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In-beam PET (Positron Emission Tomography) is one of the most precise techniques for in-vivo range monitoring in hadron therapy. Our objective was to demonstrate the feasibility of a short irradiation run for range verification before a carbon-ion treatment. To do so a PMMA target was irradiated with a 220 MeV/u carbon-ion beam and annihilation coincidences from short-lived positron emitters were acquired after irradiations lasting 0.6 s. The experiments were performed at the synchrotron-based facility CNAO (Italian National Center of Oncological Hadrontherapy) by using the INSIDE in-beam PET detector. The results show that, with 3·107 carbon ions, the reconstructed positron emitting nuclei distribution is in good agreement with the predictions of a detailed FLUKA Monte Carlo study. Moreover, the radio-nuclei production is sufficiently abundant to determine the average ion beam range with a σ of 1 mm with a 6 s measurement of the activity distribution. Since the data were acquired when the beam was off, the proposed rapid calibration method can be applied to hadron beams extracted from accelerators with very different time structures.
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Electrones , Radioterapia de Iones Pesados , Tomografía de Emisión de Positrones/métodos , Carbono/uso terapéutico , Sincrotrones , Método de MontecarloRESUMEN
PURPOSE: Carbon ion therapy treatments can be monitored non-invasively with in-beam Positron Emission Tomography (PET). At CNAO the INSIDE in-beam PET scanner has been used in a clinical trial (NCT03662373) to monitor cancer treatments with proton and carbon therapy. In this work we present the analysis results of carbon therapy data, acquired during the first phase of the clinical trial, analyzing data of nine patients treated at CNAO for various malignant tumors in the head-and-neck region. MATERIALS AND METHODS: The patient group contained two patients requiring replanning, and seven patients without replanning, based on established protocols. For each patient the PET images acquired along the course of treatment were compared with a reference, applying two analysis methods: the beam-eye-view (BEV) method and the γ-index analysis. Time trends in several parameters were investigated, as well as the agreement with control CTs, if available. RESULTS: Regarding the BEV-method, the average sigma value σ was 3.7 mm of range difference distributions for patients without changes (sensitivity of the INSIDE detector). The 3D-information obtained from the BEV analysis was partly in agreement with what was observed in the control CT. The data quality and quantity was insufficient for a definite interpretation of the time trends. CONCLUSION: We analyzed carbon therapy data acquired with the INSIDE in-beam PET detector using two analysis methods. The data allowed to evaluate sensitivity of the INSIDE detector for carbon therapy and to make several recommendations for the future.
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Objective.This study addresses a fundamental limitation of in-beam positron emission tomography (IB-PET) in proton therapy: the lack of direct anatomical representation in the images it produces. We aim to overcome this shortcoming by pioneering the application of deep learning techniques to create synthetic control CT images (sCT) from combining IB-PET and planning CT scan data.Approach.We conducted simulations involving six patients who underwent irradiation with proton beams. Leveraging the architecture of a visual transformer (ViT) neural network, we developed a model to generate sCT images of these patients using the planning CT scans and the inter-fractional simulated PET activity maps during irradiation. To evaluate the model's performance, a comparison was conducted between the sCT images produced by the ViT model and the authentic control CT images-serving as the benchmark.Main results.The structural similarity index was computed at a mean value across all patients of 0.91, while the mean absolute error measured 22 Hounsfield Units (HU). Root mean squared error and peak signal-to-noise ratio values were 56 HU and 30 dB, respectively. The Dice similarity coefficient exhibited a value of 0.98. These values are comparable to or exceed those found in the literature. More than 70% of the synthetic morphological changes were found to be geometrically compatible with the ones reported in the real control CT scan.Significance.Our study presents an innovative approach to surface the hidden anatomical information of IB-PET in proton therapy. Our ViT-based model successfully generates sCT images from inter-fractional PET data and planning CT scans. Our model's performance stands on par with existing models relying on input from cone beam CT or magnetic resonance imaging, which contain more anatomical information than activity maps.
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Procesamiento de Imagen Asistido por Computador , Terapia de Protones , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Terapia de Protones/métodos , Tomografía Computarizada por Rayos X/métodos , Redes Neurales de la Computación , Imagen por Resonancia Magnética/métodos , Tomografía de Emisión de Positrones , Planificación de la Radioterapia Asistida por Computador/métodosRESUMEN
GOAL: In-beam Positron Emission Tomography (PET) is a technique for in-vivo non-invasive treatment monitoring for proton therapy. To detect anatomical changes in patients with PET, various analysis methods exist, but their clinical interpretation is problematic. The goal of this work is to investigate whether the gamma-index analysis, widely used for dose comparisons, is an appropriate tool for comparing in-beam PET distributions. Focusing on a head-and-neck patient, we investigate whether the gamma-index map and the passing rate are sensitive to progressive anatomical changes. METHODS/MATERIALS: We simulated a treatment course of a proton therapy patient using FLUKA Monte Carlo simulations. Gradual emptying of the sinonasal cavity was modeled through a series of artificially modified CT scans. The in-beam PET activity distributions from three fields were evaluated, simulating a planar dual head geometry. We applied the 3D-gamma evaluation method to compare the PET images with a reference image without changes. Various tolerance criteria and parameters were tested, and results were compared to the CT-scans. RESULTS: Based on 210 MC simulations we identified appropriate parameters for the gamma-index analysis. Tolerance values of 3 mm/3% and 2 mm/2% were suited for comparison of simulated in-beam PET distributions. The gamma passing rate decreased with increasing volume change for all fields. CONCLUSION: The gamma-index analysis was found to be a useful tool for comparing simulated in-beam PET images, sensitive to sinonasal cavity emptying. Monitoring the gamma passing rate behavior over the treatment course is useful to detect anatomical changes occurring during the treatment course.
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Terapia de Protones , Humanos , Terapia de Protones/métodos , Método de Montecarlo , Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada por Rayos X/métodos , Simulación por Computador , Etopósido , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodosRESUMEN
The TRIMAGE project aims to develop a brain-dedicated PET/MR/EEG (Positron Emission Tomography/Magnetic Resonance/Electroencephalogram) system that is able to perform simultaneous PET, MR and EEG acquisitions. The PET component consists of a full ring with 18 sectors. Each sector includes three square detector modules based on dual sstaggered LYSO:Ce matrices read out by SiPMs. Using Monte Carlo simulations and following NEMA (National Electrical Manufacturers Association) guidelines, image quality procedures have been applied to evaluate the performance of the PET component of the system. The performance are reported in terms of spatial resolution, uniformity, recovery coefficient, spill over ratio, noise equivalent count rate (NECR) and scatter fraction. The results show that the TRIMAGE system is at the top of the current brain PET technologies.
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Objective. Monolithic scintillator crystals coupled to silicon photomultiplier (SiPM) arrays are promising detectors for PET applications, offering spatial resolution around 1 mm and depth-of-interaction information. However, their timing resolution has always been inferior to that of pixellated crystals, while the best results on spatial resolution have been obtained with algorithms that cannot operate in real-time in a PET detector. In this study, we explore the capabilities of monolithic crystals with respect to spatial and timing resolution, presenting new algorithms that overcome the mentioned problems.Approach.Our algorithms were tested first using a simulation framework, then on experimentally acquired data. We tested an event timestamping algorithm based on neural networks which was then integrated into a second neural network for simultaneous estimation of the event position and timestamp. Both algorithms are implemented in a low-cost field-programmable gate array that can be integrated in the detector and can process more than 1 million events per second in real-time.Results.Testing the neural network for the simultaneous estimation of the event position and timestamp on experimental data we obtain 0.78 2D FWHM on the (x,y) plane, 1.2 depth-of-interaction FWHM and 156 coincidence time resolution on a25mm×25mm×8mm×LYSO monolith read-out by 643mm×3mmHamamatsu SiPMs.Significance.Our results show that monolithic crystals combined with artificial intelligence can rival pixellated crystals performance for time-of-flight PET applications, while having better spatial resolution and DOI resolution. Thanks to the use of very light neural networks, event characterization can be done on-line directly in the detector, solving the issues of scalability and computational complexity that up to now were preventing the use of monolithic crystals in clinical PET scanners.
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Inteligencia Artificial , Tomografía de Emisión de Positrones , Algoritmos , Simulación por Computador , Redes Neurales de la Computación , Tomografía de Emisión de Positrones/métodos , Conteo por CintilaciónRESUMEN
PURPOSE: In-beam positron emission tomography (PET) is one of the modalities that can be used for in vivo noninvasive treatment monitoring in proton therapy. Although PET monitoring has been frequently applied for this purpose, there is still no straightforward method to translate the information obtained from the PET images into easy-to-interpret information for clinical personnel. The purpose of this work is to propose a statistical method for analyzing in-beam PET monitoring images that can be used to locate, quantify, and visualize regions with possible morphological changes occurring over the course of treatment. METHODS: We selected a patient treated for squamous cell carcinoma (SCC) with proton therapy, to perform multiple Monte Carlo (MC) simulations of the expected PET signal at the start of treatment, and to study how the PET signal may change along the treatment course due to morphological changes. We performed voxel-wise two-tailed statistical tests of the simulated PET images, resembling the voxel-based morphometry (VBM) method commonly used in neuroimaging data analysis, to locate regions with significant morphological changes and to quantify the change. RESULTS: The VBM resembling method has been successfully applied to the simulated in-beam PET images, despite the fact that such images suffer from image artifacts and limited statistics. Three dimensional probability maps were obtained, that allowed to identify interfractional morphological changes and to visualize them superimposed on the computed tomography (CT) scan. In particular, the characteristic color patterns resulting from the two-tailed statistical tests lend themselves to trigger alarms in case of morphological changes along the course of treatment. CONCLUSIONS: The statistical method presented in this work is a promising method to apply to PET monitoring data to reveal interfractional morphological changes in patients, occurring over the course of treatment. Based on simulated in-beam PET treatment monitoring images, we showed that with our method it was possible to correctly identify the regions that changed. Moreover we could quantify the changes, and visualize them superimposed on the CT scan. The proposed method can possibly help clinical personnel in the replanning procedure in adaptive proton therapy treatments.
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Terapia de Protones , Humanos , Método de Montecarlo , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos XRESUMEN
Morphological changes that may arise through a treatment course are probably one of the most significant sources of range uncertainty in proton therapy. Non-invasive in-vivo treatment monitoring is useful to increase treatment quality. The INSIDE in-beam Positron Emission Tomography (PET) scanner performs in-vivo range monitoring in proton and carbon therapy treatments at the National Center of Oncological Hadrontherapy (CNAO). It is currently in a clinical trial (ID: NCT03662373) and has acquired in-beam PET data during the treatment of various patients. In this work we analyze the in-beam PET (IB-PET) data of eight patients treated with proton therapy at CNAO. The goal of the analysis is twofold. First, we assess the level of experimental fluctuations in inter-fractional range differences (sensitivity) of the INSIDE PET system by studying patients without morphological changes. Second, we use the obtained results to see whether we can observe anomalously large range variations in patients where morphological changes have occurred. The sensitivity of the INSIDE IB-PET scanner was quantified as the standard deviation of the range difference distributions observed for six patients that did not show morphological changes. Inter-fractional range variations with respect to a reference distribution were estimated using the Most-Likely-Shift (MLS) method. To establish the efficacy of this method, we made a comparison with the Beam's Eye View (BEV) method. For patients showing no morphological changes in the control CT the average range variation standard deviation was found to be 2.5 mm with the MLS method and 2.3 mm with the BEV method. On the other hand, for patients where some small anatomical changes occurred, we found larger standard deviation values. In these patients we evaluated where anomalous range differences were found and compared them with the CT. We found that the identified regions were mostly in agreement with the morphological changes seen in the CT scan.
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Particle therapy in which deep seated tumours are treated using 12C ions (Carbon Ions RadioTherapy or CIRT) exploits the high conformity in the dose release, the high relative biological effectiveness and low oxygen enhancement ratio of such projectiles. The advantages of CIRT are driving a rapid increase in the number of centres that are trying to implement such technique. To fully profit from the ballistic precision achievable in delivering the dose to the target volume an online range verification system would be needed, but currently missing. The 12C ions beams range could only be monitored by looking at the secondary radiation emitted by the primary beam interaction with the patient tissues and no technical solution capable of the needed precision has been adopted in the clinical centres yet. The detection of charged secondary fragments, mainly protons, emitted by the patient is a promising approach, and is currently being explored in clinical trials at CNAO. Charged particles are easy to detect and can be back-tracked to the emission point with high efficiency in an almost background-free environment. These fragments are the product of projectiles fragmentation, and are hence mainly produced along the beam path inside the patient. This experimental signature can be used to monitor the beam position in the plane orthogonal to its flight direction, providing an online feedback to the beam transverse position monitor chambers used in the clinical centres. This information could be used to cross-check, validate and calibrate, whenever needed, the information provided by the ion chambers already implemented in most clinical centres as beam control detectors. In this paper we study the feasibility of such strategy in the clinical routine, analysing the data collected during the clinical trial performed at the CNAO facility on patients treated using 12C ions and monitored using the Dose Profiler (DP) detector developed within the INSIDE project. On the basis of the data collected monitoring three patients, the technique potential and limitations will be discussed.
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In vivo range monitoring techniques are necessary in order to fully take advantage of the high dose gradients deliverable in hadrontherapy treatments. Positron emission tomography (PET) scanners can be used to monitor beam-induced activation in tissues and hence measure the range. The INSIDE (Innovative Solutions for In-beam DosimEtry in Hadrontherapy) in-beam PET scanner, installed at the Italian National Center of Oncological Hadrontherapy (CNAO, Pavia, Italy) synchrotron facility, has already been successfully tested in vivo during a proton therapy treatment. We discuss here the system performance evaluation with carbon ion beams, in view of future in vivo tests. The work is focused on the analysis of activity images obtained with therapeutic treatments delivered to polymethyl methacrylate (PMMA) phantoms, as well as on the test of an innovative and robust Monte Carlo simulation technique for the production of reliable prior activity maps. Images are reconstructed using different integration intervals, so as to monitor the activity evolution during and after the treatment. Three procedures to compare activity images are presented, namely Pearson correlation coefficient, Beam's eye view and overall view. Images of repeated irradiations of the same treatments are compared to assess the integration time necessary to provide reproducible images. The range agreement between simulated and experimental images is also evaluated, so as to validate the simulation capability to provide sound prior information. The results indicate that at treatment end, or at most 20 s afterwards, the range measurement is reliable within 1-2 mm, when comparing both different experimental sessions and data with simulations. In conclusion, this work shows that the INSIDE in-beam PET scanner performance is promising towards its in vivo test with carbon ions.
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Radioterapia de Iones Pesados , Fantasmas de Imagen , Tomografía de Emisión de Positrones/métodos , Terapia de Protones , Radiometría/instrumentación , Planificación de la Radioterapia Asistida por Computador/métodos , Humanos , Método de Montecarlo , Radiometría/métodos , SincrotronesRESUMEN
Particle therapy exploits the energy deposition pattern of hadron beams. The narrow Bragg Peak at the end of range is a major advantage but range uncertainties can cause severe damage and require online verification to maximise the effectiveness in clinics. In-beam Positron Emission Tomography (PET) is a non-invasive, promising in-vivo technique, which consists in the measurement of the ß+ activity induced by beam-tissue interactions during treatment, and presents the highest correlation of the measured activity distribution with the deposited dose, since it is not much influenced by biological washout. Here we report the first clinical results obtained with a state-of-the-art in-beam PET scanner, with on-the-fly reconstruction of the activity distribution during irradiation. An automated time-resolved quantitative analysis was tested on a lacrimal gland carcinoma case, monitored during two consecutive treatment sessions. The 3D activity map was reconstructed every 10 s, with an average delay between beam delivery and image availability of about 6 s. The correlation coefficient of 3D activity maps for the two sessions (above 0.9 after 120 s) and the range agreement (within 1 mm) prove the suitability of in-beam PET for online range verification during treatment, a crucial step towards adaptive strategies in particle therapy.
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Carcinoma/radioterapia , Aparato Lagrimal/patología , Tomografía de Emisión de Positrones/métodos , Terapia de Protones/métodos , Humanos , Imagenología Tridimensional/métodos , Resultado del TratamientoRESUMEN
Simultaneous PET/MR/EEG (Positron Emission Tomography - Magnetic Resonance - Electroencephalography), a new tool for the investigation of neuronal networks in the human brain, is presented here within the framework of the European Union Project TRIMAGE. The trimodal, cost-effective PET/MR/EEG imaging tool makes use of cutting edge technology both in PET and in MR fields. A novel type of magnet (1.5T, non-cryogenic) has been built together with a PET scanner that makes use of the most advanced photodetectors (i.e., SiPM matrices), scintillators matrices (LYSO) and digital electronics. The combined PET/MR/EEG system is dedicated to brain imaging and has an inner diameter of 260â¯mm and an axial Field-of-View of 160â¯mm. It enables the acquisition and assessment of molecular metabolic information with high spatial and temporal resolution in a given brain simultaneously. The dopaminergic system and the glutamatergic system in schizophrenic patients are investigated via PET, the same physiological/pathophysiological conditions with regard to functional connectivity, via fMRI, and its electrophysiological signature via EEG. In addition to basic neuroscience questions addressing neurovascular-metabolic coupling, this new methodology lays the foundation for individual physiological and pathological fingerprints for a wide research field addressing healthy aging, gender effects, plasticity and different psychiatric and neurological diseases. The preliminary performances of two components of the imaging tool (PET and MR) are discussed. Initial results of the search of possible candidates for suitable schizophrenia biomarkers are also presented as obtained with PET/MR systems available to the collaboration.
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Encéfalo/diagnóstico por imagen , Electroencefalografía/métodos , Espectroscopía de Resonancia Magnética/métodos , Imagen Multimodal/métodos , Tomografía de Emisión de Positrones/métodos , Esquizofrenia/diagnóstico por imagen , Adulto , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Monolithic scintillators read out by arrays of photodetectors represent a promising solution to obtain high spatial resolution and the depth of interaction (DOI) of the annihilation photon. We have recently investigated a detector geometry composed of a monolithic scintillator readout on two sides by silicon photomultiplier (SiPM) arrays, and we have proposed two parameters for the DOI determination: the difference in the number of triggered SiPMs on the two sides of the detector and the difference in the maximum collected signal on a single SiPM on each side. This work is focused on the DOI calibration and on the determination of the capability of our detector. For the DOI calibration, we studied a method which can be implemented also in detectors mounted in a full PET scanner. We used a PET detector module composed of a monolithic 20 × 20 × 10 mm3 LYSO scintillator crystal coupled on two opposite faces to two arrays of SiPMs. On each side, the scintillator was coupled to 6 × 6 SiPMs. In this paper, the two parameters previously proposed for the DOI determination were calibrated with two different methods. The first used a lateral scan of the detector with a collimated 511 keV pencil beam at steps of 0.5 mm to study the detector DOI capability, while the second used the background radiation of the 176Lu in the scintillator. The DOI determination capability was tested on different regions of the detector using each parameter and the combination of the two. RESULTS: With both parameters for the DOI determination, in the lateral scan, the bias between the mean reconstructed DOI and the real beam position was lower than 0.3 mm, and the DOI distribution had a standard deviation of about 1.5 mm. When using the calibration with the radioactivity of the LYSO, the mean bias increased of about 0.2 mm but with no degradation of the standard deviation of the DOI distribution. CONCLUSIONS: The two parameters allow to achieve a DOI resolution comparable with the state of the art, giving a continuous information about the three-dimensional interaction position of the scintillation. These results were obtained by using simple estimators and a detector scalable to a whole PET system. The DOI calibration obtained using lutetium natural radioactivity gives results comparable to the other standard method but appears more readily applicable to detectors mounted in a full PET scanner.
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The quality assurance of particle therapy treatment is a fundamental issue that can be addressed by developing reliable monitoring techniques and indicators of the treatment plan correctness. Among the available imaging techniques, positron emission tomography (PET) has long been investigated and then clinically applied to proton and carbon beams. In 2013, the Innovative Solutions for Dosimetry in Hadrontherapy (INSIDE) collaboration proposed an innovative bimodal imaging concept that combines an in-beam PET scanner with a tracking system for charged particle imaging. This paper presents the general architecture of the INSIDE project but focuses on the in-beam PET scanner that has been designed to reconstruct the particles range with millimetric resolution within a fraction of the dose delivered in a treatment of head and neck tumors. The in-beam PET scanner has been recently installed at the Italian National Center of Oncologic Hadrontherapy (CNAO) in Pavia, Italy, and the commissioning phase has just started. The results of the first beam test with clinical proton beams on phantoms clearly show the capability of the in-beam PET to operate during the irradiation delivery and to reconstruct on-line the beam-induced activity map. The accuracy in the activity distal fall-off determination is millimetric for therapeutic doses.