The objective is to find a practical balance between quality and performance for daily high volume whole slide imaging. We evaluated whole slide images created by various scanners at different compression factors to determine the best suitable quality factor (QF) needed for pathological images of special stains.Method: We scanned two sets of eight special stains slides each at 0.50 &#x3bc;m/pixel resolution in Hamamatsu scanner at six and five QF levels respectively to generate 72 images which were observed at a calibrated monitor by imaging specialists, a histo-technician, and a pathologist to find the most suitable QF level for special stains in digital slides.Results: Most special stains images were acceptable at QF 30 except for the stain Reticulin where the lowest acceptable QF was 50. The compression of images from QF 90 to QF 50 reduced the size of the images by 62.73&#x25;.Conclusion: 0.50 &#x3bc;m/pixel images at QF 50 or above were found suitable 12 special stain.

Anurag Sharma

Pinky Bautista

Yukako Yagi

Balancing Image Quality and Compression Factor for Special Stains Whole Slide Images

Despite the prognostic importance of mitotic count as one of the components of the Bloom &#x2013; Richardson grade &#x5B;3&#x5D;, several studies (&#x5B;2, 9, 10&#x5D;) have found that pathologists&#x2019; agreement on the mitotic grade is fairly modest. Collecting a set of more than 4,200 candidate mitotic figures, we evaluate pathologists' agreement on individual figures, and train a computerized system for mitosis detection, comparing its performance to the classifications of three pathologists. The system&#x2019;s and the pathologists&#x2019; classifications are based on evaluation of digital micrographs of hematoxylin and eosin stained breast tissue. On figures where the majority of pathologists agree on a classification, we compare the performance of the trained system to that of the individual pathologists. We find that the level of agreement of the pathologists ranges from slight to moderate, with strong biases, and that the system performs competitively in rating the ground truth set. This study is a step towards automatic mitosis count to accelerate a pathologist's work and improve reproducibility.

Christopher Malon

Elena Brachtel

Eric Cosatto

Hans Peter Graf

Atsushi Kurata

Masahiko Kuroda

John S. Meyer

Akira Saito

Shulin Wu

Mitotic Figure Recognition: Agreement among Pathologists and Computerized Detector

Background: Telepathology, the practice of pathology at a long distance, has advanced continuously since 1986. The progress of telepathology passed through four stages: Static, Dynamic, Hybrid &#x26; Whole Slide Imaging.Materials and Methods: A pilot project between the Italian Hospital in Cairo &#x26; the Civico Hospital in Palermo was completed successfully, applying the static &#x26; dynamic techniques of telepathology. This project began in 2003 and continued till now. In 2004, centers in Venice, London and Pittsburgh participated actively in our project.Results: Over eight years we consulted on many problematic pathological cases with specialized pathological centers in Italy, UK &#x26; USA. In addition to the highly specialized scientific value, we saved a lot of time and money.Conclusion: We concluded from our experience that telepathology is a very useful and applicable tool for additional consulting on difficult pathological cases especially for emerging countries. In view of this success we have already established our Digital Telepathology Unit in Cairo University, using the WSI technique in teaching which was greatly successful and encouraged us to build a huge digital pathology library which will expand our telepathology &#x26; E-learning programs to cover staff and students in Egypt and Eastern Mediterranean.

Essam Ayad

Virtual Microscopy Beyond the Pyramids, Applications of WSI in Cairo University for E-Education &#x26; Telepathology

Background: Intraoperative consultations in neuropathology are often assessed by smear preparations rather than by frozen sections. Both techniques are standard practice for light microscopic examination on site, but there is little data comparing these techniques in a telepathology setting.Methods: Thirty cases of brain tumours submitted for intraoperative consultation at our institution between July and December 2010 were identified in which both frozen section and tissue smear preparations were available for digitization at 20&#xd7; magnification. Slides were digitized using a Hamamatsu Nanozoomer 2.0 HT whole slide scanner, and resulting digital images were visualized at 1680 &#xd7; 1050 pixel resolution with NDP. view software.Results: The original intraoperative diagnosis was concordant with the sign out diagnosis in 29/30 cases; one tumeur was initially interpreted as a high grade glioma but proved to be a lymphoma at sign out.Digitized frozen section slides were sufficient for diagnosis at 10&#xd7; magnification in 27/30 cases. Digitized tissue smears were sufficient for diagnosis at 10&#xd7; magnification in 28/30 cases. In two cases tumour was present on the tissue smear but not the frozen section (one case of recurrent astrocytoma, one case of meningeal carcinomatosis). In one case of lymphoma, tumour was present on frozen section only. These discrepancies were attributed to tissue sampling rather than image quality.Examination of digitized slides at higher magnfication (20&#xd7;) permitted confirmation of mitoses and Rosenthal fibers on tissue smear preparations, but did not change the primary diagnosis. Intra-slide variations in tissue thickness on smear preparations led to variable loss of focus in digitized images, but did not affect image quality in thinner areas of the smear or impede diagnosis.Conclusion: Digitized tissue smears are suitable for intraoperative neurotelepathology and provide comparable information to digitized frozen sections at medium power magnification.

Peter V. Gould

Stephan Saikali

A Comparison of Digitized Frozen Section and Smear Preparations for Intraoperative Neurotelepathology

Background: Three-dimensional (3D)-reconstruction from paraffin embedded sections has been considered laborious and time-consuming. However, the high-resolution images of large object areas and different fields of view obtained by 3D-reconstruction make one wonder whether it can add a new insight into lung adenocarcinoma, the most frequent histology type of lung cancer characterized by its morphological heterogeneity.Objective: In this work, we tested whether an automated tissue sectioning machine and slide scanning system could generate precise 3D-reconstruction of microanatomy of the lung and help us better understand and define histologic subtypes of lung adenocarcinoma.Methods: Four formalin-fixed human lung adenocarcinoma resections were studied. Paraffin embedded tissues were sectioned with Kurabo-Automated tissue sectioning machine and serial sections were automatically stained and scanned with a Whole Slide Imaging system. The resulting stacks of images were 3D reconstructed by Pannoramic Viewer software.Results: Two of the four specimens contained islands of tumor cells detached in alveolar spaces that had not been described in any of the existing adenocarcinoma classifications. 3D-reconstruction revealed the details of spatial distribution and structural interaction of the tumor that could hardly be observed by 2D light microscopy studies. The islands of tumor cells extended into a deeper aspect of the tissue, and were interconnected with each other and with the main tumor with a solid pattern that was surrounded by the islands. The finding raises the question whether the islands of tumor cells should be classified into a solid pattern in the current classification.Conclusion: The combination of new technologies enabled us to build an effective 3D-reconstruction of resected lung adenocarcinomas. 3D-reconstruction may help us refine the classification of lung adenocarcinoma by adding detailed spatial/structural information to 2D light microscopy evaluation.

Maristela L. Onozato

Veronica E. Klepeis

Mari Mino-Kenudson

A Role of Three-Dimensional (3D)-Reconstruction in the Classification of Lung Adenocarcinoma

Pathology has recently entered the era of personalized medicine. This brings new expectations for the accuracy and precision of tissue-based diagnosis, in particular, when quantification of histologic features and biomarker expression is required. While for many years traditional pathologic diagnosis has been regarded as ground truth, this concept is no longer sufficient in contemporary tissue-based biomarker research and clinical use. Another major change in pathology is brought by the advancement of virtual microscopy technology enabling digitization of microscopy slides and presenting new opportunities for digital image analysis. Computerized vision provides an immediate benefit of increased capacity (automation) and precision (reproducibility), but not necessarily the accuracy of the analysis. To achieve the benefit of accuracy, pathologists will have to assume an obligation of validation and quality assurance of the image analysis algorithms. Reference values are needed to measure and control the accuracy. Although pathologists' consensus values are commonly used to validate these tools, we argue that the ground truth can be best achieved by stereology methods, estimating the same variable as an algorithm is intended to do. Proper adoption of the new technology will require a new quantitative mentality in pathology. In order to see a complete and sharp picture of a disease, pathologists will need to learn to use both their analogue and digital eyes.

Arvydas Laurinavicius

Aida Laurinaviciene

Darius Dasevicius

Nicolas Elie

Beno&#xee;t Plancoulaine

Catherine Bor

Paulette Herlin

Digital Image Analysis in Pathology: Benefits and Obligation

Background: One of the goals for a Whole Slide Imaging (WSI) system is implementation in the clinical practice of pathology. One of the unresolved problems in accomplishing this goal is the speed of the entire process, i.e., from viewing the slides through making the final diagnosis. Most users are not satisfied with the correct viewing speeds of available systems. We have evaluated a new WSI viewing station and tool that focuses on speed.Method: A prototype WSI viewer based on PlayStation&#xae;3 with wireless controllers was evaluated at the Department of Pathology at MGH for the following reasons: 1. For the simulation of signing-out cases; 2. Enabling discussion at a consensus conference; and 3. Use at slide seminars during a Continuing Medical Education course.Results: Pathologists were being able to use the system comfortably after 0&#x2013;15 min training. There were no complaints regarding speed. Most pathologists were satisfied with the functionality, usability and speed of the system. The most difficult situation was simulating diagnostic sign-out.Conclusion: The preliminary results of adapting the Sony PlayStation&#xae;3 (PS3&#xae;) as an ultra-high speed WSI viewing system were promising. The achieved speed is consistent with what would be needed to use WSI in daily practice.

Shigeatsu Yoshioka

Hiroshi Kyusojin

Maristela Onozato

Yoichi Mizutani

Kiyoshi Osato

Hiroaki Yada

Eugene J. Mark

Matthew P. Frosch

David N. Louis

An Ultra-High Speed Whole Slide Image Viewing System

Background: Whole slide Imaging (WSI) has been touted by many as the future of pathology, with estimates of full adoption occurring sometime in the next 5 to 15 years. While WSI devices have become increasingly capable since their inception, there has been little consideration of how WSI will be implemented and subsequently affect the workflow of high volume histology laboratories.Methods: Histology workflow process data was collected from a high-volume histology laboratory (Massachusetts General Hospital) and a process model developed using business process management software. Computerized workflow simulations were performed and total histology process time evaluated under a number of different WSI conditions.Results: Total histology process time increased approximately 10-fold to 20-fold over baseline with the presence of one WSI robot in the histology workflow. Depending on the specifications of the WSI robot, anywhere from 9 to 14 WSI robots were required within the histology workflow to minimize the effects of WSI.Conclusion: Placing a WSI robot into the current workflow of a high-volume histology laboratory with the intent of full adoption is not feasible. Implementing WSI without making significant changes to the current workflow of the histology laboratory would prove to be both disruptive and costly to surgical pathology.

David S. McClintock

Roy E. Lee

John R. Gilbertson

Using Computerized Workflow Simulations to Assess the Feasibility of Whole Slide Imaging Full Adoption in a High-Volume Histology Laboratory

Marcial Garcia Rojo

Klaus Kayser

Gian Kayser

Vincenzo Della Mea

Bruce Levy

Jacques Klossa

Gary Tearney

Janus Szymas

Yasunari Tsuchihashi

Bernard T&#xea;tu

The First Congress of the International Academy of Digital Pathology: Digital Pathology Comes of Age

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Analytical Cellular Pathology provides a forum for pathologists and medical practitioners working in the cellular pathology field. Topics covered include cytology, carcinogenesis, cell receptors, biomarkers, diagnostic pathology, and immunopathology.

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Chief Editor&nbsp;Professor Dimitrios Karamichos&nbsp;focuses on investigating corneal wound healing and dystrophies with a particular interest in the effect of transforming growth factor-β3 or TGF- β3 on corneal stromal cells and their extracellular environment.

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title

Analytical Cellular Pathology provides a forum for pathologists and medical practitioners working in the cellular pathology field. Topics covered include cytology, carcinogenesis, cell receptors, biomarkers, diagnostic pathology, and immunopathology.

Analytical Cellular Pathology