Whole-slide imaging in cytopathology: state of the art and future directions

Abstract Whole slide imaging (WSI) has been increasingly adopted for digital evaluation of surgical pathology specimens. Unlike histological slides, cytological preparations frequently display a heterogeneous distribution of cells throughout slides in different focal planes sometimes admixed with obscuring material, therefore requiring multiple scanning planes which significantly lengthens image acquisition and evaluation times. Although examination of digital images can be more advantageous than conventional glass slides, the challenges of focusing, scanning and screening cytological specimens and the associated increase in scan times and data storage needs have limited the routine application of WSI in cytopathology practice. Emerging digital systems designed to overcome image acquisition obstacles coupled with artificial intelligence algorithms augmenting screening of digital cytology slides offer innovative solutions to address these limitations. The aim of this review is to critically address the potential benefits and pitfalls of employing WSI in cytopathology practice and to introduce promising state-of-the-art solutions on the horizon.

[1]  M. Chilosi,et al.  Digital reporting of whole-slide images is safe and suitable for assessing organ quality in preimplantation renal biopsies. , 2016, Human pathology.

[2]  Roy A. Ruddle,et al.  The Design and Evaluation of Interfaces for Navigating Gigapixel Images in Digital Pathology , 2016, ACM Trans. Comput. Hum. Interact..

[3]  S. Saikali,et al.  A Comparison of Digitized Frozen Section and Smear Preparations for Intraoperative Neurotelepathology , 2012, Analytical cellular pathology.

[4]  Rebecca Randell,et al.  The Diagnostic Concordance of Whole Slide Imaging and Light Microscopy: A Systematic Review. , 2017, Archives of pathology & laboratory medicine.

[5]  T. Legesse,et al.  Digital image‐assisted quantitative nuclear analysis improves diagnostic accuracy of thyroid fine‐needle aspiration cytology , 2019, Cancer cytopathology.

[6]  Johannes Bernarding,et al.  Virtual 3D microscopy using multiplane whole slide images in diagnostic pathology. , 2008, American journal of clinical pathology.

[7]  Boris Lesner,et al.  Adaptation of CytoProcessor for cervical cancer screening of challenging slides , 2019, Diagnostic cytopathology.

[8]  P. V. van Diest,et al.  Working toward consensus among professionals in the identification of classical cervical cytomorphological characteristics in whole slide images , 2015, Journal of pathology informatics.

[9]  Maheswari S. Mukherjee,et al.  Optimal z-axis scanning parameters for gynecologic cytology specimens , 2013, Journal of pathology informatics.

[10]  Liron Pantanowitz,et al.  Validation of Remote Digital Frozen Sections for Cancer and Transplant Intraoperative Services , 2018, Journal of pathology informatics.

[11]  L. Pantanowitz,et al.  The utility of cell blocks for international cytopathology teleconsultation by whole slide imaging , 2020, Cytopathology : official journal of the British Society for Clinical Cytology.

[12]  Liron Pantanowitz,et al.  The impact of digital imaging in the field of cytopathology , 2009, CytoJournal.

[13]  N. Dudding,et al.  Accuracy and perceptions of virtual microscopy compared with glass slide microscopy in cervical cytology , 2011, Cytopathology : official journal of the British Society for Clinical Cytology.

[14]  High throughput slanted scanning whole slide imaging system for digital pathology , 2021, Journal of biophotonics.

[15]  B. Shulruf,et al.  Digital vs traditional: Are diagnostic accuracy rates similar for glass slides vs whole slide images in a non‐gynaecological external quality assurance setting? , 2018, Cytopathology : official journal of the British Society for Clinical Cytology.

[16]  Liron Pantanowitz,et al.  Artificial intelligence in cytopathology: a review of the literature and overview of commercial landscape. , 2019, Journal of the American Society of Cytopathology.

[17]  C. VandenBussche,et al.  Morphologists overestimate the nuclear‐to‐cytoplasmic ratio , 2016, Cancer cytopathology.

[18]  Darren Treanor,et al.  Display evaluation for primary diagnosis using digital pathology , 2020, Journal of medical imaging.

[19]  Marius Nap,et al.  Conventional Microscopical versus Digital Whole-Slide Imaging-Based Diagnosis of Thin-Layer Cervical Specimens: A Validation Study , 2018, Journal of pathology informatics.

[20]  Anil Vasdev Parwani,et al.  Digital imaging in pathology. , 2012, Clinics in laboratory medicine.

[21]  In Sun Kim,et al.  Accuracy and reproducibility of telecytology diagnosis of cervical smears. A tool for quality assurance programs. , 2003, American journal of clinical pathology.

[22]  Shellaine R. Frazier,et al.  Accuracy and Reproducibility of Nuclear/Cytoplasmic Ratio Assessments in Urinary Cytology Specimens , 2017, Diagnostic cytopathology.

[23]  L. Pantanowitz,et al.  Performance of an artificial intelligence algorithm for reporting urine cytopathology , 2019, Cancer cytopathology.

[24]  M. Quek,et al.  The Paris System for Reporting Urinary Cytology: The Quest to Develop a Standardized Terminology. , 2016, Advances in anatomic pathology.

[25]  F. Schmitt,et al.  Thyroid fine‐needle aspiration cytology: Is there a place to virtual cytology? , 2013, Diagnostic cytopathology.

[26]  T. Ozaki,et al.  Study of parameters in focus simulation functions of virtual slide , 2011, Diagnostic pathology.

[27]  N. Linder,et al.  Point-of-Care Digital Cytology With Artificial Intelligence for Cervical Cancer Screening in a Resource-Limited Setting , 2021, JAMA network open.

[28]  M. Siddiqui,et al.  Digital image analysis supports a nuclear‐to‐cytoplasmic ratio cutoff value below 0.7 for positive for high‐grade urothelial carcinoma and suspicious for high‐grade urothelial carcinoma in urine cytology specimens , 2018, Cancer cytopathology.

[29]  Ioan C. Cucoranu,et al.  Screening and dotting virtual slides: A new challenge for cytotechnologists , 2013, CytoJournal.

[30]  Jimmie Stewart,et al.  Virtual microscopy for cytology proficiency testing: Are we there yet? , 2007, Cancer.

[31]  Maheswari S Mukherjee,et al.  Utilization of virtual microscopy in cytotechnology educational programs in the United States , 2016, Journal of pathology informatics.

[32]  B. Collins,et al.  Assessment of malignancy for atypia of undetermined significance in thyroid fine-needle aspiration biopsy evaluated by whole-slide image analysis. , 2013, American journal of clinical pathology.

[33]  Philippe Delvenne,et al.  Evaluation of CellSolutions BestPrep® Automated Thin-Layer Liquid-Based Cytology Papanicolaou Slide Preparation and BestCyte® Cell Sorter Imaging System , 2014, Acta Cytologica.

[34]  Yukako Yagi,et al.  An ultra-high speed Whole Slide Image viewing system. , 2012, Studies in health technology and informatics.

[35]  C. VandenBussche,et al.  Digital image analysis supports a nuclear‐to‐cytoplasmic ratio cutoff value of 0.5 for atypical urothelial cells , 2017, Cancer cytopathology.

[36]  L. Pantanowitz,et al.  Impact of image analysis and artificial intelligence in thyroid pathology, with particular reference to cytological aspects , 2020, Cytopathology : official journal of the British Society for Clinical Cytology.

[37]  L. Pantanowitz,et al.  Diagnostic concordance between whole slide imaging and conventional light microscopy in cytopathology: A systematic review , 2020, Cancer cytopathology.

[38]  Maheswari S. Mukherjee,et al.  Investigation of scanning parameters for thyroid fine needle aspiration cytology specimens: A pilot study , 2015, Journal of pathology informatics.

[39]  Nektarios A. Valous,et al.  Semantic Focusing Allows Fully Automated Single-Layer Slide Scanning of Cervical Cytology Slides , 2013, PloS one.

[40]  Lawrence Carin,et al.  Weakly supervised instance learning for thyroid malignancy prediction from whole slide cytopathology images , 2019, Medical Image Anal..

[41]  D. Treanor,et al.  Digital cytology: A short review of technical and methodological approaches and applications , 2018, Cytopathology : official journal of the British Society for Clinical Cytology.

[42]  L. Pantanowitz,et al.  Experience Reviewing Digital Pap Tests using a Gallery of Images , 2021, Journal of pathology informatics.

[43]  Navid Farahani,et al.  A Practical Guide to Whole Slide Imaging: A White Paper From the Digital Pathology Association. , 2018, Archives of pathology & laboratory medicine.

[44]  Subhendu Chakraborty,et al.  Digital slide imaging in cervicovaginal cytology: a pilot study. , 2013, Archives of pathology & laboratory medicine.

[45]  A. Bradley,et al.  A method for quantitative analysis of clump thickness in cervical cytology slides. , 2016, Micron.

[46]  Christopher R Pierson,et al.  The College of American Pathologists Guidelines for Whole Slide Imaging Validation are Feasible for Pediatric Pathology: A Pediatric Pathology Practice Experience , 2015, Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society.

[47]  L. Pantanowitz,et al.  Panoramic Digital Images (Panoptiq) for Cytopathology Screening and Interpretation , 2015 .

[48]  Claudia Mello-Thoms,et al.  Virtual reality microscope versus conventional microscope regarding time to diagnosis: an experimental study , 2013, Histopathology.

[49]  Liron Pantanowitz,et al.  Artificial Intelligence and Digital Pathology: Challenges and Opportunities , 2018, Journal of pathology informatics.