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Multimodal Imaging in Life Science Requires<br />

Intelligent Digital D<strong>at</strong>a <strong>Management</strong><br />

Abstract<br />

Within the last decade, digital imaging<br />

techniques replaced the classical neg<strong>at</strong>ives<br />

and dark rooms. Thus, in many<br />

microscopic facilities a tremendous<br />

amount of digital d<strong>at</strong>a piles up in various<br />

d<strong>at</strong>a form<strong>at</strong>s and has to be stored, administered<br />

and documented. Moreover, due to<br />

technical improvements, i.e. the increased<br />

resolution of images, autom<strong>at</strong>ed image<br />

acquisition tools and the growing number<br />

of 3D and 4D applic<strong>at</strong>ions, the d<strong>at</strong>a is<br />

overwhelming the storage and administr<strong>at</strong>ion<br />

capacities. Only by using dedic<strong>at</strong>ed<br />

image management systems the whole<br />

process of image acquisition, document<strong>at</strong>ion<br />

and storage can be autom<strong>at</strong>ed, standardised<br />

and, most important, will keep<br />

the value of your image over a long period<br />

of time. In addition to loss-free and effective<br />

document<strong>at</strong>ion, the stored knowledge<br />

can be further reinvestig<strong>at</strong>ed under different<br />

new aspects and kept in use even<br />

after the oper<strong>at</strong>or left the labor<strong>at</strong>ory.<br />

However, the introduction of image<br />

d<strong>at</strong>abases is the first step towards a final<br />

solution for d<strong>at</strong>a handling, since there is<br />

a lot more inform<strong>at</strong>ion th<strong>at</strong> has to be<br />

handled, e.g. sample specific<strong>at</strong>ions,<br />

prepar<strong>at</strong>ion protocols, analytical d<strong>at</strong>a<br />

and measurements. Future labor<strong>at</strong>ory<br />

d<strong>at</strong>a management systems must provide<br />

a convincing solution for storing all essential<br />

d<strong>at</strong>a th<strong>at</strong> arise during the process<br />

flow of labor<strong>at</strong>ory investig<strong>at</strong>ion. These<br />

systems might even replace the old-fashioned<br />

hand-written labor<strong>at</strong>ory journal.<br />

From Neg<strong>at</strong>ive to Digital Imaging: A<br />

Change of Paradigm<br />

The most prominent change th<strong>at</strong> microscopy<br />

facilities have undergone in the<br />

last 10 years is the replacement of<br />

darkroom technology by digital imaging.<br />

This change does not only affect the<br />

photographers, who had to switch from<br />

classical handcraft to computer work,<br />

but also the microscopist.<br />

Keywords :<br />

image d<strong>at</strong>abases, image processing, image<br />

server, multimodal imaging, d<strong>at</strong>a management,<br />

digital imaging<br />

Reprint from<br />

Today, the number of images th<strong>at</strong> can be<br />

recorded is virtually unlimited. Moreover,<br />

the broad range of image processing tools<br />

leads to even more images with modified<br />

inform<strong>at</strong>ion content. This flood of digital<br />

d<strong>at</strong>a, however, poses challenges for the organis<strong>at</strong>ion<br />

and document<strong>at</strong>ion of the image<br />

pool. Requirements for a d<strong>at</strong>a management<br />

system following the work-flow in an<br />

imaging facility are…<br />

� Each respective image file has to be<br />

uniquely named<br />

� Experimental inform<strong>at</strong>ion as well as a<br />

brief description of the motif have to<br />

be documented together with the image<br />

files and loc<strong>at</strong>ion on d<strong>at</strong>a carriers<br />

� The image files must be linked to<br />

other analogue and/or digital experimental<br />

d<strong>at</strong>a from the same project<br />

� Raw image d<strong>at</strong>a must be clearly<br />

distinguishable from modified or<br />

processed images<br />

� The storage of digital d<strong>at</strong>a on local<br />

drives with personalised folder<br />

architecture has to be replaced by a<br />

standardized storage process on a<br />

central file server.<br />

� <strong>Image</strong> d<strong>at</strong>a must be stored on a<br />

common server, accessible from all<br />

workst<strong>at</strong>ions<br />

� To facilit<strong>at</strong>e viewing and sharing of<br />

images, the image file form<strong>at</strong> should<br />

be standardised and independent<br />

from the image source<br />

� A backup routine must guarantee<br />

long-term availability of all important<br />

image d<strong>at</strong>a independent from file<br />

form<strong>at</strong> or d<strong>at</strong>a carrier technology<br />

� The transfer of complete inform<strong>at</strong>ion<br />

has to be assured when personnel<br />

changes<br />

In general, there are two distinct levels<br />

of inform<strong>at</strong>ion flow: the classical labor<strong>at</strong>ory<br />

workflow, usually documented in<br />

the labor<strong>at</strong>ory journal, and the d<strong>at</strong>a<br />

backbone, necessary for storage and<br />

retrieval. These levels have to be rel<strong>at</strong>ionally<br />

linked (see also Fig. 2).<br />

<strong>Image</strong> D<strong>at</strong>abases and Their Surplus Value<br />

for Microscopy Units: A Field Report<br />

The gener<strong>at</strong>ion of digital image d<strong>at</strong>a today<br />

ranges from simple digital photography<br />

to the highly sophistic<strong>at</strong>ed recording<br />

of light and electron microscopic d<strong>at</strong>a in<br />

3D, 4D and 5D. Many of the digital<br />

recording devices in high-end microscopy<br />

are using non-standardised file<br />

form<strong>at</strong>s, depending on the manufacturer<br />

and the complexity of the image d<strong>at</strong>a<br />

(e.g. *.lsm, *.zvi, *.lei, *.ics, *.pic, *.ome).<br />

For each of these systems, recording inform<strong>at</strong>ion<br />

should be digitally linked to<br />

the image files, either within the image<br />

file or within an additional text file (e.g.<br />

*.lei, *.txt, *.xml), in order to facilit<strong>at</strong>e<br />

the restor<strong>at</strong>ion of the imaging conditions<br />

l<strong>at</strong>er on. Such image/info packages are<br />

transferred to a central image server, secured<br />

by regular backups. This usually<br />

leads to a complex process-architecture<br />

as shown in Fig. 1.<br />

Although <strong>at</strong> first glance this architecture<br />

seems to solve most problems in handling<br />

digital image d<strong>at</strong>a, <strong>at</strong> closer inspection<br />

it does not. Even if d<strong>at</strong>a storage and<br />

backup might assure d<strong>at</strong>a safety, this<br />

system is hardly to search through for a<br />

specific inform<strong>at</strong>ion. Just imagine how<br />

long it takes to find this inform<strong>at</strong>ion,<br />

from screening the labor<strong>at</strong>ory files for<br />

the name and searching the file of interest<br />

on the image server or within the<br />

backup files? How is the retrieval of relevant<br />

inform<strong>at</strong>ion from the labor<strong>at</strong>ory<br />

files guaranteed? Who other than the author<br />

is able to find inform<strong>at</strong>ion within his<br />

labor<strong>at</strong>ory journal? Even worse: wh<strong>at</strong>, if<br />

one searches not for inform<strong>at</strong>ion from<br />

one defined experiment but looking for<br />

general image d<strong>at</strong>a, e.g. on the distribution<br />

of cell organelles within a certain tissue<br />

type? Is it possible to search for relevant<br />

image files in running and finished<br />

projects by screening the lab files? At this<br />

point, <strong>at</strong> l<strong>at</strong>est, image d<strong>at</strong>abases really<br />

become a mand<strong>at</strong>ory tool for d<strong>at</strong>a management<br />

within a microscopic facility.<br />

<strong>Image</strong> management systems, e.g.<br />

<strong>Image</strong>Access provide complete solutions<br />

for handling images and the corresponding<br />

inform<strong>at</strong>ion, from image acquisition<br />

and storage through image evalu<strong>at</strong>ion<br />

Reprint from Imaging & Microscopy 04/2005, pp 45-47 GIT VERL<strong>AG</strong> GmbH & Co. KG, Darmstadt, Germany, www.gitverlag.com


Fig. 1: Digital imaging in life sciences<br />

Each digital imaging device is usually linked to a computer-based image management software (based on e.g.<br />

Windows, Mac OS or Linux), especially adapted to the recording device. For a proper info management, i.e. document<strong>at</strong>ion<br />

of the raw image d<strong>at</strong>a, the image files must be linked to the (handwritten) labor<strong>at</strong>ory journal, and this link has<br />

also to be established on the image server. Finally, for long term storage a regular server backup must be established<br />

to guarantee full d<strong>at</strong>a recovery to the image server after system crashes; this backup regime should also cover the inform<strong>at</strong>ion<br />

from the labor<strong>at</strong>ory journals.<br />

Fig. 2: Process and inform<strong>at</strong>ion flow in a microscopy unit<br />

For optimal process control, every experimental d<strong>at</strong>a produced for a certain sample has to be stored in the image d<strong>at</strong>abase.<br />

Standardised sample inform<strong>at</strong>ion must be linked to every image of the respective sample within the d<strong>at</strong>abase by<br />

the oper<strong>at</strong>or. For each image, microscope and camera metad<strong>at</strong>a (e.g. instrument settings, calibr<strong>at</strong>ion inform<strong>at</strong>ion)<br />

should be autom<strong>at</strong>ically stored to the d<strong>at</strong>abase. All stored inform<strong>at</strong>ion is afterwards used for further processing of the<br />

images, and the newly gener<strong>at</strong>ed inform<strong>at</strong>ion, e.g. measurements, is again autom<strong>at</strong>ically stored to the d<strong>at</strong>abase.<br />

Finally, all inform<strong>at</strong>ion can be directly used for the semi-autom<strong>at</strong>ed gener<strong>at</strong>ion of reports using standardised report<br />

forms based on customisable templ<strong>at</strong>es.<br />

and analysis up to the semi-autom<strong>at</strong>ed<br />

gener<strong>at</strong>ion of reports and present<strong>at</strong>ions<br />

(Fig. 2). All d<strong>at</strong>a gener<strong>at</strong>ors in the lab are<br />

ideally linked to the d<strong>at</strong>abase via a grabbing<br />

interface. The image files are stored<br />

in a standardised, uncompressed file form<strong>at</strong>,<br />

and all acquisition inform<strong>at</strong>ion<br />

stored in the header of the image file or<br />

in a separ<strong>at</strong>e file is now available as<br />

search fields within the image d<strong>at</strong>abase<br />

(e.g. magnific<strong>at</strong>ion, objective, calibr<strong>at</strong>ion).<br />

Moreover, unambiguous naming of<br />

folders and image files is guaranteed and<br />

administered by the d<strong>at</strong>abase.<br />

On top of these autom<strong>at</strong>ically stored image<br />

d<strong>at</strong>a, the d<strong>at</strong>abase can handle additional<br />

inform<strong>at</strong>ion from the labor<strong>at</strong>ory<br />

files such as sample d<strong>at</strong>a, prepar<strong>at</strong>ion<br />

protocols or specific comments on sample<br />

and/or images. For essential inform<strong>at</strong>ion,<br />

the input should be made mand<strong>at</strong>ory<br />

– i.e. image recording is not possible<br />

without entering this inform<strong>at</strong>ion into<br />

the d<strong>at</strong>abase. Customisable d<strong>at</strong>abase<br />

layouts allow a tailor-made organis<strong>at</strong>ion<br />

of the images together with all accompanying<br />

inform<strong>at</strong>ion in order to cover the<br />

labor<strong>at</strong>ory needs in both, university or<br />

industry. In the end, even the semi-autom<strong>at</strong>ed<br />

compil<strong>at</strong>ion of experimental reports<br />

is possible directly from the<br />

d<strong>at</strong>abase, using customised templ<strong>at</strong>es.<br />

Benefits of Using <strong>Image</strong> D<strong>at</strong>a<br />

<strong>Management</strong> Tools<br />

Besides the evident advantages, i.e. (1)<br />

the autom<strong>at</strong>ion and standardis<strong>at</strong>ion of<br />

image acquisition and inform<strong>at</strong>ion storage<br />

and (2) the reduction of complexity<br />

regarding the number of necessary software<br />

packages for image recording, evalu<strong>at</strong>ion<br />

and measurement, the most important<br />

gain is the searching capability of<br />

such d<strong>at</strong>abases. This leads to reliable and<br />

fast results. Moreover, the search result is<br />

independent from individual bias, as long<br />

as common rules for d<strong>at</strong>a input are defined<br />

and obeyed by the staff. Although<br />

the resources needed for implementing<br />

such a system in our labs were formidable<br />

in both aspects, finances as well as<br />

manpower, we learned th<strong>at</strong> the advantages<br />

we now see are tremendous:<br />

� All image d<strong>at</strong>a accessible through the<br />

intranet or even internet<br />

� Independent and safe access through<br />

flexible user management<br />

� <strong>Image</strong> archiving directly <strong>at</strong> acquisition<br />

or processing workst<strong>at</strong>ion<br />

� One point of entry for all different file<br />

form<strong>at</strong>s<br />

� No loss of files anymore<br />

� D<strong>at</strong>a mining across all different project<br />

and experiments possible


Fig. 3: Integr<strong>at</strong>ed labor<strong>at</strong>ory d<strong>at</strong>a management<br />

Today, the digitalis<strong>at</strong>ion r<strong>at</strong>e of experimental d<strong>at</strong>a has already reached almost 100%. This is true for the gener<strong>at</strong>ion of<br />

d<strong>at</strong>a (e.g. images, spectra) as well as for d<strong>at</strong>a processing (e.g. measurements, st<strong>at</strong>istics) and the final public<strong>at</strong>ion in internal<br />

reports or scientific journals.<br />

Thus, the traditionally handwritten, i.e. non-digital labor<strong>at</strong>ory journal is no longer the adequ<strong>at</strong>e tool to overlook this<br />

huge amount of inform<strong>at</strong>ion, and it might soon be replaced by software-based solutions providing an Integr<strong>at</strong>ed Labor<strong>at</strong>ory<br />

<strong>Management</strong> System th<strong>at</strong> will go along with the complete experimental project flow and integr<strong>at</strong>es all digital<br />

d<strong>at</strong>a gener<strong>at</strong>ors and processors, e.g. image d<strong>at</strong>abases (red frame).<br />

� Massively reduced resources for d<strong>at</strong>a<br />

maintenance and retrieval<br />

We feel th<strong>at</strong> image d<strong>at</strong>abases will evolve<br />

from “nice-to-have but expensive addons”<br />

to absolutely essential tools for<br />

inform<strong>at</strong>ion management and process<br />

control in integr<strong>at</strong>ed microscopy facilities.<br />

Future of <strong>Image</strong> D<strong>at</strong>abases: A New Era<br />

of Viewing and Retrieving <strong>Image</strong>s and<br />

Metad<strong>at</strong>a<br />

Although the standardis<strong>at</strong>ion of the whole<br />

imaging work flow as shown in Fig. 2 is an<br />

important step towards an optimal inform<strong>at</strong>ion<br />

handling, this is r<strong>at</strong>her the beginning<br />

than the endpoint of an evolution. A<br />

lot of additional digital inform<strong>at</strong>ion has to<br />

be stored, e.g. Excel sheets with sample<br />

lists, Word documents with prepar<strong>at</strong>ion<br />

protocols or Adobe Acrob<strong>at</strong> files with rel<strong>at</strong>ed<br />

liter<strong>at</strong>ure. Moreover, images are just<br />

one class of digital inform<strong>at</strong>ion th<strong>at</strong> is gener<strong>at</strong>ed<br />

during experiments, and only the<br />

combin<strong>at</strong>ion of microscopic inform<strong>at</strong>ion<br />

with results from e.g. molecular biology<br />

approaches or spectroscopic examin<strong>at</strong>ions<br />

might finally lead to s<strong>at</strong>isfying results.<br />

The most prominent link between all experimental<br />

d<strong>at</strong>a th<strong>at</strong> may contribute to<br />

the final report still is the labor<strong>at</strong>ory<br />

journal. This leads to the idea th<strong>at</strong> a<br />

management system for all available labor<strong>at</strong>ory<br />

d<strong>at</strong>a should simply be replaced<br />

by a digital labor<strong>at</strong>ory journal and avoid<br />

multiple input procedures of the same<br />

d<strong>at</strong>a <strong>at</strong> different working st<strong>at</strong>ions (Fig.<br />

3). Similar to the carry-around book,<br />

such a software package has to be present<br />

<strong>at</strong> every d<strong>at</strong>a source in the labor<strong>at</strong>ory<br />

as well as on every desktop, and it<br />

should autom<strong>at</strong>ically provide rel<strong>at</strong>ional<br />

links to the respective d<strong>at</strong>a gener<strong>at</strong>or.<br />

For future applic<strong>at</strong>ions, also the distinction<br />

between available d<strong>at</strong>a and essential<br />

d<strong>at</strong>a might become more and more important.<br />

The declining costs of disk space<br />

together with the increasing computer<br />

performance enable the storage of<br />

literally all inform<strong>at</strong>ion available, while<br />

eventually only a small portion of this<br />

inform<strong>at</strong>ion is necessary for a future eval-<br />

u<strong>at</strong>ion. So the final question might be: do<br />

we really need all the inform<strong>at</strong>ion we can<br />

store and, if not, how do we know in the<br />

beginning wh<strong>at</strong> inform<strong>at</strong>ion we need in<br />

the future? Until we find an answer to this<br />

question, semi-autom<strong>at</strong>ed storage of all<br />

available d<strong>at</strong>a in qualified d<strong>at</strong>abase systems<br />

seems to be the only solution to<br />

avoid loss of inform<strong>at</strong>ion and d<strong>at</strong>a. This<br />

turns d<strong>at</strong>a mining and realloc<strong>at</strong>ion of old<br />

d<strong>at</strong>a into a real scientific work field in order<br />

to provide a knowledge gener<strong>at</strong>ion<br />

environment for future challenges in various<br />

applic<strong>at</strong>ion fields.<br />

Roger Wepf, Stefan Biel, P<strong>at</strong>rick Schwarb<br />

Stefan Biel<br />

Advanced Development Deo/AP<br />

Tel.: +49 40 4909 6671<br />

stefan.biel@beiersdorf.com<br />

Roger Wepf<br />

GM Research Microscopy<br />

Tel: +49 40 4909 2588<br />

roger.wepf@beiersdorf.com<br />

Beiersdorf <strong>AG</strong><br />

Unnastraße 48<br />

20245 Hamburg, Germany<br />

P<strong>at</strong>rick Schwarb<br />

Friedrich Miescher Institute for Biomedical<br />

Research<br />

Microscopy and Imaging Facility<br />

Maulbeerstr. 66<br />

4058 Basel, Switzerland<br />

Tel : +41 79 353 49 65<br />

p<strong>at</strong>rick.schwarb@fmi.ch


<strong>Image</strong> <strong>Management</strong> <strong>at</strong> <strong>FMI</strong><br />

(Friedrich Miescher Institut, Part of the Novartis Research Found<strong>at</strong>ion, Basel)<br />

Founded in 1970, the Friedrich Miescher<br />

Institute is devoted to fundamental<br />

biomedical research. It employs new<br />

technologies to explore basic molecular<br />

mechanisms of cells and organisms in<br />

health and disease. The current research<br />

focuses on the fields of epigenetic,<br />

growth control and neurobiology. The<br />

<strong>FMI</strong> is an intern<strong>at</strong>ionally recognized research<br />

center th<strong>at</strong> has initi<strong>at</strong>ed key developments<br />

in molecular biology over the<br />

years. It also provides young scientists<br />

from all over the world with an opportunity<br />

to particip<strong>at</strong>e in scientific research.<br />

<strong>FMI</strong> employs 22 research groups and a<br />

core of technicians and support staff, and<br />

is home to 90 PhD students and 75 postdoctoral<br />

fellows from almost 40 different<br />

countries.<br />

In May 2005 the <strong>Image</strong> <strong>Management</strong> System<br />

<strong>Image</strong>Access by <strong>Imagic</strong> <strong>Bildverarbeitung</strong><br />

<strong>AG</strong>, Switzerland, has been introduced<br />

<strong>at</strong> the <strong>FMI</strong>.<br />

The goal was a complete solution to handle<br />

the fast increasing amount of image<br />

rel<strong>at</strong>ed d<strong>at</strong>a <strong>at</strong> the institute. In order to<br />

cope with the wide variety of image ac-<br />

quisition systems (wide field, confocal<br />

and two-photon microscopes) and to<br />

meet the requirements of other imaging<br />

systems (Blot, Gel and Scanner) and<br />

desktop users, the system was designed<br />

to provide several different d<strong>at</strong>a views<br />

and keyword lists.<br />

<strong>Image</strong>Access, as a well established <strong>Image</strong><br />

<strong>Management</strong> System in general microscopy<br />

and one of the leaders in handling<br />

microscope oper<strong>at</strong>ing parameters<br />

and metad<strong>at</strong>a, was extended with experiment<br />

and project inform<strong>at</strong>ion in order to<br />

achieve a long term value of each picture.<br />

All meta d<strong>at</strong>a are autom<strong>at</strong>ically stored<br />

within the d<strong>at</strong>abase, and the linked image<br />

and document files are kept on a<br />

dedic<strong>at</strong>ed file server. This allows instant<br />

access from any work place to images,<br />

documents and meta d<strong>at</strong>a throughout<br />

the whole <strong>FMI</strong> intranet for further processing<br />

and present<strong>at</strong>ion. Due to the variety<br />

of image types (2D, 3D, 4D, movies),<br />

they are linked to specific external viewers<br />

(e.g. IMARIS) or can be dropped to<br />

Figure 1: <strong>Image</strong>Acess user interface showing thumbnails, project and experimental d<strong>at</strong>a<br />

any other imaging software (e.g. <strong>Image</strong>-<br />

Pro, Metamoroph, Photoshop) for visualiz<strong>at</strong>ion.<br />

After a year of experience using the system,<br />

some important facts are to be considered:<br />

� Advanced autom<strong>at</strong>ed microscopy requires<br />

individual setups to maintain<br />

speed and resolution. This customis<strong>at</strong>ion<br />

process may take quite some time<br />

and involves local IT<br />

� Dedic<strong>at</strong>ed user trainings for the different<br />

tasks like image acquisition,<br />

processing and present<strong>at</strong>ion are key<br />

requirements of a successful system<br />

implement<strong>at</strong>ion<br />

� Due to the typically large fluctu<strong>at</strong>ions<br />

of students and post docs, it is essential<br />

to maintain and build up system<br />

know how by assigning in-house super<br />

users within the various groups<br />

<strong>Image</strong>Access by <strong>Imagic</strong> <strong>Bildverarbeitung</strong><br />

<strong>AG</strong> is one of the only Imaging<br />

Systems on the market not only to manage<br />

2D images, but also to cope with the<br />

fast growing amount of multidimensional<br />

d<strong>at</strong>asets and metad<strong>at</strong>a. The user interface<br />

reflects nicely the scientist’s work<br />

flow, increases productivity and is a<br />

gre<strong>at</strong> help to achieve the real scientific<br />

goals.<br />

<strong>Imagic</strong> <strong>Bildverarbeitung</strong> <strong>AG</strong><br />

Europastrasse 27<br />

CH-8152 Gl<strong>at</strong>tbrugg<br />

Tel. +41 (0)44 809 40 60<br />

Fax +41 (0)44 809 40 61<br />

www.imagic-imaging.com

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