Review
. 2016 Jul; 18:387-412.
doi: 10.1146/annurev-bioeng-112415-114722.

Emerging Themes in Image Informatics and Molecular Analysis for Digital Pathology

Rohit Bhargava 1 Anant Madabhushi 2 
Affiliations
  • PMID: 27420575
  •     135 References
  •     40 citations

Abstract

Pathology is essential for research in disease and development, as well as for clinical decision making. For more than 100 years, pathology practice has involved analyzing images of stained, thin tissue sections by a trained human using an optical microscope. Technological advances are now driving major changes in this paradigm toward digital pathology (DP). The digital transformation of pathology goes beyond recording, archiving, and retrieving images, providing new computational tools to inform better decision making for precision medicine. First, we discuss some emerging innovations in both computational image analytics and imaging instrumentation in DP. Second, we discuss molecular contrast in pathology. Molecular DP has traditionally been an extension of pathology with molecularly specific dyes. Label-free, spectroscopic images are rapidly emerging as another important information source, and we describe the benefits and potential of this evolution. Third, we describe multimodal DP, which is enabled by computational algorithms and combines the best characteristics of structural and molecular pathology. Finally, we provide examples of application areas in telepathology, education, and precision medicine. We conclude by discussing challenges and emerging opportunities in this area.

Keywords: FT-IR spectroscopy; algorithms; chemical imaging; computational; diagnosis; digital pathology; infrared spectroscopic imaging; microenvironment; outcome; precision medicine; prognosis; stainless staining.

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Hum Pathol, 2015 Jun 22; 46(9). PMID: 26093936
The use of virtual microscopy and a wiki in pathology education: Tracking student use, involvement, and response.
Zev Leifer.
J Pathol Inform, 2015 Jun 26; 6. PMID: 26110097    Free PMC article.
Mitosis detection in breast cancer pathology images by combining handcrafted and convolutional neural network features.
Haibo Wang, Angel Cruz-Roa, +6 authors, Anant Madabhushi.
J Med Imaging (Bellingham), 2015 Jul 15; 1(3). PMID: 26158062    Free PMC article.
Feature Importance in Nonlinear Embeddings (FINE): Applications in Digital Pathology.
Shoshana B Ginsburg, George Lee, Sahirzeeshan Ali, Anant Madabhushi.
IEEE Trans Med Imaging, 2015 Jul 18; 35(1). PMID: 26186772
Wide-field FTIR microscopy using mid-IR pulse shaping.
Arnaldo L Serrano, Ayanjeet Ghosh, Joshua S Ostrander, Martin T Zanni.
Opt Express, 2015 Jul 21; 23(14). PMID: 26191843    Free PMC article.
Machine learning approaches to analyze histological images of tissues from radical prostatectomies.
Arkadiusz Gertych, Nathan Ing, +7 authors, Beatrice S Knudsen.
Comput Med Imaging Graph, 2015 Sep 13; 46 Pt 2. PMID: 26362074    Free PMC article.
Validation of digital pathology imaging for primary histopathological diagnosis.
David R J Snead, Yee-Wah Tsang, +16 authors, Ian A Cree.
Histopathology, 2015 Sep 27; 68(7). PMID: 26409165
"Score the Core" Web-based pathologist training tool improves the accuracy of breast cancer IHC4 scoring.
Jesse A Engelberg, Hanna Retallack, +15 authors, Robert D Cardiff.
Hum Pathol, 2015 Sep 28; 46(11). PMID: 26410019
TissueCypher(™): A systems biology approach to anatomic pathology.
Jeffrey W Prichard, Jon M Davison, +7 authors, Rebecca J Critchley-Thorne.
J Pathol Inform, 2015 Oct 03; 6. PMID: 26430536    Free PMC article.
Transition to Virtual Microscopy in Medical Undergraduate Pathology Education: First Experience of Turkey in Dokuz Eylül University Hospital.
Özgül Sağol, Kutsal Yörükoğlu, +6 authors, Erdener Özer.
Turk Patoloji Derg, 2015 Oct 13; 31(3). PMID: 26456963
Can mid-infrared biomedical spectroscopy of cells, fluids and tissue aid improvements in cancer survival? A patient paradigm.
Caryn Hughes, Matthew J Baker.
Analyst, 2015 Oct 27; 141(2). PMID: 26501136
Review.
Development of a practical spatial-spectral analysis protocol for breast histopathology using Fourier transform infrared spectroscopic imaging.
F Nell Pounder, Rohith K Reddy, Rohit Bhargava.
Faraday Discuss, 2016 Apr 21; 187. PMID: 27095431    Free PMC article.
Digital pathology image analysis: opportunities and challenges.
Anant Madabhushi.
Imaging Med, 2009 Jan 01; 1(1). PMID: 30147749    Free PMC article.
The analysis of cell images.
J M Prewitt, M L Mendelsohn.
Ann N Y Acad Sci, 1966 Jan 31; 128(3). PMID: 5220765
Highly Cited.
Computer-aided detection of clustered microcalcifications: an improved method for grouping detected signals.
R M Nishikawa, M L Giger, +2 authors, R A Schmidt.
Med Phys, 1993 Nov 01; 20(6). PMID: 8309438
Normalization of the minimum spanning tree.
R Marcelpoil.
Anal Cell Pathol, 1993 May 01; 5(3). PMID: 8343435
Deep learning for digital pathology image analysis: A comprehensive tutorial with selected use cases.
Andrew Janowczyk, Anant Madabhushi.
J Pathol Inform, 2016 Aug 27; 7. PMID: 27563488    Free PMC article.
Highly Cited.
Automated Tubule Nuclei Quantification and Correlation with Oncotype DX risk categories in ER+ Breast Cancer Whole Slide Images.
David Romo-Bucheli, Andrew Janowczyk, +2 authors, Anant Madabhushi.
Sci Rep, 2016 Sep 08; 6. PMID: 27599752    Free PMC article.
Multi-Pass Adaptive Voting for Nuclei Detection in Histopathological Images.
Cheng Lu, Hongming Xu, +3 authors, Anant Madabhushi.
Sci Rep, 2016 Oct 04; 6. PMID: 27694950    Free PMC article.
Training a cell-level classifier for detecting basal-cell carcinoma by combining human visual attention maps with low-level handcrafted features.
Germán Corredor, Jon Whitney, +2 authors, Eduardo Romero.
J Med Imaging (Bellingham), 2017 Apr 07; 4(2). PMID: 28382314    Free PMC article.
An oral cavity squamous cell carcinoma quantitative histomorphometric-based image classifier of nuclear morphology can risk stratify patients for disease-specific survival.
Cheng Lu, James S Lewis, +3 authors, Anant Madabhushi.
Mod Pathol, 2017 Aug 05; 30(12). PMID: 28776575    Free PMC article.
Digital pathology in nephrology clinical trials, research, and pathology practice.
Laura Barisoni, Jeffrey B Hodgin.
Curr Opin Nephrol Hypertens, 2017 Sep 01; 26(6). PMID: 28858910    Free PMC article.
Review.
Development of a Whole Slide Imaging System on Smartphones and Evaluation With Frozen Section Samples.
Hong Yu, Feng Gao, Liren Jiang, Shuoxin Ma.
JMIR Mhealth Uhealth, 2017 Sep 17; 5(9). PMID: 28916508    Free PMC article.
An Assessment of Imaging Informatics for Precision Medicine in Cancer.
C Chennubhotla, L P Clarke, +9 authors, A Sharma.
Yearb Med Inform, 2017 Oct 25; 26(1). PMID: 29063549    Free PMC article.
Review.
An Image Analysis Resource for Cancer Research: PIIP-Pathology Image Informatics Platform for Visualization, Analysis, and Management.
Anne L Martel, Dan Hosseinzadeh, +6 authors, Metin N Gurcan.
Cancer Res, 2017 Nov 03; 77(21). PMID: 29092947    Free PMC article.
Quantitative Chemical Analysis at the Nanoscale Using the Photothermal Induced Resonance Technique.
Georg Ramer, Vladimir A Aksyuk, Andrea Centrone.
Anal Chem, 2017 Nov 23; 89(24). PMID: 29165992    Free PMC article.
Correlative imaging reveals physiochemical heterogeneity of microcalcifications in human breast carcinomas.
Jennie A M R Kunitake, Siyoung Choi, +11 authors, Lara A Estroff.
J Struct Biol, 2017 Dec 10; 202(1). PMID: 29221896    Free PMC article.
The changing face of cancer diagnosis: From computational image analysis to systems biology.
Fabian Kiessling.
Eur Radiol, 2018 Mar 01; 28(8). PMID: 29488085
Advanced Morphologic Analysis for Diagnosing Allograft Rejection: The Case of Cardiac Transplant Rejection.
Eliot G Peyster, Anant Madabhushi, Kenneth B Margulies.
Transplantation, 2018 Mar 24; 102(8). PMID: 29570167    Free PMC article.
Review.
A deep-learning classifier identifies patients with clinical heart failure using whole-slide images of H&E tissue.
Jeffrey J Nirschl, Andrew Janowczyk, +4 authors, Anant Madabhushi.
PLoS One, 2018 Apr 04; 13(4). PMID: 29614076    Free PMC article.
High-throughput adaptive sampling for whole-slide histopathology image analysis (HASHI) via convolutional neural networks: Application to invasive breast cancer detection.
Angel Cruz-Roa, Hannah Gilmore, +6 authors, Fabio González.
PLoS One, 2018 May 26; 13(5). PMID: 29795581    Free PMC article.
Advances in the computational and molecular understanding of the prostate cancer cell nucleus.
Neil M Carleton, George Lee, Anant Madabhushi, Robert W Veltri.
J Cell Biochem, 2018 Jun 21; 119(9). PMID: 29923622    Free PMC article.
Review.
Identifying the morphologic basis for radiomic features in distinguishing different Gleason grades of prostate cancer on MRI: Preliminary findings.
Gregory Penzias, Asha Singanamalli, +13 authors, Anant Madabhushi.
PLoS One, 2018 Sep 01; 13(8). PMID: 30169514    Free PMC article.
Multimodal Chemical Analysis of the Brain by High Mass Resolution Mass Spectrometry and Infrared Spectroscopic Imaging.
Elizabeth K Neumann, Troy J Comi, +5 authors, Jonathan V Sweedler.
Anal Chem, 2018 Sep 07; 90(19). PMID: 30188687    Free PMC article.
Machine Learning Methods for Histopathological Image Analysis.
Daisuke Komura, Shumpei Ishikawa.
Comput Struct Biotechnol J, 2018 Oct 03; 16. PMID: 30275936    Free PMC article.
Highly Cited. Review.
Stable and discriminating features are predictive of cancer presence and Gleason grade in radical prostatectomy specimens: a multi-site study.
Patrick Leo, Robin Elliott, +3 authors, Anant Madabhushi.
Sci Rep, 2018 Oct 10; 8(1). PMID: 30297720    Free PMC article.
Artificial intelligence in digital pathology - new tools for diagnosis and precision oncology.
Kaustav Bera, Kurt A Schalper, +2 authors, Anant Madabhushi.
Nat Rev Clin Oncol, 2019 Aug 11; 16(11). PMID: 31399699    Free PMC article.
Highly Cited. Review.
All-digital histopathology by infrared-optical hybrid microscopy.
Martin Schnell, Shachi Mittal, +6 authors, Rohit Bhargava.
Proc Natl Acad Sci U S A, 2020 Feb 06; 117(7). PMID: 32015103    Free PMC article.
MEDI3039, a novel highly potent tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) receptor 2 agonist, causes regression of orthotopic tumors and inhibits outgrowth of metastatic triple-negative breast cancer.
Yoshimi Endo Greer, Samuel F Gilbert, +5 authors, Stanley Lipkowitz.
Breast Cancer Res, 2019 Feb 20; 21(1). PMID: 30777098    Free PMC article.
HistoQC: An Open-Source Quality Control Tool for Digital Pathology Slides.
Andrew Janowczyk, Ren Zuo, +2 authors, Anant Madabhushi.
JCO Clin Cancer Inform, 2019 Apr 17; 3. PMID: 30990737    Free PMC article.
Contrast-enhanced T1-weighted image radiomics of brain metastases may predict EGFR mutation status in primary lung cancer.
Sung Jun Ahn, Hyeokjin Kwon, +4 authors, Jong-Min Lee.
Sci Rep, 2020 Jun 03; 10(1). PMID: 32483122    Free PMC article.
Novel quantitative signature of tumor stromal architecture: polarized light imaging differentiates between myxoid and sclerotic human breast cancer stroma.
Blake Jones, Georgia Thomas, +3 authors, Mohammadali Khorasani.
Biomed Opt Express, 2020 Jul 09; 11(6). PMID: 32637252    Free PMC article.
Artificial intelligence-based morphological fingerprinting of megakaryocytes: a new tool for assessing disease in MPN patients.
Korsuk Sirinukunwattana, Alan Aberdeen, +7 authors, Daniel Royston.
Blood Adv, 2020 Jul 25; 4(14). PMID: 32706893    Free PMC article.
Computer-Aided Laser Dissection: A Microdissection Workflow Leveraging Image Analysis Tools.
Jason D Hipp, Donald J Johann, +12 authors, Michael A Tangrea.
J Pathol Inform, 2019 Jan 10; 9. PMID: 30622835    Free PMC article.
The revolving door for AI and pathologists-docendo discimus?
Simone L Van Es, Anant Madabhushi.
J Med Artif Intell, 2019 Aug 03; 2. PMID: 31372599    Free PMC article.
A bird's-eye view of deep learning in bioimage analysis.
Erik Meijering.
Comput Struct Biotechnol J, 2020 Oct 01; 18. PMID: 32994890    Free PMC article.
Review.
Development and interpretation of a pathomics-based model for the prediction of microsatellite instability in Colorectal Cancer.
Rui Cao, Fan Yang, +17 authors, Zhong-Yi Dong.
Theranostics, 2020 Oct 13; 10(24). PMID: 33042271    Free PMC article.
Immune contexture analysis in immuno-oncology: applications and challenges of multiplex fluorescent immunohistochemistry.
Reshma Shakya, Tam Hong Nguyen, Nigel Waterhouse, Rajiv Khanna.
Clin Transl Immunology, 2020 Oct 20; 9(10). PMID: 33072322    Free PMC article.
Review.
Artificial intelligence in automatic classification of invasive ductal carcinoma breast cancer in digital pathology images.
Mohammad Abdolahi, Mohammad Salehi, Iman Shokatian, Reza Reiazi.
Med J Islam Repub Iran, 2021 Jan 14; 34. PMID: 33437736    Free PMC article.
Classification of Hematoxylin and Eosin-Stained Breast Cancer Histology Microscopy Images Using Transfer Learning with EfficientNets.
Chanaleä Munien, Serestina Viriri.
Comput Intell Neurosci, 2021 Apr 27; 2021. PMID: 33897774    Free PMC article.
Next-Generation Digital Histopathology of the Tumor Microenvironment.
Felicitas Mungenast, Achala Fernando, +4 authors, Rupert C Ecker.
Genes (Basel), 2021 May 01; 12(4). PMID: 33917241    Free PMC article.
Review.
Prediction of Remnant Liver Regeneration after Right Hepatectomy in Patients with Hepatocellular Carcinoma Using Preoperative CT Texture Analysis and Clinical Features.
Tong Zhang, Yi Wei, +6 authors, Bin Song.
Contrast Media Mol Imaging, 2021 Jul 06; 2021. PMID: 34220379    Free PMC article.
Dissecting the Business Case for Adoption and Implementation of Digital Pathology: A White Paper from the Digital Pathology Association.
Giovanni Lujan, Jennifer C Quigley, +16 authors, Doug Bowman.
J Pathol Inform, 2021 Jul 06; 12. PMID: 34221633    Free PMC article.
The Immune Subtypes and Landscape of Gastric Cancer and to Predict Based on the Whole-Slide Images Using Deep Learning.
Yan Chen, Zepang Sun, +9 authors, Zhongqing Xu.
Front Immunol, 2021 Jul 16; 12. PMID: 34262565    Free PMC article.
Assessment of a computerized quantitative quality control tool for whole slide images of kidney biopsies.
Yijiang Chen, Jarcy Zee, +11 authors, Andrew Janowczyk.
J Pathol, 2020 Nov 17; 253(3). PMID: 33197281    Free PMC article.
Using Delaunay triangulation to sample whole-specimen color from digital images.
Jennifer J Valvo, Jose David Aponte, +4 authors, Kimberly A Hughes.
Ecol Evol, 2021 Oct 02; 11(18). PMID: 34594513    Free PMC article.