The growing demand for precision medicine is leading to the development of highly innovative detection systems optimized for the specific energies involved. BNCT is a hadrontherapy based on the reaction 10B(n,α)7Li induced by low-energy neutrons. Thanks to the short ranges in tissues of the high LET secondary ions, the lethal damages preferentially affect tumor cells, sparing the nearby healthy cells. Real-time knowledge of 10B concentrations and local thermal neutron flux distribution must be known to exploit its selectivity properly. Today, these quantities are measured independently and through indirect methods, leading to a lack of precision in dose estimation. The intensity of 478 keV gamma rays emitted after the 10B reaction is a direct measurement of the 10B capture reaction rate, being proportional to the 10B concentration multiplied by the local neutron flux. Thus, the intensity measurement of the 478 keV photon equals real-time monitoring of the 10B dose, giving an online treatment verification. To date, CZT semiconductor detectors represent the latest and most advanced technology for small-FOV molecular imaging, in particular for MBI and cardiac SPECT due to their excellent spectroscopic resolution and their possible use at room-temperature. As the newest commercially available technology, CZT detectors are one of the first options to be studied to develop systems for other innovative applications. At the UNIPV Physics Department, a new system composed of four modules, each one relying on an array of four CZT sensors, is under test for single photon detection. Each module, named DoseCapture, has been designed and manufactured by the Italian SME due2lab s.r.l. and developed in collaboration with the BNCT group active at the UNIPV Physics Department, with the specific goal of monitoring in real-time the 10B therapeutic dose during the BNCT treatment. The system represents a very preliminary prototype of a preclinical BNCT-SPECT because it exploits the single 478 keV photon to realize a tomographic reconstruction of the 10B dose in vivo. Each module contains an array of 4 Frisch-grid CZT sensors coupled to a squared parallel-hole lead collimator and a 6Li-enriched thermal neutron shield. The signals are managed by a digital system developed specifically for the DoseCapture. The work carried out within this thesis is part of the Dipartimento di Eccellenza project, awarded to the UNIPV Physics Department by MUR for the 2018-2022 period and of the INFN project ENTER_BNCT, ending in 2023. Among the different goals, a specific branch is dedicated to innovative online dosimetry systems to be installed in the next-generation BNCT treatment rooms, like the one under installation since November 2021 at CNAO in Pavia. This thesis mainly focuses on the characterization of the four DoseCapture modules, and its final goal is to obtain a preliminary proof of concept of the feasibility of the DoseCapture-based BNCT-SPECT for the 10B dose verification using an experimental neutron beam. After an initial characterization with radioactive standard sources, studies moved on the n + γ mixed field at the PGNAA facility installed at LENA, where a research nuclear reactor is operated. Although the spectrum and the intensities of the neutron beam at PGNAA are different from those expected in a BNCT treatment room, these first measurements were useful to verify the energy resolution and the ability to measure the 478 keV photon in the presence of a mixed field background. In addition, preliminary tomographic images were successfully reconstructed and represent a preliminary evaluation of the imaging capability of the whole detection system. All the measurements and simulations produced during this thesis are the necessary starting point for subsequent research and development steps of the DoseCapture system, to fully make the prototype an eligible candidate for the 10B dose control in BNCT.
La medicina di precisione sta portando allo sviluppo di sistemi di rilevamento innovativi e ottimizzati per le energie specifiche coinvolte. La BNCT è un'adroterapia basata sulla reazione 10B(n,α)7Li indotta da neutroni a bassa energia. Grazie ai corti ranges nei tessuti degli ioni secondari ad alto LET, i danni letali colpiscono preferenzialmente le cellule tumorali, risparmiando le cellule sane vicine. La conoscenza in tempo reale della concentrazione di 10B e della distribuzione locale del flusso di neutroni termici deve essere nota per sfruttare adeguatamente la sua selettività. Ad oggi, queste quantità vengono misurate indipendentemente e con metodi indiretti, portando a una mancanza di precisione nella stima della dose. L'intensità dei raggi gamma a 478 keV emessi dopo la reazione su 10B è misura diretta del reaction rate, essendo proporzionale alla concentrazione di 10B moltiplicata per il flusso di neutroni locale. Pertanto, la misura dell'intensità del fotone a 478 keV monitora in tempo reale la dose da 10B. Ad oggi, i rivelatori a semiconduttore CZT rappresentano la tecnologia più recente e avanzata per l'imaging molecolare a piccola FOV, in particolare MBI e SPECT cardiaca, grazie alla loro eccellente risoluzione spettroscopica e al possibile utilizzo a temperatura ambiente. Essendo la più recente tecnologia disponibile, i rivelatori CZT sono una delle prime opzioni da studiare per sviluppare sistemi per altre applicazioni innovative. Presso il Dip. di Fisica UNIPV, un nuovo sistema composto da 4 moduli, ciascuno basato su un array di 4 sensori CZT, è in fase di test per il rilevamento di singolo fotone. Ogni modulo, chiamato DoseCapture, è stato progettato e realizzato dalla SME italiana due2lab s.r.l. e sviluppato in collaborazione col gruppo BNCT attivo presso il Dip. di Fisica UNIPV, con l'obiettivo specifico di monitorare in tempo reale la dose terapeutica da 10B durante la BNCT. Il sistema rappresenta un prototipo molto preliminare di BNCT-SPECT preclinica perché sfrutta il singolo fotone a 478 keV per realizzare ricostruzioni tomografiche della dose da 10B in vivo. Ogni modulo contiene un array di 4 sensori CZT Frisch-grid accoppiati a un collimatore di piombo a fori paralleli quadrati e uno shielding di neutroni termici arricchito in 6Li. I segnali sono gestiti da un sistema digitale sviluppato per il DoseCapture. Il lavoro svolto in questa tesi fa parte del progetto Dipartimento di Eccellenza, assegnato al Dip. di Fisica UNIPV dal MUR (2018-2022) e del progetto INFN ENTER_BNCT, che si concluderà nel 2023. Tra i diversi obiettivi, un ramo specifico è dedicato a sistemi innovativi di dosimetria online da installare nelle sale di trattamento BNCT di nuova generazione, come quella in installazione da novembre 2021 al CNAO di Pavia. Questa tesi si concentra principalmente sulla caratterizzazione dei 4 moduli DoseCapture e il suo obiettivo finale è ottenere una prova preliminare della fattibilità di BNCT-SPECT basata sui DoseCapture, utilizzando un fascio di neutroni sperimentale. Dopo una prima caratterizzazione con sorgenti standard radioattive, gli studi si sono spostati sul campo misto n + γ presso l'impianto PGNAA installato al LENA, dove opera un reattore nucleare per ricerca. Sebbene lo spettro e le intensità del fascio di neutroni in PGNAA siano diversi da quelli attesi in una sala di trattamento BNCT, queste prime misurazioni sono state utili per verificare la risoluzione energetica e la capacità di misurare il fotone a 478 keV in presenza di un background misto. Le immagini tomografiche preliminari sono state ricostruite con successo e rappresentano una valutazione preliminare della capacità di imaging dell'intero sistema. Tutte le misurazioni e simulazioni prodotte durante questa tesi sono il punto di partenza necessario per successive fasi di ricerca e sviluppo del sistema DoseCapture, per rendere il prototipo un candidato idoneo per il controllo della dose da 10B in BNCT.
Caratterizzazione dei rivelatori DoseCapture CZT per BNCT-SPECT e prime misure di risposta al campo di neutroni
PALMACCI, FEDERICO
2021/2022
Abstract
The growing demand for precision medicine is leading to the development of highly innovative detection systems optimized for the specific energies involved. BNCT is a hadrontherapy based on the reaction 10B(n,α)7Li induced by low-energy neutrons. Thanks to the short ranges in tissues of the high LET secondary ions, the lethal damages preferentially affect tumor cells, sparing the nearby healthy cells. Real-time knowledge of 10B concentrations and local thermal neutron flux distribution must be known to exploit its selectivity properly. Today, these quantities are measured independently and through indirect methods, leading to a lack of precision in dose estimation. The intensity of 478 keV gamma rays emitted after the 10B reaction is a direct measurement of the 10B capture reaction rate, being proportional to the 10B concentration multiplied by the local neutron flux. Thus, the intensity measurement of the 478 keV photon equals real-time monitoring of the 10B dose, giving an online treatment verification. To date, CZT semiconductor detectors represent the latest and most advanced technology for small-FOV molecular imaging, in particular for MBI and cardiac SPECT due to their excellent spectroscopic resolution and their possible use at room-temperature. As the newest commercially available technology, CZT detectors are one of the first options to be studied to develop systems for other innovative applications. At the UNIPV Physics Department, a new system composed of four modules, each one relying on an array of four CZT sensors, is under test for single photon detection. Each module, named DoseCapture, has been designed and manufactured by the Italian SME due2lab s.r.l. and developed in collaboration with the BNCT group active at the UNIPV Physics Department, with the specific goal of monitoring in real-time the 10B therapeutic dose during the BNCT treatment. The system represents a very preliminary prototype of a preclinical BNCT-SPECT because it exploits the single 478 keV photon to realize a tomographic reconstruction of the 10B dose in vivo. Each module contains an array of 4 Frisch-grid CZT sensors coupled to a squared parallel-hole lead collimator and a 6Li-enriched thermal neutron shield. The signals are managed by a digital system developed specifically for the DoseCapture. The work carried out within this thesis is part of the Dipartimento di Eccellenza project, awarded to the UNIPV Physics Department by MUR for the 2018-2022 period and of the INFN project ENTER_BNCT, ending in 2023. Among the different goals, a specific branch is dedicated to innovative online dosimetry systems to be installed in the next-generation BNCT treatment rooms, like the one under installation since November 2021 at CNAO in Pavia. This thesis mainly focuses on the characterization of the four DoseCapture modules, and its final goal is to obtain a preliminary proof of concept of the feasibility of the DoseCapture-based BNCT-SPECT for the 10B dose verification using an experimental neutron beam. After an initial characterization with radioactive standard sources, studies moved on the n + γ mixed field at the PGNAA facility installed at LENA, where a research nuclear reactor is operated. Although the spectrum and the intensities of the neutron beam at PGNAA are different from those expected in a BNCT treatment room, these first measurements were useful to verify the energy resolution and the ability to measure the 478 keV photon in the presence of a mixed field background. In addition, preliminary tomographic images were successfully reconstructed and represent a preliminary evaluation of the imaging capability of the whole detection system. All the measurements and simulations produced during this thesis are the necessary starting point for subsequent research and development steps of the DoseCapture system, to fully make the prototype an eligible candidate for the 10B dose control in BNCT.È consentito all'utente scaricare e condividere i documenti disponibili a testo pieno in UNITESI UNIPV nel rispetto della licenza Creative Commons del tipo CC BY NC ND.
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https://hdl.handle.net/20.500.14239/14941