. 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 
  • PMID: 27420575
  •     135 References
  •     40 citations


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.

Combined E-cadherin and high molecular weight cytokeratin immunoprofile differentiates lobular, ductal, and hybrid mammary intraepithelial neoplasias.
Gary L Bratthauer, Farid Moinfar, +4 authors, Fattaneh A Tavassoli.
Hum Pathol, 2002 Aug 02; 33(6). PMID: 12152161
Automated subcellular localization and quantification of protein expression in tissue microarrays.
Robert L Camp, Gina G Chung, David L Rimm.
Nat Med, 2002 Oct 22; 8(11). PMID: 12389040
Highly Cited.
Active shape model segmentation with optimal features.
Bram van Ginneken, Alejandro F Frangi, +2 authors, Max A Viergever.
IEEE Trans Med Imaging, 2002 Dec 11; 21(8). PMID: 12472265
Imaging of colorectal adenocarcinoma using FT-IR microspectroscopy and cluster analysis.
Peter Lasch, Wolfgang Haensch, Dieter Naumann, Max Diem.
Biochim Biophys Acta, 2004 Mar 03; 1688(2). PMID: 14990348
A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer.
Soonmyung Paik, Steven Shak, +12 authors, Norman Wolmark.
N Engl J Med, 2004 Dec 14; 351(27). PMID: 15591335
Highly Cited.
Mie-type scattering and non-Beer-Lambert absorption behavior of human cells in infrared microspectroscopy.
Brian Mohlenhoff, Melissa Romeo, Max Diem, Bayden R Wood.
Biophys J, 2005 Mar 08; 88(5). PMID: 15749767    Free PMC article.
Infrared spectroscopic imaging for histopathologic recognition.
Daniel C Fernandez, Rohit Bhargava, Stephen M Hewitt, Ira W Levin.
Nat Biotechnol, 2005 Mar 29; 23(4). PMID: 15793574
Fourier transform infrared vibrational spectroscopic imaging: integrating microscopy and molecular recognition.
Ira W Levin, Rohit Bhargava.
Annu Rev Phys Chem, 2005 Mar 31; 56. PMID: 15796707
20-year outcomes following conservative management of clinically localized prostate cancer.
Peter C Albertsen, James A Hanley, Judith Fine.
JAMA, 2005 May 05; 293(17). PMID: 15870412
Highly Cited.
Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy.
Conor L Evans, Eric O Potma, +3 authors, X Sunney Xie.
Proc Natl Acad Sci U S A, 2005 Nov 03; 102(46). PMID: 16263923    Free PMC article.
Highly Cited.
Static telepathology consultation service between Tata Memorial Centre, Mumbai and Nargis Dutt Memorial Charitable Hospital, Barshi, Solapur, Maharashtra: an analysis of the first 100 cases.
Sangeeta Desai, Rajasa Patil, +4 authors, Roshni Chinoy.
Indian J Pathol Microbiol, 2005 Nov 22; 47(4). PMID: 16295371
Applications of ATR-FTIR spectroscopic imaging to biomedical samples.
S G Kazarian, K L A Chan.
Biochim Biophys Acta, 2006 Mar 29; 1758(7). PMID: 16566893
High throughput assessment of cells and tissues: Bayesian classification of spectral metrics from infrared vibrational spectroscopic imaging data.
Rohit Bhargava, Daniel C Fernandez, Stephen M Hewitt, Ira W Levin.
Biochim Biophys Acta, 2006 Jul 11; 1758(7). PMID: 16822477
Chemical mapping of tumor progression by FT-IR imaging: towards molecular histopathology.
Cyril Petibois, Gérard Déléris.
Trends Biotechnol, 2006 Aug 29; 24(10). PMID: 16935373
13-year outcomes following treatment for clinically localized prostate cancer in a population based cohort.
Peter C Albertsen, James A Hanley, +2 authors, Judith Fine.
J Urol, 2007 Feb 14; 177(3). PMID: 17296379
Bioconjugated quantum dots for multiplexed and quantitative immunohistochemistry.
Yun Xing, Qaiser Chaudry, +9 authors, Shuming Nie.
Nat Protoc, 2007 Jun 05; 2(5). PMID: 17546006
Quantum cascade laser.
J Faist, F Capasso, +3 authors, A Y Cho.
Science, 1994 Apr 22; 264(5158). PMID: 17732739
Highly Cited.
Towards a practical Fourier transform infrared chemical imaging protocol for cancer histopathology.
Rohit Bhargava.
Anal Bioanal Chem, 2007 Sep 06; 389(4). PMID: 17786414
Chemical imaging of the stratum corneum under controlled humidity with the attenuated total reflection Fourier transform infrared spectroscopy method.
K L Andrew Chan, Sergei G Kazarian.
J Biomed Opt, 2007 Sep 18; 12(4). PMID: 17867814
Predicting survival for men with clinically localized prostate cancer: what do we need in contemporary practice?
Peter Albertsen.
Cancer, 2007 Nov 15; 112(1). PMID: 18000802
Cell-graph mining for breast tissue modeling and classification.
Cagatay Bilgin, Cigdem Demir, Chandandeep Nagi, Bulent Yener.
Annu Int Conf IEEE Eng Med Biol Soc, 2007 Nov 16; 2007. PMID: 18003206
A color-based approach for automated segmentation in tumor tissue classification.
Yi-Ying Wang, Shao-Chien Chang, +2 authors, Yung-Nien Sun.
Annu Int Conf IEEE Eng Med Biol Soc, 2007 Nov 16; 2007. PMID: 18003532
Assessing and improving the stability of chemometric models in small sample size situations.
Claudia Beleites, Reiner Salzer.
Anal Bioanal Chem, 2008 Jan 30; 390(5). PMID: 18228011
A contemporary study correlating prostate needle biopsy and radical prostatectomy Gleason score.
Samson W Fine, Jonathan I Epstein.
J Urol, 2008 Feb 22; 179(4). PMID: 18289601
The Alzheimer's Disease Neuroimaging Initiative (ADNI): MRI methods.
Clifford R Jack, Matt A Bernstein, +32 authors, Michael W Weiner.
J Magn Reson Imaging, 2008 Feb 28; 27(4). PMID: 18302232    Free PMC article.
Highly Cited.
Infrared hyperspectral imaging using a broadly tunable external cavity quantum cascade laser and microbolometer focal plane array.
Mark C Phillips, Nicolas Ho.
Opt Express, 2008 Jun 11; 16(3). PMID: 18542262
Quantitative multiplexed quantum dot immunohistochemistry.
E Sweeney, T H Ward, +5 authors, R Byers.
Biochem Biophys Res Commun, 2008 Jul 16; 374(2). PMID: 18621021
Investigating the efficacy of nonlinear dimensionality reduction schemes in classifying gene and protein expression studies.
George Lee, Carlos Rodriguez, Anant Madabhushi.
IEEE/ACM Trans Comput Biol Bioinform, 2008 Aug 02; 5(3). PMID: 18670041    Free PMC article.
Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy.
Christian W Freudiger, Wei Min, +6 authors, X Sunney Xie.
Science, 2008 Dec 20; 322(5909). PMID: 19095943    Free PMC article.
Highly Cited.
Digital slides: present status of a tool for consultation, teaching, and quality control in pathology.
Rafael Rocha, José Vassallo, +2 authors, Helenice Gobbi.
Pathol Res Pract, 2009 Jun 09; 205(11). PMID: 19501988
Computerized image-based detection and grading of lymphocytic infiltration in HER2+ breast cancer histopathology.
Ajay Nagesh Basavanhally, Shridar Ganesan, +5 authors, Anant Madabhushi.
IEEE Trans Biomed Eng, 2009 Nov 04; 57(3). PMID: 19884074
An update of the Gleason grading system.
Jonathan I Epstein.
J Urol, 2009 Dec 17; 183(2). PMID: 20006878
Highly Cited. Review.
Resonant Mie scattering (RMieS) correction of infrared spectra from highly scattering biological samples.
Paul Bassan, Achim Kohler, +7 authors, Peter Gardner.
Analyst, 2010 Jan 26; 135(2). PMID: 20098758
Expectation-maximization-driven geodesic active contour with overlap resolution (EMaGACOR): application to lymphocyte segmentation on breast cancer histopathology.
Hussain Fatakdawala, Jun Xu, +5 authors, Anant Madabhushi.
IEEE Trans Biomed Eng, 2010 Feb 23; 57(7). PMID: 20172780
RMieS-EMSC correction for infrared spectra of biological cells: extension using full Mie theory and GPU computing.
Paul Bassan, Achim Kohler, +7 authors, Peter Gardner.
J Biophotonics, 2010 Apr 24; 3(8-9). PMID: 20414907
Treatment of localized prostate cancer: when is active surveillance appropriate?
Peter C Albertsen.
Nat Rev Clin Oncol, 2010 May 05; 7(7). PMID: 20440282
Characterization of tumor progression in engineered tissue using infrared spectroscopic imaging.
Rong Kong, Rohith K Reddy, Rohit Bhargava.
Analyst, 2010 May 26; 135(7). PMID: 20498913    Free PMC article.
IR spectral imaging of secreted mucus: a promising new tool for the histopathological recognition of human colonic adenocarcinomas.
Adrian Travo, Olivier Piot, +5 authors, Pierre Jeannesson.
Histopathology, 2010 May 27; 56(7). PMID: 20500531
Narrowband midinfrared reflectance filters using guided mode resonance.
Anil K Kodali, Matthew Schulmerich, +3 authors, Rohit Bhargava.
Anal Chem, 2010 Jun 10; 82(13). PMID: 20527738    Free PMC article.
A boosted Bayesian multiresolution classifier for prostate cancer detection from digitized needle biopsies.
Scott Doyle, Michael Feldman, John Tomaszewski, Anant Madabhushi.
IEEE Trans Biomed Eng, 2010 Jun 24; 59(5). PMID: 20570758
Histopathological image analysis: a review.
Metin N Gurcan, Laura E Boucheron, +3 authors, B Yener.
IEEE Rev Biomed Eng, 2009 Jan 01; 2. PMID: 20671804    Free PMC article.
Highly Cited. Review.
Accurate histopathology from low signal-to-noise ratio spectroscopic imaging data.
Rohith K Reddy, Rohit Bhargava.
Analyst, 2010 Sep 11; 135(11). PMID: 20830324
Multimodal microscopy for automated histologic analysis of prostate cancer.
Jin Tae Kwak, Stephen M Hewitt, Saurabh Sinha, Rohit Bhargava.
BMC Cancer, 2011 Feb 10; 11. PMID: 21303560    Free PMC article.
Spatially Invariant Vector Quantization: A pattern matching algorithm for multiple classes of image subject matter including pathology.
Jason D Hipp, Jerome Y Cheng, +2 authors, Ulysses J Balis.
J Pathol Inform, 2011 Mar 09; 2. PMID: 21383936    Free PMC article.
High-resolution Fourier-transform infrared chemical imaging with multiple synchrotron beams.
Michael J Nasse, Michael J Walsh, +5 authors, Carol J Hirschmugl.
Nat Methods, 2011 Mar 23; 8(5). PMID: 21423192    Free PMC article.
Digital pathology: current status and future perspectives.
Shaimaa Al-Janabi, André Huisman, Paul J Van Diest.
Histopathology, 2011 Apr 12; 61(1). PMID: 21477260
Review of the current state of whole slide imaging in pathology.
Liron Pantanowitz, Paul N Valenstein, +5 authors, Terence J Colgan.
J Pathol Inform, 2011 Sep 03; 2. PMID: 21886892    Free PMC article.
Highly Cited.
Label-free characterization of cancer-activated fibroblasts using infrared spectroscopic imaging.
S E Holton, M J Walsh, A Kajdacsy-Balla, R Bhargava.
Biophys J, 2011 Sep 29; 101(6). PMID: 21943433    Free PMC article.
Systematic analysis of breast cancer morphology uncovers stromal features associated with survival.
Andrew H Beck, Ankur R Sangoi, +6 authors, Daphne Koller.
Sci Transl Med, 2011 Nov 11; 3(108). PMID: 22072638
Highly Cited.
Optimally designed narrowband guided-mode resonance reflectance filters for mid-infrared spectroscopy.
Jui-Nung Liu, Matthew V Schulmerich, Rohit Bhargava, Brian T Cunningham.
Opt Express, 2011 Nov 24; 19(24). PMID: 22109445    Free PMC article.
Analysis of variance in spectroscopic imaging data from human tissues.
Jin Tae Kwak, Rohith Reddy, Saurabh Sinha, Rohit Bhargava.
Anal Chem, 2011 Dec 14; 84(2). PMID: 22148458    Free PMC article.
Supervised regularized canonical correlation analysis: integrating histologic and proteomic measurements for predicting biochemical recurrence following prostate surgery.
Abhishek Golugula, George Lee, +4 authors, Anant Madabhushi.
BMC Bioinformatics, 2011 Dec 21; 12. PMID: 22182303    Free PMC article.
Detection of prostate cancer on histopathology using color fractals and Probabilistic Pairwise Markov models.
Elaine Yu, James P Monaco, +3 authors, Anant Madabhushi.
Annu Int Conf IEEE Eng Med Biol Soc, 2012 Jan 19; 2011. PMID: 22255076
Consensus embedding: theory, algorithms and application to segmentation and classification of biomedical data.
Satish Viswanath, Anant Madabhushi.
BMC Bioinformatics, 2012 Feb 10; 13. PMID: 22316103    Free PMC article.
An integrated region-, boundary-, shape-based active contour for multiple object overlap resolution in histological imagery.
Sahirzeeshan Ali, Anant Madabhushi.
IEEE Trans Med Imaging, 2012 Apr 14; 31(7). PMID: 22498689
Graphical processing unit implementation of an integrated shape-based active contour: Application to digital pathology.
Sahirzeeshan Ali, Anant Madabhushi.
J Pathol Inform, 2011 Jan 01; 2. PMID: 22811957    Free PMC article.
Infrared spectroscopic imaging: the next generation.
Rohit Bhargava.
Appl Spectrosc, 2012 Oct 04; 66(10). PMID: 23031693    Free PMC article.
Cascaded discrimination of normal, abnormal, and confounder classes in histopathology: Gleason grading of prostate cancer.
Scott Doyle, Michael D Feldman, +2 authors, Anant Madabhushi.
BMC Bioinformatics, 2012 Nov 01; 13. PMID: 23110677    Free PMC article.
Discrete frequency infrared microspectroscopy and imaging with a tunable quantum cascade laser.
Matthew R Kole, Rohith K Reddy, +2 authors, Rohit Bhargava.
Anal Chem, 2012 Nov 02; 84(23). PMID: 23113653    Free PMC article.
FTIR microspectroscopy of selected rare diverse sub-variants of carcinoma of the urinary bladder.
Caryn Hughes, Junaid Iqbal-Wahid, +7 authors, Peter Gardner.
J Biophotonics, 2012 Nov 06; 6(1). PMID: 23125109
Digital imaging in pathology: whole-slide imaging and beyond.
Farzad Ghaznavi, Andrew Evans, Anant Madabhushi, Michael Feldman.
Annu Rev Pathol, 2012 Nov 20; 8. PMID: 23157334
Invariant delineation of nuclear architecture in glioblastoma multiforme for clinical and molecular association.
Hang Chang, Ju Han, +4 authors, Bahram Parvin.
IEEE Trans Med Imaging, 2012 Dec 12; 32(4). PMID: 23221815    Free PMC article.
Immunohistochemistry, histopathology and infrared spectral histopathology of colon cancer tissue sections.
Angela Kallenbach-Thieltges, Frederik Großerüschkamp, +3 authors, Klaus Gerwert.
J Biophotonics, 2012 Dec 12; 6(1). PMID: 23225612
Image segmentation with implicit color standardization using spatially constrained expectation maximization: detection of nuclei.
James Monaco, J Hipp, +3 authors, Anant Madabhushi.
Med Image Comput Comput Assist Interv, 2013 Jan 05; 15(Pt 1). PMID: 23285572
Multi-kernel graph embedding for detection, Gleason grading of prostate cancer via MRI/MRS.
Pallavi Tiwari, John Kurhanewicz, Anant Madabhushi.
Med Image Anal, 2013 Jan 09; 17(2). PMID: 23294985    Free PMC article.
Infrared imaging as a cancer diagnostic tool: introducing a new concept of spectral barcodes for identifying molecular changes in colon tumors.
Jayakrupakar Nallala, Olivier Piot, +4 authors, Ganesh D Sockalingum.
Cytometry A, 2013 Jan 11; 83(3). PMID: 23303722
High-definition infrared spectroscopic imaging.
Rohith K Reddy, Michael J Walsh, +2 authors, Rohit Bhargava.
Appl Spectrosc, 2013 Jan 16; 67(1). PMID: 23317676    Free PMC article.
Multi-field-of-view framework for distinguishing tumor grade in ER+ breast cancer from entire histopathology slides.
Ajay Basavanhally, Shridar Ganesan, +4 authors, Anant Madabhushi.
IEEE Trans Biomed Eng, 2013 Feb 09; 60(8). PMID: 23392336    Free PMC article.
Histological grading of prostatic carcinoma in prostatectomy specimens. Comparison of prognostic accuracy of five grading systems.
M P Gallee, F J Ten Kate, +2 authors, R O van der Heul.
Br J Urol, 1990 Apr 01; 65(4). PMID: 2340371
Digital pathology: Attitudes and practices in the Canadian pathology community.
Magdaleni Bellis, Shereen Metias, +3 authors, George M Yousef.
J Pathol Inform, 2013 Apr 20; 4. PMID: 23599903    Free PMC article.
Validating whole slide imaging for diagnostic purposes in pathology: guideline from the College of American Pathologists Pathology and Laboratory Quality Center.
Liron Pantanowitz, John H Sinard, +8 authors, College of American Pathologists Pathology and Laboratory Quality Center.
Arch Pathol Lab Med, 2013 May 03; 137(12). PMID: 23634907    Free PMC article.
Highly Cited. Review.
Recovery of absorption spectra from Fourier transform infrared (FT-IR) microspectroscopic measurements of intact spheres.
Thomas van Dijk, David Mayerich, P Scott Carney, Rohit Bhargava.
Appl Spectrosc, 2013 May 07; 67(5). PMID: 23643044
Nanoscale infrared (IR) spectroscopy and imaging of structural lipids in human stratum corneum using an atomic force microscope to directly detect absorbed light from a tunable IR laser source.
Curtis Marcott, Michael Lo, +3 authors, Gustavo S Luengo.
Exp Dermatol, 2013 May 09; 22(6). PMID: 23651342
Real-time interactive data mining for chemical imaging information: application to automated histopathology.
David Mayerich, Michael Walsh, Matthew Schulmerich, Rohit Bhargava.
BMC Bioinformatics, 2013 May 09; 14. PMID: 23651487    Free PMC article.
Change in the microenvironment of breast cancer studied by FTIR imaging.
S Kumar, C Desmedt, +2 authors, E Goormaghtigh.
Analyst, 2013 May 11; 138(14). PMID: 23662300
Rapid spectral-domain localization.
Thomas van Dijk, David Mayerich, Rohit Bhargava, P Scott Carney.
Opt Express, 2013 Jun 06; 21(10). PMID: 23736501    Free PMC article.
Explicit shape descriptors: novel morphologic features for histopathology classification.
Rachel Sparks, Anant Madabhushi.
Med Image Anal, 2013 Jul 16; 17(8). PMID: 23850744    Free PMC article.
Statistical Shape Model for Manifold Regularization: Gleason grading of prostate histology.
Rachel Sparks, Anant Madabhushi.
Comput Vis Image Underst, 2013 Jul 28; 117(9). PMID: 23888106    Free PMC article.
Whole-slide imaging and automated image analysis: considerations and opportunities in the practice of pathology.
J D Webster, R W Dunstan.
Vet Pathol, 2013 Oct 05; 51(1). PMID: 24091812
Optical spectroscopic methods for intraoperative diagnosis.
Gerald Steiner, Matthias Kirsch.
Anal Bioanal Chem, 2013 Oct 19; 406(1). PMID: 24136252
A quantitative histomorphometric classifier (QuHbIC) identifies aggressive versus indolent p16-positive oropharyngeal squamous cell carcinoma.
James S Lewis, Sahirzeeshan Ali, +2 authors, Anant Madabhushi.
Am J Surg Pathol, 2013 Oct 23; 38(1). PMID: 24145650    Free PMC article.
Molecular pathology via IR and Raman spectral imaging.
Max Diem, Antonella Mazur, +5 authors, Jürgen Popp.
J Biophotonics, 2013 Dec 07; 6(11-12). PMID: 24311233
Spatially aware cell cluster(spACC1) graphs: predicting outcome in oropharyngeal pl6+ tumors.
Sahirzeeshan Ali, James Lewis, Anant Madabhushi.
Med Image Comput Comput Assist Interv, 2014 Feb 08; 16(Pt 1). PMID: 24505693
Cell orientation entropy (COrE): predicting biochemical recurrence from prostate cancer tissue microarrays.
George Lee, Sahirzeeshan Ali, +3 authors, Anant Madabhushi.
Med Image Comput Comput Assist Interv, 2014 Feb 08; 16(Pt 3). PMID: 24505786
Mitosis detection in breast cancer histology images with deep neural networks.
Dan C Cireşan, Alessandro Giusti, Luca M Gambardella, Jürgen Schmidhuber.
Med Image Comput Comput Assist Interv, 2014 Mar 01; 16(Pt 2). PMID: 24579167
Highly Cited.
Multiplexed ion beam imaging of human breast tumors.
Michael Angelo, Sean C Bendall, +9 authors, Garry P Nolan.
Nat Med, 2014 Mar 04; 20(4). PMID: 24584119    Free PMC article.
Highly Cited.
An image processing pipeline to detect and segment nuclei in muscle fiber microscopic images.
Yanen Guo, Xiaoyin Xu, +3 authors, Zhong Yang.
Microsc Res Tech, 2014 Apr 30; 77(8). PMID: 24777764
Methods for nuclei detection, segmentation, and classification in digital histopathology: a review-current status and future potential.
Humayun Irshad, Antoine Veillard, Ludovic Roux, Daniel Racoceanu.
IEEE Rev Biomed Eng, 2014 May 08; 7. PMID: 24802905
Highly Cited. Review.
Integration of molecular profiling and chemical imaging to elucidate fibroblast-microenvironment impact on cancer cell phenotype and endocrine resistance in breast cancer.
Sarah E Holton, Anna Bergamaschi, Benita S Katzenellenbogen, Rohit Bhargava.
PLoS One, 2014 May 13; 9(5). PMID: 24816718    Free PMC article.
Co-occurring gland angularity in localized subgraphs: predicting biochemical recurrence in intermediate-risk prostate cancer patients.
George Lee, Rachel Sparks, +6 authors, Anant Madabhushi.
PLoS One, 2014 May 31; 9(5). PMID: 24875018    Free PMC article.
Large scale infrared imaging of tissue micro arrays (TMAs) using a tunable Quantum Cascade Laser (QCL) based microscope.
Paul Bassan, Miles J Weida, Jeremy Rowlette, Peter Gardner.
Analyst, 2014 Jun 27; 139(16). PMID: 24965124
Quantum cascade laser-based hyperspectral imaging of biological tissue.
Niels Kröger, Alexander Egl, +9 authors, Wolfgang Petrich.
J Biomed Opt, 2014 Jun 27; 19(11). PMID: 24967840
Using Fourier transform IR spectroscopy to analyze biological materials.
Matthew J Baker, Júlio Trevisan, +18 authors, Francis L Martin.
Nat Protoc, 2014 Jul 06; 9(8). PMID: 24992094    Free PMC article.
Highly Cited.
Supervised multi-view canonical correlation analysis (sMVCCA): integrating histologic and proteomic features for predicting recurrent prostate cancer.
George Lee, Asha Singanamalli, +7 authors, Anant Madabhushi.
IEEE Trans Med Imaging, 2014 Sep 10; 34(1). PMID: 25203987
Multiplexed immunohistochemistry, imaging, and quantitation: a review, with an assessment of Tyramide signal amplification, multispectral imaging and multiplex analysis.
Edward C Stack, Chichung Wang, Kristin A Roman, Clifford C Hoyt.
Methods, 2014 Sep 23; 70(1). PMID: 25242720
Highly Cited. Review.
Students' performance during practical examination on whole slide images using view path tracking.
Slawomir Walkowski, Mikael Lundin, Janusz Szymas, Johan Lundin.
Diagn Pathol, 2014 Nov 02; 9. PMID: 25358824    Free PMC article.
Nuclear fractal dimension in oral squamous cell carcinoma: a novel method for the evaluation of grading, staging, and survival.
Gabriella Mincione, Marta Di Nicola, +8 authors, Luciano Artese.
J Oral Pathol Med, 2014 Nov 05; 44(9). PMID: 25367085
American Telemedicine Association clinical guidelines for telepathology.
Liron Pantanowitz, Kim Dickinson, +12 authors, Jordana Bernard.
J Pathol Inform, 2014 Nov 08; 5(1). PMID: 25379345    Free PMC article.
A FTIR imaging characterization of fibroblasts stimulated by various breast cancer cell lines.
Saroj Kumar, Thankaraj Salammal Shabi, Erik Goormaghtigh.
PLoS One, 2014 Nov 13; 9(11). PMID: 25390361    Free PMC article.
Interinstitutional whole slide imaging teleconsultation service development: assessment using internal training and clinical consultation cases.
Nicholas C Jones, Rosalynn M Nazarian, +10 authors, David C Wilbur.
Arch Pathol Lab Med, 2014 Nov 22; 139(5). PMID: 25415180
Selective invocation of shape priors for deformable segmentation and morphologic classification of prostate cancer tissue microarrays.
Sahirzeeshan Ali, Robert Veltri, +2 authors, Anant Madabhushi.
Comput Med Imaging Graph, 2014 Dec 04; 41. PMID: 25466771    Free PMC article.
Fast infrared chemical imaging with a quantum cascade laser.
Kevin Yeh, Seth Kenkel, Jui-Nung Liu, Rohit Bhargava.
Anal Chem, 2014 Dec 05; 87(1). PMID: 25474546    Free PMC article.
Marker-free automated histopathological annotation of lung tumour subtypes by FTIR imaging.
Frederik Großerueschkamp, Angela Kallenbach-Thieltges, +5 authors, Klaus Gerwert.
Analyst, 2014 Dec 23; 140(7). PMID: 25529256
Assessment of algorithms for mitosis detection in breast cancer histopathology images.
Mitko Veta, Paul J van Diest, +26 authors, Josien P W Pluim.
Med Image Anal, 2014 Dec 31; 20(1). PMID: 25547073
Infrared imaging of primary melanomas reveals hints of regional and distant metastases.
N Wald, E Goormaghtigh.
Analyst, 2015 Jan 13; 140(7). PMID: 25574519
High-definition Fourier Transform Infrared (FT-IR) spectroscopic imaging of human tissue sections towards improving pathology.
Hari Sreedhar, Vishal K Varma, +6 authors, Michael J Walsh.
J Vis Exp, 2015 Feb 05; (95). PMID: 25650759    Free PMC article.
A method for the comparison of multi-platform spectral histopathology (SHP) data sets.
Ayşegül Ergin, Frederik Großerüschkamp, +4 authors, Max Diem.
Analyst, 2015 Feb 11; 140(7). PMID: 25664352
Improving prediction of prostate cancer recurrence using chemical imaging.
Jin Tae Kwak, André Kajdacsy-Balla, +3 authors, Rohit Bhargava.
Sci Rep, 2015 Mar 05; 5. PMID: 25737022    Free PMC article.
Imaging file management to support international telepathology.
Liron Pantanowitz, Jeffrey McHugh, +2 authors, Anil V Parwani.
J Pathol Inform, 2015 Apr 04; 6. PMID: 25838969    Free PMC article.
Whole slide imaging: uses and limitations for surgical pathology and teaching.
B F Boyce.
Biotech Histochem, 2015 Apr 23; 90(5). PMID: 25901738
Infrared Imaging and Spectroscopy Beyond the Diffraction Limit.
Andrea Centrone.
Annu Rev Anal Chem (Palo Alto Calif), 2015 May 24; 8. PMID: 26001952
Spatial genomic heterogeneity within localized, multifocal prostate cancer.
Paul C Boutros, Michael Fraser, +62 authors, Robert G Bristow.
Nat Genet, 2015 May 26; 47(7). PMID: 26005866
Highly Cited.
Classification of malignant and benign tumors of the lung by infrared spectral histopathology (SHP).
Ali Akalin, Xinying Mu, +5 authors, Max Diem.
Lab Invest, 2015 May 28; 95(6). PMID: 26012705
New breast cancer prognostic factors identified by computer-aided image analysis of HE stained histopathology images.
Jia-Mei Chen, Ai-Ping Qu, +7 authors, Yan Li.
Sci Rep, 2015 May 30; 5. PMID: 26022540    Free PMC article.
Extracting knowledge from chemical imaging data using computational algorithms for digital cancer diagnosis.
Saumya Tiwari, Rohit Bhargava.
Yale J Biol Med, 2015 Jun 02; 88(2). PMID: 26029012    Free PMC article.
Stain-less staining for computed histopathology.
David Mayerich, Michael J Walsh, +3 authors, Rohit Bhargava.
Technology (Singap World Sci), 2015 Jun 02; 3(1). PMID: 26029735    Free PMC article.
High definition infrared spectroscopic imaging for lymph node histopathology.
L Suzanne Leslie, Tomasz P Wrobel, +3 authors, Rohit Bhargava.
PLoS One, 2015 Jun 04; 10(6). PMID: 26039216    Free PMC article.
Overview of Telepathology.
Navid Farahani, Liron Pantanowitz.
Surg Pathol Clin, 2015 Jun 13; 8(2). PMID: 26065796
Mobile Technologies for the Surgical Pathologist.
Douglas J Hartman.
Surg Pathol Clin, 2015 Jun 13; 8(2). PMID: 26065797
Cytopathology whole slide images and adaptive tutorials for postgraduate pathology trainees: a randomized crossover trial.
Simone L Van Es, Rakesh K Kumar, +2 authors, Gary M Velan.
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
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.
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.
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.
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.
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.
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.
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.
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.