Hybrid PET/Compton-camera imaging: an imager for the next generation.

Compton cameras can offer advantages over gamma cameras for some applications, since they are well suited for multitracer imaging and for imaging high-energy radiotracers, such as those employed in radionuclide therapy. While in conventional clinical settings state-of-the-art Compton cameras cannot compete with well-established methods such as PET and SPECT, there are specific scenarios in which they can constitute an advantageous alternative. The combination of PET and Compton imaging can benefit from the improved resolution and sensitivity of current PET technology and, at the same time, overcome PET limitations in the use of multiple radiotracers. Such a system can provide simultaneous assessment of different radiotracers under identical conditions and reduce errors associated with physical factors that can change between acquisitions. Advances are being made both in instrumentation developments combining PET and Compton cameras for multimodal or three-gamma imaging systems, and in image reconstruction, addressing the challenges imposed by the combination of the two modalities or the new techniques. This review article summarizes the advances made in Compton cameras for medical imaging and their combination with PET.

Proton range verification with MACACO II Compton camera enhanced by a neural network for event selection.

The applicability extent of hadron therapy for tumor treatment is currently limited by the lack of reliable online monitoring techniques. An active topic of investigation is the research of monitoring systems based on the detection of secondary radiation produced during treatment. MACACO, a multi-layer Compton camera based on LaBr3 scintillator crystals and SiPMs, is being developed at IFIC-Valencia for this purpose. This work reports the results obtained from measurements of a 150 MeV proton beam impinging on a PMMA target. A neural network trained on Monte Carlo simulations is used for event selection, increasing the signal to background ratio before image reconstruction. Images of the measured prompt gamma distributions are reconstructed by means of a spectral reconstruction code, through which the 4.439 MeV spectral line is resolved. Images of the emission distribution at this energy are reconstructed, allowing calculation of the distal fall-off and identification of target displacements of 3 mm.

A spectral reconstruction algorithm for two-plane Compton cameras.

One factor limiting the current applicability extent of hadron therapy is the lack of a reliable method for real time treatment monitoring. The use of Compton imaging systems as monitors requires the correct reconstruction of the distribution of prompt gamma productions during patient irradiation. In order to extract the maximum information from all the measurable events, we implemented a spectral reconstruction method that assigns to all events a probability of being either partial or total energy depositions. The method, implemented in a list-mode maximum likelihood expectation maximization algorithm, generates a four dimensional image in the joint spatial-spectral domain, in which the voxels containing the emission positions and energies are obtained. The analytical model used for the system response function is also employed to derive an analytical expression for the sensitivity, which is calculated via Monte Carlo integration. The performance of the method is evaluated through reconstruction of various experimental and simulated sources with different spatial and energy distributions. The results show that the proposed method can recover the spectral and spatial information simultaneously, but only under the assumption of ideal measurements. The analysis of the Monte Carlo simulations has led to the identification of two important degradation sources: the mispositioning of the gamma interaction point and the missing energy recorded in the interaction. Both factors are related to the high energy transferred to the recoil electrons, which can travel far from the interaction point and even escape the detector. These effects prevent the direct application of the current method in more realistic scenarios. Nevertheless, experimental point-like sources have been accurately reconstructed and the spatial distributions and spectral emission of complex simulated phantoms can be identified.

Study of sensitivity and resolution for full ring PET prototypes based on continuous crystals and analytical modeling of the light distribution.

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.

Study and comparison of different sensitivity models for a two-plane Compton camera.

Given the strong variations in the sensitivity of Compton cameras for the detection of events originating from different points in the field of view (FoV), sensitivity correction is often necessary in Compton image reconstruction. Several approaches for the calculation of the sensitivity matrix have been proposed in the literature. While most of these models are easily implemented and can be useful in many cases, they usually assume high angular coverage over the scattered photon, which is not the case for our prototype. In this work, we have derived an analytical model that allows us to calculate a detailed sensitivity matrix, which has been compared to other sensitivity models in the literature. Specifically, the proposed model describes the probability of measuring a useful event in a two-plane Compton camera, including the most relevant physical processes involved. The model has been used to obtain an expression for the system and sensitivity matrices for iterative image reconstruction. These matrices have been validated taking Monte Carlo simulations as a reference. In order to study the impact of the sensitivity, images reconstructed with our sensitivity model and with other models have been compared. Images have been reconstructed from several simulated sources, including point-like sources and extended distributions of activity, and also from experimental data measured with 22Na sources. Results show that our sensitivity model is the best suited for our prototype. Although other models in the literature perform successfully in many scenarios, they are not applicable in all the geometrical configurations of interest for our system. In general, our model allows to effectively recover the intensity of point-like sources at different positions in the FoV and to reconstruct regions of homogeneous activity with minimal variance. Moreover, it can be employed for all Compton camera configurations, including those with low angular coverage over the scatterer.

Performance evaluation of MACACO: a multilayer Compton camera.

Compton imaging devices have been proposed and studied for a wide range of applications. We have developed a Compton camera prototype which can be operated with two or three detector layers based on monolithic lanthanum bromide ([Formula: see text]) crystals coupled to silicon photomultipliers (SiPMs), to be used for proton range verification in hadron therapy. In this work, we present the results obtained with our prototype in laboratory tests with radioactive sources and in simulation studies. Images of a [Formula: see text]Na and an [Formula: see text]Y radioactive sources have been successfully reconstructed. The full width half maximum of the reconstructed images is below 4 mm for a [Formula: see text]Na source at a distance of 5 cm.

Performance of MACACO Compton telescope for ion-beam therapy monitoring: first test with proton beams.

In order to exploit the advantages of ion-beam therapy in a clinical setting, delivery verification techniques are necessary to detect deviations from the planned treatment. Efforts are currently oriented towards the development of devices for real-time range monitoring. Among the different detector concepts proposed, Compton cameras are employed to detect prompt gammas and represent a valid candidate for real-time range verification. We present the first on-beam test of MACACO, a Compton telescope (multi-layer Compton camera) based on lanthanum bromide crystals and silicon photo-multipliers. The Compton telescope was first characterized through measurements and Monte Carlo simulations. The detector linearity was measured employing (22)Na and Am-Be sources, obtaining about 10% deviation from linearity at 3.44 MeV. A spectral image reconstruction algorithm was tested on synthetic data. Point-like sources emitting gamma rays with energy between 2 and 7 MeV were reconstructed with 3-5 mm resolution. The two-layer Compton telescope was employed to measure radiation emitted from a beam of 150 MeV protons impinging on a cylindrical PMMA target. Bragg-peak shifts were achieved via adjustment of the PMMA target location and the resulting measurements used during image reconstruction. Reconstructed Bragg peak profiles proved sufficient to observe peak-location differences within 10 mm demonstrating the potential of the MACACO Compton Telescope as a monitoring device for ion-beam therapy.

3D position determination in monolithic crystals coupled to SiPMs for PET.

The interest in using continuous monolithic crystals in positron emission tomography (PET) has grown in the last years. Coupled to silicon photomultipliers (SiPMs), the detector can combine high sensitivity and high resolution, the two main factors to be maximized in a positron emission tomograph. In this work, the position determination capability of a detector comprised of a [Formula: see text] mm(3) LYSO crystal coupled to an [Formula: see text]-pixel array of SiPMs is evaluated. The 3D interaction position of γ-rays is estimated using an analytical model of the light distribution including reflections on the facets of the crystal. Monte Carlo simulations have been performed to evaluate different crystal reflectors and geometries. The method has been characterized and applied to different cases. Intrinsic resolution obtained with the position estimation method used in this work, applied to experimental data, achieves sub-millimetre resolution values. Average resolution over the detector surface for 5 mm thick crystal is ∼0.9 mm FWHM and ∼1.2 mm FWHM for 10 mm thick crystal. Depth of interaction resolution is close to 2 mm FWHM in both cases, while the FWTM is ∼5.3 mm for 5 mm thick crystal and ∼9.6 mm for 10 mm thick crystal.

First Images of a Three-Layer Compton Telescope Prototype for Treatment Monitoring in Hadron Therapy.

A Compton telescope for dose monitoring in hadron therapy is under development at IFIC. The system consists of three layers of LaBr3 crystals coupled to silicon photomultiplier arrays. (22)Na sources have been successfully imaged reconstructing the data with an ML-EM code. Calibration and temperature stabilization are necessary for the prototype operation at low coincidence rates. A spatial resolution of 7.8 mm FWHM has been obtained in the first imaging tests.

Simulation study of PET detector limitations using continuous crystals.

Continuous crystals can potentially obtain better intrinsic detector spatial resolution compared to pixelated crystals, additionally providing depth of interaction (DoI) information from the light distribution. To achieve high performance sophisticated interaction position estimation algorithms are required. There are a number of algorithms in the literature applied to different crystal dimensions and different photodetectors. However, the different crystal properties and photodetector array geometries have an impact on the algorithm performance. In this work we analysed, through Monte Carlo simulations, different combinations of realistic crystals and photodetector parameters to better understand their influence on the interaction position estimation accuracy, with special emphasis on the DoI. We used an interaction position estimation based on an analytical model for the present work. Different photodetector granulation schemes were investigated. The impact of the number of crystal faces readout by photodetectors was studied by simulating scenarios with one and two photodetectors. In addition, crystals with different levels of reflection and aspect ratios (AR) were analysed. Results showed that the impact of photodetector granularity is mainly shown near the edges and specially in the corners of the crystal. The resulting intrinsic spatial resolution near the centre with a 12 × 12 × 10 mm(3) LYSO crystal was 0.7-0.9 mm, while the average spatial resolution calculated on the entire crystal was 0.77 ± 0.18 mm for all the simulated geometries with one and two photodetectors. Having front and back photodetectors reduced the DoI bias (Euclidean distance between estimated DoI and real DoI) and improved the transversal resolution near the corners. In scenarios with one photodetector, small AR resulted in DoI inaccuracies for absorbed events at the entrance of the crystal. These inaccuracies were slightly reduced either by increasing the AR or reducing the amount of reflected light, and highly mitigated using two photodetectors. Using one photodetector, we obtained a piecewise DoI error model with a DoI resolution of 0.4-0.9 mm for a 1.2 AR crystal, and we observed that including a second photodetector or reducing the amount of reflections reduced the DoI bias but did not significantly improve the DoI resolution. Translating the piecewise DoI error model obtained in this study to image reconstruction we obtained a spatial resolution variability of 0.39 mm using 85% of the FoV, compared to 2.59 mm and 1.87 mm without DoI correction or with a dual layer system, respectively.

A prototype of very high resolution small animal PET scanner using silicon pad detectors.

A very high resolution small animal positron emission tomograph (PET) which can achieve sub-millimeter spatial resolution is being developed using silicon pad detectors. The prototype PET for a single slice instrument consists of two 1 mm thick silicon pad detectors, each containing a 32 x 16 array of 1.4 mm x 1.4 mm pads read out with four VATAGP3 chips which have 128 channels low-noise self triggering ASIC in each chip, coincidence units, a source turntable and tungsten slice collimator. The silicon detectors were located edgewise on opposite sides of a 4 cm field-of-view to maximize efficiency. Energy resolution is dominated by electronic noise, which is 0.98% (1.38 keV) FWHM at 140.5 keV. Coincidence timing resolution is 82.1 ns FWHM and coincidence efficiency was measured to be 1.04 x 10(-3) % from two silicon detectors with annihilation photons of (18)F source Image data were acquired and reconstructed using conventional 2-D filtered-back projection (FBP) and a maximum likelihood expectation maximization (ML-EM) method. Image resolution of approximately 1.45 mm FWHM is obtained from 1-D profile of 1.1 mm diameter (18)F line source image. Even better resolution can be obtained with smaller detector element sizes. While many challenges remain in scaling up the instrument to useful efficiency including densely packed detectors and significantly improved timing resolution, performance of the test setup in terms of easily achieving submillimeter resolution is compelling.

Performance evaluation of a very high resolution small animal PET imager using silicon scatter detectors.

A very high resolution positron emission tomography (PET) scanner for small animal imaging based on the idea of inserting a ring of high-granularity solid-state detectors into a conventional PET scanner is under investigation. A particularly interesting configuration of this concept, which takes the form of a degenerate Compton camera, is shown capable of providing sub-millimeter resolution with good sensitivity. We present a Compton PET system and estimate its performance using a proof-of-concept prototype. A prototype single-slice imaging instrument was constructed with two silicon detectors 1 mm thick, each having 512 1.4 mm x 1.4 mm pads arranged in a 32 x 16 array. The silicon detectors were located edgewise on opposite sides and flanked by two non-position sensitive BGO detectors. The scanner performance was measured for its sensitivity, energy, timing, spatial resolution and resolution uniformity. Using the experimental scanner, energy resolution for the silicon detectors is 1%. However, system energy resolution is dominated by the 23% FWHM BGO resolution. Timing resolution for silicon is 82.1 ns FWHM due to time-walk in trigger devices. Using the scattered photons, time resolution between the BGO detectors is 19.4 ns FWHM. Image resolution of 980 microm FWHM at the center of the field-of-view (FOV) is obtained from a 1D profile of a 0.254 mm diameter (18)F line source image reconstructed using the conventional 2D filtered back-projection (FBP). The 0.4 mm gap between two line sources is resolved in the image reconstructed with both FBP and the maximum likelihood expectation maximization (ML-EM) algorithm. The experimental instrument demonstrates sub-millimeter resolution. A prototype having sensitivity high enough for initial small animal images can be used for in vivo studies of small animal models of metabolism, molecular mechanism and the development of new radiotracers.