UW Small Animal Imaging MISSION The overall mission of the UW Small Animal Imaging Facility is to provide innovative state-of-the-art, affordable, noninvasive, high-resolution in-vivo and ex-vivo imaging support to University of Wisconsin investigators and cancer center members who utilize small animal models in their research. Consultation The facility director in conjunction with the micro-IRAT provide consultation with investigators about imaging methodologies most suited to answer their biological questions. Suggestions typically include which modality(s) may be the most appropriate, whether or not contrast agents will provide additional information and if so which ones are most appropriate, the degree of spatial resolution needed, choice of anesthesia, timing of scanning, inclusion of appropriate controls, and statistical relevance. Investigators are able to select various levels of support ranging from image acquisition alone, to acquisition and reconstruction, to image interpretation and finally to media presentation. It is our intent to acquire the data set and then to educate the investigators to be able to work up and interpret the images on their own. We provide Amira (v4.1, TGS, Inc, San Diego, CA) based workstations operating on a 64-bit Windows platform (XP Pro-64) which is both user friendly and extremely powerful in terms of 2- and 3-D image viewing, manipulation, and quantitative analysis of large files. We have a Siemens Inveon Research Workplace 3D image image fusion and analysis workstation. This state-of-the-art workstation, which is based on a 64-bit/16GB RAM Windows platform, permits sophisticated 3-D visualization and manipulation of multiple data sets in a single image as well as analysis of static, gated, and dynamic data as well as output in DICOM format for use with other imaging platforms. Anatomic MicroCT Scanning We have utilized a commercial first generation microCT scanner since 2001. In December 2005 we acquired a new large field-of-view MicroCAT-2 from Siemens. The new scanner was funded entirely by an NCRR shared instrumentation grant awarded to Dr Weichert. It is equipped with a large fieldof-view detector, thus allowing high resolution scanning (18 micron) of rats up to 300 grams. The system is equipped with a rodent isoflurane gas anesthesia system and physiologic monitoring system which allows image gating. Functional MicroPETand Hybrid MicroPET/CT Scanning In late December, 2006, we received the first Inveon microCT/microPET hybrid scanner from Siemens. This first hybrid scanner coupled with our own proprietary cell-selective imaging and contrast agents affords our investigators unique disease detection and evaluation technologies which can only be provided at UW. This new scanner provides unsurpassed PET sensitivity (>10%), resolution (1.2 mm), and axial field of view (13 mm) as well as 15-micron spatial CT resolution and real time image reconstruction. This system is equipped with a built in BioVet physiologic monitoring system which permits gated image acquisition and animal monitoring, integrated isoflurane anesthesia system, and internal infrared video camera which allows visual monitoring of animals during scan acquisition. High Resolution MRI Scanning Installation of a Varian 4.7T small animal scanner was completed in April of 2007. The horizontal bore imaging/spectroscopy system gives us the capability to scan rodents up to 600 grams with an inplane resolution on the order of 50 microns. The system is also equipped with a rodent isoflurane gas anesthesia system and physiologic monitoring system that allows image gating. It has broadband capability allowing us to scan a variety of nuclei including 1H, 31P, 19F and 13C. T1 and T2 anatomical scans are possible as well as the creation of T1, T2 and T2* maps. The system is also capable of functional MRI (EPI), diffusion and diffusion tensor imaging, localized spectroscopy (STEAM and PRESS) as well as chemical-shift imaging, and perfusion imaging with Gd-based contrast agents. These specifications allow investigators to visualize and quantify a variety of moieties and processes including metabolites (NMR spectroscopy), anatomical structures, tumor morphology, blood flow/vessels, fiber pathways, drug effects, brain activity, and heart motion. In early 2008, we became one of only 5 institutions in the US to receive a commercial dynamic nuclear polarization system from GE. This system allows rapid in vivo investigation of biochemical events enhanced with carbon-13 labeled substrates at enhanced sensitivity levels. New Micro-Imaging Suite We have enjoyed tremendous institutional support for establishing a first rate small animal imaging facility and will be centralizing our efforts into a newly designed 2000 gsf facility specifically designed for small animal and molecular imaging in the new WIMR (Wisconsin Institutes for Medical Research), building, a 7-story research building attached to the hospital and adjacent to the School of Pharmacy and the Waisman Research Institute. This new facility houses the microCT and microCT/microPET hybrid scanners, optical (currently fund raising) and Visual Sonics bioacoustic microscopy systems, 4.7T MRI and associated hyperpolarization apparatus. Several Siemens (IRW) and Amira based image reconstruction and analysis workstations are also located here. An important aspect of this new facility is the adjacent animal holding room which contains new passively ventilated rodent housing racks (Animal Care Systems, Inc) for holding radioactive animals and those involved in longterm tumor monitoring studies. The new WIMR complex is strategically located adjacent to the new animal vivarium and non radioactive animals involved in imaging studies are housed there. This preclinical and molecular imaging suite is designed with translational research in mind as supported by the fact the microCT/microPET hybrid is located adjacent to the new research clinical GE 64-slice PET/CT hybrid scanner. Also located adjacent to the small animal imaging suite will be the cyclotron and radiochemistry facilities which will provide expertise on PET agent synthesis in a collaborative or fee for service basis. The small animal imaging director currently coordinates PET synthesis with Drs. Nickles and DeJesus in the Medical Physics Department. Agents may alternatively be acquired from commercial sources such as PET Net or IBA Molecular and the source will ultimately be determined by price, availability, and quality of the requested PET agents. Contrast Agent Development Our investigators are well known in the development of cell-selective contrast and imaging agents useful for CT, MRI, and nuclear medicine. Images from our small animal imaging lab are currently included on the preclinical molecular imaging websites of both GE Healthcare and Siemens, the two major producers of microCT, microPET and hybrid scanners. Moreover, two agents developed in our labs, FenestraTM VC and LC, are now commercially available to the world-wide research community from Advanced Research Technologies (ART, Montreal). In order to preserve the pathological integrity of the current animal facilities, investigators are required to transfer their animals to one of our general microimaging protocols prior to transferring them to our facility. Once they arrive for scanning they remain in our holding area until the end of the experiment whereupon they are euthanized or placed into a quarantine room. Under no circumstances are the animals allowed to leave our facility for placement back into their original SPF housing area. We have invested in the latest passively ventilated rodent cage systems in order to ensure healthy maintenance of the animals. Animals are allowed to be housed in our facility for long periods of time as required for longitudinal studies. Dr. Weichert is a member of the Medical School animal care committee and Dr. Moser actually serves as its director. The policies of the facility will be established and governed by an oversight committee comprised of imaging scientists and physicists as well as several cancer biologists and veterinarians. At least one member of the oversight committee will be a current member of the Medical School animal care committee. Administrative support will be provided by UWCCC management and personnel. Oversight The small animal imaging facility oversight committee consists of Jane Wegenke, Associate Director of the Cancer Center, Robert Jeraj, Assistant Professor of Medical Physics, Biomedical Engineering, and Human Oncology, Amy Moser, Associate Professor of Human Oncology and Director of the UW Medical School Animal Care Committee, Beth Meryerand Associate Professor of Medical Physics and Radiology, Jamey Weichert, Associate Professor of Radiology, Medical Physics and Pharmaceutics, and Calvin Patten, the veterinarian who oversees the facility. UWCCC Small Animal Imaging Facility Scanners and Floorplan Siemens Inveon microPET/CT Siemens MicroCAT-2 Varian 4.7T MRI Hot Lab MRI Optical/US MicroPET/CT Animal Prep New Vivarium MRI: 4.7T Varian and GE Hyperpolarizer system Animal Prep: Cell culture, radioactive animal holding (rats and mice), gamma counter, tissue distribution MicroPET/CT: Siemens Inveon Hybrid Scanner and Siemens MicroCAT-2 CT scanner both with large field of view detectors. Two Siemens IRW advanced imaging work stations. Optical/US: Will hold in vivo optical scanner and Visual Sonics high-frequency US system Hot lab: Radioactive doses stored, drawn, and assayed in this shielded room. New Vivarium: Will house rodents (B-level) and non human primates (Level 1).