• Molecular imaging
• YAP
• SPECT
• small animal scanner
• simultaneous PET/SPECT
• PET
• small animal imaging

Aims: Molecular imaging can be defined as the visual representation, characterization, and quantification of biological processes at the cellular and sub-cellular levels within intact living organisms. It is a novel multidisciplinary field, in which the produced images reflect cellular and molecular pathways and in vivo mechanisms of disease present within the context of physiological environments.
The emergence of molecular imaging strategies is largely due to recent unprecedented advances in molecular and cell biology techniques, the use of transgenic animal models, availability of newer imaging drugs and probes that are highly specific, and successful development of small-animal imaging instrumentation.
The YAP-(S)PET small animal scanner is part of this environment. It is a specifically built scanner able to perform both Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) and simultaneous PET/SPECT acquisitions.

Materials and Methods: The scanner was originally developed at the Department of Physics of the Universities of Ferrara and Pisa, Italy. From 2003, a fully engineered version of the scanner have been produced and commercialized by the small italian company I.S.E. s.r.l., Pisa, Italy.
This thesis deals with the physical calibration and characterization and with pre-clinical applications of the new version the YAP-(S)PET originally developed, the YAP-(S)PET II.
It is made up of four detector heads, each one composed of a 4 × 4 cm2 YAP:Ce matrix of 27 × 27 elements, 1.5 × 1.5 × 20 mm3 each, coupled to a Position Sensitive-Photomultiplier (PS-PMT). The heads can be positioned at different distances ranging from 10 to 20 cm. The four modules are positioned on a rotating gantry and opposing detectors are in time coincidence when used in PET mode. The scanner can be switched between PET and SPECT modalities simply replacing the tungsten septum used in PET with a high-resolution parallel hole collimator in front of each crystal. The peculiar YAP-(S)PET architecture provides also the capability to perform simultaneous PET/SPECT acquisitions.
The hardware calibrations concerned both electronics and mechanics settings such as adjustment of PMT gain or precise positioning of the center of rotation, while the software calibrations were related to definition of crystal and energy maps, and to efficiency corrections.
In PET mode, the performance of the YAP-(S)PET scanner have been evaluated following the standards proposed by the PET National Electric Manufacturers Association (NEMA) task force for small animal scanners. Since the lack of small animal SPECT performance, the SPECT performance has been evaluated by rescaling the clinical SPECT NEMA reference standards NU1-1994. For both PET and SPECT modalities, the performance were evaluated at different head-to-head distances: 10, 12.5 and 15 cm.
The simultaneous PET/SPECT dual imaging acquisition modality was realized by independently acquiring single events with two opposing heads equipped with the collimators (SPECT mode), while the other couple of heads detects coincident events (PET mode).
Different animal models and various isotopes and tracers have been used in the experiments performed in collaborations with several research groups. In this thesis only some of these studies are reported in order to point out the YAP-(S)PET imaging capabilities, particularly in neuro-pharmacology, psychiatry and oncology.

Conclusions: In PET mode the performance evaluation has regarded the spatial resolution, sensitivity, scatter fraction and count rate. The best compromise between spatial resolution and sensitivity was obtained with a head-to-head distance of 10 cm. In this configuration, the volume resolution is about 8 microliters, the sensitivity reaches 3% at the center fo the Field of View (CFOV), the scatter fraction is 27% and the peak Noise Equivalent Count rate is about 38 kcps at an activity concentration in the FOV of about 370 kBq/ml.
Also in SPECT modality, the best results are obtained for 10 cm head-to-head distance. The spatial resolution is about 2.8 mm at CFOV and the sensitivity is (3.7 E-3)% for 140-250 keV energy window.
Due to reduced working space at 10 cm, particularly evident in rats experiments, the best compromise between scanner performance and rats experiments is 12.5 cm for both PET and SPECT modality. On the contrary, mice experiments can be better performed at 10 cm head-to-head distance.