Abstract: Thin tissue autoradiography is an imaging modality where ex-vivo tissue sections are placed in direct contact with autoradiographic film. These tissue sections contain a radiolabelled ligand bound to a specific biomolecule under study. This radioligand emits beta- or beta+ particles ionizing silver halide crystals in the film. High spatial resolution autoradiograms are obtained using low energy radioisotopes, such as H-3 where an intrinsic 0.1-1 μm spatial resolution can be achieved. Several digital alternatives have been presented over the past few years to replace conventional film but their spatial resolution has yet to equal film, although silicon-based imaging technologies have demonstrated higher sensitivity compared to conventional film. It will be shown in this work how pixel size is a critical parameter for achieving high spatial resolution for low energy uncollimated beta imaging. In this work we also examine the confounding factors impeding silicon-based technologies with respect to spatial resolution. The study considers charge diffusion in silicon and detector noise, and this is applied to a range of radioisotopes typically used in autoradiography. Finally an optimal detector geometry to obtain the best possible spatial resolution for a specific technology and a specific radioisotope is suggested.

Abstract: Random coincidences ('randoms') are one of the main sources of image degradation in PET imaging. In order to correct for this effect, an accurate method to estimate the contribution of random events is necessary. This aspect becomes especially relevant for high-resolution PET scanners where the highest image quality is sought and accurate quantitative analysis is undertaken. One common approach to estimate randoms is the so-called singles rate method (SR) widely used because of its good statistical properties. SR is based on the measurement of the singles rate in each detector element. However, recent studies suggest that SR systematically overestimates the correct random rate. This overestimation can be particularly marked for low energy thresholds, below 250 keV used in some applications and could entail a significant image degradation. In this work, we investigate the performance of SR as a function of the activity, geometry of the source and energy acceptance window used. We also investigate the performance of an alternative method, which we call 'singles trues' (ST) that improves SR by properly modeling the presence of true coincidences in the sample. Nevertheless, in any real data acquisition the knowledge of which singles are members of a true coincidence is lost. Therefore, we propose an iterative method, STi, that provides an estimation based on ST but which only requires the knowledge of measurable quantities: prompts and singles. Due to inter-crystal scatter, for wide energy windows ST only partially corrects SR overestimations. While SR deviations are in the range 86-300% (depending on the source geometry), the ST deviations are systematically smaller and contained in the range 4-60%. STi fails to reproduce the ST results, although for not too high activities the deviation with respect to ST is only a few percent. For conventional energy windows, i.e. those without inter-crystal scatter, the ST method corrects the SR overestimations, and deviations from the true random rate are of the order of 1% or less. In addition, in the case of conventional energy window STi results reproduce ST results and therefore the former can be used to obtain the true random rate.