EXIRAD-HE: multi-pinhole high-resolution ex vivo imaging of high-energy isotopes

We recently developed a dedicated focusing multi-pinhole collimator for a stationary SPECT system that offers down to 120 µm (or 1.7 nL) spatial resolution SPECT images of cryo-cooled tissue samples (EXIRAD-3D). This collimator is suitable for imaging isotopes that are often used in small animal and diagnostic SPECT such as ¹²⁵I (27 keV), ²⁰¹Tl (71 keV), ^99mTc (140 keV), and ¹¹¹In (171 and 245 keV). The goal of the present work is to develop high-resolution pinhole imaging of tissue samples containing isotopes with high-energy photon emissions, for example, therapeutic alpha and beta emitters that co-emit high energy gammas (e.g. ²¹³Bi (440 keV) and ¹³¹I (364 keV)) or 511 keV annihilation photons from PET isotopes. To this end, we optimise and evaluate a new high energy small-bore multi-pinhole collimator through simulations. The collimator-geometry was first optimised by simulating a Derenzo phantom scan with a biologically realistic activity concentration of ¹⁸F at two system sensitivities (0.30% and 0.60%) by varying pinhole placements. Subsequently, the wall thickness was selected based on reconstructions of a Derenzo phantom and a uniform phantom. The obtained collimators were then evaluated for ¹³¹I (364 keV), ²¹³Bi (440 keV), ⁶⁴Cu (511 keV), and ¹²⁴I (511 + 603 keV) with biologically realistic activity concentrations, and also for some high activity concentrations of ¹⁸F, using digital resolution, mouse knee joint, and xenograft phantoms. Our results show that placing pinhole centres at a distance of 8 mm from the collimator inner wall yields good image quality, while a wall thickness of 43 mm resulted in sufficient shielding. The collimators offer resolutions down to 0.35 mm, 0.6 mm, 0.5 mm, 0.6 mm, and 0.5 mm when imaging ¹³¹I, ²¹³Bi, ¹⁸F, ⁶⁴Cu, and ¹²⁴I, respectively, contained in tissue samples at biologically achievable activity concentrations.