The Yale University PET Center is a state-of-the-art molecular imaging facility. Resources include a GE PETtrace cyclotron, with targetry for producing positron-emitting isotopes such as C-11, F-18, N-13 and 0-15; a radiochemistry laboratory with 12 hot cells and modules for the production of a wide variety of radiotracers; a Siemens mCT whole body PET/CT scanner, a Siemens HR+ whole body scanner; a Siemens HRRT scanner for imaging the brain and small animals; and 2 Focus-220 small animal scanners. The Center also has a fully equipped laboratory for blood and metabolite analyses and an image analysis laboratory for investigators, with several workstations running image analysis software applications. Details for each of these resources follow:
Radiotracer Chemistry Laboratories
The Radiotracer Laboratory Complex at the PET Center, Yale University School of Medicine, is fully equipped for radiotracer synthesis with 4 mini hot cells, 4 full size hot cells, and automated or remote synthesis devices for preparation of radiotracers labeled with C-11, F-18, N-13 and O-15. There is a water target (H216O) for the production of N-13 ammonia and a water target (H218O) for the production of [18F] fluoride, as well as nitrogen gas targets for the production of carbon-11 and oxygen-15, and an automated system for the production of [11C]cyanide. The lab is also equipped with several automated synthesis modules from GE Medical Systems, including Microlab for the production of [11C]methyl iodide, two FXc-Pro methylation boxes for synthesis of various C-11 tracers, an FDG synthesis machine and two F-18 synthesis modules (nucleophilic substitution box and electrophilic substitution box). Another automated synthesis module for C-11 labeling is the Bioscan Autoloop. A semi-automated module for carrying out multi-step synthesis has also been set up. The Radiotracer Laboratory has TLC scanners, HPLCs with UV, radioactivity detectors, LC/MS, and counting equipment (ion chambers, pin diode detectors and well counters). There are also facilities for the preparation of sterile radiopharmaceuticals, including pyrogen burning ovens and laminar flow hoods, and for LAL testing of pyrogens, which is performed in-house. Cold chemistry laboratories in the LMP building are equipped for the purpose of developing new synthetic strategies for C-11 and F-18 labeled radiotracers and to synthesize the unlabeled precursors required for radiotracer development and production.
The PET Center has a new GE PETtrace cyclotron for radioisotope production, with 19 MeV protons and 10 MeV deuterons for production of [11C]cyanide and [11C]methyl iodide (GE Medical Systems unit). This cyclotron has a total of six targets. In addition to the two C-11 targets, it also has a target to produce O-15, a water target (H216O) for the production of N-13 ammonia, a water target (H218O) for the production of [18F]fluoride, and a gas target for the production of [18F]F2.
PET Imaging Suites
The PET Imaging suites have one whole body PET CT System (Siemens mCT), one whole body PET scanner (Siemens HR+ with 32 rings and 63 planes with a resolution of ~ 5 x 5 x 5 mm at center of field of view), one dedicated brain scanner (Siemens HRRT, 104 rings, 207 slices with resolution of better than 3 x 3 x 3 mm) and two small animal PET scanners (Focus 220, 48 rings, 95 slices with a resolution of ~ 1.4 x 1.4 x 1.4 mm at center field of view). Adjacent to each scanner room are patient prep and post-scan rooms. The HR+ has a SUN workstation dedicated to image acquisition, reconstruction, and archiving. The HRRT acquires its list-mode data on a high-end PC with 1 TB of disk. The list-mode data files are transferred over the local Gigabit network (behind a hardware firewall) to a dedicated Linux cluster with 58 nodes and 136 processors (3.0-3.2 MHz) and ~ 17.5 TB of disk storage. Images are reconstructed with the MOLAR algorithm (Motion-compensation OSEM List-mode Algorithm for Resolution-recovery Reconstruction). Subject motion information is collected with a Vicra (NDI, Canada), which records head motion at a rate of up to 20 Hz. These are stored in a time-synced file and used by MOLAR to correct head motion. The Focus 220 also acquires its list-mode data on a high-end PC, which is also used to reconstruct images using the manufacturer’s software. Continuous bed motion and dual-gated acquisitions are features of the Focus 220.
For both the HR+ and HRRT, final images are converted to DICOM format and saved on the 17.5 TB disk farm. The disk farm is backed up to tape nightly. Image processing is performed on one of 4 Linux (Redhat WS4) workstations housed in a data processing room connected to the network with NFS mounts to the 17.5 TB disk array. These systems may be used at their consoles or over the network via X windows. Image data are accessed via the HAVEN image database using scripts and programs employing the commercial programs IDL and MEDx. All data are identified with a code created at the time of the subject's first PET scan. Patient identification can only be obtained from password restricted access to the HAVEN database. Programs and scripts developed for image processing include PET-MR image registration, region-of-interest placement (on PET or MR), time-activity curve creation, input function creation (see Metabolite lab, below), mathematical modeling routines to create parametric images of flow, metabolism, binding potential, etc. and partial volume correction.
Blood/Metabolite Analysis Lab
An analytical laboratory is adjacent to the PET Imaging suites, with pass-through doors to allow direct passing of samples. This lab includes two Perkin Elmer Wizard gamma counters, scales, centrifuges, blood glucose analyzer and HPLC equipment to analyze plasma samples for unchanged radiotracer, enabling generation of input functions required for kinetic analysis and image quantization. As appropriate, all devices are connected to the network (some via a terminal server) to allow direct reading of the data by IDL programs on the Linux machines.
Adjacent to the scanner suites is a hot lab for dose preparation and assay. The Capintec CRC-15PET is connected to a terminal server to allow web-based reading of activity in the syringe. These measurements are automatically stored in the HAVEN database and can be displayed in real time via web browsers throughout the facility, with the current activity calculated using the appropriate decay constant.
The Yale University PET Center research facility is located at 801 Howard Avenue. Offices for the scientific and professional staff are located in the PET Center and in a newly renovated section of the Laboratory for Medicine and Pediatrics (LMP) at 15 York Street. Construction is underway for an additional research section that will also be housed in the LMP building.