Introduction: Critical values are reported to clinicians when laboratory values are life threatening and require immediate attention. To date no definitive critical value limit recommendations have been produced regarding therapeutic drug monitoring. Some laboratories choose to publish critical value lists online. These publicly available values may be accessed and potentially utilized by laboratory staff, patient care providers, and patients. Materials and Methods: A web-based search of laboratories associated with the Accreditation Council for Graduate Medical Education pathology residency programs was initiated to determine which therapeutic drugs had critical values and to examine the degree of variation in published critical values for these institutions. Results: Of the 107 institutions with university-based pathology training programs, 36 had published critical values online for review. Thirteen therapeutic drugs were investigated and the number of institutions reporting critical value limits for the drug, as well as the median, range, standard deviation, and the coefficient of variation of critical value concentration limits for each drug were determined. A number of the online critical value limits were deemed to be erroneous, most likely due to incorrectly listed units of measurement. Conclusions: There was a large degree of heterogeneity with regard to the chosen critical value limits for therapeutic drugs. This wide variance in critical values appears to be greater than that observed in interassay proficiency testing. Institutions should reexamine the rationale for their current critical value parameters and ensure that critical value limits and associated units are accurately published online.

Increased type I error resulting from multiple statistical comparisons remains a common problem in the scientific literature. This may result in the reporting and promulgation of spurious findings. One approach to this problem is to correct groups of P-values for "family-wide significance" using a Bonferroni correction or the less conservative Bonferroni-Holm correction or to correct for the "false discovery rate" with a Benjamini-Hochberg correction. Although several solutions are available for performing this correction through commercially available software there are no widely available easy to use open source programs to perform these calculations. In this paper we present an open source program written in Python 3.2 that performs calculations for standard Bonferroni, Bonferroni-Holm and Benjamini-Hochberg corrections.

Telecytology is the interpretation of cytology material at a distance using digital images. For more than a decade, pioneering efforts to introduce telecytology into clinical practice have been reported. A Medline search for "telecytology" and "cytology" reveals a voluminous literature, though much of what has been published to date is based on technologies that are rapidly becoming obsolete. The technological limitations of previous techniques, including the transmission of static digital images and dynamic streaming images, have limited telecytology to minor niches. The primary problem with these technologies is that the remote viewer can only see a small fraction of the material on the original slides, introducing the possibility of diagnostic error based not only on image quality but also on image selection. Remote robotic microscopy offers one possible solution to this problem, but to date has found limited acceptance, principally attributable to slow operating times. Whole slide imaging seems to be a much more promising solution, though cytology-specific literature regarding its use is still scant. The advent of whole slide imaging opens up new possibilities for telecytology by enabling high-quality images of entire cytology specimens to be available to anyone, anywhere via the Internet. Although challenges remain, especially with regard to capturing the full microscopy experience including multiple planes of focus and sharp high-powered images, rapidly advancing technology promises to overcome these limitations. Increasing application of whole slide imaging technology in surgical pathology will undoubtedly also increase its application to cytology due to the increasing affordability and practicality of the equipment as it serves a larger number of useful roles within a pathology department. The current and expanding applications of telecytology for clinical practice, education, quality assurance, and testing will be reviewed.

For many years pathologists have used Hematoxylin and Eosin (H&E), single marker immunohistochemistry (IHC) and in situ hybridization with manual analysis by microscopy or at best simple digital imaging. There is a growing trend to update pathology to a digital workflow to improve objectivity and productivity, as has been done in radiology. There is also a need for tissue-based multivariate biomarker assays to improve the accuracy of diagnostic, prognostic, and predictive testing. Multivariate tests are not compatible with the traditional single marker, manual analysis pathology methods but instead require a digital platform with brightfield and fluorescence imaging, quantitative image analysis, and informatics. Here we describe the use of the Hamamatsu NanoZoomer Digital Pathology slide scanner with HCImage software for combined brightfield and multiplexed fluorescence biomarker analysis and highlight its applications in biomarker research and pathology testing. This combined approach will be an important aid to pathologists in making critical diagnoses.

Background: In histopathology, the quantitative assessment of various morphologic features is based on methods originally conceived on specific areas observed through the microscope used. Failure to reproduce the same reference field of view using a different microscope will change the score assessed. Visualization of a digital slide on a screen through a dedicated viewer allows selection of the magnification. However, the field of view is rectangular, unlike the circular field of optical microscopy. In addition, the size of the selected area is not evident, and must be calculated. Materials and Methods: A digital slide morphometric system was conceived to reproduce the various methods published for assessing tumor budding in colorectal cancer. Eighteen international experts in colorectal cancer were invited to participate in a web-based study by assessing tumor budding with five different methods in 100 digital slides. Results: The specific areas to be tested by each method were marked by colored circles. The areas were grouped in a target-like pattern and then saved as an .xml file. When a digital slide was opened, the .xml file was imported in order to perform the measurements. Since the morphometric tool is composed of layers that can be freely moved on top of the digital slide, the technique was named digital slide dynamic morphometry. Twelve investigators completed the task, the majority of them performing the multiple evaluations of each of the cases in less than 12 minutes. Conclusions: Digital slide dynamic morphometry has various potential applications and might be a useful tool for the assessment of histologic parameters originally conceived for optical microscopy that need to be quantified.

Introduction: The increasing availability of whole slide imaging (WSI) data sets (digital slides) from glass slides offers new opportunities for the development of computer-aided diagnostic (CAD) algorithms. With the all-digital pathology workflow that these data sets will enable in the near future, literally millions of digital slides will be generated and stored. Consequently, the field in general and pathologists, specifically, will need tools to help extract actionable information from this new and vast collective repository. Methods: To address this limitation, we designed and implemented a tool (dCORE) to enable the systematic capture of image tiles with constrained size and resolution that contain desired histopathologic features. Results: In this communication, we describe a user-friendly tool that will enable pathologists to mine digital slides archives to create image microarrays (IMAs). IMAs are to digital slides as tissue microarrays (TMAs) are to cell blocks. Thus, a single digital slide could be transformed into an array of hundreds to thousands of high quality digital images, with each containing key diagnostic morphologies and appropriate controls. Current manual digital image cut-and-paste methods that allow for the creation of a grid of images (such as an IMA) of matching resolutions are tedious. Conclusion: The ability to create IMAs representing hundreds to thousands of vetted morphologic features has numerous applications in education, proficiency testing, consensus case review, and research. Lastly, in a manner analogous to the way conventional TMA technology has significantly accelerated in situ studies of tissue specimens use of IMAs has similar potential to significantly accelerate CAD algorithm development.

Background: Cytology poses different obstacles in whole slide imaging compared to surgical pathology slides. A single focal plane suffices for most of the latter, but cytology slides are thicker, potentially requiring multiple focal planes for adequate diagnostic information. Multiple focal planes adversely impact scanning time per slide, evaluation times, and file sizes. In this pilot study, we evaluated and compared the multilayer stack method to the extended focus algorithm as an alternative which collapses multiple focal planes into a single image, retaining only focused areas from each plane. Materials and Methods: 10 SurePath^; cervical cytology slides were scanned at three thickness settings: 18, 24, and 30 μm. Three scanners were used: (1) Hamamatsu Nanozoomer 2.0-HT, (2) 3DHISTECH Mirax scan, and (3) Bioimagene iScan Coreo Au. The Nanozoomer and iScan utilized multilayer stacking, while the Mirax files were composited by extended focus. Scan times and file sizes were recorded, and image quality compared. Results: The Nanozoomer stacks averaged 1.58 gb and around 25 min for each slide, while the iScan stacks ranged from 6.23 to 9.3 gb and took 34-50 min to scan. The Mirax images averaged 210 mb and took 13-20 min to scan. Multilayer stack image quality from both Nanozoomer and iScan was fairly comparable. The iScan revealed significant mechanical issues that did not correspond to user settings. The Mirax images showed worrisome loss of crisp focus detail, worsening with increasing focal planes and impacting assessment of nuclear contours and chromatin detail. Conclusions: The optimal number of focal planes remains unknown for cytology. Multilayer stacks require excessive scanning time, network bandwidth, and file storage. Extended focus was evaluated as an alternative, but significant image quality issues were revealed. Further large-scale studies are needed to assess their clinical impact.

Introduction: A lot of attention has been generated in recent years by digital pathology and telepathology. Multiple reasons for and barriers to effective adoption are discussed in the current literature. Digital slides are the most promising medium at this time. The goal of our study was to evaluate whether the change in the methodology, particularly utilizing the so-called high-definition hematoxylin and eosin (H and E) slides, enhanced the quality of the final digital slide, and whether pathologists who tested the results perceived this as a difference in quality. Methods: The study was a blinded comparison of digital slides prepared using two methods: standard H&E batch staining and automated individual "high definition" HD HE staining. Four pathologists have compared 80 cases stained with each method. Results: The results discussed in this study show potential promise that the utilization of protocol(s) adapted for tissue and for imaging might be preferable for digital pathology in at least some of the pathology subspecialties. In particular, the protocol evaluated here was capable of turning out digital slides that had more contrast and detail, and therefore were perceived to provide enhanced diagnostically significant information for the pathologist.

Accurate focusing is a critical challenge of whole slide imaging, primarily due to inherent tissue topography variability. Traditional line scanning and tile-based scanning systems are limited in their ability to acquire a high degree of focus points while still maintaining high throughput. This review examines limitations with first-generation whole slide scanning systems and explores a novel approach that employs continuous autofocus, referred to as independent dual sensor scanning. This "second-generation" concept decouples image acquisition from focusing, allowing for rapid scanning while maintaining continuous accurate focus. The technical concepts, merits, and limitations of this method are explained and compared to that of a traditional whole slide scanning system.

Background: Quality assurance (QA) programs in cytopathology laboratories in the USA currently primarily involve the review of Pap tests per clinical laboratory improvement amendments of 1988 federal regulations. A pre-signout quality assurance tool (PQAT) at our institution allows the laboratory information system (LIS) to also automatically and randomly select an adjustable percentage of non-gynecological cytopathology cases for review before release of the final report. The aim of this study was to review our experience and the effectiveness of this novel PQAT tool in cytology. Materials and Methods: Software modifications in the existing LIS application (CoPathPlus, Cerner) allow for the random QA of 8% of cases prior to signout. Selected cases are assigned to a second QA cytopathologist for review and all agreement and disagreements tracked. Detected errors are rectified before the case is signed out. Data from cases selected for PQAT over an 18-month period were collected and analyzed. Results: The total number of non-gynecological cases selected for QA review was 1339 (7.45%) out of 17,967 cases signed out during this time period. Most (1304) cases (97.4%) had an agreement in diagnosis. In 2.6% of cases, there were disagreements, including 34 minor and only 1 major disagreement. Average turnaround time of cases selected for review was not significantly altered. Conclusion: The PQAT provides a prospective QA mechanism in non-gynecological cytopathology to prevent diagnostic errors from occurring. This LIS-driven tool allows for peer review and corrective action to be taken prior to reporting without delaying turnaround time, thereby improving patient safety.

Introduction: With recent advances, it is now possible to view whole slide images (WSI) on mobile, high-resolution, viewing devices (MVD). This creates a new paradigm in which MVDs may be used for consultation and/or diagnosis. Validation of the results with devices is important for practitioners and regulators. We evaluated the use of MVDs in frozen section (FS) interpretation. Methods: A series of 72 consecutive FS cases were selected for potential inclusion in the study. A 67 case subset of these were successfully scanned at 20x magnification. Scan times were recorded. A sample of WSI FS cases, with gross and clinical information, was presented to six pathologists on an iPad MVD using the Interpath application. Times to diagnosis were recorded. Results were compared with the original reported and final diagnosis. Participants also completed a survey assessing image quality, interface, and diagnostic comfort level. Results: Scan times averaged two minutes and 46 seconds per slide, (standard deviation [SD] 2 minutes 46 seconds). Evaluation times averaged 4 minutes and 59 seconds per case, range to 13 minutes and 50 seconds, SD 3 minutes 48 seconds. Concordance between initial FS diagnosis and rendered through the MVD was 89%. Minor discrepancies made up 8% and major disagreements 3%. The kappa statistic for this series is 0.85. Participants rated the experience at 5 on a 10-point scale, range 3 to 7. Two-thirds found the image quality to be adequate, half were satisfied with image resolution, and 33% would be willing to make a diagnosis on the iPad, plus one only for special cases. Five of six respondents (83%) found the navigation with the study software difficult. Conclusion: Image fidelity and resolution makes the iPad potentially suitable for WSI evaluation of FS. Acceptable accuracy is attainable for FS interpretation. But, although possible to obtain acceptable results, use of the iPad with Interpath to view WSI is not easy and meets user resistance. The obstacle of slide navigation at high magnification could introduce frustrations, delays, or errors.

Background: The Tissue Microarray Data Exchange Specification (TMA DES) is an XML specification for encoding TMA experiment data. While TMA DES data is encoded in XML, the files that describe its syntax, structure, and semantics are not. The DTD format is used to describe the syntax and structure of TMA DES, and the ISO 11179 format is used to define the semantics of TMA DES. However, XML Schema can be used in place of DTDs, and another XML encoded format, RDF, can be used in place of ISO 11179. Encoding all TMA DES data and metadata in XML would simplify the development and usage of programs which validate and parse TMA DES data. XML Schema has advantages over DTDs such as support for data types, and a more powerful means of specifying constraints on data values. An advantage of RDF encoded in XML over ISO 11179 is that XML defines rules for encoding data, whereas ISO 11179 does not. Materials and Methods: We created an XML Schema version of the TMA DES DTD. We wrote a program that converted ISO 11179 definitions to RDF encoded in XML, and used it to convert the TMA DES ISO 11179 definitions to RDF. Results: We validated a sample TMA DES XML file that was supplied with the publication that originally specified TMA DES using our XML Schema. We successfully validated the RDF produced by our ISO 11179 converter with the W3C RDF validation service. Conclusions: All TMA DES data could be encoded using XML, which simplifies its processing. XML Schema allows datatypes and valid value ranges to be specified for CDEs, which enables a wider range of error checking to be performed using XML Schemas than could be performed using DTDs.

Background: Whole slide imaging (WSI) makes it possible to capture images of an entire histological slide. WSI has established roles in surgical pathology, including support of off-site frozen section interpretation, primary diagnosis, educational activities, and laboratory quality assurance (QA) activities. Analyses of the cost of WSI have traditionally been based solely on direct costs and diagnostic accuracy; however, these types of analyses largely ignore workflow and cost issues that arise as a result of redundancy, the need for additional staffing, and customized software development when WSI is integrated into routine diagnostic surgical pathology. The pre-scan, scan, and post-scan costs; quality control and QA costs; and IT process costs can be significant, and consequently, pathology groups can find it difficult to perform a realistic cost-benefit analysis of adding WSI to their practice. Materials and Methods: In this paper, we report a "value added" approach developed to guide our decisions regarding integration of WSI into surgical pathology practice. The approach focuses on specific operational measures (cost, time, and enhanced patient care) and practice settings (clinical, education, and research) to identify routine activities in which the addition of WSI can provide improvements. Results: When applied to our academic pathology group practice, the value added approach resulted in expanded and improved operations, as demonstrated by outcome based measures. Conclusion: A value added can be used to perform a realistic cost-benefit analysis of integrating WSI into routine surgical pathology practice.

Context: Whole slide imaging (WSI) for digital pathology involves the rapid automated acquisition of multiple high-power fields from a microscope slide containing a tissue specimen. Capturing each field in the correct focal plane is essential to create high-quality digital images. Others have described a novel focusing method which reduces the number of focal planes required to generate accurate focus. However, this method was not applied dynamically in an automated WSI system under continuous motion. Aims: This report measures the accuracy of this method when applied in a rapid continuous scan mode using a dual sensor WSI system with interleaved acquisition of images. Methods: We acquired over 400 tiles in a "stop and go" scan mode, surveying the entire z depth in each tile and used this as ground truth. We compared this ground truth focal height to the focal height determined using a rapid 3-point focus algorithm applied dynamically in a continuous scanning mode. Results: Our data showed the average focal height error of 0.30 (±0.27) μm compared to ground truth, which is well within the system's depth of field. On a tile by tile assessment, approximately 95% of the tiles were within the system's depth of field. Further, this method was six times faster than acquiring tiles compared to the same method in a non-continuous scan mode. Conclusions: The data indicates that the method employed can yield a significant improvement in scan speed while maintaining highly accurate autofocusing.

Introduction: Spatially invariant vector quantization (SIVQ) is a texture and color-based image matching algorithm that queries the image space through the use of ring vectors. In prior studies, the selection of one or more optimal vectors for a particular feature of interest required a manual process, with the user initially stochastically selecting candidate vectors and subsequently testing them upon other regions of the image to verify the vector's sensitivity and specificity properties (typically by reviewing a resultant heat map). In carrying out the prior efforts, the SIVQ algorithm was noted to exhibit highly scalable computational properties, where each region of analysis can take place independently of others, making a compelling case for the exploration of its deployment on high-throughput computing platforms, with the hypothesis that such an exercise will result in performance gains that scale linearly with increasing processor count. Methods: An automated process was developed for the selection of optimal ring vectors to serve as the predicate matching operator in defining histopathological features of interest. Briefly, candidate vectors were generated from every possible coordinate origin within a user-defined vector selection area (VSA) and subsequently compared against user-identified positive and negative "ground truth" regions on the same image. Each vector from the VSA was assessed for its goodness-of-fit to both the positive and negative areas via the use of the receiver operating characteristic (ROC) transfer function, with each assessment resulting in an associated area-under-the-curve (AUC) figure of merit. Results: Use of the above-mentioned automated vector selection process was demonstrated in two cases of use: First, to identify malignant colonic epithelium, and second, to identify soft tissue sarcoma. For both examples, a very satisfactory optimized vector was identified, as defined by the AUC metric. Finally, as an additional effort directed towards attaining high-throughput capability for the SIVQ algorithm, we demonstrated the successful incorporation of it with the MATrix LABoratory (MATLAB ^TM ) application interface. Conclusion: The SIVQ algorithm is suitable for automated vector selection settings and high throughput computation.

Whole slide imaging (WSI), or "virtual" microscopy, involves the scanning (digitization) of glass slides to produce "digital slides". WSI has been advocated for diagnostic, educational and research purposes. When used for remote frozen section diagnosis, WSI requires a thorough implementation period coupled with trained support personnel. Adoption of WSI for rendering pathologic diagnoses on a routine basis has been shown to be successful in only a few "niche" applications. Wider adoption will most likely require full integration with the laboratory information system, continuous automated scanning, high-bandwidth connectivity, massive storage capacity, and more intuitive user interfaces. Nevertheless, WSI has been reported to enhance specific pathology practices, such as scanning slides received in consultation or of legal cases, of slides to be used for patient care conferences, for quality assurance purposes, to retain records of slides to be sent out or destroyed by ancillary testing, and for performing digital image analysis. In addition to technical issues, regulatory and validation requirements related to WSI have yet to be adequately addressed. Although limited validation studies have been published using WSI there are currently no standard guidelines for validating WSI for diagnostic use in the clinical laboratory. This review addresses the current status of WSI in pathology related to regulation and validation, the provision of remote and routine pathologic diagnoses, educational uses, implementation issues, and the cost-benefit analysis of adopting WSI in routine clinical practice.

Clinicians have traditionally ordered laboratory tests using paper-based orders and requisitions. However, paper orders are becoming increasingly incompatible with the complexities, challenges, and resource constraints of our modern healthcare systems and are being replaced by electronic order entry systems. Electronic systems that allow direct provider input of diagnostic testing or medication orders into a computer system are known as Computerized Provider Order Entry (CPOE) systems. Adoption of laboratory CPOE systems may offer institutions many benefits, including reduced test turnaround time, improved test utilization, and better adherence to practice guidelines. In this review, we outline the functionality of various CPOE implementations, review the reported benefits, and discuss strategies for using CPOE to improve the test ordering process. Further, we discuss barriers to the implementation of CPOE systems that have prevented their more widespread adoption.

Patient safety initiatives throughout the anatomic laboratory and in biorepository laboratories have mandated increasing emphasis on the need for accurately identifying and tracking biospecimen assets throughout their production lifecycle and for archiving/retrieval purposes. However, increasing production volume along with complex workflow characteristics, reliance on manual production processes, and required asset movement to disparate destinations throughout asset lifecycles continue to challenge laboratory efforts. Radio Frequency Identification (RFID) technology, use of radio waves to communicate data between electronic tags attached to objects and a reader, shows significant potential to facilitate and overcome these hurdles. Advantages over traditional barcode labeling include readability without direct line-of-sight alignment to the reader, ability to read multiple tags simultaneously, higher data storage capacity, faster data transmission rate, and capacity to perform multiple read-writes of data to the tag. Most importantly, use of radio waves decreases the need to manually scan each asset, and at each step, identification or tracking event is needed. Temperature monitoring by on-board sensors and three-dimensional position tracking are additional potential benefits of using RFID technology. To date, barriers to implementation of RFID systems in the anatomic laboratory include increased associated costs of tags and readers, system software, data security concerns, lack of specific data standards for stored information, and potential for technological obsolescence during decades of specimen storage. Novel RFID production techniques and increased production capacity are projected to lower costs of some tags to a few cents each. Potentially, information security concerns can be addressed by techniques such as shielding, data encryption, and tag pseudonyms. Commitment by stakeholder groups to develop RFID tag data standards for anatomic pathology and biorepository laboratories could avoid or mitigate the "islands of data" dilemma presented by barcode usage where there are innumerable standards and a consequent paucity of hardware or software "plug and play" interoperability. Work remains to be done to establish the durability and appropriate shielding of individual tag types for use in harsh laboratory environmental conditions, and for long-term archival storage. Finally, given the requirements for long-term storage of biospecimen assets, consideration should be given to ways of mitigating data isolation due to eventual technological obsolescence of a particular RFID technology or software.

Background: Identification of individual prostatic glandular structures is an important prerequisite to quantitative histological analysis of prostate cancer with the aid of a computer. We have developed a computer method to segment individual glandular units and to extract quantitative image features, for computer identification of prostatic adenocarcinoma. Methods: Two sets of digital histology images were used: database I (n = 57) for developing and testing the computer technique, and database II (n = 116) for independent validation. The segmentation technique was based on a k-means clustering and a region-growing method. Computer segmentation results were evaluated subjectively and also compared quantitatively against manual gland outlines, using the Jaccard similarity measure. Quantitative features that were extracted from the computer segmentation results include average gland size, spatial gland density, and average gland circularity. Linear discriminant analysis (LDA) was used to combine quantitative image features. Classification performance was evaluated with receiver operating characteristic (ROC) analysis and the area under the ROC curve (AUC). Results: Jaccard similarity coefficients between computer segmentation and manual outlines of individual glands were between 0.63 and 0.72 for non-cancer and between 0.48 and 0.54 for malignant glands, respectively, similar to an interobserver agreement of 0.79 for non-cancer and 0.75 for malignant glands, respectively. The AUC value for the features of average gland size and gland density combined via LDA was 0.91 for database I and 0.96 for database II. Conclusions: Using a computer, we are able to delineate individual prostatic glands automatically and identify prostatic adenocarcinoma accurately, based on the quantitative image features extracted from computer-segmented glandular structures.

Background: The systematic analysis of imaged pathology specimens often results in a vast amount of morphological information at both the cellular and sub-cellular scales. While microscopy scanners and computerized analysis are capable of capturing and analyzing data rapidly, microscopy image data remain underutilized in research and clinical settings. One major obstacle which tends to reduce wider adoption of these new technologies throughout the clinical and scientific communities is the challenge of managing, querying, and integrating the vast amounts of data resulting from the analysis of large digital pathology datasets. This paper presents a data model, which addresses these challenges, and demonstrates its implementation in a relational database system. Context: This paper describes a data model, referred to as Pathology Analytic Imaging Standards (PAIS), and a database implementation, which are designed to support the data management and query requirements of detailed characterization of micro-anatomic morphology through many interrelated analysis pipelines on whole-slide images and tissue microarrays (TMAs). Aims: (1) Development of a data model capable of efficiently representing and storing virtual slide related image, annotation, markup, and feature information. (2) Development of a database, based on the data model, capable of supporting queries for data retrieval based on analysis and image metadata, queries for comparison of results from different analyses, and spatial queries on segmented regions, features, and classified objects. Settings and Design: The work described in this paper is motivated by the challenges associated with characterization of micro-scale features for comparative and correlative analyses involving whole-slides tissue images and TMAs. Technologies for digitizing tissues have advanced significantly in the past decade. Slide scanners are capable of producing high-magnification, high-resolution images from whole slides and TMAs within several minutes. Hence, it is becoming increasingly feasible for basic, clinical, and translational research studies to produce thousands of whole-slide images. Systematic analysis of these large datasets requires efficient data management support for representing and indexing results from hundreds of interrelated analyses generating very large volumes of quantifications such as shape and texture and of classifications of the quantified features. Materials and Methods: We have designed a data model and a database to address the data management requirements of detailed characterization of micro-anatomic morphology through many interrelated analysis pipelines. The data model represents virtual slide related image, annotation, markup and feature information. The database supports a wide range of metadata and spatial queries on images, annotations, markups, and features. Results: We currently have three databases running on a Dell PowerEdge T410 server with CentOS 5.5 Linux operating system. The database server is IBM DB2 Enterprise Edition 9.7.2. The set of databases consists of 1) a TMA database containing image analysis results from 4740 cases of breast cancer, with 641 MB storage size; 2) an algorithm validation database, which stores markups and annotations from two segmentation algorithms and two parameter sets on 18 selected slides, with 66 GB storage size; and 3) an in silico brain tumor study database comprising results from 307 TCGA slides, with 365 GB storage size. The latter two databases also contain human-generated annotations and markups for regions and nuclei. Conclusions: Modeling and managing pathology image analysis results in a database provide immediate benefits on the value and usability of data in a research study. The database provides powerful query capabilities, which are otherwise difficult or cumbersome to support by other approaches such as programming languages. Standardized, semantic annotated data representation and interfaces also make it possible to more efficiently share image data and analysis results.

All hospitals deal with patient deaths. Multiple departments and personnel must be coordinated to ensure that decedents are safely managed. Prior to 2004, at the University of Pittsburgh Medical Center (UPMC), when a patient passed away, the process of alerting involved personnel, transporting the decedent, and tracking the completion of clinical documents was cumbersome and inefficient. In order to address these concerns, UPMC Remains Tracker, a web-based application, was developed to improve the efficiency and simplify the logistics related to the management of patient deaths. The UPMC Information Services division developed UPMC Remains Tracker, an application that tracks decedents' locations, documentation status, and autopsy status within UPMC hospitals. We assessed qualitative improvement in decedent remains tracking, decedent paperwork management, and staff satisfaction and compliance. UPMC Remains Tracker improved the process of tracking decedents' locations, identifying involved personnel, monitoring autopsy requests, and determining the availability for funeral home transportation. Resident satisfaction with UPMC Remains Tracker was generally positive and scored as "Improved efficiency" and makes identifying and tracking decedents "Much easier". Additionally, the nursing staff reacted favorably to the application. A retrospective review of the use of the application in the management of 100 decedents demonstrated a 93% compliance rate. Among the cases requiring an autopsy, there was a 90% compliance rate. The process of tracking decedents, their paperwork, involved staff, and decedent autopsy status is often inefficient. This assessment suggests that incorporating new technologies such as UPMC Remains Tracker into the management of hospital deaths provides accurate tracking of remains, streamlines the administrative tasks associated with deaths, and increases nursing and resident satisfaction and compliance.

Background: Here, we report the first use of a commercial prototype of full-field optical coherence tomography called Light-CT ^TM . Based on the principle of white light interferometry, Light-CT ^TM generates quick high-resolution three-dimensional tomographic images from unprocessed tissues. Its advantage over the current intra-surgical diagnostic standard, i.e. frozen section analysis, lies in the absence of freezing artifacts, which allows real-time diagnostic impressions, and/or for the tissues to be triaged for subsequent conventional histopathology. Materials and Methods: In this study, we recapitulate known normal histology in nine formalin fixed ex vivo rat organs (skin, heart, lung, liver, stomach, kidney, prostate, urinary bladder, and testis). Large surface and virtually sectioned stacks of images at varying depths were acquired by a pair of 10x/0.3 numerical aperture water immersion objectives, processed and visualized in real time. Results: Normal histology of the following organs was recapitulated by identifying various tissue microstructures. Skin: epidermis, dermal-epidermal junction and hair follicles with surrounding sebaceous glands in the dermis. Stomach: mucosa with surface pits, submucosa, muscularis propria and serosa. Liver: hepatocytes separated by sinusoidal spaces, central veins and portal triad. Kidney: convoluted tubules, medullary rays (straight tubules) and collecting ducts. Prostate: acini and fibro-muscular stroma. Lung: bronchi, bronchioles, alveolar ducts, alveoli and pleura. Urinary bladder: urothelium, lamina propria, muscularis propria, and serosa. Testis: seminiferous tubules with intra-tubular sperms. Conclusion: Light-CT ^TM is a powerful imaging tool to perform fast histology on fresh and fixed tissues, without introducing artifacts. Its compact size, ease of handling, fast image acquisition and safe incident light levels makes it well-suited for various intra-operative and intra-procedural triaging and decision making applications.

Whole slide digital imaging technology has matured considerably over the past decade. Applications in pathology education are widespread and are rapidly transforming the manner in which medical students learn pathology and histology, and they have a novel and significant impact on postgraduate continuing medical education. Whole slide digital images for use in pathology graduate education have been slower in adoption and remain much less widespread. Emphasis on professional competency by the Accreditation Council on Graduate Medical Education (ACGME) and credentialing organizations, however, appear poised to significantly increase. The convergence of these two forces is propitious for pathology training. This article examines the opportunities for the use of whole slide images (WSI) in pathology residency training along with the developing potential uses in each of the areas of competency, as categorized by the ACGME. Barriers to WSI adoption in the pathology community are identified along with potentially significant promoters for adoption in training and practice. Current literature and recent presentations are reviewed. Digital pathology coupled with emphasis on competency is a shift of tremendous magnitude that can dramatically improve our abilities to help trainees acquire, demonstrate, and maintain the skills to practice pathology in the generation ahead.

As digital slides need a lot of storage space, lack of a singular method to acquire and store these large, two-dimensional images has been a major stumbling block in the universal acceptance of this technology. The DICOMS Standard Committee Working Group 26 has put in a tremendous effort to standardize storage methods so that they are more in line with currently available PACS in most hospitals for storage of radiology images. A recent press release (Supplement 145) of these standards was hailed by one and all involved in the field of digital pathology as it will make it easier for hospitals to integrate digital pathology into their already established systems without adding too much overhead costs. Besides, it will enable different vendors developing the scanners to upgrade their products to storage systems that are common across all systems.

Background: Patient identification (ID) errors in point-of-care testing (POCT) can cause test results to be transferred to the wrong patient's chart or prevent results from being transmitted and reported. Despite the implementation of patient barcoding and ongoing operator training at our institution, patient ID errors still occur with glucose POCT. The aim of this study was to develop a solution to reduce identification errors with POCT. Materials and Methods: Glucose POCT was performed by approximately 2,400 clinical operators throughout our health system. Patients are identified by scanning in wristband barcodes or by manual data entry using portable glucose meters. Meters are docked to upload data to a database server which then transmits data to any medical record matching the financial number of the test result. With a new model, meters connect to an interface manager where the patient ID (a nine-digit account number) is checked against patient registration data from admission, discharge, and transfer (ADT) feeds and only matched results are transferred to the patient's electronic medical record. With the new process, the patient ID is checked prior to testing, and testing is prevented until ID errors are resolved. Results: When averaged over a period of a month, ID errors were reduced to 3 errors/month (0.015%) in comparison with 61.5 errors/month (0.319%) before implementing the new meters. Conclusion: Patient ID errors may occur with glucose POCT despite patient barcoding. The verification of patient identification should ideally take place at the bedside before testing occurs so that the errors can be addressed in real time. The introduction of an ADT feed directly to glucose meters reduced patient ID errors in POCT.

Background: Telemedicine has emerged as an efficient means of distributing professional medical expertise over a broad geographic area with few limitations to the various services that can be provided around the globe. Telepathology is particularly well suited to distributing subspecialty expertise in certain environments in an economical fashion, while preserving centers of excellence. Materials and Methods: After a decade of intrainstitutional teleneuropathology for intraoperative consultation, we expanded our practice to cross state lines and communicate between geographically and financially separate medical centers. Results: The result was an effective means of distributing neuropathological expertise while at the same time preserving a professional center of excellence. While technical and legal (i.e., physician licensing) barriers were surmounted, expected and unexpected issues related to communication required commitment on the part of multiple individuals with diverse expertise and responsibilities. Conclusion: Lessons learned from this successful venture can be used to facilitate future efforts in this ever-growing practical vehicle for distributing pathology subspecialty expertise.

Background: With the adoption of a completely electronic workflow by several journals and the advent of telepathology, digital imaging has become an integral part of every scientific research. However, manipulating digital images is very easy, and it can lead to misinterpretations. Aim: To analyse the impact of manipulating digital images on their diagnosis. Design: Digital images were obtained from Papanicolaou-stained smears of dysplastic and normal oral epithelium. They were manipulated using GNU Image Manipulation Program (GIMP) to alter their brightness and contrast and color levels. A Power Point presentation composed of slides of these manipulated images along with the unaltered originals arranged randomly was created. The presentation was shown to five observers individually who rated the images as normal, mild, moderate or severe dysplasia. Weighted k statistics was used to measure and assess the levels of agreement between observers. Results: Levels of agreement between manipulated images and original images varied greatly among observers. Variation in diagnosis was in the form of overdiagnosis or under-diagnosis, usually by one grade. Conclusion: Global manipulations of digital images of cytological slides can significantly affect their interpretation. Such manipulations should therefore be kept to a minimum, and avoided wherever possible.

Introduction: Laser capture microdissection (LCM) facilitates procurement of defined cell populations for study in the context of histopathology. The morphologic assessment step in the LCM procedure is time consuming and tedious, thus restricting the utility of the technology for large applications. Results: Here, we describe the use of Spatially Invariant Vector Quantization (SIVQ) for histological analysis and LCM. Using SIVQ, we selected vectors as morphologic predicates that were representative of normal epithelial or cancer cells and then searched for phenotypically similar cells across entire tissue sections. The selected cells were subsequently auto-microdissected and the recovered RNA was analyzed by expression microarray. Gene expression profiles from SIVQ-LCM and standard LCM-derived samples demonstrated highly congruous signatures, confirming the equivalence of the differing microdissection methods. Conclusion: SIVQ-LCM improves the work-flow of microdissection in two significant ways. First, the process is transformative in that it shifts the pathologist's role from technical execution of the entire microdissection to a limited-contact supervisory role, enabling large-scale extraction of tissue by expediting subsequent semi-autonomous identification of target cell populations. Second, this work-flow model provides an opportunity to systematically identify highly constrained cell populations and morphologically consistent regions within tissue sections. Integrating SIVQ with LCM in a single environment provides advanced capabilities for efficient and high-throughput histological-based molecular studies.

Background: The Tissue Microarray Data Exchange Specification (TMA DES) is an eXtensible Markup Language (XML) specification for encoding TMA experiment data in a machine-readable format that is also human readable. TMA DES defines Common Data Elements (CDEs) that form a basic vocabulary for describing TMA data. TMA data are routinely subjected to univariate and multivariate statistical analysis to determine differences or similarities between pathologically distinct groups of tumors for one or more markers or between markers for different groups. Such statistical analysis tests include the t-test, ANOVA, Chi-square, Mann-Whitney U, and Kruskal-Wallis tests. All these generate output that needs to be recorded and stored with TMA data. Materials and Methods: We propose extending the TMA DES to include syntactic and semantic definitions of CDEs for describing the results of statistical analyses performed upon TMA DES data. These CDEs are described in this paper and it is illustrated how they can be added to the TMA DES. We created a Document Type Definition (DTD) file defining the syntax for these CDEs, and a set of ISO 11179 entries providing semantic definitions for them. We describe how we wrote a program in R that read TMA DES data from an XML file, performed statistical analyses on that data, and created a new XML file containing both the original XML data and CDEs representing the results of our analyses. This XML file was submitted to XML parsers in order to confirm that they conformed to the syntax defined in our extended DTD file. TMA DES XML files with deliberately introduced errors were also parsed in order to verify that our new DTD file could perform error checking. Finally, we also validated an existing TMA DES XML file against our DTD file in order to demonstrate the backward compatibility of our DTD. Results: Our experiments demonstrated the encoding of analysis results using our proposed CDEs. We used XML parsers to confirm that these XML data were syntactically correct and conformed to the rules specified in our extended TMA DES DTD. We also demonstrated that this extended DTD was capable of being used to successfully perform error checking, and was backward compatible with pre-existing TMA DES data which did not use our new CDEs. Conclusions: The TMA DES allows Tissue Microarray data to be shared. A variety of statistical tests are used to analyze such data. We have proposed a set of CDEs as an extension to the TMA DES which can be used to annotate TMA DES data with the results of statistical analyses performed on that data. We performed experiments which demonstrated the usage of TMA DES data containing our proposed CDEs.

Background: The surgical pathology report remains the primary source for information to guide the treatment of patients with cancer. Failure to report critical elements in a cancer report is an increasing problem in pathology because of the heightened complexity of these reports and number of elements that are important for patient care. The American College of Surgeons Commission on Cancer (ACS-CoC) in concert with the College of American Pathologists (CAP) developed checklists that contain all of the scientifically validated data elements that are to be reported for cancer specimens. Most institutions do not as of yet have pathology information systems in which CAP checklists are embedded into the laboratory information system (LIS). Entering the required elements often requires extensive text editing, secretarial support and deletion of extraneous elements that can be an arduous task. Materials and Methods: We sought to develop a web-based system that was available throughout the workstations in our department and was capable of generating synoptic reports based on the CAP guidelines. The program was written in a manner that allowed automatic generation of the web-based checklists through a parsing algorithm. Results: Multiple web-based synoptic report generators have been developed to encompass required elements of cancer synoptic reports as required by the ACS-CoC/ CAP. In addition, utilizing the same program, report generators for certain molecular tests (KRAS mutation) and FISH studies (UroVysion ^tm ) have also been developed. The output of these reports can be cut-and-pasted into any text-based anatomic pathology LIS. In addition, the elements can be compiled in a database. Conclusions: We describe a simple method to automate the development of web-based synoptic reports that can be entered into the anatomic pathology LIS and database.

Background: Tissue MicroArrays (TMAs) are a high throughput technology for rapid analysis of protein expression across hundreds of patient samples. Often, data relating to TMAs is specific to the clinical trial or experiment it is being used for, and not interoperable. The Tissue Microarray Data Exchange Specification (TMA DES) is a set of eXtensible Markup Language (XML)-based protocols for storing and sharing digitized Tissue Microarray data. XML data are enclosed by named tags which serve as identifiers. These tag names can be Common Data Elements (CDEs), which have a predefined meaning or semantics. By using this specification in a laboratory setting with increasing demands for digital pathology integration, we found that the data structure lacked the ability to cope with digital slide imaging in respect to web-enabled digital pathology systems and advanced scoring techniques. Materials and Methods: By employing user centric design, and observing behavior in relation to TMA scoring and associated data, the TMA DES format was extended to accommodate the current limitations. This was done with specific focus on developing a generic tool for handling any given scoring system, and utilizing data for multiple observations and observers. Results: DTDs were created to validate the extensions of the TMA DES protocol, and a test set of data containing scores for 6,708 TMA core images was generated. The XML was then read into an image processing algorithm to utilize the digital pathology data extensions, and scoring results were easily stored alongside the existing multiple pathologist scores. Conclusions: By extending the TMA DES format to include digital pathology data and customizable scoring systems for TMAs, the new system facilitates the collaboration between pathologists and organizations, and can be used in automatic or manual data analysis. This allows complying systems to effectively communicate complex and varied scoring data.

Background: Clinical pathology laboratories increasingly use complex instruments that incorporate chromatographic separation, e.g. liquid chromatography, with mass detection for rapid identification and quantification of biochemicals, biomolecules, or pharmaceuticals. Electronic data management for these instruments through interfaces with laboratory information systems (LIS) is not generally available from the instrument manufacturers or LIS vendors. Unavailability of a data management interface is a limiting factor in the use of these instruments in clinical laboratories where there is a demand for high-throughput assays with turn-around times that meet patient care needs. Materials and Methods: Professional society guidelines for design and transfer of data between instruments and LIS were used in the development and implementation of the interface. File transfer protocols and support utilities were written to facilitate transfer of information between the instruments and the LIS. An interface was created for liquid chromatography-tandem mass spectroscopy and inductively coupled plasma-mass spectroscopy instruments to manage data in the Sunquest^® LIS. Results: Interface validation, implementation and data transfer fidelity as well as training of technologists for use of the interface was performed by the LIS group. The technologists were familiarized with the data verification process as a part of the data management protocol. The total time for the technologists for patient/control sample data entry, assay results data transfer, and results verification was reduced from approximately 20 s per sample to <1 s per sample. Sample identification, results data entry errors, and omissions were eliminated. There was electronic record of the technologist performing the assay runs and data management. Conclusions: Development of a data management interface for complex, chromatography instruments in clinical laboratories has resulted in rapid, accurate, verifiable information transfers between instruments and LIS. This has eliminated manual data entry that is prone to errors and enabled technologists to focus on analytical applications on the instruments.

Introduction: Historically, effective clinical utilization of image analysis and pattern recognition algorithms in pathology has been hampered by two critical limitations: 1) the availability of digital whole slide imagery data sets and 2) a relative domain knowledge deficit in terms of application of such algorithms, on the part of practicing pathologists. With the advent of the recent and rapid adoption of whole slide imaging solutions, the former limitation has been largely resolved. However, with the expectation that it is unlikely for the general cohort of contemporary pathologists to gain advanced image analysis skills in the short term, the latter problem remains, thus underscoring the need for a class of algorithm that has the concurrent properties of image domain (or organ system) independence and extreme ease of use, without the need for specialized training or expertise. Results: In this report, we present a novel, general case pattern recognition algorithm, Spatially Invariant Vector Quantization (SIVQ), that overcomes the aforementioned knowledge deficit. Fundamentally based on conventional Vector Quantization (VQ) pattern recognition approaches, SIVQ gains its superior performance and essentially zero-training workflow model from its use of ring vectors, which exhibit continuous symmetry, as opposed to square or rectangular vectors, which do not. By use of the stochastic matching properties inherent in continuous symmetry, a single ring vector can exhibit as much as a millionfold improvement in matching possibilities, as opposed to conventional VQ vectors. SIVQ was utilized to demonstrate rapid and highly precise pattern recognition capability in a broad range of gross and microscopic use-case settings. Conclusion: With the performance of SIVQ observed thus far, we find evidence that indeed there exist classes of image analysis/pattern recognition algorithms suitable for deployment in settings where pathologists alone can effectively incorporate their use into clinical workflow, as a turnkey solution. We anticipate that SIVQ, and other related class-independent pattern recognition algorithms, will become part of the overall armamentarium of digital image analysis approaches that are immediately available to practicing pathologists, without the need for the immediate availability of an image analysis expert.

Electronic health records (EHRs) have emerged as a major topic in health care and are central to the federal government's strategy for transforming healthcare delivery in the United States. Recent federal actions that aim to promote the use of EHRs promise to have significant implications for laboratories and for pathology practices. Under the HITECH (Health Information Technology Economic and Clinical Health) Act, an EHR incentive program has been established through which individual physicians and hospitals can qualify to receive incentive payments if they achieve "meaningful use" of "certified" EHR technology. The rule also establishes payment penalties in future years for eligible providers who have not met the requirements for meaningful use of EHRs. Meaningful use must be achieved using EHR technology that has been certified in accordance with functional and technical criteria that are set forth a regulation that parallels the meaningful use criteria in the incentive program. These actions and regulations are important to laboratories and pathologists for a number of reasons. Several of the criteria and requirements in the meaningful use rules and EHR certification criteria relate directly or indirectly to laboratory testing and laboratory information management, and future stage requirements are expected to impact the laboratory as well. Furthermore, as EHR uptake expands, there will be greater expectations for electronic interchange of laboratory information and laboratory information system (LIS)-EHR interfaces. Laboratories will need to be aware of the technical, operational, and business challenges that they may face as expectations for LIS-EHR increase. This paper reviews the important recent federal efforts aimed at accelerating EHR use, including the incentive program for EHR meaningful use, provider eligibility, and EHR certification criteria, from a perspective of their relevance for laboratories and pathology practices.

Virtual blood bank is the computer-controlled, electronically linked information management system that allows online ordering and real-time, remote delivery of blood for transfusion. It connects the site of testing to the point of care at a remote site in a real-time fashion with networked computers thus maintaining the integrity of immunohematology test results. It has taken the advantages of information and communication technologies to ensure the accuracy of patient, specimen and blood component identification and to enhance personnel traceability and system security. The built-in logics and process constraints in the design of the virtual blood bank can guide the selection of appropriate blood and minimize transfusion risk. The quality of blood inventory is ascertained and monitored, and an audit trail for critical procedures in the transfusion process is provided by the paperless system. Thus, the virtual blood bank can help ensure that the right patient receives the right amount of the right blood component at the right time.

The day has not arrived when pathology departments freely distribute their collected anatomic and clinical data for research purposes. Nonetheless, several valuable public domain data sets are currently available, from the U.S. Government. Two public data sets of special interest to pathologists are the SEER (the U.S. National Cancer Institute's Surveillance, Epidemiology and End Results program) public use data files, and the CDC (Center for Disease Control and Prevention) mortality files. The SEER files contain about 4 million de-identified cancer records, dating from 1973. The CDC mortality files contain approximately 85 million de-identified death records, dating from 1968. This editorial briefly describes both data sources, how they can be obtained, and how they may be used for pathology research.

The 13 ^th World Congress on Medical and Health Informatics (Medinfo) was held in 2010 between 12 and 15 September in Cape Town, South Africa. This triennial international gathering is the official conference of the International Medical Informatics Association (IMIA) and brings together leading health informatics leaders, scientists, clinicians, researchers, vendors, developers and government and health care planners from around the globe. The conference attracted 905 submissions and resulted in a program that included 260 oral presentations, 349 posters presentations and 21 scientific demonstrations representing contributions from 58 countries. The Medinfo program covered all aspects of health informatics from traditional areas, such as hospital information systems, patient registries, nursing informatics, data integration, standards, interoperability issues and decision support, to innovative topics, such as translational bioinformatics, text mining, intelligent data analysis, emerging technologies, quality, social networking, workflow and organizational issues. The outgoing President of the IMIA, Professor Reinhold Haux, presented on health informatics challenges into the future, reinforcing that today and in the future, health care has to be considered as part of a continuous and coordinated life-time journey and not just as episodes of disease. Medical informatics has a key role to play in this paradigm shift. The new IMIA President, Professor Antoine Geissbuhler, was announced at the closing ceremony. The next Medinfo congress will take place in Copenhagen, Denmark, in September 2013.

The Transfusion Medicine Service (TMS) covers diverse clinical and laboratory-based services that must be delivered with accuracy, efficiency and reliability. TMS oversight is shared by multiple regulatory agencies that cover product manufacturing and validation standards geared toward patient safety. These demands present significant informatics challenges. Over the past few decades, TMS information systems have improved to better handle blood product manufacturing, inventory, delivery, tracking and documentation. Audit trails and access to electronic databases have greatly facilitated product traceability and biovigilance efforts. Modern blood bank computing has enabled novel applications such as the electronic crossmatch, kiosk-based blood product delivery systems, and self-administered computerized blood donor interview and eligibility determination. With increasing use of barcoding technology, there has been a marked improvement in patient and specimen identification. Moreover, the emergence of national and international labeling standards such as ISBT 128 have facilitated the availability, movement and tracking of blood products across national and international boundaries. TMS has only recently begun to leverage the electronic medical record to address quality issues in transfusion practice and promote standardized documentation within institutions. With improved technology, future growth is expected in blood bank automation and product labeling with applications such as radio frequency identification devices. This article reviews several of these key informatics issues relevant to the contemporary practice of TMS.

Virtual microscopy, which is the diagnostic work on completely digitized histological and cytological slides as well as blood smears, is at the stage to be implemented in routine diagnostic surgical pathology (tissue-based diagnosis) in the near future, once it has been accepted by the US Food and Drug Administration. The principle of content-based image information, its mandatory prerequisites to obtain reproducible and stable image information as well as the different compartments that contribute to image information are described in detail. Automated extraction of content-based image information requires shading correction, constant maximum of grey values, and standardized grey value histograms. The different compartments to evaluate image information include objects, structure, and texture. Identification of objects and derived structure depend on segmentation accuracy and applied procedures; textures contain pixel-based image information only. All together, these image compartments posses the discrimination power to distinguish between object space and background, and, in addition, to reproducibly define regions of interest (ROIs). ROIs are image areas which display the information that is of preferable interest to the viewing pathologist. They contribute to the derived diagnosis to a higher level when compared with other image areas. The implementation of content-based image information algorithms to be applied for predictive tissue-based diagnoses is described in detail.

Background: Adoption of digital images for pathological specimens has been slower than adoption of digital images in radiology, despite a number of anticipated advantages for digital images in pathology. In this paper, we explore the factors that might explain this slower rate of adoption. Materials and Method: Semi-structured interviews on barriers and facilitators to the adoption of digital images were conducted with two radiologists, three pathologists, and one pathologist's assistant. Results: Barriers and facilitators to adoption of digital images were reported in the areas of performance, workflow-efficiency, infrastructure, integration with other software, and exposure to digital images. The primary difference between the settings was that performance with the use of digital images as compared to the traditional method was perceived to be higher in radiology and lower in pathology. Additionally, exposure to digital images was higher in radiology than pathology, with some radiologists exclusively having been trained and/or practicing with digital images. The integration of digital images both improved and reduced efficiency in routine and non-routine workflow patterns in both settings, and was variable across the different organizations. A comparison of these findings with prior research on adoption of other health information technologies suggests that the barriers to adoption of digital images in pathology are relatively tractable. Conclusions: Improving performance using digital images in pathology would likely accelerate adoption of innovative technologies that are facilitated by the use of digital images, such as electronic imaging databases, electronic health records, double reading for challenging cases, and computer-aided diagnostic systems.