Design and Optimization of Next-Generation Broad Energy Pinhole PET /SPECT

Small-animal PET and SPECT are essential tools in the development of pharmaceutical drugs, radionuclide therapies, and diagnostic radiotracers. In particular, theranostic tracers, which combine predictive imaging biomarkers with therapeutic agents, have become increasingly important in preclinical research. Imaging these tracers is challenging because their gamma emissions often span a wide energy range, sometimes extending beyond conventional energies, and because activity concentrations can be low. These challenges highlight the need for imaging systems capable of operating over a broad energy range while maintaining high sensitivity and quantitative accuracy.
To address these challenges, the Biomedical Imaging group at TU Delft, in close collaboration with MILabs B.V., has focused on extending the maximum imageable gamma energy in preclinical imaging. This work resulted in the development of the Versatile Emission Computed Tomography (VECTor) system, a fully integrated preclinical PET/SPECT platform employing pinhole collimation for both modalities. VECTor has demonstrated high performance across an extended gamma energy range up to 1 MeV, achieving 0.4 mm resolution in collimated ⁹⁹ᵐTc-SPECT and 0.6 mm resolution in ¹⁸F-PET. Building on this foundation, this simulation-based study investigates software and hardware optimizations to improve the system’s quantitative imaging performance and sensitivity across this wide energy range.
On the software side, several joint reconstruction techniques were evaluated to improve image quality under low-count conditions. Three approaches, Single-Band Joint Reconstruction (SB-JR), Mixed Multi-Band Joint Reconstruction (mMB-JR), and Multi-Band Joint Reconstruction (MB-JR), were assessed using Monte Carlo simulations of resolution phantoms filled with ²²⁵Ac, ²²⁶Ac, or ⁸⁹Zr. Among these methods, MB-JR consistently provided the best image resolution and highest contrast-to-noise ratio across all isotopes and activity levels.
In parallel, hardware optimizations of the gamma camera were explored to improve performance at high energies. Simulations examined the effect of increasing the NaI(Tl) scintillation crystal thickness from the conventional 9.5 mm to 20 mm and 40 mm, combined with optimized light guides and four photomultiplier tube (PMT) geometries. For 511 keV photons, increased crystal thickness yielded substantial sensitivity gains (27% for 20 mm and 57% for 40 mm), with only modest spatial resolution losses when using cost-effective PMTs and potential resolution improvements when smaller PMTs were employed.
Finally, two novel collimator designs optimized for high-energy gamma emissions were evaluated. The Twisted Clustered Pinhole (TCP) collimator retains the clustered geometry of the standard clustered pinhole (CP) design while enabling narrower pinhole opening angles by twisting pinholes around their cluster central axis. For 511 keV (¹⁸F) and 909 keV (⁸⁹Zr) gamma emissions, TCP improved both sensitivity (15.6% for ¹⁸F and 29.4% for ⁸⁹Zr) and spatial resolution compared to CP.
The Super-Cluster (SC) collimator employs a simpler geometry with uniformly distributed pinholes, allowing larger pinhole diameters and a more flexible adjustment of the resolution–sensitivity trade-off. Relative to CP, SC achieved sensitivity gains of up to threefold for ¹⁸F and twofold for ⁸⁹Zr, particularly benefiting low-activity imaging through improved resolution and contrast recovery.
Together, these results demonstrate effective targeted strategies to extend VECTor applicability for high-energy and low-activity preclinical PET/SPECT imaging.