Virtual microscopy in pathology education

Transcription

1 Human Pathology (2009) 40, Special Section on Telepathology Virtual microscopy in pathology education Fred R. Dee MD Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA Received 23 March 2009; accepted 9 April 2009 Keywords: Virtual microscopy; Virtual slides; Pathology education Summary Technology for acquisition of virtual slides was developed in 1985; however, it was not until the late 1990s that desktop computers had enough processing speed to commercialize virtual microscopy and apply the technology to education. By 2000, the progressive decrease in use of traditional microscopy in medical student education had set the stage for the entry of virtual microscopy into medical schools. Since that time, it has been successfully implemented into many pathology courses in the United States and around the world, with surveys indicating that about 50% of pathology courses already have or expect to implement virtual microscopy. Over the last decade, in addition to an increasing ability to emulate traditional microscopy, virtual microscopy has allowed educators to take advantage of the accessibility, efficiency, and pedagogic versatility of the computer and the Internet. The cost of virtual microscopy in education is now quite reasonable after taking into account replacement cost for microscopes, maintenance of glass slides, and the fact that 1-dimensional microscope space can be converted to multiuse computer laboratories or research. Although the current technology for implementation of virtual microscopy in histopathology education is very good, it could be further improved upon by better low-power screen resolution and depth of field. Nevertheless, virtual microscopy is beginning to play an increasing role in continuing education, house staff education, and evaluation of competency in histopathology. As Z-axis viewing (focusing) becomes more efficient, virtual microscopy will also become integrated into education in cytology, hematology, microbiology, and urinalysis Elsevier Inc. All rights reserved. 1. Introduction Virtual microscopy is in the process of revolutionizing the teaching of microscopic pathology. Multiple medical schools have implemented this novel technology, and virtual microscopy is being introduced into the continuing educational and self-assessment programs of pathology educational organizations. Virtual microscopy is very attractive to educators because it nearly perfectly emulates the pan and zoom features of traditional microscopy, with the added advantages of the efficiency, accessibility, and versatility of 100 Medical Laboratories, University of Iowa, Iowa City, IA 52242, USA. address: fred-dee@uiowa.edu. computer-assisted education. This article aims to provide an overview of the following: (1) technological development of virtual microscopy for education, (2) advantages and disadvantages of virtual microscopy in education, (3) implementation of virtual microscopy in education ( ), and (4) future challenges and opportunities for virtual microscopy in education. 2. Technological development of virtual microscopy for education Web-based virtual microscopy requires multiple technical steps for optimal educational implementation: (1) acquisition /$ see front matter 2009 Elsevier Inc. All rights reserved. doi: /j.humpath

2 Virtual microscopy in pathology education of digital information equivalent to hundreds of high power fields of view; (2) creation a seamless giant montage, called a virtual slide or whole slide image; (3) converting the virtual slide into a file format that allows panning in the x-y axis and zooming from one magnification to another; (4) serving the virtual slide file (over a network or the Web) in a pan and zoom viewer; and (5) integrating virtual slides and editors via databases that facilitate superimposed annotations and accompanying text. Early technology for acquisition of multiple microscopic fields of view (called digital tiles) with a precision motorized microscope stage and creation of a digital montage (now called a virtual slide) was initially described in [1,2]. Then in the late 1990s, when desktop computers had enough processing speed and RAM to acquire a digital facsimile of the majority of the information on a glass slide, virtual slide acquisition technology using digital tiles was improved upon and commercialized by BacusLabs ( and MicroBrightField ( Another technologic advance in acquisition of virtual slides came several years later when 2 novel methods of acquisition that did not rely on creating digital 1113 tiles with a traditional microscope were developed and commercialized in the United States. Aperio ( com) released a linear scanner that rapidly acquired digital stripes across the whole slide, and Dmetrix ( net/) released an array microscope for rapid simultaneous digital capture of the whole slide by multiple microlenses [3]. In the late 1990s, simultaneous with the commercialization of virtual slide acquisition solutions, Kodak and others introduced a multiresolution pyramidal file format called FlashPix, and Live Picture/MGI developed a FlashPix image file converter and server to stream virtual slides over the Web to a pan and zoom viewer [4]. At about the same time, BacusLabs adapted a method for transmission of digital tiles over the intranet, which were then assembled into a montage (called a WebSlide) in a pan and zoom client viewer. Another major innovation that further increased the educational value of virtual microscopy came in 2001 when developers began to integrate virtual slides with an annotator applet in a database structure. This educational model provided educators the ability to label virtual slides with arrows, circles, and text labels using overlays. Integration with a database structure also allowed educators to Fig. 1 This screen shot from the Virtual Slidebox/Human Histopathology Atlas demonstrates text and arrow overlays that are activated by clicking on annotation buttons and text in the left frame. The entire content of the browser window is dynamically generated via a Perl scripted MySQL database and editor interface. Note that the location and navigation box (upper right) provides a thumbnail for orientation to the whole slide. This virtual slide is a fortuitous cut through a bronchus showing transition from normal to invasive carcinoma shown at a traditional microscope magnification equivalent of Areas of interest can be zoomed to the equivalent of 20.

3 1114 F. R. Dee easily link descriptive text specific to the virtual slide in a separate browser window, as well as create links to supplemental gross images and normal virtual slides. Some of these features are illustrated in Fig. 1, which is a screen shot of an annotated slide in the Virtual Slidebox / Human Histopathology Atlas ( Manipulation of an annotator via a scripted database editor can also be used to provide initially hidden feedback to trainees via instructor-generated labels after they independently examine the slide or allow trainees to add their own labels to the virtual slide. These functions are particularly important in teaching and evaluating locator and identification skills of trainees who will use the traditional microscope in their future practice. The standard virtual slide technology described above does not provide the ability to focus because only 1 focal plane (in the x-y axis) is acquired. Multiple planes of focus are not needed for most histopathologic applications in education; however, as will be pointed out later in this article, the ability to focus up and down is critical for education in disciplines such as cytology, hematology, microbiology, and urinalysis that use smears and liquidbased preparations [5-8]. On these preparations, the cells do not all lay flat on the slide, and in some cases, 3- dimentional (3-D) clusters of cells or objects need to be visualized. Focusing can also occasionally be important in histologic sections where the depth of focus afforded by only 1 plane of focus cannot adequately visualize microbes or other small objects [9]. Virtual focusing can be accomplished by 3-D scanning (also called z-axis scanning), which consists of acquiring the equivalent of 6 or more virtual slides separated by several microns of focus perfectly aligned in the z-axis, sometimes called z-stacks. In the 3-D viewer, panning and focusing are carried out by jumping from 1 virtual slide focus level in the z-stack to another using up-down arrows or the mouse roller bar; simultaneously, each virtual slide level in the z-stack can be panned in the x-y plane similar to standard virtual slides. Currently, 3-D scanning of multiple perfectly aligned focal planes over the whole slide is possible, but is technically complex and time consuming. In addition, efficient viewing of 3-D slides, which requires the ability to simultaneously pan and focus over the whole slide at several magnifications, is much slower than examining a standard virtual slide, especially over the Web. Unfortunately, 3-D solutions that have been well evaluated for efficiency of synchronous Table 1 Advantages and disadvantages of virtual microscopy versus traditional microscopy Advantages Accessibility Access can be anywhere anytime there is a computer (and the Web) available. One slide can be viewed by many or duplicated and shared. Multiple recuts are not needed. One-of-a-kind slides that cannot be recut can be duplicated into an unlimited number of copies and shared with others, eg, the fortuitous cut in Fig. 1. Efficiency Focus, proper condenser adjustment, and lighting are not required. Technical competence in viewing is easier to achieve and less frustrating for trainees who do not have an aptitude for traditional microscopy. There is rapid access to the next slide in the slide box. Pedagogic Very-low-power overview ( 4) allows trainee to better visualize relationship of pathologic to normal tissue. A thumbnail and location box allows trainee to remain oriented to the whole slide while viewing at high magnification. Marking x-y and magnification coordinates of multiple key areas and movement among these areas at the click of the mouse is possible. Side-by-side viewing, annotation overlays, and integration with descriptions, case scenarios, gross and radiological images or digital photomicrographs is possible. Group discussion is enhanced as each computer screen can serve as a multihead microscope. Cost Cost may be significantly less depending on the educational venue. Disadvantages Pedagogic Trainees do not learn how to use a traditional microscope if virtual microscopy is used exclusively. Technology: Low magnification has less resolution when viewed on a standard computer screen. Refractile objects do not refract well. Original glass slide tissue artifact and imperfections are difficult to scan. Virtual focus acquisition and viewing is inefficient, especially over the Web.

4 Virtual microscopy in pathology education Table 2 Advantages and disadvantages of virtual microscopy versus digital photomicrographs Advantages Disadvantages Pedagogic Cost Ability to pan and zoom. Cost is significantly more. Very-low-power overview Technology ( 4) allows trainee to better visualize relationship of pathologic to normal tissue. A thumbnail and location box Transmission speed, allows trainee to remain reliability of acquisition oriented to the whole slide and serving, and relative while viewing at high lack of standards all add magnification. complexity to implementation. Marking x-y and magnification coordinates of multiple key areas and movement among these areas at the click of the mouse is possible. simultaneous panning and focusing (CytoView and a MicroBrightField solution) are primarily intended for proficiency testing and research applications, respectively, and are not being distributed for education [5,6,8]. A recent report using a Hamamatsu system showed promising results for educational application, but speed and efficiency of viewing were not reported [9]. Other vendors (including BacusLabs and Aperio in the United States) also have 3-D solutions. Zeiss ( has developed a variation on the above called extended focus, in which z-stacks are acquired as described above. Then, the sharp contrast details from each focal plane are extracted and collapsed into a single virtual slide where the best focused detail derived from each of the multiple focal planes is viewed. The acquisition and processing are still technically complex and time consuming, but transmission over the Web is as fast as with a standard virtual slide (personal observation/ communication). Thus, cells laying on the slide at different levels are all in focus, and 3-D objects are in focus top to bottom; however, the sensation of being able to focus through a 3-D cell cluster or object is missing. Although early development and implementation were driven primarily by educators and research applications, more recent commercial development has been driven by the potential applications in service pathology. Subsequent to the early development described above, there has been an explosion in virtual slide technology in both quality and quantity. For example, in 2006, it was reported that there were 31 commercial vendors in the field virtual microscopy [10]. Scanning and serving of virtual slides are now much more rapid, of higher quality, of higher resolution, of larger file size, and more versatile than was even conceivable when virtual microscopy was first implemented in education in Advantages and disadvantages of virtual microscopy in education Tables 1 and 2 outline the advantages and disadvantages of virtual microscopy for teaching microscopic pathology, compared with traditional (real) microscopy and digital photomicrographs, respectively. The advantages and disadvantages listed are recurrent themes derived from articles describing implementation of virtual slides in education (Table 3) and from personal communication among educators at education and informatics meetings Virtual microscopy versus traditional (real) microscopy Because virtual microscopy can nearly perfectly emulate traditional microscopy, it can be applied to almost any discipline or educational venue where traditional microscopy is currently used. Plus, computerization adds the accessibility, efficiency, and pedagogic advantages of virtual microscopy, which are detailed in Table 1. The cost of virtual microscopy in medical student education may be quite comparable with traditional microscopy. For example, when we at Iowa cost-accounted virtual microscopy versus traditional microscopy, taking into account the replacement cost for microscopes, generation of and maintenance of multiple sets of glass microscope slides, and the fact that microscope space can be converted to multiuse computer laboratories or research space, we estimated that startup costs, including acquisition equipment and computer software and hardware, could be recouped. Although the cost for virtual microscopy remains high, the cost should eventually come down with innovation and competition among vendors. In addition, there can be cost sharing as virtual microscopy becomes integrated into education, clinical service, and research in the same institution. Finally, for continuing education Table 3 Venues for virtual microscopy implementation 1115 Education in pathology References 3.1 Medical student education Pathology small group teaching [11-13] Histopathology laboratories/large groups [12,16,17] Integrated and problem-based curricula [15] Repositories for sharing among [13] institutions 3.2 Cytology [6,8,18-21] 3.3 Hematology [7] 3.4 House staff education and evaluation [22] 3.5 Continuing medical education [23-25] 3.6 Veterinary pathology and comparative [26-29] pathology 3.7 Histology as a prerequisite for pathology [30-36] education

5 1116 F. R. Dee (and competency evaluation), costs saved by not having to create and mail glass slides can offset acquisition and serving costs Virtual microscopy versus digital photomicrographs Because virtual slides are single (although complex) giant images, they can be placed on a server with a URL and thus can be used in Web-based education as you would a photomicrograph, but with the added pedagogic advantages detailed in Table 2. Although photomicrographs can be nested to provide the semblance of pan and zoom, and annotations can be added, these functions are much more readily performed with virtual slides and associated annotation editors. The disadvantages of virtual microscopy versus digital photomicrographs are primarily cost related. Cost is a minimum of about $80,000 for scanner, and serving and viewing software. Cost for serving and viewing software, with commercial scanning of slide sets at approximately $40/ slide, can be less than $10,000 startup. Compared to teaching with digital photomicrographs, the transmission speed, technical complexity, reliability, and relative lack of standards in the virtual microscopy industry are still somewhat of an issue, but these have significantly improved over the last 8 years. 4. Implementation of virtual microscopy in education Table 3 lists the variety of educational venues in which virtual microscopy has been implemented. The references point to articles describing implementation and evaluation [6-8,11-36] Medical student education in pathology Results of a small survey of pathology chairs in 2007 showed little difference between the United States Medical Licensing Examination (USMLE) pathology scores from institutions with or without microscopes in their curricula [37]. Based on this finding, the authors suggested that a possible conclusion is that the microscope is now irrelevant for teaching pathology to medical students, although indicating that a larger study would be needed to test the validity of their suggested conclusion. The suggestion in this article was already preceded by a progressive devaluation of the microscope in medical student education. Before the early 1990s, most pathology courses relied on lectures and laboratories or pathology case based exercises built around traditional microscopy [38]. Over the last several decades, a number of curricular reforms have impacted this old paradigm [37-41]: (1) decreased time has been allotted for pathology and other basic sciences because of the need to introduce more student contact to foundations of clinical practice in the first 2 years of medical school; (2) accrediting bodies recommended a move away from department-based didactic teaching with lectures and laboratories toward more centrally managed integrated curricula, with an emphasis on problem-based or case-based learning and self-directed study; (3) traditional microscopy has been progressively augmented and in some cases replaced by digital photomicrographs because of the efficiency, accessibility, and flexibility provided by computer-assisted education; (4) there is a perception that practicing physicians (other than pathologists) do not need to know how to use a microscope (especially for histopathology); (5) single-dimensional microscope laboratories are expensive to maintain and occupy valuable space that could be used for computer laboratories or research. A limited survey of pathology chairs presented at the Association of Pathology Chairs (APC) meeting in 2007 indicated that only about 45% of medical school curricula have pathology laboratories or large groups for teaching histopathology, and only about 18% used glass slides in their curricula (personal communication from Patricia Thomas). Another limited survey in 2007 indicated that up to 40% of medical schools still used traditional microscopes and glass slides in their teaching of pathology [37]. Combining this 2007 data, and comparing it with 1997 survey data reported by Kumar et al, suggests that the number of curricula with pathology laboratories has decreased over the last decade from 98% to less than 50% and that the use of glass slides has decreased from 85% in 1997 to about 30% in 2007 [37,38]. This progressive decrease in use of traditional microscopy set the stage for the entry of virtual microscopy into education of medical students in Since that time, this new technology, with its promise to expand on the pedagogic advantages of traditional microscopy, has been successfully implemented into many pathology courses in the United States and around the world. A survey in 2004 indicated that virtual microscopy in US medical student education had increased from its inception in 2000 to 22% in 2004 [42]. This survey also indicted that of those course directors not using virtual microscopy at that time, 50% expected to implement virtual microscopy within 3 to 5 years. In 2007, based on a combination of 2 limited surveys presented at the APC meeting (by PatriciaThomas) and the data from the Group for Research in Pathology Education (GRIPE; personal communication), it appears that as of 2007, perhaps up to 33% of medical schools in the United States had integrated virtual microscopy into their pathology curricula. In addition to US medical schools, there is also increasing international implementation. Personal communication with several educators outside the United States indicates 4 of 5 medical schools in Switzerland, 4 of 12 medical schools in Poland, and 3 of 18 medical schools in Australia are using virtual microscopy in their pathology courses (Kathrin Glatz, Janusz Szymas, and Rakesh Kumar, respectively).

6 Virtual microscopy in pathology education A wide variety of settings can be used to teach histopathology to medical students, ranging from large laboratories (up to 150 or more students), to smaller laboratories or large groups (15-50 students), to small group settings (6-10 students). Virtual microscopy can be implemented in any of these educational settings, assuming computer access and space is available. Weather a medical school decides to implement virtual microscopy depends on a number of factors, not the least of which is computer availability. The following 3 sections discuss several implementations of virtual microscopy in medical student education. Although no outcomes research has been done to prove that the pedagogic advantages of virtual microscopy make it superior to traditional microscopy or digital photomicrographs for teaching histopathology to medical students, it is clear that virtual microscopy provides an efficient, accessible, and enjoyable way to do so Pathology small group teaching At Iowa in our second-year pathology course for medical students, we converted from traditional pathology microscope laboratories to small group teaching (called pathology case analysis) in the early 1970s. Each week in preparation for pathology case analysis, students examine 4 microscope slides with associated patient scenarios and gross and radiographic images during independent learning time. Then, during a 2-hour case analysis small group session (8 students), they present the gross and microscopic pathology, clinical pathologic correlation, and pathogenesis to their classmates under the guidance of a pathology faculty or resident facilitator. Before implementation of virtual microscopy in case analysis, students had 60 h/wk access to a laboratory equipped with double-headed microscopes, and histopathology was presented by the students to the small group using a microscope equipped with a video camera and monitor. In 1999, we purchased virtual slide acquisition and delivery hardware and software and digitized our 67 caseassociated glass slides. In 2000, we implemented the virtual slides into our pathology case analysis exercises and integrated them via a database with other case materials [11,13]. These case analysis materials can be viewed on the Web ( cases.cgi). After implementation, students were given the option of preparing for small group presentation using glass slides or using virtual microscopy. In the first year of implementation, use of traditional microscopy by students decreased to 25% of that in 1999, which was 100%. Over the next 3 years, the use of traditional microscopy in case analysis fell to near zero, where it has remained. On formative evaluations, students indicated that image quality of virtual slides was nearly equal to that of traditional microscopy and felt that they learned better using the virtual slides because of efficiency and accessibility. Facultysubjective evaluations indicated an increase in students' skill in demonstrating histopathology in small group. In addition, faculty found the virtual slides very useful in their 1117 own preparation for small group because they could prepare to facilitate case analysis small group in their office or at home. There was no change in student scores on pathology examinations. Over the last 8 years, we have upgraded both our scanner and our delivery software several times. Our large single-use microscope room has become a multipurpose laboratory with computers, microscopes, and bench top space for point of care and venipuncture training. In the near future, this laboratory will be downsized and moved to another site, and the large laboratory will be converted to research space Pathology laboratory or large group teaching Most medical student pathology courses, when microscope slides are used in the curriculum, use a variety of permutations on the pathology laboratory rather than the pathology case analysis model described above, although smaller laboratories (sometimes called large groups ) frequently have associated cases scenarios. A very successful incorporation of virtual microscopy was carried out in 2003 at the University of New South Wales (UNSW) [12]. Their weekly sessions (45-55 students) use 2 to 3 cases with 4 to 5 microscope slides. In the large group room, before implementation of virtual microscopy, each student had a microscope and slides, and the tutor would supervise the learning process. In 2002, they digitized their glass slides and added 32 computers (side-by-side with microscopes) with 2 students per computer. In addition, the tutor could project the virtual slide and move to key areas of the slide with premarked coordinates. No other component of the course was changed. Evaluation of the implementation indicated most students preferred using virtual slides. Formative evaluations pointed out that virtual slides were always in focus, faster to use, and efficient and were especially appreciated by students with low aptitude for using traditional microscopy. In addition, everyone sees the same slide, the computer facilitated more student-to-student and student-to-faculty interaction, and students could review at home. They also implemented virtual microscopy into their progress examinations and found no difference in performance from previous years using glass slides. At the other end of the spectrum of large group/pathology laboratory teaching is a recent report from the Seoul National University College of Medicine [16]. They implemented virtual microscopy into a previously traditional pathology laboratory consisting of 160 students with 3 tutors. Implementation of virtual microscopy was carried out by having students download the digitized class slide set and a viewer on to their personal laptops from the university server. In the same laboratory setting as before, students used their laptops. After implementation, students were asked to compare virtual microscopy with traditional microscopy. Students (142 respondents) strongly preferred virtual microscopy. Formative evaluations showed a range from 79% to 98% affirmative responses to each of the following statements concerning virtual microscopy: less stressful

7 1118 F. R. Dee better image quality less time to find lesions better for changing magnification easier to use...had better focus better for group discussion easier to switch to another slide more enjoyable and better to find artifacts. Students also appreciated the ability to review slides at home. Virtual microscopy was implemented into the annual Pathobiology of Cancer Workshop laboratories in 2002 [17]. After implementation, students (18 per laboratory) continued to study a set of glass slides using a traditional doubleheaded microscope; however, the facilitator projected a virtual slide acquired from the slide being studied by the students. Although this workshop is for bioscience trainees, the implementation provides a model for implementation in medical student laboratories that might use a similar format. This model allows students to continue to learn from traditional microscopy, whereas virtual slides are used to facilitate classroom instruction. The advantage of this model is that students can more easily find areas of interest on the glass slide as the instructor points them out on the virtual slide. It also allows the students to study on the Web outside of laboratory time Virtual microscopy in an integrated curriculum Integration of pathology with other disciplines can take a variety of forms, ranging from integration with basic science courses to integration with introduction to clinical medicine, or totally integrated with both, and the pathology teaching can be in a large or small group. Integration of pathology and histology into a large group setting using virtual slides was carried out at UNSW in , 1 year after implementing it into their standalone pathology course [15]. Based on the success of virtual slides the year before, they abandoned traditional microscopes and used virtual slides only. Both histologists and pathology tutors were in attendance. The results of this integration had a similar positive outcome to the pathology implementation the year before. There are no articles describing implementation of virtual microscopy into a fully integrated preclinical curriculum or a Problem-Based Learning (PBL) curriculum; however, it is likely that some programs are doing so. There is no logistic reason why virtual slides cannot be integrated with PBL if the cases are online and small group rooms have computer access. Learning issues could then be developed that require students to study and present histopathology via virtual slides along with clinical and pathophysiologic correlations Repositories for sharing among institutions The University of Iowa Department of Pathology obtained a grant from the National Library of Medicine ( ) to develop a virtual slide database for sharing among medical schools. The data set is composed of a comprehensive set of slides for use in general and systemic pathology. The slides were initially selected based a list of core morphologic concepts of disease for second-year medical students [43]. Using the Iowa course data set as a foundation, we have added slides from institutions around the world, thus creating an open source virtual slide box. A histology data set is also included. The approximately 1000 virtual slides in the data set are in a nonproprietary file format, which can be converted for use with a wide variety of virtual slide server and viewer combinations. Slides in the data set can be viewed in the Virtual Slidebox at uiowa.edu/virtualslidebox. Directions for acquisition of the data set can be found in the Copyright and Fair Use link on the Virtual Slidebox home page. The entire data set and associated metadata, which are available to course directors for the cost of processing and mailing, has now been shared with more than 30 institutions in the United States and around the world. In Australia, UNSW has developed a repository of virtual slides, with associated worksheets illustrating approaches to teaching with these slides (personal communication from Rakesh Kumar). This repository has been funded by the Australian Learning & Teaching Council. The slides include teaching sets for not only anatomy (histology) and pathology but also botany and zoology. The virtual slide collections are available without charge to Australian tertiary education institutions. Data sets for sharing among institutions provide distinct advantages, not the least of which is decreasing the high cost of acquisition. In addition, slides with exceptional education value can be used by all. As has occurred with photomicrographs, creation of virtual slide data sets by educational organizations or consortia of medical schools should also be feasible Although it is also technically and logistically possible for consortia of institutions to share a server, given the uncertainty of the Web and the fact that serving and viewing software still has variable performance, institutions should still purchase their own serving and viewing software, if virtual microscopy is to be a required part of their curriculum Cytology As outlined in Section 2, the standard virtual slide, with only one focal plane, does not work as well for cytologic preparations as it does for histologic sections. Evaluation of two 3-D solutions indicated that they have diagnostic accuracy and acceptable viewing efficiency [6,8]. These solutions allowed simultaneous panning and focusing in a continuous seamless manner, as is done in real microscopy by cytologists. Efficiency of viewing was facilitated by bringing all of the z-stacks in a field of view into RAM and ready to focus as soon as new fields are panned into view. When this was done directly off of a desktop hard drive or DVD, it still took cytologists 4 times as long to carefully examine the same surface area of a slide with virtual microscopy as with traditional microscopy; however, cytologists thought this level of viewing efficiency tolerable for cytology education [8]. Viewing over the Web is even slower and would not be acceptable for clinical work. Finally, there have been a

8 Virtual microscopy in pathology education number of other reports describing virtual microscopy for cytology, including description of software interfaces to teach locate and identify skills [18-21]. The above activity, and the fact that a number of vendors appear to be working on efficient 3-D solutions, offers promise for the future of virtual microscopy in cytology education Hematology Hematology (as well as microbiology and urinalysis) microscopic preparations have some of the same focus issues as cytology; however, there has been less activity among educators in these areas as evidenced by a paucity of reports in the literature [7] House staff education and evaluation The American Board of Pathology has been augmenting the practical component of their examination with virtual microscopy for a number of years, and as of 2006, 15 of 75 microscopic questions used virtual slides [22]. Their continued use in board examinations suggests that virtual microscopy should be an efficient and reliable way to train and evaluate pathology house staff. In addition, as discussed elsewhere in this issue, there are studies showing a high level of agreement between virtual slides and the original glass slides in diagnostic telepathology and competency testing. Thus, there is tremendous opportunity in house staff education to create virtual slide sets, annotate them, develop atlases and self-assessment exercises, and develop consortia for sharing among training programs. In compliance with the Accreditation Council for Graduate Medical Examination (ACGME) requirement for programs to implement objectively measurable performancebased education and assessment, we at Iowa developed an inhouse exercise designed to measure progress in development of competency in morphologic skill in general surgical pathology. We administered a Web-based extended multiplechoice examination with 20 virtual slides and minimal clinical information to our 20 residents. This examination showed very high internal reliability, as well as significant validity as measured by strong correlation with months in training in surgical pathology and performance on the surgical pathology section of the Resident In-Service Examination (RISE) examination. This study was presented at the 2008 APC meeting, and is published in this issue of Human Pathology (Bruch L, DeYoung B, Dee FR). It is also of interest that in Europe, the first progress test for trainees and pathologists called European Pathology Learning System was administered on October 1, 2008 (personal communication from JG van den Tweel). In addition, virtual slides may make it possible to more objectively measure and improve the skills that house staff need to examine a microscopic slide. Up to this point, subjective methods have been used as a trainee and expert interact over glass slides at a multiheaded microscope. Krupinsky et al [44] have recently shown that virtual slides can be used to facilitate study of eye movement of trainees and experts as they look at a slide and thus objectively document the approach experts take as they evaluate a microscopic slide. An expansion of this type of educational research may facilitate construction of computerized self-assessment exercises that compare trainees' eye movement and panning and zooming actions with experts and thus provide trainees objective feedback for improvement. In addition, software solutions with an interface to teach cytology locator skills described by Stewart et al [21] have application not only in cytology but also in histopathology and hematology Continuing education Virtual microscopy appears to be well established in histopathology continuing education. The diagnostic concordance with glass slides, cost savings provided by Web accessibility, and the need for only 1 original glass slide to provide virtual slide viewing to all participants underline the impact that virtual microscopy can have on continuing education in pathology. Several articles have described the use of virtual slides in continuing education-like activities [23-25]. In addition, a number of major pathology organizations have recently implemented virtual microscopy into their offerings, including the American Society for Clinical Pathology (ASCP), the College of American Pathologists, and the United States and Canadian Association of Pathologists. The ASCP uses virtual slides to supplement instruction during meetings and self-assessment activities: meetings focusing on in-depth topics will use virtual microscopy during the session to illustrate morphology, and then provide participants with a DVD with the images as a reference; online self-assessment activities will incorporate virtual microscopy to allow further study of the images used in the case studies (personal communication from Becky Harris, ASCP). Finally, on an international level, virtual microscopy is being used by the European Virtual Microscopy Network ( and the Canadian Association of Pathologists ( Veterinary and comparative pathology 1119 Similar to human pathology, there is a role for virtual microscopy in veterinary pathology teaching and comparative pathology [26-29]. Simms et al [29] described the successful implementation in an undergraduate veterinary medical curriculum. Virtual microscopy is also prominent on several comparative pathology Web sites [26]. These include the Comparative Pathology link on the Iowa Virtual Slidebox home page ( and a University of California at Davis Web site, which has many human cancers and mouse models of human cancer (

9 1120 F. R. Dee 4.7. Histology a prerequisite for pathology education Virtual microscopy is applicable to the study of histology, as it is to histopathology [30-36]. In addition, the same curricular pressures that apply to pathology also apply to the teaching of histology in medical schools. Thus, it is not surprising that a review of trends in histology teaching in US medical schools indicated that as of 2005, approximately 25% of schools had implemented virtual microscopy into their histology teaching with an additional 25% indicating that they would implement virtual microscopy by the following year [34]. Thus, virtual microscopy implementation in histology is probably at least as prevalent as in pathology, and the 2 disciplines frequently share hardware and software in the same institution. Harris et al [30] described implementation of virtual microscopy into histology in the medical school curriculum at the University of Iowa in 2000, simultaneous with its implementation in pathology [31]. The first step in this implementation was to put the existing histology syllabus on line side-by-side with virtual slides of the entire histology glass slide set. After carrying out introductory laboratories in a traditional laboratory to orient students to the use of the microscope, students were then allowed to choose among 4 different venues for learning for the balance of the semester: (1) the old microscope-only laboratory, (2) a laboratory equipped with both computers and traditional microscopes, (3) a computer-only laboratory, and (4) self-study on the computer. Most students opted for the combined laboratory, probably in part because the final practical examination continued to be given using traditional microscopy. The following year, extensive annotations were added to the virtual slides. In addition, virtual slide practice exercises were added in which the trainee was first given an unknown slide. They were asked to identify the tissue, then an arrow appeared pointing at a structure to identify, then an answer followed. The annotations and exercises increased self-study and markedly increased student satisfaction. Performance levels on examinations have been maintained. Subsequently, a number of other novel implementations of virtual microscopy in histology have been described [32,33,35,36]. 5. Future opportunities and challenges for virtual microscopy in education Commercial vendors and advancing technology have had and will probably continue to have an impact on the development of virtual microscopy for education in the United States. The proprietary nature of some systems and the lack of interchangeability of file formats among the products continue to be of concern; however, these appear to be less significant an impediment to innovation in education than in the early years of virtual microscopy. The literature devoted to virtual microscopy innovation and implementation in education is small but rapidly expanding. Excluding repeat discipline-specific articles from the same institution, there were 3 articles in 2000 to 2002, 8 articles 2003 to 2004, and already 12 articles in 2006 to 2008 as of September 2008 on the reference list for this review. In addition, there are increasing numbers of presentations and abstracts at education and informatics meetings; for example, at the most recent International Association of Medical Science Educators meeting in July 2008, there were 5 virtual microscopy articles, a 6-hour faculty development course, and a focus session devoted to virtual microscopy for student teaching in histology and pathology ( Although initial implementation of virtual microscopy in pathology education was in medical student education, there is little doubt that virtual microscopy will have an increasing role in continuing education and house staff education. The technology for implementation in continuing education in histopathology is already quite good; however, it could be improved upon by better low-power screen resolution. Virtual focus (3-D, Z-axis viewing) will need to become more efficient before virtual microscopy becomes fully integrated into continuing education in cytology, hematology, microbiology, and urinalysis. The American Board of Pathology implementation, the diagnostic concordance with glass slides, the positive results of the competency study at Iowa, and the potential to develop novel ways to use the computer to teach microscopic skills suggest there is tremendous opportunity for the use of virtual slides for training and self-assessment for pathology house staff. Given the estimate that perhaps only 30% of medical schools still use glass slides sets to teach microscopic pathology, that only about 45% still have laboratories and large groups, and that virtual microscopy may already be incorporated in at least 33% of curricula, the incorporation into pathology medical school curricula may begin to level off unless virtual microscopy is incorporated in novel ways into small group teaching and/or independent learning exercises. Apart from local circumstances in a medical school, a decision to implement virtual microscopy will depend on the level of commitment that pathology chairs and their faculty have to the proposition that active learning of histopathology by panning and zooming whole (virtual) slides, and the associated ability to develop innovative computer-assisted educational programs, have an important role in the education of future physicians. References [1] Silage DA, Gil J. Digital image tiles: a method for the processing of large sections. J Microsc 1985;138: [2] Westerkamp D, Gahm T. Non-distorted assemblage of the digital images of adjacent fields in histological sections. Anal Cell Pathol 1993;5:

10 Virtual microscopy in pathology education [3] Weinstein RS, Descour MR, Liang C, et al. An array microscope for ultrarapid virtual slide processing and telepathology. Design, fabrication, and validation study. HUM PATHOL 2004;35: [4] Jao CS, Hier DB, Brint SU. The display of photographic-quality images on the Web: a comparison of two technologies. IEEE Trans Inf Technol Biomed 1999;3:70-3. [5] Taylor RN, Gagnon M, Lange J, Lee T, Draut R, Kujawski E. CytoView: a prototype image-based Papanicolaou smear proficiency test. Acta Cytol 1999;43: [6] Gagnon M, Inhorn S, Hancock J, et al. Comparison of cytology proficiency testing: glass slides vs. virtual slides. Acta Cytol 2004; 48: [7] Lee SH. Virtual microscopy: applications to hematology. Lab Hematol 2005;11: [8] Dee F, Donnelly A, Radio S, Leaven T, Kreiter C, Zaleski MS. Utility of 2-D and 3-D virtual microscopy in cervical cytology education and testing. Acta Cytol 2007;51: [9] Kalinski T, Zwonitzer R, Sel S, et al. Virtual 3-D microscopy using multiplane whole slide images in diagnostic pathology. Am J Clin Pathol 2008;130: [10] Rojo MG. Critical comparison of 31 commercially available digital slide systems in pathology. Int J Surg Pathol 2006;14: [11] Dick(Dee) FR. Web-based Virtual Microscope Laboratories. Pathol Educ ;25:58-62 [ v25n2.pdf]. [12] Kumar RK, Velan GM, Korell SO, Kandara M, Dee FR, Wakefield D. Virtual microscopy for learning and assessment in Pathology. J Pathol 2004;204: [13] Dee FR, Heidger P. Virtual slides for teaching histology and pathology. In: Gu J, Ogilvie RW, editors. Virtual Microscopy and Virtual Slides in Teaching, Diagnosis and Research, Taylor & Francis Group. Boca Raton: CRC Press; p [Chapter 9]. [14] Glatz-Krieger K, Spornitz U, Spatz A, Mihatsch MJ, Dieter Glatz D. Factors to keep in mind when introducing virtual microscopy. Virchows Arch 2006;448: [15] Kumar RK, Freeman B, Velan GM, De Permentier PJ. Integrating histology and histopathology teaching in practical classes using virtual slides. Anat Rec B New Anat 2006;289: [16] Kim MH, Park Y, Seo D, et al. Virtual microscopy as a practical alternative to conventional microscopy in pathology education. Basic Appl Pathol 2008;1:46-8. [17] Dee FR, Lehman JM, Consoer D, Leaven T, Cohen M. Implementation of virtual microscope slides in the annual Pathobiology of Cancer Workshop Laboratory. HUM PATHOL 2003;34: [18] Steinberg DM, Syed ZA. Application of virtual microscopy in clinical cytopathology. Diagn Cytopathol 2001;25: [19] Grant KL. Virtual microscopy as a tool for proficiency testing in cytopathology. Arch Pathol Lab Med 2003;127: [20] Marchevsky AM, Khurana R, Thomas P, Scharre K, Farias P, Bose S. The use of virtual microscopy for proficiency testing in gynecologic cytopathology: a feasibility study using ScanScope. Arch Pathol Lab Med 2006;130: [21] Stewart J, Bevans-Williams K, Bhattacharya A, Ye C, Miyazaki K, Kurtycz D. Virtual microscopy: an educator's tool for the enhancement of cytotechnology student's locator skills. Diagn Cytopathol 2008;36: [22] Bennett B. Certification from the American Board of Pathology: getting it and keeping it. HUM PATHOL 2006;37: [23] Romer D. Use of virtual microscopy for didactic live-audience presentation in anatomic pathology. Ann Diagn Pathol 2003;7: [24] Lundin M, Lundin J, Helin H, Isola J. A digital atlas of breast histopathology: an application of Web based virtual microscopy. J Clin Pathol 2004;57: [25] Helina H, Lundin M, Lundin J, et al. Web-based virtual microscopy in teaching and standardizing Gleason grading. HUM PATHOL 2005; 36: [26] Dee FR. Virtual microscopy for comparative pathology. Toxicol Pathol 2006;34: [27] Ward JM. So many Web sites, so little time! Toxicol Pathol 2006;34: [28] Dee F, Meyerholz D. Teaching pathology in the 21st century virtual microscopy applications. J Vet Med Educ 2007;34: [29] Simms MH, Mendis-Handagama C, Moore RN. Virtual microscopy in a veterinary curriculum. J Vet Med Educ 2007;34: [30] Harris T, Leaven T, Heidger P, Kreiter C, Duncan J, Dick(Dee) FR. Comparison of a virtual microscope versus a regular microscope laboratory for teaching histology. Anat Rec (New Anat) 2001;265: [31] Heidger P, Dee FR, Consoer D, Leaven T, Kreiter C. An integrated approach to teaching and testing in histology with real and virtual imaging. Anat Rec (New Anat) 2002;269: [32] Blake CA, Lavoie HA, Millette CF. Teaching medical histology at the University of South Carolina School of Medicine: transition to virtual slides and virtual microscopes. Anat Rec (New Anat) 2003; 275: [33] Krippendorf BB, Lough J. Complete and rapid switch from light microscopy to virtual microscopy for teaching medical histology. Anat Rec (New Anat) 2005;285: [34] Bloodgood RA, Ogilvie RW. Trends in histology laboratory teaching in United States medical schools. Anat Rec (New Anat) 2006;289B: [35] Goldberg HR, Dintzis R. The positive impact of team based virtual microscopy on student learning in physiology and histology. Adv Physiol Educ 2007;31: [36] Scoville SA, Buskirk TD. Traditional and virtual microscopy compared experimentally in a classroom setting. Clin Anat 2007;20: [37] Taylor CR, DeYoung BR, Cohen MB. Pathology education: quo vadis? HUM PATHOL 2008;39: [38] Kumar K, Daniel J, Doig K, Agamanolis D. Teaching pathology in United States medical schools, 1996/1997 survey. HUM PATHOL 1998;29: [39] Kumar K, Indurkhya A, Nguyen H. Curricular trends in instruction of pathology: a nationwide longitudinal study from 1993 to present. HUM PATHOL 2001;32: [40] Marshall R, Cartwright N, Mattick K. Teaching and learning in pathology: a critical review of the English literature. Med Educ 2004;38: [41] Burton J. Teaching pathology to medical undergraduates. Curr Diagn Pathol 2005;11: [42] Roullet M, Feldman M, Shea J, Phillips (Cambor) CC. The use of virtual slides in North American Medical Schools. Presented at the Slice of Life Meeting in Portland; [43] Dick(Dee) F, Leaven T, Dillman D, Torner R, Finken L. Core morphologic concepts of disease for second-year medical students. HUM PATHOL 1998;29: [44] Krupinsky EA, Tillack AA, Richter L, et al. Eye-movement study and human performance using telepathology virtual slides. Implications for medical education and differences with experience. HUM PATHOL 2006;37: