NeuroNET Research Center


UT Medical Center Facilities

Contact: Dr. Jon Wall, Professor of Medicine
Director, Amyloid and Preclinical Molecular Imaging Laboratory
University of Tennessee Graduate School of Medicine
1924 Alcoa Highway
Knoxville, TN 37920
Tel:  (865) 305 5447
Imaging Lab: (865) 305 8497
Fax: (865) 305 6865
JWall@mc.utmck.edu

Alan Stuckey (astuckey@utmck.edu)

Preclinical and Diagnostic Molecular Imaging Laboratory
Amyloidosis and Cancer Theranostics Program
Anesthesiology Research

Preclinical and Diagnostic Molecular Imaging Program at the University of Tennessee Graduate School of Medicine, Knoxville

In September 2005 the Preclinical and Diagnostic Molecular Imaging Laboratory (PDMIL), was constructed in the UT Medical Center immediately below a suite of radiochemistry laboratories, the cyclotron and a, high-resolution, low-count research mCT PET scanner with a 52 cm axial field of view (Siemens Medical Solutions, Knoxville).
The imaging facility boasts 4 imaging suites the first housing a microCAT II +SPECT hybrid scanner (Siemens Preclinical Solutions, Knoxville), the second, a P4 microPET (Siemens Preclinical Solutions) and lastly, a trimodality Inveon SPETC/PET/CT system (Siemens Preclinical Solutions) in suite 3.  All suites are equipped with oxygen and vacuum lines and a full anesthesia (vaporizer) station (Summit Medical, Seattle, WA) with heated mouse chambers and pads for live animal imaging.  A BioVet™ system (Summit Medical) for monitoring respiration rate, ECG, body temperature provides a signal for cardiac PET gating or respiratory CT gated imaging.  The PDMIL has a dedicated image analysis office (computer lab) with 2 seats of Amira 3.1 or higher (TGS, San Diego, CA), a real-time CT reconstruction station, and 2 seats of Inveon research Workplace software (Siemens Preclinical Solutions).  Data is stored securely on a 7 TB server with RAID configuration that is backed up to tape at a centralized location.
The animal preparation and analysis laboratory contains a gamma counter for biodistribution studies and areas for tissues collection and storage. An Animal Care and Use Committee (ACUC)-approved satellite holding facility, with 3 rooms and preparation area is also located in the PIL.  This permits the housing of up to 3 different species indefinitely to allow time for longitudinal studies and using tracers with extended clearance rates.

The microCAT II +SPECT (currently needs repair) is a fully shielded high-resolution hybrid x-ray (CT) and single photon emission computed tomography (SPECT) in vivo imaging system.  The x-ray source is a 40 W, tungsten anode, 35-80 kVp source mounted on a rotating gantry capable of step-and-shoot acquisition over the full 360° around the subject positioned on the animal bed.  The x-ray detector is a 2048 ´ 3096 pixel CCD coupled to a high-resolution phosphor screen via a fiber optic taper.  It boasts a 61 ´ 91 mm field of view and a resolution of 27 mm.  The digitized images are 12 bit depth and the detector dynamic range when using 2 ´ 2 or 4 ´ 4 binning (standard in our mode of operation) is 72 dB.  The CT data are reconstructed using the cone-beam Feldkamp algorithm, although iterative reconstruction methods are being developed and evaluated in our program.  Real time reconstruction is performed using the Cobra software package (Exxim Computing Corporation, Pleasanton, CA) running on a dual-processor Dell workstation with 8 GB of memory.  A standard 512 ´ 512 ´ 768 (4 ´ 4 binned image) volumetric reconstruction onto 77 mm3 voxels usually completes within 2 minutes after the final projection of a 360-projection acquisition (1° azimuths).  Offline reconstruction can alternatively be conducted using an in-house developed parallel implementation of the Feldkamp algorithm.  This code is capable of providing volumetric images of the same dimensions as above in less than 5 mins using a small group of PCs.

The SPECT detectors are mounted on stepper motor driven stages so that they can be readily retracted form the CT field of view.  Detectors are available optimized for either high or low energy photon emitting nuclides and are housed within a 10 mm-thick casing of 6% antimonial lead.  For low energy nuclides (< 170 KeV; such as 125I, 123I, and 99mTc) we employ two large-area detectors mounted facing each other on the rotating gantry and at 90° to the x-ray source and detector.  The detector heads are 150 ´ 150 mm2 and composed of 5 mm-thick sodium iodide (NaI) crystals with a 1.5 ´ 1.5 mm or 1.25 ´ 1.45 mm crystal spacing.  For high energy photon imaging (up to 300 KeV, e.g. 111In) similarly sized detectors (150 ´ 150 mm2) are available with 10 mm long NaI crystals and a crystal spacing of 2.2 ´ 2.2 mm.

For both sets of detectors parallel, pinhole and multi-pinhole collimator configurations are available.  Composed of 12 mm-thick 6% antimonial lead, the collimators can be fitted with pinholes made of 15 mm-thick tungsten containing either a 0.5, 1.0, 2.0, or 3.0 mm diameter aperture.  For our standard mouse scans using ~ 100 mCi of tracer we use the 2.0 mm pinhole collimators on both detectors, which provides a modest degree of magnification and statistically good count rates (even when each detector is reconstructed independently).  The SPECT data from each detector may be reconstructed either independently or following summation as a single ("multiple-detector") file. Reconstruction is performed post-acquisition using a dedicated ordered subset expectation maximization (EM) algorithm.  A 52 ´ 52 ´ 68 image typically computes in approximately 2 minutes.  Further upsampling of the image to smaller voxel sizes is normally performed post-reconstruction using the Lanczos filtering kernel in Amira.

Inveon SPECT/PET/CT: The Inveon high resolution SPECT detectors deliver sub-millimeter resolution with the largest pixelated detector heads in the industry. The SPECT module detects gamma rays from 30 keV to 300 keV, providing sensitivity to the most widely used research and clinical single photon isotopes.  The detector head has a large active area (150 mm x 150 mm) that permits greater pinhole magnification, improving sensitivity while maintaining a large field of view (FOV) while maintaining small detector crystals (2 mm x 2 mm x 10 mm) to provide high intrinsic detector resolution.  The Inveon collimators are numerous and include 0.5, 1.0, 2.0, and 3.0 mm single pinhole collimators, a LEAP (low-energy all-purpose) parallel hole collimator for planar imaging and a pair of mouse brain or mouse whole-body multi-pinhole collimators.
Multi-pinhole image reconstruction and calibration software permits the production of high resolution images in a fraction of the time required with traditional collimators.

The Inveon PET system is a third generation PET imaging system that incorporates several key technical features and advancements that deliver exceptional image quality and quantitative accuracy.  The detector design in Inveon includes an innovative high efficiency light guide that delivers more photons to the photomultiplier tube, thereby improving energy and timing resolution. The detector also features a large 20 x 20 crystal array that increases the scanners axial field of view (FOV) and improves system sensitivity. With minimal gap between crystal elements and a 92% packing fraction, the net result is a PET system with exceptional spatial resolution and sensitivity.
The new Inveon data processing architecture improves PET count rate performance, energy resolution, and timing resolution. Count rate performance is improved through a store and forward coincidence processing technique that virtually eliminates the electronic deadtime associated with traditional multiplexing architectures. Improved energy resolution using high speed analog-to-digital converters and improved timing resolution through the use of 312 ps time bins, results in a PET system with exceedingly high singles and coincidence data rates, as well as, excellent random and scattered event rejection.  Attenuation Correction is achieved using a rapidly-acquired low resolution CT dataset.

The Inveon CT has an 80 W, tungsten anode, 35-80 kVp standard source (less than a 50 micron focal spot) that provides a high X-ray flux for high speed scanning and a large cone angle for high magnification studies. The maximum achievable resolution with this X-ray source and the standard detector is 40 microns. Typical scan times are less than 5 minutes.  The 125 mm Detector: The detector has 3072 x 2048 pixels and may be configured for a FOV as large as 8.4 cm x 5.5 cm. With a 12 bit deep readout of the raw data, this detector has a dynamic range of 69 dB (1 x 1 binning) to 72 dB (2 x 2 and 4 x 4 binning), providing excellent signal-to-noise ratio.

Data is reconstructed in real time on a dedicated high speed platform during a scan. The real time reconstruction engine allows reconstruction to start as the projection data is being acquired.

In addition to the small animal imaging systems described above, for larger animals we have recently added a clinical research PET/CT to the floor above the PDMIL.  The Biograph 6 (Siemens Medical Solutions USA, Inc.) is a dedicated research PET/CT for use in large animal and human studies. This is an LSO-based PET system with a 6-slice CT. The system boasts a 21.6 cm axial PET FOV with TrueV™ technology and a 190 cm patient scan range. This extended FOV also provides an increased sensivity and count rate performance. This system is equipped with HD•PET™ enabling point spread function-based reconstruction that provides improved resolution and a uniform FOV.

The CT system has an isotropic resolution of 0.33 mm with z-Sharp™ technology. Data from the CT unit are automatically registered to the acquired PET data. The CT data is used for attenuation and scatter correction enabling quantitative PET imaging with anatomical CT imaging.

Radiolabeling Area:  We have a dedicated radiolabeling area for the preparation of radio-iodinated tracers for human use.  The room contains a positive pressure sealed inner room that has a dedicated sterile-filtered air flow.  This inner area has a chemical cabinet in which we perform the radiolabeling.  This room also houses (outside the sterile area) a spectrophotometer for assessing the concentration of radiolabeled biological molecules, a certified well counter (Capintec), 37° incubator for performing sterility testing, a small refrigerator, and bench space.  GLP-grade peptide p31 will be radiolabeled in this area for use in Shar pei dogs.

Summary of Major Equipment Preclinical and Diagnostic Molecular Imaging Program at the University of Tennessee Graduate School Of Medicine, Knoxville

  • A microPET P4 as well as MicroCAT II + SPECTmCT clinical PET/CT, and Inveon trimodailty SPECT/PET/CT, all described in detail above.
  • 1480 Wallac Wizard 3 Automatic Gamma counter (Perkin Elmer) – A single detector universal counter with a 75 mm solid lead shield. It counts vials or tubes of any shape up to 20 mL in volume and up to 28 mm in diameter. There are up to 20 simultaneous counting regions and its energy range is up to 2000 keV.
  • Capintec CRC 15 PET digitally controlled dose calibrator.
  • Anesthesia apparatus for delivering isoflurane:oxygen anesthesia for small animal imaging.
  • BioVet apparatus for monitoring for small animal respiration rate, ECG, temperature and provided an output trigger for gated PET and CT image acquisition



 

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