Monte Carlo (MC) simulation method plays an essential role in the refinement and development of positron emission tomography (PET) systems. However, most existing MC simulation packages suffer from long execution time for practical PET simulations. To fully address this issue, we developed and validated gPET, a graphics processing unit (GPU)-based MC simulation tool for PET. gPET was built on the NVidia CUDA platform. The simulation process was modularized into three functional parts and carried out by the GPU parallel threads: (1) source management, including positron decay, transport and annihilation; (2) gamma transport inside the phantom; and (3) signal detection and processing inside the detector. A hybrid of voxelized (for patient phantoms) and parametrized (for detectors) geometries were employed to sufficiently support particle navigations. Multiple inputs and outputs were available. Hence, a user can flexibly examine different aspects of a PET simulation. We evaluated the performance of gPET in three test cases with benchmark work from GATE8.0, in terms of the testing of the functional modules, the physics models used for gamma transport inside the detector, and the geometric configuration of an irregularly shaped PET detector. Both accuracy and efficiency were quantified. In all test cases, the differences between gPET and GATE for the coincidences with respect to the energy and crystal index distributions are below 3.18% and 2.54%, respectively. The speedup factor is 500 for gPET on a single Titan Xp GPU (1.58 GHz) over GATE8.0 on a single core of Intel i7-6850K CPU (3.6 GHz) for all test cases. In summary, gPET is an accurate and efficient MC simulation tool for PET.

Particle therapy can achieve excellent dose localization but is sensitive to range uncertainty. Therefore, online in vivo range verification before treatment is critical for treatment safety and quality assurance. We introduce a novel range-probing technique that uses mid-range treatment spots selected from the treatment plan as probing beams to be delivered before other treatment spots in pencil beam scanning. The probing spot signal can be acquired by an in-beam positron emission tomography (PET) scanner, and the reconstructed spot positions are compared with pre-calculated positions to measure the range shift. Mid-range probing ensures that the Bragg peaks stay inside the tumor even with significant range variation from the plan. Single-layered spots enable easier spot detection than multi-layered spots without cross-layered spot smearing. With therapeutic dose, the probing beam offers higher positron activities and range detectability than the low-dose imaging beam by up to two orders of magnitude, without exposing patients to extra radiation. Higher positron activities allow sufficient signal statistics in shorter acquisition time, therefore reducing metabolic washout of positron emitters. Thus, range shifts from the plan can be measured easily. We also describe two online range-compensated plan modification methods. We apply correction, if the range shift is above a certain tolerance. We studied feasibility using simulated particle treatment plans with online anatomical changes. For illustration, we demonstrate range shift measurement using simulated probing dose. The proposed range probing and correction effectively handled range shifts in the simulated cases. Both range-compensated adaptation and optimization accounted for online changes so that the delivered dose matched the planned dose. With a dedicated online in-beam PET scanner and phantom and clinical studies, which are currently being developed, this novel strategy may open up a range-guided particle therapy ¹ paradigm.

Objective. Develop a prototype on-line positron emission tomography (PET) scanner and evaluate its capability of on-line imaging and intra-fractionated proton-induced radioactivity range measurement. Approach. Each detector consists of 32 × 32 array of 2 × 2 × 30 mm³ Lutetium–Yttrium Oxyorthosilicate scintillators with single-scintillator-end readout through a 20 × 20 array of 3 × 3 mm² Silicon Photomultipliers. The PET can be configurated with a full-ring of 20 detectors for conventional PET imaging or a partial-ring of 18 detectors for on-line imaging and range measurement. All detector-level readout and processing electronics are attached to the backside of the system gantry and their output signals are transferred to a field-programable-gate-array based system electronics and data acquisition that can be placed 2 m away from the gantry. The PET imaging performance and radioactivity range measurement capability were evaluated by both the offline study that placed a radioactive source with known intensity and distribution within a phantom and the online study that irradiated a phantom with proton beams under different radiation and imaging conditions. Main results. The PET has 32 cm diameter and 6.5 cm axial length field-of-view (FOV), ∼2.3–5.0 mm spatial resolution within FOV, 3% sensitivity at the FOV center, 18%–30% energy resolution, and ∼9 ns coincidence time resolution. The offline study shows the PET can determine the shift of distal falloff edge position of a known radioactivity distribution with the accuracy of 0.3 ± 0.3 mm even without attenuation and scatter corrections, and online study shows the PET can measure the shift of proton-induced positron radioactive range with the accuracy of 0.6 ± 0.3 mm from the data acquired with a short-acquisition (60 s) and low-dose (5 MU) proton radiation to a human head phantom. Significance. This study demonstrated the capability of intra-fractionated PET imaging and radioactivity range measurement and will enable the investigation on the feasibility of intra-fractionated, range-shift compensated adaptive proton therapy.

Objective: In contrast to clinical radiation therapy (RT) that ubiquitously uses PET/CT image to accurately guide RT, all current commercial animal irradiators can only provide CT image-guided preclinical RT that severely limits their capability for preclinical and compatibility for translational radiation oncology research. To address this problem, we have developed a compact and lightweight PET with uniform, high spatial resolution that is suited to be installed inside an existing animal irradiator for potential onboard PET/CT image-guided preclinical RT research. Approach: The design focused on the balance of achieving sufficient imaging performance for practical preclinical RT guidance with constrained size and weight. The detector head consists of a ring of 12 detector panels in a dodecagon configuration and 12 front-end electronics boards that are closely attached to the detector panels. The overall size and weight of the detector head are 33.0 cm diameter, 11.0 cm axial length and ∼6.5 kg weight that can be installed inside an existing irradiator. Each detector panel has a 30 × 30 array of 1 × 1 × 20 mm ³ LYSO scintillators with depth-of-interaction (DOI) measurement. The front-end electronics boards process and convert detected signals to digital signals and transfer them to system electronics and data acquisition located outside the irradiator through low-voltage-differential-signaling cables. Main results: The typical energy, DOI and coincidence timing resolutions are around 22.1%, 3.1 mm, and 1.92 ns. The imaging field-of-view (FOV) is 8.0 cm diameter and 3.5 cm axial length. The performance evaluations show a 1.8% sensitivity at the center FOV, uniform ∼1.1 mm resolution within 6 cm diameter FOV, and all rods of 1.0 mm diameter can be clearly resolved from the image of an ultra-micro hot-rods phantom. Significance: Overall, this compact and lightweight PET has demonstrated its designed capability and performance sufficient for providing onboard functional/biological/molecular image to guide the preclinical RT research.

We previously proposed range-guided adaptive proton therapy (RGAPT) that uses mid-range treatment beams as probing beams and intra-fractionated range measurements for online adaptation. In this work, we demonstrated experimental verification and reported the dosimetric accuracy for RGAPT. A STEEV phantom was used for the experiments, and a 3 × 3 × 3 cm³ cube inside the phantom was assigned to be the treatment target. We simulated three online range shift scenarios: reference, overshoot, and undershoot, by placing upstream Lucite sheets, 4, 0, and 8 that corresponded to changes of 0, 6.8, and −6.8 mm, respectively, in water-equivalent path length. The reference treatment plan was to deliver single-field uniform target doses in pencil beam scanning mode and generated on the Eclipse treatment planning system. Different numbers of mid-range layers, including single, three, and five layers, were selected as probing beams to evaluate beam range (BR) measurement accuracy in positron emission tomography (PET). Online plans were modified to adapt to BR shifts and compensate for probing beam doses. In contrast, non-adaptive plans were also delivered and compared to adaptive plans by film measurements. The mid-range probing beams of three (5.55MU) and five layers (8.71MU) yielded accurate range shift measurements in 60 s of PET acquisition with uncertainty of 0.5 mm while the single-layer probing (1.65MU) was not sufficient for measurements. The adaptive plans achieved an average gamma (2%/2 mm) passing rate of 95%. In contrast, the non-adaptive plans only had an average passing rate of 69%. RGAPT planning and delivery are feasible and verified by the experiments. The probing beam delivery, range measurements, and adaptive planning and delivery added a small increase in treatment delivery workflow time but resulted in substantial dose improvement. The three-layer mid-range probing was most suitable considering the balance of high range measurement accuracy and the low number of probing beam layers.

Online positron emission tomography (PET) image-based method uses an initial particle beam to measure the particle beam range (BR) within the same fraction so that any measured range-shift with respect to the predicted BR can be compensated before the rest therapeutic beam deliveries. However, the method requires to use a low-dose initial beam to minimize the risk of beam overshooting, which leads to low image count and inaccurate BR measurement. In this in-silico study, we evaluate the feasibility of a new online PET imaging method that measures BR at the mid-plane of a target volume with part of the high-dose therapy beams to verify BR and guide adaptive treatment replanning. Simulations included various processes of proton beam radiations to a tumor inside a human-brain phantom, positron, and PET image generation at the mid-plane with initial beams, activity range measurement, and range-shift compensated beam delivery. The results demonstrated that the new method, under the simulated conditions, can achieve ~1.1-mm mid-plane BR measurement accuracy and closely match the delivered range-shift compensated dose distribution with the planned one. Overall, it is promising that this new method may significantly improve the particle therapy accuracy.