Equipment - In vivo Translational Imaging
The following is a list of major equipment installed in the Center for Molecular and Genomic Imaging:
Positron Emission Tomography:
We have two dedicated small animal PET scanners with the following specifications:
microPET P4 (Concorde Microsystems Inc.): Commercial animal PET scanner with 22 cm bore, 20 cm transaxial field of view, 8 cm axial field of view. Sensitivity is 2.25% at the center of the field of view with an energy window of 250-750 keV and a timing window of 10 ns (default values). With maximum a posteriori (MAP) reconstruction incorporating accurate system model (standard reconstruction algorithm that we use), image resolution is ~ 1.8 mm isotropically (6 µL volumetric resolution).
microPET II: This system has 90 LSO detector modules in a 16 cm diameter ring, with each detector module containing 14 x 14 individual LSO crystals of size 0.975 x 0.975 x 12.5 mm. The scanner aperture is 15.3 cm, with an 8 cm transaxial field of view and a 4.9 cm axial field of view. Sensitivity is 2.26% at the center of the field of view with an energy window of 250-750 keV and a timing window of 10 ns (default values). With maximum a posteriori (MAP) reconstruction incorporating accurate system model (standard reconstruction algorithm that we use), image resolution is ~ 1.0 mm isotropically (1 µL volumetric resolution).
Each scanner has custom designed mouse holders that help in accurate positioning of the animal and optimal organ separation and animal comfort. The holders have built in heating to maintain body temperature and are connected with an isoflurane gas anesthetic system. We also have dose calibrators for each scanner to measure the injected dose.
IVIS 100 (Xenogen Corp.): We have a commercial high-sensitivity bioluminescence imaging system for whole-body mouse imaging that consists of a Roper 1300 EB cooled CCD camera, a 50 mm f0.95 lens, a IGC-APD Crogenics CRYOTIGER® cryogenic refrigeration unit, Xenogen imaging chamber with standard components, PC running windows with high resolution monitor, control software, 2 copies of the Living Image® analysis software and a Sirius-2 Tube luminometer accessory.
A Siemens SONOLINE Antares imaging system is available within the imaging center including the following transducers: VF14-7, VF10-5, PH4-1, and C5-2. This system is also equipped with the research interface, partially developed at UC Davis. With our research interface, unique pulse sequences can be developed and applied. Peripherals include a black and white printer, color printer, and physiology module for cardiac gating. The system includes support for contrast agent imaging, color flow, Doppler, and all current software releases. Video data and intermediate frequency can also be acquired. Two additional Sonoline Elegra 256 systems with custom research interfaces are also available with probes 7.5 L40, 3.5C40, and 3.5PL28. These systems also have unique pulsing capabilities and the intermediate frequency data can be acquired. A high frequency ultrasound system can also be accessed within the Biomedical Engineering department laboratories. This system can create 2D and color flow images at center frequencies through 50 MHz.
Ex vivo Autoradiography, Fluorescence Imaging and Biodistribution Studies:
Cryostat CM1850 (Leica): The CM1850 microtome allows fresh frozen tissue sectioning with thicknesses from 1 µm up to 60 µm. The thickness can be set in increments of 1 µm (0-10 µm, 2 µm (10-20 µm), and 5 µm (20-60 µm). The temperature in the chamber can be chosen between 0 °C and -35 °C. The maximum specimen size is 55 mm. Tissue samples are fixated and frozen in OCT (TissueTek, USA) by liquid nitrogen or ice spray. In addition, the cryostat has a peltier unit which cools down up to -60 °C. Protocols for histological staining (H&E), immunohistochemistry and autoradiography are set up. A vertical specimen stroke of 59 mm allows sectioning of a whole mouse (up to 6 weeks of age) for whole body autoradiography. Special specimen holders and protocols for whole-body sectioning have been set up.
Phosphor Imager STORM 860 (Amersham Biosciences):
The STORM imager comprises "filmless" autoradiography with storage phosphor screens as well as fluorescence imaging of fresh frozen sections, gels, blotting assays, and microarray imaging. The spatial resolution of the laser is about 100 µm. Since the laser scans the probes perpendicularly, even well plates can be analyzed quantitatively with minimal "blooming effect". The two built in lasers (blue and red) in combination with 520 nm and 650 nm filters make fluorescence imaging of the most common dyes (GFP, Cy5, Cy3, etc.) feasible. Two phosphor screens with a size of 35 cm x 43 cm and an intrinsic resolution of 50 µm are available for autoradiography. The ImageQuant software package allows qualitative and quantitative analysis of the data.
Gamma Counter Wallac 1470 WIZARD (Perkin Elmer, USA):
The Wallac 1470 gamma counter is equipped with 5 detectors, allowing high throughput measurements of tissue samples for biodistribution studies. The well-type detectors, with an almost 4p-geometry, ensure high sensitivity and counting results independent of the exact location of small samples in the tubes. The Wallac 1470 accepts up to 500 tubes with a diameter up to 13 mm in automated mode and up to 17 mm in manual mode. All radioisotopes with gamma energies less than 900 keV can be measured without significant cross talk between the probes. A 10-bit multi-channel-analyzer ensures high resolution data acquisition. The software includes all necessary setup and quality control procedures (e.g. norm, energy resolution, background, detector stability, calibration). The data are readout in ASCII format and imported in a custom EXCEL worksheet for further calculations such as "% injected dose per gram tissue".
Biomedical Cyclotron and Radiochemistry:
The laboratory contains an RDS 111 (CTI Inc.) 11 MeV negative ion biomedical cyclotron, primarily for the production of 18F and 11C to support PET and autoradiography imaging studies. Radiochemistry labs have 3 VonGahlen research hot cells all with tweezer manipulators, glove ports as well as full front and rear door access, 1 hot cell with a set of CRL manipulators as well as a set of dual minicells. Each hot cell houses a shielded dose calibrator (Capintec, CRC-15). Automated modules for remote synthesis include SYNTHIA, an automated synthesis unit for C-11 chemistry, and the GE nucleophilic and electrophilic boxes for fluorination chemistry. Analytical equipment includes 2 Beckmann Gold HPLC systems with on line diode array detection (126 detector), UV detection (116 detector) and radiochemical detection (3200 flow cell, Bioscan) as well as an Agilent 6890 gas chromatography system and an AR200 thin layer chromatography scanner (Bioscan).
There is also a dedicated tissue culture area for radioactive cell labeling studies to be performed. This houses a Class II Type B2 biosafety cabinet (Thermo Forma), a Sanyo CO2 incubator (Model MCO-17AC), an Eppendorf centrifuge (model 5702) and a Zeiss inverted microscope (Televal 30).
The cyclotron and radiochemistry facilities are dedicated to preclinical animal studies and are not used for human studies. 64Cu will be obtained from Washington University, St. Louis. The production of 64Cu at Washington University School of Medicine is supported by NCI grant R24 CA86307. 18F-FDG will be obtained from PETNET in Sacramento (13 miles away) as in small quantities, it is cheaper to buy it commercially than to make it ourselves.
The NMR facility houses several NMR spectrometers, and relevant to this proposal, a Bruker Biospec 7.05T (300 MHz) horizontal bore system and a Bruker Advance 9.4T (400 MHz) vertical bore system, both equipped for in vivo small-animal imaging and spectroscopy. Both systems utilize Bruker’s Paravision imaging software, which incorporates all standard as well as recently developed imaging protocols in a user-friendly interface that also allows reasonably sophisticated image processing. The Biospec 7T has two gradient sets. The larger is 125 mm i.d and is capable of ~10 g/cm gradient strength. The smaller (microimaging) gradient set is 60 mm i.d and is capable of gradient strengths up to 100 g/cm. There are two Bruker volume proton imaging coils of 70 mm i.d for use with the large gradient set; one coil can work with a actively decoupled surface coil for use with volume coil transmit/surface coil detect experiments. There are two Bruker proton imaging coils of 35 mm i.d for use with the small diameter gradient set. There are additional coils which have been built here for custom experiments such as 23Na imaging. A wide variety of non-magnetic animal holders have been constructed in-house for MRI experiments, along with various customized equipment for animal anesthesia, ventilation, etc. Physiological (respiratory, cardiac) gating of the MRI experiment (when needed) is done with the Bruker PhysioTool interface to the Paravision MRI software. The Biospec 7T is primarily used for imaging but is also utilized for spectroscopy. It has a broadband (15N-31P) Rf channel in addition to proton, and a number of surface coils have been built in house for spectroscopy of nuclei such as 13C, 23Na, 31P, and 19F.
The 9.4T scanner has a single gradient set of mm i.d, capable of ~100 g/cm. It is equipped with a total of eight imaging coils: 2.5 mm proton solenoid, and birdcage type coils of 10 mm proton, 10 mm 13C/1H, 10 mm 31P/1H, 15 mm 31P/1H, 20 mm 13C/1H, 20 mm 31P/1H, and 25 mm proton. The double tuned coils are for image-guided localized spectroscopy experiments. The 9.4T scanner also can be fitted with a wide variety of custom-built animal handling equipment. It is a three Rf channel instrument.
The NMR Facility has both the necessary expertise and equipment for maintenance, repair, and modification to its systems. The Facility possesses machine tools, frequency synthesizers, oscilloscopes, rf amplifiers, a vector impedance meter, a digital LCR meter, and network analyzer, along with all routine test and repair equipment. In addition, the Facility has its own machine shop for building surface coils and animal holders. Soldering stations, a milling machine, and band saw are available. The center runs a practical laboratory course on using its NMR spectrometers and MR imaging systems for graduate students and postdoctoral fellows, enabling them to learn to both run the instruments themselves and understand the principles involved in guiding the choice of parameters for successful data collection. The Facility can also train users one-on-one throughout the year.
The following is a list of major equipment installed in the Center for Imaging Sciences in the School of Veterinary Medicine.
X-ray Computed Tomography (CT):
A General Electric fx/i Helical CT scanner was installed in 2002 for cross-sectional imaging of small and large animals as well as anatomical specimens and other inert objects. This is a standard clinical scanner with a 70 cm gantry, 30 degree gantry tilt, solid state detectors with a spatial resolution of 0.38 mm, a 36 kW high frequency generator and scan time of 0.7 seconds. In addition to the 450 lb rated standard patient table, a custom designed large animal table has been installed and linked to the table drive to allow for imaging of subjects up to approximately 2,000 lb. The system is fully DICOM compliant, has a large capacity internal drive data storage and interfaces with a custom designed PACS system for imaging data storage and retrieval and viewing. Imaging data is stored long term on a large capacity mirrored server system.
This system provides both analog and digital radiographic acquisition as well as digital fluoroscopy capability. This new system is fully DICOM compliant and is also integrated into the facility’s PACS system for image archival. This system is used for survey and contrast radiographic imaging of both small and large animals as well as specimens. The CIS also maintains two high-resolution radiographic units (Faxitron) for ultra-high detail specimen imaging.
Magnetic Resonance Imaging (MRI):
The General Electric superconducting 1.5 Tesla Signa Horizon HiSpeed magnetic resonance imaging system with and EchoPlus applications package with high performance shielded gradients with amplitude/strength of 23 mT/m and rise time/speed of slew rate of 77 T/m/s. The system has a 60 cm aperture and field-of-view options ranging from 2-48 cm and slice thickness capability of 0.1 mm using 3D acquisition sequences. RF coils include, body, quadrature head, knee, phased array CTL spine coil, dual 3 inch and 5 inch TMJ coils and a flexible array coil. Capabilities include conventional anatomical imaging, diffusion/perfusion, H spectroscopy (single and multiple voxel) and functional imaging. The system is fully DICOM compliant, has a large capacity internal drive data storage and interfaces with a custom designed PACS system for imaging data storage and retrieval and viewing. Imaging data is stored long term on a large capacity mirrored server system. Additional equipment includes an Aestiva 5 (Datex Ohmeda) magnetic resonance compatible anesthesia machine and Millennia 3155MVS (In Vivo) telemetry systems for monitoring temperature, heart rate, direct and indirect blood pressure, sp O2, capnography and anesthetic agent concentration.
Diagnostic Ultrasound (US):
The CIS maintains an ATL (Philips) HDI 5000 Ultrasound Unit for two-dimensional real-time imaging, pulsed and continuous wave Doppler, color Doppler, Power Doppler and ultrasound-guided interventional procedures. The system includes a wide range of phased-array and linear transducers for routine and high-resolution imaging. The system is fully DICOM compliant and is also connected to the PACS network and image workstations for image archiving and review.
Nuclear Medicine (NM):
The CIS maintains a rectangular large field-of-view gamma camera and dedicated computer system (Technicare Omega 500) for planar scintigraphic imaging of small and large animals using a variety of radiopharmaceuticals and radionuclides. A hot lab is also maintained on premises for preparation and handling of radiopharmaceuticals. Other instrumentation includes a well counter for quantification of tissue or fluid sample radioactivity following administration of radiotracers.
We have two linear accelerators available for research use. The first is a Varian Clinac 4MV linear accelerator. The second is a Clinac 2100C with dual 6 and 10MeV photon energies and electron energies from 6-20MeV available. The treatment planning system available is Varian's Eclipse 3-D planning system which includes 3-D treatment planning software including contouring, image registration, beam placement, plan review, and plan templates. Also included are a dose calculation server, 3-D dose calculation client, 2-D calculation client, Beam configuration, Helios inverse treatment planning, electronic compensation with dMLC and planar compensation and is capable of CT and MR image import. We also have a SR-90 ophthalmic applicator.
CIS also maintains gas anesthesia machines and scavenging systems for both large and small animals, a fully equipped minor surgery facility, an array of monitoring equipment for anesthetized subjects, automated pressure injectors for radiographic, CT, and ultrasound applications, calibration phantoms for quantitative CT studies and other ancillary equipment.