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Pile-up and dead-time are two main causes of nonlinearity in the response of a PET scanner as a function of activity in the field of view (FOV). For a given scanner and acquisition system, pile-up effects depend on the material and size of the object being imaged and on the distribution of activity inside and outside the FOV, because these factors change the singles-to-coincidences ratio (SCR). Thus, it is difficult to devise an accurate correction that would be valid for any acquisition. In this work, we demonstrate a linear relationship between SCR and effective dead-time, which measures the effects of both dead-time (losses) and pile-up (gains and losses). This relationship allows us to propose a simple method to accurately estimate dead-time and pile-up corrections using only two calibration acquisitions with, respectively, a high and low SCR. The method has been tested with simulations and experimental data for two different scanner geometries: a scanner with large area detectors and no pile-up rejection, and a scanner composed of two full rings of smaller detectors. Our results show that the SCR correction method is accurate within 7%, even for high activities in the FOV, and avoids the bias of the standard single-parameter method. [ABSTRACT FROM AUTHOR]

Compared to indirect methods, direct parametric image reconstruction (PIR) has the advantage of high quality and low statistical errors. However, it is not yet clear if this improvement in quality is beneficial for physiological quantification. This study aimed to evaluate direct PIR for the quantification of tumor hypoxia using the hypoxic fraction (HF) assessed from immunohistological data as a physiological reference. Sixteen mice with xenografted human squamous cell carcinomas were scanned with dynamic [18F]FMISO PET. Afterward, tumors were sliced and stained with H&E and the hypoxia marker pimonidazole. The hypoxic signal was segmented using k-means clustering and HF was specified as the ratio of the hypoxic area over the viable tumor area. The parametric Patlak slope images were obtained by indirect voxel-wise modeling on reconstructed images using filtered back projection and ordered-subset expectation maximization (OSEM) and by direct PIR (e.g., parametric-OSEM, POSEM). The mean and maximum Patlak slopes of the tumor area were investigated and compared with HF. POSEM resulted in generally higher correlations between slope and HF among the investigated methods. A strategy for the delineation of the hypoxic tumor volume based on thresholding parametric images at half maximum of the slope is recommended based on the results of this study. [ABSTRACT FROM AUTHOR]

The PDF file provided contains web links to all articles in this volume. [ABSTRACT FROM AUTHOR]

Technical advances towards high resolution PET imaging try to overcome the inherent physical limitations to spatial resolution. Positrons travel in tissue until they annihilate into the two gamma photons detected. This range is themain detector-independent contribution to PET imaging blurring. To a large extent, it can be remedied during image reconstruction if accurate estimates of positron range are available. However, the existing estimates differ, and the comparison with the scarce experimental data available is not conclusive. In this work we present positron annihilation distributions obtained from Monte Carlo simulations with the PeneloPET simulation toolkit, for several common PET isotopes (18F, 11C, 13N, 15O, 68Ga and 82Rb) in different biological media (cortical bone, soft bone, skin, muscle striated, brain, water, adipose tissue and lung).We compare PeneloPET simulations against experimental data and other simulation results available in the literature. To this end the different positron range representations employed in the literature are related to each other by means of a new parameterization for positron range profiles. Our results are generally consistent with experiments and with most simulations previously reported with differences of less than 20% in the mean and maximum range values. From these results, we conclude that better experimental measurements are needed, especially to disentangle the effect of positronium formation in positron range. Finally, with the aid of PeneloPET, we confirm that scaling approaches can be used to obtain universal, material and isotope independent, positron range profiles, which would considerably simplify range correction. [ABSTRACT FROM AUTHOR]

Low energy x-ray intra-operative radiation therapy (IORT) is used mostly for breast cancer treatment with spherical applicators. X-ray IORT treatment delivered during surgery (ex: INTRABEAM®, Carl Zeiss) can benefit from accurate and fast dose prediction in a patient 3D volume. However, full Monte Carlo (MC) simulations are time-consuming and no commercial treatment planning system (TPS) was available for this treatment delivery technique. Therefore, the aim of this work is to develop a dose computation tool based on MC phase space information, which computes fast and accurate dose distributions for spherical and needle INTRABEAM® applicators. First, a database of monoenergetic phase-space (PHSP) files and depth dose profiles (DDPs) in water for each applicator is generated at factory and stored for on-site use. During commissioning of a given INTRABEAM® unit, the proposed fast and optimized phase-space (FOPS) generation process creates a phase-space at the exit of the applicator considered, by fitting the energy spectrum of the source to a combination of the monoenergetic precomputed phase-spaces, by means of a genetic algorithm, with simple experimental data of DDPs in water provided by the user. An in-house hybrid MC (HMC) algorithm which takes into account condensed history simulations of photoelectric, Rayleigh and Compton interactions for x-rays up to 1 MeV computes the dose from the optimized phase-space file. The whole process has been validated against radiochromic films in water as well as reference MC simulations performed with penEasy in heterogeneous phantoms. From the pre-computed monoenergetic PHSP files and DDPs, building the PHSP file optimized to a particular depth-dose curve in water only takes a few minutes in a single core (i7@2.5 GHz), for all the applicators considered in this work, and this needs to be done only when the x-ray source (XRS) is replaced. Once the phase-space file is ready, the HMC code is able to compute dose distributions within 10 min. For all the applicators, more than 95% of voxels from dose distributions computed with the FOPS+hybrid code agreed within 7%–0.5 mm with both reference MC simulations and measurements. The method proposed has been fully validated and it is now implemented into radiance (GMV SA, Spain), the first commercial IORT TPS. [ABSTRACT FROM AUTHOR]

A detection system of the conventional PET tomograph is set-up to record data from annihilation into two photons with energy of 511 keV, and it gives information on the density distribution of a radiopharmaceutical in the body of the object. In this paper we explore the possibility of performing the three gamma photons imaging based on ortho-positronium annihilation, as well as the possibility of positronium mean lifetime imaging with the J-PET tomograph constructed from plastic scintillators. For this purposes simulations of the ortho-positronium formation and its annihilation into three photons were performed taking into account distributions of photons’ momenta as predicted by the theory of quantum electrodynamics and the response of the J-PET tomograph. In order to test the proposed ortho-positronium lifetime image reconstruction method, we concentrate on the decay of the ortho-positronium into three photons and applications of radiopharmaceuticals labeled with isotopes emitting a prompt gamma. The proposed method of imaging is based on the determination of hit-times and hit-positions of registered photons which enables the reconstruction of the time and position of the annihilation point as well as the lifetime of the ortho-positronium on an event-by-event basis. We have simulated the production of the positronium in point-like sources and in a cylindrical phantom composed of a set of different materials in which the ortho-positronium lifetime varied from 2.0 ns to 3.0 ns, as expected for ortho-positronium created in the human body. The presented reconstruction method for total-body J-PET like detector allows to achieve a mean lifetime resolution of  ∼40 ps. Recent positron annihilation lifetime spectroscopy measurements of cancerous and healthy uterine tissues show that this sensitivity may allow to study the morphological changes in cell structures. [ABSTRACT FROM AUTHOR]

Sensitivity and spatial resolution are the main parameters to maximize in the performance of a PET scanner. For this purpose, detectors consisting of a combination of continuous crystals optically coupled to segmented photodetectors have been employed. With the use of continuous crystals the sensitivity is increased with respect to the pixelated crystals. In addition, spatial resolution is no longer limited to the crystal size. The main drawback is the difficulty in determining the interaction position. In this work, we present the characterization of the performance of a full ring based on cuboid continuous crystals coupled to SiPMs. To this end, we have employed the simulations developed in a previous work for our experimental detector head. Sensitivity could be further enhanced by using tapered crystals. This enhancement is obtained by increasing the solid angle coverage, reducing the wedge-shaped gaps between contiguous detectors. The performance of the scanners based on both crystal geometries was characterized following NEMA NU 4-2008 standardized protocol in order to compare them. An average sensitivity gain over the entire axial field of view of 13.63% has been obtained with tapered geometry while similar performance of the spatial resolution has been proven with both scanners. The activity at which NECR and true peak occur is smaller and the peak value is greater for tapered crystals than for cuboid crystals. Moreover, a higher degree of homogeneity was obtained in the sensitivity map due to the tighter packing of the crystals, which reduces the gaps and results in a better recovery of homogeneous regions than for the cuboid configuration. Some of the results obtained, such as spatial resolution, depend on the interaction position estimation and may vary if other method is employed. [ABSTRACT FROM AUTHOR]

Non-pure positron emitters, with their long half-lives, allow for the tracing of slow biochemical processes which cannot be adequately examined by the commonly used short-lived positron emitters. Most of these isotopes emit high-energy cascade gamma rays in addition to positron decay that can be detected and create a triple coincidence with annihilation photons. Triple coincidence is discarded in most scanners, however, the majority of the triple coincidence contains true photon pairs that can be recovered. In this study, we propose a strategy for recovering triple coincidence events to raise the sensitivity of PET imaging for non-pure positron emitters. To identify the true line of response (LOR) from a triple coincidence, a framework utilizing geometrical, energy and temporal information is proposed. The geometrical criterion is based on the assumption that the LOR with the largest radial offset among the three sub pairs of triple coincidences is least likely to be a true LOR. Then, a confidence time window is used to test the valid LOR among those within triple coincidence. Finally, a likelihood ratio discriminant rule based on the energy probability density distribution of cascade and annihilation gammas is established to identify the true LOR. An Inveon preclinical PET scanner was modeled with GATE (GEANT4 application for tomographic emission) Monte Carlo software. We evaluated the performance of the proposed method in terms of identification fraction, noise equivalent count rates (NECR), and image quality on various phantoms. With the inclusion of triple coincidence events using the proposed method, the NECR was found to increase from 11% to 26% and 19% to 29% for I-124 and Br-76, respectively, when 7.4–185 MBq of activity was used. Compared to the reconstructed images using double coincidence, this technique increased the SNR by 5.1–7.3% for I-124 and 9.3–10.3% for Br-76 within the activity range of 9.25–74 MBq, without compromising the spatial resolution or contrast. We conclude that the proposed method can improve the counting statistics of PET imaging for non-pure positron emitters and is ready to be implemented on current PET systems. [ABSTRACT FROM AUTHOR]

In Positron Emission Tomography, there are several causes of quantitative inaccuracy, such as partial volume or spillover effects. The impact of these effects is greater when using radionuclides that have a large positron range, e.g. 68Ga and 124I, which have been increasingly used in the clinic. We have implemented and evaluated a local projection algorithm (LPA), originally evaluated for SPECT, to compensate for both partial-volume and spillover effects in PET. This method is based on the use of a high-resolution CT or MR image, co-registered with a PET image, which permits a high-resolution segmentation of a few tissues within a volume of interest (VOI) centered on a region within which tissue-activity values need to be estimated. The additional boundary information is used to obtain improved activity estimates for each tissue within the VOI, by solving a simple inversion problem. We implemented this algorithm for the preclinical Argus PET/CT scanner and assessed its performance using the radionuclides 18F, 68Ga and 124I. We also evaluated and compared the results obtained when it was applied during the iterative reconstruction, as well as after the reconstruction as a postprocessing procedure. In addition, we studied how LPA can help to reduce the ‘spillover contamination’, which causes inaccurate quantification of lesions in the immediate neighborhood of large, ‘hot’ sources. Quantification was significantly improved by using LPA, which provided more accurate ratios of lesion-to-background activity concentration for hot and cold regions. For 18F, the contrast was improved from 3.0 to 4.0 in hot lesions (when the true ratio was 4.0) and from 0.16 to 0.06 in cold lesions (true ratio  =  0.0), when using the LPA postprocessing. Furthermore, activity values estimated within the VOI using LPA during reconstruction were slightly more accurate than those obtained by post-processing, while also visually improving the image contrast and uniformity within the VOI. [ABSTRACT FROM AUTHOR]

In this work a comparison between experimental and simulated data using GATE and PeneloPET Monte Carlo simulation packages is presented. All simulated setups, as well as the experimental measurements, followed exactly the guidelines of the NEMA NU 4-2008 standards using the microPET R4 scanner. The comparison was focused on spatial resolution, sensitivity, scatter fraction and counting rates performance. Both GATE and PeneloPET showed reasonable agreement for the spatial resolution when compared to experimental measurements, although they lead to slight underestimations for the points close to the edge. High accuracy was obtained between experiments and simulations of the system’s sensitivity and scatter fraction for an energy window of 350–650 keV, as well as for the counting rate simulations. The latter was the most complicated test to perform since each code demands different specifications for the characterization of the system’s dead time. Although simulated and experimental results were in excellent agreement for both simulation codes, PeneloPET demanded more information about the behavior of the real data acquisition system. To our knowledge, this constitutes the first validation of these Monte Carlo codes for the full NEMA NU 4-2008 standards for small animal PET imaging systems. [ABSTRACT FROM AUTHOR]

A procedure to characterize beams of a medical linear accelerator for their use in Monte Carlo (MC) dose calculations for intraoperative electron radiation therapy (IOERT) is presented. The procedure relies on dose measurements in homogeneous media as input, avoiding the need for detailed simulations of the accelerator head. An iterative algorithm (EM-ML) has been employed to extract the relevant details of the phase space (PHSP) of the particles coming from the accelerator, such as energy spectra, spatial distribution and angle of emission of particles. The algorithm can use pre-computed dose volumes in water and/or air, so that the machine-specific tuning with actual data can be performed in a few minutes. To test the procedure, MC simulations of a linear accelerator with typical IOERT applicators and energies, have been performed and taken as reference. A solution PHSP derived from the dose produced by the simulated accelerator has been compared to the reference PHSP. Further, dose delivered by the simulated accelerator for setups not included in the fit of the PHSP were compared to the ones derived from the solution PHSP. The results show that it is possible to derive from dose measurements PHSP accurate for IOERT MC dose estimations. [ABSTRACT FROM AUTHOR]

This work analysed the feasibility of using a fast, customized Monte Carlo (MC) method to perform accurate computation of dose distributions during pre- and intraplanning of intraoperative electron radiation therapy (IOERT) procedures. The MC method that was implemented, which has been integrated into a specific innovative simulation and planning tool, is able to simulate the fate of thousands of particles per second, and it was the aim of this work to determine the level of interactivity that could be achieved. The planning workflow enabled calibration of the imaging and treatment equipment, as well as manipulation of the surgical frame and insertion of the protection shields around the organs at risk and other beam modifiers. In this way, the multidisciplinary team involved in IOERT has all the tools necessary to perform complex MC dosage simulations adapted to their equipment in an efficient and transparent way. To assess the accuracy and reliability of this MC technique, dose distributions for a monoenergetic source were compared with those obtained using a general-purpose software package used widely in medical physics applications. Once accuracy of the underlying simulator was confirmed, a clinical accelerator was modelled and experimental measurements in water were conducted. A comparison was made with the output from the simulator to identify the conditions under which accurate dose estimations could be obtained in less than 3 min, which is the threshold imposed to allow for interactive use of the tool in treatment planning. Finally, a clinically relevant scenario, namely early-stage breast cancer treatment, was simulated with pre- and intraoperative volumes to verify that it was feasible to use the MC tool intraoperatively and to adjust dose delivery based on the simulation output, without compromising accuracy. The workflow provided a satisfactory model of the treatment head and the imaging system, enabling proper configuration of the treatment planning system and providing good accuracy in the dosage simulation. [ABSTRACT FROM AUTHOR]