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J Pathol Inform
Editor-in-Chief:
Anil V. Parwani ,
Liron Pantanowitz,
Pittsburgh, PA, USA
Pittsburgh, PA, USA
OPEN ACCESS
HTML format
For entire Editorial Board visit : www.jpathinformatics.org/editorialboard.asp
SHORT ABSTRACT PRESENTATIONS
Wednesday, May 14, 2014
Locations: Wyndham Grand Pittsburgh Hotel, Grand Ballroom 1, Kings Garden South/
LeBateau, Kings Garden North
Advanced Pathology Informatics
Grand Ballroom 1
Mongo on FHIR - A Governable
Linked-Data Approach to
HL7-Based Interoperability for
Web Computing
Jonas S. Almeida, Alexander Grüneberg
Department of Pathology, Division of Informatics University of Alabama at
Birmingham. E-mail: jalmeida@uab.edu
CONTENT
HL7 has recently developed the Fast Health
Interoperable Resources specification (FHIR www.hl7.
org/fhir) of the application programming interface (API)
for interoperability with modern web computing (HTTP
REST interface for CRUD operations). This development
creates a framework to approach HL7 data streams
as open linked data, using the JSON-LD formalism
recently established by W3C (www.w3.org/TR/json-ld).
This new level of syntactic interoperability proposed
by HL7 is unprecedented for patient data. However, by
itself, this would lead to an absence of governance that
would also be unprecedented for this type of data. We
have approached this implicit requirement for a portable
(data-embedded) governance by extending the JSON-LD
formalism to include user operators.
TECHNOLOGY
JSON-LD stands for Javascript Object Notation (JSON)
for the Semantic Web’s Linked Data (LD) framework.
The critical advantage is that it allows the use of the
rich toolbox of Web 3.0 technologies developed around
W3C’s Resource Description Framework (RDF), which
underlies the Web’s evolution towards effectively being a
global Data Space.
DESIGN
Web technologies have now reached the point where
the regular web browser has become a full-stack software
development platform. The development of FHIR
by HL7 was the missing component to enable web
computing approaches to patient derived data streams in
clinical environments.
RESULTS
The goal of embedding the governance of CRUD
operations in JSON-LD formatted HL7 data streams
was pursued, and achieved, without any redesign of
the data itself, or the FIHR itself. We have validated
this web computing for Health Informatics proposition
with the development of a web service using only
open source libraries. Specifically, the REST middle
layer was developed in NodeJS, articulating a Big Data
backend (NoSQL + MapReduce distribution) using
MongoDB. A client-side JavaScript library to facilitate
the development of web application was also developed.
The open source library and a demonstration deployment
with data about the 7,000+ patients described by The
Cancer Genome Atlas (TCGA) are maintained at https://
github.com/ibl/fhir.
CONCLUSION
HL7 Fast Health Interoperable Resources specification
(FHIR) was found to deliver exactly what it was set out
to do: a Web friendly programmatic interface for CRUD
operations. This narrow configuration of FHIR API caused
governance of those data streams to be defined as an
entirely orthogonal pursuit. This created the opportunity,
explored in the data modeling work described here, to
embed governance within the data in a manner that does
not intrude into the representation itself. The tools to
achieve this goal have only emerged recently, and are found
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J Pathol Inform 2014 - Abstracthttp://www.jpathinformatics.org
within the third generation of Web Technologies (Web
3.0 - Semantic Web). Specifically, the Linked Data approach
to W3C’s Resource Description Framework (RDF) now
has a native representation as JSON-LD. The novel, nonintrusive, governance modeling described in this report was
validated with an open source prototype and a public web
service accompanying this report (see Results for address).
Finally, a bi-directional HL7 interface was implemented
which allowed status messages to be communicated from
the IHC AIPs back to our AP-LIS. We then implemented
the same interface between our AP-LIS the automated
special stains platforms.
Automating Anatomic Pathology
Stain Orders in Histology
The first phase simplified the staining run’s setup
process, while the second phase eliminated the slide
relabeling. Currently, the Dako AIPs operate by scanning
CoPath labels directly. By automating these processes,
time savings of approximately 56 minutes (IHC) and
7.75 minutes (special stains) per run have been achieved.
Total annual labor savings are estimated to be 570 hours
for IHC and 100.75 hours for special stains workflows.
Robert Stapp, Michael Czechowski,
Kathy Roszka, J. Mark Tuthill
Department of Pathology, Henry Ford Hospital, Detroit, MI.
E-mail: rstapp1@hfhs.org
CONTENT
Immunoperoxidase and special tissue stains are important
routine aspects of pathology practice, with automated
instrument platforms (AIPs) available to perform these
assays. Orders in the anatomic pathology laboratory
information system (AP-LIS), should be able to interface
to these AIPs. Our goal was to eliminate dual order entry
and reduce the tissue misidentification due to relabeling
slides. We partnered with our vendors to implement bidirectional Health Level 7 (HL7) interfaces between our
AP-LIS and AIP’s for immunohistochemistry (IHC) and
special staining platforms.
TECHNOLOGY
RESULTS
CONCLUSION
Elimination of dual order entry and relabeling has
markedly decreased our assay run times. The potential for
patient misidentification has been significantly reduced.
In addition, automating these processes has increased
stain order accuracy, improved laboratory throughput,
and improved turnaround times.
KRAS Mutations in Pancreatic
Adenocarcinoma: Caveats
for Data Mining in Cancer
Genomics
CoPath Plus v6.0 was used as the AP-LIS (Sunquest
Information Systems, Tuscon, AZ). Three AutoLink 48
automatic IHC stainers, two Artisan Link Pro automated
special stains platforms, and one DakoLink interface
server, were utilized (Dako, Denmark).
Edward Stites, David H. Spencer,
Eric J. Duncavage, Ian S. Hagemann
DESIGN
CONTENT
Initially, a unidirectional HL7 interface was implemented
between CoPath and DakoLink. This allowed IHC orders
placed in the AP-LIS to be received into the DakoLink
instrument control software which sends electronic orders
the IHC platforms.
An effort to determine the observed frequency of KRAS
mutations within our clinical next-generation sequencing
experience identified several potential issues in mining
clinical cancer genomic data.
Secondly, Copath was upgraded to a new version which
provided the capability to assign pathology assets a
unique identifier. This allowed our AP-LIS to send
unique slide identifiers to the IHC platforms. Once
implemented, the IHC AIPs could utilize native CoPath
labels, eliminating slide relabeling.
TECHNOLOGY
S2
Department of Pathology and Immunology, Washington University School of
Medicine, St. Louis, MO. E-mail: estites@path.wustl.edu
Targeted sequencing of all exons of KRAS was performed
as part of a multi-gene assay using DNA extracted from
formalin-fixed, paraffin-embedded tumor tissue. Agilent
SureSelect hybrid capture was followed by Illumina
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J Pathol Inform 2014 - Abstracthttp://www.jpathinformatics.org
HiSeq or MiSeq sequencing. Single-nucleotide variants
and insertion/deletion events were called by a custom
bioinformatics pipeline based in the Genome Analysis
Toolkit, with a variant allele frequency greater than 10%
required for automated mutation reporting.
DESIGN
A database of clinical cancer genome sequencing results
was queried to retrieve cases of pancreatic cancer and
their bioinformatically called KRAS genotypes. Chart
reviews were then performed on all patients that satisfied
the initial query to confirm the diagnoses and reported
KRAS mutation status.
RESULTS
Among 857 total patients, a naïve search identified
65 patients with pancreatic cancer, 39 of whom (60%)
had a KRAS mutation. Examination of the electronic
medical record revealed 11 of these patients had a
diagnosis other than pancreatic adenocarcinoma. Review
of clinical genomics reports identified 6 cases where the
pathologist identified and reported a KRAS mutation that
did not meet thresholds for automated mutation calling.
This revised search therefore identified 54 patients with
pancreatic cancer in the database, 42 of whom (78%) had
KRAS mutations.
CONCLUSIONS
Our analysis highlights that caution must be used when
querying clinical cancer genomic data. False positives
and false negatives complicate the ability for clinical
summary statistics to contribute to quality control and
quality assurance. The “big data” movement claims that
statisticians and informaticians can make important
insights without understanding the underlying biology or
medicine. Our work suggests that content-area knowledge
is needed to execute maximally informative queries and
recognize the limitations of data mining.
Adaptive Learning Based Data
Extraction for Patient Search
from Pathology Reports
Shuai Zheng', James J. Lu,1 Daniel J. Brat,
Fusheng Wang
Department of Mathematics and Computer Science, 2Department of Pathology and
Laboratory Medicine, 3Department of Biomedical Informatics, Emory University,
Atlanta, GA. E-mail: szheng5@emory.edu
1
CONTENT
Extracting information from pathology reports, which
usually contains both free-text and semi structured
data, can improve the utility of the information to
both human researchers and computing systems. The
extracted information, when appropriately restructured
and organized, enables complex and interesting queries
such as, find all patients that have certain diagnosis
and been treated with a specific therapy within a given
period. We have developed an interactive, adaptive
learning based information extraction system that,
compared to existing techniques, greatly simplifies the
identification, extraction and structuring of information
in pathology reports.
TECHNOLOGY
ASLForm supports convenient transformation of
information in free-text reports. The workflow
follows
the
conventional
process
of
manual
annotation and extraction. It addition, through user
interaction monitoring, ASLForm transparently and
incrementally learns key data element contexts to
improve its ability to automatically identify pertinent
information in subsequent reports. ASLForm employs
OpenNLP for basic natural language processing tasks,
and implements an adaptive learning model based on
Hidden Markov model (HMM).
DESIGN
ASLForm consists of three components. The
preprocessing component parses and indexes input
text. The Answer generating component locates target
values to fill the output form. System generated answers
along with user revisions are analyzed by the adaptive
learning component, to incrementally (and often
quickly) improve the precision of the answer generating
component. As the answer identification accuracy
improves, the user’s primary role evolves from annotator
to verifier.
RESULTS
ASLForm supports extraction of the following
information: personal information such as gender and
age, diagnosis, therapy and genetic marker, which
consist of embedded attribute values from both semistructured and unstructured text. Experiments over
50 patient records demonstrate high reliability and
accuracy of ASLForm for pathology reports. For most
attributes, the extraction has yielded a precision rate of
over 90%.
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J Pathol Inform 2014 - Abstracthttp://www.jpathinformatics.org
CONCLUSIONS
Information from pathology reports holds great research
and clinical values. ASLForm provides an effective tool
for making such information available. The usability,
adaptability and accuracy of ASLForm make it a
convenient and powerful tool for extracting information
from diverse pathology reports.
Imaging Informatics
Wednesday, May 14, 2014
Kings Garden South/LeBateau
Automated Detection
and Characterization of
Prostate Cancer-Containing
Tissue Regions Using Slides
Stained with AMACR, HMW
Cytokeratin, and P63
Benjamin Brasseur1, Andrew Johnson2, Jonathan
Henriksen3, Joseph Koopmeiners4, Anthony
Rizzardi3, Gregory Metzger5, Stephen Schmechel3
University of Minnesota, Medical School, Minneapolis, MN, 2Department of
Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN,
3
Department of Pathology, University of Washington, Seattle, WA, 4School of Public
Health, University of Minnesota, Minneapolis, MN, 5Department of Radiology,
University of Minnesota, Minneapolis, MN, USA.
E-mail: bras0072@umn.edu
1
CONTENT
Our laboratories are engaged in improving multi-parametric
magnetic resonance imaging (mpMRI) detection of
prostate cancer (PCa). Central to these efforts is spatial
co-registration of pre-operative mpMRI data with postprostatectomy pathology data (the “gold standard” for PCa
presence in tissue sections). Pathologist manual annotations
is prohibitively time consuming. Further, manual
annotations provide partial data: PCa shows infiltrative
growth such that regions of interest (ROIs) annotated
as “cancer” are composed of admixed malignant and
benign epithelial and stromal elements and gland lumens.
Automated methods are desired to identify PCa-containing
ROIs and assess fractional composition within ROIs.
TECHNOLOGY
We previously reported innovative SigMap software
that aligns serial whole slide images (WSI), and
S4
overlay grids onto WSI images, to develop spatially
arrayed pathology data. We used SigMap and image
analysis software (Aperio ePathology, Leica Biosystems,
Vista, CA, USA) on slides stained with triple antibody
cocktail to a) identify grid ROIs containing PCa and
to b) assess fractional tissue composition within ROIs.
Pathologist manual annotations were benchmarks for
these analyses.
DESIGN
PCa-containing blocks were randomly selected and
randomly-ordered adjacent sections were stained
with H and E or triple antibody cocktail (AMACR in
FastRed,34βE12 and p63 in diaminobenzidine/brown,
and hematoxylin counterstain). Slides were digitized
(ScanScopeXT, Aperio) and tissue areas were annotated
by pathology trainees (BMB/ADJ) and validated by a
pathologist (SCS). SigMap aligned adjacent sections and
generated grids of 0.5 × 0.5 mm for analysis.
RESULTS
Grid ROIs were identified using Color Deconvolution
(Aperio) as PCa-containing or nonPCa-containing with
85% sensitivity and 85% specificity, versus pathologist
manual annotation. Regression modeling revealed good
correlation between computer-assessed composition
within ROIs (%red, %brown, %blue, and %clear) and
manually annotated fractional composition (cancer,
benign epithelium, stroma, and luminal spaces) with
correlations of 0.749, 0.598, 0.603, and 0.511, respectively.
CONCLUSIONS
Software methods can automatically detect PCacontaining ROIs, and assess fractional composition within
ROIs. These methods will be useful for identification and
validation of mpMRI signals useful to assess PCa extent
preoperatively.
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J Pathol Inform 2014 - Abstracthttp://www.jpathinformatics.org
Interface of Biosample Whole
Slide Images with Daedalus’
Biomaterial Tracking and
Management Research Software
(BTM)
into Spectrum. The barcode links the slide image to the
BTM sample family. One can search BTM for sample
families with linked images, or directly check a sample’s
image tab. If a linked image exists, an image thumbnail
appears adjacent to the image URL; clicking on the
thumbnail directs the user to Webscope for viewing. To
date, over 400 slides of banked sample families have been
digitized and linked.
Clara E Magyar1, Juan Sebastian1, Azita Sharif2,
Sarah M Dry1
CONCLUSION
Department of Pathology and Laboratory Medicine, UCLA School of Medicine,
Los Angeles, CA, 2Daedalus, Inc., Cambridge, MA.
E-mail: cmagyar@mednet.ucla.edu
1
CONTENT
The UCLA CAP accredited Institutional Biorepository
uses Daedalus’ BTM for biosample management. Before
releasing banked samples, pathologists review a quality
assurance (QA) slide to verify diagnosis and tumor
content. We created a bidirectional interface between
BTM’s database and Aperio Spectrum (whole slide
image database), to streamline subsequent tissue release
requests and sample selection. This solution makes digital
pathology a rich annotation for an integrated content
approach for UCLA Biobanking/biomedical research.
TECHNOLOGY
Whole slide scanner: Aperio AT (Leica Biosystems,
Buffalo Grove, IL) Biobanking database: BTM (Daedalus
Software Inc., Cambridge, MA).
DESIGN
We wanted to add rich content (scalable to millions
of large pathology images) without affecting responsetime and storage requirements. We accomplished this
by adding another architectural tier. Rather than moving
numerous bits around the network on every click, we
show thumbnails of large images for each sample. Only
on specific requests from the users do we fetch the entire
image which opens in Aperio’s web browser, Webscope.
Adding another architectural tier introduces an identity
problem among related entities (Bank Samples and their
Pathology Images). We addressed this by using an identity
hash-code. This solution works on SOAP protocol for webbased services. For performance enhancement, we wrote
proprietary user-authenticators and SOAP response parsers.
RESULTS
Integration was finalized January 2013. QA slides are
labeled with the Daedalus Matrix barcode and scanned
We created a seamless, bidirectional interface of our
biorepository sample tracking system (BTM) with our
whole slide image database (Spectrum) creating a more
efficient and rich annotation system when searching
for and releasing specimens. This facilitates researcher
selection of samples and improves efficiency of QA
review as consulting pathologists view digital images on
demand.
Automated Identification
of Glomeruli in Volumetric
Multiphoton Images Using
Texture Features
Eben Olson, Richard Torres
Department of Laboratory Medicine,Yale University School of Medicine,
New Haven, CT. E-mail: olson@yale.edu
CONTENT
Optical tissue clearing allows large volumes of tissue
to be imaged in three dimensions with subcellular
resolution. While additional qualitative and quantitative
morphometric information is made available by the use
of these techniques, the size of the resulting data sets
make manual analysis more difficult or, in some cases,
infeasible. An example of some research and clinical
importance is identification, counting, and volumetric
measurement of glomeruli in kidney samples. We report
the development of an automated method for glomerular
detection in volumetric multiphoton images of mouse
kidney employing frequency-based texture segmentation
algorithms.
TECHNOLOGY
A custom built multiphoton microscope was used in
conjunction with optical tissue clearing to image millimeterthick sections of mouse kidney tissue stained with protein
dye. Images were segmented using several texture feature
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J Pathol Inform 2014 - Abstracthttp://www.jpathinformatics.org
analysis techniques including binary Gabor patterns with
a random forest classifier. Additional gradient-based and
morphometric analysis was used to refine the results of this
segmentation. The software was built using open-source
libraries and custom code written in Python.
DESIGN
A dataset consisting of 71 stacks of 300 images covering
a total volume of approximately 9 mm^3 was analyzed.
A subset of 100 randomly selected images were hand
labeled for classifier training and testing. An additional
15 randomly selected sub-volumes of 100 images were
manually segmented and used as the basis for validation
testing. The full dataset was then automatically
segmented by the newly developed software. An
overlap of greater than 50% of the glomerular volume
between manually determined region and automated
segmentation was counted as adequate detection.
RESULTS
Binary Gabor pattern-based texture segmentation was
successfully applied to histologic image analysis on large
three-dimensional data sets. Automated analysis achieved
high accuracy, correctly detecting 163/174 glomeruli
(sensitivity = 94%), while maintaining a small false
discovery rate (10/173).
CONCLUSIONS
Machine learning of texture features provides a valuable
tool for segmentation and preliminary analysis of
large volumetric data sets. Binary Gabor pattern-based
analysis is a robust approach for segmentation that is
not dependent on color thresholding. Our automated
image processing system can effectively identify regions
containing glomeruli, allowing the extraction of volumes
of interest for further analysis.
A MapReduce Based High
Performance Whole Slide Image
Analysis Framework in the
Cloud
Hoang Vo1, Dejun Teng1, Yanhui Liang2,
Ablimit Aji1, Jun Kong2, Fusheng Wang2,
Department of Mathematics and Computer Science, Emory University, Atlanta, GA,
Department of Biomedical Informatics, Emory University, Atlanta, GA.
E-mail: hoang.vo@emory.edu
1
2
S6
CONTENT
Systematic analysis of high resolution whole slide images
has many potential applications to support biomedical
research and disease diagnosis. Due to the enormous
size and dimensions of whole slide images, traditional
image analysis techniques cannot be performed directly
due to memory limitation and extremely long execution
time for each image. In-house computing infrastructures
often have limited computing capacity to process large
batches of such images. We develop a scalable and
cost effective MapReduce based high performance
image analysis framework for massive whole slide image
processing in the cloud by integrating image analysis
algorithms and spatial queries. The framework is
general and can be adapted to different image analysis
algorithms.
TECHNOLOGY
We develop a MapReduce-based framework by adapting
image analysis algorithms into MapReduce based
processing pipelines running on commodity clusters and
Amazon Elastic MapReduce (EMR), where image tiles
are stored in distributed file systems (Hadoop Distributed
File System and Amazon S3 respectively). Tile based
parallelization is performed where task management and
load balancing is automated by MapReduce. We use a
cloud based spatial querying engine Hadoop-GIS to amend
the problem of boundary objects due to partitioning and
integrate it into the image processing pipeline.
DESIGN
Tiles are extracted from whole slide images using a
grid based overlapping partitioning scheme. Each data
file consisting of single tile is supplied to a “map”
function, where they are processed producing segmented
boundaries. Segmented boundaries are further processed
in a “reduce” function which provides geometry correction
and duplicate elimination. File results are aggregated and
stored in the distributed file system.
RESULTS
We have performed an experiment for nuclei
segmentation from a dataset of 500 whole slide pathology
images using Amazon Elastic MapReduce (EMR). The
framework achieves an almost perfectly linear scalability.
In addition, the duplicate elimination step handling
objects spanning tile boundaries takes a very small
portion of execution time, indicating an insignificant
overhead for producing sound results.
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CONCLUSIONS
Our experiments have demonstrated a very effective,
scalable and cost effective framework for pathology
image analysis. The framework can handle cases of
objects spanning multiple boundaries, while incurring a
small addition execution time overhead. Furthermore,
the post-processing function can be effortlessly
extended to perform addition image analysis and
result validation. The framework is highly adaptive for
different image segmentation and feature extraction
algorithms.
Applied Pathology Informatics
Wednesday, May 14, 2014
Kings Garden North
Alchemy: A Web 2.0 Real-Time
Quality Assurance Platform
for Human Immunodeficiency
Virus and Hepatitis C Virus
Quantitation Tests
Human Immunodeficiency Virus (HIV) and Hepatitis
C Virus (HCV) quantitation tests. Alchemy was fed
with data autogenerated monthly as comma-separated
value (CSV) files from the clinical pathology laboratory
information system. Alchemy calculates key QA
statistics in real time, including average TAT in days,
tests falling outside expected TAT ranges, and test
result ranges.
Emmanuel Agosto-Arroyo, Gina M. Coshatt,
Seung Lyung Park
RESULTS
Department of Pathology, University of Alabama at Birmingham, Birmingham AL.
E-mail: eagosto@uab.edu
CONTENT
Quality assurance (QA) is integral to a well-run molecular
diagnostics laboratory. QA statistical calculations are
usually manual, time consuming, and often error-prone.
The aim of this project was to develop a web-based realtime QA platform that would (a) Aautomate quality
control reporting at the molecular diagnostics laboratory
of the University of Alabama at Birmingham, and (b)
minimize the time expended in preparing these reports.
Before Alchemy, reporting QA for the HIV and HCV
quantitation tests took 45-60 minutes of personnel time
per test per month. With Alchemy, that has shrunk to
15 minutes total per month.
CONCLUSIONS
Alchemy has significantly decreased the time and the
human error associated with QA report generation
in our molecular diagnostics lab. Other tests will be
added in future updates. This effort shows the utility
of informaticist-supervised resident/fellow programming
projects as learning opportunities and workflow
improvements.
TECHNOLOGY
A Dell Precision T3600 (Intel Xeon E5-1603 @ 2.8 GHz;
16GB DDR3 SDRAM; 256GB SSD; 1TB HDD; Microsoft
Windows 7 × 64) was used to host a standard LEMP
(Ubuntu Linux Server 12.04 LTS; ngin×1.5.6; MariaDB
5.5.32; PHP 5.4) stack virtual machine on Oracle VM
Virtualbox virtualization software.
A Real-time Web 2.0
Antibiogram System for
the Clinical Microbiology
Laboratory
DESIGN
Matthew Cain1, Stephen Moser2, Seung Park3
Using the LEMP stack, we designed, built, and deployed
a QA platform code-named “Alchemy”, targeting our
University of Alabama at Birmingham, 1Department of Pathology, 2Department
of Pathology, Division of Microbiology, 3Department of Pathology, Division of
Informatics, Birmingham, AL. E-mail: mdcain@uabmc.edu
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J Pathol Inform 2014 - Abstracthttp://www.jpathinformatics.org
CONTENT
Committees composed of microbiologist, pharmacists,
and Infectious Disease clinicians, serve an important
role in efficacious antimicrobial therapy. Currently,
our institution releases annual antibiograms detailing
summary antibiotic susceptibility data. Prior to this
project, a tab-separated value (TSV) file was generated
by the electronic medical record system, which was then
imported into Microsoft Access for further manipulation
and data harmonization. In this project, we sought to
automate this process as well as provide an efficient
means for clinicians to see real-time data regarding
antibiotic susceptibilities.
TECHNOLOGY
Server Hardware: Dell Precision T3600; Host
Virtualization Hypervisor: VMWare ESXi 4.1.0; Guest
Operating System: Ubuntu Linux Server 12.04 LTS
64-bit; Web Server: nginx 1.5; Database Management
System: MariaDB 5.5; Programming Language: PHPFPM 5.3; User Interface Framework: Twitter Bootstrap
2.3.
DESIGN
The TSV files were structurally analyzed. Tables for
patient information, antibiotics, bacteria, bacterial source,
and observations were created in MariaDB. A complete
web application was written in PHP-FPM, its relational
database connector (mysqli), and Twitter Bootstrap
with the following functionality: (1) One-click upload of
new monthly data, complete with automated detection
and removal of duplicate/extraneous data; (2) dynamic
generation of monthly reports; (3) real-time database
search [Figure 1].
RESULTS
Development of an upload system that parses and
prepares data reduces the microbiologist workload by
approximately 16 hours annually. Furthermore, the
database represents real-time susceptibilities with easy
access. Previously, antibiograms were released annually
and only contained the number of isolates and the
percent susceptibility on a given bacteria-antibiotic pair.
Our database not only supplies up-to-date information,
but provides the ability to search by bacterial source and
hospital location.
CONCLUSIONS
We successfully developed software that reduces the
time to develop conventional antibiograms, provides
real-time data, and easy accessibility to highly detailed
susceptibility statistics. The system parses and processes
text files exported in Health Level 7 (HL7) format.
Hospitals commonly use this format; therefore, this
program could be used in other institutions with minor
adjustments. Future goals include the incorporation of
advanced statistics, such as cluster analysis to identify
resistances in specific hospital units, as well as panels
focused to specific patient populations.
Figure 1: Design, implementation, and go-live phases of this project. Important milestones indicated
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J Pathol Inform 2014 - Abstracthttp://www.jpathinformatics.org
Development of an Informatics
Tracking Solution to Enhance
Flow Cytometric Specimen
Processing
Raymond E Felgar1 Christine G Roth2, Anthony
L Piccoli2, Karen L Freilino2, Kevin J Nauman2,
Ralph A Nauman2, Michael Fitzgerald2, Liron
Pantanowitz2, Anil V Parwani2, Steven H
Swerdlow2
University of Pittsburgh Medical Center, Department of Pathology, Division
of Hematopathology, Pittsburgh, PA 2University of Pittsburgh Medical Center,
Department of Pathology, Pittsburgh, PA. E-mail: felgarre@upmc.edu
1
CONTENT
Tracking of specimen status in high volume flow
cytometric laboratories can be problematic. Laboratory
efficiency may be reduced if this hampers determination
of panel choice, sample priority, and estimated time left
to completion of specimens being processed prior to
pathologist staff review and sign-out. Our aim was to
design a tracking system for processing flow cytometry
specimens in a large academic medical center, with use
of pre-existing tools in our anatomic pathology laboratory
information system (AP-LIS), provide realtime display
of case status for technologists and assist with short and
long-term laboratory management issues.
TECHNOLOGY
The anatomic pathology laboratory information system
(AP-LIS; CoPath, Cerner) histology tracking function was
customized to record accessioning, sample type, priority,
staining, acquisition, and completion of analysis steps for
flow cytometry specimens. A tracking report was designed
to allow for real-time assessment of specimen status
within the lab on large screen monitors in the laboratory
and updated in real-time by employing dedicated
computers and System Scheduler software (Splinterware
Software Solutions).
Figure 1a: Screenshot of the flow cytometry color coded tracking monitor
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J Pathol Inform 2014 - Abstracthttp://www.jpathinformatics.org
Figure 1b: Sample off-line procedure tracking log report
DESIGN
Flow panel choices, coupled to technical billing for markers,
were captured using the LIS stain ordering function.
Tracking log report(s) also allow end users to determine
the current stage of processing of a particular specimen in
question or for a range of specimens, including completed
cases (based on accession date, for example).
RESULTS
The tracking report successfully displayed the dynamic
status of all flow cytometry procedures and markers being
tested [Figure 1a]. The display included color- coding by
status. The report was also available on demand in the LIS
to pathologists and technical staff. Tracking log reports
[Figure 1b] allow one to track both pending and completed
work and can also serve as a data reservoir for functions
such as turn-around-times for specific steps in specimen
processing; this can also facilitate work-flow analysis.
CONCLUSION
Real-time tracking of flow cytometric specimen processing
and analysis status can be performed using existing APS10
LIS functions. This tracking tool allows technical and
supervisory staff to readily monitor laboratory workflow.
The tracking data collected also allows for subsequent
workflow analyses.
The Ongoing Evolution of the
Core Curriculum of a Clinical
Pathology Informatics Fellowship
Andrew M. Quinn1, John R. Gilbertson2
Departments of Pathology, 1Brigham and Women’s Hospital, Boston, MA,
2
Massachusetts General Hospital, Boston, MA.
E-mail: aquinn3@partners.org
CONTENT
The Partners Healthcare System’s Clinical Fellowship in
Pathology Informatics (Boston, MA, USA) faces ongoing
challenges to the delivery of its core curriculum in the
form of a new class of fellows with new and varying
educational needs and increasingly fractured, enterprisewide commitments; taxing electronic health record and
laboratory information system implementations; and
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Figure 1: Approaches to delivering the core curriculum of a pathology informatics fellowship. IS – Information systems. EHR – Electronic
health record, LIS – Laboratory information system, AMC – Academic medical center
increasing interest in the subspecialty at the academic
medical centers in the network.
TECHNOLOGY
(There is no relevant technology to discuss.).
DESIGN
In response, the fellowship has piloted a networkwide pathology informatics lecture series and regular
learning laboratories, as well as a modification of the
existing didactic sessions [Figure 1]. Lectures are given
by the informatics faculty, current and former fellows
and information systems members in the network, and
are open to all professional members of the pathology
departments at the academic medical centers. Learning
laboratories consist of small-group exercises geared
toward a variety of learning styles and are driven by
both the fellows and a member of the informatics
faculty. These learning laboratories have also created a
forum for discussing real-time and real-world pathology
informatics matters, and incorporating awareness of
and timely discussions about the latest pathology
informatics literature. Didactic sessions now focus on
group discussions of fellows’ ongoing projects as well as
updates on the enterprise-wide electronic health record
and laboratory information system implementations
and directed questions about weekly readings, whereas
they had previously included more formal discussions of
the four objectives of the core curriculum: information
fundamentals, information systems, workflow and
process, and governance and management.
RESULTS
These changes have diversified the delivery of the
fellowship’s core curriculum, increased exposure of
faculty, fellows and trainees to one another, and better
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J Pathol Inform 2014 - Abstracthttp://www.jpathinformatics.org
distributed teaching responsibilities among the entirety
of the pathology informatics asset in the network.
CONCLUSIONS
Though the above approach has only been in place
S12
for seven months, its characterization herein allows
for continued discussion of evolving educational
opportunities in pathology informatics and medical
informatics in general, and highlights the importance of
having a flexible fellowship with active participation from
its fellows.
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J Pathol Inform
Editor-in-Chief:
Anil V. Parwani ,
Liron Pantanowitz,
Pittsburgh, PA, USA
Pittsburgh, PA, USA
OPEN ACCESS
HTML format
For entire Editorial Board visit : www.jpathinformatics.org/editorialboard.asp
PLATFORM SHORT ABSTRACT PRESENTATIONS
Wednesday, May 14, 2014 (9:00 am - 5:20 pm)
Thursday, May 15, 2014 (9:00 am - Noon)
Location: Wyndham Grand Pittsburgh Hotel, Kings Garden North
Informatics Infrastructure
Requirements for Clinical
Next Generation Sequencing:
Challenges and Solutions
Somak Roy1, Ryan Mitchell2, Gary Burdelski2,
Jeff McHugh2, Shan Zhong1, Kevin Nauman2,
Marina N. Nikiforova1, Yuri E. Nikiforov1,
Anil V. Parwani1, Liron Pantanowitz1
Department of Pathology, 2Information Services Division, University of Pittsburgh
Medical Center. E-mail: roys@upmc.edu
1
CONTENT
Introduction of Next Generation Sequencing (NGS)
in clinical molecular laboratories has unveiled obtrusive
informatics challenges. Successful hardware and software
solutions to support NGS data analysis and storage for
the laboratory need to be scalable, redundant, secure and
support sharing in an enterprise environment of a large
academic center. We present our institution’s experience
in developing an informatics framework to support
clinical NGS testing.
DESIGN
Using high-bandwidth network connections, raw signal
files were moved to the SONAS archives (45TB) whereas
data files starting and downstream to FASTQ files were
stored in the HPES pool (1TB/sequencer). The latter
provided immediate access to FASTQ and other files
for bioinformatics analysis on VMs. Multiple laboratory
staff access VMs using Microsoft Windows native remote
desktop solution and are able to run concurrent resource
intensive NGS data analyses.
RESULTS
This enterprise informatics infrastructure initially provided
highly redundant and secure storage to prevent accidental
loss of clinical test data. However, the off-site location
of raw data slowed data analysis. As a result, VMs were
created to provide direct access to archived data, avoiding
the need for transfer of massive data files over the
network. To optimize NGS analysis time on VMs, input
data for bioinformatics analysis was stored using HPES.
CONCLUSION
Informatics
infrastructure
required
significant
TECHNOLOGY
The clinical molecular laboratory at our institution
houses five NGS sequencers and accompanying vendor
provided high-performance workstation servers with 7 to
10 terabytes of local storage per server. Scale out network
attached storage (SONAS) and high-performance
enterprise storage (HPES) at our institution’s
HIPAA-compliant data center were used for archiving
clinical NGS test data. High-bandwidth network
connections (up to 1GB/s) facilitated data transfer
[Figure 1]. Dynamically scalable Windows-based Virtual
Machines (VM) facilitated data processing virtually and
new algorithm development for NGS molecular testing.
Figure 1
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customization and close collaboration with laboratory
professionals to successfully optimize NGS data analysis
and storage. This highly scalable infrastructure has
facilitated the implementation of HIPAA-compliant
NGS testing in our high volume clinical molecular
laboratory. This framework may provide a model for other
institutions planning to pursue clinical NGS testing.
A Free-Standing Clinical
Laboratory Data Warehouse in
the Era of Enterprise Clinical
and Research Warehouses:
16 Years of Experience,
Future Options, and Strategic
Considerations
Philip J. Boyer1, Bradley B. Brimhall3,
Connie Williamson2, Thurston Matsuura2,
Chad Vanderbilt1, Joan Coleman2,
Ronald Lepoff1
Department of Pathology, University of Colorado School of Medicine and
University of Colorado Hospital, 2Clinical Laboratory, University of Colorado
Hospital, Aurora, CO, 3Department of Pathology, University of Mississippi, Jackson.
E-mail: philip.boyer@ucdenver.edu
1
CONTENT
A clinical laboratory data warehouse (CLDW) was
established over 16 years ago at the University of
Colorado Hospital (UCH). Laboratory Information
system (LIS) data is downloaded to the warehouse daily.
UCH will be transitioning from Cerner Classic to Epic
Beaker in 2015 and the continued need for the CLDW
has been questioned.
TECHNOLOGY
A SQL server database was established with several tables
and over 70 fields (patient demographics, billing, and test
information). As it contains protected health information,
access is strictly limited. Laboratory personnel access data
by either (1) Web page-based SQL queries or (2) request
to an LIS technologist for a complex query.
DESIGN
The cost and utilization of the CLDW is evaluated and
the feasibility of using current and future enterprise
database options for queries is considered.
S14
RESULTS
The initial cost to create the CLDW (hardware, software,
professional time) was approximately $61,000; annual
upkeep costs are less than $20,000. The CLDW is
extensively utilized for both routine and ad hoc queries
including assessment of turn-around time, test utilization,
infectious disease monitoring, quality improvement, and
workflow management. The UCH Epic database contains
over 8 years of test result data; however, LIS test-specific
information is not present. That database will contain
Beaker LIS data beginning in 2015. An enterprise research
data warehouse will go live in 2015; while detailed LIS data
could be incorporated, historic data would likely not be sent.
CONCLUSIONS
The UCH CLDW contains over 1.5 decades of patient and
test-related data. It facilitates routine and ad hoc queries
to meet clinical, operational, financial, and research goals,
justifying the modest development and maintenance
costs. Maintaining the CLDW and interfacing Beaker data
is justified, particularly given (1) the need to accumulate
many months of data prior to meaningful data mining
in one of the enterprise databases and (2) the inherent
value of over 16 years of longitudinal data. Maintaining
the CLDW also presents critical strategic advantages to
the laboratory, particularly during the time of transition to
a new LIS, by allowing laboratory autonomy, with direct
data access, using familiar and time-tested query tools.
“WSI ZoomViewer”: A Vendor
Neutral HTML5 Whole Slide
Image Viewer
Eugene Tseytlin2, Anil V. Parwani1,
William Cable3, Liron Pantanowitz1
1
Department of Pathology, University of Pittsburgh Medical Center, 2Department of
Biomedical Informatics, University of Pittsburgh, 3University of Pittsburgh Medical
Center, Information Services Division, Pittsburgh, PA.
E-mail: tseytlin@pitt.edu
CONTENT
Digital whole slide images (WSI) are being increasingly
used in Pathology for a variety of clinical, education and
research purposes. Unfortunately, unlike other medical
fields such as Radiology, viewing of digital images from
various WSI vendors continues to be a challenge as there
are no standard image formats. Most vendors offer their
own proprietary WSI solutions for various use cases. Their
software is often bundled with WSI scanners, is expensive
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and does not always inter-operate well with other vendors
and image formats. There are currently limited viewer
solutions that can open WSI files from multiple vendors,
such as SlideViewer (http://slidetutor.upmc.edu/viewer)
and OpenSlide (http://openslide.org/). SlideViewer uses
Java technology which requires frequent updates, is no
longer popular for the web front-end applications, and is
not supported by Apple mobile devices. Therefore, our
aim was to develop a new vendor neutral WSI viewer
based on the latest HTML5 technology.
TECHNOLOGY
The WSI viewer was based on the OpenSeadragon
(http://openseadragon.github.io/) HTML5 framework,
which is an open source implementation of Microsoft
DeepZoom technology.
DESIGN
OpenSeadragon allows users to view very large image files
by breaking underlying images into tiles and transmitting
only tiles at an appropriate zoom level and view position
to save on bandwidth. Instead of converting WSI files
to an OpenSeadragon format, the new viewer permits
the application programming interface to interact with a
vendor’s WSI server software natively. This allowed the
new viewer to access remote WSI hosting sites without
the need to install any additional software on servers.
RESULTS
The new HTML5 viewer (“WSI ZoomViewer”) worked
on all modern web browsers and all mobile platforms,
including Apple devices. The current version supports Leica
and Hamamatsu vendors, with the ability to add additional
formats in the future. Additional features that were
developed specifically for our institution’s telepathology
consultation portal were multiple slide support, navigation
panel, orientation specific layout for mobile devices, and
slide snapshot uploading and viewing [Figure 1].
CONCLUSION
WSI ZoomViewer is a vendor neutral HTML5 digital
slide viewer that fills an important niche in today’s digital
pathology market. The advantage of HTML5 is its ease of
deployment. This novel WSI viewer will allow institutions
to avoid vendor lock-in by working with digital files from
different vendor’s, and facilitate collaboration by allowing
heterogeneous WSI repositories hosted by different
institutions to be easily accessed.
Reader Studies for Digital
Pathology: Software for
Simulation, Analysis, and Sizing
Weijie Chen, Adam Wunderlich, Nicholas
Petrick, Brandon D. Gallas
Food and Drug Administration, Center for Devices and Radiological Health, Office
of Science and Engineering Laboratories, Silver Spring, MD.
E-mail: weijie.chen@fda.hhs.gov
CONTENT
In certain types of clinical studies comparing Whole Slide
Imaging with optical microscopy, multiple pathologists
(i.e. readers) read/evaluate images of multiple cases from
both modalities and the pathologist’s diagnostic assessment
for each case is converted to a binary score by comparing
with a reference standard (1: Agree, 0: Disagree). The
summary metric is the probability of agreement obtained
by averaging the binary scores for each modality. The
study hypothesis is that Whole Slide Imaging is noninferior to optical microscopy where the conclusion should
generalize to both the population of readers (pathologists)
and the population of cases (patients). In order to achieve
such a generalization, both readers and cases in the study
should be treated as random samples representative of
their respective populations. We present a framework for
simulation, analysis, and sizing of such studies.
TECHNOLOGY
Figure 1: Vendor neutral HTML5 digital slide viewer
We introduce a computational model that simulates binary
data with a correlation structure that allows for accounting
for two sources of variation observed in real studies:
variability due to the random reader sample and the random
cases. We illustrate procedures for using our simulation
model to validate a statistical analysis method and to
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estimate the sample size (both the number of readers and
cases) needed to achieve a desired statistical power.
DESIGN
We adopt two methods for the analysis of reader study
data: (a) The method of Obuchowski-Rockette-Hillis that
uses a correlated analysis of variance model; and (b) the
method of Gallas that is based on the U statistics. We
use our simulation model to validate these two methods
in terms of coverage probability of 95% confidence
intervals for percentage agreement.
RESULTS
We found that the 95% confidence intervals from both
methods have satisfactory coverage probability and
therefore are appropriate for the analysis of binary reader
study data. We also demonstrated the application of our
simulation model to sizing a study.
CONCLUSIONS
The general methodological framework we present here
and the associated freely-available software package
(http://code.google.com/p/imrmc/wiki/iMRMC_Binary) are
useful for simulation, analysis, and sizing of multireader
multicase reader studies with binary assessments.
An Open Standards, Enterprise
Whole Slide Imaging Warehouse
and Layered Governance Model
Seung Park2, Sean Wilkinson1
Department of Biomedical Engineering, University of Alabama at Birmingham,
Department of Pathology, Division of Informatics, University of Alabama at
Birmingham. E-mail: seungp@uab.edu
1
2
CONTENT
Many whole slide imaging (WSI) solutions exist, most
with a coupled client-server viewer model. These solutions
(a) are hardware intensive, (b) assume unified metadata
governance, (c) are Windows-only, and (d) provide zero
meaningful interoperability. We have developed an openstandards, Web 2.0 WSI repository and layered governance
model that allows for divergent metadata access depending
on the use case (educational, research, clinical).
TECHNOLOGY
Hardware: Dell PowerEdge 2950; Host Virtualization
S16
Hypervisor: VMWare ESXi 4.1.0; Guest Operating System:
Ubuntu Linux Server 12.04 LTS 64-bit; Web Server:
nginx 1.5; Database Management System: MariaDB 5.5;
Programming Language: PHP-FPM 5.3; WSI Decode
Library: OpenSlide 3.4; Image Processing Library: VIPS 4.38;
Deep Zoom Image (DZI) Viewer: OpenSeadragon 1.0.
DESIGN
Upon WSI file generation, these files are converted
into DZI pyramids by an OpenSlide + VIPS powered
application. DZI pyramids, written in a self-describing
tiled JPEG file-based interchange format, allow for
direct, high-performance access to arbitrary regions
of interest. The deidentified DZIs are uploaded to a
public-facing web server. The corresponding clinical
metadata are uploaded to a hospital-access-only database
server (code-named ‘ASPIRE’). Public accession numbers
(PANs) on the public server are unrelated to the true
clinical accession numbers (CANs). An OpenSeadragonbased viewing app on ASPIRE translates CANs into
PANs and embeds the appropriate WSI from the public
server, allowing clinicians to utilize CANs only within the
hospital intranet. Researchers and educational users do
not have access to CANs, and simply use PANs instead.
RESULTS
Our WSI governance system successfully provides
interchange for disparate user groups who have
hitherto utilized disparate WSI file formats. Prior to
implementation of our system, there were 8 different
WSI repositories maintained in individual silos; these
have been unified. All WSIs are available for real-time
viewing, and our system supports hundreds of concurrent
users with no discernable performance degradation.
CONCLUSION
Our system is now the department-mandated solution
for WSI interchange and data governance going
forward. It has supplanted individual slide boxes at our
medical school, and forms the basis of our electronic
consult slide archiving repository. Multiple advanced
image analytics pipelines for our system are also in
development.
Integrating Robotic Analyzer
with LIS to Reduce Human
Errors in HPV Reporting
Peter Gershkovich, John Sinard
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Yale Medical School, Department of Pathology, New Haven, CT.
E-mail: peter.gershkovich@yale.edu
CONTENT
Human errors in reporting lab results for high-risk Human
Papilloma Virus (HPV)– a sexually transmitted viral
infection that causes cervical cancer - may lead to a wrong
treatment and can damage personal relationships. Despite
rigorous quality control, manual transfer of data from
the analyzer to the LIS resulted in a 0.04% undetected
error rate in our lab, or approximately 24 cases per year.
In addition, we found 0.2% of cases where existing QA
processes identified human errors leading to approximately
120 amended reports per year. An electronic link that sends
results from the analyzer to our LIS, eliminating the need
for manual entry of the results, can prevent these errors.
and Robotic Analyzers of HPV eliminates manual transfer
of results and improves the accuracy of HPV reporting.
This is Your Brain on
Informatics: A Total-Immersion
Data Sciences Course for
the Next Generation of
Informaticists
Timothy Kennell Jr.1, Vincent Laufer1, Robinna
Lorenz1, Seung Park2
NIH Medical Scientist Training Program, University of Alabama at Birmingham
School of Medicine, 2Department of Pathology, Division of Informatics, University
of Alabama at Birmingham. E-mail: tikenn@uab.edu
1
TECHNOLOGY
Software was written using the Java programming language
and Open Source frameworks (Quartz, Apache Mina,
Apache Commons, etc.). It consists of two modules: ASTM
interface with a Cobas 4800 analyzer from Roche and the
specimen-tracking and reporting module linked to the LIS.
DESIGN
An HPV Result Interface Module was added to our inhouse custom-built Histology Asset Tracking system.
A new concept of “derived specimen” was introduced to
track the HPV samples and to provide a link between the
tests accessioned in the LIS and the tests tubes placed
in the analyzer. The interface between the HPV analyzer
and the LIS is a web-based application that communicates
over Ethernet with the LIS and the analyzer using
TCP/IP and ASTM protocols. The results are automatically
incorporated as addenda into Final Reports of the core LIS.
RESULTS
The system enabled tracking and automatic transmission
of the results from the analyzer to the LIS eliminating the
manual transfer of results for HPV screening. There were
no errors in HPV reporting after the implementation of the
project based on the evaluation of 2321 cases. There were
no amendments related to incorrect reporting of results.
CONCLUSIONS
The logic of assembling HPV results and recommendations
in a Cytology Report is algorithmic. The exceptions are
rare and easy to detect. The integration between the LIS
CONTENT
The need to train informaticists is critical, yet such training
is rarely built into standard curricula. Even at informaticssavvy institutions, informatics education in medicine is
almost invariably an afterthought, usually focusing on
imparting testable knowledge rather than on building
technical prowess. We have developed and implemented
a one week, 40 hour long, total-immersion experience in
clinical and research informatics/data sciences that enables
trainees at all levels (medical students to faculty; most
with zero prior exposure to informatics) to independently
create and administer complex informatics systems.
DESIGN
On day 1, students are introduced to computer science
in an axiomatic fashion, learning the fundamentals of
systems architecture and algorithmic thinking while they
assemble a functional LEMP (Linux, nginx, MariaDB,
PHP-FPM) stack from the ground up, and write their first
set of exploratory programs in both procedural and objectoriented programming languages. Day 2 covers relational
database design, normalization, querying and maintenance.
Day 3 covers Web 2.0 user interface elements. Days 4-5
comprise a supervised hackathon in which students form
into groups, design real-world informatics projects, and
begin implementation. Students continue working on their
projects until completion (usually with light supervision).
TECHNOLOGY
Virtualization Software: Oracle VirtualBox4.3; Guest
Operating System: Ubuntu Linux Server 12.04 LTS
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64-bit; Web Server: Nginx1.5; Database Management
System: MariaDB 5.5; Programming Languages: PHPFPM 5.3, HTML5, CSS3, JavaScript, and SQL; User
Interface Library: Twitter Bootstrap 3.3.
TECHNOLOGY
RESULTS
DESIGN
Over two sessions of this class thus far, 21 students have
undertaken 10 major informatics projects, with a current
total of 14 abstracts submitted to national research
conferences. 3 are medical education projects, all of
which have been formally adopted by our institution.
4 are research-oriented analysis projects, in various stages
of completion. 3 are clinical informatics projects, each of
which (a) generates significant time and money savings
in clinical operations and (b) has been formally adopted
by our institution.
It is common practice in intensive care units to use
arterial blood for POC glucose measurements, often
with simultaneous draws for other laboratory testing.
We queried our SQL database for all events in which
both an intensive care unit POC and standard glucose
measurement (automated hexokinase or whole-blood
glucose oxidase) were collected within the same 5-minute
period. For comparison, we used 144 data points
from annual POC instrument correlation studies with
hexokinase methodology.
CONCLUSIONS
Engineering education-derived practices, including realworld group projects and technical skill building, reap
major dividends when applied to informatics education.
Future iterations of this class will see the completion and
deployment of more major informatics systems.
Large-Scale Retrospective Data
Analysis for Postmarketing
Surveillance of Point-Of-Care
Glucose Meter Accuracy
Lee Schroeder, May Louie, Nigam Shah
Department of Pathology, Stanford University, Stanford, CA.
E-mail: lschroed@stanford.edu
CONTENT
Tight glycemic control protocols for critically ill patients
routinely incorporate point-of-care (POC) glucose meters.
This is despite FDA warnings against such use due to
concerns with accuracy and a scarcity of postmarketing
surveillance. We demonstrate the utility of mining
retrospective laboratory information system data for
ongoing surveillance of POC glucose meters.
S18
Sunquest extracts into a SQL database allowing direct
query of aggregated data.
RESULTS
We found 20,537 pairs of POC and standard glucose
measurements meeting criteria over 4 years. 32% of
events exceeded recent FDA draft guidance (+/-7 mg/dL
for values <70 mg/dL, +/-10% for values >=70 mg/dL).
Systematic bias of the POC glucose meter was +5.0%
(ci +4.8%/+5.2%) within the interval of 60 to 200 mg/
dl. Bias increased to +18.4% (ci +4.3%/+32.6%) at
lower standard glucose values and decreased to -20.8%
(ci -25.4%/-16.1%) for glucose values above 350 mg/
dl. A similar bias was found whether POC collection
occurred before or after the standard (P < 0.59), or
whether standard measurements were resulted 0-30 or
30-60 minutes after POC results (P < 0.34). Correlation
study bias was not statistically different than that of
retrospective analysis (P < 0.075). Of 364 hypoglycemic
events, 117 were missed by POC testing. Of these, only
2 were misclassified such that an insulin dose would have
been administered according to our tight glycemic control
protocol. Multiple linear regression against POC bias was
performed on concurrent testing from the comprehensive
metabolic, cbc, and arterial blood gas panels. A robust
interference by hemoglobin was found such that a shift
of hemoglobin from 14.0 to 7.0 g/dl was associated
with +13.7% (ci +12.7%/+14.8%) bias.
CONCLUSION
This analysis shows proof-of-concept for harnessing
retrospective patient data in postmarketing surveillance
of POC instruments.
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journal
J Pathol Inform
Editor-in-Chief:
Anil V. Parwani ,
Liron Pantanowitz,
Pittsburgh, PA, USA
Pittsburgh, PA, USA
OPEN ACCESS
HTML format
For entire Editorial Board visit : www.jpathinformatics.org/editorialboard.asp
ELECTRONIC POSTER SESSION
Wednesday, May 14, 2014
Presented in the Grand Foyer, 2nd Floor, Wyndham Grand Pittsburgh Hotel
Archival System for Pathology
Informatics, Research and
Education: A Web-Based Image
Platform for Molecular Pathology
These images were uploaded to ASPIRE, organized based
on our test menu and placed in individual subgalleries
by their case number. They were tagged according to the
test type and result. All 2014 images have been directly
saved to ASPIRE, without the need of saving into other
drives.
Emmanuel Agosto-Arroyo, Mary P. Branscomb,
Shuko Harada, Seung Lyung Park
RESULTS
Department of Pathology, University of Alabama at Birmingham, Birmingham, AL.
E-mail: eagosto@uab.edu
CONTENT
Image collection and retention are an imperative part of
the Fluorescence In Situ Hybridization (FISH) analysis
process. Photographic or digitized microscopic images
are retained for documentation of all FISH assays.
For neoplastic disorders, the minimum required time
for retention is 10 years, which can translate to the
requirement of a large storage volume, if the images are
being saved in a local or shared drive.
TECHNOLOGY
A Dell Precision T3600 (Intel Xeon E5-1603 @ 2.8 GHz;
16GB DDR3 SDRAM; 256GB SSD; 1TB HDD; Microsoft
Windows 7 × 64) was used to host a standard LEMP
(Ubuntu Linux Server 12.04 LTS; nginx 1.5.6; MariaDB
5.5.34; PHP 5.3.10; Graphic library: ImageMagick
6.6.9-7).
DESIGN
Piwigo 2.5.3 – an open-source PHP-based image gallery
program – was customized in order to support image
file upload from a departmental shared drive and then
codenamed ASPIRE. This shared drive was slow and prone
to network congestion-derived errors, yet was the place
where all FISH images had been archived since 2012.
Before ASPIRE, saving a FISH image was a tedious
process, including creating a folder, saving the images and
copying them in a shared drive. These tasks used to take
up to 7 minutes. After developing the ASPIRE web page,
it has been an easier and direct process taking less than
2 minutes. ASPIRE has also allow for other capacities,
like tagging the images with important information,
facilitating the image search process, allowing quick
searches based on case number, as well as, on results
or test type. File search time has been decreased from
4-5 minutes to 3 seconds.
CONCLUSIONS
Aspire has proven to be an excellent tool for saving
images from the different FISH cases performed in
our laboratory. It has improved the workflow for saving
these images and also accessing them for revision,
decreasing the amount of time spent in these activities.
Other image folders are being and will be added to the
system.
ETOX: A Real-time Web 2.0
Toxicology Database
Matthew Cain1, Gregory G. Davis2, Seung Park3
Department of Pathology, University of Alabama at Birmingham, 2Department of
Pathology, Division of Forensic Pathology, University of Alabama at Birmingham,
3
Department of Pathology, Division of Informatics, University of Alabama at
Birmingham. E-mail: mdcain@uabmc.edu
1
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journal
J Pathol Inform 2014 - Abstracthttp://www.jpathinformatics.org
CONTENT
Forensic pathologists often rely on toxicology results to
explain cause of death. Case reports and compilations of
case reports are the mainstay of toxicology information
when determining if a drug caused or contributed to
an individual’s death. We report our development of a
real-time searchable toxicology database that catalogues
not only all toxicology results, but demographics, body
habitus, health conditions, and manner of death.
TECHNOLOGY
Server Hardware: Dell Precision T3600; Host
Virtualization Hypervisor: VMWare ESXi 4.1.0; Guest
Operating System: Ubuntu Linux Server 12.04 LTS
64-bit; Web Server: nginx 1.5; Database Management
System: MariaDB 5.5; Programming Language: PHP-FPM
5.3; User Interface Framework: Twitter Bootstrap 2.3.
(P = 0.0002 and P = 0.002). Our extraction program
reduces this time to 1 second/report. Currently, even
complex searches yield near instantaneous results. These
search results provide averages and statistics on the
following: demographics, organ masses, health conditions,
cause and manner of death, drug results and an option
to select individual autopsies that concluded drug
intoxication as the cause of death.
CONCLUSIONS
Our system significantly reduces the time to extract
autopsy and toxicology information. It provides real-time
toxicology data as well as the ability to easily search for
complex scenarios. While published case reports provide
data on only a few deaths per report, our system provides
detailed information on thousands of cases. Future
goals include the incorporation of advanced statistics
and a more sophisticated upload system so that other
institutions can join our database.
DESIGN
Our system consists of two parts: an extraction program
and the Web 2.0 searchable database. First we created
the extraction program, which harvests data from autopsy
and toxicology reports and then compiles these sets of
data into a common spreadsheet that can be divided
appropriately for our online database. Then, tables
for pathologist, institution, patient information, case,
measurements, and observations were created in MariaDB
[Figure 1]. A complete web application was written in
PHP-FPM, its relational database connector (mysqli),
and Twitter Bootstrap with the ability to form complex
queries including multiple drugs, health conditions, and
demographics.
RESULTS
Manual extraction of autopsy and toxicology data
averages 204 and 145 seconds per report, respectively
PEIR-VM: A Universal, Open
Standards, Web 2.0 Whole Slide
Imaging Repository
Alex Feldman1, Jeremie Lever2, Timothy Awtrey3,
Israel Ponce-Rodriguez3, Peter Anderson4,
Matthew Anderson4, Seung Park5
Department of Pathology, University of Alabama at Birmingham, 2School of
Medicine, NIH Medical Scholars Training Program, University of Alabama at
Birmingham, 3Department of Pathology, Division of Information Services,
University of Alabama at Birmingham, 4Department of Pathology, Division
of Molecular and Cellular Pathology, University of Alabama at Birmingham,
5
Department of Pathology, Division of Informatics, University of Alabama at
Birmingham. E-mail: feldm001@gmail.com
1
CONTENT
Whole slide imaging (WSI) technology is increasingly
used in medical education and research. However,
significant barriers (e.g. closed file formats, lack of
appropriate viewers for operating systems other than
Windows) to universal adoption remain. We present
an open source, open standards, Web 2.0 whole slide
imaging repository system designed and implemented for
ease of deployment, ease of use, and infinite extensibility.
TECHNOLOGY
Figure 1: Database schema. Boxes represent tables, underlined text
indicates primary keys, and red font indicates foreign keys
S20
Hardware: Dell PowerEdge 2950; Host Virtualization
Hypervisor: VMWare ESXi 4.1.0; Guest Operating System:
Ubuntu Linux Server 12.04 LTS 64-bit; Web Server:
nginx 1.5; Database Management System: MariaDB 5.5;
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journal
J Pathol Inform 2014 - Abstracthttp://www.jpathinformatics.org
Programming Language: PHP-FPM 5.3; WSI Decode
Library: OpenSlide 3.4; Image Processing Library: VIPS
4.38; Deep Zoom Image Viewer: OpenSeadragon 1.0.
DESIGN
OpenSlide and VIPS were linked and cross-compiled
from Linux to Windows 32-bit binaries. A graphical user
interface (code-named ‘WholeBuddy’) enabling singleclick conversion of multiple WSI formats (notably.SVS
and.BIF) was created. Previously-generated pathology
and histology teaching WSIs were converted into DZI
pyramids using WholeBuddy. A virtual machine running
a LEMP (Linux, nginx, MariaDB, PHP-FPM) stack
was generated, and a web app was created allowing for
(a) Easy upload of WSIs with their associated metadata
and (b) real-time display of WSIs via OpenSeadragon.
RESULTS
PEIR-VM currently contains over 300 WSIs for teaching
and research. It is viewable with any modern web
browser; this is critical at an institution where 61%
of students use Mac OS X instead of Windows. The
tiling schema for DZI pyramids is into JPEG files with
regularized filenames, making regions of interest trivial
to access once identified. Conversion of WSIs into DZIs
increases file size by a factor of 1.26-2.01 (average 1.52);
we find this an acceptable tradeoff, as this removes the
processing bottleneck that live WSI streaming platforms
traditionally display. For instance, even once ported to
an underpowered Raspberry Pi, PEIR-VM can support
over 300 concurrent users with no appreciable drop in
performance.
CONCLUSIONS
PEIR-VM has enjoyed rapid adoption among our students
and researchers. Future revisions will include region of
interest annotations, live tutorial sessions, and updated
application programming interfaces for further extensibility.
Evaluation and Actualization of a
Pathology Department/Residency
Program Website: Developing
an Enhanced Educational and
Informational Tool
Emilio Madrigal, Mark T. Friedman
Department of Pathology, Mount Sinai Health System, St. Luke’s, Roosevelt and
Beth Israel Hospitals, Icahn School of Medicine at Mount Sinai, New York, NY.
E-mail: emadrigal@chpnet.org
CONTENT
The potential to be a learning resource as well as an upto-date information hub creates marked variability in
content and quality amongst pathology departments’/
residency programs’ websites. Although no clear
guidelines have been designated to balance this material,
we evaluated our previous website (continuumpathology.
org) and identified enough deficiencies to warrant its
reconstruction altogether (slrbimcpathology.com).
TECHNOLOGY
A well-architectured content management system and
blogging tool was deemed necessary to maintain a
dynamic website and for this, WordPress, an open source
engine, was chosen. A suitable template was identified,
and once installed the PHP, HTML and CSS codes were
further manipulated. The rich plug-in architecture and
multi-user capabilities enhanced customizability, allowing
for the development of interactive activities.
DESIGN
Evaluation of our previous website revealed that it was last
updated in 2011, rendering its listed schedules, faculty,
residents, and contact information outdated and incorrect.
Further, the limited educational content was highly
disorganized and without any interactivity. A completely
indexed environment with a clean user interface was
designed, consisting of: a security-encrypted page for current
residents with monthly rotation schedules, contact sheets,
and educational resources; interactive ‘Case of the Month’
presentations by residents; daily didactic lecture schedules.
Multiple facets of the previous and current websites were
evaluated using a newly developed validated tool that assesses
the quality of medical education websites in pathology.
RESULTS
The medical educational website quality evaluation
tool (MEWQET) was used by two observers within
our department. The previous domain yielded
MEWQET scores of 36 and 37: ‘not recommended’
website. The current domain resulted in scores of
73 and 72: ‘recommended’ website [Table 1]; with
Table 1: MEWQET scores for previous and current
websites as evaluated by two different observers
URL address
evaluated
continuumpathology.org
slrbimcpathology.com
First observer
Second
MEWQET score
observer
(R, RC, NR)
MEWQET score
36 (NR)
73 (R)
37 (NR)
72 (R)
M E W Q E T: M e d i c a l E d u c a t i o n a l We b s i t e Q u a l i t y E v a l u a t i o n To o l ;
Categories: 65: R (recommended), 65‑50: RC (recommended with caution), <50: NR (not
recommended)
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journal
J Pathol Inform 2014 - Abstracthttp://www.jpathinformatics.org
complete concordance in these categories: aim,
comprehensiveness, navigability, design, interactivity,
and disclosures.
CONCLUSION
In its current form, our website is serving to improve
workflow within our program by creating a centralized
hub for grossing, frozen-section, and on-call schedules,
allowing attendings and residents to know with
whom they have been paired with on any given date.
Residents have also gained an opportunity to advance
their core competencies by creating interactive cases,
with educational discussions. Future aims include the
integration of: grossing dictation manual/atlas; secured
laboratory protocols; and educational case presentations
by faculty.
Challenges Developing a Model
Digital Pathology Network in
a Major Military Healthcare
Environment
Anil V. Parwani3, Leslie Anthony1, Charles R Bond1,
Jonhan Ho2, Liron Pantanowitz3, David Glinski1,
Orly Aridor1, Daniel B. Smith4
Office of Sponsored Programs and Research Support, University of Pittsburgh
Medical Center, Pittsburgh, PA, 2Department of Dermatopathology, University of
Pittsburgh Medical Center, Pittsburgh, PA, 3Department of Pathology, University
of Pittsburgh School of Medicine, Pittsburgh, PA, 4Department of Pathology,
81st Medical Group, Keesler Air Force Base. E-mail: parwaniav@upmc.edu
1
CONTENT
The United States Air Force Medical Service (AFMS)
and University of Pittsburgh Medical Center (UPMC)
collaborated on a congressionally-funded initiative
focused on the tactical design and implementation of
a model digital pathology (DP) network for the AFMS.
This presentation highlights unique technology and
operational requirements that had to be addressed to
form a functional AFMS DP infrastructure.
Technology
Aperio ScanScope AT (400-slide capacity) WSI systems
were installed at four regional centers and Aperio
ScanScope CS (5-slide capacity) systems at two smaller
centers. IT certifications prerequisite to connection of
WSI systems to the AFMS network were required, known
as Department of Defense (DoD) Information Assurance
Certification and Accreditation Process (DIACAP).
S22
DESIGN
Close collaborations and shared decision making
between UPMC researchers, AFMS pathologists,
and military information technology (IT) leadership
were conducted throughout project phases. AFMS
pathology needs and workflow were assessed, using
the contextual inquiry method, to identify clinical
application targets. Commercial WSI systems were
critically evaluated and a single system that met
AFMS needs was selected for the model AFMS
network. UPMC IT coordinated deployment of WSI
scanners at various military bases. Research studies
were designed for targeted clinical applications,
including consultations, quality assurance, and
education, to support DP adoption and demonstrate
value. Unique technologies, processes, regulatory
and people challenges associated with formation of
this DP infrastructure were critically reviewed and
documented.
RESULTS
The recently established WSI network, is the
largest and most geographically-dispersed WSIbased DP network within the DoD. DIACAP and
other information assurance certifications proved
to be a formidable, lengthy process; which resulted
in waning pathology interest and suspension of
planned research activities. Early use of technology
by pathologists varied across sites. A legacy
Laboratory Information System loomed as a
challenge to integration with barcoding and workflow
management software. Constant movement of
personnel, inherent in the military, disrupted
AFMS commitment to clinical process change. The
autonomous nature of AFMS base operations further
jeopardized AFMS-wide DP adoption. Grant limited
time and funding placed post-project network
sustainment and expansion to all AFMS pathology labs
at high risk.
CONCLUSIONS
The emerging DP network was successfully established
and is ready to be leveraged to optimize collaborative
approaches within AFMS pathology and to serve as
a model for other branches of the military. While
DP implementation obstacles are not exclusive to a
military healthcare environment, DoD IT requirements
pose distinct challenges. Dedicated management and
leadership commitment is paramount to the stability,
sustainability, growth, and maturity of this model DP
military network.
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J Pathol Inform 2014 - Abstracthttp://www.jpathinformatics.org
Pros and Cons of Using Digital
Pathology for Genitourinary
Tumor Board
and other devices (laptop computer) to display radiology
images, text and gross pathology images, as well as
difficulties accessing WSI during network outages.
Somak Roy, Jon Duboy, Ishtiaque Ahmed,
Rajiv Dhir, Anil V. Parwani, Liron Pantanowitz
The benefits of using digital pathology for genitourinary
tumor boards outweighed the difficulties encountered
employing this technology. Viewing WSI on an iPad
was perceived to be cutting-edge, engaging and more
informative for clinicians attending these conferences.
Our aim is to further enhance this experience by more
seamlessly integrating digitized slides with accompanying
text and static gross images.
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA.
E-mail: roys@upmc.edu
CONTENT
Multidisciplinary clinicopathologic conferences are a key
component in clinical practice, which allows physicians
to determine consensus based treatment options for their
patients. Pathology and radiology data contribute significantly
to the discussion. Unlike radiology, pathology data has been
traditionally presented using glass slides and/or static images
in slideshow format. This requires substantial preparation
time for the pathologist. We aimed to determine the benefits
and difficulties using digital technology to present pathology
at our institution’s genitourinary tumor boards.
CONCLUSION
Utilizing Raspberry PI to
Provide Educational Material for
Medical Students in Zambia
Stephanie Simmons1, Peter Anderson2,
Alex Feldman1, Jeremie Lever3, Seung Park4
Department of Pathology, University of Alabama at Birmingham, 2Division of
Molecular and Cellular Pathology, University of Alabama at Birmingham, 3School of
Medicine, University of Alabama at Birmingham, 4Department of Pathology, Division of
Informatics, University of Alabama at Birmingham. E-mail: sdsimmons@uabmc.edu
1
TECHNOLOGY
Whole slide images (WSI) were prepared using an Aperio
ScanScope XT scanner (Leica Biosystems). Digitized
slides stored on an image server were accessed via our
institution’s secure wireless network and viewed on
an Apple iPad3 (5th Gen, late 2013) using the Aperio
ePathViewer. VGA adapters and switchers facilitated large
screen projection.
DESIGN
Weekly tumor board preparation involved glass slide
retrieval and WSI scanning of selected slides. Digital
slides were previewed for quality assurance.
RESULTS
The new digital workflow has been used for 12 tumor
boards so far involving 45 cases with 3 to 8 slides
per case. Digitizing slides improved the efficiency of
conference preparation for pathology. Total preparation
time decreased from 2-3 hours/week to 1 hour/week. WSI
presentations were received favorably by clinicians in the
audience. The feature they most appreciated was shared
real-time overview of entire slides. Margin status, tumor
in relation to adjacent anatomical structures, and pattern
of infiltration were better appreciated. WSI could also
be later shared with the clinical team whenever desired.
Drawbacks included the inability to annotate WSI with
the ePathViewer, the need to toggle between the iPad
CONTENT
Sub-Saharan Africa is one of the most medically
underserved regions in the world. Medical schools are
in short supply of faculty, educational resources, and
technology. Though the use of information technology
has been proposed to mitigate these shortfalls, the main
obstacle is lack of quality internet service, which makes
online access to educational materials difficult or even
impossible.
DESIGN
The Pathology Education Instructional Resource
(PEIR) (http://peir.path.uab.edu) was developed at
the University of Alabama, Birmingham and been an
instrumental component in first-year medical student
pathology education. PEIR was recently updated to
include a repository of web-viewable whole slide images
(WSI) (http://peir-vm.path.uab.edu). Our goal was
to take PEIR to Zambia in a way that could be easily
accessible, even in regions with poor connectivity, by
turning the Raspberry Pi, an inexpensive credit cardsized single-board computer, into a combination server
and local Wi-Fi router that could provide access to
PEIR within the medical school without the need of an
internet connection.
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J Pathol Inform 2014 - Abstracthttp://www.jpathinformatics.org
TECHNOLOGY
TECHNOLOGY
Hardware: Raspberry Pi Model B, EdiMax USB WiFi dongle and Western Digital 500GB USB HDD;
Operating System: Raspbian Linux; Web Server: nginx
1.5; Database: MySQL 5.5; Programming Language:
PHP-FPM 5.3; Web-Based WSI: OpenSlide 3.4.0,
OpenSeadragon 1.0.0; Wireless Routing: DNSMasq 2.68
SPOT Imaging Solutions TM PathStation2 (SPOT Imaging
Solutions, a division of Diagnostic Instruments, Inc.
Sterling Heights, MI, USA). The imaging system includes
a 1080p/30 frames per second compact, high definition
digital camera with 16x optical zoom lens, 18” 1920 ×
1080 resolution TFT touch screen All-In-One Computer
and PathSuite2 software. TeamViewer (version 8) was
employed to view live image feeds on remote desktops.
The PathStation2 can be configured for mounting on a
wall, stand, or inside a grossing hood. The configuration
we evaluated was the stand version that included an
adjustable height copy stand with high intensity 5000 K
color balanced lighting.
RESULTS
The Raspberry Pi system project, code-named “Raspberry
PEIR”, was completed in less than one month with a
cost of approximately $90 for the hardware. It includes a
collection of over 30,000 histopathology images organized
by topic with full keyword-based searching, over 300 whole
slide images organized by topic, and an online pathology
curriculum “in a box” that directly utilizes the images and
WSIs. Raspberry PEIR also serves as an independent WiFi router that directly serves PEIR content to connected
wireless devices (e.g. smartphones and tablets), whether or
not a stable connection to the Internet at large exists.
CONCLUSIONS
The use of cheap commodity computing in medical
education in developing countries is a cost-effective and
sustainable approach. To the best of our knowledge, this
is the first usage of a Raspberry Pi in medical education
in Sub-Saharan Africa. We will continue to add
functionality with future versions.
Evaluation of the SPOT
PathStation2 for Gross
Telepathology
DESIGN
A PathStation2 desktop instrument was installed in the
UPMC Shadyside hospital gross pathology laboratory (see
figure) and configured on our institution’s secure network.
Various pathology specimens ranging from small needle
core biopsies to large resections (e.g. kidney, prostate, and
pancreas) were selected. Inked specimens were included
to grossly evaluate margins. Three surgical pathologists
remotely evaluated the live image quality of specimens
by logging on to the PathStation2 workstation from their
respective offices using TeamViewer. Remote acquisition
of snapshots and the use of annotation tools to guide the
prosector in the grossing room were also assessed.
RESULTS
Muhammad Syed, Ishtiaque Ahmed, Anil
V. Parwani, Ralph Anderson, Kara Balatincz,
Douglas Hartman, Somak Roy, Liron Pantanowitz
The PathStation2 provided high quality images of all
specimens during live gross telepathology [Figure 1].
Specimen details and inked margins were easy to examine
at low fields of view and when zooming in close to inspect
specific areas. “Sharpness” and “depth of focus” setting
tools facilitated viewing of specimens at low and high
magnifications, respectively. The TeamViewer banner on
remote workstations obscured some of the PathSuite2
icons available for annotation.
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA.
E-mail: syedma2@upmc.edu
CONCLUSION
CONTENT
Gross pathology evaluation is an important component
of intraoperative pathology consultations and subsequent
triaging of specimens by pathology staff to document
findings, appropriately sample tissue for histological
evaluation and ancillary testing or tissue banking, and to
help render final diagnoses. Currently there are limited
digital imaging systems that facilitate gross telepathology.
Our aim was to evaluate the SPOT PathStation2 system
for performing gross telepathology.
S24
The
SPOT
PathStation2
gross
imaging
system
Figure 1: (Left) Desktop SPOT Imaging SolutionTM PathStation 2
used for gross telepathology. (Right) Gross telepathology image of
a prostatectomy image
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J Pathol Inform 2014 - Abstracthttp://www.jpathinformatics.org
incorporates
excellent
hardware
components
(high resolution digital camera with 16x optical zoom)
and essential software features (annotation tools)
that permit real-time gross telepathology for clinical
use. Although TeamViewer provided adequate remote
collaboration, future versions of the SPOT PathSuite
software will improve the interactivity of the system for
the remote pathologist.
VisionTek® Live Robotic Digital
Telecytology Validation at
UPMC
Muhammad Syed, Anil V. Parwani, Walid
Khalbuss, Payam Arya, Ishtiaque Ahmed,
Ioan Cucoranu, Jackie Cuda, Liron Pantanowitz
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA.
E-mail: syedma2@upmc.edu
CONTENT
Telecytology for rapid on-site evaluation (ROSE) is
being increasingly used in the practice of pathology.
To date, real-time telecytology has been accomplished
largely by means of streaming live video images. Very
few studies have employed robotic telemicroscopy for
remote cytologic evaluation. New technology, such as
the VisionTek® digital microscope, has emerged on
the market where whole slide image (WSI) scanners
now incorporate robotic microscopy capabilities. These
hybrid instruments can therefore be used for static
whole slide imaging and/or live robotic telepathology by
permitting remote control of their microscope. The aim
of this study was to validate the utility of VisionTek® for
telecytology.
TECHNOLOGY
A VisionTek® Digital Microscope (Sakura, Finetrek, USA)
desktop instrument was installed at University of Pittsburgh
Medical Center Shadyside hospital in Pittsburgh, PA, USA.
This brightfield system permitted live robotic review of
up to 4 glass slides. For remote viewing of digital images
TeamViewer (version 8.0.18051) was used.
DESIGN
Fifty (50) archival de-identified cytology glass slides
of fine needle aspiration (FNA) direct smears (DiffQuik stained) were selected. These cases represented a
broad range of diagnoses (benign and malignant) and
complexity (common and difficult diagnoses). Three
board certified cytopathologists each evaluated these
cases. Digital images using VisionTek® were remotely
reviewed using similar monitors. Glass slides of all cases
were examined 2 weeks later using a conventional light
microscope. The participants were provided with a
brief clinical history and site of the FNA for all cases.
Pathologists recorded their diagnoses, time to reach
a diagnosis, and any technical errors encountered.
Discordant diagnoses were categorized into major (likely
to impact patient care) or minor (unlikely to impact
patient care) discrepancies.
RESULTS
Table 1 summarizes intraobserver study findings.
Intraobserver concordance between digital and glass slides
was high (average 95%) when cytopathologists had to
determine if a cytology FNA contained adequate material.
However, the intraobserver concordance when rendering
a specific cytologic diagnosis was lower (average 84%).
Cases in which there was diagnostic discordance were of
major impact in 7% and minor clinical significance in 9%
of cases. Technical errors were reported in 23 instances,
and were related to failure of the microscope to autofocus
or to interruptions with the TeamViewer application.
Cases hampered by technical difficulty caused a delay in
reaching a final diagnosis.
CONCLUSION
Employing the VisionTek® Digital Microscope’s real-time
robotic feature for rapid telecytology evaluation was reliable
for determining specimen adequacy in FNA specimens
and for providing preliminary diagnoses of most cases in
a timely manner. Discrepancies were attributed mainly
to misinterpretation of digital images. Remote viewing
Table 1: Intraobserver accuracy and experience
with VisionTek® robotic telecytology
Pathologist
Level of digital pathology
experience
1
2
High Low
3
High
Digital vs. glass concordance
98
90
96
for satisfactory evaluation (%)
Digital vs. glass concordance
92
82
78
for diagnosis (%)
Diagnostic discrepancy (%)
Major
2
10
8
Minor
6
8
14
Average time to diagnose
(minutes)
Digital
1.98 2.74
1.86
Glass
2.14 0.98
1.12
Number of reported
1 (2) 7 (14) 15 (30)
technical errors (%)
Result
averages
95
84
7
9
2.19
1.41
8 (15)
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of digital images was problematic in a few cases due to
hardware or third party application software technical errors.
An Automated Assessment of
Tumor Viability in Digitized
Whole-Slide Sections of a Lung
Cancer Mouse Model
Riku Turkki1, Nina Linder1, Yinhai Wang1,
Tanja Holopainen2, Anne Grote1,
Mikael Lundin1, Kari Alitalo2,3, Johan Lundin1
Institute for Molecular Medicine (FIMM), University of Helsinki, Finland,
Translational Cancer Biology Program, Biomedicum Helsinki, University of
Helsinki, Finland, 3Wihuri Research Institute Biomedicum, University of Helsinki,
Finland. E-mail: riku.turkki@fimm.fi
1
2
CONTENT
In histological analysis tumor viability is measured as a
fraction of viable tissue region within the whole tumor.
Tumor viability is commonly assessed in pre-clinical
research, especially in drug screening settings to measure
and compare the treatment responses of antitumor
therapies. Nonetheless, due to the challenging nature of
visual examination, the quantification of tumor viability
is problematic and methods suited for high-throughput
analysis are needed. Visual examination is associated
with intra- and inter observer variability and is not easily
scaled up for analysis of larger samples sets.
In this study, we developed an automated segmentation
for detecting the tissue subtypes required for the viability
assessment. The approach is validated on sections of
human non-small cell lung cancer xenograft tumors
treated with antiangiogenic agents.
TECHNOLOGY
The tumor sections were digitally scanned with a
whole-slide scanner and archived in a digital content
management environment. A multi-class support vector
machine classifier combined with rotation invariant
texture descriptors and feature mapping, was used to
construct a supervised segmentation tool to identify
tissue subtypes. Tumor viability score was then derived
from the ratio between recognized necrotic tissue area
and whole tumor area.
DESIGN
Altogether, 56 hematoxylin-eosin stained tumor
sections were used in this study. Two experienced
S26
researchers annotated the digitized sections into 3
categories, i.e. necrotic tumor, viable tumor and other
tissue types (e.g. including normal host tissue, stroma
and muscle tissue). The annotations were used for
training the algorithm (4 sections) and for testing
(52 sections).
RESULTS
The method achieved a median accuracy of F-score = 0.92
to assess the tumor viability when tested on 52 whole
tumor sections. The correlation between the human
experts and the automated method to measure the
viability ratio was r = 0.79 (CI95% 0.65-0.87; P < 0.0001).
CONCLUSIONS
In this study, a novel automated tumor viability
assessment was presented. Preliminary results indicated
that the proposed method offer objective and reliable
tumor viability assessment in xenograft samples when
compared to human observers. Therefore, the method
has the potential to further benefit pre-clinical xenograft
studies and similar research settings where there is a need
to quantify tumor viability.
Automated Grading of Renal
Cell Carcinoma Using Whole
Slide Imaging
Fang-Cheng Yeh1, Anil V. Parwani2, Liron
Pantanowitz2, Chien Ho3
Carnegie Mellon University, Biomedical Engineering, Pittsburgh, PA,
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA,
3
Department of Biological Science, Pittsburgh NMR Center for Biomedical Research,
Carnegie Mellon, University, Pittsburgh, PA. E-mail: frank.yeh@gmail.com
1
2
CONTENT
Grading of clear cell renal cell carcinoma using Fuhrman
nuclear grade for prognostic evaluation is a manual task
traditionally performed by pathologists. Recent technology
developments have demonstrated the benefit of applying
image analysis tools to whole slide imaging (WSI). The
aim of this study was to determine the feasibility of using
automated image analysis to grade clear cell RCC.
TECHNOLOGY
Automatic analysis was applied to 39 H and E-stained
digitized slides of clear cell RCC with varying grades
that calculated nuclear size across the entire slide. The
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analysis results were correlated with manual Fuhrman
nuclear grades.
DESIGN
A total of 39 de-identified H and E-stained glass slides
of clear cell RCC were selected from the archives at
the University of Pittsburgh Medical Center following
Institutional Review Board approval. The stain quality,
diagnosis, and Fuhrman nuclear grade of RCC were
determined by an experienced genitourinary surgical
pathologist (AVP).A total of 3, 11, 12, and 13 cases
were selected for grades I, II, III, and IV, respectively.
We selected only 3 cases for grade I because of its rarity
(5~10%) among clear cell RCC cases.
RESULTS
The spatial distribution of nuclear size provided
a panoramic view of the tissue sections that can
facilitate locating high-grade tumor regions and areas
with necrosis. The statistical analysis showed that
maximum nuclear size was significantly different
(P value < 0.001) between low-grade (grades I and II)
and high-grade tumors (grades III and IV). The receiver
operating characteristics (ROC) analysis showed that
the maximum nuclear size distinguished high-grade and
low-grade tumors with a false positive rate of 0.2 and
a true positive rate of 1.0. The area under the curve is
0.97143.
CONCLUSION
Image analysis algorithms that employ nuclear size can
be used to differentiate low-grade and high-grade clear
cell RCC with good sensitivity and specificity. These
data suggest that automatic WSI analysis of clear
cell RCC may facilitate pathologic grading of renal
tumors and reduce variability encountered with manual
grading.
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journal
J Pathol Inform
Editor-in-Chief:
Anil V. Parwani ,
Liron Pantanowitz,
Pittsburgh, PA, USA
Pittsburgh, PA, USA
OPEN ACCESS
HTML format
For entire Editorial Board visit : www.jpathinformatics.org/editorialboard.asp
SHORT ABSTRACT PRESENTATIONS
Locations: Wyndham Grand Pittsburgh Hotel, Kings Garden South/LeBateau,
Kings Garden North
Imaging Informatics
Thursday, May 15, 2014
Grand Ballroom 1
HemaVue: A Web-Based Tool
for Clinician Access to Digital
Peripheral Blood Smears
William Cable1, Liron Pantanowitz2,
Denine Maglicco1, Ryan Mitchell1,
Jeff McHugh1, Anil V. Parwani2, Lydia Contis2
University of Pittsburgh Medical Center, 1Information Services Division,
2
Department of Pathology, Pittsburgh, PA. E-mail: cablew@upmc.edu
CONTENT
The peripheral blood smear (PBS) is an important
component of a patient’s clinical evaluation and provides
a means to morphologically evaluate blood cells. The
traditional approach has been to review blood smears
in the hematology laboratory, which may not easily
accessible. With advances in technology, the PBS can now
be digitized and analyzed. The aim of our project was to
develop a web-based tool to allow clinicians, residents
and fellows to view PBS scans digitized by CellaVision®.
The tool facilitates the teaching of residents and fellows
without the need for a microscope.
TECHNOLOGY
CellaVision DM96 analyzer, Windows Server 2008, MS
Active Directory, Internet Information Services (IIS)
Manager, Coldfusion 9, SQL Server 11.0.3128, IBM®
Scale Out Network Attached Storage (SONAS).
DESIGN
The CellaVision® analyzer scans blood smear glass
slides and automatically identifies and classifies white
blood cells. Images of these blood cells are stored in the
CellaVision database (Microsoft Access) as binary data.
A technologist creates an archive file with this data,
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which is moved to our SONAS. A scheduled job employs
SQL Server Integration Services to convert the Access
archive file and insert it into a SQL Server database.
A Coldfusion web application was written to interface
with the SQL database, query against the patient medical
record number, generate the associated JPG image files
of scanned blood cells, and display a grid of thumbnail
images.
RESULTS
CellaVision® data including all digital images are securely
archived. The “HemaVue” tool we developed permits
CellaVision® scan results to be viewed by authorized
personnel on any terminal in the institution’s network.
Users are presented with an organized display of the digital
PBS. Access to this tool is restricted to authenticated
users via Active Directory and IIS. Clinician and trainee
experience with this tool has been very positive and is
widely and readily accepted as a teaching tool.
CONCLUSION
The HemaVue web-based tool has successfully allowed
clinicians and trainees at our academic institution
to remotely access digitized PBS generated by the
CellaVision® instrument. Future efforts are aimed at
incorporating these digital blood smears into the electronic
medical record for improved access to patient data.
Pilot Reader Studies Comparing
Whole Slide Images with
Different Gamma Settings
Brandon D. Gallas1, Marios Gavrielides1,
Adam Wunderlich1, Jeffrey D. Seidman2,
Jason Hipp3, Stephen M. Hewitt3
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journal
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US Food and Drug Administration, Division of Imaging and Applied Mathematics,
OSEL/CDRH, 2Division of Immunology and Hematology Devices, OIR/CDRH,
Silver Spring, 3National Institutes of Health, Laboratory of Pathology, Center for Cancer
Research, National Cancer Institute, Bethesda. E-mail: brandon.gallas@fda.hhs.gov
1
CONTENT
We report on reader studies comparing whole slide images
with two different gamma settings in a quantitative
assessment that removes sources of measurement
uncertainty. We use an evaluation environment called
eeDAP that allows cell-to-cell correspondence between
digital and analog pathology. The pre-compiled,
stand-alone, license-free, software component of eeDAP
is described below and is freely available from http://code.
google.com/p/eedap/.
CONCLUSIONS
This was a pilot study for our evaluation environment
(eeDAP), workflow, and analysis methodologies. We
will use these results to design a pivotal study to test a
specific hypothesis at a target statistical power.
TelePath: Commodity
Telepathology for the Web 2.0 Age
Timothy Kennell Jr1, Kelly Taylor2,
Samuel Borak2, Walter Bell2, Israel
Ponce-Rodriguez3, Timothy Awtrey3, Seung Park4
NIH Medical Scientist Training Program, University of Alabama at Birmingham
School of Medicine, 2Departments of Pathology, Community Practice Pathology
Program, University of Alabama at Birmingham, 3Division of Information Services,
University of Alabama at Birmingham, 4Division of Informatics, University of
Alabama at Birmingham. E-mail: tikenn@uab.edu
1
TECHNOLOGY
We used a Hamamatsu Nanozoomer 2.0HT to scan
H and E stained slides at 40x. eeDAP is a Matlab
application that registers glass slides to corresponding
whole slide images and collects reader study data.
The registration uses a microscope-mounted camera,
motorized stage, and software that is minimally guided
by the user. The reader study collects quantitative
evaluations of histopathological features; it runs in
digital mode (showing ROIs from whole slide images) or
microscope mode (stage automatically navigates to ROI
locations on the slide). Using a reticle and corresponding
digital overlay, eeDAP isolates the same individual cells
for evaluation by pathologists in both modes. This
registration allows the reduction or elimination of a large
source of variability in comparing these modalities in the
hands of the pathologist: The field of view (the tissue)
being evaluated.
DESIGN
We have executed two studies: (1) Readers had to decide
if a cell was a mitotic figure or not (and their confidence)
in H and E stained sarcoma tissue; (2) the readers had
to decide if a cell was a plasma cell or not (and their
confidence) in H and E stained colon tissue. For each
study, five readers evaluated 50 cells in two digital modes
(gamma = 1.0 and 1.8). The reference for digital-mode
performance was a pathologist evaluating the same cells
in microscope mode.
RESULTS
The gamma setting did not appear to affect the digitalto-microscope agreement. Additionally, the intra-reader
agreement across the digital modes was higher than the
digital-to-microscope agreement, indicating that reader,
not mode, is the dominant effect.
CONTENT
Telepathology remains underutilized despite its
decades-long existence. Common roadblocks to adoption
include high startup cost, unsatisfactory user interfaces,
and unpredictable video latency. At our institution, we
have created a telepathology system from commodity
components that has proven to be cost-effective,
user-friendly, and highly-utilized.
TECHNOLOGY
Microscope Camera: Lumenera Infinity HD; Digital
Signal Processor: AVerMedia Live Gamer HD; Server
Hardware: Dell PowerEdge 2590; Host Virtualization
Hypervisor: VMWare ESXi 4.1.0; Guest Operating
System: Ubuntu Linux Server 12.04 LTS 64-bit; Web
Server: nginx 1.5; Real Time Messaging Protocol
Server: nginx-rtmp-module 1.1; Database Management
System: MariaDB 5.5; Programming Languages: PHPFPM 5.3 and Javascript; User Interface Library: Twitter
Bootstrap 3.3; Client Video Playback: JWPlayer 6.8.
DESIGN
Infinity HD cameras are installed on pathologist
microscopes; these stream video via HDMI to the Live
Gamer HD, which H.264 encodes the video feed in realtime. The feed is automatically routed to an nginx +
nginx-rtmp-module server for user viewing (Figure 1).
The originating pathologist needs to only press a single
hardware button to start the live stream. The consultant
pathologist needs only to visit a website to view the stream.
No additional hardware or software installation is required.
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CONTENT
This abstract reports on the use of caMicroscope to
provide web-based access to digitized pathology images
from the National Lung Screening Trial. caMicroscope is
a web based data management and visualization system
for digitized whole slide images.
TECHNOLOGY
caMicroscope follows the Software as a Service delivery
model. It consists of four primary modules.
Figure 1
RESULTS
TelePath is universally commended by its users for its
ease of operation, and adds minimal cost ($150 for the
Live Gamer HD; $3000 for the camera, but any existing
microscope camera with video output can be used). 100%
of consultant pathologists consider the video stream
to be of adequate quality for diagnostic consultation.
Latency ranges from 1-3 seconds, but is a constant
(thereby predictable) latency per session that can easily
be adjusted for. Originating pathologists utilize TelePath
1-5 times per week, each time avoiding the 24-48 hour
turnaround time delay associated with delivering a case
via courier to the consultants.
CONCLUSIONS
TelePath is an integral part of our pathology practice (most
notably our community outreach program), and is available
at every site we serve. By using commodity components
and programming user-friendly interfaces, we have seen
widespread adoption of telepathology as a consultation
medium in our practice. Future versions will add robotic
remote control capabilities and increased quality of service.
Framework for Data Management
and Visualization of The National
Lung Screening Trial Pathology
Images
Ashish Sharma1, Ameen Kazerouni1, Yusuf Nadir
Saghar1, Paul Commean2, Lawrence Tarbox2,
Fred Prior2
Department of Biomedical Informatics, Emory University, Atlanta, GA,
2
Mallinckrodt Institute of Radiology, Washington University, St. Louis,
MO. E-mail: ashish.sharma@emory.edu
1
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Data Loader: Utilizes the OpenSlide and VIPS open
source libraries to perform data preparation. This includes,
(1) Identification of images to process; (2) Conversion of
the images from its vendor specific format to the open
standard BigTIFF; (3) The extraction of image meta-data
that is necessary for visualization of images and markups.
Image Viewer: A HTML5 based viewer that leverages
OpenSeadragon and IIPServer for the visualization of the
pathology images.
Markup Tools: Provide the user the ability to draw, store
and retrieve annotations and markups.
Data Services: A collection of web data services that
provide access to databases that manage images,
metadata and markup data via secure REST API’s.
DESIGN
caMicroscope deployed for the National Lung Screening
Trial, required a semi-automated data preparation process,
that included the retrieval of anonymized identifiers from
the image labels, and reconciliation of these labels with
global identifiers. The Cancer Imaging Archive’s Query
Tool, allows investigators to access and query repositories
of Clinical, Pathology and Radiology metadata. It is
then used to launch the caMicroscope image viewer to
visualize selected subjects. User generated markups are
stored along with image identifiers, and can be restored
on launch. The deployment facilitates, (1) Visualization
of images; (2) Efficient sharing of images; (3) Rendering
and sharing of Annotations and Markups.
RESULTS
Performance tests have been performed to validate the
scalability and reliability of caMicroscope. The system,
shown in Figure 1, has been live for 9 months. It provides
access to 1253 pathology images to authorized users.
CONCLUSION
caMicroscope is a generic digital pathology data
management and visualization system that was used to
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provide access to images in this project. It integrates with
external metadata exploration clients such as the Query
Tool and gives users the ability to visualize and annotate
images.
Imaging Informatics
Thursday, May 15, 2014
Kings Garden South/LeBateau
Web-Based Pathology Practice
Examination Usage
Edward C. Klatt
Mercer University School of Medicine, Biomedical Sciences, Savannah, GA.
E-mail: klatt_ec@mercer.edu
CONTENT
General, organ, and subject specific pathology practice
examinations were placed onto a public access interent
web site. Users had to make 4 clicks from the home web
page at: (http://library.med.utah.edu/WebPath/EXAM/
EXAMIDX.html).
TECHNOLOGY
Multiple choice questions were developed in United
Stated Medical Licensing Examination style and coded
into.html files with javascript functions that presented
a common interface for web browser viewing in a timed
format. A PERL programming script with common
gateway interface for web page forms scored examinations
and placed results for each question and total score per
accession into a log file on an internet server.
DESIGN
The 4 general review examinations of 30 questions each
could be completed in up to 30 minutes. The 17 organ
and subject specific examinations of 10 questions each,
with accompanying gross or microscopic images, could
be completed in up to 15 minutes each. The results of
log files were compiled from June 2006 through January
2014.
RESULTS
The 4 general review examinations had 31,639 accesses
with completion of all questions, for an overall completion
rate of 54% and average score of 75%. A score of 100%
was achieved in 7% of accesses, 21% of users achieved a
score ≥90%, and 95% of users achieved ≥50%. In top to
bottom web page menu order, review examination usage
was 44%, 24%, 17%, and 15% of all accessions. The 17
organ and subject specific examinations had 103,028
completions, with completion rate 73% and average score
74%. Mastery at 100% was 19.6% overall, 36.8% of users
achieved a score ≥90%, and 90% achieved ≥50%. The
first 3 menu items on the web page accounted for 12.6%,
10.0%, and 8.2% of all completions, and the bottom 3
accounted for no more than 2% each.
CONCLUSION
Completion rates were higher for shorter examinations of
10 questions in a single subject area. Usage was higher for
examinations at the top of the web page menu. Though
internet user attention span appeared limited based
upon completion rates, scores achieved suggest that
serious users completing the examinations had sufficient
preparation to make use of the examinations to support
their pathology education.
Defining the Next Generation
of Digital Pathology in Swedish
Clinical Routine
Claes Lundström
Linköping University and Sectra AB, Center for Medical Image Science and
Visualization, Linköping, Sweden. E-mail: claes.lundstrom@liu.se
CONTENT
In 2012 a research and clinical development project
regarding Whole-Slide Imaging was launched, involving
care providers covering almost half of Sweden as well
as academic and industrial actors. We here present
the results of the design phase, where the objective
was to design optimal work practices for a fully digital
environment and to establish all benefits of digital
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pathology in clinical routine. A notable foundation for
this effort was the extensive experience of digital primary
review practice in Kalmar and Linköping, where over
550,000 slides have been scanned to date.
TECHNOLOGY
Experiences from various digital pathology software and
equipment have been one type of input to the design work.
DESIGN
The analysis and design of work practices were carried
out through a series of workshops. Input was gathered
from experts in clinical pathology (pathologists,
managers, technicians), process improvement and
imaging informatics. The designs were documented
and subsequently reviewed. Information with bearing
on supportive IT tools was used as a requirement
specification for prototype development including a
pathologist’s workstation.
RESULTS
The designed workflows and prototypes point to many
benefits of the digitization, some perhaps being less
established. For example, fully digitizing the grossing
documentation and deeply integrating it with the slide viewer
is of significant diagnostic value. The enterprise scope is also
underlined. Clinical value beyond MDT meetings arise when
pathology is one part of an enterprise image management
setup, and there are cost synergies with existing IT
infrastructures for radiology imaging. Nevertheless, a major
hurdle for adoption is the cost of long-term data storage
and the need for smart information lifecycle management
is highlighted. Finally, nation-wide collaboration in the form
of a centralized image repository for primary review has been
investigated and found to be technically feasible.
CONCLUSION
A strong knowledge base has been established to support
continued adoption of digital pathology in Sweden. There
is convincing rationale for this development, but a broad
scope is necessary to meet all challenges and exploit all
opportunities.
CONTENT
Incomplete sample evaluation, artifacts of preparation,
poorly quantitative measures, limited growth pattern
information, and an extended manual preparative process
are some of the aspects of traditional slide-based histologic
analysis of human samples that limit further advancements
in histology. With the increasing use of ancillary tests, these
limitations are particularly relevant for small core biopsies.
In an effort to expand the capabilities of tissue analysis,
we report on the potential of a modified tissue processing
method that can be used to image non-destructively
through entire core biopsy specimens, eliminates the need
for wax-embedding, and avoids cutting artifacts, while
preserving tissue for ancillary studies.
TECHNOLOGY
The technique of multiphoton (MP) microscopy was
combined with a benzyl alcohol benzyl benzoate (BABB)
tissue-clearing protocol for deep tissue imaging. The
microscope is based on a Ti: Sapphire pulsed laser,
high numerical aperture objectives, and multichannel
detection with Scanimage (Janelia Farm, Ashburn, VA)
control software. Non-fluorescent second harmonic
generation signal, corresponding to collagen fibers, was
collected concurrently.
DESIGN
Neoplastic and non-neoplastic samples of formalin-fixed
human lung, breast, and kidney were obtained from discarded
pathologic tissue specimens after resection. Core biopsysized fragments were dehydrated in alcohol before being
cleared in BABB. Fluorescent dyes were used for staining.
Specimens were imaged overnight. Fluorescence images
were transformed into H and E-like images via a custom
script that inverts the logarithmic matrix conversion of
H and E color values. A subset of samples were subsequently
processed using traditional techniques for comparison.
RESULTS
High Resolution Virtual Histology
of Uncut, Unembedded Tissue
Excellent image quality was obtained on all tissue types
obtained using multiphoton microscopy and BABB
clearing at depths greater than 1mm, sufficient for
complete core biopsy evaluation. Faithful H and E-like
reproduction was achieved. Second harmonic signals
offered quantifiable fibrosis measures throughout the
samples. There were no appreciable degradation effects or
artifacts on subsequent wax-embedding and staining.
Richard Torres1, Eben Olson1, Michael J. Levene2
CONCLUSIONS
Yale University School of Medicine, 1Laboratory Medicine, 2Biomedical Engineering
New Haven, CT. E-mail: richard.torres@yale.edu
The combination of multiphoton imaging and tissue
clearing shows great promise as a practical tool for
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histology that offers
traditional techniques.
significant
advantages
over
International Telepathology
Consultation: Two Years of
Experience Between the
University of Pittsburgh Medical
Center and Kingmed (China)
Chengquan Zhao1, Tao Wu2, Xiangdong Ding2,
Anil V Parwani1, Hualin Chen2,
Gonzalo Romero Lauro1, Xiaodong Feng2,
Shangwei Wu2, Samuel Yousem1,
Liron Pantanowitz1,
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA,
Department of Surgical Pathology, KingMed Diagnostics, Guangzhou, Guangdong,
China. E-mail: zhaoc@upmc.edu
1
2
CONTENT
Telepathology is increasingly being employed to support
diagnostic consultation services. Most telepathology
publications have dealt more with the technology aspects
than clinical experience of this practice. KingMed
Diagnostics is a large network with 21 central laboratories
serving 9,000 hospitals and clinics in China. Since 2012,
the University of Pittsburgh Medical Center (UPMC) and
KingMed have established an international telepathology
consultation service. The aim of this study was to review the
experience of this international telepathology partnership.
TECHNOLOGY
Whole slide images acquired using a NanoZoomer
2.0-HT were stored on a server in China using the NDP.
serve database management system. Digital slides were
accessed via a portal server in Pittsburgh, PA, USA. Using a
customized portal and associated viewer software, UPMC
pathologists were notified of incoming digital consultations,
viewed digital slides and generated diagnostic reports.
DESIGN
This is a retrospective study that summarizes telepathology
consultation results between UPMC and KingMed over a
2 year period (January 2012 - December 2013).
RESULTS
Most (59%) submitted cases were referred by Chinese
pathologists, 38% per request of clinicians, and 3% by
patients in China. There were 144 cases sent in 2012
and 614 in 2013 (P < 0.05). Case volume increased
in the past 9 months, with an average of 61 cases per
month. A summary of case distribution and turnaround
time is listed in Table 1. Hematopathology received the
most cases (25.3%), followed by bone/soft tissue (20.6%)
and gynecologic/breast (18.6%) subspecialties. Average
turnaround time was 6.8 days in 2012 and 5.3 days in
2013 (P < 0.05). For many cases immunostains were
ordered. For certain cases, especially hematopathology,
more than one round of immunostains was needed
which delayed turnaround time. For 360 (47.5%)
cases digital slides were sent for consultation without
a primary diagnosis, whereas in 398 (52.5%) cases
a primary diagnosis or impression was provided by
the referring local hospital in China. Malignancies
accounted for 66.4% of cases, benign entities for
19.9%, and borderline neoplasms for 13.7% of consults.
In most (84.8%) cases there was a definite diagnosis
provided, 9.4% a favored/suggestive diagnosis, and 5.8%
an atypical/uncertain diagnosis. For the 398 cases where
a primary diagnosis/impression was included, the final
diagnoses rendered by UPMC was identical in 22.9%
of cases, mildly modified in 23.4%, and significantly
modified (treatment plan altered) in 53.8% of cases.
CONCLUSION
These results indicate that international telepathology
consultation can improve patient care by facilitating
access to pathology expertise. The success of this
international digital consultation service was dependent
on strong commitment and support from leadership,
information technology expertise, and dedicated
pathologists who understood the language and culture
Table 1: Telepathology case distribution and
turnaround time
Subspecialty
Bone/soft tissue
Breast/gynecology
Head/neck
Hematopathology
GI
Liver
Thoracic
GU
Derm/melanoma
Neuropathology
Cardiac
Pediatric
Infection
Non‑Gyn cytology
Total
2012
TAT
2013
TAT
32
32
17
2
14
9
12
11
7
5
0
0
1
2
144
6.2
5.4
7.7
6.5
7.4
8.1
5.1
11.4
3.9
6.0
0
0
15
5
6.8
124
109
44
190
45
9
26
21
30
12
1
3
0
0
614
4.6
4.1
6.0
6.8
5.0
7.2
4.8
7.4
5.0
2.4
10.0
4.7
0
0
5.4
TAT: Turnaround time
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on both sides. Challenges included internet speed and
firewalls, difference in cultures and health care systems,
lack of clinical information and gross pathology
descriptions with cases, insufficient tissue sections
submitted for evaluation, and difficulties related to
direct communication with Chinese clinicians.
Applied Pathology Informatics
Thursday, May 15, 2014
Kings Garden North
Automated Pathology Workflow
for the 21st Century
Navid Farahani1, Jeffrey L Fine2
Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center,
Los Angeles, CA, 2Department of Pathology, University of Pittsburgh School of
Medicine, Pittsburgh, PA. E-mail: nfarahan@gmail.com
sign-out work consists of an interactive review of the
ROIs that is driven by the diagnostic tasks. The results
of this are then utilized to automatically construct a
final report.
1
CONTENT
Many whole slide image (WSI) systems claim to be highly
automated, but largely emulate and maintain traditional
surgical pathology workflow. Pathologists read laboratory
information system (LIS) data and review slides manually,
one at a time and in order, and then manually construct
a report. A previously outlined “21st century workflow
proposal" presented a hypothetical, automated sign-out
workflow. This project is a prototype mock-up of an
advanced sign-out of a breast cancer specimen, intended
to provide a concrete example of automated sign-out that
can be used to guide and facilitate WSI adoption.
TECHNOLOGY
Slides and reports from two breast cancer cases were
de-identified: A core biopsy and a lumpectomy with
axillary sentinel lymph node biopsy. WSIs were created
using an Aperio ScanScope XT, and screen captures were
created using vendor-provided software (Leica, Vista CA
USA). The advanced workflow prototype was constructed
using PowerPoint software (Microsoft, Redmond WA
USA).
RESULTS
The created mock-up models a possible automated
workflow for a breast cancer resection specimen
[Figure 1]. It is an animated slide show that presents the
hypothetical sign-out stepwise, illustrating the various
interactions and explaining how these steps can be
automated (publicly available at http://pitt.edu/~jlf60/
supplemental.html).
CONCLUSION
Our prototype demonstrates a radical rethinking of
pathology workflow that focuses pathologists on work that
only they can do. Partly based on hypothetical intelligent
computer systems, it also relies on existing, under-utilized
LIS and WSI data. There are precedents: imaged Pap testing
and automated hematology are two microscopy-based tests
that are now automated. We have presented a concrete step
that may help digital pathology provide desperately needed
and long-awaited automation for pathologists.
DESIGN
We modeled an interactive, computer-assisted workflow:
The hypothetical computer previews the WSIs in the
context of integrated LIS data (e.g. specimen type, gross
description) and pre-defined diagnostic tasks. These
tasks include: Correlation with previous tumor diagnosis;
tumor grading and staging; margins assessment; etc.
Relevant regions of interest (ROIs) are automatically
identified and triaged by the computer. The pathologist’s
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Figure 1
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journal
J Pathol Inform 2014 - Abstractshttp://www.jpathinformatics.org
Interfacing Automated
Immunostainers with an
Anatomic Pathology Laboratory
Information System
John Sinard M, Peter Gershkovich
Department of Pathology, Yale Medical School,Yale University School of Medicine,
New Haven, CT. E-mail: john.sinard@yale.edu
CONTENT
Integration of laboratory information systems (LIS) with
automated equipment has only recently begun to occur
in anatomic pathology laboratories. While many of the
newer automated immunostainers have the ability to
receive and send electronic information, few laboratories
have taken full advantage of this capability. This has
been due to both the lack of appropriate functionality
in many LISs and to the lack of standardization in
equipment requirements for integration. Integration is
even more complicated in laboratories that maintain
immunostainers from more than one vendor.
TECHNOLOGY
We have integrated our Histology Asset Tracking (HAT)
software with the Leica Bond III and the Ventana
Benchmark Ultra automated immunostainers. Messages
outbound from the HAT system to the stainers were
programmed into HAT. An additional standalone
interface engine, dubbed Hermes, was written to receive
and process messages from the stainers. All software
was written using the Java programming language
and Open Source frameworks (Apache Mina, Apache
Commons, etc.). Our LIS is Cerner CoPath Plus.
DESIGN
Stainer protocol codes were loaded into the
“Stain/Process” dictionary of our LIS. As barcoded slides
are scanned onto a stainer batch, an HL-7 message is sent
from the HAT system to the appropriate stainer with the
order information. For one vendor’s stainer, a relabeling
step is required. The stainer is then able to recognize
the barcode on the slide, perform the appropriate stain,
and inform the Hermes middleware (via another HL-7
message) when the stain is complete. Hermes updates
stain status in the LIS.
RESULTS
Electronic integration of automated immunostainers
has greatly facilitated the workflow within the
immunohistochemistry lab, improving staff efficiency and
reducing errors. The interfaces integrate the instruments
into the asset tracking process.
CONCLUSIONS
Integration of immunostainers reduces the manual labor
or retyping staining orders and reprinting slide labels
and, through that, eliminates opportunities for errors.
While some degree of user customization is needed
to integrate this equipment with anatomic pathology
laboratory information systems, the newer stainers are
increasingly able to support this integration, and vendors
are recognizing the importance of helping customers with
this process in order to maintain a competitive edge.
Analysis of the Impact and Value
of a Specimen Tracking System
Implementation for Anatomic
Pathology
Buer Song1, Robert Stapp2, J. Mark Tuthill2
Department of Pathology and Laboratory Medicine, The State University of
New York at Buffalo, Buffalo, NY, 2Henry Ford Health System, Detroit MI.
Email: buersong@buffalo.edu
1
CONTENT
Accurate and effective specimen tracking and routing in
a surgical pathology laboratory is critical for improving
efficiency, reducing error, and improving patient care.
Performing specimen tracking and routing in the
traditional manner could cost significant time and
resources, with minimal to no, real-time workflow
monitoring. An automated system, integrated with the
laboratory information system, would provide accurate
routing, detailed tracking, real-time workflow monitoring,
and reduce costs. Here, we analyzed the elements
required to set up an automated tracking and routing
system at Buffalo General Medical Center. We examined
the needs and expectations of a medium-large scale
pathology laboratory, established objectives, and planned
a system implementation capable of reaching them.
TECHNOLOGY
The proposed system consists of Sunquest CoPath, as the
laboratory information system, integrated with specimen
management routing and tracking (SMART). Additional
hardware requirements would include Windows based
workstations, 2-D barcode scanners, slide label and cassette
printers/etchers, and network with wireless capabilities.
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journal
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DESIGN
Specimen volume, workflow, existing problems, and desired
improvements in the histology laboratory were analyzed.
Required elements of the CoPath+SMART system were
listed according to the needs of the laboratory. The system
was then virtually run through the entire workflow to explore
the potential for process improvements. Tentative solutions
for anticipated problems were also proposed. A brief
comparison with Vantage from Roche was also performed.
RESULTS
An automated tracking and routing system could be
successfully implemented with the necessary hardware and
software. Compared to our current laboratory information
system, CoPath+SMART could provide more accurate
routing, detailed tracking, and valuable workflow monitoring
functions. Potential issues include major workflow changes
for the entire workforce, protocol compliance issues, and
possible technical glitches that might arise.
CONCLUSION
As the major histology lab for a tertiary regional medical
center, the lab would benefit from an automated
specimen tracking and routing system. Increased work
efficiency, reduced error, and better lab management
would be expected. However, it would require major
changes in laboratory culture, workforce adjustment, and
a well-tailored plan to increase benefit/cost ratio.
Application of an Anatomic
Pathology Tracking System in
Specimen Management and
Beyond
Robert Stapp1, Marc Levine1, Ron Brown1,
Mehrvash Haghighi2, J. Mark Tuthill1
Henry Ford Hospital, Detroit, Michigan, 2Columbia University Medical Center,
New York, NY. E-mail: rstapp1@hfhs.org
and potential usefulness of automated tracking systems
in anatomic pathology has been widely accepted. Herein,
we examine how tracking data could be utilized with
standard tools within the AP-LIS as well as applications
beyond asset tracking.
TECHNOLOGY
CoPath Plus v6.0 was used as the AP-LIS (Sunquest
Information Systems, Tuscon, AZ), along with the
specimen management routing and tracking (SMART)
module. Customized InfoMaker reports were created
using PowerBuilder software (Sybase, Dublin, CA).
DESIGN
Utilizing CoPath SMART, we defined specimen points
of tracking (SPOTs) in the AP-LIS dictionary. Each
SPOT was linked to a specific workstation as defined on
the health system’s internal network. As each asset was
scanned and processed at designated tracking points;
their location, scan time, status, and associated user data
were automatically recorded. Standard tracking tools
within the AP-LIS allowed us to monitor assets in realtime throughout the laboratory workflow. We then used
this data to create customized reports, which could be
leveraged in lab management and workflow monitoring.
RESULTS
We utilized both tracking functions and customized
reports for analyzing a variety of workflow processes.
Standard AP-LIS tracking tools allowed us to evaluate each
case’s hierarchy of assets in a single view. This enabled
individuals to evaluate each case asset and their statuses in
the laboratory workflow. The tools also provided valuable
error checking capability, in that individual assets could be
reconciled for completeness and/or technical errors resulting
from workflow defects. Beyond asset tracking, customized
reports allowed technicians and lab managers to monitor
workload distribution, productivity, defects in specimen
processing, and the quality control of asset labeling.
1
CONTENT
Advances in anatomic pathology laboratory information
systems (AP-LIS) have allowed us to greatly enhance and
streamline our workflow processes. Historically laborious
processes, have now been automated as new functionality
in the AP-LIS have become available. The applicability
S36
CONCLUSION
An automated tracking system, integrated with the APLIS has potential to enhance laboratory efficiency, reduce
errors, and add a component of accountability (i.e. chainof-custody) as specimens travel through the laboratory.
The availability of granular tracking data can enhance
the management of laboratory practices in anatomic
pathology.
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journal
J Pathol Inform
Editor-in-Chief:
Anil V. Parwani ,
Liron Pantanowitz,
Pittsburgh, PA, USA
Pittsburgh, PA, USA
For entire Editorial Board visit : www.jpathinformatics.org/editorialboard.asp
ELECTRONIC POSTER SESSION
Thursday, May 15, 2014
Presented in the Grand Foyer, 2nd Floor, Wyndham Grand Pittsburgh Hotel
Neuropathology Specialty
Training Using Wikis for Case
Presentation of Unknowns
James R. Hackney, Seung Park
Department of Pathology, Division of Informatics, University of Alabama at
Birmingham. E-mail:jhackney@uab.edu
CONTENT
While a few publicly available pathology image archives
are now in existence, curated collections of digital
neuropathology images, presented within their clinical
context, are needed. The wiki format is ideal for the
presentation of contextualized medical images in any
number of interesting formats for instructional purposes.
We have recently built an instructional neuropathology
wiki for the education of Residents and Fellows using the
case presentation format.
TECHNOLOGY
Server Hardware: Dell Precision T3600; Host Virtualization
Hypervisor: VMWare ESXi 4.1.0; Guest Operating System:
Ubuntu Linux Server 12.04 LTS 64-bit; Web Server:
Nginx 1.5; Database Management System: MariaDB 5.5;
Programming Language: PHP-FPM 5.3; Rapid Publication
Environment: MediaWiki 1.21; Image Editor: GNU Image
Manipulation Program (GIMP) 2.8.
DESIGN
A virtual machine with a standard LEMP (Linux, nginx,
MariaDB, PHP) stack was generated and deployed;
MediaWiki was installed atop this stack. A selection of
interesting neuropathology cases was identified; case
report pages for these cases were constructed using
MediaWiki’s markup language, WikiText. Histopathology
and radiology images from these cases were then
post-processed in GIMP, uploaded into MediaWiki,
and added to the pertinent pages, completing the case
reports.
RESULTS
Our educational wiki for surgical neuropathology
simulates the clinical approach to any difficult
diagnostic case, including patient presentation with
pertinent history, laboratory studies, radiological images,
and histopathology. Where appropriate, we present
images of the squash preparation and the frozen
section, asking the observer to construct a differential
diagnosis prior to moving on to the permanent sections,
immunohistochemical stains, and case discussion.
CONCLUSION
Use of this wiki exposes residents to a much greater
number of cases than they are likely to see during their
rotation in Neuropathology. It also exposes them gently
to informatics, as we teach our residents WikiText and
have them upload a case per week over the course of their
Neuropathology rotation. This wiki will therefore become
an integral part of our Neuropathology rotation, giving
our residents the opportunity to (a) Learn neuropathology
by generating teaching content and (b) learn informatics
by editing and administering a wiki in a well-supported
and beginner-friendly environment.
Smartphone Adapters for
Digital Photomicrography
Douglas J. Hartman, Somak Roy, Liron Pantanowitz,
Milon Amin, Raja R. Seethala, Ishtiaque Ahmed,
Samuel A. Yousem, Anil Parwani, Ioan Cucoranu
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA.
E-mail: hartmandj@upmc.edu
CONTENT
Photomicrographs in Anatomic Pathology provide a
means of quickly sharing information from a glass
slide for consultation, education, documentation and
publication. While static image acquisition historically
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involved the use of a permanently mounted camera
unit on a microscope, such cameras may be expensive,
need to be connected to a computer, and often require
proprietary software to acquire and process images.
Another novel approach for capturing digital microscopic
images is to use smartphones coupled with the eyepiece
of a microscope.
TECHNOLOGY
Recently, eight smartphone adapters have been
developed that allow a user to capture digital images
from an optical device (microscope, binoculars,
telescope or gun scope). The aim of this study was
to test the utility of smartphone adapters for digital
photomicrography.
DESIGN
We surveyed the market for adapters to attach
smartphones to the ocular lens of a conventional light
microscope. Three adapters (Magnifi, Skylight and
Snapzoom) were tested. We assessed the designs of
these adapters and their effectiveness at acquiring static
microscopic digital images.
RESULTS
All adapters facilitated the acquisition of digital
microscopic images with a smartphone. The optimal
adapter was dependent on the type of phone used. The
Magnifi adapters for iPhone were incompatible when
using a protective case. The Snapzoom adapter was
easiest to use with iPhones and other smartphones even
with protective cases.
CONCLUSION
Smartphone adapters are inexpensive and easy to use
for acquiring digital microscopic images. However,
they require some adjustment by the user in order
to optimize focus and obtain good quality images.
There are numerous possible applications for which
acquisition of images via a smartphone may be ideal:
(a) Capturing images for tumor board presentation,
(b) sharing occasional interesting cases for educational
purposes, (c) for rapid consultations, such as for frozen
sections, (d) screening select cases to assess the need for
submitting the entire case for consultation, (e) for quality
assurance to document using static images, and (f) for
submitting static images of single microscopic fields
for teleconsultation. Smartphone microscope adapters
provide an economically-feasible method of acquiring
and sharing digital pathology photomicrographs.
S38
Use of Time-of-Day Dependence
of Running Averages as Input to
Patient-Based Quality Control
(PBQC): An Example Using K+
Data for a University Hospital
Bryon P. Jackson, Laura J. McCloskey,
Douglas F. Stickle
Jefferson University Hospital, Philadelphia, PA. E-mail: bryonpjackson@gmail.com
CONTENT
In many hospital laboratories, significant time-of-day
(TOD) variation in running averages of hospital patient
data may be operative for certain analytes, due to regular
TOD-dependent variation in proportions of inpatient and
outpatient subjects. Where such patterns are stable, it is
anticipated that use of TOD-dependent running averages
as inputs to PBQC algorithms could improve receiveroperator characteristics of PBQC. We examined this
premise for PBQC applied to measurement of K+ in a
university hospital.
TECHNOLOGY
Primary patient K+ datasets for two successive months
(M1, M2) were obtained from the Sunquest LIS system.
Data reduction and simulations of PBQC were performed
using Visual Basic.
DESIGN
Running means of length 30 (A30) were calculated
across the datasets with input restricted to samples
within the K+ reference range (3.5-5.0 mmol/L). For
both M1 (n = 17342) and M2 (n = 17199), average
A30 was 4.13 ± 0.075 mmol/L (standard deviation, s).
Average A30 as a function of time-of-day (TOD) was
calculated for 48 half-hour intervals across 24 hours.
Low-frequency-filter Fourier transforms produced
continuous, smooth functions (F1, F2) characterizing
A30 vs. TOD. Simulations (n = 1000) to determine
length-of-sequence of PBQC to detect 1x(2.5s)
deviations of A30 from average A30 (false positives,
assuming in-control data) were performed using
random starting points within the sequence of data
points for M2, when using either a time-invariant
average A30 from M1 as input (control), or when using
TOD-dependent F1 for average A30 from M1 as input
(experiment).
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RESULTS
TOD pattern of variation of A30 was stable across M1
and M2, with high correlation of F2 vs. F1 (r2 = 0.929).
Control simulations (using fixed A30 from M1) yielded a
false-positive rate of 23.8 per month (1 per 1.3 days) for
M2. Experiment simulations (using TOD-dependent A30
function F1 from M1) yielded a false-positive rate of 14.4
per month (1 per 2.1 days) for M2.
CONCLUSIONS
In this example, use of TOD-dependent data for A30
as input for PBQC analysis of K+ data decreased the
false positive rate by 40%. In some settings, use of TODdependent patterns of running averages of patient data may
improve overall receiver-operator characteristics of PBQC.
Data Explorer:A Tool for Data
Exploration and Cohort Discovery
in Massive Multidimensional
Datasets
Ameen Kazerouni, Darryl Tharpe, Ashish Sharma
Department of Biomedical Informatics, Emory University, Atlanta, GA.
E-mail: ameen.kazerouni@emory.edu
CONTENT
decisions. The Data Explorer, exposes The Cancer
Genome Atlas BRCA clinical dataset and images. A pivot
collection requires two primary components, (1) Data for
querying and filtering; (2) Images to visualize the data.
RESULTS
The Data Explorer is used to filter the collection on
one or more clinical attributes. It allows users to explore
the dataset as an interactive whole rather than just one
patient at a time. As exploration progresses, a query is
formulated and maintained. Cohorts of interests can be
pivoted on an additional attribute and the distribution
of the cohort across that attribute can be visualized as
histograms. As seen in Figure 1, histogram bins can be
clicked on to create additional data subsets. Individual
tiles can be single clicked on to view all associated
metadata. Fields within the metadata can be used
to further expand the query. Double clicking on an
individual tile will launch the digitized pathology image
in our image viewer, caMicroscope, for further analysis.
CONCLUSION
The Data Explorer allows you to visualize large
multidimensional datasets and allows efficient exploration
and cohort discovery within multidimensional datasets.
Future work on this system will include the integration
of the Data Explorer into a data analysis workflow. The
workflow would allow for the extraction of formulated
queries and redirection of discovered cohorts to analysis
engines.
Large collections of multidimensional data, accumulated
from multiple sources, are integral components of
integrative studies. Here we report on a system that
provides interactive, visualization of multidimensional
data that facilitates data exploration and cohort discovery
within the datasets.
TECHNOLOGY
The system uses the Silverlight based PivotViewer
Technology. PivotViewer is a framework to interactively
explore massive multidimensional datasets. Such
interactive explorations help expose hidden patterns and
help create cohorts, non-trivial tasks if the data is not
being explored interactively.
DESIGN
Multidimensional biomedical datasets include clinical
data, genomic data, imaging data etc. Interactive
visualization of such collections can provide the
information needed to formulate hypothesis, create
cohorts for validation, and help make data driven
Cytologically Yours:The Utility
of a Wiki as a Teaching Tool in
Cytopathology and Informatics
Jessica A Levesque,1 Stephanie Simmons,1
Isam-Eldin Eltoum,1 Seung Park2
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J Pathol Inform 2014 - Abstracthttp://www.jpathinformatics.org
Department of Pathology, Division of Cytopathology, University of Alabama at
Birmingham, 2 Department of Pathology, Division of Informatics, University of
Alabama at Birmingham. E-mail: jalevesque@uabmc.edu
1
CONTENT
Informatics platforms – most notably rapid publication
environments (e.g. wikis) – are poised to disrupt current
models of resident and fellow education. The benefit of
wikis in education is well-documented, but adoption of
this technology in cytopathology has been slow. In our
cytopathology fellowship program, we have built a wiki
ecosystem in order to provide trainees with (a) A searchable
archive of teaching material, (b) experience in programming
and administering of a complex, stack computing-enabled
web application, and (c) a curated virtual machine that
can be arbitrarily redeployed on any x86-64 computer.
TECHNOLOGY
Server Hardware: Dell PowerEdge 2950; Server Host
Virtualization Hypervisor: VMWare ESXi 4.1.0; Development
Host Virtualization Hypervisor: Oracle VM Virtualbox 4.3;
Guest Operating System: Ubuntu Linux Server 12.04 LTS
64-bit; Web Server: nginx 1.5; Database Management
System: MariaDB 5.5; Programming Language: PHP-FPM
5.3; Rapid Publication Environment: MediaWiki 1.21.
DESIGN
Under the guidance of a pathology informaticist, two
cytopathology fellows, both without prior informatics
experience, built a field-deployable LEMP (Linux, nginx,
MariaDB, PHP) stack as a virtual machine; MediaWiki was
then installed atop the stack. One fellow catalogued extant
cytopathology teaching materials (organ based cytology
lectures, “unknown” conferences, cytologic/histologic
correlation conferences) and converted them directly
into wiki-based case presentations. The other fellow
programmed several PHP-based extensions for MediaWiki,
one of which allows for the direct display of Microsoft
PowerPoint slide shows in the wiki. This combination
approach allowed for both (a) Rapid generation of teaching
content and (b) easy reuse of current teaching content.
RESULTS
The wiki has become an integral part of both the
cytopathology fellowship and the resident cytopathology
rotation. Case studies, didactic material, and “unknowns”
are added to the wiki on a monthly basis.
CONCLUSION
The creation of a wiki page for teaching allows for a
centralized location for residents, students, and fellows
S40
to read and learn about cases from our institution.
Furthermore, it gives residents and fellows the
opportunity to learn informatics by actually “doing
informatics” – in this case administering and maintaining
a relatively complex Web 2.0 platform. We will continue
to add functionality (videos, live telecytology, whole slide
imaging) in future versions.
Automated Registration of
Multimodal Microscopy Images
for Integrative Analysis of Tumor
Tissue Sections
Giuseppe Lippolis,1 Anders Edsjö,2
Leszek Helczynski,3 Anders Bjartell,1
Niels Chr Overgaard,4
Department of Clinical Sciences, Division of Urological Cancers, Lund University,
Malmö, Sweden, 2Department of Pathology, University of Gothenburg, Gothenburg,
Sweden, 3University and Regional Laboratories Region Skåne, Clinical Pathology,
Malmö, Sweden, 4Centre for Mathematical Sciences, Lund University, Malmö,
Sweden. E-mail: giuseppe.lippolis@med.lu.se
1
CONTENT
Morphological and molecular information from tissue
samples may be integrated by aligning microscopic
histological images in a multiplex fashion. This process
is usually time-consuming and exhibiting intra- and interuser variability. Our aim is to investigate the feasibility
of applying modern image analysis methods to automatic
alignment of microscopic images from differently stained
adjacent paraffin sections from tissue specimens.
TECHNOLOGY
The algorithm has been initially tested in Matlab
and then implemented in a C++ framework using
free libraries like OpenCV. Image pairs were aligned
allowing for translation, rotation and scaling. The
registration was performed automatically by first
detecting landmarks in both images, using the scale
invariant image transform (SIFT), followed by the
well-known RANSAC protocol for finding point
correspondences and finally aligned by Procrustes fit.
The Registration results were evaluated using both
visual and quantitative criteria.
DESIGN
Tissue samples, obtained from biopsy or radical
prostatectomy, were sectioned and stained with either
hematoxylin and eosin (H and E), immunohistochemistry
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J Pathol Inform 2014 - Abstracthttp://www.jpathinformatics.org
for p63 and AMACR or Time Resolved Fluorescence
(TRF) for androgen receptor (AR). Another set of
breast biopsies was also used for 12 biomarkers on
12 consecutive tissue sections.
RESULTS
Images of consecutive tissue sections stained with
H and E and p63/AMACR were successfully aligned
in 85 of 88 cases (96.6%). The performance of the
algorithm was evaluated in different Gleason scores
classes. The failures occurred only in 3 out of 13 cores
with highly aggressive cancer (Gleason score ≥8) but
these cases showed also some damage in the tissue.
Secondly, TRF and H and E image pairs were aligned
correctly in 103 out of 106 cases (97%). The third
experiment considered the alignment of image pairs from
large breast biopsies progressively further away. The initial
results show a success rate of ca. 80%.
CONCLUSION
The proposed method is both feasible and fast and
well suited for automatic segmentation and analysis
of specific areas of interest. It can enable multiplex
biomarker analysis, TMA alignment and integration of
morphological information with protein expression data
from a stack of consecutive tissue sections.
Texture Analysis and Gleason
Sub-Pattern Classification in
Prostate Cancer Staging
The 20 images used in the dataset were scanned at 40x
on a Leica SCN400 Slide-Scanner. Features are extracted
using an OpenCV and C++ based framework. Linear
SVM models are used to classify image sub-regions as one
of the described classes.
DESIGN
We perform a discrete mapping of an image in a tilebased classification framework. Images were annotated
with 5 classes: Gleason 3, 4, 5 and intermediary
patterns. Annotated regions were validated by a panel of
pathologists. Random-forest feature selection is performed
to improve accuracy and determine good feature subsets.
RESULTS
Choosing correct parameters for some feature sets will in
general perform just as well as a feature subset chosen
from a larger set using feature selection. Feature selection
also improves accuracy of Gleason pattern classification,
and lowers feature extraction time. Sub-pattern clustering
for subsequent classification improves base model
accuracy and can help the model and feature selection
process by visualizing the different clusters present with
given image parameters. When classifying tumour versus
benign stromal regions we have achieved an accuracy of
86.9% accuracy. Additionally, we have reached 80.99%
accuracy when discriminating Gleason 3 and Gleason 4
patterns, and 90.68% for Gleason 4 and Gleason 5.
CONCLUSIONS
Nicholas P. McCarthy , Padraig Cunningham ,
Jim Diamond2, Gillian O’Hurley1
1
TECHNOLOGY
1
University College Dublin, Computer Science and Informatics, Dublin, Ireland,
PathXL Ltd., Belfast, Northern Ireland. E-mail: (nicholas.mccarthy@gmail.com)
1
2
CONTENT
We investigate the identification and classification of
tumour and Gleason patterns in prostate histopathology
images using different texture methods. Most recent
papers in this area have concentrated in the binary
(tumour vs non-tumour) and multi-class (Gleason
pattern) cases. Our dataset includes intermediary
patterns where Gleason 3 is evolving into Gleason 4, and
Gleason 4 into Gleason 5. We also investigate the use of
clustering as a classification pre-processing step in the
identification of global and intra-Grade tissue patterns,
and how they relate to increases in accuracy in the multiclass case.
Feature selection should be performed routinely in
cases where there are many disparate feature sets and
large feature vectors, as is often the case in automated
histopathology analysis. This does not increase accuracy
in all cases, but should reduce feature extraction time by
removing redundant and highly-correlated features, and
avoid overfitting a model to a particular set of images,
thereby increasing model generalization on unseen images.
Diagnostic Differences
between Glass Slide and
Digital Slide Image Evaluation:
A Morphological Feature Based
Study
Anil V. Parwani1, David Glinski2, Orly Aridor2,
Liron Pantanowitz1, Leslie Anthony2, Jonhan Ho3
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Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh,
PA, 2Office of Sponsored Programs and Research Support, University of Pittsburgh
Medical Center, Pittsburgh, PA, 3Department of Dermatopathology, University of
Pittsburgh Medical Center, Pittsburgh, PA. E-mail: (parwaniav@upmc.edu)
1
experience may have contributed to comments favoring
glass slide examinations. Additional studies are needed to
determine if intra-pathologist concordance improves with
increased digital experience.
CONTENT
Prior pathology validation studies comparing glass to digital
slides report excellent diagnostic concordance. These studies
focused largely on diagnoses and not specific morphology.
TECHNOLOGY
The aim of this study was to assess diagnostic differences
between glass and digital slides focusing on morphologic
features. A second intent of the study was to provide an
opportunity for practical application of recently installed
scanning equipment at five United States Air Force
Medical Service (AFMS) pathology centers.
DESIGN
Utilization of Computerized
Physician Order Entry and
Electronic Medical Record
In-Patient Documentation to
Improve Fine Needle Aspiration
Service
Matthew A. Smith1, Sara E. Monaco,1
Joel Weinberg 2, Anil V. Parwani, 1 Liron
Pantanowitz,1
Departments of Pathology and 2Internal Medicine, University of Pittsburgh Medical
Center, Pittsburgh, PA. E-mail: smithma@upmc.edu
1
Surgical pathology cases with H and E slides were
randomly selected from AFMS and University of
Pittsburgh Medical Center pathology labs. Representative
slides (1-2 key slides/case) were scanned at 20x using
Aperio AT scanners (Vista, CA). Of 131 digitized cases,
7 were excluded due to either levels/tissue fragments
missed during scanning (n = 4) or pathologist deferral
for subspecialist consultation (n = 3). Nine pathologists
at six locations reviewed the remaining 124 cases.
Case-related clinical histories were provided. Each
participating pathologist viewed both digital and glass
slides with no wash out period and documented detailed
histomorphologic features required for diagnosis.
CONTENT
Benefits of a patient electronic medical record (EMR)
include computerized physician order entry (CPOE)
and electronic documentation. Currently, these features
are typically not used in Anatomical Pathology practice.
We describe our experience of customizing the EMR to
facilitate fine needle aspiration (FNA) consultations for
inpatients and the creation of a cytopathology-specific
template for documenting these procedures directly in
the patient’s electronic chart.
RESULTS
TECHNOLOGY
Overall intra-pathologist concordance for morphologic
features was 96.8% (120/124 cases). Pathologists reported
a total of 7 cases for which digital slide evaluation of
morphologic features was problematic; in addition to the
4 cases that pointed to specific differences in morphologic
features, 3 cases referenced better color and resolution
with glass slides viewed under the microscope. Three
additional cases referenced multiple tissue fragments
being easier to examine on the glass slide. Though it
was not a focus of the study, diagnostic concordance was
95.9% (119/124); discordance ranged from minor (n = 4)
to moderate (n = 1).
EMR used is PowerChart (Cerner, Kansas City, MO).
CONCLUSIONS
The current study is unique because no wash out period
challenged study pathologists to compare and document
differences in morphological features between these two
modalities in real time. Limited AFMS digital pathology
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DESIGN
Requests for FNA consultations on inpatients were
added to the CPOE menu in the EMR. The order was
named “Cytology, Fine Needle Aspiration FNA Consult”,
with synonyms “biopsy and “fine needle aspiration”.
Data fields captured patient details, reason for FNA,
anatomical site to be biopsied, and requesting physician’s
contact details in the order. An electronic template was
subsequently designed to generate a note in the EMR
after completing an inpatient FNA.
RESULTS
Electronic orders for a bedside FNA triggered three
simultaneous actions: (1) Automatic notification of the
hospital operator to alert the cytopathology secretary
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to schedule the FNA, (2) printing of the order on
a networked printer located in the cytopathology
department, and (3) addition of the order to a daily
cytology log. Offering FNA orders in the CPOE
menu made it easier for clinicians to request these
procedures and for their orders to contain helpful clinical
information. Recording completed FNA procedures in the
EMR by cytopathology staff promoted standardization
of reports, ensured accurate and complete paperless
documentation in the EMR, and reduced the number of
calls to cytology from clinical house staff inquiring about
preliminary diagnoses. Forms completed by cytopathology
fellows participating in a bedside FNA were designed to
be forwarded to their attending’s queue to be endorsed.
TECHNOLOGY
CONCLUSION
After establishing a secure WiFi network connection
Glass was tested in the autopsy suite [Figure 1a].
The pathologist initiated video calls using a shared
Google+ hangout. Remote pathologists invited to join
Google+ could view live feeds from the autopsy suite.
The ergonomics during autopsy, ability to acquire static
images and perform telepathology were evaluated.
Our experience demonstrates the benefits our
cytopathology division derived by leveraging available
features in the institutional EMR. Employing CPOE
for clinicians to order FNAs on inpatients made it userfriendly and more in line with how they currently order
other tests and consultations. Electronic templates for
procedures notes on inpatient FNAs within the EMR
improved documentation in the patient chart, streamlined
the workflow, reduced the need for transcription, and
made the preliminary cytology findings accessible to
clinical teams caring for inpatients. Efforts are underway
at our institution to add similar CPOE orders to our
outpatient EMR (Epic) to promote our FNA clinic service.
Applications of Google
Glass [GLΛSSTM] in Autopsy
Pathology
Muhammad A. Syed1, Jeffrey Nine1,
Ishtiaque Ahmed2, Anil V. Parwani1,
Chris Saylor3, Jeff McHugh2, Brian Kolowitz2,
Jeffrey Taylor2, George Michalopoulos1,
Liron Pantanowitz1
Google Glass (explorer edition) runs the Android operating
system with a 640×360 display and 5-megapixel camera
capable of taking photos and recording video. Glass can use
Wi-Fi 802.11b/g or Bluetooth for connectivity. The device
has a built-in 16GB hard drive for storage with 682MB RAM.
Unique features include a motion sensitive accelerometer
for gestural commands, ambient light sensing, proximity
sensor and a bone conduction transducer. An extended
external battery pack and charger for USB Mobile Devices
(9000 mAh) was employed during testing.
DESIGN
RESULTS
Google Glass use in the autopsy room had pros and
cons. Streaming video and audio quality to participants
in other hospitals was clear. Hands-free capturing of
static images was easy and image quality of organs being
examined was acceptable at a 2-3 foot distance from the
specimen [Figure 1b and c]. Problems included distracting
background noise in the autopsy suite from ventilation,
echoing and presence of multiple people. Voice navigation
failed when the wearer used a surgical mask/shield. Fingerswipe navigations were difficult because of bloody gloves.
CONCLUSIONS
Overall there are potential positive uses of Google
Glass in the autopsy room. The best use of Glass was
streaming video to others during an autopsy. Finger-swipe
navigation of Glass is best avoided during an autopsy.
Department of Pathology, University of Pittsburgh Medical Center, 2Information
Services Division, University of Pittsburgh Medical Center, 3Center for Medical
Innovation, University of Pittsburgh. E-mail: (syedma2@upmc.edu)
1
CONTENT
Google Glass (GLΛSSTM) are glasses that consist of a
head-mounted, wearable computer that can connect to
the Internet and display information in a smartphonelike format. Only a few individuals in the United States
have been selected to test Google Glass as an Explorer
Program. Our aim was to explore the utilization of
Google Glass in gross autopsy pathology.
Figure 1: (a) Google Glass use during autopsy. (b and c) Autopsy
images captured using Glass. (d) Glass protective eye lenses
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Problems related to voice recognition could be alleviated
by adding a headset microphone and installing clear eye
lenses provided with the glasses instead of a protective
face shield [Figure 1d].
Mapping LOINC Codes:The
UPMC Experience
Muhammad Syed1, Tony Gigliotti2,
Michael Sendek2, Anil V. Parwani1,
Liron Pantanowitz1,
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA,
2
Information Services Division, University of Pittsburgh Medical Center, Pittsburgh,
PA. E-mail: syedma2@upmc.edu
1
CONTENT
Under the Health Information Technology (HITECH)
Act, Meaningful Use supports using Logical Observation
Identifiers Names and Codes (LOINC) as a standard
for electronic exchange of laboratory data between the
laboratory information system (LIS) and electronic
medical records (EMRs). As a result, pathology
laboratories that do not routinely use LOINC need to
map their lab catalogues to the LOINC standards. The
aim of this communication is to share our experience
with mapping LOINC codes at the Univeristy of
Pittsburgh Medical Center (UPMC).
TECHNOLOGY
Tools used to identify LOINC definitions were the LOINC
dictionary portal and RELMA desktop mapping program
found on the LOINC homepage: https://loinc.org/LOINC
mapping employed our Sunquest LIS (v7.1, Sunquest
Information Systems, Tucson, AZ) and dbMotion™ clinical
data repository (v5.0, dbMotion Inc., Pittsburgh, PA).
DESIGN
All lab tests utilized during one year at UPMC recorded
in the dbMotion™ clinical data repository were analyzed.
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We identified over 23,000 laboratory test results. The
tests were sorted according to frequency of use. A Pareto
analysis demonstrated that 80% of tests ordered occurred
in the first 300 highest volume tests. LOINC codes
for lab tests were mapped in two phases; first applying
LOINC to the top 300 tests, then to the remainder of
the data set. Each discrete code was manually evaluated
utilizing LOINC web tools, except for send out tests
where codes were supplied by our primary reference
laboratory. Verified LOINC codes were maintained in the
Sunquest LIS and mapped with all downstream EMRs
receiving lab results.
RESULTS
Phase 1 required 2 months of analyst time and phase
2 another 7 months to code the remaining tests. An
estimated 1000 hours was needed. Test descriptors
entered in the LOINC search tool often brought back
many hits, each needing evaluation for “Best fit” of
LOINC mapping. Various lab supervisors and clinical
pathology directors were consulted to code difficult tests,
specifically microbiology and molecular tests. For newer
lab tests, such as molecular genetics and next generation
sequencing, no LOINC codes were found.
CONCLUSION
LOINC mapping is a challenging task that requires
many manual hours to accomplish. Difficulties were
experienced with manual data entry errors, lack of
analyst knowledge regarding the meaning of esoteric
lab tests, and no codes for new molecular tests.
While defined LOINC codes could be maintained
in the Sunquest LIS to support interoperability with
our multiple EMRs, the LIS was limited by a lack of
hierarchy for test nomenclature. There were limited
options for us to perform quality assurance on our
LOINC database to verify the accuracy of codes.
Successful LOINC mapping has enabled UPMC to not
only fulfil the requirements required to comply with
Meaningful Use, but to use these codes for electronic
laboratory reporting with state agencies and enable
enterprise data analytics ventures.