, P. S. Rabinovitch, and R. A. Risques, “Mitochondria and tumor progression in ulcerative colitis,” J. Natl. Cancer Inst. 105(16), 1239–1248 (2013).
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Y. Cao, Z.-L. Zhang, M. Zhou, P. Elson, B. Rini, H. Aydin, K. Feenstra, M.-H. Tan, B. Berghuis, R. Tabbey, J. H. Resau, F.-J. Zhou, B. T. Teh, and C.-N. Qian, “Pericyte coverage of differentiated vessels inside tumor vasculature is an independent unfavorable prognostic factor for patients with clear cell renal cell carcinoma,” Cancer 119(2), 313–324 (2013).
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E. L. Spaeth, C. M. Booth, and F. C. Marini, “Quantitative multispectral analysis following fluorescent tissue transplant for visualization of cell origins, types, and interactions,” J. Visualized Exp. 79, e50385 (2013).
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H. Duong and M. Han, “A multispectral LED array for the reduction of background autofluorescence in brain tissue,” J. Neurosci. Methods 220(1), 46–54 (2013).
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P. G. Ellingsen, N. K. Reitan, B. D. Pedersen, and M. Lindgren, “Hyperspectral analysis using the correlation between image and reference,” J. Biomed. Opt. 18(2), 020501 (2013).
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P. G. Ellingsen, S. Nystrom, N. K. Reitan, M. Lindgren, S. Nyström, N. K. Reitan, and M. Lindgren, “Spectral correlation analysis of amyloid beta plaque inhomogeneity from double staining experiments,” J. Biomed. Opt. 18(10), 101313 (2013).
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J.-R. Duann, C.-I. Jan, M. Ou-Yang, C.-Y. Lin, J.-F. Mo, Y.-J. Lin, M.-H. Tsai, and J.-C. Chiou, “Separating spectral mixtures in hyperspectral image data using independent component analysis: Validation with oral cancer tissue sections,” J. Biomed. Opt. 18(12), 126005 (2013).
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M. Bouzid, A. Khalfallah, A. Bouchot, M. S. Bouhlel, and F. S. Marzani, “Automatic cell nuclei detection: A protocol to acquire multispectral images and to compare results between color and multispectral images,” Proc. SPIE 8587, 85871J (2013).
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Q. Li, D. Xu, X. He, Y. Wang, Z. Chen, H. Liu, Q. Xu, and F. Guo, “AOTF based molecular hyperspectral imaging system and its applications on nerve morphometry,” Appl. Opt. 52(17), 3891–3901 (2013).
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W. Huang, K. Hennrick, and S. Drew, “A colorful future of quantitative pathology: Validation of Vectra technology using chromogenic multiplexed immunohistochemistry and prostate tissue microarrays,” Hum. Pathol. 44(1), 29–38 (2013).
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T. M. Nicholson, P. D. Sehgal, S. A. Drew, W. Huang, and W. A. Ricke, “Sex steroid receptor expression and localization in benign prostatic hyperplasia varies with tissue compartment,” Differentiation 85(4-5), 140–149 (2013).
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L. Roux, D. Racoceanu, N. Lomenie, M. Kulikova, H. Irshad, J. Klossa, F. Capron, C. Genestie, G. Le Naour, and M. N. Gurcan, “Mitosis detection in breast cancer histological images An ICPR 2012 contest,” J Pathol Inform 4(1), 8 (2013).
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C. D. Malon and E. Cosatto, “Classification of mitotic figures with convolutional neural networks and seeded blob features,” J Pathol Inform 4(1), 9 (2013).
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L. D. Hahn, C. Hoyt, D. L. Rimm, and C. Theoharis, “Spatial spectral imaging as an adjunct to the Bethesda classification of thyroid fine-needle aspiration specimens,” Cancer Cytopathol. 121(3), 162–167 (2013).
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A. Merdasa, M. Brydegaard, S. Svanberg, and J. T. Zoueu, “Staining-free malaria diagnostics by multispectral and multimodality light-emitting-diode microscopy,” J. Biomed. Opt. 18(3), 036002 (2013).
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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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2012 (14)

R. Khelifi, M. Adel, and S. Bourennane, “Multispectral texture characterization: application to computer aided diagnosis on prostatic tissue images,” EURASIP J. Adv. Signal Process. 2012(1), 118 (2012).
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H. Akbari, L. V Halig, D. M. Schuster, A. Osunkoya, V. Master, P. T. Nieh, G. Z. Chen, and B. Fei, “Hyperspectral imaging and quantitative analysis for prostate cancer detection,” J. Biomed. Opt. 17(7), 0760051 (2012).
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S. Dabo-Niang and J. T. Zoueu, “Combining kriging, multispectral and multimodal microscopy to resolve malaria-infected erythrocyte contents,” J. Microsc. 247(3), 240–251 (2012).
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Y. Guan, “Pathological leucocyte segmentation algorithm based on hyperspectral imaging technique,” Opt. Eng. 51(5), 053202 (2012).
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X. Wu, M. Amrikachi, and S. K. Shah, “Embedding topic discovery in conditional random fields model for segmenting nuclei using multispectral data,” IEEE Trans. Biomed. Eng. 59(6), 1539–1549 (2012).
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Q. Li, Z. Chen, X. He, Y. Wang, H. Liu, and Q. Xu, “Automatic identification and quantitative morphometry of unstained spinal nerve using molecular hyperspectral imaging technology,” Neurochem. Int. 61(8), 1375–1384 (2012).
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H. Akbari, L. V Halig, H. Zhang, D. Wang, Z. G. Chen, and B. Fei, “Detection of cancer metastasis using a novel macroscopic hyperspectral method,” Proc. SPIE 8317, 831711 (2012).
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S. J. Leavesley, N. Annamdevula, J. Boni, S. Stocker, K. Grant, B. Troyanovsky, T. C. Rich, and D. F. Alvarez, “Hyperspectral imaging microscopy for identification and quantitative analysis of fluorescently-labeled cells in highly autofluorescent tissue,” J. Biophotonics 5(1), 67–84 (2012).
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S. Safayi, N. Korn, A. Bertram, R. M. Akers, A. V Capuco, S. L. Pratt, and S. Ellis, “Myoepithelial cell differentiation markers in prepubertal bovine mammary gland: effect of ovariectomy,” J. Dairy Sci. 95(6), 2965–2976 (2012).
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C. Fiore, D. Bailey, N. Conlon, X. Wu, N. Martin, M. Fiorentino, S. Finn, K. Fall, S.-O. Andersson, O. Andren, M. Loda, and R. Flavin, “Utility of multispectral imaging in automated quantitative scoring of immunohistochemistry,” J. Clin. Pathol. 65(6), 496–502 (2012).
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P. A. Bautista and Y. Yagi, “Multispectral enhancement towards digital staining,” Anal. Cell. Pathol. 35(1), 51–55 (2012).
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P. A. Bautista and Y. Yagi, “Multispectral enhancement method to increase the visual differences of tissue structures in stained histopathology images,” Anal. Cell. Pathol. 35(5-6), 407–420 (2012).
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P. A. Bautista and Y. Yagi, “Digital simulation of staining in histopathology multispectral images: enhancement and linear transformation of spectral transmittance,” J. Biomed. Opt. 17(5), 056013 (2012).
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J. M. Bioucas-Dias, A. Plaza, N. Dobigeon, M. Parente, Q. Du, P. Gader, and J. Chanussot, “Hyperspectral unmixing overview: Geometrical, statistical, and sparse regression-based approaches,” IEEE J. Sel. Top. Appl. Earth Observations Remote Sensing 5(2), 354–379 (2012).
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2011 (11)

H. Akbari, K. Uto, Y. Kosugi, K. Kojima, and N. Tanaka, “Cancer detection using infrared hyperspectral imaging,” Cancer Sci. 102(4), 852–857 (2011).
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L. Gao, N. Bedard, N. Hagen, R. T. Kester, and T. S. Tkaczyk, “Depth-resolved image mapping spectrometer (IMS) with structured illumination,” Opt. Express 19(18), 17439–17452 (2011).
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Y. Yagi, “Color standardization and optimization in whole slide imaging,” Diagn. Pathol. 6(Suppl. 1), S15 (2011).
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