Recent Developments in Instrumentation for Pre-Clinical Imaging Studies

Full text: Recent advances in imaging instrumentation have led to a variety of tomograph designs for dedicated pre clinical imaging of laboratory animals. These advances make it possible to image and quantify the kinetics of radiolabelled pharmaceuticals in a wide range of animal models from rodents to non-human primates. Applications include evaluation of promising new radiopharmaceuticals, study of the molecular origins of human disease and evaluation of new forms of therapy. These applications and advances in instrumentation are equally applicable to positron emitters and single photon emitters. This paper provides an overview of recent advances which have led to the current state-of-the-art in pre clinical imaging. The common inorganic scintillators that have been used for SPECT and PET, including some of the promising materials recently studied. The current crystal of choice for SPECT imaging is NaI(Tl) because of its high light output and density which make it well suited to imaging photons in the 100-200 keV range. However, NaI(Tl) has the disadvantage that it must be hermetically sealed to prevent absorption of moisture from the environment. Therefore, investigators have explored a number of alternative inorganic crystals, including CsI(Tl) and cerium-doped yttrium aluminium perovskite (YAP), as well as solid state detectors such as cadmium zinc telluride (CZT). Many of the crystals used in SPECT have also been tried for PET, including NaI(Tl) and YAP. However these crystals have lower stopping power than BGO and NaI(Tl) is also relatively slow. A very promising scintillator for PET is cerium-doped lutetium oxyorthosilicate (LSO) (1) which has similar stopping power to BGO and relatively high light output and fast decay. The first PET scanner to use LSO was the UCLA animal scanner, microPET, which also makes use of a number of other new technologies and unique design features. Recently, improvements in multi-anode and crossed wire position sensitive photomultiplier tubes (PS-PMT) have enabled a single photodetector to decode signals produced in a crystal slab or array of small crystals. While these devices are relatively bulky and include a large dead area at the periphery, a number of investigators have been able to make use of their high intrinsic spatial resolution in small animal detectors. For example, the microPET scanner uses optical fibres to couple PS-PMTs indirectly to LSO crystal arrays which overcomes the dead space problem. Similarly, at RPAH we are developing the CoALA-SPECT camera with detectors based on a PS-PMT, pixellated NaI(Tl) crystal and multi-pinhole aperture. Solid state photodetectors, including silicon photodiodes and avalanche photodiodes (APD), provide promising alternatives to PMTs. It is possible to achieve one-to-one coupling of these devices to small scintillator crystals (2-3 mm wide), as seen in the small animal PET system developed at the University of Munich. A number of promising new detector technologies have been developed and refined over the past 5-10 years. These include: new scintillators, such as LSO and YAP, position sensitive PMTs, photodiode arrays and fibre optic light guides. The current state-of-the-art in small animal PET and SPECT scanners employ one or more of these technologies to achieve isotropic spatial resolution approaching 1 mm full width at half maximum (FWHM). Further advances are likely to see the spatial resolution of these systems fall below 1 mm FWHM which will challenge the fundamental limit of resolution that can be achieved with PET due to positron range and non-colinearity. The challenge in the design of such systems will be to improve sensitivity without sacrificing resolution, so that a wide range of tracers and methods can be applied to the study of animal models of disease