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16 prscientific rofile esearch
Under the microscope
Greg Blackman looks at
the need for automated
image analysis in scientific
research, among other
scientific applications of
imaging technology
Many scientific investigations deal with
huge data sets, running tests on large numbers
of samples to gain statistically-meaningful
results. Imaging is a potential bottleneck in
these studies; microscopy, in particular, can be
time-consuming and tiring for the human eye.
There is also a degree of subjectivity involved
in human analysis of microscope slides; even
an experienced technician’s capacity to evaluate
the images will waver after several hours of
visual analysis. Automated image analysis
techniques can increase throughput of samples
and standardise test results.
The Preclinical Safety Unit at pharmaceutical
company Novartis is concerned with assessing The iXonEM+ 860 back-illuminated EMCCD camera from Andor Technology was used to capture
the safety of potential drug candidates prior to images of the movement of restriction enzymes along DNA.
administration to humans. Dr Wilfried Frieauff,
laboratory head within the genetic toxicology are all tests used to identify the extent of MIL formed the basis of the image analysis
unit in preclinical safety at Novartis in Basel, genetic damage caused by the drug candidate algorithms Frieauff developed on the ROBIAS
Switzerland, has developed ROBIAS (ROBotic under investigation, and each can be handled platform. ‘The number and variance of measured
Image Analysis System) for automated image by ROBIAS. The micronucleus test looks at features used for pattern recognition algorithms
om
analysis of samples. The system uses a Sony CCD chromosomal damage during cell division, will be a lot higher for biological image analysis
ope.c
colour camera, mounted to a fully automated whereas the comet assay assesses the direct than for an industrial environment,’ comments
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Leica microscope, and custom-developed action of the drug candidate on nuclear DNA. Frieauff. In an industrial environment there is
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image algorithms based on the Matrox Imaging ‘The assays in isolation are not sufficient generally greater prior knowledge about the
www Library (MIL). to tell the scientist whether the compound is patterns under consideration (such as CAD
Toxicologists make assessments on the safe or not but, by combining numerous tests features) and the deviation from a standard

2009 
ch
negative aspects of a drug candidate, which looking at different possible aspects of how prototype model can be better estimated.
could potentially cause side-effects. A range the drug candidate will affect the cell or the Frieauff uses the micronucleus assay as an
of in vitro and in vivo assays are carried out whole organism, potential side-effects can be example: ‘The micronucleus assay is dealing
to determine any deleterious effects of the identified,’ explains Frieauff. The majority of the with cells each showing individual visual

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ebruary/mar
compound. Part of the work undertaken by range of assays required cannot be addressed characteristics (shape, size, spectral features)
ope the preclinical safety unit involves conducting by automated image analysis techniques, but that may well alter from image to image and
various genetic toxicology assays relying on ROBIAS was designed to automate as many of sample to sample.’ In addition, other variables
images to provide quantifiable data on the the assays conducted routinely at the preclinical such as the age of cells in culture, or the batch
genotoxicity (deleterious effect on genetic safety unit as possible. of dye used to stain the nuclear material will
material) of the compound. Substances that ‘Hundreds of studies for a variety of differ from test to test, and there is also potential
interact with the genetic material can potentially toxicological tests are run annually in genetic human error during laboratory work.
be mutagenic or carcinogenic. toxicology at Novartis, and automated Image analysis for micronucleus detection
In vitro and in vivo micronucleus tests, comet image analysis is vital to ensure accurate and starts off with the segmentation of thousands
assay, and chromosome aberration analysis standardised test results,’ states Frieauff. of potential candidates; there will be stained
imaging and machine vision eur
IMVEfeb09 pp16-19 science.indd 16 17/2/09 17:09:38
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