Introduction to Digital Image Analysis in Whole-slide Imaging: A White Paper from the Digital Pathology Association

Journal of Pathology Informatics - Tập 10 Số 1 - Trang 9 - 2019
Famke Aeffner1, Mark D. Zarella2, Nathan Buchbinder3, Marilyn M. Bui4, Matthew R. Goodman5, Douglas J. Hartman6, Giovanni Lujan7, Mariam Molani8, Anil V. Parwani9, Kate Lillard10, Oliver C. Turner11, Venkata Naga Pranathi Vemuri5, Ana Yuil‐Valdes8, Douglas Bowman10
1Amgen Inc., Amgen Research, Comparative Biology and Safety Sciences, South San Francisco, CA
2Department of Pathology and Laboratory Medicine, Drexel University, College of Medicine, Philadelphia, PA
3Proscia, Philadelphia, PA
4Department of Pathology, Moffitt Cancer Center, Tampa, FL
53scan, San Francisco, CA
6University of Pittsburg Medical Center, Pittsburgh, PA
7Inform Diagnostics, Irving, TX
8Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE
9The Ohio State University Medical Center, Columbus, OH
10Indica Labs, Inc., Corrales, NM
11Novartis, Novartis Institutes for BioMedical Research, Preclinical Safety, East Hannover, NJ, USA

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Tài liệu tham khảo

Meijer, 1997, Origins of … image analysis in clinical pathology, J Clin Pathol, 50, 365, 10.1136/jcp.50.5.365

Zarella, 2018, A practical guide to whole slide imaging: A White paper from the digital pathology association, Arch Pathol Lab Med

Griffin, 2017, Digital pathology in clinical use: Where are we now and what is holding us back?, Histopathology, 70, 134, 10.1111/his.12993

Aeffner, 2016, Commentary: Roles for pathologists in a high-throughput image analysis team, Toxicol Pathol, 44, 825, 10.1177/0192623316653492

Aeffner, 2017, The gold standard paradox in digital image analysis: Manual versus automated scoring as ground truth, Arch Pathol Lab Med, 141, 1267, 10.5858/arpa.2016-0386-RA

Wuttisarnwattana, 2016, Automatic stem cell detection in microscopic whole mouse cryo-imaging, IEEE Trans Med Imaging, 35, 819, 10.1109/TMI.2015.2497285

Blacher, 2016, Quantitative assessment of mouse mammary gland morphology using automated digital image processing and TEB detection, Endocrinology, 157, 1709, 10.1210/en.2015-1601

Aeffner, 2016, Quantitative assessment of pancreatic cancer precursor lesions in IHC-stained tissue with a tissue image analysis platform, Lab Invest, 96, 1327, 10.1038/labinvest.2016.111

Aeffner, 2018, Validation of a muscle-specific tissue image-analysis tool for quantitative assessment of dystrophin staining in frozen muscle biopsies, Arch Pathol Lab Med

Chen, 2017, Computer-aided prognosis on breast cancer with hematoxylin and eosin histopathology images: A review, Tumour Biol, 39, 10.1177/1010428317694550

Reisenbichler, 2012, Evaluation of dual immunohistochemistry and chromogenic in situ hybridization for HER2 on a single section, Am J Clin Pathol, 137, 102, 10.1309/AJCPLNHINN9O6YSF

Chaudhuri, 2013, Combined fluorescent in situ hybridization for detection of microRNAs and immunofluorescent labeling for cell-type markers, Front Cell Neurosci, 7, 160, 10.3389/fncel.2013.00160

Elmore, 2017, Proceedings of the 2017 national toxicology program satellite symposium, Toxicol Pathol, 45, 799, 10.1177/0192623317733924

Henson, 1989, End points and significance of reproducibility in pathology, Arch Pathol Lab Med, 113, 830

Bolon, 2017, A primer for oncoimmunology (Immunooncology), Toxicol Pathol, 45, 584, 10.1177/0192623317713318

Pavlides, 2017, Interobserver variability in histologic evaluation of liver fibrosis using categorical and quantitative scores, Am J Clin Pathol, 147, 364, 10.1093/ajcp/aqx011

Lee, 2013, Liver steatosis assessment: Correlations among pathology, radiology, clinical data and automated image analysis software, Pathol Res Pract, 209, 371, 10.1016/j.prp.2013.04.001

Lloyd, 2016, Image analysis of the tumor microenvironment, Adv Exp Med Biol, 936, 1, 10.1007/978-3-319-42023-3_1

Watanabe, 1996, Relationship between immunostaining intensity and antigen content in sections, J Histochem Cytochem, 44, 1451, 10.1177/44.12.8985137

Daunoravicius, 2014, Quantification of myocardial fibrosis by digital image analysis and interactive stereology, Diagn Pathol, 9, 114, 10.1186/1746-1596-9-114

Wittekind, 2003, Traditional staining for routine diagnostic pathology including the role of tannic acid 1. Value and limitations of the hematoxylin-eosin stain, Biotech Histochem, 78, 261, 10.1080/10520290310001633725

Chan, 2014, The wonderful colors of the hematoxylin-eosin stain in diagnostic surgical pathology, Int J Surg Pathol, 22, 12, 10.1177/1066896913517939

Zarella, 2015, An optimized color transformation for the analysis of digital images of hematoxylin & eosin stained slides, J Pathol Inform, 6, 33, 10.4103/2153-3539.158910

Humphrey, 2004, Gleason grading and prognostic factors in carcinoma of the prostate, Mod Pathol, 17, 292, 10.1038/modpathol.3800054

Bloom, 1957, Histological grading and prognosis in breast cancer; a study of 1409 cases of which 359 have been followed for 15 years, Br J Cancer, 11, 359, 10.1038/bjc.1957.43

Irshad, 2014, Methods for nuclei detection, segmentation, and classification in digital histopathology: A review-current status and future potential, IEEE Rev Biomed Eng, 7, 97, 10.1109/RBME.2013.2295804

Qi, 2012, Robust segmentation of overlapping cells in histopathology specimens using parallel seed detection and repulsive level set, IEEE Trans Biomed Eng, 59, 754, 10.1109/TBME.2011.2179298

Al-Kofahi, 2010, Improved automatic detection and segmentation of cell nuclei in histopathology images, IEEE Trans Biomed Eng, 57, 841, 10.1109/TBME.2009.2035102

Ballarò, 2008, An automated image analysis methodology for classifying megakaryocytes in chronic myeloproliferative disorders, Med Image Anal, 12, 703, 10.1016/j.media.2008.04.001

Korde, 2009, Automatic segmentation of cell nuclei in bladder and skin tissue for karyometric analysis, Anal Quant Cytol Histol, 31, 83

Gurcan, 2006, Image analysis for neuroblastoma classification: Segmentation of cell nuclei, Conf Proc IEEE Eng Med Biol Soc, 1, 4844, 10.1109/IEMBS.2006.260837

Veta, 2013, Automatic nuclei segmentation in H&E stained breast cancer histopathology images, PLoS One, 8, 10.1371/journal.pone.0070221

Nandy, 2012, Automatic segmentation and supervised learning-based selection of nuclei in cancer tissue images, Cytometry A, 81, 743, 10.1002/cyto.a.22097

Latson, 2003, Automated cell nuclear segmentation in color images of hematoxylin and eosin-stained breast biopsy, Anal Quant Cytol Histol, 25, 321

Yang, 2005, Unsupervised segmentation based on robust estimation and color active contour models, IEEE Trans Inf Technol Biomed, 9, 475, 10.1109/TITB.2005.847515

Mouelhi, 2013, Automatic image segmentation of nuclear stained breast tissue sections using color active contour model and an improved watershed method, Biomed Signal Proce Control, 8, 421, 10.1016/j.bspc.2013.04.003

Ali, 2011, Adaptive energy selective active contour with shape priors for nuclear segmentation and gleason grading of prostate cancer, Med Image Comput Comput Assist Interv, 14, 661

Fatakdawala, 2010, Expectation-maximization-driven geodesic active contour with overlap resolution (EMaGACOR): Application to lymphocyte segmentation on breast cancer histopathology, IEEE Trans Biomed Eng, 57, 1676, 10.1109/TBME.2010.2041232

Zarella, 2017, A Template Matching Model for Nuclear Segmentation in Digital Images of H&E Stained Slides

Naik S, Doyle S, Agner S, Madabhushi A, Feldman M, Tomaszewski J. Automated Gland and Nuclei Segmentation for Grading of Prostate and Breast Cancer Histopathology. Paper presented at: Biomedical Imaging: From Nano to Macro, 2008. ISBI 2008. 5th IEEE International Symposium on; 14-17 May, 2008.

Ali, 2012, An integrated region-, boundary-, shape-based active contour for multiple object overlap resolution in histological imagery, IEEE Trans Med Imaging, 31, 1448, 10.1109/TMI.2012.2190089

Jelen L, Fevens T, Krzyzak A. Influence of Nuclei Segmentation on Breast Cancer Malignancy Classification. Paper presented at: SPIE Medical Imaging; 2009.

Gelasca, 2008, Evaluation and Benchmark for biological image segmentation

Hammond, 2010, American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version), Arch Pathol Lab Med, 134, e48, 10.5858/134.7.e48

1998, Tamoxifen for early breast cancer: An overview of the randomised trials. Early breast cancer trialists’ collaborative group, Lancet, 351, 1451, 10.1016/S0140-6736(97)11423-4

Stålhammar, 2016, Digital image analysis outperforms manual biomarker assessment in breast cancer, Mod Pathol, 29, 318, 10.1038/modpathol.2016.34

Lykkegaard Andersen, 2018, Virtual double staining: A digital approach to immunohistochemical quantification of estrogen receptor protein in breast carcinoma specimens, Appl Immunohistochem Mol Morphol, 26, 620, 10.1097/PAI.0000000000000502

Stålhammar, 2018, Digital image analysis of Ki67 in hot spots is superior to both manual Ki67 and mitotic counts in breast cancer, Histopathology, 72, 974, 10.1111/his.13452

Ruifrok, 2003, Comparison of quantification of histochemical staining by hue-saturation-intensity (HSI) transformation and color-deconvolution, Appl Immunohistochem Mol Morphol, 11, 85, 10.1097/00129039-200303000-00014

Zarella, 2018, BCL-2 expression aids in the immunohistochemical prediction of the oncotype DX breast cancer recurrence score, BMC Clin Pathol, 18, 14, 10.1186/s12907-018-0082-3

Flanagan, 2008, Histopathologic variables predict oncotype DX recurrence score, Mod Pathol, 21, 1255, 10.1038/modpathol.2008.54

Clark, 2013, Impact of progesterone receptor semiquantitative immunohistochemical result on oncotype DX recurrence score: A quality assurance study of 1074 cases, Appl Immunohistochem Mol Morphol, 21, 287, 10.1097/PAI.0b013e31826f80c9

Romond, 2005, Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer, N Engl J Med, 353, 1673, 10.1056/NEJMoa052122

Piccart-Gebhart, 2005, Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer, N Engl J Med, 353, 1659, 10.1056/NEJMoa052306

Gilcrease, 2009, Even low-level HER2 expression may be associated with worse outcome in node-positive breast cancer, Am J Surg Pathol, 33, 759, 10.1097/PAS.0b013e31819437f9

Wolff, 2007, American Society of Clinical Oncology/College of American Pathologists Guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer, Arch Pathol Lab Med, 131, 18, 10.5858/2007-131-18-ASOCCO

Wolff, 2013, Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American society of clinical oncology/College of american pathologists clinical practice guideline update, J Clin Oncol, 31, 3997, 10.1200/JCO.2013.50.9984

Wolff, 2018, Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update, J Clin Oncol, 36, 2105, 10.1200/JCO.2018.77.8738

Reck, 2016, Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer, N Engl J Med, 375, 1823, 10.1056/NEJMoa1606774

Aguiar, 2016, A pooled analysis of nivolumab for the treatment of advanced non-small-cell lung cancer and the role of PD-L1 as a predictive biomarker, Immunotherapy, 8, 1011, 10.2217/imt-2016-0032

Keytruda

Kuenen-Boumeester, 1984, Prognostic scoring using cytomorphometry and lymph node status of patients with breast carcinoma, Eur J Cancer Clin Oncol, 20, 337, 10.1016/0277-5379(84)90079-8

Larsimont, 1989, Correlation between nuclear cytomorphometric parameters and estrogen receptor levels in breast cancer, Cancer, 63, 2162, 10.1002/1097-0142(19890601)63:11<2162::AID-CNCR2820631116>3.0.CO;2-J

Aaltomaa, 1991, The significance of nuclear morphometric variables as prognostic predictors in breast cancer, Anticancer Res, 11, 1663

Pienta, 1991, Correlation of nuclear morphometry with progression of breast cancer, Cancer, 68, 2012, 10.1002/1097-0142(19911101)68:9<2012::AID-CNCR2820680928>3.0.CO;2-C

Baak, 1985, The value of morphometry to classic prognosticators in breast cancer, Cancer, 56, 374, 10.1002/1097-0142(19850715)56:2<374::AID-CNCR2820560229>3.0.CO;2-9

Baak, 1982, Prognostic indicators in breast cancer – Morphometric methods, Histopathology, 6, 327, 10.1111/j.1365-2559.1982.tb02727.x

Zarella, 2015, Lymph node metastasis status in breast carcinoma can be predicted via image analysis of tumor histology, Anal Quant Cytopathol Histpathol, 37, 273

Whitney, 2018, Quantitative nuclear histomorphometry predicts oncotype DX risk categories for early stage ER+ breast cancer, BMC Cancer, 18, 610, 10.1186/s12885-018-4448-9

Kashyap, 2017, Study of nuclear morphometry on cytology specimens of benign and malignant breast lesions: A study of 122 cases, J Cytol, 34, 10, 10.4103/0970-9371.197591

Lu, 2018, Nuclear shape and orientation features from H&E images predict survival in early-stage estrogen receptor-positive breast cancers, Lab Invest, 98, 1438, 10.1038/s41374-018-0095-7

Veta, 2015, Assessment of algorithms for mitosis detection in breast cancer histopathology images, Med Image Anal, 20, 237, 10.1016/j.media.2014.11.010

Sethi, 2016, Empirical comparison of color normalization methods for epithelial-stromal classification in H and E images, J Pathol Inform, 7, 17, 10.4103/2153-3539.179984

Bautista, 2014, Color standardization in whole slide imaging using a color calibration slide, J Pathol Inform, 5, 4, 10.4103/2153-3539.126153

Kayser, 2008, How to measure image quality in tissue-based diagnosis (diagnostic surgical pathology), Diagn Pathol, 3, S11, 10.1186/1746-1596-3-S1-S11

Macenko M, Niethammer M, Marron JS, Borland D, Woosley JT, Xiaojun G, et al. A Method for Normalizing Histology Slides for Quantitative Analysis. Paper presented at: 2009 IEEE International Symposium on Biomedical Imaging: From Nano to Macro; 28 June, 2009.

Tani, 2012, Color standardization method and system for whole slide imaging based on spectral sensing, Anal Cell Pathol (Amst), 35, 107, 10.1155/2012/154735

Ruifrok, 2001, Quantification of histochemical staining by color deconvolution, Anal Quant Cytol Histol, 23, 291

Khan, 2014, A nonlinear mapping approach to stain normalization in digital histopathology images using image-specific color deconvolution, IEEE Trans Biomed Eng, 61, 1729, 10.1109/TBME.2014.2303294

Zarella, 2017, An alternative reference space for H&E color normalization, PLoS One, 12, 10.1371/journal.pone.0174489

Bejnordi, 2016, Stain specific standardization of whole-slide histopathological images, IEEE Trans Med Imaging, 35, 404, 10.1109/TMI.2015.2476509

Vahadane, 2016, Structure-preserving color normalization and sparse stain separation for histological images, IEEE Trans Med Imaging, 35, 1962, 10.1109/TMI.2016.2529665

Wild, 2000, Quantitative assessment of angiogenesis and tumor vessel architecture by computer-assisted digital image analysis: Effects of VEGF-toxin conjugate on tumor microvessel density, Microvasc Res, 59, 368, 10.1006/mvre.1999.2233

Webster, 2014, Whole-slide imaging and automated image analysis: Considerations and opportunities in the practice of pathology, Vet Pathol, 51, 211, 10.1177/0300985813503570

Potts, 2012, Evaluating tumor heterogeneity in immunohistochemistry-stained breast cancer tissue, Lab Invest, 92, 1342, 10.1038/labinvest.2012.91

Pagès, 2018, International validation of the consensus immunoscore for the classification of colon cancer: A prognostic and accuracy study, Lancet, 391, 2128, 10.1016/S0140-6736(18)30789-X

Brown, 2017, Bias in image analysis and its solution: Unbiased stereology, J Toxicol Pathol, 30, 183, 10.1293/tox.2017-0013

Fonyad, 2015, 3-dimensional digital reconstruction of the murine coronary system for the evaluation of chronic allograft vasculopathy, Diagn Pathol, 10, 16, 10.1186/s13000-015-0248-6

Mendis-Handagama, 1992, Estimation error of leydig cell numbers in atrophied rat testes due to the assumption of spherical nuclei, J Microsc, 168, 25, 10.1111/j.1365-2818.1992.tb03247.x

Gundersen, 1986, Stereology of arbitrary particles. A review of unbiased number and size estimators and the presentation of some new ones, in memory of william R. Thompson, J Microsc, 143, 3, 10.1111/j.1365-2818.1986.tb02764.x

Dorph-Petersen, 2011, Stereological approaches to identifying neuropathology in psychosis, Biol Psychiatry, 69, 113, 10.1016/j.biopsych.2010.04.030

Gundersen, 1988, Some new, simple and efficient stereological methods and their use in pathological research and diagnosis, APMIS, 96, 379, 10.1111/j.1699-0463.1988.tb05320.x

Mattfeldt, 1990, Estimation of surface area and length with the orientator, J Microsc, 159, 301, 10.1111/j.1365-2818.1990.tb03036.x

Reed, 2010, One-stop stereology: The estimation of 3D parameters using isotropic rulers, J Microsc, 239, 54, 10.1111/j.1365-2818.2009.03356.x

Ameisen D, Deroulers C, Perrier V, Bouhidel F, Battistella M, Legrès L, et al. Towards Better Digital Pathology Workflows: Programming Libraries for High-Speed Sharpness Assessment of Whole Slide Images. Paper presented at: Diagnostic Pathology; 2014.

Shakeri, 2015, Optical quality assessment of whole slide imaging systems for digital pathology, Opt Express, 23, 1319, 10.1364/OE.23.001319

Dunstan, 2011, The use of immunohistochemistry for biomarker assessment – Can it compete with other technologies?, Toxicol Pathol, 39, 988, 10.1177/0192623311419163

Potts, 2010, The role and impact of quantitative discovery pathology, Drug Discov Today, 15, 943, 10.1016/j.drudis.2010.09.001

Weigelt, 2010, Molecular profiling currently offers no more than tumour morphology and basic immunohistochemistry, Breast Cancer Res, 12, S5, 10.1186/bcr2734

Hughes, 2018, Quanti.us: A tool for rapid, flexible, crowd-based annotation of images, Nat Methods, 15, 587, 10.1038/s41592-018-0069-0

Webster, 2011, Quantifying histological features of cancer biospecimens for biobanking quality assurance using automated morphometric pattern recognition image analysis algorithms, J Biomol Tech, 22, 108

Tadrous, 2010, On the concept of objectivity in digital image analysis in pathology, Pathology, 42, 207, 10.3109/00313021003641758

Park, 2018, Methodologic guide for evaluating clinical performance and effect of artificial intelligence technology for medical diagnosis and prediction, Radiology, 286, 800, 10.1148/radiol.2017171920

Wu, 2017, A novel measure and significance testing in data analysis of cell image segmentation, BMC Bioinformatics, 18, 168, 10.1186/s12859-017-1527-x

Weese, 2016, Four challenges in medical image analysis from an industrial perspective, Med Image Anal, 33, 44, 10.1016/j.media.2016.06.023

Aeffner, 2018, Digital microscopy, image analysis, and virtual slide repository, ILAR J, 10.1093/ilar/ily007

NEQAS

IQNPath

Bini, 2018, Artificial intelligence, machine learning, deep learning, and cognitive computing: What do these terms mean and how will they impact health care?, J Arthroplasty, 33, 2358, 10.1016/j.arth.2018.02.067

Lewis-Kraus, 2016, The great AI awakening, N Y Times Mag

Nilsson, 1998

Handelman, 2018, EDoctor: Machine learning and the future of medicine, J Intern Med, 284, 603, 10.1111/joim.12822

Ching, 2018, Opportunities and obstacles for deep learning in biology and medicine, J R Soc Interface, 15, 10.1098/rsif.2017.0387

Khosravi, 2018, Deep convolutional neural networks enable discrimination of heterogeneous digital pathology images, EBioMedicine, 27, 317, 10.1016/j.ebiom.2017.12.026

Litjens, 2016, Deep learning as a tool for increased accuracy and efficiency of histopathological diagnosis, Sci Rep, 6, 10.1038/srep26286

Komura, 2018, Machine learning methods for histopathological image analysis, Comput Struct Biotechnol J, 16, 34, 10.1016/j.csbj.2018.01.001

Pivetta, 2013, Development and validation of a general approach to predict and quantify the synergism of anti-cancer drugs using experimental design and artificial neural networks, Talanta, 115, 84, 10.1016/j.talanta.2013.04.031

Agatonovic-Kustrin, 2000, Basic concepts of artificial neural network (ANN) modeling and its application in pharmaceutical research, J Pharm Biomed Anal, 22, 717, 10.1016/S0731-7085(99)00272-1

Dande, 2018, Acquaintance to artificial neural networks and use of artificial intelligence as a diagnostic tool for tuberculosis: A review, Tuberculosis (Edinb), 108, 1, 10.1016/j.tube.2017.09.006

Cireşan

Fuchs, 2008, Computational pathology analysis of tissue microarrays predicts survival of renal clear cell carcinoma patients, Med Image Comput Comput Assist Interv, 11, 1

Shu

Janowczyk, 2016, Deep learning for digital pathology image analysis: A comprehensive tutorial with selected use cases, J Pathol Inform, 7, 29, 10.4103/2153-3539.186902

Lambin, 2017, Radiomics: The bridge between medical imaging and personalized medicine, Nat Rev Clin Oncol, 14, 749, 10.1038/nrclinonc.2017.141

Ganesan, 2009, Computerized histologic image-based risk score (IbRiS) classifier for ER+ breast cancer, Cancer Research, 10.1158/0008-5472.SABCS-09-3046

LeCun, 2015, Deep learning, Nature, 521, 436, 10.1038/nature14539

Farahani, 2017, Pathologists’ computer-assisted diagnosis: A Mock-up of a prototype information system to facilitate automation of pathology sign-out, Arch Pathol Lab Med, 141, 1413, 10.5858/arpa.2016-0214-OA

Bándi, 2018, From detection of individual metastases to classification of lymph node status at the patient level: The CAMELYON17 challenge. IEEE Transactions on Medical Imaging, EEE Transactions on Medical Imaging, 38, 550, 10.1109/TMI.2018.2867350

Healey, 2017, Assessment of ki67 expression for breast cancer subtype classification and prognosis in the nurses’ health study, Breast Cancer Res Treat, 166, 613, 10.1007/s10549-017-4421-3

Stålhammar, 2018, Digital image analysis of Ki67 in hot spots is superior to both manual Ki67 and mitotic counts in breast cancer, Histopathology, 72, 974, 10.1111/his.13452

Wang, 2010, Detection and classification of thyroid follicular lesions based on nuclear structure from histopathology images, Cytometry A, 77, 485, 10.1002/cyto.a.20853

He, 2012, Histology image analysis for carcinoma detection and grading, Comput Methods Programs Biomed, 107, 538, 10.1016/j.cmpb.2011.12.007

Mohammed, 2014, Peripheral blood smear image analysis: A comprehensive review, J Pathol Inform, 5, 9, 10.4103/2153-3539.129442

Bui, 2013

Administration TFaD, 2018

Baruch, 2018

Bui, 2019, Quantitative Image Analysis of Human Epidermal Growth Factor Receptor 2 Immunohistochemistry for Breast Cancer: Guideline From the College of American Pathologists, Arch Pathol Lab Med, 10.5858/arpa.2018-0378-CP

Skacel, 2002, Tissue microarrays: A powerful tool for high-throughput analysis of clinical specimens: A review of the method with validation data, Appl Immunohistochem Mol Morphol, 10, 1, 10.1097/00129039-200203000-00001

Steele, 2018, Measuring multiple parameters of CD8+tumor-infiltrating lymphocytes in human cancers by image analysis, J Immunother Cancer, 6, 20, 10.1186/s40425-018-0326-x

Bankhead, 2017, QuPath: Open source software for digital pathology image analysis, Sci Rep, 7, 10.1038/s41598-017-17204-5

Lewis, 2005, Analysis of intratumoral heterogeneity and amplification status in breast carcinomas with equivocal (2+) HER-2 immunostaining, Am J Clin Pathol, 124, 273, 10.1309/J9VXABUGKC4Y07DL

Seol, 2012, Intratumoral heterogeneity of HER2 gene amplification in breast cancer: Its clinicopathological significance, Mod Pathol, 25, 938, 10.1038/modpathol.2012.36

Ghaznavi, 2013, Digital imaging in pathology: Whole-slide imaging and beyond, Annu Rev Pathol, 8, 331, 10.1146/annurev-pathol-011811-120902

Butler, 2013, Marked expansion of exocrine and endocrine pancreas with incretin therapy in humans with increased exocrine pancreas dysplasia and the potential for glucagon-producing neuroendocrine tumors, Diabetes, 62, 2595, 10.2337/db12-1686

Forest, 2014, Characterization of the exocrine pancreas in the male zucker diabetic fatty rat model of type 2 diabetes mellitus following 3 months of treatment with sitagliptin, Endocrinology, 155, 783, 10.1210/en.2013-1781

Golson, 2014, Automated quantification of pancreatic β-cell mass, Am J Physiol Endocrinol Metab, 306, E1460, 10.1152/ajpendo.00591.2013

Chakrabarty, 2010, IFN-gamma promotes complement expression and attenuates amyloid plaque deposition in amyloid beta precursor protein transgenic mice, J Immunol, 184, 5333, 10.4049/jimmunol.0903382

Villarreal, 2017, Chronic verubecestat treatment suppresses amyloid accumulation in advanced aged tg2576-aβPPswe mice without inducing microhemorrhage, J Alzheimers Dis, 59, 1393, 10.3233/JAD-170056

Villarreal, 2010, Evaluation of amyloid plaque in an Alzheimer’s disease mouse model with the use of stereological versus aperio analysis, J Histotechnol, 33, 161, 10.1179/his.2010.33.4.161

Karumuthil-Melethil, 2016, Intrathecal administration of AAV/GALC vectors in 10-11-day-old twitcher mice improves survival and is enhanced by bone marrow transplant, J Neurosci Res, 94, 1138, 10.1002/jnr.23882

Varghese, 2014, IHC profiler: An open source plugin for the quantitative evaluation and automated scoring of immunohistochemistry images of human tissue samples, PLoS One, 9, 10.1371/journal.pone.0096801

Carpenter, 2012, A call for bioimaging software usability, Nat Methods, 9, 666, 10.1038/nmeth.2073

Wiesmann, 2015, Review of free software tools for image analysis of fluorescence cell micrographs, J Microsc, 257, 39, 10.1111/jmi.12184

Vonnegut S. Open Source vs. Commercial Tools: Static Code Analysis Showdown. Vol. 2018. Checkmarx; 2015.