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Indiana Institute for Biomedical Imaging Sciences
Resources and Capabilities

New research laboratory space was opened in early 2003 that will support the activities of the Indiana
Institute for Biomedical Imaging Sciences (IIBIS). A new research imaging center is located in the
Research Institute II (R2) building which is in close proximity to all of the cancer research activities on
our campus. The first floor and basement level of the R2 building house comprehensive facilities for
human and animal imaging (MRI, PET, and CT) along with ancillary support space including wet
laboratories, surgery suites, an image processing laboratory, a machine shop, and an electronics shop.
The imaging center is housed within approximately 30,000gsf space. A second new building, the
Biomedical Research and Training Center (BRTC), houses our tracer and contrast agent development
program. This space can accommodate 2 medical cyclotrons (1 is currently located in the facility) and has
extensive synthetic chemistry space, radiochemistry space, molecular biology laboratories, cell culture
labs, and ancillary support labs for shared instrumentation and device construction. The total space in the
BRTC for this program is approximately 15,000 gsf. The two buildings are linked by a pneumatic tube
system that permits the rapid transfer of short-lived PET radiopharmaceuticals from the chemistry
laboratories to the PET imaging systems.

Biomedical Imaging Systems

Multiple biomedical imaging systems are available to investigators at IU to investigators from other
institutions and industry through the IIBIS. The imaging systems are categorized below as base and
alternative systems.
Small Animal Imaging Systems

EVS-R9 microCT. The EVS-R9 microCT scanner (Enhanced Vision Systems Corp, London, Ontario
N6G 4X8) operates at 50 kVp and 1 mA maximum tube current. It is capable of 50 micron or 100 micron
voxel resolution with 2x2 or 4x4 binning in the detector panel. The radiation dose associated with various
imaging parameters (exposure time and angular samplings) is measured to obtain a guideline on imaging
protocol designing. For each radiation dose level, image noise is also measured by the standard deviation
of CT number in the water region. The noise to dose relationship is established for various detector-
binning modes.
IndyPET II. The IndyPET-II scanner has been developed at Indiana University by Dr. Hutchins as a high
resolution, high sensitivity research PET scanner for use in small animal imaging studies. The system
consists of four, approximately planar detector banks mounted on a rotating gantry. The detectors cover a
transaxial FOV of 23cm and an axial FOV of 15 cm. This configuration reduces parallax distortions and
produces a relatively uniform resolution throughout the FOV. The two pairs of opposing detectors banks
are offset to give increased sampling density and increased spatial resolution. The average (radial and
transverse) FWHM resolution is 2.5mm at the center of the FOV and increases to less than 3.5mm at the
edge of the FOV. The NEMA-2001 sensitivity is 9030 cps/MBq at the center of the scanner and 4250
cps/MBq at a radius of 10cm. The NEMA-1994 sensitivity is 23.0 cps/MBq/ml.
IndyPET III. The IndyPET III scanner was developed at Indiana University by Dr. Hutchins The system
was designed to achieve 1 uL volumetric spatial resolution suitable for whole body mouse imaging. The
scanner uses 8 planar detector banks consisting of 48/spl times/108 array of 20 mm long LSO crystals
with an array pitch of 0.87 mm coupled to two Hamamatsu H8500 large area, 64-anode photomultiplier
tubes. The detector modules are mounted on a rotatable gantry offset from the center of rotation to allow
increased sampling density. Transaxial resolution is 1.1 mm FWHM with an axial resolution of 1.5 mm
FWHM. Sensitivity has been measured to be 4.0% of all decays. The scanner design allows for the
addition of 14 additional detector banks for improved resolution and sensitivity.

Varian 9.4T MRI Horizontal Bore.
The Varian 9.4 T / 31 cm actively shielded horizontal bore MR
system is suitable for in vivo imaging and sprectroscopy investigations of small animals ranging from
mice to rabbits. The system is equipped with two sets of actively shielded gradient sets: 1) a 21 cm inner
diameter gradient set capable of generating 20 G/cm, and 2) a 12 cm inner diameter gradient set capable
of generating 40 G/cm. The state-of-the-art Varian Unity Inova console on the system is capable of
performing multinuclear investigations and has waveform generators on all RF and gradient channels,
which allow arbitrary pulse shaping and easy implementation of sophisticated imaging and spectroscopy
pulse sequences. A number of single-tuned quadrature and dual-tuned linear imaging coils, slotted tube
resonators and surface coils are available for multinuclear MR studies. MR methods, which are used for a
variety of applications, include echo-planar imaging, diffusion weighted imaging, back-plane
reconstruction, single voxel localized spectroscopy, chemical-shift imaging, gradient-enhanced spectral
editing, multiple-quantum techniques and other specialty pulse sequences.
Berthold LB981 NightOwl The NightOWL system consists of a Peltier cooled CCD camera (578 x 385
pixels) housed within a 102x60x40 cm light tight enclosure for imaging luciferase and GFP expression in
small animals. The system is interfaced to a Pentium 200 MHz for data acquisition and analysis.

Interventional Radiology Research Laboratory.
This laboratory is focused on research in
atherosclerosis, restenosis, and directed drug delivery for the treatment of the cancer and vascular disease.
The laboratory includes an animal operating room for microsurgeries as well as intraabdominal and
intrathoracic surgeries, two Toshiba X-ray machines with fluoroscopic and DSA imaging capabilities, and
associated ancillary equipment for subject monitoring and support.

Human Imaging Systems
Siemens MAGNETOM Trio 3T Unlimited MRI.
The Trio 3T MRI, located in the R2 building, is a 3
tesla whole body imaging system operating with Syngo software. The system is equipped with a 200
T/m/s gradient system and 8 RF-channels. The flexible RF system has the capability of performing
multinuclear and spectroscopy studies.
GE Signa Advantage 1.5T MRI. A dedicated research MRI system is located in the high technology
imaging center of University Hospital. This system is a 1.5 tesla General Electric Signa Advantage
system operating under software version 9.0. The system currently has the capability to perform
hydrogen magnetic resonance spectroscopy and functional brain imaging studies using Echospeed. Two
additional 1.5T General Electric MRI systems (1 each in University and Riley hospitals) have echo-planar
imaging capabilities and are available on a limited basis for research studies.
Siemens ECAT HR+ PET. The Siemens ECAT HR+ PET scanner is located in the R2 building. The
whole body imaging system has an axial field-of-view of 15 cm, is equipped with BGO detector
technology and has retractable septa for 3-D volumetric imaging. Both conventional filtered
backprojection and OSEM reconstruction algorithms are available and used routinely.
Siemens Biograph PET/CT. The Biograph PET/CT scanner is located in the Clinical building located in
the IUPUI campus and is scheduled to be relocated to the R2 building. This system is a whole-body static
imaging system equipped with BGO detector technology and capable of 3-D volumetric imaging. The
axial field-of-view is 15 cm. Both conventional filtered backprojection and OSEM reconstruction
algorithms are available and used routinely.

Alternative Animal Imaging Systems
Optosonics Thermoacoustic Tomography System.
This new imaging modality, conceived and developed
at Optosonics, Inc (Indianapolis, IN) in collaboration with the Indiana-CEBI, produces images of tissue
RF absorption contrast by detecting sonic waves produced by thermal expansion of tissue. A small
animal system has been constructed using a tunable laser enabling optical absorption spectroscopy and
imaging. The current system has a spatial resolution of 200 microns and can image using optical
wavelengths in 532-1064nm wavelength range using an Optotek, Inc laser.
Radionuclide Production Systems
RDS-Eclipse Cyclotron:
Housed within the BRTC building is a Siemens RDS-Eclipse cyclotron. This
system consists of an 11 MeV proton cyclotron, target systems for the production of 11C, 18F,13N and 15O
used in the synthesis of PET tracers.
IIBIS Imaging Services Core

The IIBIS provides a range of services that include education of cancer center investigators on the
capabilities and application of imaging technologies, consultation to assist with imaging study design,
production of PET tracers, performance of imaging studies, resources for image processing and data
analysis, and quality control for all chemistry and imaging systems housed within the R2 and BRTC
facilities. A brief description of the core services follows:
PET Tracer Production: PET Carbon-11, Nitrogen-13, Oxygen-15 and Fluorine-18 tracers are
produced for PET imaging studies. Numerous tracers are in various stages of development for support of
cancer, cardiovascular and neuroscience research.
PET Research & Routine Production Radiotracers
1. Heart acetylcholinesterase imaging agents (dog and rat heart imaging):

Cardiac acetylcholinesterase imaging agents [11C]edrophonium, [11C]pyridostigmine 2. Choline kinase imaging agent (tumor mice):
3. MMP (Matrix metalloproteinase) imaging agents (tumor mice):
[C-11]Me-CGS 27023A and its analogs [C-11]Me-halo-CGS 27023A analogs [C-11]Biphenylsulfonamide analogs 4. Alkylguanine-DNA alkyltransferase (AGT) imaging agents (tumor mice):
5. Herpes simplex virus thymidine kinase (HSV-TK) reporter probes (tumor mice):
[18F]FHBG and other fluorine-18 labeled penciclovir and ganciclovir analogs _____________________________________________________________________________________ 6. Brain dopamine and serotonin transporters ligands (human, pig and rat brain imaging):
[11C]β-CFT, [11C]β-CIT, [11C]β-CNT for the study of Parkinson’s Disease. 7. Muscarinic Receptor Ligands (dog heart imaging):

8. Peripheral Benzodiazepine Receptor Ligand (tumor mice and rat):
9. D2/D3 receptor ligand (human and rat brain imaging):
10. β-Amyloid Plaques Ligand for Alzheimer’s Disease (human brain imaging):
11. Vesicular monoamine transporter ligand (rat brain imaging):

12. Sympathetic Nervous System (human and dog heart imaging) :
13. High-affinity choline uptake (HACU) ligands (rats and mice, tumor and heart imaging):
14. SKCa channels ligand (rat heart imaging):

15. Vagal Nervous System (dog heart imaging):

16. Luciferase reporter probes (tumor mice):
[C-11]D-luciferin methyl ester and [C-11]D-luciferin methyl ether 17. Blood Flow (human and dog):

18. Glucose Metabolism (human and animal):

19. Blood Volume (tumor mice):
20. Free Fatty Oxidation Rates (human and animal):

Performance of Imaging Studies: The imaging center provides experienced and trained technologist for
the acquisition and basic image processing required for all studies. Investigators, or their staff, work
closely with the imaging center technologists in the performance of specific studies. The imaging center
staff administer anesthesia to the animals, administer PET tracers or contrast agents, and operate the
imaging systems. The only exception to this model is for bioluminescence/biofluorescence imaging
where investigators can operate the system without support once trained. The imaging center staff is also
responsible for all necessary image reconstruction or processing needed for the study. An emphasis for
all imaging studies is placed on the collection of data that permits quantitative or semi-quantitative
analysis of results.
Image Processing and Data Analysis: The imaging center maintains numerous servers and software
packages for the analysis of imaging data. A large base of in-house developed imaging processing
software (based upon IDL and/or MATLAB) is maintained by the faculty and staff in the imaging center.
_____________________________________________________________________________________ This software enables the generation of multimodality fusion images, navigation throughout image volumes in standard and non-standard image planes, definition of region-of-interests, application of semi-quantitative data analysis methods (SUVs), application of quantitative data analysis methods (compartmental models), and 3-D visualization tools (projections, maximum intensity projections) for subjective evaluation of image data. Tools for the registration of multimodality images have been developed and validated in our laboratory and are utilized routinely so that fused data sets can be easily generated. Access to all software and servers is made available to interested cancer center investigators using X-window emulators and VPN clients. A limited number of image processing workstations are also available in the imaging processing laboratory housed in the imaging center.


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