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

Full-beam PET monitoring in hadron therapy and related coincidence logic

La terapia adronica è una tecnica che usa protoni e ioni positivi per trattare il cancro. Essa permette di applicare distribuzioni di dose sul tessuto tumorale con precisioni irraggiungibili attraverso altre tecniche, come per esempio quelle radioterapiche convenzionali. Tale precisione fa sì che la tossicità sul tessuto sano circostante venga ridotta al minimo. Al fine di sfruttare a pieno le potenzialità della terapia adronica, è necessario disporre di una tecnica di monitoraggio in-vivo, che permetta di ridurre l'incertezza di range delle particelle e quindi i margini di sicurezza del trattamento. La tomografia ad emissione positronica (PET) è considerata una delle tecniche di imaging non invasivo in-vivo più mature per il monitoraggio del range nei trattamenti radioterapici. Quando l'acquisizione dei dati PET viene eseguita durante l'irraggiamento, il monitoraggio viene indicato come in-beam. Il problema del monitoraggio in-beam è che i dati acquisiti durante l'irraggiamento (in-spill) sono molto rumorosi mentre quelli acquisiti nelle pause (inter-spill) lo sono molto meno. Durante l'inter-spill, tuttavia, il segnale è anche molto debole perché molti degli emettitori β+ non sono stati ancora prodotti. Il rumore di fondo durante l'in-spill è dovuto alla forte radiazione rivelata mentre il fascio colpisce il tessuto bersaglio. Tale radiazione aumenta la probabilità di rivelazione di coincidenze random, a loro volta fonte di rumore nell'imaging PET. La radiazione di fondo può essere causata dal decadimento di emettitori β+ con vita media nell'ordine dei millisecondi, da raggi γ prodotti immediati (prompt) di reazioni nucleari non correlate al decadimento β+, da produzioni di coppie positrone-elettrone o da neutroni. Gli eventi random non possono essere discriminati dai decadimenti β+ utili, e non possono essere corretti con le tecniche convenzionali di stima delle coincidenze random a causa della mancanza di correlazione temporale tra i decadimenti β+ e i prodotti nucleari immediati. Allo stato dell'arte sono stati proposti due metodi per separare le coincidenze in-spill che si verificano durante la fase di estrazione dall'acceleratore da quelle che si verificano durante la fase di accelerazione. Le prime sono naturalmente più rumorose delle seconde, in quanto durante la fase di accelerazione sono assenti gli eventi prompt. Entrambi i metodi utilizzano informazioni sulla microstruttura del fascio da fonti esterne. Nel primo metodo, il segnale RF dall'acceleratore viene utilizzato per generare un segnale di gate all'interno del sistema di acquisizione PET. Nel secondo, il segnale di gate viene prodotto da un rivelatore di particelle inserito nel percorso del fascio prima del bersaglio. In questa tesi, le fasi della microstruttura del fascio vengono rivelate direttamente analizzando la distribuzione temporale degli eventi PET acquisiti in-spill. A tal fine, un nuovo algoritmo è stato sviluppato e validato in simulazione e sperimentalmente per il rilevamento della microstruttura temporale del fascio. I risultati di simulazione mostrano che e possibile implementare l'algoritmo su un FPGA e sfruttare le informazioni da esso prodotte per discriminare le coincidenze avvenute durante le fasi di estrazione da quelle avvenute durante le fasi di accelerazione. La distribuzione spaziale 3D ei profili di attività 1D degli eventi di coincidenza sono ricavati con un algoritmo di ricostruzione tomografica ML-EM per i dati interspill e in-spill. Il rumore di background è visibile nelle immagini ricostruite da dati sperimentali in-spill. Dopo aver filtrato i dati in-spill, scartando gli eventi di coincidenza che si verificano durante la fase di estrazione, si dimostra che l'immagine ricostruita migliora significativamente. Nel profilo di attività 1D si osserva una forte diminuzione della baseline del segnale, corrispondente al contributo delle coincidenze random. In particolare, il rapporto fra il picco di attività nel target diviso per il livello di fondo migliora di un fattore 4.8. Questa attività è stata sviluppata all'interno dei progetti INSIDE e INFIERI (FP7-PEOPLE-2012-ITN project number 317446), finanziati rispettivamente da MIUR e EU.Hadron therapy is a widely employed technique that uses protons and heavy ions to treat cancer. It has the potential of delivering highly conformal dose distributions to the tumor volume while sparing the surrounding healthy tissue, thanks to the dose distribution characterized by the Bragg peak at the end of charged particles range. In order to exploit the full potential of hadron therapy, an in vivo monitoring technique is desirable in order to reduce the uncertainties and therefore the treatment safety margins. Positron emission tomography (PET) is considered one of the most promising in vivo non-invasive imaging techniques for monitoring the particle range in radiation treatments. One of the data acquisition methods is the so-called in-beam which is performed during irradiation at the treatment site. The problem of in-beam monitoring is that in-spill data are much noisier while inter-spill data for accelerators with high duty cycles, are much less due to the small number of acquired decays. During the spills, the noisy background is due to the presence of strong beam-induced radiation that increases the random coincidence rates. This background might originate from the decay of β+ emitters with half-lives in millisecond range and high endpoint energies, by γ-rays following nuclear reactions not related to β+ decay or by pair productions and neutrons. The noisy events cannot be separated from the usable decays of long-lived β+ emitters and cannot be corrected with standard random coincidence correction techniques because of the time-correlation of the beam-induced background with the ion beam microstructure. Until now, only two methods exist for identifying coincident events that occur during the microbunches in the spills. Both of them use information about the beam microstructure from external sources. In the first method, the RF signal from the accelerator is used externally and the data processing is done offline. In the second one, a fast particle detector placed in the beam path before the target is used and the process is triggered only when a particle arrives. With this thesis, the correlation between the beam microstructure and the RF of the synchrotron is confirmed by analyzing the events in the spills without the need of an external signal. An algorithm for the calculation of the period of the beam microstructure is developed. Small differences in the period between the spills impose the separate analysis for every spill. The period is calculated with 4 digits precision in nanosecond time scale, making a significant difference to the representation of the microbunch. In the end, the firmware related to the algorithm for the calculation of the period of the beam microstructure is developed using only the events in the spills. The simulation results show that it is possible the algorithm to be implemented in an FPGA and provide information about the period of the beam microstructure in real time. Moreover, a coincidence sorter is developed in order to provide real time coincidence detection. The simulation results for the two different architectures of the sorter that uses comparators with two and three inputs, are presented. The 3D spatial distribution and the 1D activity profiles of the coincidence events are constructed for inter-spill and in-spill data. The strong radiation background is visible in the reconstructed images, especially before the entrance surface of the phantom and at the end of the activity range with a tail. After filtering out the in-spill data by discarding the coincidence events that occur in a sub-interval of the microbunch, it is shown that the reconstructed image improves severely. In the 1D activity profile, one can observe that the number of coincidence events before the entrance surface of the phantom decreases significantly. This might happen because neutrons are discarded since they are detected a few ns later after the interaction of the beam with the nuclei. Results show that the signal to noise ratio (SNR), defined as the activity peak in the phantom divided by the background level, is improved by a factor of about 4.8 with respect to the in-spill signal. In the end, it is important to mention that this activity has been developed within the projects INSIDE and INFIERI (FP7-PEOPLE-2012-ITN project number 317446) funded by MIUR and EU respectively

Development of the coincidence sorter for the INSIDE PET system

Positron emission tomography (PET) has gained interest as one of the most reliable techniques for in-vivo range monitoring in particle therapy. The INSIDE project uses a new SiPM based PET implementation that processes individually each single photon acquired by two detector plates placed close to the patient. In order to detect coincidences in the single photons stream, a fast sorter architecture has to be developed. This work proposes an implementation compatible with the Altera Cyclone V available in the main data acquisition board of the INSIDE PET acquisition system. The sorting is performed by several merging steps on the incoming data packets. Two different sorter architectures have been implemented and tested. The first one uses 2-input comparators, the second one uses 3-input comparators. A test-bench is developed to verify the functionality and the performance of the event sorter. The sorter functionality is validated by comparing its results with off-line post-processed data. For the given maximum clock of 200 MHz, 28 MHz throughput rate is achieved with the 2-input comparators and 40 MHz with the 3-input comparators

Metodo e apparato per l'acquisizione dati per tomografia ad emissione di positroni in adroterapia a fascio acceso

Apparatus for acquiring positron emission tomography data when irradiating an object (20) with a hadron beam (B), the apparatus comprising a plurality of detectors (10) and a data processing system (12, 15). The data processing system (12, 15) is configured to process the detection data according to the following steps: a) determining a temporal distribution of the coincidence event rate acquired by the respective detector (10), b) sampling each spill interval with a sampling frequency of the order of magnitude of GHz to obtain a respective fine grained event rate distribution; c) for each spill interval: - c1) analysing frequencies of the fine grained event rate distribution to find an initial frequency value fo compatible with the radiofrequency signal of the hadron beam; - c2) from the initial frequency value, estimating period Ts of the micro-bunches and transforming time values of the coincidence events in the spill interval into values of phase relative to an arbitrary phase, based on the estimated period of the micro-bunches; and - c3) at each micro-bunch of the spill interval, executing filtering to remove coincidence events around a peak associated with background noise induced by the hadron beam and keep the remaining coincidence events of the micro-bunch

INSIDE in-beam positron emission tomography system for particle range monitoring in hadrontherapy

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