Background: Gamma camera imaging, including single photon emission computed tomography (SPECT), is crucial for research, diagnostics, and radionuclide therapy. Gamma cameras are predominantly based on arrays of photon multipliers tubes (PMTs) that read out NaI(Tl) scintillation crystals. In this way, standard gamma cameras can localize ɣ-rays with energies typically ranging from 30 to 360 keV. In the last decade, there has been an increasing interest towards gamma imaging outside this conventional clinical energy range, for example, for theragnostic applications and preclinical multi-isotope positron emission tomography (PET) and PET-SPECT. However, standard gamma cameras are typically equipped with 9.5 mm thick NaI(Tl) crystals which can result in limited sensitivity for these higher energies. Purpose: Here we investigate to what extent thicker scintillators can improve the photopeak sensitivity for higher energy isotopes while attempting to maintain spatial resolution. Methods: Using Monte Carlo simulations, we analyzed multiple PMT-based configurations of gamma detectors with monolithic NaI (Tl) crystals of 20 and 40 mm thickness. Optimized light guide thickness together with 2-inch round, 3-inch round, 60 × 60 mm2 square, and 76 × 76 mm2 square PMTs were tested. For each setup, we assessed photopeak sensitivity, energy resolution, spatial, and depth-of-interaction (DoI) resolution for conventional (140 keV) and high (511 keV) energy ɣ using a maximum-likelihood algorithm. These metrics were compared to those of a “standard” 9.5 mm-thick crystal detector with 3-inch round PMTs. Results: Estimated photopeak sensitivities for 511 keV were 27% and 53% for 20 and 40 mm thick scintillators, which is respectively, 2.2 and 4.4 times higher than for 9.5 mm thickness. In most cases, energy resolution benefits from using square PMTs instead of round ones, regardless of their size. Lateral and DoI spatial resolution are best for smaller PMTs (2-inch round and 60 × 60 mm2 square) which outperform the more cost-effective larger PMT setups (3-inch round and 76 × 76 mm2 square), while PMT layout and shape have negligible (< 10%) effect on resolution. Best spatial resolution was obtained with 60 × 60 mm2 PMTs; for 140 keV, lateral resolution was 3.5 mm irrespective of scintillator thickness, improving to 2.8 and 2.9 mm for 511 keV with 20 and 40 mm thick crystals, respectively. Using the 3-inch round PMTs, lateral resolutions of 4.5 and 3.9 mm for 140 keV and of 3.5 and 3.7 mm for 511 keV were obtained with 20 and 40 mm thick crystals respectively, indicating a moderate performance degradation compared to the 3.5 and 2.9 mm resolution obtained by the standard detector for 140 and 511 keV. Additionally, DoI resolution for 511 keV was 7.0 and 5.6 mm with 20 and 40 mm crystals using 60 × 60 mm2 square PMTs, while with 3-inch round PMTs 12.1 and 5.9 mm were obtained. Conclusion: Depending on PMT size and shape, the use of thicker scintillator crystals can substantially improve detector sensitivity at high gamma energies, while spatial resolution is slightly improved or mildly degraded compared to standard crystals.@en

Photomultiplier tube (PMT)-based scintillation cameras are predominant in molecular imaging but have the drawback that position estimation is severely degraded near the edges (dead edge effect). This leads to sensitivity losses and can cause severe problems in applications like molecular breast imaging and in certain SPECT devices. Using smaller light sensors or semiconductor detectors can solve this issue but leads to increased costs. Here we present a gamma detector based on standard PMTs with a novel light-guide-PMT geometry that strongly reduces dead edges. In our design, a monolithic NaI(Tl) scintillator is read out by square PMTs placed in a staggered arrangement. At the edge of the scintillator we inserted additional light-guides to emulate half-size PMTs. Detector performance was assessed for 99m Tc imaging; an average spatial resolution of 3.6 mm was measured over the whole detector, degrading to 4.0 mm within 30 mm to the critical edge. The dead edge of the scintillator is <; 3 mm. Since a 12-mm seal was used, the overall dead edge is <; 15 mm, which is a significant improvement over conventional Anger cameras (~40-mm dead edge). Therefore, the presented geometry can be useful in creating economical gamma detectors with reduced dead edges.@en

In recent years, breast imaging using radiolabelled molecules has attracted significant interest. Our group has proposed a multi-pinhole molecular breast tomosynthesis (MP-MBT) scanner to obtain 3D functional molecular breast images at high resolutions. After conducting extensive optimisation studies using simulations, we here present a first prototype of MP-MBT and evaluate its performance using physical phantoms. The MP-MBT design is based on two opposing gamma cameras that can image a lightly compressed pendant breast. Each gamma camera consists of a 250 × 150 mm2 detector equipped with a collimator with multiple pinholes focusing on a line. The NaI(Tl) gamma detector is a customised design with 3.5 mm intrinsic spatial resolution and high spatial linearity near the edges due to a novel light-guide geometry and the use of square PMTs. A volume-of-interest is scanned by translating the collimator and gamma detector together in a sequence that optimises count yield from the scan region. Derenzo phantom images showed that the system can reach 3.5 mm resolution for a clinically realistic 99mTc activity concentration in an 11-minute scan, while in breast phantoms the smallest spheres visible were 6 mm in diameter for the same scan time. To conclude, the experimental results of the novel MP-MBT scanner showed that the setup had sub-centimetre breast tumour detection capability which might facilitate 3D molecular breast cancer imaging in the future.@en

Breast cancer, being the most common cancer among females, is nowadays routinely diagnosed using X-ray mammography. Though this technique has proven its effectiveness in many cases, X-ray mammography has some disadvantages like reduced diagnostic sensitivity for dense breasts, need for strong breast compression and inability to assess tissues at the molecular level.  Therefore, there is a need for alternative imaging modalities to improve breast cancer diagnosis. One option is breast scintigraphy, which images the distribution of radiolabelled molecules, called tracers, that concentrate in the tumours in breasts with a planar gamma detector. Different tracers react in different physiological processes with tumours. Therefore imaging a specific tracer can reveal the specific pathological process that is specific for a certain kind of breast tumour. Despite the fact that breast scintigraphy has been reported to have improved diagnostic sensitivity in dense breasts compared to X-ray mammography and does not require strong compression, it offers only 2D images and information on the third dimension is thus lost. In this research we proposed a molecular breast tomosynthesis scanner which provides 3D images of the radiotracers in the breast. In the proposed system, the patient would lie prone on a patient bed with a hole in which the breast is inserted. Subsequently, two gamma cameras equipped with multi-pinhole collimators (therefore the technique is called multi-pinhole molecular breast tomosynthesis, MP-MBT) scan the pendant breast from both sides.  To estimate the performance of MP-MBT, the system was modelled in Monte Carlo simulations in a clinically realistic setting. The results assured us that it was worth building a prototype of MP-MBT to further investigate its imaging capability. Besides, voxelized raytracing (VRT) software developed earlier in our group to accelerate simulations and facilitate system optimisations was validated with the Monte Carlo simulation results. Subsequently, VRT was used in further studies in this project.  The promising results of MP-MBT simulations partly relied on a gamma detector with high spatial linearity over the whole detector surface. However, conventional gamma detectors used in clinical practice have large dead edges, i.e. about 4 cm from the detector edges is unusable, and a detector with small dead edges would be very expensive, which may make MP-MBT a less competitive technology. Therefore, in order to have a gamma detector suitable for MP-MBT, we came up with a few different designs with NaI(Tl) scintillators and photomultiplier tube (PMT) array readouts and evaluated their performances with Monte Carlo simulations. From the simulation results, we eventually chose a design with a staggered layout of 15 square PMTs, among which two PMTs detected the optical photons from the scintillator through extra-long additional light-guides. This gamma detector was built in our lab, and it turned out to have only about 15 mm dead edge (mainly due to the 12 mm sealing).  The customised gamma detector was equipped with a lead multi-pinhole collimator design based on previous research. The whole gamma camera was mounted on a robot arm to create a movable scanner. We calibrated the scanner with a point source and scanned a resolution phantom and a breast phantom to evaluate MP-MBT's performance. In the phantom study, the scanner showed the capability of detecting tumours down to 5 mm when a realistic tracer (technetium sestamibi) concentration was administered.  However, the current prototype is still far from a device that can be used in the clinic and we have found several problems with MP-MBT, especially the noise pattern in the reconstructed images, which should be given special attention in the future research.@en

Anger cameras based on monolithic NaI scintillators read out by an array of PMTs are predominant in planar gamma imaging and SPECT. However, position estimation of gamma interactions is usually severely degraded near the edges of the scintillator which can be extremely undesirable for applications like breast imaging. Here we propose a relatively cost-effective solution based on the use of scintillators with absorptive edges with an unconventional light-guide-PMT layout employing a maximum likelihood positioning algorithm. The basic design on which we aim to improve consists of a monolithic NaI(Tl) scintillator read out by 3 × 5 square PMTs (conventional layout, CL) that could be suitable for molecular breast imaging. To better detect gamma interactions near the crystal's critical edge, we tried different set-ups: we replaced the 5 large PMTs near the edge by 11 smaller PMTs (small-sensor layout, SSL); we emulated rectangular PMTs along the critical edge by inserting a row of 5 rectangular light-guides that direct the light toward square PMTs placed behind (shifted layout, SL); we inserted rectangular light-guides alternatingly, such that the PMTs are in an interlocking pattern (alternating shifted layout, ASL). The performance of our designs was tested with Monte Carlo simulations. Results showed that SSL, SL, and ASL gave better spatial resolution near the critical edge than CL (3.4, 3.6, and 4.1 mm near the edge compared with 5.3 mm for CL), and thus resulted in a larger usable detector area. To conclude, for applications where small dead edges are crucial, our designs may be cost-effective solutions.@en

Accurate gamma photon transport simulations of emission tomography systems are important to optimise system geometries and for iterative image reconstruction. Monte Carlo simulation (MCS) is widely established for this purpose but has the disadvantage of being prohibitively slow. Voxelized ray tracing (VRT) can be used as an alternative but the accuracy of VRT needs to be assessed for each simulation task at hand. The aim of this work is to propose and validate a dedicated VRT code for a novel radionuclide-based multi-pinhole molecular breast tomosynthesis (MP-MBT) scanner. The MP-MBT system images radionuclide distributions in a mildly compressed breast using two opposing gamma cameras, each equipped with a focusing multi-pinhole collimator, that slide along opposite sides of the breast. VRT simulates gamma photon transport by tracing rays efficiently through the voxelized phantom, collimator, and detector volumes using Siddon's raytracing algorithm, accelerated by dual-grid methods. To assess its accuracy, we compare point spread functions (PSFs) calculated with VRT for different voxel sizes with those generated by the established MCS toolkit GATE. Furthermore, VRT and MCS-simulated projections of realistic anthropomorphic XCAT phantoms with different compressed breast sizes are compared, as well as reconstructed images obtained from these projections. With VRT, PSFs for MP-MBT can be simulated accurately when the fine voxel size of the VRT's dual-grid is 1/8 mm. Reaching a similar deviation from noiseless PSFs takes 29 300 times longer with full MCS than with VRT. Furthermore, XCAT phantom simulations show that VRT-generated projections are very close to MCS-generated low-noise projections when these are corrected for scatter by the triple energy window method. However, we also find that primary gamma photons from the torso may in some cases reach the detector, meaning that torso activity should not be neglected in VRT. Finally, reconstructed images obtained from projections generated by VRT and MCS are visually very similar and have no significant difference in contrast and noise characteristics. We conclude that VRT can accurately and efficiently simulate MP-MBT even though it neglects scattered photons originating from the torso.@en