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Background: The National Cancer Institute Informatics Technology for Cancer Research (ITCR) program provides a series of funding mechanisms to create an ecosystem of open-source software (OSS) that serves the needs of cancer research. As the ITCR ecosystem substantially grows, it faces the challenge of the long-term sustainability of the software being developed by ITCR grantees. To address this challenge, the ITCR sustainability and industry partnership working group (SIP-WG) was convened in 2019., Objective: The charter of the SIP-WG is to investigate options to enhance the long-term sustainability of the OSS being developed by ITCR, in part by developing a collection of business model archetypes that can serve as sustainability plans for ITCR OSS development initiatives. The working group assembled models from the ITCR program, from other studies, and from the engagement of its extensive network of relationships with other organizations (eg, Chan Zuckerberg Initiative, Open Source Initiative, and Software Sustainability Institute) in support of this objective., Methods: This paper reviews the existing sustainability models and describes 10 OSS use cases disseminated by the SIP-WG and others, including 3D Slicer, Bioconductor, Cytoscape, Globus, i2b2 (Informatics for Integrating Biology and the Bedside) and tranSMART, Insight Toolkit, Linux, Observational Health Data Sciences and Informatics tools, R, and REDCap (Research Electronic Data Capture), in 10 sustainability aspects: governance, documentation, code quality, support, ecosystem collaboration, security, legal, finance, marketing, and dependency hygiene., Results: Information available to the public reveals that all 10 OSS have effective governance, comprehensive documentation, high code quality, reliable dependency hygiene, strong user and developer support, and active marketing. These OSS include a variety of licensing models (eg, general public license version 2, general public license version 3, Berkeley Software Distribution, and Apache 3) and financial models (eg, federal research funding, industry and membership support, and commercial support). However, detailed information on ecosystem collaboration and security is not publicly provided by most OSS., Conclusions: We recommend 6 essential attributes for research software: alignment with unmet scientific needs, a dedicated development team, a vibrant user community, a feasible licensing model, a sustainable financial model, and effective product management. We also stress important actions to be considered in future ITCR activities that involve the discussion of the sustainability and licensing models for ITCR OSS, the establishment of a central library, the allocation of consulting resources to code quality control, ecosystem collaboration, security, and dependency hygiene., (©Ye Ye, Seemran Barapatre, Michael K Davis, Keith O Elliston, Christos Davatzikos, Andrey Fedorov, Jean-Christophe Fillion-Robin, Ian Foster, John R Gilbertson, Andras Lasso, James V Miller, Martin Morgan, Steve Pieper, Brigitte E Raumann, Brion D Sarachan, Guergana Savova, Jonathan C Silverstein, Donald P Taylor, Joyce B Zelnis, Guo-Qiang Zhang, Jamie Cuticchia, Michael J Becich. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 02.12.2021.)

Context.—: Recent developments in machine learning have stimulated intense interest in software that may augment or replace human experts. Machine learning may impact pathology practice by offering new capabilities in analysis, interpretation, and outcomes prediction using images and other data. The principles of operation and management of machine learning systems are unfamiliar to pathologists, who anticipate a need for additional education to be effective as expert users and managers of the new tools., Objective.—: To provide a background on machine learning for practicing pathologists, including an overview of algorithms, model development, and performance evaluation; to examine the current status of machine learning in pathology and consider possible roles and requirements for pathologists in local deployment and management of machine learning systems; and to highlight existing challenges and gaps in deployment methodology and regulation., Data Sources.—: Sources include the biomedical and engineering literature, white papers from professional organizations, government reports, electronic resources, and authors' experience in machine learning. References were chosen when possible for accessibility to practicing pathologists without specialized training in mathematics, statistics, or software development., Conclusions.—: Machine learning offers an array of techniques that in recent published results show substantial promise. Data suggest that human experts working with machine learning tools outperform humans or machines separately, but the optimal form for this combination in pathology has not been established. Significant questions related to the generalizability of machine learning systems, local site verification, and performance monitoring remain to be resolved before a consensus on best practices and a regulatory environment can be established., Competing Interests: All authors are members of the Machine Learning Workgroup, College of American Pathologists Informatics Committee.

Background: The alumni of today's Pathology Informatics and Clinical Informatics fellowships fill diverse roles in academia, large health systems, and industry. The evolving training tracks and curriculum of Pathology Informatics fellowships have been well documented. However, less attention has been given to the posttraining experiences of graduates from informatics training programs. Here, we examine the career paths of subspecialty fellowship-trained pathology informaticians., Methods: Alumni from four Pathology Informatics fellowship training programs were contacted for their voluntary participation in the study. We analyzed various components of training, and the subsequent career paths of Pathology Informatics fellowship alumni using data extracted from alumni provided curriculum vitae., Results: Twenty-three out of twenty-seven alumni contacted contributed to the study. A majority had completed undergraduate study in science, technology, engineering, and math fields and combined track training in anatomic and clinical pathology. Approximately 30% (7/23) completed residency in a program with an in-house Pathology Informatics fellowship. Most completed additional fellowships (15/23) and many also completed advanced degrees (10/23). Common primary posttraining appointments included chief medical informatics officer (3/23), director of Pathology Informatics (10/23), informatics program director (2/23), and various roles in industry (3/23). Many alumni also provide clinical care in addition to their informatics roles (14/23). Pathology Informatics alumni serve on a variety of institutional committees, participate in national informatics organizations, contribute widely to scientific literature, and more than half (13/23) have obtained subspecialty certification in Clinical Informatics to date., Conclusions: Our analysis highlights several interesting phenomena related to the training and career trajectory of Pathology Informatics fellowship alumni. We note the long training track alumni complete in preparation for their careers. We believe flexible training pathways combining informatics and clinical training may help to alleviate the burden. We highlight the importance of in-house Pathology Informatics fellowships in promoting interest in informatics among residents. We also observe the many important leadership roles in academia, large community health systems, and industry available to early career alumni and believe this reflects a strong market for formally trained informaticians. We hope this analysis will be useful as we continue to develop the informatics fellowships to meet the future needs of our trainees and discipline., Competing Interests: There are no conflicts of interest.

Background: Postoperative intracranial hypotension-associated venous congestion (PIHV) is an uncommon cause of clinical deterioration after a neurosurgical procedure that is often unrecognized until late in its course. Functional outcomes range from remarkable neurological recovery to death. Little is understood about the reason for deterioration in certain patients compared with improvement in others. A 68-year-old man with a progressive cervical myelopathy underwent an uncomplicated cervical decompression and alignment restoration at our hospital and suffered violent generalized tonic-clonic seizures intraoperatively and postoperatively. A postoperative head CT showed a right parietal hematoma, but no other cranial findings. A subsequent MRI demonstrated what we describe as early PIHV with symmetric T2 signal changes in the bilateral deep gray structures. No diffusion restriction corresponded to these areas. A CT myelogram revealed a considerable CSF collection within the operative bed. Upon returning to the operating room to localize the source of the leak, a large dural tear was identified off of midline with a bone chip alongside the defect. The defect was repaired, and the patient remained comatose for over a week postoperatively. He made a remarkable gradual recovery, and after a month in the hospital and rehabilitation, he returned home with relatively minimal neurological deficits., Conclusions: We postulate that if caught early and treated aggressively, neurologic injury resulting from PIHV may be reversible despite initially ominous imaging. Neurosurgeons and neurointensivists should therefore be compelled to search for dural defects and return to the operating room for immediate repair.

Background: Although pathology informatics (PI) is essential to modern pathology practice, the field is often poorly understood. Pathologists who have received little to no exposure to informatics, either in training or in practice, may not recognize the roles that informatics serves in pathology. The purpose of this study was to characterize perceptions of PI by noninformatics-oriented pathologists and to do so at two large centers with differing informatics environments., Methods: Pathology trainees and staff at Cleveland Clinic (CC) and Massachusetts General Hospital (MGH) were surveyed. At MGH, pathology department leadership has promoted a pervasive informatics presence through practice, training, and research. At CC, PI efforts focus on production systems that serve a multi-site integrated health system and a reference laboratory, and on the development of applications oriented to department operations. The survey assessed perceived definition of PI, interest in PI, and perceived utility of PI., Results: The survey was completed by 107 noninformatics-oriented pathologists and trainees. A majority viewed informatics positively. Except among MGH trainees, confusion of PI with information technology (IT) and help desk services was prominent, even in those who indicated they understood informatics. Attendings and trainees indicated desire to learn more about PI. While most acknowledged that having some level of PI knowledge would be professionally useful and advantageous, only a minority plan to utilize it., Conclusions: Informatics is viewed positively by the majority of noninformatics pathologists at two large centers with differing informatics orientations. Differences in departmental informatics culture can be attributed to the varying perceptions of PI by different individuals. Incorrect perceptions exist, such as conflating PI with IT and help desk services, even among those who claim to understand PI. Further efforts by the PI community could address such misperceptions, which could help enable a better understanding of what PI is and is not, and potentially lead to increased acceptance by non-informaticist pathologists.

Context: We define the scope and needs within the new discipline of computational pathology, a discipline critical to the future of both the practice of pathology and, more broadly, medical practice in general., Objective: To define the scope and needs of computational pathology., Data Sources: A meeting was convened in Boston, Massachusetts, in July 2014 prior to the annual Association of Pathology Chairs meeting, and it was attended by a variety of pathologists, including individuals highly invested in pathology informatics as well as chairs of pathology departments., Conclusions: The meeting made recommendations to promote computational pathology, including clearly defining the field and articulating its value propositions; asserting that the value propositions for health care systems must include means to incorporate robust computational approaches to implement data-driven methods that aid in guiding individual and population health care; leveraging computational pathology as a center for data interpretation in modern health care systems; stating that realizing the value proposition will require working with institutional administrations, other departments, and pathology colleagues; declaring that a robust pipeline should be fostered that trains and develops future computational pathologists, for those with both pathology and nonpathology backgrounds; and deciding that computational pathology should serve as a hub for data-related research in health care systems. The dissemination of these recommendations to pathology and bioinformatics departments should help facilitate the development of computational pathology.

Background and Purpose: Requests for after-hours emergent spine MR imaging seem to be increasing. We sought to review the trend in after hours spine MRI utilization at our institution and to determine how these results impacted therapeutic intervention., Methods: Following Institutional Review Board approval, reports from 179 after hours spinal MRI's performed over the past 13 years were obtained and the relevant electronic medical records were reviewed., Results: Emergent after hours spine MRI utilization increased from 7 per year to 23 over 13 years. Fifty-eight percent (104/179) had significant findings. Twenty-nine percent (52/179) of all patients imaged underwent surgery to treat pathologies identified on MR. Surgery was performed in only 2% (4/179) of these patients within 3 hours and 6% (10/179) within 6 hours of MRI completion. Five percent (8/179) had findings that were treated with radiation therapy and in 78% of these it was performed within 6-12 hours. Of those in whom steroids or antibiotics were initiated, 41% and 50% were treated within 3 hours of MR scanning, respectively., Discussion: Clinical use of emergent after hours spine MRI is steadily increasing at our institution. While MR imaging often discerned significant pathologies, performing these emergent studies rarely resulted in immediate surgical or radiotherapeutic intervention., (Copyright © 2014 by the American Society of Neuroimaging.)

Background: The use of digital whole slide imaging for human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) could create improvements in workflow and performance, allowing for central archiving of specimens, distributed and remote interpretation, and the potential for additional computerized automation., Procedures: The accuracy, precision, and reproducibility of manual digital interpretation for HER2 IHC were determined by comparison to manual glass slide interpretation. Inter- and intra-pathologist reproducibility and precision between the glass slide and digital interpretations of HER2 IHC were determined in 5 studies using DAKO HercepTest-stained breast cancer slides with the Philips Digital Pathology System. In 2 inter-method studies, 3 pathologists interpreted glass and digital slides in sequence or in random order with a minimum of 7 days as a washout period. These studies also measured inter-observer reproducibility and precision. Another two studies measured intra-pathologist reproducibility on cases read 10 times by glass and digital methods. One additional study evaluated the effects of adding IHC control slides with each run, using 1 pathologist interpreting glass and digital slides randomized from the sets above along with appropriate controls for each slide in the set., Results: The overall results show that there is no statistical difference between the variance of performance when comparing glass and digital HER2 interpretations; and there were no effects noted when control tissues were evaluated in conjunction with the test slides., Conclusions: The results show that there is an equivalence of result when interpreting HER2 IHC slides in breast cancer by either glass slides or digital images. Digital interpretation can therefore be safely and effectively used for this purpose.

Background and Purpose: The purpose of this study was to determine if magnetic resonance (MR) susceptibility-weighted imaging (SWI) can increase the conspicuity of corticomedullary veins within the white matter lesions of multiple sclerosis (MS) and, thus, aid in distinguishing plaques from leukoaraiosis., Methods: We retrospectively reviewed MR examinations in 21 patients with a clinical diagnosis of MS and 18 patients with a clinical diagnosis of dementia. Examinations included fluid-attenuated inversion recovery (FLAIR) and SWI sequences obtained in the axial plane. Lesions greater than 5 mm in diameter on the axial FLAIR sequence were identified as periventricular or subcortical. Three neuroradiologists evaluated SWI images, compared with FLAIR, for a centrally located signal void in each lesion that was scored as present, absent, or indeterminate., Results: In patients with MS, central veins were present in both periventricular lesions (75%, P < 0.001) and subcortical lesions (52%, P < 0.005). In patients with dementia, central veins were seen much less frequently in subcortical lesions (14%, P < 0.001); their association with periventricular lesions was not significant., Conclusions: Central veins were detected in MS lesions with a significantly greater frequency than that in patients with dementia. Susceptibility-weighted imaging increases the conspicuity of corticomedullary veins and may improve the specificity of MR findings in MS.

Objectives: The intersecting of pathology training and practice and the utilization of information technology has become an increasingly common occurrence, and the most effective means of teaching residents informatics during these invaluable years has yet to be firmly established., Methods: In offering the idea of longitudinal engagement that stresses early and extended trainee involvement, we attempt to provide a different manner of helping address some of the leading time-limited issues surrounding education in informatics., Results: The proposed model is intended to allow building off a base of fundamentals reached through introductory didactics, exposure to and active participation in departmental and hospital-wide administrative bodies, refining of initial skills gained through frequent mentoring and coaching, and combining these cumulative knowledge and experiential underpinnings with graduated responsibility in a particular area of expertise., Conclusions: In transforming the ways in which pathology residencies teach their trainees informatics, the prospects of realizing its potential utility are heightened., (Copyright© by the American Society for Clinical Pathology.)

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 forms of: (1) New classes of fellows annually with new and varying educational needs and increasingly fractured, enterprise-wide commitments; (2) taxing electronic health record (EHR) and laboratory information system (LIS) implementations; and (3) increasing interest in the subspecialty at the academic medical centers (AMCs) in what is a large health care network. In response to these challenges, the fellowship has modified its existing didactic sessions and piloted both a network-wide pathology informatics lecture series and regular "learning laboratories". Didactic sessions, which had previously included more formal discussions of the four divisions of the core curriculum: Information fundamentals, information systems, workflow and process, and governance and management, now focus on group discussions concerning the fellows' ongoing projects, updates on the enterprise-wide EHR and LIS implementations, and directed questions about weekly readings. Lectures are given by the informatics faculty, guest 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 AMCs. 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. The learning laboratories have created a forum for discussing real-time and real-world pathology informatics matters, and for incorporating awareness of and timely discussions about the latest pathology informatics literature. These changes have diversified the delivery of the fellowship's core curriculum, increased exposure of faculty, fellows and trainees to one another, and more equitably distributed teaching responsibilities among the entirety of the pathology informatics asset in the network. Though the above approach has been in place less than a year, we are presenting it now as a technical note to allow for further discussion of evolving educational opportunities in pathology informatics and clinical informatics in general, and to highlight the importance of having a flexible fellowship with active participation from its fellows.

Background: Pathology informatics is both emerging as a distinct subspecialty and simultaneously becoming deeply integrated within the breadth of pathology practice. As specialists, pathology informaticians need a broad skill set, including aptitude with information fundamentals, information systems, workflow and process, and governance and management. Currently, many of those seeking training in pathology informatics additionally choose training in a second subspecialty. Combining pathology informatics training with molecular pathology is a natural extension, as molecular pathology is a subspecialty with high potential for application of modern biomedical informatics techniques., Methods and Results: Pathology informatics and molecular pathology fellows and faculty evaluated the current fellowship program's core curriculum topics and subtopics for relevance to molecular pathology. By focusing on the overlap between the two disciplines, a structured curriculum consisting of didactics, operational rotations, and research projects was developed for those fellows interested in both pathology informatics and molecular pathology., Conclusions: The scope of molecular diagnostics is expanding dramatically as technology advances and our understanding of disease extends to the genetic level. Here, we highlight many of the informatics challenges facing molecular pathology today, and outline specific informatics principles necessary for the training of future molecular pathologists.

Background: Pathologists and informaticians are becoming increasingly interested in electronic clinical decision support for pathology, laboratory medicine and clinical diagnosis. Improved decision support may optimize laboratory test selection, improve test result interpretation and permit the extraction of enhanced diagnostic information from existing laboratory data. Nonetheless, the field of pathology decision support is still developing. To facilitate the exchange of ideas and preliminary studies, we convened a symposium entitled: Pathology data integration and clinical decision support., Methods: The symposium was held at the Massachusetts General Hospital, on May 10, 2013. Participants were selected to represent diverse backgrounds and interests and were from nine different institutions in eight different states., Results: The day included 16 plenary talks and three panel discussions, together covering four broad areas. Summaries of each presentation are included in this manuscript., Conclusions: A number of recurrent themes emerged from the symposium. Among the most pervasive was the dichotomy between diagnostic data and diagnostic information, including the opportunities that laboratories may have to use electronic systems and algorithms to convert the data they generate into more useful information. Differences between human talents and computer abilities were described; well-designed symbioses between humans and computers may ultimately optimize diagnosis. Another key theme related to the unique needs and challenges in providing decision support for genomics and other emerging diagnostic modalities. Finally, many talks relayed how the barriers to bringing decision support toward reality are primarily personnel, political, infrastructural and administrative challenges rather than technological limitations.

Brain metastases are a major cause of morbidity and mortality in patients with advanced melanoma. With the development of targeted agents for the treatment of metastatic melanoma, a great deal of interest has focused on whether selective BRAF inhibitors may play a role in the treatment of brain metastases in lieu of or in addition to surgery and/or radiation therapy. However, relatively little is known about the intracranial effectiveness of vemurafenib, the only US Food and Drug Administration-approved selective BRAF V600E inhibitor, because patients with brain metastases have historically been excluded from vemurafenib clinical trials. We describe 3 patients with BRAF V600E mutation metastatic melanoma in whom treatment with vemurafenib resulted in prompt extracranial disease response but progression of metastatic disease in the brain. Further, we discuss possible mechanisms responsible for the suboptimal central nervous system response observed in these patients and alternative therapies for patients with melanoma metastatic to the brain., (Copyright © 2012 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: In 2007, our healthcare system established a clinical fellowship program in pathology informatics. In 2011, the program benchmarked its structure and operations against a 2009 white paper "Program requirements for fellowship education in the subspecialty of clinical informatics", endorsed by the Board of the American Medical Informatics Association (AMIA) that described a proposal for a general clinical informatics fellowship program., Methods: A group of program faculty members and fellows compared each of the proposed requirements in the white paper with the fellowship program's written charter and operations. The majority of white paper proposals aligned closely with the rules and activities in our program and comparison was straightforward. In some proposals, however, differences in terminology, approach, and philosophy made comparison less direct, and in those cases, the thinking of the group was recorded. After the initial evaluation, the remainder of the faculty reviewed the results and any disagreements were resolved., Results: The most important finding of the study was how closely the white paper proposals for a general clinical informatics fellowship program aligned with the reality of our existing pathology informatics fellowship. The program charter and operations of the program were judged to be concordant with the great majority of specific white paper proposals. However, there were some areas of discrepancy and the reasons for the discrepancies are discussed in the manuscript., Conclusions: After the comparison, we conclude that the existing pathology informatics fellowship could easily meet all substantive proposals put forth in the 2009 clinical informatics program requirements white paper. There was also agreement on a number of philosophical issues, such as the advantages of multiple fellows, the need for core knowledge and skill sets, and the need to maintain clinical skills during informatics training. However, there were other issues, such as a requirement for a 2-year fellowship and for informatics fellowships to be done after primary board certification, that pathology should consider carefully as it moves toward a subspecialty status and board certification.

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

Background: In 2007, our healthcare system established a clinical fellowship program in Pathology Informatics. In 2010 a core didactic course was implemented to supplement the fellowship research and operational rotations. In 2011, the course was enhanced by a formal, structured core curriculum and reading list. We present and discuss our rationale and development process for the Core Curriculum and the role it plays in our Pathology Informatics Fellowship Training Program., Materials and Methods: The Core Curriculum for Pathology Informatics was developed, and is maintained, through the combined efforts of our Pathology Informatics Fellows and Faculty. The curriculum was created with a three-tiered structure, consisting of divisions, topics, and subtopics. Primary (required) and suggested readings were selected for each subtopic in the curriculum and incorporated into a curated reading list, which is reviewed and maintained on a regular basis., Results: Our Core Curriculum is composed of four major divisions, 22 topics, and 92 subtopics that cover the wide breadth of Pathology Informatics. The four major divisions include: (1) Information Fundamentals, (2) Information Systems, (3) Workflow and Process, and (4) Governance and Management. A detailed, comprehensive reading list for the curriculum is presented in the Appendix to the manuscript and contains 570 total readings (current as of March 2012)., Discussion: The adoption of a formal, core curriculum in a Pathology Informatics fellowship has significant impacts on both fellowship training and the general field of Pathology Informatics itself. For a fellowship, a core curriculum defines a basic, common scope of knowledge that the fellowship expects all of its graduates will know, while at the same time enhancing and broadening the traditional fellowship experience of research and operational rotations. For the field of Pathology Informatics itself, a core curriculum defines to the outside world, including departments, companies, and health systems considering hiring a pathology informatician, the core knowledge set expected of a person trained in the field and, more fundamentally, it helps to define the scope of the field within Pathology and healthcare in general.

Background: Pathology Informatics is a new field; a field that is still defining itself even as it begins the formalization, accreditation, and board certification process. At the same time, Pathology itself is changing in a variety of ways that impact informatics, including subspecialization and an increased use of data analysis. In this paper, we examine how these changes impact both the structure of Pathology Informatics fellowship programs and the fellows' goals within those programs., Materials and Methods: As part of our regular program review process, the fellows evaluated the value and effectiveness of our existing fellowship tracks (Research Informatics, Clinical Two-year Focused Informatics, Clinical One-year Focused Informatics, and Clinical 1 + 1 Subspecialty Pathology and Informatics). They compared their education, informatics background, and anticipated career paths and analyzed them for correlations between those parameters and the fellowship track chosen. All current and past fellows of the program were actively involved with the project., Results: Fellows' anticipated career paths correlated very well with the specific tracks in the program. A small set of fellows (Clinical - one or two year - Focused Informatics tracks) anticipated clinical careers primarily focused in informatics (Director of Informatics). The majority of the fellows, however, anticipated a career practicing in a Pathology subspecialty, using their informatics training to enhance that practice (Clinical 1 + 1 Subspecialty Pathology and Informatics Track). Significantly, all fellows on this track reported they would not have considered a Clinical Two-year Focused Informatics track if it was the only track offered. The Research and the Clinical One-year Focused Informatics tracks each displayed unique value for different situations., Conclusions: It seems a "one size fits all" fellowship structure does not fit the needs of the majority of potential Pathology Informatics candidates. Increasingly, these fellowships must be able to accommodate the needs of candidates anticipating a wide range of Pathology Informatics career paths, be able to accommodate Pathology's increasingly subspecialized structure, and do this in a way that respects the multiple fellowships needed to become a subspecialty pathologist and informatician. This is further complicated as Pathology Informatics begins to look outward and takes its place in the growing, and still ill-defined, field of Clinical Informatics, a field that is not confined to just one medical specialty, to one way of practicing medicine, or to one way of providing patient care.

Introduction: The advent of digital slides offers new opportunities within the practice of pathology such as the use of image analysis techniques to facilitate computer aided diagnosis (CAD) solutions. Use of CAD holds promise to enable new levels of decision support and allow for additional layers of quality assurance and consistency in rendered diagnoses. However, the development and testing of prostate cancer CAD solutions requires a ground truth map of the cancer to enable the generation of receiver operator characteristic (ROC) curves. This requires a pathologist to annotate, or paint, each of the malignant glands in prostate cancer with an image editor software - a time consuming and exhaustive process. Recently, two CAD algorithms have been described: probabilistic pairwise Markov models (PPMM) and spatially-invariant vector quantization (SIVQ). Briefly, SIVQ operates as a highly sensitive and specific pattern matching algorithm, making it optimal for the identification of any epithelial morphology, whereas PPMM operates as a highly sensitive detector of malignant perturbations in glandular lumenal architecture., Methods: By recapitulating algorithmically how a pathologist reviews prostate tissue sections, we created an algorithmic cascade of PPMM and SIVQ algorithms as previously described by Doyle el al. [1] where PPMM identifies the glands with abnormal lumenal architecture, and this area is then screened by SIVQ to identify the epithelium., Results: The performance of this algorithm cascade was assessed qualitatively (with the use of heatmaps) and quantitatively (with the use of ROC curves) and demonstrates greater performance in the identification of malignant prostatic epithelium., Conclusion: This ability to semi-autonomously paint nearly all the malignant epithelium of prostate cancer has immediate applications to future prostate cancer CAD development as a validated ground truth generator. In addition, such an approach has potential applications as a pre-screening/quality assurance tool.

Background: Last year, our pathology informatics fellowship added informatics-based interactive case studies to its existing educational platform of operational and research rotations, clinical conferences, a common core curriculum with an accompanying didactic course, and national meetings., Methods: The structure of the informatics case studies was based on the traditional business school case study format. Three different formats were used, varying in length from short, 15-minute scenarios to more formal multiple hour-long case studies. Case studies were presented over the course of three retreats (Fall 2011, Winter 2012, and Spring 2012) and involved both local and visiting faculty and fellows., Results: Both faculty and fellows found the case studies and the retreats educational, valuable, and enjoyable. From this positive feedback, we plan to incorporate the retreats in future academic years as an educational component of our fellowship program., Conclusions: Interactive case studies appear to be valuable in teaching several aspects of pathology informatics that are difficult to teach in more traditional venues (rotations and didactic class sessions). Case studies have become an important component of our fellowship's educational platform.

Background: The need for informatics training as part of pathology training has never been so critical, but pathology informatics is a wide and complex field and very few programs currently have the resources to provide comprehensive educational pathology informatics experiences to their residents. In this article, we present the "pathology informatics curriculum wiki", an open, on-line wiki that indexes the pathology informatics content in a larger public wiki, Wikipedia, (and other online content) and organizes it into educational modules based on the 2003 standard curriculum approved by the Association for Pathology Informatics (API)., Methods and Results: In addition to implementing the curriculum wiki at http://pathinformatics.wikispaces.com, we have evaluated pathology informatics content in Wikipedia. Of the 199 non-duplicate terms in the API curriculum, 90% have at least one associated Wikipedia article. Furthermore, evaluation of articles on a five-point Likert scale showed high scores for comprehensiveness (4.05), quality (4.08), currency (4.18), and utility for the beginner (3.85) and advanced (3.93) learners. These results are compelling and support the thesis that Wikipedia articles can be used as the foundation for a basic curriculum in pathology informatics., Conclusions: The pathology informatics community now has the infrastructure needed to collaboratively and openly create, maintain and distribute the pathology informatics content worldwide (Wikipedia) and also the environment (the curriculum wiki) to draw upon its own resources to index and organize this content as a sustainable basic pathology informatics educational resource. The remaining challenges are numerous, but largest by far will be to convince the pathologists to take the time and effort required to build pathology informatics content in Wikipedia and to index and organize this content for education in the curriculum wiki.

Telepathology, the practice of pathology at a long distance, has advanced continuously since 1986. Today, fourth-generation telepathology systems, so-called virtual slide telepathology systems, are being used for education applications. Both conventional and innovative surgical pathology diagnostic services are being designed and implemented as well. The technology has been commercialized by more than 30 companies in Asia, the United States, and Europe. Early adopters of telepathology have been laboratories with special challenges in providing anatomic pathology services, ranging from the need to provide anatomic pathology services at great distances to the use of the technology to increase efficiency of services between hospitals less than a mile apart. As to what often happens in medicine, early adopters of new technologies are professionals who create model programs that are successful and then stimulate the creation of infrastructure (ie, reimbursement, telecommunications, information technologies, and so on) that forms the platforms for entry of later, mainstream, adopters. The trend at medical schools, in the United States, is to go entirely digital for their pathology courses, discarding their student light microscopes, and building virtual slide laboratories. This may create a generation of pathology trainees who prefer digital pathology imaging over the traditional hands-on light microscopy. The creation of standards for virtual slide telepathology is early in its development but accelerating. The field of telepathology has now reached a tipping point at which major corporations now investing in the technology will insist that standards be created for pathology digital imaging as a value added business proposition. A key to success in teleradiology, already a growth industry, has been the implementation of standards for digital radiology imaging. Telepathology is already the enabling technology for new, innovative laboratory services. Examples include STAT QA surgical pathology second opinions at a distance and a telehealth-enabled rapid breast care service. The innovative bundling of telemammography, telepathology, and teleoncology services may represent a new paradigm in breast care that helps address the serious issue of fragmentation of breast cancer care in the United States and elsewhere. Legal and regulatory issues in telepathology are being addressed and are regarded as a potential catalyst for the next wave of telepathology advances, applications, and implementations.

This study examined the effect of tissue section thickness and consistency--parameters outside the direct control of the imaging devices themselves--on WSI capture speed and image quality. Preliminary data indicates that thinner, more consistent tissue sectioning (such as those produced by automated tissue sectioning robots) results in significantly faster WSI capture times and better image quality. A variety of tissue types (including human breast, mouse embryo, mouse brain, etc.) were sectioned using an (AS-200) Automated Tissue Sectioning System (Kurabo Industries, Osaka Japan) at thicknesses from 2 - 9 microm (at one microm intervals) and stained with H&E by a standard method. The resulting slides were imaged with 5 different WSI devices (ScanScope CS, Aperio, CA; iScan, BioImagene, CA; DX40, DMetrix, AZ; NanoZoomer, Hamamatsu Photonics K.K., Japan; Mirax Scan, Carl Zeiss Inc., Germany) with sampling periods of 0.43 - 0.69 microm/pixel. Slides with different tissue thicknesses were compared for image quality, appropriate number of focus points, and overall scanning speed. Thinner sections (i.e. 3 microm sections versus 7 microm) required significantly fewer focus points and had significantly lower (10-15%) capture times. Improvement was seen with all devices and tissues tested. Furthermore, a panel of experienced pathologist judged image quality to be significantly better (for example, with better apparent resolution of nucleoli) with the thinner sections. Automated tissue sectioning is a very new technology; however, the AS-200 seems to be able to produce thinner, more consistent, flatter sections than manual methods at reasonably high throughput. The resulting tissue sections seem to be easier for a WSI system's focusing systems to deal with (compared to manually cut slides). Teaming an automated tissue-sectioning device with a WSI device shows promise in producing faster WSI throughput with better image quality.

In the last 10 years, whole slide imaging (WSI) has seen impressive progress not only in image quality and scanning speed but also in the variety of systems available to pathologists. However, we have noticed that most systems have relatively simple optics axes and rely on software to optimize image quality and colour balance. While much can be done in software, this study examines the importance of optics, in particular optical filters, in WSI.Optical resolution is a function of the wavelength of light used and the numerical aperture of the lens system (Resolution = (f) wavelength/2 NA). When illumining light is not conditioned correctly with filters, there is a tendency for the wavelength to shift to longer values (more red) because of the characteristics of the lamps in common use. Most microscopes (but remarkably few WSI devices) correct for this with ND filter for brightness and Blue filter (depends on the light source) for colour correction.Using H&E slides research microscopes (Axiophot, Carl Zeiss MicroImaging, Inc. NY. Eclipse 50i., Nikon Inc. NY) at 20x, an attached digital camera (SPOT RT741 Slider Color, Diagnosis Instruments., MI USA), and a filter set, we examined the effect of filters and software enhancement on digital image quality. The focus value (as evaluated by focus evaluation software developed in house and SPOT imaging Software v4.6) was used as a proxy for image quality. Resolution of tissue features was best with the use of both the Blue and ND filters (in addition to software enhancement). Images without filters but with software enhancement while superficially good, lacked some details of specimen morphology and were unclear compared with the images with filters.The results indicate that the appropriate use of optical filters could measurably improve the appearance and resolution of WSI images.

Objective: Arrested skull base pneumatization is a benign developmental variant that can be confused with significant skull base disease processes. This study reviews the imaging findings in 30 suspected cases of arrested skull base pneumatization., Conclusion: When encountering a nonexpansile lesion with osteosclerotic borders, internal fat, and curvilinear calcifications in the basisphenoid bone or adjacent skull base, radiologists should strongly consider the diagnosis of arrested pneumatization.

Whole slide images (WSIs), also known as virtual slides, can support electronic distribution of immunohistochemistry (IHC) stains to pathologists that rely on remote sites for these services. This may lead to improvement in turnaround times, reduction of courier costs, fewer errors in slide distribution, and automated image analyses. Although this approach is practiced de facto today in some large laboratories, there are no clinical validation studies on this approach. Our retrospective study evaluated the interpretation of IHC stains performed in difficult prostate biopsies using WSIs. The study included 30 foci with IHC stains identified by the original pathologist as both difficult and pivotal to the final diagnosis. WSIs were created from the glass slides using a scanning robot (T2, Aperio Technologies, Vista, CA). An evaluation form was designed to capture data in 2 phases: (1) interpretation of WSIs and (2) interpretation of glass slides. Data included stain interpretations, diagnoses, and other parameters such as time required to diagnose and image/slide quality. Data were also collected from an expert prostate pathologist, consensus meetings, and a poststudy focus group. WSI diagnostic validity (intraobserver pairwise kappa statistics) was "almost perfect" for 1 pathologist, "substantial" for 3 pathologists, and "moderate" for 1 pathologist. Diagnostic agreement between the final/consensus diagnoses of the group and those of the domain expert was "almost perfect" (kappa = 0.817). Except for one instance, WSI technology was not felt to be the cause of disagreements. These results are encouraging and compare favorably with other efforts to quantify diagnostic variability in surgical pathology. With thorough training, careful validation of specific applications, and regular postsignout review of glass IHC slides (eg, quality assurance review), WSI technology can be used for IHC stain interpretation.

Background: The Pennsylvania Cancer Alliance Bioinformatics Consortium (PCABC, http://www.pcabc.upmc.edu) is one of the first major project-based initiatives stemming from the Pennsylvania Cancer Alliance that was funded for four years by the Department of Health of the Commonwealth of Pennsylvania. The objective of this was to initiate a prototype biorepository and bioinformatics infrastructure with a robust data warehouse by developing a statewide data model (1) for bioinformatics and a repository of serum and tissue samples; (2) a data model for biomarker data storage; and (3) a public access website for disseminating research results and bioinformatics tools. The members of the Consortium cooperate closely, exploring the opportunity for sharing clinical, genomic and other bioinformatics data on patient samples in oncology, for the purpose of developing collaborative research programs across cancer research institutions in Pennsylvania. The Consortium's intention was to establish a virtual repository of many clinical specimens residing in various centers across the state, in order to make them available for research. One of our primary goals was to facilitate the identification of cancer-specific biomarkers and encourage collaborative research efforts among the participating centers., Methods: The PCABC has developed unique partnerships so that every region of the state can effectively contribute and participate. It includes over 80 individuals from 14 organizations, and plans to expand to partners outside the State. This has created a network of researchers, clinicians, bioinformaticians, cancer registrars, program directors, and executives from academic and community health systems, as well as external corporate partners - all working together to accomplish a common mission. The various sub-committees have developed a common IRB protocol template, common data elements for standardizing data collections for three organ sites, intellectual property/tech transfer agreements, and material transfer agreements that have been approved by each of the member institutions. This was the foundational work that has led to the development of a centralized data warehouse that has met each of the institutions' IRB/HIPAA standards., Results: Currently, this "virtual biorepository" has over 58,000 annotated samples from 11,467 cancer patients available for research purposes. The clinical annotation of tissue samples is either done manually over the internet or semi-automated batch modes through mapping of local data elements with PCABC common data elements. The database currently holds information on 7188 cases (associated with 9278 specimens and 46,666 annotated blocks and blood samples) of prostate cancer, 2736 cases (associated with 3796 specimens and 9336 annotated blocks and blood samples) of breast cancer and 1543 cases (including 1334 specimens and 2671 annotated blocks and blood samples) of melanoma. These numbers continue to grow, and plans to integrate new tumor sites are in progress. Furthermore, the group has also developed a central web-based tool that allows investigators to share their translational (genomics/proteomics) experiment data on research evaluating potential biomarkers via a central location on the Consortium's web site., Conclusions: The technological achievements and the statewide informatics infrastructure that have been established by the Consortium will enable robust and efficient studies of biomarkers and their relevance to the clinical course of cancer. Studies resulting from the creation of the Consortium may allow for better classification of cancer types, more accurate assessment of disease prognosis, a better ability to identify the most appropriate individuals for clinical trial participation, and better surrogate markers of disease progression and/or response to therapy.

Background: Shared Pathology Informatics Network (SPIN) is a tissue resource initiative that utilizes clinical reports of the vast amount of paraffin-embedded tissues routinely stored by medical centers. SPIN has an informatics component (sending tissue-related queries to multiple institutions via the internet) and a service component (providing histopathologically annotated tissue specimens for medical research). This paper examines if tissue blocks, identified by localized computer searches at participating institutions, can be retrieved in adequate quantity and quality to support medical researchers., Methods: Four centers evaluated pathology reports (1990-2005) for common and rare tumors to determine the percentage of cases where suitable tissue blocks with tumor were available. Each site generated a list of 100 common tumor cases (25 cases each of breast adenocarcinoma, colonic adenocarcinoma, lung squamous carcinoma, and prostate adenocarcinoma) and 100 rare tumor cases (25 cases each of adrenal cortical carcinoma, gastro-intestinal stromal tumor [GIST], adenoid cystic carcinoma, and mycosis fungoides) using a combination of Tumor Registry, laboratory information system (LIS) and/or SPIN-related tools. Pathologists identified the slides/blocks with tumor and noted first 3 slides with largest tumor and availability of the corresponding block., Results: Common tumors cases (n = 400), the institutional retrieval rates (all blocks) were 83% (A), 95% (B), 80% (C), and 98% (D). Retrieval rate (tumor blocks) from all centers for common tumors was 73% with mean largest tumor size of 1.49 cm; retrieval (tumor blocks) was highest-lung (84%) and lowest-prostate (54%). Rare tumors cases (n = 400), each institution's retrieval rates (all blocks) were 78% (A), 73% (B), 67% (C), and 84% (D). Retrieval rate (tumor blocks) from all centers for rare tumors was 66% with mean largest tumor size of 1.56 cm; retrieval (tumor blocks) was highest for GIST (72%) and lowest for adenoid cystic carcinoma (58%)., Conclusion: Assessment shows availability and quality of archival tissue blocks that are retrievable and associated electronic data that can be of value for researchers. This study serves to compliment the data from which uniform use of the SPIN query tools by all four centers will be measured to assure and highlight the usefulness of archival material for obtaining tumor tissues for research.

Pleomorphic adenomas (PAs), also known as benign mixed tumors, are common tumors of the parotid gland. These tumors occasionally undergo malignant transformation, with potentially devastating consequences. This case report presents the clinical and radiographic features of a rare case of biopsy proved brain and spinal cord metastases arising from carcinoma ex PA of the parotid gland.

Background: Advances in molecular biology and growing requirements from biomarker validation studies have generated a need for tissue banks to provide quality-controlled tissue samples with standardized clinical annotation. The NCI Cooperative Prostate Cancer Tissue Resource (CPCTR) is a distributed tissue bank that comprises four academic centers and provides thousands of clinically annotated prostate cancer specimens to researchers. Here we describe the CPCTR information management system architecture, common data element (CDE) development, query interfaces, data curation, and quality control., Methods: Data managers review the medical records to collect and continuously update information for the 145 clinical, pathological and inventorial CDEs that the Resource maintains for each case. An Access-based data entry tool provides de-identification and a standard communication mechanism between each group and a central CPCTR database. Standardized automated quality control audits have been implemented. Centrally, an Oracle database has web interfaces allowing multiple user-types, including the general public, to mine de-identified information from all of the sites with three levels of specificity and granularity as well as to request tissues through a formal letter of intent., Results: Since July 2003, CPCTR has offered over 6,000 cases (38,000 blocks) of highly characterized prostate cancer biospecimens, including several tissue microarrays (TMA). The Resource developed a website with interfaces for the general public as well as researchers and internal members. These user groups have utilized the web-tools for public query of summary data on the cases that were available, to prepare requests, and to receive tissues. As of December 2005, the Resource received over 130 tissue requests, of which 45 have been reviewed, approved and filled. Additionally, the Resource implemented the TMA Data Exchange Specification in its TMA program and created a computer program for calculating PSA recurrence., Conclusion: Building a biorepository infrastructure that meets today's research needs involves time and input of many individuals from diverse disciplines. The CPCTR can provide large volumes of carefully annotated prostate tissue for research initiatives such as Specialized Programs of Research Excellence (SPOREs) and for biomarker validation studies and its experience can help development of collaborative, large scale, virtual tissue banks in other organ systems.

The effect of different amplification and labeling methods on DNA microarray expression results has not been previously delineated. To analyze the variation associated with widely accepted T7-based RNA amplificationand labeling methods, aliquots of the Stratagene Human Universal Reference RNA were labeled using three eukaryotic target preparation methods followed by uniform replicate array hybridization (Affymetrix U95Av2). Method-dependent variability was observed in the yield and size distribution of labeled products, as well as in the gene expression results. A significant increase in short transcripts, when compared to unamplified mRNA, was observed in methods with long in vitro transcription reactions. Intramethod reproducibility showed correlation coefficients >0.99, whereas intermethod comparisons showed coefficients ranging from 0.94 to 0.98 and a nearly twofold increase in coefficient of variation. Fold amplification for each method positively correlated with the number of genes present. Our experiments uncovered two factors that introduced significant bias in gene expression data: the number of labeled nucleotides, which introduces sequence-dependent bias, and the length of the in vitro transcription reaction, which introduces transcript size-dependent bias. This study provides evidence that variability in expression data may be caused, in part, by differences in amplification and labeling protocols.

Background: Only prototypes 5 years ago, high-speed, automated whole slide imaging (WSI) systems (also called digital slide systems, virtual microscopes or wide field imagers) are becoming increasingly capable and robust. Modern devices can capture a slide in 5 minutes at spatial sampling periods of less than 0.5 micron/pixel. The capacity to rapidly digitize large numbers of slides should eventually have a profound, positive impact on pathology. It is important, however, that pathologists validate these systems during development, not only to identify their limitations but to guide their evolution., Methods: Three pathologists fully signed out 25 cases representing 31 parts. The laboratory information system was used to simulate real-world sign-out conditions including entering a full diagnostic field and comment (when appropriate) and ordering special stains and recuts. For each case, discrepancies between diagnoses were documented by committee and a "consensus" report was formed and then compared with the microscope-based, sign-out report from the clinical archive., Results: In 17 of 25 cases there were no discrepancies between the individual study pathologist reports. In 8 of the remaining cases, there were 12 discrepancies, including 3 in which image quality could be at least partially implicated. When the WSI consensus diagnoses were compared with the original sign-out diagnoses, no significant discrepancies were found. Full text of the pathologist reports, the WSI consensus diagnoses, and the original sign-out diagnoses are available as an attachment to this publication., Conclusion: The results indicated that the image information contained in current whole slide images is sufficient for pathologists to make reliable diagnostic decisions and compose complex diagnostic reports. This is a very positive result; however, this does not mean that WSI is as good as a microscope. Virtually every slide had focal areas in which image quality (focus and dynamic range) was less than perfect. In some cases, there was evidence of over-compression and regions made "soft" by less than perfect focus. We expect systems will continue to get better, image quality and speed will continue to improve, but that further validation studies will be needed to guide development of this promising technology.

By imaging large numbers of slides automatically at high resolution, modem automated whole slide imaging (WSI) systems have the potential to become useful tools in pathology practice. This article describes a pilot validation study for use of automated high-speed WSI systems for surgical pathology quality assurance (QA). This was a retrospective comparative study in which 24 full genitourinary cases (including 47 surgical parts and 391 slides) were independently reviewed with traditional microscopy and whole slide digital images. Approximately half the cases had neoplasia in the diagnostic line. At the end of the study, diagnostic discrepancies were evaluated by a pathology consensus committee. The study pathologists felt that the traditional and WSI methods were comparable for case review. They reported no difference in perceived case complexity or diagnostic confidence between the methods. There were 4 clinically insignificant discrepancies with the signed-out cases: 2 from glass slide and 2 with WSI review. Of the 2 discrepancies reported by the WSI method, the committee agreed with the reviewer once and the original report once. At the end of the study, the participants agreed that automated WSI is a viable potential modality for surgical pathology QA, especially in multifacility health systems that would like to establish interfacility QA. The participants felt that major issues limiting the implementation of WSI-based QA did not involve image acquisition or quality but rather image management issues such as the pathologist's interface, the hospital's network, and integration with the laboratory information system.

A critical component of improving patient safety is reducing medical errors. "Improving Patient Safety by Examining Pathology Errors" is a project designed to collect data about and analyze diagnostic errors voluntarily reported by 4 academic anatomic pathology laboratories and to develop and implement interventions to reduce errors and improve patient outcomes. The study database is Web-mediated and Oracle-based, and it houses de-identified error data detected by cytologic-histologic correlation and interdepartmental conference review. We describe the basic design of the database with a focus on challenges faced as a consequence of the absence of standardized and detailed laboratory workload and quality assurance data sets in widely used laboratory information systems and the lack of efficient and comprehensive electronic de-identification of unlinked institutional laboratory information systems and clinical data. Development of these electronic data abstraction capabilities is critical for efforts to improve patient safety through the examination of pathology diagnostic errors.

We report five cases of symptomatic delayed cyst formation after radiosurgery for intracranial arterial venous malformations. Median time to discovery of the cysts following most recent radiosurgery was 59 months (range, 34-89 months). In all five patients, the radiation therapy-induced cysts exhibited tumefactive characteristics, including vasogenic edema, mass effect, and nodular enhancement. Despite these malignant features, these cystic lesions should be recognized as a benign complication of radiosurgery so that proper treatment (i.e., cystoperitoneal shunt surgery or excision) can be initiated.

Background and Purpose: The detection and localization of spinal dural arteriovenous fistulas (AVFs) remain diagnostic challenges. This study tested the hypothesis that elliptic centric contrast-enhanced MR angiography (MRA) can be used to detect spinal dural AVFs, predict the level of fistulas, and reduce the radiation dose and volume of iodinated contrast material associated with conventional angiography., Methods: We examined 31 patients who presented with suspected spinal dural AVF between December 2000 and March 2004. All patients underwent MRA and conventional angiography. The effect of MRA on subsequent conventional angiography was assessed by analyzing total fluoroscopy time and volume of iodinated contrast material used., Results: At angiography, spinal dural AVFs were diagnosed in 22 of 31 patients, and MRA depicted an AVF in 20 of the 22 patients. MRA findings correctly predicted a negative angiogram in seven of nine cases. Of the 20 true-positive MRA results, the level of the fistula was included in the imaging volume in 14. In 13 of these 14 cases, MRA results correctly predicted the side and the level of the fistula to within one vertebral level. Fluoroscopy time and the volume of contrast agent was reduced by more than 50% in the 13 patients with a spinal dural AVF in whom MRA prospectively indicated the correct level., Conclusion: Contrast-enhanced MRA can be used to detect spinal dural AVFs, predict the level of fistulas, and substantially reduce the radiation dose and volume of contrast agent associated with catheter spinal angiography.

The process of digital imaging in microscopy is a series of operations, each contributing to the quality of the final image that is displayed on the computer monitor. The operations include sample preparation and staining by histology, optical image formation by the microscope, digital image sampling by the camera sensor, postprocessing and compression, transmission across the network and display on the monitor. There is an extensive literature about digital imaging and each step of the process is fairly well understood. However, the complete process is very hard to standardize or even to understand fully. The important concepts for pathology imaging standards are: (1) systems should be able to share image files, (2) the standards should allow the transmission of information on baseline colours and recommended display parameters, (3) the images should be useful to the pathologist, not necessarily better or worse than direct examination of a slide under the microscope, (4) a mechanism to evaluate image quality objectively should be present, (5) a mechanism to adjust and correct the minor errors of tissue processing should be developed, (6) a public organization should support pathologists in the development of standards.

Understanding the role of pathology informatics in patient safety entails an introduction to terminology and projects that have represented efforts to date in this area. The authors provide a short alphabetized introduction to several "buzzwords" and terms related to tools and processes that are used by health care research experts and workers involved in patient safety initiatives. The authors also include short descriptions of key health care research and patient safety projects that are relevant to pathology. They aim to highlight the areas where pathology informatics in all of its flavors (production systems provided by vendors as well as research and development efforts) can play a role in promoting patient safety.

As academic pathology departments have become increasingly based in large, regional medical systems spread across hundreds of square miles, new methods are needed to tie these increasingly distributed departments together as integrated units. An important part of that integration is the ability to share academic and teaching conferences across long distances. In this article we present an effective, low-cost webcasting system that has evolved at the University of Pittsburgh Medical Center Department of Pathology over the past several years based on inexpensive, widely available software. To date, the system has broadcast and archived more than 400 conferences and currently serves approximately 80 to 100 requests each week. Important factors in the success of the program include the creation of a faculty steering committee to control resources and manage growth, the availability of informatics faculty and support for technical staff, and the decision to operate the service as part of the core information technology infrastructure of the department. Webcasting will likely become an even more important academic and operational tool in the future as more of the department's conferences, seminars, and even working meetings are communicated through the webcasting infrastructure.

Modern, molecular bio-medicine is driving a growing demand for extensively annotated tissue bank specimens. With careful clinical, pathologic and outcomes annotation, samples can be better matched to the research question at hand and experimental results better understood and verified. However, the difficulty and expense of detailed specimen annotation is well beyond the capability of most banks and has made access to well documented tissue a major limitation in medical re-search. In this context, we have implemented automated annotation of banked tissue by integrating data from three clinical systems--the cancer registry, the pathology LIS and the tissue bank inventory system--through a classical data warehouse environment. The project required modification of clinical systems, development of methods to identify patients between and map data elements across systems and the creation of de-identified data in data marts for use by researchers. The result has been much more extensive and accurate initial tissue annotation with less effort in the tissue bank, as well as dynamic ongoing annotation as the cancer registry follows patients over time.

Purpose: To examine the clinical and radiographic findings in a large group of patients having or suspected of having a spinal dural arteriovenous fistula., Methods: An analysis of 240 spinal angiograms in 132 patients revealed 97 vascular malformations that included 66 spinal dural arteriovenous fistulas. Sixteen patients had 1 or more normal spinal angiograms that were performed for suspected spinal dural arteriovenous fistulas on other imaging studies. The imaging and clinical data were reviewed in all patients who had or were suspected of having a spinal dural arteriovenous fistula and who had a spinal MR (n = 44) and a myelogram (n = 37)., Results: Spinal dural arteriovenous fistulas were more common in males (3.4:1) with an average age of 62 years (range, 37 to 81 years). The average time from onset of symptoms to diagnosis was 27 months. Clinical findings included weakness (55%), a progressive clinical course (100%), and a myelopathy on exam (84%). The nidus of the fistula was located between T-6 and T-12 in 61%, in the sacrum in 9%, and intracranially in 8%. In the spinal dural arteriovenous fistula group, vessels were seen on supine myelography in all patients. MR findings in this group included increased T2 signal in the cord (100%), gadolinium enhancement (88%), mass effect (45%), and flow voids (T1, 35%; T2, 45%). The patients in the negative spinal angiogram group were younger (average age, 51 years), had symptoms longer (average time from symptom onset to spinal angiogram, 59 months), and presented with numbness or pain (76%). When compared with the patients with spinal dural arteriovenous fistula, acute or stable deficits were more common (31%), and myelopathy on exam was less common (56%). Although the angiogram-negative patients commonly had vessels on the myelogram (92%), abnormal T2 signal in the cord was unusual (17%)., Conclusions: In the appropriate clinical setting, high T2 signal of the spinal cord is the most sensitive imaging finding in spinal dural arteriovenous fistula. The presence of mass effect and enhancement should not discourage this diagnosis. The likelihood of finding a spinal dural arteriovenous fistula in a patient without T2 signal on MR is low.

In this report, we describe the inhibitory activity of long-chain alcohols on the growth of Mycoplasma gallisepticum and Mycoplasma pneumoniae. Peak inhibition was recorded with saturated primary alcohols (64 microM) varying in chain length from 16 to 19 carbon atoms. The unsaturated alcohols (oleyl, linoleyl, and linolenyl) and the secondary alcohol (pentadecan-2-ol), when employed in the same test conditions, were considerably less effective growth inhibitors than the primary saturated alcohols. Stearic and palmitic acids were also ineffective as growth inhibitors of M. pneumoniae and M. gallisepticum at a 128 microM concentration. Because these antimycoplasma agents are fatty alcohols and cholesterol is known to be required for the growth of some mycoplasmas, additional cholesterol was added in an attempt to reverse the inhibition observed with these agents. Cholesterol at a 128 microM concentration did not significantly relieve the growth inhibition observed with stearyl alcohol at a 48 microM concentration. Mammalian cell cultures were found to be significantly more resistant to the effects of these inhibitory alcohols than were the mycoplasmas. Electron micrographs showed that inclusion of stearyl alcohol in the culture medium produced changes in the cellular morphology of the treated mycoplasmas.