Abstract--A small animal SPECT system has been developed for acquiring in vivo images of the bio-distribution of radiopharmaceuticals in unrestrained, unanesthetized small animal models. This system uses two dedicated gamma-ray cameras and an infrared based animal position tracking system mounted on a rotational gantry with an infrared transparent mouse burrow in the center. The original implementation of this system had two compact gamma cameras with an active area of 5 cm x 5 cm. Two new gamma camera detector heads with active areas of 10 cm x 20 cm have been built, tested and installed in the SPECT gantry to replace the 5 cm x 5 cm detectors. The new gamma cameras are based on pixellated NaI(Tl) crystal scintillator arrays, coupled to arrays of compact position- sensitive photomultiplier tubes (PSPMT) to achieve high spatial resolution in a compact, low profile device. A novel cost- effective readout is utilized. The two detector heads are based on a 4 x 8 array of Hamamatsu R8520-C12 (1” x 1”; 6X x 6Y anodes) position sensitive photomultiplier tubes. Each PSPMT array is coupled to a pixellated 10 cm x 20 NaI(Tl) scintillator crystal array with individual crystal elements of 2 mm x 2 mm x 15 mm in size and a septum of 0.25 mm between elements. Samples of phantom and animal studies are presented. I. INTRODUCTION E are developing a new methodology for imaging unrestrained, non-anesthetized animals in which the animal position is recorded during image acquisition and the gamma-ray image data is registered to the time-varying animal orientation[1, 2, 3]. The goal of the project is to develop tools and techniques to acquire high-resolution volumetric Manuscript received October 21, 2004. The Southeastern Universities Research Association (SURA) operates the Thomas Jefferson National Accelerator Facility (Jefferson Lab) for the United States Department of Energy under contract DE-AC05-84ER40150. This work is supported by the DOE Office of Biological and Environmental Research in the Office of Science through the DOE Medical Imaging program and from the DOE Office of Nuclear Physics. A.G. Weisenberger, B. Kross, S. Majewski, V. Popov, M.F. Smith, B. Welch and R. Wojcik are with Jefferson Lab, Newport News, VA, USA, (telephone: 757-269-7090, e-mail: drew @jlab.org). J. Baba, S. Gleason, J. Goddard and M. Paulus are with Oak Ridge National Laboratory, Oak Ridge, TN, USA, (telephone: 865-576-6589, e- mail: babajs@ornl.gov). S.R. Meikle is with the University of Sydney, Sydney, Australia (telephone: +61 2 9351 9519, e-mail: smeikle@fhs.usyd.edu.au). M. Pomper, Johns Hopkins University School of Medicine, Baltimore, MD, USA, (telephone: 410-955-2789, e-mail: mpomper@jhmi.edu). SPECT images of the head region of an unrestrained mouse and to register the image volumes with previously acquired microCT (50 – 100 micron resolution) data sets. The mouse will be anesthetized during the microCT data acquisition. The microCT images will serve as a reference frame for the SPECT data. An infrared (IR) based tracking system we have developed provides the position and pose of the mouse’s head during imaging. Two IR cameras are used in a stereo approach to determine 3D point locations of three markers that have been glued on three locations on the animal’s head. The markers are retro-reflective spheres. During acquisition of the SPECT scan, the mouse will be allowed to move freely in an IR transparent cylindrical mouse burrow 3 cm in diameter that is aligned with the center of rotation of the gantry and located 2 cm from the gamma cameras. The gamma camera image acquisition, the IR tracking system and the gantry motion are each controlled by a separate desktop Dell computer. Gamma event data, animal tracking data and gantry position data are all stored on their respective computers time stamped via a common external clock. The data files are later used to reconstruct SPECT images to the small animal reference frame based on a previously obtained microCT of the animal. II. DETECTOR HEADS We have reported before [1] on the development of a SPECT system composed of two prototype SPECT gamma cameras utilizing position sensitive photomultiplier tubes (PSPMTs). The prototype detector heads were based on the Hamamatsu R2487 PSPMT in which the active area of each detector head is 5 cm x 5 cm. The PSPMTs are coupled to NaI(Tl) arrays also obtained from Saint Gobain in which the crystal elements are 1 mm x 1mm x 5mm in size. There is a 0.25 mm septum between each element. The 5 cm x 5 cm active areas of these initial gamma cameras are too small to image a whole mouse and to accommodate a reasonable amount of animal motion. While the size was sufficient to allow us to test the concept of animal tracking with simple phantoms, it was clear larger detector heads were necessary to facilitate actual mouse imaging. We are reporting here on the successful construction, testing and installation of two new 10 cm x 20 cm detector heads. Dual Low Profile Detector Heads for a Restraint Free Small Animal SPECT Imaging System A.G. Weisenberger, J.S. Baba, B. Kross, S. S. Gleason, J. Goddard, S. Majewski, S.R. Meikle, Senior Member, IEEE, M.J. Paulus, M. Pomper, V. Popov, M.F. Smith, Member, IEEE, B.L. Welch and R. Wojcik W