Journal of Pathology Informatics Journal of Pathology Informatics
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Original Article: Routine digital pathology workflow: The Catania experience
Filippo Fraggetta, Salvatore Garozzo, Gian Franco Zannoni, Liron Pantanowitz, Esther Diana Rossi
J Pathol Inform 2017, 8:51 (19 December 2017)
Introduction: Successful implementation of whole slide imaging (WSI) for routine clinical practice has been accomplished in only a few pathology laboratories worldwide. We report the transition to an effective and complete digital surgical pathology workflow in the pathology laboratory at Cannizzaro Hospital in Catania, Italy. Methods: All (100%) permanent histopathology glass slides were digitized at ×20 using Aperio AT2 scanners. Compatible stain and scanning slide racks were employed to streamline operations. eSlide Manager software was bidirectionally interfaced with the anatomic pathology laboratory information system. Virtual slide trays connected to the two-dimensional (2D) barcode tracking system allowed pathologists to confirm that they were correctly assigned slides and that all tissues on these glass slides were scanned. Results: Over 115,000 glass slides were digitized with a scan fail rate of around 1%. Drying glass slides before scanning minimized them sticking to scanner racks. Implementation required introduction of a 2D barcode tracking system and modification of histology workflow processes. Conclusion: Our experience indicates that effective adoption of WSI for primary diagnostic use was more dependent on optimizing preimaging variables and integration with the laboratory information system than on information technology infrastructure and ensuring pathologist buy-in. Implementation of digital pathology for routine practice not only leveraged the benefits of digital imaging but also creates an opportunity for establishing standardization of workflow processes in the pathology laboratory.
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Original Article: Preconceived stakeholders' attitude toward telepathology: Implications for successful implementation
Elahe Gozali, Reza Safdari, Malihe Sadeghi, Marjan Ghazi Saeidi, Sharareh R Niakan Kalhori, Farahnaz Noroozinia, Zahra Zare Fazlollahi, Bahlol Rahimi
J Pathol Inform 2017, 8:50 (19 December 2017)
Introduction: Telepathology is a subdiscipline of telemedicine. It has opened new horizons to pathology, especially to the field of organizing consultations. This study aims to determine the capabilities and equipment required for the implementation of telepathology from the viewpoints of managers, IT professionals, and pathologists of the hospitals of West Azerbaijan, Iran. Methods: This is a descriptive-analytical study conducted as a cross-sectional study in 2015. All public and private hospitals of West Azerbaijan were selected as the study sites. The population of the study was the managers, directors, pathologists, and IT professionals of the hospitals. The study population was considered as the study sample. Data were collected using questionnaires. The validity and reliability of the questionnaires were assessed, and data were analyzed using SPSS (Statistical Product and Services Solutions, version 16.0, SPSS Inc, Chicago, IL, USA). Results: The mean awareness of the study population of telepathology in the studied hospitals was 2.43 with a standard deviation of 0.89. According to analysis results (F = 7.211 and P = 0.001), in the studied hospitals, the mean awareness of pathologists, managers, directors, and IT professionals' of telepathology is significant. In addition, the mean awareness of pathologists is higher than that of managers, directors, and IT professionals, and this relation is significant (P = 0.001). According to IT professionals, among the influential dimensions of the implementation of telepathology in the studied hospitals, the effect of all dimensions, except hardware capabilities, was above moderate level. Conclusion: According to our findings, stakeholders believe that the implementation of telepathology promotes the quality of health-care services and caring patients on the one hand and decreases health-care costs on the other hand. Therefore, it crucial and important to consider users' viewpoints into the process of implementing such systems as they play a vital role in the success or failure, and the accurate estimation of required sources, of the systems.
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Commentary: Commentary: Improving the efficiency of the ova and parasite examination using cloud-based image analysis
Daniel D Rhoads
J Pathol Inform 2017, 8:49 (14 December 2017)
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Original Article: Application of text information extraction system for real-time cancer case identification in an integrated healthcare organization
Fagen Xie, Janet Lee, Corrine E Munoz-Plaza, Erin E Hahn, Wansu Chen
J Pathol Inform 2017, 8:48 (14 December 2017)
Background: Surgical pathology reports (SPR) contain rich clinical diagnosis information. The text information extraction system (TIES) is an end-to-end application leveraging natural language processing technologies and focused on the processing of pathology and/or radiology reports. Methods: We deployed the TIES system and integrated SPRs into the TIES system on a daily basis at Kaiser Permanente Southern California. The breast cancer cases diagnosed in December 2013 from the Cancer Registry (CANREG) were used to validate the performance of the TIES system. The National Cancer Institute Metathesaurus (NCIM) concept terms and codes to describe breast cancer were identified through the Unified Medical Language System Terminology Service (UTS) application. The identified NCIM codes were used to search for the coded SPRs in the back-end datastore directly. The identified cases were then compared with the breast cancer patients pulled from CANREG. Results: A total of 437 breast cancer concept terms and 14 combinations of “breast” and “cancer” terms were identified from the UTS application. A total of 249 breast cancer cases diagnosed in December 2013 was pulled from CANREG. Out of these 249 cases, 241 were successfully identified by the TIES system from a total of 457 reports. The TIES system also identified an additional 277 cases that were not part of the validation sample. Out of the 277 cases, 11% were determined as highly likely to be cases after manual examinations, and 86% were in CANREG but were diagnosed in months other than December of 2013. Conclusions: The study demonstrated that the TIES system can effectively identify potential breast cancer cases in our care setting. Identified potential cases can be easily confirmed by reviewing the corresponding annotated reports through the front-end visualization interface. The TIES system is a great tool for identifying potential various cancer cases in a timely manner and on a regular basis in support of clinical research studies.
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Technical Note: Implementation of epic beaker anatomic pathology at an academic medical center
John Larry Blau, Joseph D Wilford, Susan K Dane, Nitin J Karandikar, Emily S Fuller, Debbie J Jacobsmeier, Melissa A Jans, Elisabeth A Horning, Matthew D Krasowski, Bradley A Ford, Kent R Becker, Jeanine M Beranek, Robert A Robinson
J Pathol Inform 2017, 8:47 (14 December 2017)
Background: Beaker is a relatively new laboratory information system (LIS) offered by Epic Systems Corporation as part of its suite of health-care software and bundled with its electronic medical record, EpicCare. It is divided into two modules, Beaker anatomic pathology (Beaker AP) and Beaker Clinical Pathology. In this report, we describe our experience implementing Beaker AP version 2014 at an academic medical center with a go-live date of October 2015. Methods: This report covers preimplementation preparations and challenges beginning in September 2014, issues discovered soon after go-live in October 2015, and some post go-live optimizations using data from meetings, debriefings, and the project closure document. Results: We share specific issues that we encountered during implementation, including difficulties with the proposed frozen section workflow, developing a shared specimen source dictionary, and implementation of the standard Beaker workflow in large institution with trainees. We share specific strategies that we used to overcome these issues for a successful Beaker AP implementation. Several areas of the laboratory-required adaptation of the default Beaker build parameters to meet the needs of the workflow in a busy academic medical center. In a few areas, our laboratory was unable to use the Beaker functionality to support our workflow, and we have continued to use paper or have altered our workflow. In spite of several difficulties that required creative solutions before go-live, the implementation has been successful based on satisfaction surveys completed by pathologists and others who use the software. However, optimization of Beaker workflows has continued to be an ongoing process after go-live to the present time. Conclusions: The Beaker AP LIS can be successfully implemented at an academic medical center but requires significant forethought, creative adaptation, and continued shared management of the ongoing product by institutional and departmental information technology staff as well as laboratory managers to meet the needs of the laboratory.
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Abstracts: The digital pathology association's annual conference october 1-3,manchester grand hyatt,San Diego, CA

J Pathol Inform 2017, 8:46 (28 November 2017)
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Technical Note: Variation in results release and patient portal access to diagnostic test results at an academic medical center
Matthew D Krasowski, Caleb V Grieme, Brian Cassady, Nicholas R Dreyer, Karolyn A Wanat, Maia Hightower, Kenneth G Nepple
J Pathol Inform 2017, 8:45 (23 November 2017)
Background: Electronic health records (EHRs) are commonplace in industrialized countries. Many hospitals are granting their patients access to their medical information through online patient portals. In this report, we describe a retrospective analysis of patient access to diagnostic test results released through the patient portal (MyChart; Epic, Inc.) at a state academic medical center. Methods: We analyzed 6 months of data for anatomic pathology, clinical laboratory, and radiology test results to evaluate variations in results release (automated vs. manual) and subsequent patient access to the institutional patient portal. During this period, diagnostic test results were released for all patient encounters including inpatient units, outpatient clinics, and the emergency department. Results: Manual results release by providers before automated release time occurred most commonly in the outpatient setting. The highest rates of access of diagnostic test results occurred for outpatients (about 30% overall view rate), females (two times or more compared to males in nearly every age bracket), and 20–45-year-old. Access rates of diagnostic tests in the emergency department or inpatient units were <10% across all populations. Access of diagnostic test results was very low for 12–17-year-old, likely influenced by institutional policies limiting parental proxy access within this pediatric age range. Approximately 20% of outpatient laboratory results were viewed by patients within 8 h of release from the EHR to the patient portal and 10% within 2 h of release. Conclusions: Patient accessing of diagnostic test results were generally higher for females, outpatients, and 20–45-year-old. Approximately, 20% of outpatient results were viewed quickly by patients after release to the EHR.
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Original Article: Houston Methodist variant viewer: An application to support clinical laboratory interpretation of next-generation sequencing data for cancer
Paul A Christensen, Yunyun Ni, Feifei Bao, Heather L Hendrickson, Michael Greenwood, Jessica S Thomas, S Wesley Long, Randall J Olsen
J Pathol Inform 2017, 8:44 (23 November 2017)
Introduction: Next-generation-sequencing (NGS) is increasingly used in clinical and research protocols for patients with cancer. NGS assays are routinely used in clinical laboratories to detect mutations bearing on cancer diagnosis, prognosis and personalized therapy. A typical assay may interrogate 50 or more gene targets that encompass many thousands of possible gene variants. Analysis of NGS data in cancer is a labor-intensive process that can become overwhelming to the molecular pathologist or research scientist. Although commercial tools for NGS data analysis and interpretation are available, they are often costly, lack key functionality or cannot be customized by the end user. Methods: To facilitate NGS data analysis in our clinical molecular diagnostics laboratory, we created a custom bioinformatics tool termed Houston Methodist Variant Viewer (HMVV). HMVV is a Java-based solution that integrates sequencing instrument output, bioinformatics analysis, storage resources and end user interface. Results: Compared to the predicate method used in our clinical laboratory, HMVV markedly simplifies the bioinformatics workflow for the molecular technologist and facilitates the variant review by the molecular pathologist. Importantly, HMVV reduces time spent researching the biological significance of the variants detected, standardizes the online resources used to perform the variant investigation and assists generation of the annotated report for the electronic medical record. HMVV also maintains a searchable variant database, including the variant annotations generated by the pathologist, which is useful for downstream quality improvement and research projects. Conclusions: HMVV is a clinical grade, low-cost, feature-rich, highly customizable platform that we have made available for continued development by the pathology informatics community.
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Original Article: Next generation quality: Assessing the physician in clinical history completeness and diagnostic interpretations using funnel plots and normalized deviations plots in 3,854 prostate biopsies
Michael Bonert, Ihab El-Shinnawy, Michael Carvalho, Phillip Williams, Samih Salama, Damu Tang, Anil Kapoor
J Pathol Inform 2017, 8:43 (23 November 2017)
Background: Observational data and funnel plots are routinely used outside of pathology to understand trends and improve performance. Objective: Extract diagnostic rate (DR) information from free text surgical pathology reports with synoptic elements and assess whether inter-rater variation and clinical history completeness information useful for continuous quality improvement (CQI) can be obtained. Methods: All in-house prostate biopsies in a 6-year period at two large teaching hospitals were extracted and then diagnostically categorized using string matching, fuzzy string matching, and hierarchical pruning. DRs were then stratified by the submitting physicians and pathologists. Funnel plots were created to assess for diagnostic bias. Results: 3,854 prostate biopsies were found and all could be diagnostically classified. Two audits involving the review of 700 reports and a comparison of the synoptic elements with the free text interpretations suggest a categorization error rate of <1%. Twenty-seven pathologists each read >40 cases and together assessed 3,690 biopsies. There was considerable inter-rater variability and a trend toward more World Health Organization/International Society of Urologic Pathology Grade 1 cancers in older pathologists. Normalized deviations plots, constructed using the median DR, and standard error can elucidate associated over- and under-calls for an individual pathologist in relation to their practice group. Clinical history completeness by submitting medical doctor varied significantly (100% to 22%). Conclusion: Free text data analyses have some limitations; however, they could be used for data-driven CQI in anatomical pathology, and could lead to the next generation in quality of care.
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Technical Note: Preferred names, preferred pronouns, and gender identity in the electronic medical record and laboratory information system: Is pathology ready?
Katherine L Imborek, Nicole L Nisly, Michael J Hesseltine, Jana Grienke, Todd A Zikmund, Nicholas R Dreyer, John L Blau, Maia Hightower, Robert M Humble, Matthew D Krasowski
J Pathol Inform 2017, 8:42 (3 October 2017)
Background: Electronic medical records (EMRs) and laboratory information systems (LISs) commonly utilize patient identifiers such as legal name, sex, medical record number, and date of birth. There have been recommendations from some EMR working groups (e.g., the World Professional Association for Transgender Health) to include preferred name, pronoun preference, assigned sex at birth, and gender identity in the EMR. These practices are currently uncommon in the United States. There has been little published on the potential impact of these changes on pathology and LISs. Methods: We review the available literature and guidelines on the use of preferred name and gender identity on pathology, including data on changes in laboratory testing following gender transition treatments. We also describe pathology and clinical laboratory challenges in the implementation of preferred name at our institution. Results: Preferred name, pronoun preference, and gender identity have the most immediate impact on the areas of pathology with direct patient contact such as phlebotomy and transfusion medicine, both in terms of interaction with patients and policies for patient identification. Gender identity affects the regulation and policies within transfusion medicine including blood donor risk assessment and eligibility. There are limited studies on the impact of gender transition treatments on laboratory tests, but multiple studies have demonstrated complex changes in chemistry and hematology tests. A broader challenge is that, even as EMRs add functionality, pathology computer systems (e.g., LIS, middleware, reference laboratory, and outreach interfaces) may not have functionality to store or display preferred name and gender identity. Conclusions: Implementation of preferred name, pronoun preference, and gender identity presents multiple challenges and opportunities for pathology.
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Original Article: Hepatitis C virus Genie: A web 2.0 interpretation and analytics platform for the Versant Hepatitis C virus genotype Line Probe Assay version 2.0
Alex M Dussaq, Abha Soni, Christopher Willey, Seung L Park, Shuko Harada
J Pathol Inform 2017, 8:41 (3 October 2017)
Context: Hepatitis C virus (HCV) genotyping at our institution is performed using the Versant HCV genotype 2.0 Line Probe Assay (LiPA). The last steps of this procedure are manual, laborious, and error-prone process that involves the comparison of the banding pattern on a test strip to a physical reference table. Aim: We developed a web-based HCV genotype interpretation platform that utilizes a scanned image to generate the genotypes, thus minimizing interpretation time and reducing error. Subjects and Methods: HCV Genie 2 utilizes a database of banding patterns in conjuncture with image analysis algorithms to determine the genotype for any number of scanned LiPA strips. HCV Genie 2 is built with client-side JavaScript; allowing the program to run in the user' browser rather than on an unknown server, essentially eliminating data and patient privacy concerns. Results: HCV Genie 2 was tested over 2 months and proved identical to human expert interpretation for 148 samples (>1000 bands identified). Manual intervention was required only for two faint bands and one false-positive band; this was done utilizing the built-in-user interface. Utilizing the original method, the trained laboratory technician interpretation time for 16 samples was 13.8 (±0.96) min as compared to 5.0 (±1.09) min with HCV Genie 2, a 63.8% decrease. In addition to the time savings, the new method provides an additional validation step, which decreases the potential for errors. Conclusions: Our institution has moved exclusively to utilize the new techniques and tools described here. Both experienced technicians and the molecular pathologists at our institution prefer the workflow using HCV Genie. It is easier for the technicians to prepare and document, and the pathologists are more rapidly able to review and confirm results. The use of this tool will lead to increase the quality of patient care delivered through this test methodology by decreasing the potential for error. The algorithms developed here can be ported to similar band identification platforms, most directly to other LiPAs.
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Research Article: Usability evaluation of laboratory information systems
Althea Mathews, David Marc
J Pathol Inform 2017, 8:40 (3 October 2017)
Background: Numerous studies have revealed widespread clinician frustration with the usability of electronic health records (EHRs) that is counterproductive to adoption of EHR systems to meet the aims of health-care reform. With poor system usability comes increased risk of negative unintended consequences. Usability issues could lead to user error and workarounds that have the potential to compromise patient safety and negatively impact the quality of care.[1] While there is ample research on EHR usability, there is little information on the usability of laboratory information systems (LISs). Yet, LISs facilitate the timely provision of a great deal of the information needed by physicians to make patient care decisions.[2] Medical and technical advances in genomics that require processing of an increased volume of complex laboratory data further underscore the importance of developing user-friendly LISs. This study aims to add to the body of knowledge on LIS usability. Methods: A survey was distributed among LIS users at hospitals across the United States. The survey consisted of the ten-item System Usability Scale (SUS). In addition, participants were asked to rate the ease of performing 24 common tasks with a LIS. Finally, respondents provided comments on what they liked and disliked about using the LIS to provide diagnostic insight into LIS perceived usability. Results: The overall mean SUS score of 59.7 for the LIS evaluated is significantly lower than the benchmark of 68 (P < 0.001). All LISs evaluated received mean SUS scores below 68 except for Orchard Harvest (78.7). While the years of experience using the LIS was found to be a statistically significant influence on mean SUS scores, the combined effect of years of experience and LIS used did not account for the statistically significant difference in the mean SUS score between Orchard Harvest and each of the other LISs evaluated. Conclusions: The results of this study indicate that overall usability of LISs is poor. Usability lags that of systems evaluated across 446 usability surveys.
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Original Article: Impact of altering various image parameters on human epidermal growth factor receptor 2 image analysis data quality
Liron Pantanowitz, Chi Liu, Yue Huang, Huazhang Guo, Gustavo K Rohde
J Pathol Inform 2017, 8:39 (7 September 2017)
Introduction: The quality of data obtained from image analysis can be directly affected by several preanalytical (e.g., staining, image acquisition), analytical (e.g., algorithm, region of interest [ROI]), and postanalytical (e.g., computer processing) variables. Whole-slide scanners generate digital images that may vary depending on the type of scanner and device settings. Our goal was to evaluate the impact of altering brightness, contrast, compression, and blurring on image analysis data quality. Methods: Slides from 55 patients with invasive breast carcinoma were digitized to include a spectrum of human epidermal growth factor receptor 2 (HER2) scores analyzed with Visiopharm (30 cases with score 0, 10 with 1+, 5 with 2+, and 10 with 3+). For all images, an ROI was selected and four parameters (brightness, contrast, JPEG2000 compression, out-of-focus blurring) then serially adjusted. HER2 scores were obtained for each altered image. Results: HER2 scores decreased with increased illumination, higher compression ratios, and increased blurring. HER2 scores increased with greater contrast. Cases with HER2 score 0 were least affected by image adjustments. Conclusion: This experiment shows that variations in image brightness, contrast, compression, and blurring can have major influences on image analysis results. Such changes can result in under- or over-scoring with image algorithms. Standardization of image analysis is recommended to minimize the undesirable impact such variations may have on data output.
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Original Article: A methodology for texture feature-based quality assessment in nucleus segmentation of histopathology image
Si Wen, Tahsin M Kurc, Yi Gao, Tianhao Zhao, Joel H Saltz, Wei Zhu
J Pathol Inform 2017, 8:38 (7 September 2017)
Context: Image segmentation pipelines often are sensitive to algorithm input parameters. Algorithm parameters optimized for a set of images do not necessarily produce good-quality-segmentation results for other images. Even within an image, some regions may not be well segmented due to a number of factors, including multiple pieces of tissue with distinct characteristics, differences in staining of the tissue, normal versus tumor regions, and tumor heterogeneity. Evaluation of quality of segmentation results is an important step in image analysis. It is very labor intensive to do quality assessment manually with large image datasets because a whole-slide tissue image may have hundreds of thousands of nuclei. Semi-automatic mechanisms are needed to assist researchers and application developers to detect image regions with bad segmentations efficiently. Aims: Our goal is to develop and evaluate a machine-learning-based semi-automated workflow to assess quality of nucleus segmentation results in a large set of whole-slide tissue images. Methods: We propose a quality control methodology, in which machine-learning algorithms are trained with image intensity and texture features to produce a classification model. This model is applied to image patches in a whole-slide tissue image to predict the quality of nucleus segmentation in each patch. The training step of our methodology involves the selection and labeling of regions by a pathologist in a set of images to create the training dataset. The image regions are partitioned into patches. A set of intensity and texture features is computed for each patch. A classifier is trained with the features and the labels assigned by the pathologist. At the end of this process, a classification model is generated. The classification step applies the classification model to unlabeled test images. Each test image is partitioned into patches. The classification model is applied to each patch to predict the patch's label. Results: The proposed methodology has been evaluated by assessing the segmentation quality of a segmentation method applied to images from two cancer types in The Cancer Genome Atlas; WHO Grade II lower grade glioma (LGG) and lung adenocarcinoma (LUAD). The results show that our method performs well in predicting patches with good-quality segmentations and achieves F1 scores 84.7% for LGG and 75.43% for LUAD. Conclusions: As image scanning technologies advance, large volumes of whole-slide tissue images will be available for research and clinical use. Efficient approaches for the assessment of quality and robustness of output from computerized image analysis workflows will become increasingly critical to extracting useful quantitative information from tissue images. Our work demonstrates the feasibility of machine-learning-based semi-automated techniques to assist researchers and algorithm developers in this process.
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Book Review: Review of “Digital Pathology” by Liron Pantanowitz and Anil V Parwani
Tushar Patel
J Pathol Inform 2017, 8:37 (7 September 2017)
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Original Article: Three-dimensional imaging and scanning: Current and future applications for pathology
Navid Farahani, Alex Braun, Dylan Jutt, Todd Huffman, Nick Reder, Zheng Liu, Yukako Yagi, Liron Pantanowitz
J Pathol Inform 2017, 8:36 (7 September 2017)
Imaging is vital for the assessment of physiologic and phenotypic details. In the past, biomedical imaging was heavily reliant on analog, low-throughput methods, which would produce two-dimensional images. However, newer, digital, and high-throughput three-dimensional (3D) imaging methods, which rely on computer vision and computer graphics, are transforming the way biomedical professionals practice. 3D imaging has been useful in diagnostic, prognostic, and therapeutic decision-making for the medical and biomedical professions. Herein, we summarize current imaging methods that enable optimal 3D histopathologic reconstruction: Scanning, 3D scanning, and whole slide imaging. Briefly mentioned are emerging platforms, which combine robotics, sectioning, and imaging in their pursuit to digitize and automate the entire microscopy workflow. Finally, both current and emerging 3D imaging methods are discussed in relation to current and future applications within the context of pathology.
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Research Article: Robotic telecytology for remote cytologic evaluation without an on-site cytotechnologist or cytopathologist: an active quality assessment and experience of over 400 cases
Sahussapont Joseph Sirintrapun, Dorota Rudomina, Allix Mazzella, Rusmir Feratovic, William Alago, Robert Siegelbaum, Oscar Lin
J Pathol Inform 2017, 8:35 (7 September 2017)
Background: The first satellite center to offer interventional radiology procedures at Memorial Sloan Kettering Cancer Center opened in October 2014. Two of the procedures offered, fine needle aspirations and core biopsies, required a rapid on-site cytologic evaluation of smears and biopsy touch imprints for cellular content and adequacy. The volume and frequency of such evaluations did not justify hiring on-site cytotechnologists, and therefore, a dynamic robotic telecytology (TC) solution was created. In this article, we provide data on our experience with this active implementation. Sakura VisionTek was selected as our robotic TC solution. Methods: A retrospective analysis of all TC evaluations from this satellite site was performed. Information was collected on demographics, lesion location, imaging modality; a comparison of TC-assisted adequacy with final adequacy was also conducted. Results: An analysis of 439 cases was performed over a period of 23 months with perfect correlation in 92.7% (407/439) of the cases. An adequacy upgrade (inadequate specimen becomes adequate) in 6.6% (29/439) of the cases. An adequacy downgrade (adequate specimen becomes inadequate), is near zero at 0.7% (3/439) of the cases. Conclusions: Dynamic robotic TC is effective for immediate evaluations performed without on-site cytotechnology staff. The overall intent of this article is to present data and concordance rates as outcome metrics. Thus far, such outcome metrics have exceeded our expectations. Our TC implementation shows high, perfect concordance. Adequacy upgrades are minor but more relevant and impressive is a near zero adequacy downgrade. Our full implementation has been so successful that plans are in place for configurations at future satellite sites.
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Original Article: Determining image processing features describing the appearance of challenging mitotic figures and miscounted nonmitotic objects
Ziba Gandomkar, Patrick C Brennan, Claudia Mello-Thoms
J Pathol Inform 2017, 8:34 (7 September 2017)
Context: Previous studies showed that the agreement among pathologists in recognition of mitoses in breast slides is fairly modest. Aims: Determining the significantly different quantitative features among easily identifiable mitoses, challenging mitoses, and miscounted nonmitoses within breast slides and identifying which color spaces capture the difference among groups better than others. Materials and Methods: The dataset contained 453 mitoses and 265 miscounted objects in breast slides. The mitoses were grouped into three categories based on the confidence degree of three pathologists who annotated them. The mitoses annotated as “probably a mitosis” by the majority of pathologists were considered as the challenging category. The miscounted objects were recognized as a mitosis or probably a mitosis by only one of the pathologists. The mitoses were segmented using k-means clustering, followed by morphological operations. Morphological, intensity-based, and textural features were extracted from the segmented area and also the image patch of 63 × 63 pixels in different channels of eight color spaces. Holistic features describing the mitoses' surrounding cells of each image were also extracted. Statistical Analysis Used: The Kruskal–Wallis H-test followed by the Tukey-Kramer test was used to identify significantly different features. Results: The results indicated that challenging mitoses were smaller and rounder compared to other mitoses. Among different features, the Gabor textural features differed more than others between challenging mitoses and the easily identifiable ones. Sizes of the non-mitoses were similar to easily identifiable mitoses, but nonmitoses were rounder. The intensity-based features from chromatin channels were the most discriminative features between the easily identifiable mitoses and the miscounted objects. Conclusions: Quantitative features can be used to describe the characteristics of challenging mitoses and miscounted nonmitotic objects.
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Research Article: Successful secure high-definition streaming telecytology for remote cytologic evaluation
Sahussapont Joseph Sirintrapun, Dorota Rudomina, Allix Mazzella, Rusmir Feratovic, Oscar Lin
J Pathol Inform 2017, 8:33 (7 September 2017)
Background: The use of minimally invasive procedures to obtain material for diagnostic purposes has become more prevalent in recent years. As such, there is increased demand for immediate cytologic adequacy assessment of minimally invasive procedures. The array of different locations in which rapid on-site evaluation (ROSE) is expected requires an ever-increasing number of cytology personnel to provide support for adequacy assessment. In our study, we describe the implementation process of a telecytology (TC) system in a high case volume setting and evaluate the performance of this activity. Methods: We performed retrospectively an analysis of all consecutive remote TC ROSE evaluations obtained for 15 months. The specimens were evaluated using a TC system. The ROSE adequacy assessment obtained at the time of the procedure was compared to the final cytopathologist-rendered adequacy assessment when all the material was available for review, including the alcohol-fixed preparations. Results: A total of 8106 distinct cases were analyzed. TC-assisted preliminary adequacy assessment was highly concordant with the final cytopathologist-rendered adequacy assessment. Perfect concordance or accuracy was at 93.1% (7547/8106). The adequacy upgrade rate (inadequate specimen became adequate) was 6.8% (551/8106), and the initial adequacy downgrade (adequate specimen became inadequate) was <0.1% (8/8106). Conclusions: The TC outcome demonstrates high concordance between the initial adequacy assessment and final cytopathologist-rendered adequacy assessment. Adequacy upgrades were minor but, more importantly, our results demonstrate a minimal adequacy downgrade. The process implemented effectively eliminated the need for an attending pathologist to be physically present onsite during a biopsy procedure.
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Technical Note: Robotic telecytology for remote cytologic evaluation without an on-site cytotechnologist or cytopathologist: A tale of implementation and review of constraints
Sahussapont Joseph Sirintrapun, Dorota Rudomina, Allix Mazzella, Rusmir Feratovic, William Alago, Robert Siegelbaum, Oscar Lin
J Pathol Inform 2017, 8:32 (7 September 2017)
Background: The first satellite center to offer interventional radiology procedures at Memorial Sloan Kettering Cancer Center opened in October 2014. Two of the procedures offered, fine needle aspirations and core biopsies, required rapid on-site cytologic evaluation of smears and biopsy touch imprints for cellular content and adequacy. The volume and frequency of such evaluations did not justify hiring on-site cytotechnologists, and therefore, a dynamic robotic telecytology (TC) solution was created. In this technical article, we present a detailed description of our implementation of robotic TC. Methods: Pathology devised the remote robotic TC solution after acknowledging that it would not be cost effective to staff cytotechnologists on-site at the satellite location. Sakura VisionTek was selected as our robotic TC solution. In addition to configuration of the dynamic robotic TC solution, pathology realized integrating the technology solution into operations would require a multidisciplinary effort and reevaluation of existing staffing and workflows. Results: Extensively described are the architectural framework and multidisciplinary process re-design, created to navigate the constraints of our technical, cultural, and organizational environment. Also reviewed are the benefits and challenges associated with available desktop sharing solutions, particularly accounting for information security concerns. Conclusions: Dynamic robotic TC is effective for immediate evaluations performed without on-site cytotechnology staff. Our goal is providing an extensive perspective of the implementation process, particularly technical, cultural, and operational constraints. Through this perspective, our template can serve as an extensible blueprint for other centers interested in implementing robotic TC without on-site cytotechnologists.
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Research Article: A design study investigating augmented reality and photograph annotation in a digitalized grossing workstation
Joyce A Chow, Martin E Törnros, Marie Waltersson, Helen Richard, Madeleine Kusoffsky, Claes F Lundström, Arianit Kurti
J Pathol Inform 2017, 8:31 (7 September 2017)
Context: Within digital pathology, digitalization of the grossing procedure has been relatively underexplored in comparison to digitalization of pathology slides. Aims: Our investigation focuses on the interaction design of an augmented reality gross pathology workstation and refining the interface so that information and visualizations are easily recorded and displayed in a thoughtful view. Settings and Design: The work in this project occurred in two phases: the first phase focused on implementation of an augmented reality grossing workstation prototype while the second phase focused on the implementation of an incremental prototype in parallel with a deeper design study. Subjects and Methods: Our research institute focused on an experimental and “designerly” approach to create a digital gross pathology prototype as opposed to focusing on developing a system for immediate clinical deployment. Statistical Analysis Used: Evaluation has not been limited to user tests and interviews, but rather key insights were uncovered through design methods such as “rapid ethnography” and “conversation with materials”. Results: We developed an augmented reality enhanced digital grossing station prototype to assist pathology technicians in capturing data during examination. The prototype uses a magnetically tracked scalpel to annotate planned cuts and dimensions onto photographs taken of the work surface. This article focuses on the use of qualitative design methods to evaluate and refine the prototype. Our aims were to build on the strengths of the prototype's technology, improve the ergonomics of the digital/physical workstation by considering numerous alternative design directions, and to consider the effects of digitalization on personnel and the pathology diagnostics information flow from a wider perspective. A proposed interface design allows the pathology technician to place images in relation to its orientation, annotate directly on the image, and create linked information. Conclusions: The augmented reality magnetically tracked scalpel reduces tool switching though limitations in today's augmented reality technology fall short of creating an ideal immersive workflow by requiring the use of a monitor. While this technology catches up, we recommend focusing efforts on enabling the easy creation of layered, complex reports, linking, and viewing information across systems. Reflecting upon our results, we argue for digitalization to focus not only on how to record increasing amounts of data but also how these data can be accessed in a more thoughtful way that draws upon the expertise and creativity of pathology professionals using the systems.
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Original Article: Deep learning for classification of colorectal polyps on whole-slide images Highly accessed article
Bruno Korbar, Andrea M Olofson, Allen P Miraflor, Catherine M Nicka, Matthew A Suriawinata, Lorenzo Torresani, Arief A Suriawinata, Saeed Hassanpour
J Pathol Inform 2017, 8:30 (25 July 2017)
DOI:10.4103/jpi.jpi_34_17  PMID:28828201
Context: Histopathological characterization of colorectal polyps is critical for determining the risk of colorectal cancer and future rates of surveillance for patients. However, this characterization is a challenging task and suffers from significant inter- and intra-observer variability. Aims: We built an automatic image analysis method that can accurately classify different types of colorectal polyps on whole-slide images to help pathologists with this characterization and diagnosis. Setting and Design: Our method is based on deep-learning techniques, which rely on numerous levels of abstraction for data representation and have shown state-of-the-art results for various image analysis tasks. Subjects and Methods: Our method covers five common types of polyps (i.e., hyperplastic, sessile serrated, traditional serrated, tubular, and tubulovillous/villous) that are included in the US Multisociety Task Force guidelines for colorectal cancer risk assessment and surveillance. We developed multiple deep-learning approaches by leveraging a dataset of 2074 crop images, which were annotated by multiple domain expert pathologists as reference standards. Statistical Analysis: We evaluated our method on an independent test set of 239 whole-slide images and measured standard machine-learning evaluation metrics of accuracy, precision, recall, and F1 score and their 95% confidence intervals. Results: Our evaluation shows that our method with residual network architecture achieves the best performance for classification of colorectal polyps on whole-slide images (overall accuracy: 93.0%, 95% confidence interval: 89.0%–95.9%). Conclusions: Our method can reduce the cognitive burden on pathologists and improve their efficacy in histopathological characterization of colorectal polyps and in subsequent risk assessment and follow-up recommendations.
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Original Article: PathEdEx – Uncovering high-explanatory visual diagnostics heuristics using digital pathology and multiscale gaze data
Dmitriy Shin, Mikhail Kovalenko, Ilker Ersoy, Yu Li, Donald Doll, Chi-Ren Shyu, Richard Hammer
J Pathol Inform 2017, 8:29 (25 July 2017)
DOI:10.4103/jpi.jpi_29_17  PMID:28828200
Background: Visual heuristics of pathology diagnosis is a largely unexplored area where reported studies only provided a qualitative insight into the subject. Uncovering and quantifying pathology visual and nonvisual diagnostic patterns have great potential to improve clinical outcomes and avoid diagnostic pitfalls. Methods: Here, we present PathEdEx, an informatics computational framework that incorporates whole-slide digital pathology imaging with multiscale gaze-tracking technology to create web-based interactive pathology educational atlases and to datamine visual and nonvisual diagnostic heuristics. Results: We demonstrate the capabilities of PathEdEx for mining visual and nonvisual diagnostic heuristics using the first PathEdEx volume of a hematopathology atlas. We conducted a quantitative study on the time dynamics of zooming and panning operations utilized by experts and novices to come to the correct diagnosis. We then performed association rule mining to determine sets of diagnostic factors that consistently result in a correct diagnosis, and studied differences in diagnostic strategies across different levels of pathology expertise using Markov chain (MC) modeling and MC Monte Carlo simulations. To perform these studies, we translated raw gaze points to high-explanatory semantic labels that represent pathology diagnostic clues. Therefore, the outcome of these studies is readily transformed into narrative descriptors for direct use in pathology education and practice. Conclusion: PathEdEx framework can be used to capture best practices of pathology visual and nonvisual diagnostic heuristics that can be passed over to the next generation of pathologists and have potential to streamline implementation of precision diagnostics in precision medicine settings.
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Technical Note: Implementation of automated calculation of free and bioavailable testosterone in Epic Beaker laboratory information system
Michael C Chung, Saurabh Gombar, Run Zhang Shi
J Pathol Inform 2017, 8:28 (25 July 2017)
DOI:10.4103/jpi.jpi_28_17  PMID:28828199
Background: Automated calculations by laboratory information system (LIS) are efficient and accurate ways of providing calculated laboratory test results. Due to the lack of established advanced mathematical functions and equation logic in LIS software, calculations beyond simple arithmetic functions require a tedious workaround. Free and bioavailable testosterone (BT) calculations require a quadratic solver currently unavailable as ready to use the function on most commercial LIS platforms. We aimed to develop a module within the Epic Beaker LIS to enable automatic quadratic equation solving capability and real-time reporting of calculated free and BT values. Materials and Methods: We developed and implemented an advanced calculation module from the ground up using existing basic calculation programming functions in the Epic Beaker LIS. A set of calculation variables were created, and mathematical logic and functions were used to link the variables and perform the actual quadratic equation based calculations. Calculations were performed in real-time during result entry events, and calculated results populated the result components in LIS automatically. Results: Free and BT were calculated using instrument measured results of total testosterone, sex hormone binding globulin, and/or serum albumin, by applying equations widely adopted in laboratory medicine for endocrine diseases and disorders. Calculated results in Epic Beaker LIS were then compared and confirmed by manual calculations using Microsoft Excel spreadsheets and scientific calculators to have no discrepancies. Conclusions: Automated calculations of free and BT were successfully implemented and validated, the first of such implementation for the Epic Beaker LIS platform, eliminating the need of offline manual calculations, potential transcription error, and with improved turnaround time. It may serve as a model to build similarly complex equations when the clinical need arises.
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Original Article: Teaching digital pathology: The international school of digital pathology and proposed syllabus
Vincenzo Della Mea, Antonino Carbone, Carla Di Loreto, Gloria Bueno, Paolo De Paoli, Marcial García-Rojo, David de Mena, Annunziata Gloghini, Mohammad Ilyas, Arvydas Laurinavicius, Allan Rasmusson, Massimo Milione, Riccardo Dolcetti, Marco Pagani, Andrea Stoppini, Sandro Sulfaro, Michelangelo Bartolo, Emanuela Mazzon, H Peter Soyer, Liron Pantanowitz
J Pathol Inform 2017, 8:27 (25 July 2017)
DOI:10.4103/jpi.jpi_17_17  PMID:28828198
Digital pathology is an interdisciplinary field where competency in pathology, laboratory techniques, informatics, computer science, information systems, engineering, and even biology converge. This implies that teaching students about digital pathology requires coverage, expertise, and hands-on experience in all these disciplines. With this in mind, a syllabus was developed for a digital pathology summer school aimed at professionals in the aforementioned fields, as well as trainees and doctoral students. The aim of this communication is to share the context, rationale, and syllabus for this school of digital pathology.
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Abstracts: Pathology Informatics Summit 2017

J Pathol Inform 2017, 8:26 (14 July 2017)
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Technical Note: Development and implementation of a coagulation factor testing method utilizing autoverification in a high-volume clinical reference laboratory environment
Paul W Riley, Benoit Gallea, Andre Valcour
J Pathol Inform 2017, 8:25 (19 June 2017)
DOI:10.4103/jpi.jpi_95_16  PMID:28706751
Background: Testing coagulation factor activities requires that multiple dilutions be assayed and analyzed to produce a single result. The slope of the line created by plotting measured factor concentration against sample dilution is evaluated to discern the presence of inhibitors giving rise to nonparallelism. Moreover, samples producing results on initial dilution falling outside the analytic measurement range of the assay must be tested at additional dilutions to produce reportable results. Methods: The complexity of this process has motivated a large clinical reference laboratory to develop advanced computer algorithms with automated reflex testing rules to complete coagulation factor analysis. A method was developed for autoverification of coagulation factor activity using expert rules developed with on an off the shelf commercially available data manager system integrated into an automated coagulation platform. Results: Here, we present an approach allowing for the autoverification and reporting of factor activity results with greatly diminished technologist effort. Conclusions: To the best of our knowledge, this is the first report of its kind providing a detailed procedure for implementation of autoverification expert rules as applied to coagulation factor activity testing. Advantages of this system include ease of training for new operators, minimization of technologist time spent, reduction of staff fatigue, minimization of unnecessary reflex tests, optimization of turnaround time, and assurance of the consistency of the testing and reporting process.
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Research Article: A reduced set of features for chronic kidney disease prediction
Rajesh Misir, Malay Mitra, Ranjit Kumar Samanta
J Pathol Inform 2017, 8:24 (19 June 2017)
DOI:10.4103/jpi.jpi_88_16  PMID:28706750
Chronic kidney disease (CKD) is one of the life-threatening diseases. Early detection and proper management are solicited for augmenting survivability. As per the UCI data set, there are 24 attributes for predicting CKD or non-CKD. At least there are 16 attributes need pathological investigations involving more resources, money, time, and uncertainties. The objective of this work is to explore whether we can predict CKD or non-CKD with reasonable accuracy using less number of features. An intelligent system development approach has been used in this study. We attempted one important feature selection technique to discover reduced features that explain the data set much better. Two intelligent binary classification techniques have been adopted for the validity of the reduced feature set. Performances were evaluated in terms of four important classification evaluation parameters. As suggested from our results, we may more concentrate on those reduced features for identifying CKD and thereby reduces uncertainty, saves time, and reduces costs.
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Review Article: Current state of the regulatory trajectory for whole slide imaging devices in the USA Highly accessed article
Esther Abels, Liron Pantanowitz
J Pathol Inform 2017, 8:23 (15 May 2017)
DOI:10.4103/jpi.jpi_11_17  PMID:28584684
The regulatory field for digital pathology (DP) has advanced significantly. A major milestone was accomplished when the FDA allowed the first vendor to market their device for primary diagnostic use in the USA and published in the classification order that this device, and substantially equivalent devices of this generic type, should be classified into class II instead of class III as previously proposed. The Digital Pathology Association (DPA) regulatory task force had a major role in the accomplishment of getting the application request for Whole Slide Imaging (WSI) Systems recommended for a de novo. This article reviews the past and emerging regulatory environment of WSI for clinical use in the USA. A WSI system with integrated subsystems is defined in the context of medical device regulations. The FDA technical performance assessment guideline is also discussed as well as parameters involved in analytical testing and clinical studies to demonstrate that WSI devices are safe and effective for clinical use.
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Book Review: Review of “Travels on conferences: Evolution of digital pathology” by Klaus Kayser
Gabor Fischer
J Pathol Inform 2017, 8:22 (15 May 2017)
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Research Article: Training nuclei detection algorithms with simple annotations
Henning Kost, André Homeyer, Jesper Molin, Claes Lundström, Horst Karl Hahn
J Pathol Inform 2017, 8:21 (15 May 2017)
DOI:10.4103/jpi.jpi_3_17  PMID:28584683
Background: Generating good training datasets is essential for machine learning-based nuclei detection methods. However, creating exhaustive nuclei contour annotations, to derive optimal training data from, is often infeasible. Methods: We compared different approaches for training nuclei detection methods solely based on nucleus center markers. Such markers contain less accurate information, especially with regard to nuclear boundaries, but can be produced much easier and in greater quantities. The approaches use different automated sample extraction methods to derive image positions and class labels from nucleus center markers. In addition, the approaches use different automated sample selection methods to improve the detection quality of the classification algorithm and reduce the run time of the training process. We evaluated the approaches based on a previously published generic nuclei detection algorithm and a set of Ki-67-stained breast cancer images. Results: A Voronoi tessellation-based sample extraction method produced the best performing training sets. However, subsampling of the extracted training samples was crucial. Even simple class balancing improved the detection quality considerably. The incorporation of active learning led to a further increase in detection quality. Conclusions: With appropriate sample extraction and selection methods, nuclei detection algorithms trained on the basis of simple center marker annotations can produce comparable quality to algorithms trained on conventionally created training sets.
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PV16 Abstracts: Abstracts

J Pathol Inform 2017, 8:20 (10 May 2017)
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Technical Note: The need for careful data collection for pattern recognition in digital pathology
Raphaël Marée
J Pathol Inform 2017, 8:19 (10 April 2017)
DOI:10.4103/jpi.jpi_94_16  PMID:28480122
Effective pattern recognition requires carefully designed ground-truth datasets. In this technical note, we first summarize potential data collection issues in digital pathology and then propose guidelines to build more realistic ground-truth datasets and to control their quality. We hope our comments will foster the effective application of pattern recognition approaches in digital pathology.
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Original Article: Alchemy: A web 2.0 real-time quality assurance platform for human immunodeficiency Virus, hepatitis C Virus, and BK Virus quantitation assays
Emmanuel Agosto-Arroyo, Gina M Coshatt, Thomas S Winokur, Shuko Harada, Seung L Park
J Pathol Inform 2017, 8:18 (10 April 2017)
DOI:10.4103/jpi.jpi_69_16  PMID:28480121
Background: The molecular diagnostics laboratory faces the challenge of improving test turnaround time (TAT). Low and consistent TATs are of great clinical and regulatory importance, especially for molecular virology tests. Laboratory information systems (LISs) contain all the data elements necessary to do accurate quality assurance (QA) reporting of TAT and other measures, but these reports are in most cases still performed manually: a time-consuming and error-prone task. The aim of this study was to develop a web-based real-time QA platform that would automate QA reporting in the molecular diagnostics laboratory at our institution, and minimize the time expended in preparing these reports. Methods: Using a standard Linux, Nginx, MariaDB, PHP stack virtual machine running atop a Dell Precision 5810, we designed and built a web-based QA platform, code-named Alchemy. Data files pulled periodically from the LIS in comma-separated value format were used to autogenerate QA reports for the human immunodeficiency virus (HIV) quantitation, hepatitis C virus (HCV) quantitation, and BK virus (BKV) quantitation. Alchemy allowed the user to select a specific timeframe to be analyzed and calculated key QA statistics in real-time, including the average TAT in days, tests falling outside the expected TAT ranges, and test result ranges. Results: Before implementing Alchemy, reporting QA for the HIV, HCV, and BKV quantitation assays took 45–60 min of personnel time per test every month. With Alchemy, that time has decreased to 15 min total per month. Alchemy allowed the user to select specific periods of time and analyzed the TAT data in-depth without the need of extensive manual calculations. Conclusions: Alchemy has significantly decreased the time and the human error associated with QA report generation in our molecular diagnostics laboratory. Other tests will be added to this web-based platform in future updates. This effort shows the utility of informatician-supervised resident/fellow programming projects as learning opportunities and workflow improvements in the molecular laboratory.
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Letter to Editor: Compromising the security of “Generating unique identifiers from patient identification data using security models”
Arran Schlosberg
J Pathol Inform 2017, 8:17 (10 April 2017)
DOI:10.4103/jpi.jpi_1_17  PMID:28480120
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Technical Note: Evaluation of android smartphones for telepathology
Donald Ekong, Fang Liu, G Thomas Brown, Arunima Ghosh, Paul Fontelo
J Pathol Inform 2017, 8:16 (10 April 2017)
DOI:10.4103/jpi.jpi_93_16  PMID:28480119
Background: In the year 2014, Android smartphones accounted for one-third of mobile connections globally but are predicted to increase to two-thirds by 2020. In developing countries, where teleconsultations can benefit health-care providers most, the ratio is even higher. This study compared the use of two Android phones, an 8 megapixel (MP) and a 16 MP phone, for capturing microscopic images. Method: The Android phones were used to capture images and videos of a gastrointestinal biopsy teaching set of referred cases from the Armed Forces Institute of Pathology (AFIP). The acquired images and videos were reviewed online by two pathologists for image quality, adequacy for diagnosis, usefulness of video overviews, and confidence in diagnosis, on a 5-point Likert scale. Results: The results show higher means in a 5-point Likert scale for the 8 MP versus the 16 MP phone that were statistically significant in adequacy of images (4.0 vs. 3.75) for rendering diagnosis and for agreement with the reference diagnosis (2.33 vs. 2.07). Although the quality of images was found higher in the 16 MP phone (3.8 vs. 3.65), these were not statistically significant. Adding video images of the entire specimen was found to be useful for evaluating the slides (combined mean, 4.0). Conclusion: For telepathology and other image dependent practices in developing countries, Android phones could be a useful tool for capturing images.
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Original Article: Predictive nuclear chromatin characteristics of melanoma and dysplastic nevi
Matthew G Hanna, Chi Liu, Gustavo K Rohde, Rajendra Singh
J Pathol Inform 2017, 8:15 (10 April 2017)
DOI:10.4103/jpi.jpi_84_16  PMID:28480118
Background: The diagnosis of malignant melanoma (MM) is among the diagnostic challenges pathologists encounter on a routine basis. Melanoma may arise in patients with preexisting dysplastic nevi (DN) and it is still the cause of 1.7% of all cancer-related deaths. Melanomas often have overlapping histological features with DN, especially those with severe dysplasia. Nucleotyping for identifying nuclear textural features can analyze nuclear DNA structure and organization. The aim of this study is to differentiate MM and DN using these methodologies. Methods: Dermatopathology slides diagnosed as MM and DN were retrieved. The glass slides were scanned using an Aperio ScanScopeXT at ×40 (0.25 μ/pixel). Whole slide images (WSI) were annotated for nuclei selection. Nuclear features to distinguish between MM and DN based on chromatin distributions were extracted from the WSI. The morphological characteristics for each nucleus were quantified with the optimal transport-based linear embedding in the continuous domain. Label predictions for individual cell nucleus are achieved through a modified version of linear discriminant analysis, coupled with the k-nearest neighbor classifier. Label for an unknown patient was set by the voting strategy with its pertaining cell nuclei. Results: Nucleotyping of 139 patient cases of melanoma (n = 67) and DN (n = 72) showed that our method had superior classification accuracy of 81.29%. This is a 6.4% gain in differentiating MM and DN, compared with numerical feature-based method. The distribution differences in nuclei morphology between MM and DN can be visualized with biological interpretation. Conclusions: Nucleotyping using quantitative and qualitative analyses may provide enough information for differentiating MM from DN using pixel image data. Our method to segment cell nuclei may offer a practical and inexpensive solution in aiding in the accurate diagnosis of melanoma.
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Commentary: Making pathology diagnoses with glass or digital slides: Which modality is inferior?
Jonhan Ho, Liron Pantanowitz
J Pathol Inform 2017, 8:14 (10 April 2017)
DOI:10.4103/jpi.jpi_10_17  PMID:28480117
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Original Article: Performance of a web-based method for generating synoptic reports
Megan A Renshaw, Scott A Renshaw, Mercy Mena-Allauca, Patricia P Carrion, Xiaorong Mei, Arniris Narciandi, Edwin W Gould, Andrew A Renshaw
J Pathol Inform 2017, 8:13 (10 March 2017)
DOI:10.4103/jpi.jpi_91_16  PMID:28382227
Context: The College of American Pathologists (CAP) requires synoptic reporting of all tumor excisions. Objective: To compare the performance of different methods of generating synoptic reports. Methods: Completeness, amendment rates, rate of timely ordering of ancillary studies (KRAS in T4/N1 colon carcinoma), and structured data file extraction were compared for four different synoptic report generating methods. Results: Use of the printed tumor protocols directly from the CAP website had the lowest completeness (84%) and highest amendment (1.8%) rates. Reformatting these protocols was associated with higher completeness (94%, P < 0.001) and reduced amendment (1%, P = 0.20) rates. Extraction into a structured data file was successful 93% of the time. Word-based macros improved completeness (98% vs. 94%, P < 0.001) but not amendment rates (1.5%). KRAS was ordered before sign out 89% of the time. In contrast, a web-based product with a reminder flag when items were missing, an embedded flag for data extraction, and a reminder to order KRAS when appropriate resulted in improved completeness (100%, P = 0.005), amendment rates (0.3%, P = 0.03), KRAS ordering before sign out (100%, P = 0.23), and structured data extraction (100%, P < 0.001) without reducing the speed (P = 0.34) or accuracy (P = 1.00) of data extraction by the reader. Conclusion: Completeness, amendment rates, ancillary test ordering rates, and data extraction rates vary significantly with the method used to construct the synoptic report. A web-based method compares favorably with all other methods examined and does not reduce reader usability.
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Research Article: A randomized study comparing digital imaging to traditional glass slide microscopy for breast biopsy and cancer diagnosis
Joann G Elmore, Gary M Longton, Margaret S Pepe, Patricia A Carney, Heidi D Nelson, Kimberly H Allison, Berta M Geller, Tracy Onega, Anna N. A Tosteson, Ezgi Mercan, Linda G Shapiro, Tad T Brunyé, Thomas R Morgan, Donald L Weaver
J Pathol Inform 2017, 8:12 (10 March 2017)
DOI:10.4103/2153-3539.201920  PMID:28382226
Background: Digital whole slide imaging may be useful for obtaining second opinions and is used in many countries. However, the U.S. Food and Drug Administration requires verification studies. Methods: Pathologists were randomized to interpret one of four sets of breast biopsy cases during two phases, separated by ≥9 months, using glass slides or digital format (sixty cases per set, one slide per case, n = 240 cases). Accuracy was assessed by comparing interpretations to a consensus reference standard. Intraobserver reproducibility was assessed by comparing the agreement of interpretations on the same cases between two phases. Estimated probabilities of confirmation by a reference panel (i.e., predictive values) were obtained by incorporating data on the population prevalence of diagnoses. Results: Sixty-five percent of responding pathologists were eligible, and 252 consented to randomization; 208 completed Phase I (115 glass, 93 digital); and 172 completed Phase II (86 glass, 86 digital). Accuracy was slightly higher using glass compared to digital format and varied by category: invasive carcinoma, 96% versus 93% (P = 0.04); ductal carcinoma in situ (DCIS), 84% versus 79% (P < 0.01); atypia, 48% versus 43% (P = 0.08); and benign without atypia, 87% versus 82% (P < 0.01). There was a small decrease in intraobserver agreement when the format changed compared to when glass slides were used in both phases (P = 0.08). Predictive values for confirmation by a reference panel using glass versus digital were: invasive carcinoma, 98% and 97% (not significant [NS]); DCIS, 70% and 57% (P = 0.007); atypia, 38% and 28% (P = 0.002); and benign without atypia, 97% and 96% (NS). Conclusions: In this large randomized study, digital format interpretations were similar to glass slide interpretations of benign and invasive cancer cases. However, cases in the middle of the spectrum, where more inherent variability exists, may be more problematic in digital format. Future studies evaluating the effect these findings exert on clinical practice and patient outcomes are required.
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Technical Note: Turning microscopy in the medical curriculum digital: Experiences from the faculty of health and medical sciences at University of Copenhagen
Ben Vainer, Niels Werner Mortensen, Steen Seier Poulsen, Allan Have Sørensen, Jørgen Olsen, Hans Henrik Saxild, Flemming Fryd Johansen
J Pathol Inform 2017, 8:11 (10 March 2017)
DOI:10.4103/2153-3539.201919  PMID:28382225
Familiarity with the structure and composition of normal tissue and an understanding of the changes that occur during disease is pivotal to the study of the human body. For decades, microscope slides have been central to teaching pathology in medical courses and related subjects at the University of Copenhagen. Students had to learn how to use a microscope and envisage three-dimensional processes that occur in the body from two-dimensional glass slides. Here, we describe how a PathXL virtual microscopy system for teaching pathology and histology at the Faculty has recently been implemented, from an administrative, an economic, and a teaching perspective. This fully automatic digital microscopy system has been received positively by both teachers and students, and a decision was made to convert all courses involving microscopy to the virtual microscopy format. As a result, conventional analog microscopy will be phased out from the fall of 2016.
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Original Article: An open source, whole slide image-based pathology education system
Paul A Christensen, Nathan E Lee, Michael J Thrall, Suzanne Z Powell, Patricia Chevez-Barrios, S Wesley Long
J Pathol Inform 2017, 8:10 (10 March 2017)
DOI:10.4103/jpi.jpi_72_16  PMID:28382224
Background: Our institution's pathology unknown conferences provide educational cases for our residents. However, the cases have not been previously available digitally, have not been collated for postconference review, and were not accessible to a wider audience. Our objective was to create an inexpensive whole slide image (WSI) education suite to address these limitations and improve the education of pathology trainees. Materials and Methods: We surveyed residents regarding their preference between four unique WSI systems. We then scanned weekly unknown conference cases and study set cases and uploaded them to our custom built WSI viewer located at We measured site utilization and conference participation. Results: Residents preferred our OpenLayers WSI implementation to Ventana Virtuoso, Google Maps API, and OpenSlide. Over 16 months, we uploaded 1366 cases from 77 conferences and ten study sets, occupying 793.5 GB of cloud storage. Based on resident evaluations, the interface was easy to use and demonstrated minimal latency. Residents are able to review cases from home and from their mobile devices. Worldwide, 955 unique IP addresses from 52 countries have viewed cases in our site. Conclusions: We implemented a low-cost, publicly available repository of WSI slides for resident education. Our trainees are very satisfied with the freedom to preview either the glass slides or WSI and review the WSI postconference. Both local users and worldwide users actively and repeatedly view cases in our study set.
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Original Article: Identification of histological correlates of overall survival in lower grade gliomas using a bag-of-words paradigm: A preliminary analysis based on hematoxylin & eosin stained slides from the lower grade glioma cohort of the cancer genome Atlas
Reid Trenton Powell, Adriana Olar, Shivali Narang, Ganesh Rao, Erik Sulman, Gregory N Fuller, Arvind Rao
J Pathol Inform 2017, 8:9 (10 March 2017)
DOI:10.4103/jpi.jpi_43_16  PMID:28382223
Background: Glioma, the most common primary brain neoplasm, describes a heterogeneous tumor of multiple histologic subtypes and cellular origins. At clinical presentation, gliomas are graded according to the World Health Organization guidelines (WHO), which reflect the malignant characteristics of the tumor based on histopathological and molecular features. Lower grade diffuse gliomas (LGGs) (WHO Grade II–III) have fewer malignant characteristics than high-grade gliomas (WHO Grade IV), and a better clinical prognosis, however, accurate discrimination of overall survival (OS) remains a challenge. In this study, we aimed to identify tissue-derived image features using a machine learning approach to predict OS in a mixed histology and grade cohort of lower grade glioma patients. To achieve this aim, we used H and E stained slides from the public LGG cohort of The Cancer Genome Atlas (TCGA) to create a machine learned dictionary of “image-derived visual words” associated with OS. We then evaluated the combined efficacy of using these visual words in predicting short versus long OS by training a generalized machine learning model. Finally, we mapped these predictive visual words back to molecular signaling cascades to infer potential drivers of the machine learned survival-associated phenotypes. Methods: We analyzed digitized histological sections downloaded from the LGG cohort of TCGA using a bag-of-words approach. This method identified a diverse set of histological patterns that were further correlated with OS, histology, and molecular signaling activity using Cox regression, analysis of variance, and Spearman correlation, respectively. A support vector machine (SVM) model was constructed to discriminate patients into short and long OS groups dichotomized at 24-month. Results: This method identified disease-relevant phenotypes associated with OS, some of which are correlated with disease-associated molecular pathways. From these image-derived phenotypes, a generalized SVM model which could discriminate 24-month OS (area under the curve, 0.76) was obtained. Conclusion: Here, we demonstrated one potential strategy to incorporate image features derived from H and E stained slides into predictive models of OS. In addition, we showed how these image-derived phenotypic characteristics correlate with molecular signaling activity underlying the etiology or behavior of LGG.
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Symposium: Summary of the 4th nordic symposium on digital pathology
Claes Lundström, Marie Waltersson, Anders Persson, Darren Treanor
J Pathol Inform 2017, 8:8 (10 March 2017)
DOI:10.4103/jpi.jpi_5_17  PMID:28382222
The Nordic symposium on digital pathology (NDP) was created to promote knowledge exchange across stakeholders in health care, industry, and academia. In 2016, the 4th NDP installment took place in Linköping, Sweden, promoting development and collaboration in digital pathology for the benefit of routine care advances. This article summarizes the symposium, gathering 170 attendees from 13 countries. This summary also contains results from a survey on integrated diagnostics aspects, in particular radiology-pathology collaboration.
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Technical Note: Open-source software for demand forecasting of clinical laboratory test volumes using time-series analysis
Emad A Mohammed, Christopher Naugler
J Pathol Inform 2017, 8:7 (28 February 2017)
DOI:10.4103/jpi.jpi_65_16  PMID:28400996
Background: Demand forecasting is the area of predictive analytics devoted to predicting future volumes of services or consumables. Fair understanding and estimation of how demand will vary facilitates the optimal utilization of resources. In a medical laboratory, accurate forecasting of future demand, that is, test volumes, can increase efficiency and facilitate long-term laboratory planning. Importantly, in an era of utilization management initiatives, accurately predicted volumes compared to the realized test volumes can form a precise way to evaluate utilization management initiatives. Laboratory test volumes are often highly amenable to forecasting by time-series models; however, the statistical software needed to do this is generally either expensive or highly technical. Method: In this paper, we describe an open-source web-based software tool for time-series forecasting and explain how to use it as a demand forecasting tool in clinical laboratories to estimate test volumes. Results: This tool has three different models, that is, Holt-Winters multiplicative, Holt-Winters additive, and simple linear regression. Moreover, these models are ranked and the best one is highlighted. Conclusion: This tool will allow anyone with historic test volume data to model future demand.
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Original Article: WhatsApp for teaching pathology postgraduates: a pilot study
Aditi Goyal, Nadeem Tanveer, Pooja Sharma
J Pathol Inform 2017, 8:6 (28 February 2017)
DOI:10.4103/2153-3539.201111  PMID:28400995
Introduction: Postgraduate students spend a sizeable proportion of their time on social media platforms such as WhatsApp and Facebook. This change in our social interaction needs to be accommodated in our teaching methods. To engage them and arouse their curiosity, WhatsApp is an ideal platform. Digital photography by cell phone cameras has made it possible to share cases and discuss them with students round the clock. Objective: The primary aim of the study was to develop sharing and discussion of images using WhatsApp. It also aimed at gathering feedback by means of a questionnaire from pathology residents about their views about the use of WhatsApp for teaching purpose. Materials and Methods: A WhatsApp group by the name “Pathology on the Go” was created with the authors of this study as group administrators and all junior and senior resident doctors (69) as members. The group was used to discuss interesting cases, quiz questions, and other pathology-related academic issues. At the end of 4 weeks, a questionnaire was distributed among the members, and feedback was sought regarding their experience in the group. Results: Over a 4-week period, 16 cases were discussed with 647 posts. A total of 45 participants out of 69 were active participants, and they had an average of 14 posts over the 4-week period. Majority of the participants found the discussions very useful with minimal disruption of the daily routine. Conclusion: There is a need to incorporate Web 2.0 tools such as WhatsApp in our teaching methods to capture as much screen time of the students as possible.
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Research Article: Pathological diagnosis of gastric cancers with a novel computerized analysis system
Kosuke Oikawa, Akira Saito, Tomoharu Kiyuna, Hans Peter Graf, Eric Cosatto, Masahiko Kuroda
J Pathol Inform 2017, 8:5 (28 February 2017)
DOI:10.4103/2153-3539.201114  PMID:28400994
Background: Recent studies of molecular biology have provided great advances for diagnostic molecular pathology. Automated diagnostic systems with computerized scanning for sampled cells in fluids or smears are now widely utilized. Automated analysis of tissue sections is, however, very difficult because they exhibit a complex mixture of overlapping malignant tumor cells, benign host-derived cells, and extracellular materials. Thus, traditional histological diagnosis is still the most powerful method for diagnosis of diseases. Methods: We have developed a novel computer-assisted pathology system for rapid, automated histological analysis of hematoxylin and eosin (H and E)-stained sections. It is a multistage recognition system patterned after methods that human pathologists use for diagnosis but harnessing machine learning and image analysis. The system first analyzes an entire H and E-stained section (tissue) at low resolution to search suspicious areas for cancer and then the selected areas are analyzed at high resolution to confirm the initial suspicion. Results: After training the pathology system with gastric tissues samples, we examined its performance using other 1905 gastric tissues. The system's accuracy in detecting malignancies was shown to be almost equal to that of conventional diagnosis by expert pathologists. Conclusions: Our novel computerized analysis system provides a support for histological diagnosis, which is useful for screening and quality control. We consider that it could be extended to be applicable to many other carcinomas after learning normal and malignant forms of various tissues. Furthermore, we expect it to contribute to the development of more objective grading systems, immunohistochemical staining systems, and fluorescent-stained image analysis systems.
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Original Article: Criteria to screen molecular tests for the diagnosis of herpes simplex virus in the central nervous system have no propensity to harm
Ronald George Hauser, Cynthia A Brandt, Richard A Martinello
J Pathol Inform 2017, 8:4 (28 February 2017)
DOI:10.4103/2153-3539.201113  PMID:28400993
Objectives: Investigators have ruled out herpes simplex virus (HSV) infection without the detection of herpes simplex deoxyribonucleic acid in cerebrospinal fluid (CSF) (i.e., HSV polymerase chain reaction [PCR]) by laboratory (normal CSF white blood cell count and protein) and clinical criteria (age ≥2 years, no history of human immunodeficiency virus or solid-organ transplant). Compared to HSV PCR of all samples, the algorithm saves money in test costs and may decrease exposure to acyclovir by illustrating the low probability that the patient has HSV. Concern exists that algorithm use may cause harm through alteration of empiric acyclovir treatment in patients with true HSV central nervous system infection. Methods: All Department of Veterans Affair's patients with a positive HSV PCR of the CSF between 2000 and 2013 were identified and their medical records reviewed to determine the extent and possible impact of omitted HSV PCR testing by the algorithm. Results: Of 6357 total results, 101 patients had a positive CSF HSV PCR in the study period. Among the positive CSF HSV PCR results, the algorithm excluded 7 (7%) from PCR testing. Record review indicated these seven patients not tested by the algorithm with a positive CSF HSV PCR were considered by their attending physician not to have active HSV. Conclusion: The algorithm to screen HSV tests had no propensity to harm.
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Technical Note: Implementation of a software application for presurgical case history review of frozen section pathology cases
Andrew P Norgan, Mathew L Okeson, Justin E Juskewitch, Kabeer K Shah, William R Sukov
J Pathol Inform 2017, 8:3 (28 February 2017)
DOI:10.4103/2153-3539.201112  PMID:28400992
Background: The frozen section pathology practice at Mayo Clinic in Rochester performs ~20,000 intraoperative consultations a year (~70–80/weekday). To prepare for intraoperative consultations, surgical pathology fellows and residents review the case history, previous pathology, and relevant imaging the day before surgery. Before the work described herein, review of pending surgical pathology cases was a paper-based process requiring handwritten transcription from the electronic health record, a laborious and potentially error prone process. Methods: To facilitate more efficient case review, a modular extension of an existing surgical listing software application (Surgical and Procedure Scheduling [SPS]) was developed. The module (SPS-pathology-specific module [PM]) added pathology-specific functionality including recording case notes, prefetching of radiology, pathology, and operative reports from the medical record, flagging infectious cases, and real-time tracking of cases in the operating room. After implementation, users were surveyed about its impact on the surgical pathology practice. Results: There were 16 survey respondents (five staff pathologists and eleven residents or fellows). All trainees (11/11) responded that the application improved an aspect of surgical list review including abstraction from medical records (10/11), identification of possibly infectious cases (7/11), and speed of list preparation (10/11). The average reported time savings in list preparation was 1.4 h/day. Respondents indicated the application improved the speed (11/16), clarity (13/16), and accuracy (10/16) of morning report. During the workday, respondents reported the application improved real-time case review (14/16) and situational awareness of ongoing cases (13/16). Conclusions: A majority of respondents found the SPS-PM improved all preparatory and logistical aspects of the Mayo Clinic frozen section surgical pathology practice. In addition, use of the SPS-PM saved an average of 1.4 h/day for residents and fellows engaged in preparatory case review.
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Editorial: Computer science, biology and biomedical informatics academy: outcomes from 5 years of immersing high-school students into informatics research
Andrew J King, Arielle M Fisher, Michael J Becich, David N Boone
J Pathol Inform 2017, 8:2 (28 February 2017)
DOI:10.4103/2153-3539.201110  PMID:28400991
The University of Pittsburgh's Department of Biomedical Informatics and Division of Pathology Informatics created a Science, Technology, Engineering, and Mathematics (STEM) pipeline in 2011 dedicated to providing cutting-edge informatics research and career preparatory experiences to a diverse group of highly motivated high-school students. In this third editorial installment describing the program, we provide a brief overview of the pipeline, report on achievements of the past scholars, and present results from self-reported assessments by the 2015 cohort of scholars. The pipeline continues to expand with the 2015 addition of the innovation internship, and the introduction of a program in 2016 aimed at offering first-time research experiences to undergraduates who are underrepresented in pathology and biomedical informatics. Achievements of program scholars include authorship of journal articles, symposium and summit presentations, and attendance at top 25 universities. All of our alumni matriculated into higher education and 90% remain in STEM majors. The 2015 high-school program had ten participating scholars who self-reported gains in confidence in their research abilities and understanding of what it means to be a scientist.
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Original Article: Classifications of multispectral colorectal cancer tissues using convolution neural network Highly accessed article
Hawraa Haj-Hassan, Ahmad Chaddad, Youssef Harkouss, Christian Desrosiers, Matthew Toews, Camel Tanougast
J Pathol Inform 2017, 8:1 (28 February 2017)
DOI:10.4103/jpi.jpi_47_16  PMID:28400990
Background: Colorectal cancer (CRC) is the third most common cancer among men and women. Its diagnosis in early stages, typically done through the analysis of colon biopsy images, can greatly improve the chances of a successful treatment. This paper proposes to use convolution neural networks (CNNs) to predict three tissue types related to the progression of CRC: benign hyperplasia (BH), intraepithelial neoplasia (IN), and carcinoma (Ca). Methods: Multispectral biopsy images of thirty CRC patients were retrospectively analyzed. Images of tissue samples were divided into three groups, based on their type (10 BH, 10 IN, and 10 Ca). An active contour model was used to segment image regions containing pathological tissues. Tissue samples were classified using a CNN containing convolution, max-pooling, and fully-connected layers. Available tissue samples were split into a training set, for learning the CNN parameters, and test set, for evaluating its performance. Results: An accuracy of 99.17% was obtained from segmented image regions, outperforming existing approaches based on traditional feature extraction, and classification techniques. Conclusions: Experimental results demonstrate the effectiveness of CNN for the classification of CRC tissue types, in particular when using presegmented regions of interest.
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