Objective. Clustered pinhole (CP) collimation currently supports sub-millimeter resolution imaging up to ∼1 MeV, enabling SPECT of alpha and beta emitters with gamma emissions, simultaneous multi-isotope PET and PET/SPECT, and positron range-free PET. Nonetheless, increasing sensitivity in the original CP designs by enlarging pinhole diameters is limited, as the resulting pinhole opening cones would overlap. Approach. To address this limitation, the use of Super-Cluster (SC) collimation was evaluated in a simulation study. Two SC designs were assessed: a standard configuration (SC-ST) offering a resolution-sensitivity trade-off similar to CP, and a high-sensitivity variant (SC-HS) with larger pinhole diameters to enhance sensitivity. Their performance was compared to CP collimation for 18F at concentrations of 1.0, 0.1, 0.05 MBq ml−1 and ⁸⁹Zr at 2.0, 0.2, 0.1 MBq ml−1, evaluating sensitivity, image resolution, recovery coefficients, and uniformity. Main results. CP and SC-ST showed comparable sensitivity and image resolution. Both resolved 18F rods of 0.9, 1.4, and 1.8 mm at 1.0, 0.1, and 0.05 MBq ml−1, respectively. For ⁸⁹Zr, rods down to 1.0 mm and 1.6 mm were resolved at 2.0 and 0.2 MBq ml−1, but none at 0.1 MBq ml−1. Compared to CP and SC-ST, SC-HS increased sensitivity threefold for 18F and twofold for ⁸⁹Zr. At the highest activity, SC-HS showed slightly reduced resolution for 18F (1.0 mm) and similar for ⁸⁹Zr (1.0 mm). However, it clearly outperformed both other collimators at lower activities, resolving 18F rods of 1.2 and 1.4 mm at 0.1 and 0.05 MBq ml−1, respectively, and ⁸⁹Zr rods of 1.4 and 1.6 mm at 0.2 and 0.1 MBq ml−1. Additionally, SC-HS showed superior contrast recovery. Image uniformity remained consistent across all collimators, confirming effective angular sampling. Significance. The new SC geometry enables high-sensitivity collimation for high gamma energies, improving image quality at low activities. These results demonstrate SC collimation’s strong potential for sensitivity-critical applications. ... Read more

Objective. Many SPECT and PET radionuclides, along with radionuclides used in targeted alpha or beta therapy and their imaging surrogates have multiple gamma and/or positron emissions. Images of these radionuclides are usually obtained from the photopeak with the most convenient energy and/or highest intensity or by adding counts from different photopeaks. Smart utilization of multiple energy peaks may improve reconstructed images, especially in low-count scans. Approach. We investigate and compare various dual-photopeak joint reconstruction (JR) approaches, namely (i) Single-Band (SB-JR)—projections from two energy windows are summed and reconstructed with a system matrix at a single average energy, (ii) mixed Multi-Band (mMB-JR)—like SB-JR but the system matrix incorporates the element-wise contributions from the photopeak energies, (iii) Multi-Band (MB-JR)—separate projections for each window and separate system matrices at relevant gamma energies are utilized. We evaluate these methods for a multi-pinhole PET-SPECT system (VECTor, MILabs, the Netherlands) using Monte Carlo generated Derenzo phantom projections of 225Ac (218 keV and 440 keV gammas), 226Ac (158 keV and 230 keV gammas) and 89Zr (511 keV annihilation gammas and 909 keV prompt gammas) at three different activity concentrations. A contrast-to-noise ratio (CNR) based quantitative performance analysis was done. Main results. The MB-JR scheme of JR showed superior visual image quality and highest CNRs in almost all cases, across all radionuclides and activity concentrations. The CNR improvement over images acquired from the single best-performing photopeak ranged from 30%–65% for 225Ac, 20%–54% for 226Ac, and 25%–47% for 89Zr, respectively, for the smallest visible rods in the Derenzo phantom. CNR improvements/degradations for the other two methods, mMB-JR and SB-JR, were: for 225Ac, −16%–51% and −21%–51%; for 226Ac, 9%–61% and 0.2%–38%; and for 89Zr, 19%–52% and −3%–16%, respectively. Significance. We believe the proposed image reconstruction methods can enhance SPECT, PET, and PET-SPECT imaging of a wide range of radionuclides that emit gamma’s with multiple energies. ... Read more

Objective. Utilizing prompt gammas in preclinical pinhole-collimated positron emission tomography (PET) avoids image degradation due to positron range blurring and photon down scatter, enables multi-isotope PET and can improve counting statistics for low-abundance positron emitters. This was earlier reported for 124I, 89Zr and simultaneous 124I −18F PET using the VECTor scanner (MILabs, The Netherlands), demonstrating sub-mm resolution despite long positron ranges. The aim of the present study is to investigate if such sub-mm PET imaging is also feasible for a large variety of other isotopes including those with extremely high energy prompt gammas (>1 MeV) or with complex emission spectra of prompt gammas. Approach. We use Monte Carlo simulations to assess achievable image resolutions and uniformity across a broad range of spectrum types and emitted prompt gamma energies (603 keV–2.2 MeV), using 52Mn, 94Tc, 89Zr, 44Sc, 86Y, 72As, 124I, 38K, and 66Ga. Main results. Our results indicate that sub-millimeter resolution imaging may be feasible for almost all isotopes investigated, with the currently used cluster pinhole collimators. At prompt gamma energies of 603 keV of 124I, an image resolution of ∼0.65 mm was achieved, while for emissions at 703, 744, 834, and 909 keV of 94Tc, 52Mn, 72As, and 89Zr, respectively, ∼0.7 mm resolution was obtained. Finally, at ultra-high energies of 1.2 (44Sc) and 1.4 MeV (52Mn) resolutions of ∼0.75 mm and ∼0.8 mm could still be achieved although ring artifacts were observed at the highest energies (1.4 MeV). For 38K (2.2 MeV), an image resolution of 1.2 mm was achieved utilizing its 2.2 MeV prompt emission. Significance. This work shows that current cluster pinhole collimators are suitable for sub-mm resolution prompt PET up till at least 1.4 MeV. This may open up new avenues to developing new tracer applications and therapies utilizing these PET isotopes. ... Read more

Objective. Advanced pinhole collimation geometries optimized for preclinical high-energy ɣ imaging facilitate applications such as ɑ and ß emitter imaging, simultaneous multi-isotope PET and PET/SPECT, and positron range-free PET. These geometries replace each pinhole with a group of clustered pinholes (CPs) featuring smaller individual pinhole opening angles (POAs), enabling sub-mm resolution imaging up to ∼1 MeV. Further narrowing POAs while retaining field-of-view (FOV) may enhance high-energy imaging but faces geometrical constraints. Here, we detail how the novel twisted CPs (TCPs) address this challenge. Approach. We compared TCP and CP collimator sensitivity at equal system resolution (SR) and SR at matched sensitivity by tuning pinhole diameters for 18F (511 keV) and 89Zr (909 keV). Additionally, simulated Derenzo phantoms at low activity (LA: 12 MBq ml−1) and high activity (HA: 190 MBq ml−1) levels, along with uniformity images, were compared to assess image resolution and uniformity. Main results. At equal SR, TCP increased average central FOV sensitivity by 15.6% for 18F and 29.4% for 89Zr compared to CP. Image resolution was comparable, except for 89Zr at LA, where TCP resolved 0.80 mm diameter rods compared to 0.90 mm for CP. Image uniformity was equivalent for 18F, while for 89Zr TCP granted a 10.4% improvement. For collimators with matched sensitivity, TCP improved SR by 6.6% for 18F and 17.7% for 89Zr while also enhancing image resolution; for 18F, rods distinguished were 0.65 mm (CP) and 0.60 mm (TCP) for HA, and 0.70 mm (CP and TCP) for LA. For 89Zr, image resolutions were 0.75 mm (CP) and 0.65 mm (TCP) for HA, and 0.90 mm (CP) and 0.80 mm (TCP) for LA. Image uniformity with TCP decreased by 18.3% for 18F but improved by 20.1% for 89Zr. Significance. This study suggests that the TCP design has potential to improve high-energy ɣ imaging. ... Read more