Performance of digital silicon photomultipliers for time of flight PET scanners

The performance of Digital Silicon Photomultipliers (dSiPM) coupled to a LYSO array containing 15×15 pixels with a size of 2×2×22 mm3 is evaluated to determinate their potential for whole body Time of Flight (TOF) PET scanners. The detector pixels are smaller in size than the light sensors and therefore light spreading is required to determine the crystal where interaction occurred. A light guide of 1 mm was used to spread the light and neighbor logic (NL) configuration were employed to ensure correct crystals identification. We studied the energy resolution and coincidence resolving time (CRT) for different trigger levels. The measured average energy resolution across detector was 14.5 %. Prior to measurements of time resolution skew time calibration of dSiPM was performed. The average CRT achieved using trigger level 1 option was 376 ps FWHM. Finally, we studied the amount of events that are disregarded due to dark count effects for different trigger levels and temperatures. Our studies show that a trade-off must be made between the detector’s CRT and sensitivity due to its vulnerability to dark counts. To employ dSiPM in TOF PET systems without 1:1 coupling effective cooling is necessary to limit dark count influence

Clinical consequences of relative biological effectiveness variations in proton radiotherapy of the prostate, brain and liver

Proton relative biological effectiveness (RBE) is known to depend on the (alpha/beta)(x) of irradiated tissues, with evidence of similar to 60% variation over (alpha/beta)(x) values from 1-10 Gy. The range of (alpha/beta)(x) values reported for prostate tumors (1.2-5.0 Gy), brain tumors (10-15 Gy) and liver tumors (13-17 Gy) imply that the proton RBE for these tissues could vary significantly compared to the commonly used generic value of 1.1. Our aim is to evaluate the impact of this uncertainty on the proton dose in Gy(RBE) absorbed in normal and tumor tissues. This evaluation was performed for standard and hypofractionated regimens. RBE-weighted total dose (RWTD) distributions for 15 patients (five prostate tumors, five brain tumors and five liver tumors) were calculated using an in-house developed RBE model as a function of dose, dose-averaged linear energy transfer (LETd) and (alpha/beta)(x). Variations of the dose-volume histograms (DVHs) for the gross tumor volume (GTV) and the organs at risk due to changes of (alpha/beta)(x) and fractionation regimen were calculated and the RWTD received by 10% and 90% of the organ volume reported. The goodness of the plan, bearing the uncertainties, was then evaluated compared to the delivered plan, which considers a constant RBE of 1.1. For standard fractionated regimens, the prostate tumors, liver tumors and all critical structures in the brain showed typically larger RBE values than 1.1. However, in hypofractionated regimens lower values of RBE than 1.1 were observed in most cases. Based on DVH analysis we found that the RBE variations were clinically significant in particular for the prostate GTV and the critical structures in the brain. Despite the uncertainties in the biological input parameters when estimating RBE values, the results show that the use of a variable RBE with dose, LETd and (alpha/beta)(x) could help to further optimize the target dose in proton treatment planning. Most importantly, this study shows that the consideration of RBE variations could influence the comparison of proton and photon treatments in clinical trials, in particular in the case of the prostate

Effects of dark counts on digital silicon photomultipliers performance

Digital Silicon Photomultipliers (dSiPM) are novel light detector that integrates single-photon avalanche photodiodes and CMOS logic into a single silicon chip and have been used for developing new, high performance detectors for Positron Emission Tomography (PET). As a solid-state devices they suffer from thermal excitation what leads to the appearance of noise events called dark counts. However, it is unclear what effect the dark counts have on the count rate performance of dSiPM. Therefore, it is necessary to investigate the event loss caused by these dark counts and to come up with optimal configuration of these devices. Here, the effects of dark counts on the performance of are evaluated. Due to the trigger architecture of dSiPM, dark counts cause start of acquisition sequence of the device. Processing of these dark counts leads to dead time of dSiPM what cause the loss of true gamma events. We studied how trigger level, validation level and validation length influence the loss of events due to dark counts. We found that validation time should be kept long (40 ns) to minimize the loss of events. Use of high trigger level and validation level also reduce the event loss caused by dark counts. However, with the high validation level, detection of events with low number of optical photons is reduced as it more difficult for these events to pass the validation threshold. The RTL refresh option was also tested to reduce the effect of dark counts. We found that this option resulted in the achieving maximum sensitivity, i.e. the highest fraction of correctly recorded true events, of dSiPM regardless of used validation and trigger levels. In cases when the scintillation light is spread over several dies, we found that the use of RTL refresh option combined with a low validation level in order to guarantee the individual validation of all required dies ensures higher sensitivity than the use of Neighbor Logic (NL). Finally we verified the dead time of dSiPM and found that is longer than specified and equal to 50 ns

Simultaneous emission and attenuation reconstruction in time-of-flight PET using a reference object

BACKGROUND: Simultaneous reconstruction of emission and attenuation images in time-of-flight (TOF) positron emission tomography (PET) does not provide a unique solution. In this study, we propose to solve this limitation by including additional information given by a reference object with known attenuation placed outside the patient. Different configurations of the reference object were studied including geometry, material composition, and activity, and an optimal configuration was defined. In addition, this configuration was tested for different timing resolutions and noise levels. RESULTS: The proposed strategy was tested in 2D simulations obtained by forward projection of available PET/CT data and noise was included using Monte Carlo techniques. Obtained results suggest that the optimal configuration corresponds to a water cylinder inserted in the patient table and filled with activity. In that case, mean differences between reconstructed and true images were below 10%. However, better results can be obtained by increasing the activity of the reference object. CONCLUSION: This study shows promising results that might allow to obtain an accurate attenuation map from pure TOF-PET data without prior knowledge obtained from CT, MRI, or transmission scans.This work was supported by a grant from the Comunidad de Madrid (2016-T1/TIC-1099). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII); the Ministerio de Ciencia, Innovación y Universidades (MCNU); and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S

Design of a realistic PET-CT-MRI phantom

The validation of the PET image quality of new PET-MRI systems should be done against the image quality of currently available PET-CT systems. This includes the validation of new attenuation correction methods. Such validation studies should preferentially be done using a phantom. There are currently no phantoms that have a realistic appearance on PET, CT and MRI. In this work we present the design and evaluation of such a phantom. The four most important tissue types for attenuation correction are air, lung, soft tissue and bone. An attenuation correction phantom should therefore contain these four tissue types. As it is difficult to mimic bone and lung on all three modalities using a synthetic material, we propose the use of biological material obtained from cadavers. For the lung section a lobe of a pig lung was used. It was excised and inflated using a ventilator. For the bone section the middle section of a bovine femur was used. Both parts were fixed inside a PMMA cylinder with radius 10 cm. The phantom was filled with 18F-FDG and two hot spheres and one cold sphere were added. First a PET scan was acquired on a PET-CT system. Subsequently, a transmission measurement and a CT acquisition were done on the same system. Afterwards, the phantom was moved to the MRI facility and a UTE-MRI was acquired. Average CT values and MRI R 2 values in bone and lung were calculated to evaluate the realistic appearance of the phantom on both modalities. The PET data was reconstructed with CT-based, transmission-based and MRI-based attenuation correction. The activity in the hot and cold spheres in the images reconstructed using transmission-based and MRI-based attenuation correction was compared to the reconstructed activity using CT-based attenuation correction. The average CT values in lung and bone were -630 HU and 1300 HU respectively. The average R 2 values were 0.7 ms -1 and 1.05 ms -1 respectively. These values are comparable to the values observed in clinical data sets. Transmission-based and MRI-based attenuation correction yielded an average difference with CT- based attenuation correction in the hot spots of -22 % and -8 %. In the cold spot the average differences were +3 % and -8 %. The construction of a PET-CT-MRI phantom was described. The phantom has a realistic appearance on all three modalities. It was used to evaluate two attenuation correction methods for PET-MRI scanners

Development of a blood sample detector for multi-tracer positron emission tomography using gamma spectroscopy

BACKGROUND: Multi-tracer positron emission tomography (PET) imaging can be accomplished by applying multi-tracer compartment modeling. Recently, a method has been proposed in which the arterial input functions (AIFs) of the multi-tracer PET scan are explicitly derived. For that purpose, a gamma spectroscopic analysis is performed on blood samples manually withdrawn from the patient when at least one of the co-injected tracers is based on a non-pure positron emitter. Alternatively, these blood samples required for the spectroscopic analysis may be obtained and analyzed on site by an automated detection device, thus minimizing analysis time and radiation exposure of the operating personnel. In this work, a new automated blood sample detector based on silicon photomultipliers (SiPMs) for single- and multi-tracer PET imaging is presented, characterized, and tested in vitro and in vivo. RESULTS: The detector presented in this work stores and analyzes on-the-fly single and coincidence detected events. A sensitivity of 22.6 cps/(kBq/mL) and 1.7 cps/(kBq/mL) was obtained for single and coincidence events respectively. An energy resolution of 35% full-width-half-maximum (FWHM) at 511 keV and a minimum detectable activity of 0.30 ± 0.08 kBq/mL in single mode were obtained. The in vivo AIFs obtained with the detector show an excellent Pearson's correlation (r = 0.996, p < 0.0001) with the ones obtained from well counter analysis of discrete blood samples. Moreover, in vitro experiments demonstrate the capability of the detector to apply the gamma spectroscopic analysis on a mixture of 68Ga and 18F and separate the individual signal emitted from each one. CONCLUSIONS: Characterization and in vivo evaluation under realistic experimental conditions showed that the detector proposed in this work offers excellent sensibility and stability. The device also showed to successfully separate individual signals emitted from a mixture of radioisotopes. Therefore, the blood sample detector presented in this study allows fully automatic AIFs measurements during single- and multi-tracer PET studies.This work was supported by grants from the Carlos III Institute of Health of Spain and Fondo Europeo de Desarrollo Regional (FEDER, “Una manera de hacer Europa”) (FIS-FEDER PI14-01427), and from the Comunidad de Madrid (2016-T1/TIC-1099). CV holds a fellowship from the Spanish Ministry of Education (FPU014/01794). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia, Innovación y Universidades (MCNU), and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505)

Explicit measurement of multi-tracer arterial input function for PET imaging using blood sampling spectroscopy

BACKGROUND: Conventional PET imaging has usually been limited to a single tracer per scan. We propose a new technique for multi-tracer PET imaging that uses dynamic imaging and multi-tracer compartment modeling including an explicitly derived arterial input function (AIF) for each tracer using blood sampling spectroscopy. For that purpose, at least one of the co-injected tracers must be based on a non-pure positron emitter. METHODS: The proposed technique was validated in vivo by performing cardiac PET/CT studies on three healthy pigs injected with 18FDG (viability) and 68Ga-DOTA (myocardial blood flow and extracellular volume fraction) during the same acquisition. Blood samples were collected during the PET scan, and separated AIF for each tracer was obtained by spectroscopic analysis. A multi-tracer compartment model was applied to the myocardium in order to obtain the distribution of each tracer at the end of the PET scan. Relative activities of both tracers and tracer uptake were obtained and compared with the values obtained by ex vivo analysis of excised myocardial tissue segments. RESULTS: A high correlation was obtained between multi-tracer PET results, and those obtained from ex vivo analysis (18FDG relative activity: r = 0.95, p < 0.0001; SUV: r = 0.98, p < 0.0001). CONCLUSIONS: The proposed technique allows performing PET scans with two tracers during the same acquisition obtaining separate information for each tracer.This work was supported by grants from the Carlos III Institute of Health of Spain and Fondo Europeo de Desarrollo Regional (FEDER, “Una manera de hacer Europa”) (FIS-FEDER PI14-01427) and from the Comunidad de Madrid (2016-T1/TIC-1099). CV holds a fellowship from the Spanish Ministry of Education (FPU014/01794). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia, Innovación y Universidades (MCNU), and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S

Evaluation of resistive-plate-chamber-based TOF-PET applied to in-beam particle therapy monitoring

Particle therapy is a highly conformal radiotherapy technique which reduces the dose deposited to the surrounding normal tissues. In order to fully exploit its advantages, treatment monitoring is necessary to minimize uncertainties related to the dose delivery. Up to now, the only clinically feasible technique for the monitoring of therapeutic irradiation with particle beams is Positron Emission Tomography (PET). In this work we have compared a Resistive Plate Chamber (RPC)-based PET scanner with a scintillation-crystal-based PET scanner for this application. In general, the main advantages of the RPC-PET system are its excellent timing resolution, low cost, and the possibility of building large area systems. We simulated a partial-ring scannerbeam monitoring, which has an intrinsically low positron yield compared to diagnostic PET. In addition, for in-beam PET there is a further data loss due to the partial ring configuration. In order to improve the performance of the RPC-based scanner, an improved version of the RPC detector (modifying the thickness of the gas and glass layers), providing a larger sensitivity, has been simulated and compared with an axially extended version of the crystal-based device. The improved version of the RPC shows better performance than the prototype, but the extended version of the crystal-based PET outperforms all other options. based on an RPC prototype under construction within the Fondazione per Adroterapia Oncologica (TERA). For comparison with the crystal-based PET scanner we have chosen the geometry of a commercially available PET scanner, the Philips Gemini TF. The coincidence time resolution used in the simulations takes into account the current achievable values as well as expected improvements of both technologies. Several scenarios (including patient data) have been simulated to evaluate the performance of different scanners. Initial results have shown that the low sensitivity of the RPC hampers its application to hadro

Assessment of regional pulmonary blood flow using Ga-68-DOTA PET

Background: In vivo determination of regional pulmonary blood flow (PBF) is a valuable tool for the evaluation of many lung diseases. In this study, the use of Ga-68-DOTA PET for the in vivo quantitative determination of regional PBF is proposed. This methodology was implemented and tested in healthy pigs and validated using fluorescent microspheres. The study was performed on young large white pigs (n = 4). To assess the reproducibility and consistency of the method, three PET scans were obtained for each animal. Each radiotracer injection was performed simultaneously to the injection of fluorescent microspheres. PBF images were generated applying a two-compartment exchange model over the dynamic PET images. PET and microspheres values were compared by regression analysis and Bland-Altman plot. Results: The capability of the proposed technique to produce 3D regional PBF images was demonstrated. The correlation evaluation between Ga-68-DOTA PET and microspheres showed a good and significant correlation (r = 0.74, P < 0.001). Conclusions: Assessment of PBF with the proposed technique allows combining the high quantitative accuracy of PET imaging with the use of Ga-68/Ge-68 generators. Thus, Ga-68-DOTA PET emerges as a potential inexpensive method for measuring PBF in clinical settings with an extended use.This work was supported by a grant from the Spanish Ministry of Economy and Competitiveness (MINECO) (SAF2014-58920-R) and a grant from the Carlos III Institute of Health (FIS-FEDER PI14-01427). C. Velasco is a recipient of a fellowship from the Spanish Ministry of Education (FPU014/01794). S. Espana and A. Santos are recipients of M+Vision Advanced fellowships from the community of Madrid. The CNIC is supported by the MINECO and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505).S