Annals of Anatomy 192 (2010) 378382

Contents lists available at ScienceDirect

Annals of Anatomy

journa l homepage: www.e lsev ie

Virtual microscopyThe future of teaching histol

Friedricha Department o strab Department o -9105

a r t i c l

Keywords:Virtual histoloVirtual educatTelemedicine

micsing ntalizad thenariotructcroscld bee shifIn a tnicale ascept

2010 Elsevier GmbH. All rights reserved.

1. Background and history

A soundis of fundaming and coninstructionscopes (Fig.Beyond thissuitable claand of cour

In Heide(and patholstudent wo13 of 19 un(Tuchman,were introdcourse specratuses wemercury-silthe end of

CorresponUniversity ErlTel.: +49 9131

E-mail add(F.P. Paulsen).

tion, closed slide projection boxes coupled with cassette recorders

0940-9602/$ doi:10.1016/j.knowledge ofmicroscopic anatomy andhistopathologyental and indispensable importance in medical train-

tinuing education. Since the middle of the 19th century,in these subjects has taken place using light micro-1a andb) andhistological/histopathological specimens., such instruction is dependent upon the availability ofssroomspace (microscopy lab)with rigid openinghoursse an instructor.lberg, in 1846, Jacob Henle became the rst anatomistogist) to introduce a microscopy course in which everyrked at an individual microscope. After only 4 years,iversities in Germany offered such microscopy courses1993). At the beginning of the 20th century, projectorsuced to themarketwith theaidofwhich themicroscopyimens could be projected onto a screen. Such appa-

re in use for a long time, later run with high voltagever lamps and remained in use in some places up tothe 20th century. As a supplement to regular instruc-

ding author at: Department of Anatomy II, Friedrich-Alexander-angen-Nrnberg, Universittsstr. 19, D-91054 Erlangen, Germany.852 2865; fax: +49 9131 852 2862.ress: friedrich.paulsen@anatomie2.med.uni-erlangen.de

were sometimes made available to students for self study in someinstitutes in the 70ies and 80ies of the last century. Certainly, theseand other such techniques, due to their technical limitations, couldonly be used as educational supplements and could not replaceconventional microscopy. Early technology for obtaining multiplemacroscopic elds of view (called digital tiles) with a precisionmotorized microscope stage and the creation of a digital montage(now known as a virtual slide) was initially described by Silageand Gil (1985) as well as Westerkamp and Gahm (1993). In thelate 1990s, desktop computers had enough computational powerto acquire a digital facsimile of the majority of the information on aglass slide, so that virtual slide acquisition technology using digitaltiles was improved upon and commercialized. The breakthroughcame with another technologic advance several years later whennovel methods of acquisition that did not rely on creating digitaltiles with a traditional microscope were developed and commer-cialized (Weinsteinet al., 2004).Atnearly the sametime, companiesintroduced amulti-resolutionpyramidal le format called FlashPix,and others developed a FlashPix image le converter and serverto stream virtual slides over the Web to a pan and zoom viewer(Jao et al., 1999, for review see Dee, 2009). In 2001, the possibilityto integrate virtual slides with an annotator applet in a databasestructure was developed. This educational model provided edu-cators with the opportunity to label virtual slides with arrows,circles, and text labels using overlays (annotations) and as nicelydescribed by Dee (2009) integration with a database structure

see front matter 2010 Elsevier GmbH. All rights reserved.aanat.2010.09.008P. Paulsena,b,, Michael Eichhornb, Lars Bruera

f Anatomy and Cell Biology, Martin-Luther-University of Halle-Wittenberg, Groe Steinf Anatomy II, Friedrich-Alexander-University Erlangen-Nrnberg, Universittsstr. 19, D

e i n f o

gyion

s u m m a r y

Conventional continuing education inology has hitherto been carried out ulaboratory. In comparison, after digispecimens via virtual microscopy anto put innumerable new learning sceof virtual microscopy in histology insbe introduced into the teaching of mimicroscopic teaching specimens wouIn a second step, instruction would badvantages offered by the technique.other anatomical, radiological and clistudents of human and dental medicintages and disadvantages of such a conin the following.r .de /aanat

ogy in the medical curriculum?

e 52, D-06097 Halle, Saale, Germany4 Erlangen, Germany

roscopic anatomy, histopathology, hematology and microbi-umerous sets of sectioned tissue specimens in a microscopytion of the sections it would be possible to access teachinginternet at any time and place. This would make it possibles into practice. The present article elucidates the advantagesion and presents a concept of how virtual microscopy couldopic anatomy in several steps. Initially, the presently existingdigitalized and made available on-line without restriction.

ted to an emphasis on virtual microscopy, utilizing all of thehird step, the microscopic contents could be networked withcontent on-line, thus opening new learning perspectives forwell as those of medically related courses of study. The advan-as well as some possibly arising consequences are discussed

F.P. Paulsen et al. / Annals of Anatomy 192 (2010) 378382 379

Fig. 1. (a) Mic ute ofWittenberg, G Leica,Erlangen-Nure

also allowethe virtuallinks to supthese featu(2010) alsovirtual miclent to convthe purposeing conven2008).

2. Virtual m

Virtual malternativescope. Withas, e.g. the Ztem madedigitalizedtakes placecan later b

idescopeeciale lag

g it pox) aappslide

(so-chowncatimicroe siz

(zoomd simovin

catin inroscope made by Ernst Leitz in Wetzlar, ca. 1910, Original equipment of the Institermany, then known as the Botanical Institute of Halle. (b) Microscope made bymberg, Germany.

d educators to easily link descriptive text specic toslide in a separate browser window, as well as createplemental images and normal virtual slides. Most ofres have been illustrated in the article by Merk et al.found in this issue. These developments have allowedroscopy to advance to the level of a method equiva-entional microscopy, having the potential, at least fors of instruction, to replace all other methods, includ-tional microscopy (Heidger et al., 2002a; Sinn et al.,

icroscopy

icroscopy is a digital procedure providing a realisticto the examination of glass slides using a light micro-a special scanner (there are a series of suppliers, sucheiss Mirax-Midi System (Fig. 2) and the ScanScop Sys-

tual slmicrosuse spout timmakinimen bsectionon theguidetially smagnitionalthis, thboardkey anas if mmagnipositioby Aperio the histological sections are automatically

and led as virtual sections in a picture archive. Thisat such high resolution that all relevant magnicationse demonstrated on the monitor. For this reason, vir-

Fig. 2. Mirax-Midi Scanner made by Zeiss, 2009.

respectiveUsing themsupplemenfacilitate unadditional a

The vantaken by thof experien2007; Granal., 2004, 20Dee, 2006, 2Ward, 2006et al., 2007;Stewart etpresent issua histopathcept basedof its acceptinstitutesweven somesity of BasepresentatioAnatomy and Cell Biology of the Martin Luther University in Halle-ca. 2000, Institute of Anatomy II, Friedrich Alexander University of

are large les and special programs, known as virtuals, are necessary for their visualization. These programsstreaming technologies allowing demonstration with-. The digitalized sections are transferred with softwareossible to click on the respective section (virtual spec-nd thus activate the specic les. After activation, theears in a small window inset showing its appearancewithout magnication thus providing an orientation

alled navigator eld), while at the same time it is ini-as an overviewon the remainder of the screen. Various

ons corresponding to the objective sizes of a conven-scope can now be clicked on using a menu bar. Beyonde can be gradually changed via mousewheel or key-ing). At any given size, one can, by pressing the mouse

ultaneously pulling the mouse, move the entire sectiong a slide under a conventional microscope. At higherons, a crosshair aids in identifying the currently viewedthe section. Via a further button, information on thesection can be accessed (e.g. stain, gure legend, etc.).enu commands, it is possible to click on a list of relevanttary information (e.g. related specimens which couldderstanding, clinically associated illustrativematerials,ntibody markings, electron microscopic pictures, etc.).

guard role in the use of this new technology has beene pathologists, who have already gathered a great dealce using it (Steinberg and Syed, 2001; Dee et al., 2003,t, 2003; Romer, 2003; Gagnon et al., 2004; Kumar et06; Lundin et al., 2004; Helina et al., 2005; Lee, 2005;009;Glatz-Krieger et al., 2006;Marchevsky et al., 2006;; Glatz et al., 2007; Dee and Meyerholz, 2007; SimmsKalinski et al., 2008; Kim et al., 2008; Sinn et al., 2008;

al., 2008, Taylor et al., 2008; Lpez et al., 2009). In thee, Merk et al. (2010) present a report on experiences inology course at the RWTH Aachen using a didactic con-on Web-based virtual microscopy as well as an analysisance by students. There are, however, other anatomicalhich have used virtualmicroscopy over a longer period,in Germany (e.g. The University of Iowa, USA; Univer-l, Switzerland; University of the Saarland). The virtualns of these universities can be accessedwithout cost via

380 F.P. Paulsen et al. / Annals of Anatomy 192 (2010) 378382

the following internet links:Iowa University: http://www.path.uiowa.edu/virtualslidebox/Universitt Basel: http://vmic.unibas.ch/patho/topo/index.htmlUniversitt Saarland: http://wwwalt.med-rz.uniklinik-saarland.de/

med fak/anatomie/bock/vmic.htmAt some

sity of Kielas well as salready beevia passwomicroscopyversity. Thein commonthe form ofbeen implemmicroscopic

The goavirtual micanatomy assible supplewas only pcalled freeofcial cour

3. Concept

At mosttal medicalmicroscopyKiel) or moplaces for40offered in pmicroscopythe specime

The inteing histologlight microcian or medof how to utinue to besmall groupremainingmicroscopeuse of virtumatch the npresent micmicroscopycourse woumore frequaminimallyFuture coursites. Outsithe opportuAssuming ato view theout of the oand from an

4. Innovattransferabifrom such

4.1. Advant

Conventhistopatholcarried out

microscopy laboratory. In contrast, after digitalization of the seriesof sections it is possible at any time and from any place via virtualmicroscopy and the internet to access the teaching specimens. Thisopens the door for many new learning scenarios.

eachtatioformtion focan

ecimded,ecimfeatteracopyrosctomstemmpln) osfullyl-paticrosondestiond Pcomibe coars. Tor thumms:

nlimal mss tos) anrenced. Ine stughert of er orius leirtuastudlightview

renticulalledmeingsdireinistroscosysteadiogoscoger isysteork

se tuimenother universities (e.g. the Christian Albrecht Univer-, Germany), the sections used for teaching histologyupplementary electron microscopic preparations haven digitalized. However, these les are only accessiblerd and can be used exclusively by participants of thecourse or by faculty members of the respective uni-

se presentations, whether freely accessible or not, havethat the use of virtual microscopy is provided only insupplementary educational material and has not yetented as an independent training concept for teachinganatomy.

l of this article is to present a concept through whichroscopy may be fully integrated into the teaching ofwell as beingmade available to the user as freely acces-mentary educational material. Up to the present, thisossible within the framework of the very limited so-microscopy hours in the microscopy lab outside of these periods.

for the conversion to virtual microscopy

German universities the number of human and den-students is much greater than the number of availableplaces. For this reason, two (as e.g. in Erlangen, Halle,

re (as e.g. in Tbingen, where there are 100 microscopy0students) coursesofmicroscopic anatomyareusually

arallel. This makes the coordination of a period for free, during which students have the opportunity to studyns outside of regular course hours, a true challenge.

gration of virtual microscopy into the concept of teach-y cannot completely neglect the use of conventionalscopy as, in the future, the profession of the physi-ical scientist will continue to require the knowledgese a microscope. For this reason, students should con-instructed in the use of good binocular microscopes ins as is usual practice today at most universities. The

course time would be spent working with the virtual. The microscopy lab spaces must be equipped for theal microscopy. Ideally the number of workplaces shouldumber of students to be trained. At the very least, everyroscopy workplace should also be equipped for virtual. In the latter case, this would admittedly mean that theld still have to be offered two or three times or evenently in parallel. A given workplace would require onlyequipped computer terminalwithmonitor andmouse.sesofmicroscopic anatomycouldbeheldat thesework-de of regular course hours, the students would havenity to study all preparations using virtual microscopy.n internet access, students would have the opportunityvirtual specimens independently of place or time, e.g.pening hours of the institute, during vacation periodsy place, even from mobile phones.

ive content, demonstration of sustainability andlity as well as additional benets to be expecteda concept

ages

ional continuing education in microscopic anatomy,ogy, hematology and microbiology has hitherto beenusing numerous sets of sectioned tissue specimens in a

A tpresenactiveconvenof 100coursethe spare adthe spuniquesuch inmicrosof maccal anathe syfor exaDresdesuccesclinicatual mcorrespfor Qutions uare beare tofew yebasis f

In svation

An uvirtu

Accehour

Refeposeto th

At hipoinbette

Variople, vcasehigh

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Thenetw

Courspecing concept using virtual microscopy allows for then of cytological and microscopic specimens in an inter-. The observer can examine the specimen as with aal microscope in sharp focus up to a magnicationr binocular observation. As the staff mentoring of anever be as comprehensive as direct references in

en itself, markings and texts (so called annotations)making it possible for the students to actively studyens presented via virtual microscopy. This is a centralure of virtual microscopy. It is not possible to realisective markings using conventional microscopy. Virtualallows for the supplementary presentation of pictures

opic preparations as well as clinical examples (clini-y) including illustrative and lm material. In particular,can be integrated into various media data banks as,

e, in the AVMZ (Audiovisual Media Center of the TUf interest. This problem-oriented learning (POL) canbe channeled via histology as is already routine in

hological conferences in pathology. Beyond this, vir-copy allows for forward looking interactive traininging to the guidelines of the German IMPP (Institutens related to Medical and Pharmaceutical Examina-harmazeutische Prfungsfragen). The IMPP questionsng increasingly case oriented (POL) and examinationsmpleted entirely at computer working places within ahe presented concept would also form the prerequisiteis mode of examination.ary, theuse of virtual sections offers the following inno-

ited number of users can examine specimens with aicroscope at the same time.virtual microscopy independent from time (opening

d place (institute).s and explanations (annotations) could be superim-this manner, the specimen offers immediate feedbackdent.magnications, a haircross can identify the momentaryxamination on the overview of the section providingentation.arning and testing modes become possible. For exam-l preparations could be inserted into problem orientedies. The correspondingly inserted annotations wouldthe crucial characteristics of the specimen.er gains a true impression of the histological prepara-

stains can be shownparallel to or overlying one anotherrly advantageous in immunohistochemical markings,merging).diate accessing of archived cases is possible.identifying relevant regions can be added by the stu-

ctly at the workplace or by teaching personnel from anative workplace.py paths can be replayed.m can be expanded at will and combined with digi-raphy, anatomical macroscopic illustrations, electronpic or immunohistological illustrations to allow for antegration within the subject.m can be used in a seminar room equipped with ored by interactive tables (e.g. SMART Boards).tors can simultaneously view the current portion of theon the monitor with the students. Questions can thus

F.P. Paulsen et al. / Annals of Anatomy 192 (2010) 378382 381

be answered much more easily. The intensication of interactionwith and communication between students and teachers on thespecimen is thereby facilitated.

The generation of numerous preparations for the sameorgan (e.g.40 differedomly preslide on tchip on thThe preci

Using adeor visuali

5. Prerequ

5.1. Problem

The greathe nancintual microspathologistand, basedof availablethe nancianot irrelevato the commat a given ufor the studcomputer f(dependingaddition, soable on theSuch softwafor the digitsary to consof time (at linternet pla

6. Approac

A reductwho alreadbe possiblecomputer sframeworkware at lowresponsibleposition). Tcies exist, bthe situatioa biologicalor a physicisolve the prscopes haveconsidered,microscopy

7. Subsequ

Yearly ththe server onames and fmust regulwould be wtionship torunning co

years one must expect a complete replacement of the computersystem. Surely, the universitieswith apool of tuition feeswhich canbe invested in such educational projects would be at an advantagehere as with the costs of original equipment.

lity

meansed i

atioysisted oysese stunal srackparte retis o

ysis oin thctioneful

rdis

projf path. Theeadyter woulded fots oftraints offurthalso-linebe pamintem.

rspe

ny hin thes ofcientd mapeemastiecopeife sc) (Cthatl curinaryrricuurne2002oodskirnt histological sections of the liver), which can be ran-sented to the student, precludes the recognition of the

he basis of extraneous details (the specimen with thee right corner is the liver or the triangular specimen).sion in specimen diagnosis is thus increased.quate softwarewill allow3 dimensional reconstructionzation of the specimens.

isites for the implementation of the concept

s

test difculty in implementing such a concept is by farg. This is surely also the reason for the fact that vir-copy is already being much more intensively used bys, who usually have to do with smaller student cohortson their clinical activity, often have a higher volumenances for the realisation of such a concept. Indeed,l outlay necessary for the original equipment phase isnt and quickly exceeds the total yearly budget availableittee for studies and teaching or for teaching projects

niversity. In addition to the computer working placesents (approx. 500 Euro per workside) and a masteror the teacher, a specimen scanner must be acquiredupon requirements 50,00080,000Euro by itself). Inftware is necessary to make the digitalized data avail-computer and in internet in a user friendly manner.re is commercially available. Finally, staff is necessaryalization of the specimens. At least one person is neces-istently support the entire project over a lengthy periodeast 3 years). Ideally, this person should also create thetform.

hes to solutions of the problems

ion in costs can surely be achieved by asking colleaguesy have a specimen scanner to lend it to you. It may alsoto borrow the software from this person or from thecience faculty or from another institution within theof a cooperative project to acquire or prepare such soft-cost or without cost. Normally, at least one person isfor standard histology section preparation (1/21 MTAhis person could, assuming basic computer competen-e further trained to take over these tasks. Otherwise,n may lend itself for a doctoral dissertation position forcomputer specialist or a medical information specialistan with training in the eld of medical information tooblems at a reasonable cost. If the conventional micro-become old and their replacement has already been

itwouldbe a very goodopportunity to change to virtual.

ent costs and ways of dealing with them

ere will be subsequent costs for the storage space onf the computer center, additional costs for the domainor software updates. Beyond this, aminimumof repairsarly be reckoned with for the computer worksites. Itorth a thought e.g. to allow advertising having a rela-histology to appear on the homepage and to cover

sts out of the advertising income. After about 1015

8. Qua

Byaddres

Evalu Anal

quen Anal

by thcatio

By Tbeencan bwhat

Analused

Collebe us

9. Inte

Theeld otologyhas alrcompucept wpreparstudenalso bestudenManywoulding onshouldline exthe sys

10. Pe

Mabemoathe losused schange(newspscope rwell jumicrosteach lbiologyshownmedicaprelimthe cuhave tet al.,Bloodgand Buassurance

s of systematic studies, scientic questions could ben relation to the concept:

n between conventional and virtual microscopy.of how often, how long and when the system is fre-utside of the course periods.as to which specimens are particularly intensively useddents. Thiswould allow for an improvement of the edu-tructure with better generation of didactic emphases.ing (log-les) the portions of the pictures which haveicularly intensively viewed by the students specimensraced in the respective. Thus, it is possible to determinef particular relevance to the student.f the extent to which histological specimens are beinge framework of case presentations.of evidence as to whether virtual microscopy may also

for other medical disciplines.

ciplinary character

ect approach would not only be of great interest to theology but also for radiology, microbiology and derma-extension to other subjects is conceivable. The IMPPannounced intentions to perform examinations on theithin the near future. The implementation of this con-already assure that the respective institution is alreadyr this innovation. Beyond medical and dental students,molecular medicine as well as related subjects coulded on and access corresponding EKU-data banks. Even

other universities could access the system fromoutside.er extensions are imaginable. A large computer poolbe advantageous, as it is a prerequisite for administer-examinations in many disciplines beyond histology. Itointed to one charming feature of computer based on-ations, i.e. corrections are performed automatically by

ctive and future prospects

stologists and pathologists remain very skeptical anddemise of traditional laboratory teaching methods andmicroscopy skills. The microscope is the most widelyic instrument and in its most basic form has notuch over the last century. In popular science imageryrs, magazines, television drama, movies), the micro-ins the main symbol of the scientist and this is probablyd. It is hard to imagine a science laboratory withouts. Themicroscopehasbeen themain instrumentused toiences (biology, cytology, histology, pathology, micro-oleman, 2009). Preliminary evaluations have alreadythe virtual microscope is increasingly being used inricula (Drake et al., 2009). In some foreign institutions,reports of evaluations after a partial conversion of

lum to virtual microscopy have become available andd out to be very positive (Harris et al., 2001; Heidgerb,c; Blake et al., 2003; Krippendorf and Lough, 2005;and Ogilvie, 2006; Goldberg and Dintzis, 2007; Scovillek, 2007; Weaker and Herbert, 2009; Husmann et al.,

382 F.P. Paulsen et al. / Annals of Anatomy 192 (2010) 378382

2009). Once any given institute has performed its complete courseof histology using virtual microscopy for the rst time, it willbecome apparent whether other universities will follow suit. InGermany, concrete plans for the implementation of such a conceptare in progwhich alreatutes plannsupplementhat medicogy textbooparty fundsthose alreadwill furtherat universitment will aconversion

The knoand furthernology coumicroscopyings of thea given timat his compsider the Iphold the lesspecimen uMeanwhilecorner of thwould be trvia his coma large nummicroscopynecessary wis a moot pting lecturewhich the lsized studethat virtualthe anatommore serioupoorer paymhighly qual

Acknowled

We than

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Virtual microscopy-The future of teaching histology in the medical curriculum?Background and historyVirtual microscopyConcept for the conversion to virtual microscopyInnovative content, demonstration of sustainability and transferability as well as additional benefits to be expected from such a conceptAdvantages

Prerequisites for the implementation of the conceptProblems

Approaches to solutions of the problemsSubsequent costs and ways of dealing with themQuality assuranceInterdisciplinary characterPerspective and future prospectsAcknowledgmentReferences