| Proton therapy that can deliver most of the dose within Bragg peak while sparing healthy tissues is highly expected in the precise treatment of malignant tumors.However,this dose feature of proton therapy,while offering unique advantages,also make it more sensitive to range uncertainty,and small deviations from the Bragg peak area and the tumor target area can have serious consequences.Therefore,range verification technology will be crucial to precise proton therapy.In-beam Positron Emission Tomography(In-beam PET)is expected to realize simultaneous monitoring during clinical proton therapy.However,the high throughput of the secondary particles include high radiation background noise during beam irradiation and the lack of an online range verification method making the current in-beam PET technology still in an awkward situation of using beam-off data to implement range verification,which greatly limits the online potential of in-beam PET.This dissertation aims to explore in-beam beam-on proton radiotherapy monitoring by all-digital PET technology.The research revolves around signal preview analysis,signal acquisition system,signal processing and information extraction methods for solving the aforementioned challenges.Firstly,the physical mechanism of energy transportation and range monitoring for proton beam is studied.The origin of the signal to be observed was researched theoretically,that is,the β+ radioactivity of positron emitters produced by inelastic nuclear reaction between protons and targets.The yield,energy spectrum,and correlation between activity depth and dose distribution of β+ activity signals induced by70～250 Me V proton beams,which are commonly used in clinical treatment,were analyzed employing water phantom.The feasibility of measurement of proton beam generated β+ radioactivity by use of all-digital PET technology was proved.Secondly,the high throughput of the secondary particles induced by the proton beam requires a system with good count rate performance.An all-digital PET dual heads prototype is designed and built for solving the signal acquisition problem for proton therapy monitoring.A total of 2880 LYSO/Si PM one-to-one coupled channels converts high-energy rays into electrical scintillation pulses,reading out by Multi-Voltage Threshold(MVT)electronics in the form of voltage time pairs.This solution enables the system to have extremely high count rate performance to meet the requirements of the in-beam acquisition.The system was evaluated in the proton and radiotherapy center of Chang Gung Memorial Hospital.The average energy resolution of the system was 22%,and the average measured counting rate was 4.85 Mcps during the beam irradiation.The accuracy of range verification was less than 1 mm by comparing the measured activity distribution and the simulated activity distribution.Thirdly,an accurate imaging approach of in-beam PET monitoring proton therapy was developed to address the problem that the in-beam background radiation noise seriously affects the in-beam imaging quality.An accurate imaging approach of in-beam PET monitoring proton therapy is studied.By analyzing the radio frequency characteristics of the beam accelerator and the energy phase features of beam-on noise,a Radio frequency Delta time(Rf Dt)denoising method is developed.The core idea of Rf Dt method is to use the difference of phase distribution of noise particles including prompt gamma and neutron in the proton Rf period to identify the secondary particle type.Ten groups of in-beam monitoring experiments for phantoms and lab animals were performed,which show high-quality imaging results after using Rf Dt methods.For what concerns the reproducibility of the measurements,the consistency of range monitoring between two groups of comparable homogenous phantoms was about 1～2 mm.Fourthly,for the validation of proton range during irradiation,a direct proton range verification method using measured PET activity is studied.Based on the physical principle that nuclear reaction channels like(p,α)and(p,γ)which has low threshold energy is closer to the Bragg peak,a Distal Principal positron emitter Elimination(DPE)method is proposed for online range validation.The simulation results show less than 1 mm distance offset between DPE results and Bragg peak depth in both homogeneous and heterogeneous targets.The feasibility and effectiveness of the DPE method to directly verify the proton range are also verified by practical experiments.To sum up,this dissertation aims at the key scientific problem in in-beam beam-on proton therapy monitoring,covering physical mechanism behind energy transportation and range verification for proton beam,system development of an all-digital PET dual heads for proton therapy monitoring,high-quality imaging approach for the in-beam beam-on scenario,and direct range verification method by in-beam PET,which provides a set of innovative solutions for precise proton therapy by in-beam beam-on range verification. |
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