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Annals of Anatomy 192 (2010) 378382

Contents lists available at ScienceDirect

Annals of Anatomy
journal homepage: www.elsevier.de/aanat

Virtual microscopyThe future of teaching histology in the medical curriculum?


Friedrich P. Paulsen a,b, , Michael Eichhorn b , Lars Bruer a
a
b

Department of Anatomy and Cell Biology, Martin-Luther-University of Halle-Wittenberg, Groe Steinstrae 52, D-06097 Halle, Saale, Germany
Department of Anatomy II, Friedrich-Alexander-University Erlangen-Nrnberg, Universittsstr. 19, D-91054 Erlangen, Germany

a r t i c l e

i n f o

Keywords:
Virtual histology
Virtual education
Telemedicine

s u m m a r y
Conventional continuing education in microscopic anatomy, histopathology, hematology and microbiology has hitherto been carried out using numerous sets of sectioned tissue specimens in a microscopy
laboratory. In comparison, after digitalization of the sections it would be possible to access teaching
specimens via virtual microscopy and the internet at any time and place. This would make it possible
to put innumerable new learning scenarios into practice. The present article elucidates the advantages
of virtual microscopy in histology instruction and presents a concept of how virtual microscopy could
be introduced into the teaching of microscopic anatomy in several steps. Initially, the presently existing
microscopic teaching specimens would be digitalized and made available on-line without restriction.
In a second step, instruction would be shifted to an emphasis on virtual microscopy, utilizing all of the
advantages offered by the technique. In a third step, the microscopic contents could be networked with
other anatomical, radiological and clinical content on-line, thus opening new learning perspectives for
students of human and dental medicine as well as those of medically related courses of study. The advantages and disadvantages of such a concept as well as some possibly arising consequences are discussed
in the following.
2010 Elsevier GmbH. All rights reserved.

1. Background and history


A sound knowledge of microscopic anatomy and histopathology
is of fundamental and indispensable importance in medical training and continuing education. Since the middle of the 19th century,
instruction in these subjects has taken place using light microscopes (Fig. 1a and b) and histological/histopathological specimens.
Beyond this, such instruction is dependent upon the availability of
suitable classroom space (microscopy lab) with rigid opening hours
and of course an instructor.
In Heidelberg, in 1846, Jacob Henle became the rst anatomist
(and pathologist) to introduce a microscopy course in which every
student worked at an individual microscope. After only 4 years,
13 of 19 universities in Germany offered such microscopy courses
(Tuchman, 1993). At the beginning of the 20th century, projectors
were introduced to the market with the aid of which the microscopy
course specimens could be projected onto a screen. Such apparatuses were in use for a long time, later run with high voltage
mercury-silver lamps and remained in use in some places up to
the end of the 20th century. As a supplement to regular instruc-

Corresponding author at: Department of Anatomy II, Friedrich-AlexanderUniversity Erlangen-Nrnberg, Universittsstr. 19, D-91054 Erlangen, Germany.
Tel.: +49 9131 852 2865; fax: +49 9131 852 2862.
E-mail address: friedrich.paulsen@anatomie2.med.uni-erlangen.de
(F.P. Paulsen).
0940-9602/$ see front matter 2010 Elsevier GmbH. All rights reserved.
doi:10.1016/j.aanat.2010.09.008

tion, closed slide projection boxes coupled with cassette recorders


were sometimes made available to students for self study in some
institutes in the 70ies and 80ies of the last century. Certainly, these
and other such techniques, due to their technical limitations, could
only be used as educational supplements and could not replace
conventional microscopy. Early technology for obtaining multiple
macroscopic elds of view (called digital tiles) with a precision
motorized microscope stage and the creation of a digital montage
(now known as a virtual slide) was initially described by Silage
and Gil (1985) as well as Westerkamp and Gahm (1993). In the
late 1990s, desktop computers had enough computational power
to acquire a digital facsimile of the majority of the information on a
glass slide, so that virtual slide acquisition technology using digital
tiles was improved upon and commercialized. The breakthrough
came with another technologic advance several years later when
novel methods of acquisition that did not rely on creating digital
tiles with a traditional microscope were developed and commercialized (Weinstein et al., 2004). At nearly the same time, companies
introduced a multi-resolution pyramidal le format called FlashPix,
and others developed a FlashPix image le converter and server
to stream virtual slides over the Web to a pan and zoom viewer
(Jao et al., 1999, for review see Dee, 2009). In 2001, the possibility
to integrate virtual slides with an annotator applet in a database
structure was developed. This educational model provided educators with the opportunity to label virtual slides with arrows,
circles, and text labels using overlays (annotations) and as nicely
described by Dee (2009) integration with a database structure

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

379

Fig. 1. (a) Microscope made by Ernst Leitz in Wetzlar, ca. 1910, Original equipment of the Institute of Anatomy and Cell Biology of the Martin Luther University in HalleWittenberg, Germany, then known as the Botanical Institute of Halle. (b) Microscope made by Leica, ca. 2000, Institute of Anatomy II, Friedrich Alexander University of
Erlangen-Nuremberg, Germany.

also allowed educators to easily link descriptive text specic to


the virtual slide in a separate browser window, as well as create
links to supplemental images and normal virtual slides. Most of
these features have been illustrated in the article by Merk et al.
(2010) also found in this issue. These developments have allowed
virtual microscopy to advance to the level of a method equivalent to conventional microscopy, having the potential, at least for
the purposes of instruction, to replace all other methods, including conventional microscopy (Heidger et al., 2002a; Sinn et al.,
2008).
2. Virtual microscopy
Virtual microscopy is a digital procedure providing a realistic
alternative to the examination of glass slides using a light microscope. With a special scanner (there are a series of suppliers, such
as, e.g. the Zeiss Mirax-Midi System (Fig. 2) and the ScanScop System made by Aperio the histological sections are automatically
digitalized and led as virtual sections in a picture archive. This
takes place at such high resolution that all relevant magnications
can later be demonstrated on the monitor. For this reason, vir-

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

tual slides are large les and special programs, known as virtual
microscopes, are necessary for their visualization. These programs
use special streaming technologies allowing demonstration without time lag. The digitalized sections are transferred with software
making it possible to click on the respective section (virtual specimen box) and thus activate the specic les. After activation, the
section appears in a small window inset showing its appearance
on the slide without magnication thus providing an orientation
guide (so-called navigator eld), while at the same time it is initially shown as an overview on the remainder of the screen. Various
magnications corresponding to the objective sizes of a conventional microscope can now be clicked on using a menu bar. Beyond
this, the size can be gradually changed via mousewheel or keyboard (zooming). At any given size, one can, by pressing the mouse
key and simultaneously pulling the mouse, move the entire section
as if moving a slide under a conventional microscope. At higher
magnications, a crosshair aids in identifying the currently viewed
position in the section. Via a further button, information on the
respective section can be accessed (e.g. stain, gure legend, etc.).
Using the menu commands, it is possible to click on a list of relevant
supplementary information (e.g. related specimens which could
facilitate understanding, clinically associated illustrative materials,
additional antibody markings, electron microscopic pictures, etc.).
The vanguard role in the use of this new technology has been
taken by the pathologists, who have already gathered a great deal
of experience using it (Steinberg and Syed, 2001; Dee et al., 2003,
2007; Grant, 2003; Romer, 2003; Gagnon et al., 2004; Kumar et
al., 2004, 2006; Lundin et al., 2004; Helina et al., 2005; Lee, 2005;
Dee, 2006, 2009; Glatz-Krieger et al., 2006; Marchevsky et al., 2006;
Ward, 2006; Glatz et al., 2007; Dee and Meyerholz, 2007; Simms
et al., 2007; Kalinski et al., 2008; Kim et al., 2008; Sinn et al., 2008;
Stewart et al., 2008, Taylor et al., 2008; Lpez et al., 2009). In the
present issue, Merk et al. (2010) present a report on experiences in
a histopathology course at the RWTH Aachen using a didactic concept based on Web-based virtual microscopy as well as an analysis
of its acceptance by students. There are, however, other anatomical
institutes which have used virtual microscopy over a longer period,
even some in Germany (e.g. The University of Iowa, USA; University of Basel, Switzerland; University of the Saarland). The virtual
presentations of these universities can be accessed without cost via

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

the following internet links:


Iowa University:
Universitt Basel:
Universitt Saarland:

http://www.path.uiowa.edu/virtualslidebox/
http://vmic.unibas.ch/patho/topo/index.html
http://wwwalt.med-rz.uniklinik-saarland.de/
med fak/anatomie/bock/vmic.htm

At some other universities (e.g. the Christian Albrecht University of Kiel, Germany), the sections used for teaching histology
as well as supplementary electron microscopic preparations have
already been digitalized. However, these les are only accessible
via password and can be used exclusively by participants of the
microscopy course or by faculty members of the respective university. These presentations, whether freely accessible or not, have
in common that the use of virtual microscopy is provided only in
the form of supplementary educational material and has not yet
been implemented as an independent training concept for teaching
microscopic anatomy.
The goal of this article is to present a concept through which
virtual microscopy may be fully integrated into the teaching of
anatomy as well as being made available to the user as freely accessible supplementary educational material. Up to the present, this
was only possible within the framework of the very limited socalled free microscopy hours in the microscopy lab outside of the
ofcial course periods.
3. Concept for the conversion to virtual microscopy
At most German universities the number of human and dental medical students is much greater than the number of available
microscopy places. For this reason, two (as e.g. in Erlangen, Halle,
Kiel) or more (as e.g. in Tbingen, where there are 100 microscopy
places for 400 students) courses of microscopic anatomy are usually
offered in parallel. This makes the coordination of a period for free
microscopy, during which students have the opportunity to study
the specimens outside of regular course hours, a true challenge.
The integration of virtual microscopy into the concept of teaching histology cannot completely neglect the use of conventional
light microscopy as, in the future, the profession of the physician or medical scientist will continue to require the knowledge
of how to use a microscope. For this reason, students should continue to be instructed in the use of good binocular microscopes in
small groups as is usual practice today at most universities. The
remaining course time would be spent working with the virtual
microscope. The microscopy lab spaces must be equipped for the
use of virtual microscopy. Ideally the number of workplaces should
match the number of students to be trained. At the very least, every
present microscopy workplace should also be equipped for virtual
microscopy. In the latter case, this would admittedly mean that the
course would still have to be offered two or three times or even
more frequently in parallel. A given workplace would require only
a minimally equipped computer terminal with monitor and mouse.
Future courses of microscopic anatomy could be held at these worksites. Outside of regular course hours, the students would have
the opportunity to study all preparations using virtual microscopy.
Assuming an internet access, students would have the opportunity
to view the virtual specimens independently of place or time, e.g.
out of the opening hours of the institute, during vacation periods
and from any place, even from mobile phones.
4. Innovative content, demonstration of sustainability and
transferability as well as additional benets to be expected
from such a concept
4.1. Advantages
Conventional continuing education in microscopic anatomy,
histopathology, hematology and microbiology has hitherto been
carried out using numerous sets of sectioned tissue specimens in a

microscopy laboratory. In contrast, after digitalization of the series


of sections it is possible at any time and from any place via virtual
microscopy and the internet to access the teaching specimens. This
opens the door for many new learning scenarios.
A teaching concept using virtual microscopy allows for the
presentation of cytological and microscopic specimens in an interactive form. The observer can examine the specimen as with a
conventional microscope in sharp focus up to a magnication
of 100 for binocular observation. As the staff mentoring of a
course can never be as comprehensive as direct references in
the specimen itself, markings and texts (so called annotations)
are added, making it possible for the students to actively study
the specimens presented via virtual microscopy. This is a central
unique feature of virtual microscopy. It is not possible to realise
such interactive markings using conventional microscopy. Virtual
microscopy allows for the supplementary presentation of pictures
of macroscopic preparations as well as clinical examples (clinical anatomy) including illustrative and lm material. In particular,
the system can be integrated into various media data banks as,
for example, in the AVMZ (Audiovisual Media Center of the TU
Dresden) of interest. This problem-oriented learning (POL) can
successfully be channeled via histology as is already routine in
clinical-pathological conferences in pathology. Beyond this, virtual microscopy allows for forward looking interactive training
corresponding to the guidelines of the German IMPP (Institute
for Questions related to Medical and Pharmaceutical Examinations und Pharmazeutische Prfungsfragen). The IMPP questions
are becoming increasingly case oriented (POL) and examinations
are to be completed entirely at computer working places within a
few years. The presented concept would also form the prerequisite
basis for this mode of examination.
In summary, the use of virtual sections offers the following innovations:
An unlimited number of users can examine specimens with a
virtual microscope at the same time.
Access to virtual microscopy independent from time (opening
hours) and place (institute).
References and explanations (annotations) could be superimposed. In this manner, the specimen offers immediate feedback
to the student.
At higher magnications, a haircross can identify the momentary
point of examination on the overview of the section providing
better orientation.
Various learning and testing modes become possible. For example, virtual preparations could be inserted into problem oriented
case studies. The correspondingly inserted annotations would
highlight the crucial characteristics of the specimen.
The viewer gains a true impression of the histological preparation.
Different stains can be shown parallel to or overlying one another
(particularly advantageous in immunohistochemical markings,
so-called merging).
An immediate accessing of archived cases is possible.
Markings identifying relevant regions can be added by the student directly at the workplace or by teaching personnel from an
administrative workplace.
Microscopy paths can be replayed.
The system can be expanded at will and combined with digital radiography, anatomical macroscopic illustrations, electron
microscopic or immunohistological illustrations to allow for a
stronger integration within the subject.
The system can be used in a seminar room equipped with or
networked by interactive tables (e.g. SMART Boards).
Course tutors can simultaneously view the current portion of the
specimen on the monitor with the students. Questions can thus

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

be answered much more easily. The intensication of interaction


with and communication between students and teachers on the
specimen is thereby facilitated.
The generation of numerous preparations for the same organ (e.g.
40 different histological sections of the liver), which can be randomly presented to the student, precludes the recognition of the
slide on the basis of extraneous details (the specimen with the
chip on the right corner is the liver or the triangular specimen).
The precision in specimen diagnosis is thus increased.
Using adequate software will allow 3 dimensional reconstruction
or visualization of the specimens.
5. Prerequisites for the implementation of the concept
5.1. Problems
The greatest difculty in implementing such a concept is by far
the nancing. This is surely also the reason for the fact that virtual microscopy is already being much more intensively used by
pathologists, who usually have to do with smaller student cohorts
and, based on their clinical activity, often have a higher volume
of available nances for the realisation of such a concept. Indeed,
the nancial outlay necessary for the original equipment phase is
not irrelevant and quickly exceeds the total yearly budget available
to the committee for studies and teaching or for teaching projects
at a given university. In addition to the computer working places
for the students (approx. 500 Euro per workside) and a master
computer for the teacher, a specimen scanner must be acquired
(depending upon requirements 50,00080,000 Euro by itself). In
addition, software is necessary to make the digitalized data available on the computer and in internet in a user friendly manner.
Such software is commercially available. Finally, staff is necessary
for the digitalization of the specimens. At least one person is necessary to consistently support the entire project over a lengthy period
of time (at least 3 years). Ideally, this person should also create the
internet platform.
6. Approaches to solutions of the problems
A reduction in costs can surely be achieved by asking colleagues
who already have a specimen scanner to lend it to you. It may also
be possible to borrow the software from this person or from the
computer science faculty or from another institution within the
framework of a cooperative project to acquire or prepare such software at low cost or without cost. Normally, at least one person is
responsible for standard histology section preparation (1/21 MTA
position). This person could, assuming basic computer competencies exist, be further trained to take over these tasks. Otherwise,
the situation may lend itself for a doctoral dissertation position for
a biological computer specialist or a medical information specialist
or a physician with training in the eld of medical information to
solve the problems at a reasonable cost. If the conventional microscopes have become old and their replacement has already been
considered, it would be a very good opportunity to change to virtual
microscopy.
7. Subsequent costs and ways of dealing with them
Yearly there will be subsequent costs for the storage space on
the server of the computer center, additional costs for the domain
names and for software updates. Beyond this, a minimum of repairs
must regularly be reckoned with for the computer worksites. It
would be worth a thought e.g. to allow advertising having a relationship to histology to appear on the homepage and to cover
running costs out of the advertising income. After about 1015

381

years one must expect a complete replacement of the computer


system. Surely, the universities with a pool of tuition fees which can
be invested in such educational projects would be at an advantage
here as with the costs of original equipment.
8. Quality assurance
By means of systematic studies, scientic questions could be
addressed in relation to the concept:
Evaluation between conventional and virtual microscopy.
Analysis of how often, how long and when the system is frequented outside of the course periods.
Analyses as to which specimens are particularly intensively used
by the students. This would allow for an improvement of the educational structure with better generation of didactic emphases.
By Tracking (log-les) the portions of the pictures which have
been particularly intensively viewed by the students specimens
can be retraced in the respective. Thus, it is possible to determine
what is of particular relevance to the student.
Analysis of the extent to which histological specimens are being
used in the framework of case presentations.
Collection of evidence as to whether virtual microscopy may also
be useful for other medical disciplines.
9. Interdisciplinary character
The project approach would not only be of great interest to the
eld of pathology but also for radiology, microbiology and dermatology. The extension to other subjects is conceivable. The IMPP
has already announced intentions to perform examinations on the
computer within the near future. The implementation of this concept would already assure that the respective institution is already
prepared for this innovation. Beyond medical and dental students,
students of molecular medicine as well as related subjects could
also be trained on and access corresponding EKU-data banks. Even
students of other universities could access the system from outside.
Many further extensions are imaginable. A large computer pool
would also be advantageous, as it is a prerequisite for administering on-line examinations in many disciplines beyond histology. It
should be pointed to one charming feature of computer based online examinations, i.e. corrections are performed automatically by
the system.
10. Perspective and future prospects
Many histologists and pathologists remain very skeptical and
bemoan the demise of traditional laboratory teaching methods and
the loss of microscopy skills. The microscope is the most widely
used scientic instrument and in its most basic form has not
changed much over the last century. In popular science imagery
(newspapers, magazines, television drama, movies), the microscope remains the main symbol of the scientist and this is probably
well justied. It is hard to imagine a science laboratory without
microscopes. The microscope has been the main instrument used to
teach life sciences (biology, cytology, histology, pathology, microbiology) (Coleman, 2009). Preliminary evaluations have already
shown that the virtual microscope is increasingly being used in
medical curricula (Drake et al., 2009). In some foreign institutions,
preliminary reports of evaluations after a partial conversion of
the curriculum to virtual microscopy have become available and
have turned out to be very positive (Harris et al., 2001; Heidger
et al., 2002b,c; Blake et al., 2003; Krippendorf and Lough, 2005;
Bloodgood and Ogilvie, 2006; Goldberg and Dintzis, 2007; Scoville
and Buskirk, 2007; Weaker and Herbert, 2009; Husmann et al.,

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2009). Once any given institute has performed its complete course
of histology using virtual microscopy for the rst time, it will
become apparent whether other universities will follow suit. In
Germany, concrete plans for the implementation of such a concept
are in progress in Mnster and Erlangen. Beyond the universities
which already have such plans, there are further anatomical institutes planning to provide virtual microscopy at least in the form of a
supplementary option. Beyond this, it may be realistically assumed
that medical book publishers will gradually couple their histology textbooks with supplementary digital materials. Lucrative third
party funds, as e.g. from virtual institutes of higher learning such as
those already working in Baden-Wrttemberg, Bavaria and Hessen,
will further boost the creation of such virtual educational offerings
at universities and institutions of higher learning. This development will additionally strengthen and accelerate the process of
conversion from conventional to virtual microscopy.
The knowledge gained within the framework of such a concept
and further developments in the eld of communications technology could make a contribution to the fact that in future the
microscopy course may no longer take place in the solid buildings of the university (microscopy labs), but rather be offered at
a given time via the internet. Every student would sit at home
at his computer or whatever may be available at that time (consider the Ipad)and log in via a password. An instructor would
hold the lesson from his computer, discussing in detail a relevant
specimen using a built in microphone in the computer (e.g. Skype).
Meanwhile, it would even be possible to see the teacher in a small
corner of the monitor (so desired). Questions from the students
would be transmitted to a tutor who would also be participating
via his computer. This scenario offers the possibility of instructing
a large number of students all at the same time. The costs for a
microscopy lab could be dispensed with and the amount of staff
necessary would be minimal. Whether such a vision is desirable,
is a moot point at the present time. On the other hand, transmitting lectures alternatively via camera from one room to another in
which the lecturer is not even present, in order to deal with oversized student cohorts is surely an even poorer solution. Concerns
that virtual microscopy may provoke a reduction in staff number in
the anatomical institutes does not appear to be a realistic threat. A
more serious problem, rooted in the global budget restrictions and
poorer payment of the university staff, will be nding appropriate,
highly qualied personnel.
Acknowledgment
We thank Marco Gsswein for the preparation of photographs.
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