An ultra-high resolution preclinical positron emission tomography scanner

Positron Emission Tomography (PET) is a powerful functional imaging technique targeted for in vivo quantification and localization of physiological and pathophysiological functions. The possibility to develop a vast number of diseases in transgenic and knockout mice, and the chance to follow the onset of the diseases and the evolution of the treatment efficacy in an individual basis, made PET the third preferred preclinical imaging technique (20%) in research and development of new drug therapies [1]. Two features are mandatory in a preclinical PET system: a high Full Width at Half Maximum (FWHM) Spatial Resolution (SR), comprised between 0.40 and 0.27 mm for mice, so as to achieve the same level of detail of current state-of-the art PET scanners for humans [2], and a sensitivity as high as possible, to allow to differentiate and quantify a subtle signal in the presence of significant background counts [3]. Commercially available state-of-the-art preclinical PET systems make use of detectors based on segmented inorganic scintillation crystals coupled to photodetectors [2]. To reduce the complexity and cost, light multiplexing is used to decode the position of interaction of annihilation photons [3]. This scheme poses some limitations to the sensitivity and SR attained by preclinical PET systems, due to, among other problems, the difficulty of measuring efficiently the Depth-Of-Interaction [3]. The best reported values for the sensitivity and SR of current commercially available preclinical PET systems, are of, respectively, ∼10% and ∼1 mm FWHM [2]. Timing Resistive Plate Chambers (RPCs) are gaseous detectors with resistive parallel plate electrodes (made of glass) separated by small (∼300 μm thick) and precise amplification gaps filled with an appropriate gas mixture. For the detection of photons, these are first converted into electrons in the resistive plates in an electronic cascade process. Some of the originated electrons will e- entually escape to the amplification gap, where they will be accelerated by a uniform electric field, leading to a Townsend avalanche, which induces a current in a set of signal pickup strips. These low cost detectors have an excellent time resolution of 300 ps FWHM for 511 keV photon pairs, an excellent intrinsic SR, the readout being in almost full 3D mode. Recently, we developed a first fully functional prototype of a preclinical RPC-PET scanner for mice, which revealed a SR of 0.4 mm FWHM after image reconstruction by a Maximum Likelihood Expectation Maximization type algorithm. Preliminary tests with mice, preformed at the Institute of Nuclear Sciences Applied to Health (ICNAS — Instituto de Ciências Nucleares Aplicada às Saúde) of the University of Coimbra, shown the capability of the system to clearly identify the very small brain structures of mice, as well as the heart walls. The results obtained thus far are very promising, revealing unprecedented SR.