Reconstruction of multi-animal PET acquisitions with anisotropically variant PSF.

Among other factors such as random, attenuation and scatter corrections, uniform spatial resolution is key to performing accurate quantitative studies in Positron emission tomography (PET). Particularly in preclinical PET studies involving simultaneous acquisition of multiple animals, the degradation of image resolution due to the depth of interaction (DOI) effect far from the center of the Field of View (FOV) becomes a significant concern. In this work, we incorporated a spatially-variant resolution model into a real time iterative reconstruction code to obtain accurate images of multi-animal acquisition. We estimated the spatially variant point spread function (SV-PSF) across the FOV using measurements and Monte Carlo (MC) simulations. The SV-PSF obtained was implemented in a GPU-based Ordered subset expectation maximization (OSEM) reconstruction code, which includes scatter, attenuation and random corrections. The method was evaluated with acquisitions from two preclinical PET/CT scanners of the SEDECAL Argus family: a Derenzo phantom placed 2 cm off center in the 4R-SuperArgus, and a multi-animal study with 4 mice in the 6R-SuperArgus. The SV-PSF reconstructions showed uniform spatial resolution without significant increase in reconstruction time, with superior image quality compared to the uniform PSF model.

Dictionary-based software for proton dose reconstruction and submilimetric range verification.

Objective.This paper presents a new method for fast reconstruction (compatible with in-beam use) of deposited dose during proton therapy using data acquired from a PET scanner. The most innovative feature of this novel method is the production of noiseless reconstructed dose distributions from which proton range can be derived with high precision.Approach.A new MLEM & simulated annealing (MSA) algorithm, developed especially in this work, reconstructs the deposited dose distribution from a realistic pre-calculated activity-dose dictionary. This dictionary contains the contribution of each beam in the plan to the 3D activity and dose maps, as calculated by a Monte Carlo simulation. The MSA algorithm, usinga prioriinformation of the treatment plan, seeks for the linear combination of activities of the precomputed beams that best fits the observed PET data, obtaining at the same time the deposited dose.Main results.the method has been tested using simulated data to determine its performance under 4 different test cases: (1) dependency of range detection accuracy with delivered dose, (2) in-beam versus offline verification, (3) ability to detect anatomical changes and (4) reconstruction of a realistic spread-out Bragg peak. The results show the ability of the method to accurately reconstruct doses from PET data corresponding to 1 Gy irradiations, both in intra-fraction and inter-fraction verification scenarios. For this dose level (1 Gy) the method was able to spot range variations as small as 0.6 mm.Significance.out method is able to reconstruct dose maps with remarkable accuracy from clinically relevant dose levels down to 1 Gy. Furthermore, due to the noiseless nature of reconstructed dose maps, an accuracy better than one millimeter was obtained in proton range estimates. These features make of this method a realistic option for range verification in proton therapy.

Electron versus Muon Neutrino Induced Cross Sections in Charged Current Quasielastic Processes.

Differences between ν_{e} and ν_{µ} quasielastic cross sections are essential in neutrino oscillation analyses and CP violation searches for experiments such as DUNE and T2HK. The ratio of these is however poorly known experimentally and for certain kinematic regions theoretical models give contradictory answers. We use two independent mean-field based models to investigate this ratio using ^{40}Ar and ^{12}C targets. We demonstrate that a proper treatment of the final nucleon's wave function confirms the dominance of ν_{µ} over ν_{e} induced cross sections at forward lepton scattering.

Fast optimized Monte Carlo phase-space generation and dose prediction for low energy x-ray intra-operative radiation therapy.

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.

Time domain reconstruction of sound speed and attenuation in ultrasound computed tomography using full wave inversion.

Ultrasound computed tomography (USCT) is a non-invasive imaging technique that provides information about the acoustic properties of soft tissues in the body, such as the speed of sound (SS) and acoustic attenuation (AA). Knowledge of these properties can improve the discrimination between benign and malignant masses, especially in breast cancer studies. Full wave inversion (FWI) methods for image reconstruction in USCT provide the best image quality compared to more approximate methods. Using FWI, the SS is usually recovered in the time domain, and the AA is usually recovered in the frequency domain. Nevertheless, as both properties can be obtained from the same data, it is desirable to have a common framework to reconstruct both distributions. In this work, an algorithm is proposed to reconstruct both the SS and AA distributions using a time domain FWI methodology based on the fractional Laplacian wave equation, an adjoint field formulation, and a gradient-descent method. The optimization code employs a Compute Unified Device Architecture version of the software k-Wave, which provides high computational efficiency. The performance of the method was evaluated using simulated noisy data from numerical breast phantoms. Errors were less than 0.5% in the recovered SS and 10% in the AA.

223Ra-dichloride spectrometric characterization: Searching for the presence of long-lived isotopes with radiological protection implications.

223Ra-dichloride was approved with the commercial name of Xofigo in 2014 for treatment of metastatic castration-resistant prostate cancer. 223Ra is obtained by neutron irradiation of 226Ra yielding 227Ac, which decays to 227Th and 223Fr, both decaying to 223Ra. Since 223Ra is predominantly (95.3%) an alpha emitter with a 11.42days long half-life, the radiopharmaceutical, its remnants, the patient, and waste material can be managed and disposed with low radiation protection requirements. 227Ac is a long-lived (T1/2=21.77years) beta emitter that demands strong radiation protection measures. In particular waste disposal has to follow the International Atomic Energy Agency (IAEA) and European Commission (EC) regulations. Since 227Ac is involved in the production of 223Ra, an impurity analysis of each batch is required after production. Due to time restrictions, the manufacturer's detection limit (<0.001%) exceeds the one required to assure that 227Ac concentrations are below direct disposal levels. To improve the detection limit, long-term accurate spectroscopy is required. Alpha and gamma spectroscopy measurements were carried out at the Complutense University Nuclear Physics Laboratory. After twelve months follow up of a sample, 227Ac concentration was found to be smaller than 10-9. This allows for direct waste disposal and no additional radiation protection restrictions than those required for 223Ra. The presence of contamination by other radioisotopes was also ruled out by this experiment. Specifically 226Ra, involved in 223Ra production as the original parent and with a very long-lived (T1/2=1577years) alpha emitter, was also below the experimental detection limit.

Efficiency measurement and Monte Carlo simulations of a CeBr3 scintillator.

CeBr3 crystals meet many of the demands of high performance scintillators, due to their excellent timing properties, good effective Z and high photon yield. It is important to characterize their efficiency and to verify whether modern Monte Carlo codes are reliable enough to reproduced the observed values. We report here on the measurement of both total and photopeak efficiency of a 1" diameter×1" height CeBr3 crystal for gamma-ray energies up to 1.4MeV at several distances, using a variety of low energy gamma rays sources. The measured experimental efficiencies are compared with simulations developed in the framework of PENELOPE and GEANT4.

Improved quantification for local regions of interest in preclinical PET imaging.

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. (68)Ga and (124)I, 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 (18)F, (68)Ga and (124)I. 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 (18)F, 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.

Monte Carlo simulations versus experimental measurements in a small animal PET system. A comparison in the NEMA NU 4-2008 framework.

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.

Phase space determination from measured dose data for intraoperative electron radiation therapy.

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.

Simulation of triple coincidences in PET.

Although current PET scanners are designed and optimized to detect double coincidence events, there is a significant amount of triple coincidences in any PET acquisition. Triple coincidences may arise from causes such as: inter-detector scatter (IDS), random triple interactions (RT), or the detection of prompt gamma rays in coincidence with annihilation photons when non-pure positron-emitting radionuclides are used (ß(+)γ events). Depending on the data acquisition settings of the PET scanner, these triple events are discarded or processed as a set of double coincidences if the energy of the three detected events is within the scanner's energy window. This latter option introduces noise in the data, as at most, only one of the possible lines-of-response defined by triple interactions corresponds to the line along which the decay occurred. Several novel works have pointed out the possibility of using triple events to increase the sensitivity of PET scanners or to expand PET imaging capabilities by allowing differentiation between radiotracers labeled with non-pure and pure positron-emitting radionuclides. In this work, we extended the Monte Carlo simulator PeneloPET to assess the proportion of triple coincidences in PET acquisitions and to evaluate their possible applications. We validated the results of the simulator against experimental data acquired with a modified version of a commercial preclinical PET/CT scanner, which was enabled to acquire and process triple-coincidence events. We used as figures of merit the energy spectra for double and triple coincidences and the triples-to-doubles ratio for different energy windows and radionuclides. After validation, the simulator was used to predict the relative quantity of triple-coincidence events in two clinical scanners assuming different acquisition settings. Good agreement between simulations and preclinical experiments was found, with differences below 10% for most of the observables considered. For clinical scanners and pure positron emitters, we found that around 10% of the processed double events come from triple coincidences, increasing this ratio substantially for non-pure emitters (around 25% for (124)I and > 50% for (86)Y). For radiotracers labeled with (18)F we found that the relative quantity of IDS events in standard acquisitions is around 18% for the preclinical scanner and between 14 and 22% for the clinical scanners. For non-pure positron emitters like (124)I, we found a ß(+)γ triples-to-doubles ratio of 2.5% in the preclinical scanner and of up to 4% in the clinical scanners.

Positron range estimations with PeneloPET.

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 the main 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 ((18)F, (11)C, (13)N, (15)O, (68)Ga and (82)Rb) 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.

Improved dead-time correction for PET scanners: application to small-animal PET.

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.

Misalignments calibration in small-animal PET scanners based on rotating planar detectors and parallel-beam geometry.

Technological advances have improved the assembly process of PET detectors, resulting in quite small mechanical tolerances. However, in high-spatial-resolution systems, even submillimetric misalignments of the detectors may lead to a notable degradation of image resolution and artifacts. Therefore, the exact characterization of misalignments is critical for optimum reconstruction quality in such systems. This subject has been widely studied for CT and SPECT scanners based on cone beam geometry, but this is not the case for PET tomographs based on rotating planar detectors. The purpose of this work is to analyze misalignment effects in these systems and to propose a robust and easy-to-implement protocol for geometric characterization. The result of the proposed calibration method, which requires no more than a simple calibration phantom, can then be used to generate a correct 3D-sinogram from the acquired list mode data.

Regional specificity of thalamic volume deficits in male adolescents with early-onset psychosis.

BACKGROUND: Thalamic volume deficits are associated with psychosis but it is unclear whether the volume reduction is uniformly distributed or whether it is more severe in particular thalamic regions. AIMS: To quantify whole and regional thalamic volume in males with early-onset psychosis and healthy male controls. METHOD: Brain scans were obtained for 80 adolescents: 46 individuals with early-onset psychosis with a duration of positive symptoms less than 6 months and 34 healthy controls. All participants were younger than 19 years. Total thalamic volumes were assessed using FreeSurfer and FSL-FIRST, group comparisons of regional thalamic volumes were studied with a surface-based approach. RESULTS: Total thalamic volume was smaller in participants with early-onset psychosis relative to controls. Regional thalamic volume reduction was most significant in the right anterior mediodorsal area and pulvinar. CONCLUSIONS: In males with minimally treated early-onset psychosis, thalamic volume deficits may be most pronounced in the anterior mediodorsal and posterior pulvinar regions, adding strength to findings from post-mortem studies in adults with psychosis.

Relativistic descriptions of final-state interactions in charged-current quasielastic neutrino-nucleus scattering at MiniBooNE kinematics.

The results of two relativistic models with different descriptions of the final-state interactions are compared with the MiniBooNE data of charged-current quasielastic cross sections. The relativistic mean field model uses the same potential for the bound and ejected nucleon wave functions. In the relativistic Green's function model, the final-state interactions are described in the inclusive scattering consistently with the exclusive scattering using the same complex optical potential. The relativistic Green's function results describe the experimental data for total cross sections without the need to modify the nucleon axial mass.

Gyral and sulcal cortical thinning in adolescents with first episode early-onset psychosis.

BACKGROUND: Psychosis is associated with volumetric decreases of cortical structures. Whether these volumetric decreases imply abnormalities in cortical thickness, surface, or cortical folding is not clear. Due to differences in cytoarchitecture, cortical gyri and sulci might be differentially affected by psychosis. Therefore, we examined differences in gyral and sulcal cortical thickness, surface, folding, and volume between a minimally treated male adolescent population with early-onset first-episode psychosis (EOP) and a healthy control group, with surface-based morphometry. METHODS: Magnetic resonance imaging brain scans were obtained from 49 adolescent EOP patients and 34 healthy control subjects. Subjects were younger than 18 years (age range 12 years-18 years), and EOP patients had a duration of positive symptoms of <6 months. RESULTS: Early-onset first-episode psychosis was associated with local bilateral cortical thinning and volume deficits in both the gyri and sulci of the superior temporal cortex and the inferior, middle, medial, and superior prefrontal cortex. In the pars triangularis and opercularis cortex of patients, gyral cortical thickness was thinner, whereas sulcal thickness was not. Patients exhibited cortical thinning together with a decreased degree of cortical folding in the right superior frontal cortex. CONCLUSIONS: Cortical thinning of both gyri and sulci seem to underlie most cortical volume deficits in adolescent patients with EOP. Except for the right superior frontal region, the degree of cortical folding was normal in regions showing decreased cortical thickness, suggesting that the process of cortical thinning in adolescent patients with EOP primarily takes place after the formation of cortical folds.

PeneloPET, a Monte Carlo PET simulation tool based on PENELOPE: features and validation.

Monte Carlo simulations play an important role in positron emission tomography (PET) imaging, as an essential tool for the research and development of new scanners and for advanced image reconstruction. PeneloPET, a PET-dedicated Monte Carlo tool, is presented and validated in this work. PeneloPET is based on PENELOPE, a Monte Carlo code for the simulation of the transport in matter of electrons, positrons and photons, with energies from a few hundred eV to 1 GeV. PENELOPE is robust, fast and very accurate, but it may be unfriendly to people not acquainted with the FORTRAN programming language. PeneloPET is an easy-to-use application which allows comprehensive simulations of PET systems within PENELOPE. Complex and realistic simulations can be set by modifying a few simple input text files. Different levels of output data are available for analysis, from sinogram and lines-of-response (LORs) histogramming to fully detailed list mode. These data can be further exploited with the preferred programming language, including ROOT. PeneloPET simulates PET systems based on crystal array blocks coupled to photodetectors and allows the user to define radioactive sources, detectors, shielding and other parts of the scanner. The acquisition chain is simulated in high level detail; for instance, the electronic processing can include pile-up rejection mechanisms and time stamping of events, if desired. This paper describes PeneloPET and shows the results of extensive validations and comparisons of simulations against real measurements from commercial acquisition systems. PeneloPET is being extensively employed to improve the image quality of commercial PET systems and for the development of new ones.

Superscaling predictions for neutral current quasielastic neutrino-nucleus scattering.

The application of superscaling ideas to predict neutral-current (NC) quasielastic (QE) neutrino cross sections is investigated. The relativistic impulse approximation (RIA) using the same relativistic mean field potential (RMF) for both initial and final nucleons - a model that reproduces the experimental (e,e(')) scaling function - is used to illustrate our findings. While NC reactions are apparently not well suited for scaling analyses, to a large extent, the RIA-RMF predictions do exhibit superscaling. Independence of the scaled response on the nuclear species is very well fulfilled. The RIA-RMF NC superscaling function is in good agreement with the experimental (e,e(')) one. The idea that electroweak processes can be described with a universal scaling function, provided that mild restrictions on the kinematics are assumed, is shown to be valid.

FIRST: Fast Iterative Reconstruction Software for (PET) tomography.

Small animal PET scanners require high spatial resolution and good sensitivity. To reconstruct high-resolution images in 3D-PET, iterative methods, such as OSEM, are superior to analytical reconstruction algorithms, although their high computational cost is still a serious drawback. The higher performance of modern computers could make iterative image reconstruction fast enough to be viable, provided we are able to deal with the large number of probability coefficients for the system response matrix in high-resolution PET scanners, which is a difficult task that prevents the algorithms from reaching peak computing performance. Considering all possible axial and in-plane symmetries, as well as certain quasi-symmetries, we have been able to reduce the memory requirements to store the system response matrix (SRM) well below 1 GB, which allows us to keep the whole response matrix of the system inside RAM of ordinary industry-standard computers, so that the reconstruction algorithm can achieve near peak performance. The elements of the SRM are stored as cubic spline profiles and matched to voxel size during reconstruction. In this way, the advantages of 'on-the-fly' calculation and of fully stored SRM are combined. The on-the-fly part of the calculation (matching the profile functions to voxel size) of the SRM accounts for 10-30% of the reconstruction time, depending on the number of voxels chosen. We tested our approach with real data from a commercial small animal PET scanner. The results (image quality and reconstruction time) show that the proposed technique is a feasible solution.