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Tis prize is made possible with thekind support of the Knut and AliceWallenberg Foundation.Tis Founda-tion grants funding in two main areas;research projects of high scientifc poten-tial and individual support of excellentscientists.
Will you bemeeting a NobelPrize winner thisDecember?(If you have a recent PhD you could be.)
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127 1SCIENCE sciencemag.org/products
LIFE SCIENCE TECHNOLOGIES Produced by the Science/AAAS Custom Publishing Office
MICROSCOPY
Molecular Imaging, a contract research organiza-
tion (CRO) with locations in Ann Arbor, Michigan
and San Diego, California, has a largely pharma-
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but need help selecting the right candidate for clinical trials.
ìItís about trying to obtain information that cannot be ob-
tained other ways,î he says.
How do Molecular Imagingís scientists obtain such informa-
F���������DFF����E��D��F D��������F D������D�����FD������
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as well.
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approach would be to obtain a set of genetically identical
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point, and dissect out and analyze the appropriate brain re-
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probe. They can pinpoint functional dopaminergic neuronsóthe
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anatomical features using computed tomography (CT) data.
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fewer animals, richer data, and better decisions.
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Biomedical Research Imaging Center (BRIC) Small Animal
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method compared to traditional immunochemistry.î
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nance imager (MRI)ósmaller in stature but more powerful than
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����D�:���,.�D;����D��D�>$���.�$=�$��FD�:���<D���?@AA�
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from PerkinElmer.
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instance). Molecular imaging methods include nuclear medicine
*�.$�������.�$-�������F�C���������C D�������� �C ����� �
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$ D�������&������!�������'�C���F���F�The University of
Texas MD Anderson Cancer Center sports three MRI scan-
ners in its instrument stable, and they are ìby far the most
widely usedî of the labís hardware, says John Hazle, profes-
sor of imaging physics and the facility director. Among other
�D���� D�����7!�������D�1D"CD��D�F���F�F�ED���������
and the ability to image some physiology and
TranscriptomicsóJuly 31 ProteomicsóSeptember 11 GenomicsóSeptember 25
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To minimize complexity, researchers often study cellular
proteins or nucleic acids in isolation. But sometimesówhen
�� �������������� ������������ �������� ������������ ������
���������������������������� ����� ���������������� ��
�������������������������������������������� ���������� ���� �
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�������������������������� ���������������������� �����������
the ghostly outline of a mouse, with a telltale multicolored heat
bloom indicating where the action is. �����������������
continued>
Small animal imaging: Data that’s more than skin deep
1272 sciencemag.org/products SCIENCE
LIFE SCIENCE TECHNOLOGIES
MICROSCOPY
Produced by the Science/AAAS Custom Publishing Office
metabolic processes,î allowing researchers to determine, for
instance, how tumors respond to therapy.
But, by most accounts, optical imaging is the most widely
used preclinical modality overall. Capable of recording both
789:������������98�������������� ��������������������
couple advantages,î Yuan says. Among its virtues, optical im-
aging is relatively inexpensive and high throughputóresearch-
ers can image multiple animals simultaneously and rapidly,
�����������:�������������9�������������������������
population sizes. By comparison, MRI scans, which provide
�9������8������9�� ��:���9���9���9:�������������������8:�����
scanner runs around the clock, but the throughput is much
lower [than optical],î says Christopher Contag, director of the
Stanford Center for Innovation in In Vivo Imaging, where
9�������������9��������9��������8�����9��������������
optical system we process probably hundreds of mice [per
day], versus a handful on the MRI or PET.î
��������������9������������������9�8���������:���
users and they can handle the image acquisition and data inter-
�:����9���:������8��� �� 8�������������:��9�������������
�:�������������:��������!��
Better optics
�������������9��������9�7��9:�"�789:������������9-
8�������������789:������������� ���789:���������:��:�
#�8������������������9���9:�������������9����789:��-
cent protein) is introduced or expressed in the animal and ex-
cited with an external light source. Bioluminescence involves
genetically modifying the animal to produce a light-generating
protein, such as luciferase, and produces light only in re-
sponse to a supplied substrate. In either case, the abundance
�������:�8�9��9������������9��8�:���:����������8:������
recording the resulting photoemission through the skin.
But therein lies the problem. As anyone who has put a
7����������������:���������9�� ������9����9���:����
in a straight line through biological tissue; it scatters and
is absorbed. Thus, some fraction of the excitation (in the
�����9��789:�������$���������9������#789:������������
bioluminescence) is inevitably lost in optical imagingóthough
this is less true of near-infrared light. Also, the signalís exact
�9��9����9������%�8���9��9:��98���&���9��:��� �'()�����
SPECT tracers can be localized precisely, as both emit high-
energy particles that traverse the body unimpeded. As a
result, optical imaging is rarely used on any animals other
than mice, and even then, mostly for surface features such as
subcutaneous tumors.
Researchers are working to change that, however.
�������:9��������:������9����:�����*������� ��9:�
������� �����9�9��98�����9�9�:�����#'+)$��,�9������� �
the Gene K. Beare Distinguished Professor of Biomedical
Engineering at Washington University in St. Louis, Missouri
who pioneered the technique, says that while optical imaging
loses resolution beyond about a millimeter, ultrasound main-
�����:��98�9������:����:���������'+)��!��������9������
the two, using light to excite a molecular target but reading
out the ultrasonic pressure wave caused by the targetís heat-
��������*����9������������:��9��������������8���: ��
explains Andrew Needles, senior manager for product inno-
vation at FUJIFILM VisualSonics ��)9:9��9 �����:9 ������
�����9���:��-������������99�����)������������8��������
surrounding atmosphere to create a sound wave.î
������9:� ���������� �'+)�����������������9��8� ��:9-
vided the laser is tuned to the correct wavelength for molecular
absorption. His lab has imaged everything from nucleic acids
������:�9���:������9�9:������������������:�������9��9��
application, says Needles, is measuring blood oxygenation,
functional data that can be overlaid over a traditional ultrasound
������9:�����9���������.9� �����������������������:����
&�+�.����������8������9�������������9���:���9��������
animal in vivo and image action potentials.î
TriFoil Imaging, in Chatsworth, California, has developed
another optical technology. Launched in September 2014,
�����789:�������/����9���9��8�����9�9�:�����#0,(1)$���
to traditional planar imagers what CT is to X-ray.
Laser energy strikes the animal through a thin slit while ro-
tating around the whole animal in a helical scan. The resulting
789:������������9��������8:��������:���9��23�������9:���9-
sitioned around the animal, which rotates through 360 degrees
to produce a tomographic dataset, similar to PET.
Indeed, according to Staf Van Cauter, executive vice presi-
������9:���:�����������8����������9���������):09 �0,(1)�
������9��9�9������:�������9��8���:�������������8�� ��
and using it, he says, researchers can detect tumors and other
features smaller than a millimeter in size, and identify exactly
where in the body they are located.
A more accessible pet
Still, since optical modalities are for the most part not ap-
proved for human use, researchers interested in clinical medi-
�����8���99��������:���9:��9��8�:�������������9�8�:�
option is PET.
PET, explains John Gore, director of the Vanderbilt Uni-
versity Institute of Imaging Science, provides molecular
��9:���9�������*����9�������������)����:���9!���:��98-
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millimeter-sized.
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���������������in Culver City, California, a company that
develops PET imaging systems and probes. A PET probe that
works in mice can thus also, in theory, be applied in humans.
But PET probes arenít easy to work with. The most widely
Using [18F]-
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1273SCIENCE sciencemag.org/products
LIFE SCIENCE TECHNOLOGIES Produced by the Science/AAAS Custom Publishing Office
MICROSCOPY
by Bruker). According to
Patrick Goodwill, Magnetic
Insightís chief technical of-
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lar contrast, like PET and
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magnets. ìItís nuclear medi-
cine, but using an iron oxide
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Researchers can, for in-
stance, load mesenchymal
stem cells with antibody-
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says, detecting as few as
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ìWeíre using low-frequency
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about anything. If we had
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ner, we could see through a
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Contag, with Stanford
colleague Sam Gambhir,
is studying ways to
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cal structure. But 133����H�HF��� ���HF��� GHF�F�0FH�H��F
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he says.
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facilities or the clinic, most researchers agree existing modali-
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ment one another. ìThis is why you donít want to say one tech-
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half-life of 110 minutes,
meaning the material must
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to the researcher, and
used within hours. Another
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to researchers located at
greater distances from syn-
thesis laboratories. Or labs
can generate their own
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a cyclotron. But that isnít a
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The BRIC, for instance,
installed a cyclotron in late
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rounding the cyclotron. The roomís lead-shielded door weighs
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way to atta ch them to the desired molecule before they decay.
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Research ��F3������H�F���G� H���F��FH�H���HF�F
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antibody fragments.
Using an 186����H�HF �����HF��F��HF����HFH����H�F
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containing a sortase recognition sequence to create an immu-
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Optical Imaging Laboratory, Washington University in St. Louisoilab.seas.wustl.edu
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LIFE SCIENCE TECHNOLOGIES
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Research adventure at 63 degrees northRemote yet modern. Beautiful and peaceful. Qualityand equality. All that combined with long-termgovernment research funding and the UN’s rankingas one of the best countries to live in. Welcome toTrondheim and NTNU. The best minds, world-classresearch, and just the right size city for a great life.
We welcome top scientists from all cultures andnations who want to contribute to our goal:Knowledge for a better world.
TOP RESEARCH DEMANDS BRILLIANT MINDS
– WE’RE ALWAYS LOOKING FOR THE BEST
www.ntnu.edu
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NTNU neuroscientists May-Britt and Edvard
Moser were awarded the Nobel Prize in
Medicine or Physiology in December 2014.
Trondheim is the ancient Viking capital of Norway. The Nidelva River flows through the city, and you can even fish for salmon during
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