Particle beam microstructure reconstruction and coincidence discrimination in PET monitoring for hadron therapy.

Positron emission tomography is one of the most mature techniques for monitoring the particles range in hadron therapy, aiming to reduce treatment uncertainties and therefore the extent of safety margins in the treatment plan. In-beam PET monitoring has been already performed using inter-spill and post-irradiation data, i.e. while the particle beam is off or paused. The full beam acquisition procedure is commonly discarded because the particle spills abruptly increase the random coincidence rates and therefore the image noise. This is because random coincidences cannot be separated by annihilation photons originating from radioactive decays and cannot be corrected with standard random coincidence techniques due to the time correlation of the beam-induced background with the ion beam microstructure. The aim of this paper is to provide a new method to recover in-spill data to improve the images obtained with full-beam PET acquisitions. This is done by estimating the temporal microstructure of the beam and thus selecting input PET events that are less likely to be random ones. The PET detector we used was the one developed within the INSIDE project and tested at the CNAO synchrotron-based facility. The data were taken on a PMMA phantom irradiated with 72 MeV proton pencil beams. The obtained results confirm the possibility of improving the acquired PET data without any external signal coming from the synchrotron or ad hoc detectors.

Monte Carlo simulation tool for online treatment monitoring in hadrontherapy with in-beam PET: A patient study.

Hadrontherapy is a method for treating cancer with very targeted dose distributions and enhanced radiobiological effects. To fully exploit these advantages, in vivo range monitoring systems are required. These devices measure, preferably during the treatment, the secondary radiation generated by the beam-tissue interactions. However, since correlation of the secondary radiation distribution with the dose is not straightforward, Monte Carlo (MC) simulations are very important for treatment quality assessment. The INSIDE project constructed an in-beam PET scanner to detect signals generated by the positron-emitting isotopes resulting from projectile-target fragmentation. In addition, a FLUKA-based simulation tool was developed to predict the corresponding reference PET images using a detailed scanner model. The INSIDE in-beam PET was used to monitor two consecutive proton treatment sessions on a patient at the Italian Center for Oncological Hadrontherapy (CNAO). The reconstructed PET images were updated every 10 s providing a near real-time quality assessment. By half-way through the treatment, the statistics of the measured PET images were already significant enough to be compared with the simulations with average differences in the activity range less than 2.5 mm along the beam direction. Without taking into account any preferential direction, differences within 1 mm were found. In this paper, the INSIDE MC simulation tool is described and the results of the first in vivo agreement evaluation are reported. These results have justified a clinical trial, in which the MC simulation tool will be used on a daily basis to study the compliance tolerances between the measured and simulated PET images.

Evaluation of event position reconstruction in monolithic crystals that are optically coupled.

A PET detector featuring a pseudo-monolithic crystal is being developed as a more cost-effective alternative to a full monolithic crystal PET detector. This work evaluates different methods to localize the scintillation events in quartered monolithic crystals that are optically coupled. A semi-monolithic crystal assembly was formed using four 26 × 26 × 10 mm3 LYSO crystals optically coupled together using optical adhesive, to mimic a 52 × 52 × 10 mm3 monolithic crystal detector. The crystal assembly was coupled to a 64-channel multi-anode photomultiplier tube using silicon grease. The detector was calibrated using a 34 × 34 scan grid. Events were first filtered and depth separated using a multi-Lorentzian fit to the collected light distribution. Next, three different techniques were explored to generate the look up tables for the event positioning. The first technique was 'standard interpolation' across the interface. The second technique was 'central extrapolation', where a bin was placed at the midpoint of the interface and events positioned within the interface region were discarded. The third technique used a 'central overlap' method where an extended region was extrapolated at each interface. Events were then positioned using least-squares minimization and maximum likelihood methods. The least-squares minimization applied to the look up table generated with the standard interpolation technique had the best full width at half maximum (FWHM) intrinsic spatial resolution and the lowest bias. However, there were discontinuities in the event positioning that would most likely lead to artifacts in the reconstructed image. The central extrapolation technique also had discontinuities and a 30% sensitivity loss near the crystal-crystal interfaces. The central overlap technique had slightly degraded performance metrics, but it still provided ~2.1 mm intrinsic spatial resolution at the crystal-crystal interface and had a symmetric and continuously varying response function. Results using maximum likelihood positioning were similar to least-squares minimization for the central overlap data.

Full-beam performances of a PET detector with synchrotron therapeutic proton beams.

Treatment quality assessment is a crucial feature for both present and next-generation ion therapy facilities. Several approaches are being explored, based on prompt radiation emission or on PET signals by [Formula: see text]-decaying isotopes generated by beam interactions with the body. In-beam PET monitoring at synchrotron-based ion therapy facilities has already been performed, either based on inter-spill data only, to avoid the influence of the prompt radiation, or including both in-spill and inter-spill data. However, the PET images either suffer of poor statistics (inter-spill) or are more influenced by the background induced by prompt radiation (in-spill). Both those problems are expected to worsen for accelerators with improved duty cycle where the inter-spill interval is reduced to shorten the treatment time. With the aim of assessing the detector performance and developing techniques for background reduction, a test of an in-beam PET detector prototype was performed at the CNAO synchrotron-based ion therapy facility in full-beam acquisition modality. Data taken with proton beams impinging on PMMA phantoms showed the system acquisition capability and the resulting activity distribution, separately reconstructed for the in-spill and the inter-spill data. The coincidence time resolution for in-spill and inter-spill data shows a good agreement, with a slight deterioration during the spill. The data selection technique allows the identification and rejection of most of the background originated during the beam delivery. The activity range difference between two different proton beam energies (68 and 72 MeV) was measured and found to be in sub-millimeter agreement with the expected result. However, a slightly longer (2 mm) absolute profile length is obtained for in-spill data when compared to inter-spill data.

Proton range monitoring with in-beam PET: Monte Carlo activity predictions and comparison with cyclotron data.

GOAL: Proton treatment monitoring with Positron-Emission-Tomography (PET) is based on comparing measured and Monte Carlo (MC) predicted ß(+) activity distributions. Here we present PET ß(+) activity data and MC predictions both during and after proton irradiation of homogeneous PMMA targets, where protons were extracted from a cyclotron. METHODS AND MATERIALS: PMMA phantoms were irradiated with 62 MeV protons extracted from the CATANA cyclotron. PET activity data were acquired with a 10 × 10 cm(2) planar PET system and compared with predictions from the FLUKA MC generator. We investigated which isotopes are produced and decay during irradiation, and compared them to the situation after irradiation. For various irradiation conditions we compared one-dimensional activity distributions of MC and data, focussing on Δw50%, i.e., the distance between the 50% rise and 50% fall-off position. RESULTS: The PET system is able to acquire data during and after cyclotron irradiation. For PMMA phantoms the difference between the FLUKA MC prediction and our data in Δw50% is less than 1 mm. The ratio of PET activity events during and after irradiation is about 1 in both data and FLUKA, when equal time-frames are considered. Some differences are observed in profile shape. CONCLUSION: We found a good agreement in Δw50% and in the ratio between beam-on and beam-off activity between the PET data and the FLUKA MC predictions in all irradiation conditions.

Analysis of image sharpness reproducibility on a novel engineered micro-CT scanner with variable geometry and embedded recalibration software.

This study investigates the reproducibility of the reconstructed image sharpness, after modifications of the geometry setup, for a variable magnification micro-CT (µCT) scanner. All the measurements were performed on a novel engineered µCT scanner for in vivo imaging of small animals (Xalt), which has been recently built at the Institute of Clinical Physiology of the National Research Council (IFC-CNR, Pisa, Italy), in partnership with the University of Pisa. The Xalt scanner is equipped with an integrated software for on-line geometric recalibration, which will be used throughout the experiments. In order to evaluate the losses of image quality due to modifications of the geometry setup, we have made 22 consecutive acquisitions by changing alternatively the system geometry between two different setups (Large FoV - LF, and High Resolution - HR). For each acquisition, the tomographic images have been reconstructed before and after the on-line geometric recalibration. For each reconstruction, the image sharpness was evaluated using two different figures of merit: (i) the percentage contrast on a small bar pattern of fixed frequency (f = 5.5 lp/mm for the LF setup and f = 10 lp/mm for the HR setup) and (ii) the image entropy. We have found that, due to the small-scale mechanical uncertainty (in the order of the voxel size), a recalibration is necessary for each geometric setup after repositioning of the system's components; the resolution losses due to the lack of recalibration are worse for the HR setup (voxel size = 18.4 µm). The integrated on-line recalibration algorithm of the Xalt scanner allowed to perform the recalibration quickly, by restoring the spatial resolution of the system to the reference resolution obtained after the initial (off-line) calibration.

Extension and validation of an analytical model for in vivo PET verification of proton therapy--a phantom and clinical study.

The interest in positron emission tomography (PET) as a tool for treatment verification in proton therapy has become widespread in recent years, and several research groups worldwide are currently investigating the clinical implementation. After the first off-line investigation with a PET/CT scanner at MGH (Boston, USA), attention is now focused on an in-room PET application immediately after treatment in order to also detect shorter-lived isotopes, such as O15 and N13, minimizing isotope washout and avoiding patient repositioning errors. Clinical trials are being conducted by means of commercially available PET systems, and other tests are planned using application-dedicated tomographs. Parallel to the experimental investigation and new hardware development, great interest has been shown in the development of fast procedures to provide feedback regarding the delivered dose from reconstructed PET images. Since the thresholds of inelastic nuclear reactions leading to tissue ß+ -activation fall within the energy range of 15-20 MeV, the distal activity fall-off is correlated, but not directly matched, to the distal fall-off of the dose distribution. Moreover, the physical interactions leading to ß+ -activation and energy deposition are of a different nature. All these facts make it essential to further develop accurate and fast methodologies capable of predicting, on the basis of the planned dose distribution, expected PET images to be compared with actual PET measurements, thus providing clinical feedback on the correctness of the dose delivery and of the irradiation field position. The aim of this study has been to validate an analytical model and to implement and evaluate it in a fast and flexible framework able to locally predict such activity distributions directly taking the reference planning CT and planned dose as inputs. The results achieved in this study for phantoms and clinical cases highlighted the potential of the implemented method to predict expected activity distributions with great accuracy. Thus, the analytical model can be used as a powerful substitute method to the sensitive and time-consuming Monte Carlo approach.

A micro-PET/CT approach using O-(2-[18F]fluoroethyl)-L-tyrosine in an experimental animal model of F98 glioma for BNCT.

The present study focuses on a micro-PET/CT application to be used for experimental Boron Neutron Capture Therapy (BNCT), which integrates, in the same frame, micro-CT derived anatomy and PET radiotracer distribution. Preliminary results have demonstrated that (18)F-fluoroethyl-tyrosine (FET)/PET allows the identification of the extent of cerebral lesions in F98 tumor bearing rat. Neutron autoradiography and α-spectrometry on axial tissues slices confirmed the tumor localization and extraction, after the administration of fructose-boronophenylalanine (BPA). Therefore, FET-PET approach can be used to assess the transport, the net influx, and the accumulation of FET, as an aromatic amino acid analog of BPA, in experimental animal model. Coregistered micro-CT images allowed the accurate morphological localization of the radiotracer distribution and its potential use for experimental BNCT.

Contribution of organ blood flow, intrinsic tissue clearance and glycaemia to the regulation of glucose use in obese and type 2 diabetic rats: a PET study.

BACKGROUND AND AIMS: Chronic hyperglycaemia aggravates obesity and diabetes mellitus. The use of glucose by body organs depends on several factors. We sought to investigate the role of blood flow, intrinsic tissue glucose clearance and blood glucose levels in regulating tissue glucose uptake under fasting conditions (FCs) and in response to acute hyperglycaemia (AH) in obese and type 2 diabetic rats. METHODS AND RESULTS: Thirty-six Zucker rats were studied by positron emission tomography to quantify perfusion and glucose uptake during FC and after AH in the liver, myocardium, skeletal muscle and subcutaneous adipose tissue. Progressively higher glucose uptake rates were observed from lean to obese (p < 0.05) and to diabetic rats (p < 0.05) in all tissues during both FC and AH. In FC, they were increased of 7-18 times in obese rats and 11-30 times in diabetic rats versus controls. Tissue glucose uptake was increased by over 10-fold during AH in controls; this response was severely blunted in diseased groups. AH tended to stimulate organ perfusion in control rats. Tissue glucose uptake was a function of intrinsic clearance and glycaemia (mass action) in healthy animals, but the latter component was lost in diseased animals. Differences in perfusion did not account for those in glucose uptake. CONCLUSIONS: Each organ participates actively in the regulation of its glucose uptake, which is dependent on intrinsic tissue substrate extraction and extrinsic blood glucose delivery, but not on perfusion, and it is potently stimulated by AH. Obese and diabetic rats had an elevated organ glucose uptake but a blunted response to acute glucose intake.

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.

Comparison of two dedicated 'in beam' PET systems via simultaneous imaging of (12)C-induced beta(+)-activity.

The selective energy deposition of hadrontherapy has led to a growing interest in quality assurance techniques such as 'in-beam' PET. Due to the current lack of commercial solutions, dedicated detectors need to be developed. In this paper, we compare the performances of two different 'in-beam' PET systems which were simultaneously operated during and after low energy carbon ion irradiation of PMMA phantoms at GSI Darmstadt. The results highlight advantages and drawbacks of a novel in-beam PET prototype against a long-term clinically operated tomograph for ion therapy monitoring.

An optimization-based method for geometrical calibration in cone-beam CT without dedicated phantoms.

In this paper we present a new method for the determination of geometrical misalignments in cone-beam CT scanners, from the analysis of the projection data of a generic object. No a priori knowledge of the object shape and positioning is required. We show that a cost function, which depends on the misalignment parameters, can be defined using the projection data and that such a cost function has a local minimum in correspondence to the actual parameters of the system. Hence, the calibration of the scanner can be carried out by minimizing the cost function using standard optimization techniques. The method is developed for a particular class of 3D object functions, for which the redundancy of the fan beam sinogram in the transaxial midplane can be extended to cone-beam projection data, even at wide cone angles. The method has an approximated validity for objects which do not belong to that class; in that case, a suitable subset of the projection data can be selected in order to compute the cost function. We show by numerical simulations that our method is capable to determine with high accuracy the most critical misalignment parameters of the scanner, i.e., the transversal shift and the skew of the detector. Additionally, the detector slant can be determined. Other parameters such as the detector tilt, the longitudinal shift and the error in the source-detector distance cannot be determined with our method, as the proposed cost function has a very weak dependence on them. However, due to the negligible influence of these latter parameters in the reconstructed image quality, they can be kept fixed at estimated values in both calibration and reconstruction processes without compromising the final result. A trade-off between computational cost and calibration accuracy must be considered when choosing the data subset used for the computation of the cost function. Results on real data of a mouse femur as obtained with a small animal micro-CT are shown as well, proving the capability of the proposed calibration method. In principle, the method can be adapted to other cone-beam imaging modalities (e.g., single photon emission computed tomography).

A pixel detector-based single photon-counting system as fast spectrometer for diagnostic X-ray beams.

Recent advances in semiconductor pixel detectors and read-out electronics allowed to build the first prototypes of single photon-counting imaging systems that represent the last frontier of digital radiography. Among the advantages with respect to commercially available digital imaging systems, there are direct conversion of photon energy into electrical charge and the effective rejection of electronic noise by means of a thresholding process. These features allow the photon-counting systems to achieve high imaging performances in terms of spatial and contrast resolution. Moreover, the now available deep integration techniques allow the reduction of the pixel size and the improvement of the functionality of the single cell and the read-out speed so as to cope with the high fluxes found in diagnostic radiology. In particular, the single photon-counting system presented in this paper is based on a 300-microm thick silicon pixel detector bump-bonded to the Medipix2 read-out chip to form an assembly of 256 x 256 square pixels at a pitch of 55 microm. Each cell comprises a low-noise preamplifier, two pulse height discriminators and a 14-bit counter. The maximum counting rate per pixel is 1 MHz. The chip can operate in two modalities: it records the events with energy above a threshold (single mode) or between two energy thresholds (window mode). Exploiting this latter feature, a possible application of such a system as a fast spectrometer is presented to study the energy spectrum of diagnostic beams produced by X-ray tubes.

Dental radiology dosimetric data as routinely collected in an Italian hospital.

The work presented here was developed in the framework of the SENTINEL Project and is devoted to the analysis of dental radiology dosimetric data. The procedure of data processing allows the analysis of some important aspects related to the protection of the patient and the staff because of the position of the operators near the patient and their exposure to the radiation scattered by the patient. Dental radiology data was collected in an Italian hospital. Following the Italian quality assurance (QA) protocols and suggestions by the leaders of the SENTINEL Project, X-ray equipment performances have been analysed in terms of: kVp accuracy, exposure time accuracy and precision, tube output, dose reproducibility and linearity, beam collimation, artefacts and light tightness. Referring to these parameters the physical quality index (QI) was analysed. In a single numerical value between 0 and 1, QI summarises the results of quality tests for radiological devices. The actual impact of such a figure (as suggested by international QA protocols or as adopted by local QA routine) on the policy of machine maintenance and replacement is discussed.

Experimental validation of the filtering approach for dose monitoring in proton therapy at low energy.

The higher physical selectivity of proton therapy demands higher accuracy in monitoring of the delivered dose, especially when the target volume is located next to critical organs and a fractionated therapy is applied. A method to verify a treatment plan and to ensure the high quality of the hadrontherapy is to use Positron Emission Tomography (PET), which takes advantage of the nuclear reactions between protons and nuclei in the tissue during irradiation producing beta(+)-emitting isotopes. Unfortunately, the PET image is not directly proportional to the delivered radiation dose distribution; this is the reason why, at the present time, the verification of depth dose profiles with PET techniques is limited to a comparison between the measured activity and the one predicted for the planned treatment by a Monte Carlo model. In this paper we test the feasibility of a different scheme, which permits to reconstruct the expected PET signal from the planned radiation dose distribution along beam direction in a simpler and more direct way. The considered filter model, based on the description of the PET image as a convolution of the dose distribution with a filter function, has already demonstrated its potential applicability to beam energies above 70 MeV. Our experimental investigation provides support to the possibility of extending the same approach to the lower energy range ([40, 70] MeV), in the perspective of its clinical application in eye proton therapy.

Use of a fast EM algorithm for 3D image reconstruction with the YAP-PET tomograph.

OBJECTIVE: We would like to improve the image reconstructions for both signal-to-noise ratio (SNR) and spatial resolution characteristics for the small animal positron emission tomograph YAP-PET, built at the Department of Physics of Ferrara University. The three-dimensional (3D) filtered backprojection (FBP) algorithm, usually used for image reconstruction, has a limited angle restriction due to the tomograph geometry, which causes a serious loss in sensitivity. METHODS: We implemented a 3D iterative reconstruction program using the symmetry and sparse properties of the 'probability matrix', which correlates the emission from each voxel to the detector within a coincidence tube. A fraction only of matrix elements are calculated before the reconstruction and stored on disk: this allows us to avoid on-line computation. A depth dependent function differentiates the voxels in a coincidence tube. Three experimental phantoms with no background were reconstructed by using the program, in comparison with traditionally used FBP. RESULTS: The adopted method allowed us to reduce the computation time significantly. Furthermore, the simple depth dependent function improved the spatial resolution. With 64 x 64 x 20 voxels of 0.625 x 0.625 x 2.0 mm(3) in the field of view, the computation time was less than 4 min per iteration on a Sparc Ultra 450 Workstation, and less than 6 min per iteration on a Mac-PPC G3 300 MHz: the spatial resolution measured with a 0.8 mm diameter 18F-FDG filled capillary reconstructed in this way was 2.0 mm FWHM. By decreasing the voxel size to 0.3125 x 0.3125 x 2.0 mm(3) per voxel the transaxial FWHM was 1.7 mm with a computation time of 15 min per iteration on a Sparc Ultra 450. By using all the acquired data, the SNR improves from 1.3 to 6.0 in the worst measured case, a pair of 0.8mm diameter 18F-FDG filled capillaries, which are 2.5 mm apart each other. CONCLUSION: The adoption of iterative reconstruction allowed us to overcome the loss in sensitivity of previously used FBP: this improved the SNR. The studies of symmetry and sparse properties avoided a severe increase of the reconstruction time and of storing space on disk. This fast EM Algorithm is now routinely used for the image reconstruction with the YAP-PET tomograph.

Advances in animal PET scanners.

Nowadays, a growing number of research groups shows a great interest for the application of PET and SPECT techniques to the development of new drugs. Preliminary studies on small animals require high performance dedicated scanners with a higher spatial resolution and sensitivity than those of clinical systems. In this paper the potential applications of such innovative instruments are shown together with a brief review of the dedicated PET and SPECT tomographs developed worldwide. Most of the scanners have been built as research prototypes. Only two are commercially available: micro-PET(R), designed and developed at UCLA, Los Angeles as a research prototype, and now produced and distributed by Concorde Microsystems Inc. (USA) and HIDAC PET produced by Oxford Positron Systems Ltd. (UK). Also in Italy, a high performance tomograph, YAP-(S) PET able to perform both PET and SPECT studies, has been developed at the University of Ferrara. The technical characteristics and performance of this scanner are described. Tomographs with combined imaging techniques, such as PET/CT or SPECT/CT, are now under study in various international research centers. The advantages of this new generation of animal scanners will be briefly outlined.

Spatial resolution measurements in quasimonochromatic x rays with mosaic crystals for mammography application.

A novel x-ray source for mammography application is being investigated. Quasimonochromatic x rays have been produced via Bragg diffraction with a W-anode x-ray tube and a graphite mosaic crystal array. The system provides 18 keV x rays with an energy resolution deltaE/E approximately equals 0.12. A thorough analysis of the spatial resolution of the system has been performed in order to understand and quantify the effect of the introduction of an active optical element such as a mosaic crystal in the x-ray path. The focal spot of the source and its emission properties have been studied by using the slit camera method. Experiments have shown that the introduction of a mosaic crystal in the optical path modifies the resolution properties of the Bragg diffraction-based radiography system. Along the direction perpendicular to the diffraction plane the resolution properties of the imaging system mainly depend on the x-ray tube focal spot size and position. Along the diffraction plane the focal spot size depends on mosaic characteristics and on the geometrical setup. Hence, it could be modified by setting the appropriate experimental conditions.