Gamma-ray sources imaging and test-beam results with MACACO III Compton camera.

Hadron therapy is a radiotherapy modality which offers a precise energy deposition to the tumors and a dose reduction to healthy tissue as compared to conventional methods. However, methods for real-time monitoring are required to ensure that the radiation dose is deposited on the target. The IRIS group of IFIC-Valencia developed a Compton camera prototype for this purpose, intending to image the Prompt Gammas emitted by the tissue during irradiation. The system detectors are composed of Lanthanum (III) bromide scintillator crystals coupled to silicon photomultipliers. After an initial characterization in the laboratory, in order to assess the system capabilities for future experiments in proton therapy centers, different tests were carried out in two facilities: PARTREC (Groningen, The Netherlands) and the CNA cyclotron (Sevilla, Spain). Characterization studies performed at PARTREC indicated that the detectors linearity was improved with respect to the previous version and an energy resolution of 5.2 % FWHM at 511 keV was achieved. Moreover, the imaging capabilities of the system were evaluated with a line source of 68Ge and a point-like source of 241Am-9Be. Images at 4.439 MeV were obtained from irradiation of a graphite target with an 18 MeV proton beam at CNA, to perform a study of the system potential to detect shifts at different intensities. In this sense, the system was able to distinguish 1 mm variations in the target position at different beam current intensities for measurement times of 1800 and 600 s.

Influence of the background in Compton camera images for proton therapy treatment monitoring.

Objective. Background events are one of the most relevant contributions to image degradation in Compton camera imaging for hadron therapy treatment monitoring. A study of the background and its contribution to image degradation is important to define future strategies to reduce the background in the system.Approach. In this simulation study, the percentage of different kinds of events and their contribution to the reconstructed image in a two-layer Compton camera have been evaluated. To this end, GATE v8.2 simulations of a proton beam impinging on a PMMA phantom have been carried out, for different proton beam energies and at different beam intensities.Main results. For a simulated Compton camera made of Lanthanum (III) Bromide monolithic crystals, coincidences caused by neutrons arriving from the phantom are the most common type of background produced by secondary radiations in the Compton camera, causing between 13% and 33% of the detected coincidences, depending on the beam energy. Results also show that random coincidences are a significant cause of image degradation at high beam intensities, and their influence in the reconstructed images is studied for values of the time coincidence windows from 500 ps to 100 ns.Significance. Results indicate the timing capabilities required to retrieve the fall-off position with good precision. Still, the noise observed in the image when no randoms are considered make us consider further background rejection methods.

Joint image reconstruction algorithm in Compton cameras.

Objective.To demonstrate the benefits of using an joint image reconstruction algorithm based on the List Mode Maximum Likelihood Expectation Maximization that combines events measured in different channels of information of a Compton camera.Approach.Both simulations and experimental data are employed to show the algorithm performance.Main results.The obtained joint images present improved image quality and yield better estimates of displacements of high-energy gamma-ray emitting sources. The algorithm also provides images that are more stable than any individual channel against the noisy convergence that characterizes Maximum Likelihood based algorithms.Significance.The joint reconstruction algorithm can improve the quality and robustness of Compton camera images. It also has high versatility, as it can be easily adapted to any Compton camera geometry. It is thus expected to represent an important step in the optimization of Compton camera imaging.

MACACO II test-beam with high energy photons.

The IRIS group at IFIC Valencia is developing a three-layer Compton camera for treatment monitoring in proton therapy. The system is composed of three detector planes, each made of a [Formula: see text] monolithic crystal coupled to a SiPM array. Having obtained successful results with the first prototype (MACACO) that demonstrated the feasibility of the proposed technology, a second prototype (MACACO II) with improved performance has been developed, and is the subject of this work. The new system has an enhanced detector energy resolution which translates into a higher spatial resolution of the telescope. The image reconstruction method has also been improved with an accurate model of the sensitivity matrix. The device has been tested with high energy photons at the National Accelerator Centre (CNA, Seville). The tests involved a proton beam of 18 MeV impinging on a graphite target, to produce 4.4 MeV photons. Data were taken at different system positions of the telescope with the first detector at 65 and 160 mm from the target, and at different beam intensities. The measurements allowed successful reconstruction of the photon emission distribution at two target positions separated by 5 mm in different telescope configurations. This result was obtained both with data recorded in the first and second telescope planes (two interaction events) and, for the first time in beam experiments, with data recorded in the three planes (three interaction events).

Image reconstruction for a multi-layer Compton telescope: an analytical model for three interaction events.

Compton Cameras are electronically collimated photon imagers suitable for sub-MeV to few MeV gamma-ray detection. Such features are desirable to enable in vivo range verification in hadron therapy, through the detection of secondary Prompt Gammas. A major concern with this technique is the poor image quality obtained when the incoming gamma-ray energy is unknown. Compton Cameras with more than two detector planes (multi-layer Compton Cameras) have been proposed as a solution, given that these devices incorporate more signal sequences of interactions to the conventional two interaction events. In particular, three interaction events convey more spectral information as they allow inferring directly the incident gamma-ray energy. A three-layer Compton Telescope based on continuous Lanthanum (III) Bromide crystals coupled to Silicon Photomultipliers is being developed at the IRIS group of IFIC-Valencia. In a previous work we proposed a spectral reconstruction algorithm for two interaction events based on an analytical model for the formation of the signal. To fully exploit the capabilities of our prototype, we present here an extension of the model for three interaction events. Analytical expressions of the sensitivity and the System Matrix are derived and validated against Monte Carlo simulations. Implemented in a List Mode Maximum Likelihood Expectation Maximization algorithm, the proposed model allows us to obtain four-dimensional (energy and position) images by using exclusively three interaction events. We are able to recover the correct spectrum and spatial distribution of gamma-ray sources when ideal data are employed. However, the uncertainties associated to experimental measurements result in a degradation when real data from complex structures are employed. Incorrect estimation of the incident gamma-ray interaction positions, and missing deposited energy associated with escaping secondaries, have been identified as the causes of such degradation by means of a detailed Monte Carlo study. As expected, our current experimental resolution and efficiency to three interaction events prevents us from correctly recovering complex structures of radioactive sources. However, given the better spectral information conveyed by three interaction events, we expect an improvement of the image quality of conventional Compton imaging when including such events. In this regard, future development includes the incorporation of the model assessed in this work to the two interaction events model in order to allow using simultaneously two and three interaction events in the image reconstruction.

CCMod: a GATE module for Compton camera imaging simulation.

Compton cameras are gamma-ray imaging systems which have been proposed for a wide variety of applications such as medical imaging, nuclear decommissioning or homeland security. In the design and optimization of such a system Monte Carlo simulations play an essential role. In this work, we propose a generic module to perform Monte Carlo simulations and analyses of Compton Camera imaging which is included in the open-source GATE/Geant4 platform. Several digitization stages have been implemented within the module to mimic the performance of the most commonly employed detectors (e.g. monolithic blocks, pixelated scintillator crystals, strip detectors...). Time coincidence sorter and sequence coincidence reconstruction are also available in order to aim at providing modules to facilitate the comparison and reproduction of the data taken with different prototypes. All processing steps may be performed during the simulation (on-the-fly mode) or as a post-process of the output files (offline mode). The predictions of the module have been compared with experimental data in terms of energy spectra, angular resolution, efficiency and back-projection image reconstruction. Consistent results within a 3-sigma interval were obtained for the energy spectra except for low energies where small differences arise. The angular resolution measure for incident photons of 1275 keV was also in good agreement between both data sets with a value close to 13°. Moreover, with the aim of demonstrating the versatility of such a tool the performance of two different Compton camera designs was evaluated and compared.

Experimental evaluation of the resolution improvement provided by a silicon PET probe.

A high-resolution PET system, which incorporates a silicon detector probe into a conventional PET scanner, has been proposed to obtain increased image quality in a limited region of interest. Detailed simulation studies have previously shown that the additional probe information improves the spatial resolution of the reconstructed image and increases lesion detectability, with no cost to other image quality measures. The current study expands on the previous work by using a laboratory prototype of the silicon PET-probe system to examine the resolution improvement in an experimental setting. Two different versions of the probe prototype were assessed, both consisting of a back-to-back pair of 1-mm thick silicon pad detectors, one arranged in 32 × 16 arrays of 1.4 mm × 1.4 mm pixels and the other in 40 × 26 arrays of 1.0 mm × 1.0 mm pixels. Each detector was read out by a set of VATAGP7 ASICs and a custom-designed data acquisition board which allowed trigger and data interfacing with the PET scanner, itself consisting of BGO block detectors segmented into 8 × 6 arrays of 6 mm × 12 mm × 30 mm crystals. Limited-angle probe data was acquired from a group of Na-22 point-like sources in order to observe the maximum resolution achievable using the probe system. Data from a Derenzo-like resolution phantom was acquired, then scaled to obtain similar statistical quality as that of previous simulation studies. In this case, images were reconstructed using measurements of the PET ring alone and with the inclusion of the probe data. Images of the Na-22 source demonstrated a resolution of 1.5 mm FWHM in the probe data, the PET ring resolution being approximately 6 mm. Profiles taken through the image of the Derenzo-like phantom showed a clear increase in spatial resolution. Improvements in peak-to-valley ratios of 50% and 38%, in the 4.8 mm and 4.0 mm phantom features respectively, were observed, while previously unresolvable 3.2 mm features were brought to light by the addition of the probe. These results support the possibility of improving the image resolution of a clinical PET scanner using the silicon PET-probe.

Noise evaluation of Compton camera imaging for proton therapy.

Compton Cameras emerged as an alternative for real-time dose monitoring techniques for Particle Therapy (PT), based on the detection of prompt-gammas. As a consequence of the Compton scattering process, the gamma origin point can be restricted onto the surface of a cone (Compton cone). Through image reconstruction techniques, the distribution of the gamma emitters can be estimated, using cone-surfaces backprojections of the Compton cones through the image space, along with more sophisticated statistical methods to improve the image quality. To calculate the Compton cone required for image reconstruction, either two interactions, the last being photoelectric absorption, or three scatter interactions are needed. Because of the high energy of the photons in PT the first option might not be adequate, as the photon is not absorbed in general. However, the second option is less efficient. That is the reason to resort to spectral reconstructions, where the incoming γ energy is considered as a variable in the reconstruction inverse problem. Jointly with prompt gamma, secondary neutrons and scattered photons, not strongly correlated with the dose map, can also reach the imaging detector and produce false events. These events deteriorate the image quality. Also, high intensity beams can produce particle accumulation in the camera, which lead to an increase of random coincidences, meaning events which gather measurements from different incoming particles. The noise scenario is expected to be different if double or triple events are used, and consequently, the reconstructed images can be affected differently by spurious data. The aim of the present work is to study the effect of false events in the reconstructed image, evaluating their impact in the determination of the beam particle ranges. A simulation study that includes misidentified events (neutrons and random coincidences) in the final image of a Compton Telescope for PT monitoring is presented. The complete chain of detection, from the beam particle entering a phantom to the event classification, is simulated using FLUKA. The range determination is later estimated from the reconstructed image obtained from a two and three-event algorithm based on Maximum Likelihood Expectation Maximization. The neutron background and random coincidences due to a therapeutic-like time structure are analyzed for mono-energetic proton beams. The time structure of the beam is included in the simulations, which will affect the rate of particles entering the detector.

Silicon detectors for combined MR-PET and MR-SPECT imaging.

Silicon based devices can extend PET-MR and SPECT-MR imaging to applications, where their advantages in performance outweigh benefits of high statistical counts.Silicon is in many ways an excellent detector material with numerous advantages, among others: excellent energy and spatial resolution, mature processing technology, large signal to noise ratio, relatively low price, availability, versatility and malleability. The signal in silicon is also immune to effects of magnetic field at the level normally used in MR devices. Tests in fields up to 7 T were performed in a study to determine effects of magnetic field on positron range in a silicon PET device. The curvature of positron tracks in direction perpendicular to the field's orientation shortens the distance between emission and annihilation point of the positron. The effect can be fully appreciated for a rotation of the sample for a fixed field direction, compressing range in all dimensions. A popular Ga-68 source was used showing a factor of 2 improvement in image noise compared to zero field operation. There was also a little increase in noise as the reconstructed resolution varied between 2.5 and 1.5 mm.A speculative applications can be recognized in both emission modalities, SPECT and PET.Compton camera is a subspecies of SPECT, where a silicon based scatter as a MR compatible part could inserted into the MR bore and the secondary detector could operate in less constrained environment away from the magnet. Introducing a Compton camera also relaxes requirements of the radiotracers used, extending the range of conceivable photon energies beyond 140.5 keV of the Tc-99m.In PET, one could exploit the compressed sub-millimeter range of positrons in the magnetic field. To exploit the advantage, detectors with spatial resolution commensurate to the effect must be used with silicon being an excellent candidate. Measurements performed outside of the MR achieving spatial resolution below 1 mm are reported.

Olfactory bulbectomy, but not odor conditioned aversion, induces the differentiation of immature neurons in the adult rat piriform cortex.

The piriform cortex layer II of young-adult rats presents a population of prenatally generated cells, which express immature neuronal markers, such as the polysialylated form of the neural cell adhesion molecule (PSA-NCAM) or doublecortin (DCX), and display structural characteristics of immature neurons. The number of PSA-NCAM/DCX expressing cells in this region decreases markedly as age progresses, suggesting that these cells differentiate or die. Since the piriform cortex receives a major input from the olfactory bulb and participates in olfactory information processing, it is possible that the immature neurons in layer II are affected by manipulations of the olfactory bulb or olfactory learning. It is not known whether these cells can be induced to differentiate and, if so, what would be their fate. In order to address these questions, we have performed unilateral olfactory bulbectomy (OBX) and an olfactory learning paradigm (taste-potentiated odor aversion, TPOA), in young-adult rats and have studied the expression of different mature and immature neuronal markers, as well as the presence of cell death. We have found that 14 h after OBX there was a dramatic decrease in the number of both PSA-NCAM and DCX expressing cells in piriform cortex layer II, whereas that of cells expressing NeuN, a mature neuronal marker, increased. By contrast, the number of cells expressing glutamate decarboxylase, isoform 67 (GAD67), a marker for interneurons, decreased slightly. Additionally, we have not found evidence of numbers of dying cells high enough to justify the disappearance of immature neurons. Analysis of animals subjected to TPOA revealed that this paradigm does not affect PSA-NCAM expressing cells. Our results strongly suggest that OBX can induce the maturation of immature neurons in the piriform cortex layer II and that these cells do not become interneurons. By contrast, these cells do not seem to play a crucial role in olfactory memory.

Characterization of a PET detector head based on continuous LYSO crystals and monolithic, 64-pixel silicon photomultiplier matrices.

The characterization of a PET detector head based on continuous LYSO crystals and silicon photomultiplier (SiPM) arrays as photodetectors has been carried out for its use in the development of a small animal PET prototype. The detector heads are composed of a continuous crystal and a SiPM matrix with 64 pixels in a common substrate, fabricated specifically for this project. Three crystals of 12 mm × 12 mm × 5 mm size with different types of painting have been tested: white, black and black on the sides but white on the back of the crystal. The best energy resolution, obtained with the white crystal, is 16% FWHM. The detector response is linear up to 1275 keV. Tests with different position determination algorithms have been carried out with the three crystals. The spatial resolution obtained with the center of gravity algorithm is around 0.9 mm FWHM for the three crystals. As expected, the use of this algorithm results in the displacement of the reconstructed position toward the center of the crystal, more pronounced in the case of the white crystal. A maximum likelihood algorithm has been tested that can reconstruct correctly the interaction position of the photons also in the case of the white crystal.

Divergent impact of the polysialyltransferases ST8SiaII and ST8SiaIV on polysialic acid expression in immature neurons and interneurons of the adult cerebral cortex.

Polysialic acid (PSA) is a negatively charged carbohydrate polymer, which confers antiadhesive properties to the neural cell adhesion molecule NCAM and facilitates cellular plasticity during brain development. In mice, PSA expression decreases drastically during the first postnatal weeks and it gets confined to immature neurons and regions displaying structural plasticity during adulthood. In the brain, PSA is exclusively synthesized by the two polysialyltransferases ST8SiaII and ST8SiaIV. To study their individual contribution to polysialylation in the adult, we analyzed PSA expression in mice deficient for either polysialyltransferase. Focusing on the cerebral cortex, our results indicate that ST8SiaIV is solely responsible for PSA expression in mature interneurons and in most regions of cortical neuropil. By contrast, ST8SiaII is the major polysialyltransferase in immature neurons of the paleocortex layer II and the hippocampal subgranular zone. The numbers of cells expressing PSA or doublecortin, another marker of immature neurons, were increased in the paleocortex layer II of ST8SiaIV-deficient mice, indicating altered differentiation of these cells. Analysis of doublecortin expression also indicated that the production of new granule neurons in the subgranular zone of ST8SiaII-deficient mice is not affected. However, many of the immature granule neurons showed aberrant locations and morphology, suggesting a role of ST8SiaII in their terminal differentiation.

NMDA receptor antagonist treatment induces a long-lasting increase in the number of proliferating cells, PSA-NCAM-immunoreactive granule neurons and radial glia in the adult rat dentate gyrus.

During adulthood, neural precursors located in the subgranular zone of the dentate gyrus continue to proliferate, leading to the generation of new granule neurons. These recently generated cells transiently express the polysialylated form of the neural cell adhesion molecule, PSA-NCAM, and are supported by radial glia-like cells that are likely to play a role in neuronal migration and differentiation, or even act as their precursors. Previous reports indicate that treatment with NMDA receptor antagonists stimulates adult neurogenesis in the dentate gyrus, and because of the potential therapeutic value of this approach, we were interested in further characterizing the consequences of pharmacologically modulating this process. We treated adult rats with the competitive NMDA receptor antagonist, CGP43487, and examined cell proliferation, PSA-NCAM expression, and changes in the radial glia cell population in the subgranular zone at different time points. In addition, we sought to determine if this treatment led to changes in cell death or gliotic reactions. The number of proliferating cells in the subgranular region of the dentate gyrus was increased significantly 2 days after treatment and it remained elevated 7 days postinjection. PSA-NCAM-immunoreactive granule cells and nestin-expressing radial glia-like cells also increased in number 7 days after the treatment. In contrast, we did not observe any change in granule cell death, and we were unable to detect any microglial or astroglial reaction during the first 7 days after treatment. Thus, NMDA receptor antagonist treatment serves as a valuable tool to increase neurogenesis in the adult hippocampus without undesirable collateral deleterious effects.