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.

We have developed a compact and modular gamma camera system and assessed its performance when used on a small-animal SPECT prototype (rSPECT). Each camera consists of a Hamamatsu H-8500 position sensitive photomultiplier tube coupled to a 30 x 30 NaI (Tl) scintillator array (1.4mm x 1.4mm x 6mm crystal size) and electronics for pre-processing and matching the detector signals to an in-house developed data acquisition system. The camera components are enclosed in a lead-shielded case with a receptacle to insert the collimators (parallel-hole or pinhole with different tungsten apertures). System performance has been assessed for a low energy high resolution parallel-hole collimator (LEHR), and for a 0.75 mm pinhole collimator with 60º aperture angle. In this paper we present details on the system implementation and results of performance measurements, as well as first tomographic images on phantoms and animals. This SPECT was conceived for compactness and cost-effective routine small-animal imaging, and acquisitions of living mice and rats carried out with the system demonstrate its ability to provide useful high-resolution images for in vivo research. Index Terms Single Photon Emission Computed Tomography(SPECT), small-animal imaging, gamma camera.

Abstract-Lack of spatial resolution is a major drawback in small-animal SPECT imaging, particularly when parallel hole collimators are employed. This work evaluates the feasibility of enhancing the spatial resolution of a small-animal SPECT scanner by applying an approach based on a super-resolution technique combined with dedicated hardware. The detectors are based on PS-PMTs (Hamamatsu, H8500), NaI(TI) crystal arrays and parallel hole collimators. The system enables the mechanical shifting of the gamma-cameras and the object under study during the acquisition in steps smaller than the detector intrinsic sampling pitch. This fact allows using a super-resolution technique without the necessity of blind movement estimators between projections. In the absence of noise the algorithm converged to the original image, and with real noisy data it achieved improvements in resolution between 28% (tomographic) and 42% (planar) in phantom studies.

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