We present a new rodent SPECT system (U-SPECT-II) that enables molecular imaging of murine organs down to resolutions of less than half a millimeter and high-resolution total-body imaging. Methods: The U-SPECT-II is based on a triangular stationary detector set-up, an XYZ stage that moves the animal during scanning, and interchangeable cylindric collimators (each containing 75 pinhole apertures) for both mouse and rat imaging. A novel graphical user interface incorporating preselection of the field of view with the aid of optical images of the animal focuses the pinholes to the area of interest, thereby maximizing sensitivity for the task at hand. Images are obtained from list-mode data using statistical reconstruction that takes system blurring into account to increase resolution. Results: For 99m Tc, resolutions determined with capillary phantoms were smaller than 0.35 and 0.45 mm using the mouse collimator with 0.35-and 0.6-mm pinholes, respectively, and less than 0.8 mm using the rat collimator with 1.0-mm pinholes. Peak geometric sensitivity is 0.07% and 0.18% for the mouse collimator with 0.35-and 0.6-mm pinholes, respectively, and 0.09% for the rat collimator. Resolution with 111 In, compared with that with 99m Tc, was barely degraded, and resolution with 125 I was degraded by about 10%, with some additional distortion. In vivo, kidney, tumor, and bone images illustrated that U-SPECT-II could be used for novel applications in the study of dynamic biologic systems and radiopharmaceuticals at the suborgan level. Conclusion: Images and movies obtained with U-SPECT-II provide high-resolution radiomolecule visualization in rodents. Discrimination of molecule concentrations between adjacent volumes of about 0.04 mL in mice and 0.5 mL in rats with U-SPECT-II is readily possible.

Today, PET and SPECT tracers cannot be imaged simultaneously at high resolutions but require 2 separate imaging systems. This paper introduces a Versatile Emission Computed Tomography system (VECTor) for radionuclides that enables simultaneous submillimeter imaging of single-photon and positron-emitting radiolabeled molecules. Methods: g-photons produced both by electron-positron annihilation and by single-photon emitters are projected onto the same detectors by means of a novel cylindric high-energy collimator containing 162 narrow pinholes that are grouped in clusters. This collimator is placed in an existing SPECT system (U-SPECT-II) with 3 large-field-of-view g-detectors. From the acquired projections, PET and SPECT images are obtained using statistical image reconstruction that corrects for energy-dependent system blurring. Results: For PET tracers, the tomographic resolution obtained with a Jaszczak hot rod phantom was less than 0.8 mm, and 0.5-mm resolution images of SPECT tracers were acquired simultaneously. SPECT images were barely degraded by the simultaneous presence of a PET tracer, even when the activity concentration of the PET tracer exceeded that of the SPECT tracer by up to a factor of 2.5. Furthermore, we simultaneously acquired fully registered 3-and 4-dimensional multiple functional images from living mice that, in the past, could be obtained only sequentially. Conclusion: High-resolution complementary information about tissue function contained in SPECT and PET tracer distributions can now be obtained simultaneously using a fully integrated imaging device. These combined unique capabilities pave the way for new perspectives in imaging the biologic systems of rodents.

The high sensitivity achieved increases the range of mouse SPECT applications by enabling in vivo imaging with less than a megabecquerel of tracer activity or down to 1-s frame dynamics.

Limited spatial resolution of preclinical positron emission tomography (PET) and single-photon emission computed tomography (SPECT) has slowed down applications of molecular imaging in small animals. Here we present the latest-generation U-SPECT system (U-SPECT⁺, MILabs, Utrecht, the Netherlands) enabling radionuclide imaging of mice with quarter-millimeter resolution. The system was equipped with the newest high-resolution collimator with 0.25 mm diameter circular pinholes. It was calibrated with technetium-99 m point source measurements from which the system matrix was calculated. Images were reconstructed using pixel-based ordered subset expectation maximization (OSEM). Various phantoms and mouse SPECT scans were acquired. The reconstructed spatial resolution (the smallest visible capillary diameter in a hot-rod resolution phantom) was 0.25 mm. Knee joint images show tiny structures such as the femur epicondyle sulcus, as well as a clear separation between cortical and trabecular bone structures. In addition, time-activity curves of the lumbar spine illustrated that tracer dynamics in tiny tissue amounts could be measured. U-SPECT⁺ allows discrimination between molecular concentrations in adjacent volumes of as small as 0.015 μL, which is significantly better than can be imaged by any existing SPECT or PET system. This increase in the level of detail makes it more and more attractive to replace ex vivo methods and allows monitoring biological processes in tiny parts of organs in vivo.