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Facilities & Other Resources (PDF)

 Indiana Institute of Biomedical Imaging Sciences and IU Center for Neuroimaging

 Core Resources and Capabilities

 Laboratory space was opened in early 2003 that will support the activities of researchers participating in this grant. A research imaging center is located in the Research Institute II (R2) building, which is in close proximity to all of the neuroimaging 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 30,000 gsf 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 neuroimaging investigators through the Indiana University Center for Neuroimaging (CfN), a component of the Indiana Institute for Biomedical Imaging Sciences (IIBIS). The imaging systems are categorized below as base and alternative systems. The base imaging systems are routinely used by center investigators at the present time or are expected to be used routinely during the funding period of this grant. The alternative systems represent additional resources that can be made available on an as-needed basis to support imaging investigators. All base systems are located in the R2 building unless otherwise noted. Our facility includes extensive preclinical imaging systems (EVS-R9 microCT, IndyPET II & III, Varian 9.4T MRI Horizontal Bore, Berthold LB981 NightOWL, Optosonics Thermoacoustic Tomography System) which are not described in detail here due to the focus on human subjects in the current project. However, these resources are available to members of our multidisciplinary research team working in animal models relevant to MCI and AD.

Base Human Imaging Systems

 Siemens MAGNETOM Trio 3T Unlimited MRI. A research-dedicated Siemens MAGNETOM Trio 3T whole body scanner was upgraded to TIM in March 2007. Key features include: TQ-gradient providing field strength up to 45 mT/m (72 mT/m effective) and SR up to 200 T/m/s (346 T/m/s effective), 102 element and 32-channel architecture, 50 cm FOV, InLine Automated Processing, Auto Align slice positioning, AudioComfort noise reduction, Phoenix image reproducibility, Intelligent Coil Control auto coil position detection, full suite of imaging techniques (inline 3D and SSH EPI fMRI, up to 256 direction DTI, SWI, etc.), syngo advanced imaging applications, iPAT2 utilizing mSENSE and GRAPPA technologies to increase image quality and reduce susceptibility artifacts, Matrix 12-channel Head Coil, and a complete array of other anatomy coils (neck, cardiac, etc.). IDEA and ICE development and analysis packages are also available. In 2009, a 32-channel parallel RF head coil was obtained and is being evaluated.

 Siemens ECAT HR+ PET. The Siemens ECAT HR+ PET whole body imaging system has an axial FOV of 15 cm, is equipped with BGO detector technology and has retractable septa for 3D volumetric imaging. Both conventional filtered backprojection and OSEM reconstruction algorithms are available and used routinely. This scanner will be used for all studies in the proposed project.

 Siemens Biograph PET/CT. The Biograph PET/CT system is a whole-body static imaging system equipped with BGO detector technology and capable of 3D volumetric imaging. The axial FOV is 15 cm. Both conventional filtered backprojection and OSEM reconstruction algorithms are available and used routinely.

 Alternative Human Imaging Systems

 GE Signa Advantage 1.5T MRI. A research-dedicated MRI system is located in the high technology imaging center of University Hospital. This system is a 1.5T 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.

Tracer and Contrast Agent Development Facility

The Tracer and Contrast Agent Development facility is in the BRTC. This facility consists of a cyclotron laboratory for the production of short-lived radionuclides, a radiation chemistry laboratory for the synthesis of drugs labeled with the radionuclides produced by the cyclotron, an analytical chemistry laboratory for measuring the sterility and pyrogenicity of the labeled drugs, and an automated pneumatic transport system for transporting PET radiopharmaceuticals to the imaging suite for measuring the 3D distribution of these drugs in the animal and human body following administration.

Cyclotron Laboratory. Housed within the cyclotron facility is a Siemens Radionuclide Delivery System (RDS), Eclipse RDS-111 cyclotron. This system consists of an 11 MeV proton cyclotron, irradiation target systems for the production of [11C], [13N], [15O], and [18F] radioactive material transport systems, and a series of computer-controlled synthesis modules for the production of radiopharmaceuticals.

 Radiation Chemistry Laboratory. The 4 radiation chemistry laboratories at the BRTC consist of a series of shielded chemistry cells for the production of radiopharmaceuticals labeled with positron emitting radionuclides produced by the cyclotron. These cells are designed to hold several curies of radioactive material with minimal exposure to the personnel performing the syntheses. This laboratory also houses chromatography equipment for the isolation of radiopharmaceuticals from radiochemical contaminants produced in the synthetic process as well as analytical equipment for the measurement of radionuclide quantities.

Analytical Chemistry Laboratory. The analytical chemistry laboratory is used to assay small samples of the radiopharmaceuticals produced in the radiation chemistry laboratory. This laboratory contains assorted chromatography and sample assay equipment for these purposes. This laboratory is also used to assay human blood radiopharmaceutical concentrations and metabolites. Equipment used for the blood sample analysis includes an automated well counter system, centrifuge, and assorted separation columns for isolating radiopharmaceuticals from metabolites formed in the human body. The new facility at BRTC houses 3 analytical chemistry laboratories.

Cold Chemistry Laboratory. The 6 cold chemistry laboratories in the BRTC are used for the synthesis of non-radioactive precursor compounds required for the synthesis of research radiopharmaceuticals.

Automated Pneumatic Transport System for PET Radiopharmaceuticals. A pneumatic transport system was established between our cyclotron/ radiochemistry facilities and the PET imaging suites that are separated by a distance of ~2 km. Unique features of this system include a path which crosses a river, a 3-way networked computer control system, and novel carrier designs.

PET Tracer Production. PET [11C] and [18F] tracers, novel and potent enzyme-based and/or receptor-based brain, tumor and heart imaging agents are produced for PET to study brain, cancer and cardiovascular diseases. Numerous tracers are in various stages of development for support of research. The following list, although not exhaustive, illustrates the breadth of neuroscience, cancer, and cardiovascular-related radiopharmaceuticals at various stages of development, from initial evaluation in cell and animal models to evaluation in clinical trials.

Routine Tracers:

1. [18F]FDG
Glucose Metabolism
2. [18F] Fluoride
Bone Scanning
3. [18F] Fluoromethane 
Perfusion
4. [11C] CO Blood Volume
5. [11C] Acetate
Free Fatty Oxidation Rates
6. [15O] H2O Blood Flow
7. [15O] O2
Oxygen Consumption
8. [13N] NH3
Blood Flow

Neuroimaging Tracers:

1. [11C]CFT and [11C]CIT
Dopamine and Serotonin transporters
2. [11C]Raclopride 
D2 receptors
3. [11C]PIB  
ß-Amyloid plaques
4. [11C]DAA1106  
Peripheral benzodiazepine receptor
5. [11C]Flumazenil Benzodiazepine receptor
6. [11C]Choline  
Brain Tumors
7. [11C]Yohimbine  
a2 Adrenergic receptors
8. [11C]DTBZ   
Vesicular monoamine transporters

9. a-[11C]Methyl-L-tryptophan (a-[11C]AMT)

 Serotonin synthesis
10. NK-1 Radioligands NK-1 receptors
11. D2/D3 Radioligands
D2/D3 receptors 
12. Glioma Radioligands
Glioma
13. SKCa channel blockers [11C]NML
SKCa channels
14. Arylbenzothiazoles
ß-Amyloid plaques
15. Stilbene derivatives
ß-Amyloid plaques
16. Tetrahydroisoquinoline derivatives
AMPA receptors

Cancer Tracers:

1. Radiolabeled MMP inhibitors Matrix metalloproteinase (MMP) enzymes
2. Radiolabeled O6-benzylguanine analogues DNA repair protein MGMT enzyme
3. Radiolabeled PCV and GCV analogues 
Herpes simplex virus thymidine kinase (HSV-tk)
4. Radiolabeled luciferin derivatives
Luciferase gene
5. [11C]Choline 
Choline kinase
6. [11C]Iressa 
Epidermal growth factor receptor
7. [11C]T138067 and [18F]T138067 Tubulin polymerization
8. [18F]Xeloda
Thymidine phosphorylase
9. [18F]SU11248
Tyrosine kinase
10. Radiolabeled camptothecin derivatives Topoisomerase
11. Stilbene derivatives Aryl hydrocarbon receptor
12. Sulfonanilide analogues
Aromatase
13. Arylbenzothiazoles
Tyrosine kinase
14. Triphenylacetamides Nuclear factor ?-B (NF?-B)
15. [18F]FES 
Estrogen receptors
16. Radiolabeled cyclofenil derivatives Estrogen receptors
17. Tetrahydroisoquinoline derivatives
Glioma
18. Tetrahydroisoquinoline derivatives Selective estrogen receptor modulators (SERMs)

Heart Tracers

1. [11C]HED Cardiac sympathetic innervation
2. [11C]Neostigmine, Edrophonium, Pyridostigmine Acetylcholinesterase (AChE)
3. [11C]HC-15, [18F]HC-15, [11C]HC-3, [18F]HC-3 High-affinity choline uptake (HACU)
4. SKCa channel blockers [11C]NML 
SKCa channels
5. Rivastigmine derivatives Acetylcholinesterase (AChE)

Image Processing and Data Analysis Computing

 Super Computing:

 We have access to the following supercomputers:

 The following computer systems and programs are available in the Image Processing Lab in the Department of Radiology (R2 Building) to aid us in the collection and analysis of data under the proposed project:

  Ten Linux Xeon Duo 64-bit Dual CPU workstations (8 GB to 24 GB RAM, 500 GB Disk Space, DVD-RW)

MR Imaging and Stimulus Delivery Equipment