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.@en