Abstract

Proton therapy is a recent type of radiotherapy that uses high-energy proton beams, and more recently carbon ion beams, to benefit of their physical selectivity. The energy deposited by these particle beams is inversely proportional to their velocity. Therefore they release most of the energy at the end of their path into the tissue. The energy is deposited in a few millimeters, in a zone called the Bragg peak. Before and after the Bragg peak the energy deposition is minimal. The depth and the width of the Bragg peak depends on the beam energy and on the density of tissues located along the beam path. By setting the beam energy, the Bragg peak can be positioned in the tumor site, avoiding the healthy tissues. Because of the sharpness of the Bragg peak zone, proton therapy is advantageous for tumors located near to important body part, such as the brain, spine, and neck. The drawback is that small uncertainties on particle range can have a serious impact on treatment and limit the efficiency of the proton therapy. To obtain more effective treatments in proton therapy real-time range verifications are necessary to perform on-line corrections of the delivered treatment. Among different techniques presented in the literature, positron emission tomography (PET) and prompt gamma imaging (PGI) are the most promising methods for in vivo range verification. PET and PGI are indirect approaches to measure protons penetration depth inside patients because they aim to detect secondary particles resulting from the interaction between proton beams and tissue nuclei. PET imaging detects coincidence gamma rays due to the production of positron emitters and requires some minutes to achieve enough statistics to have a sufficient signal to noise ratio. PGI instead uses prompt gamma rays generated by de-excitation of target nuclei; the quantity of these rays and their temporal emission (few nanoseconds) allow to perform a range verification during treatment with the PGI. Several research groups are evaluating different approaches to realize a prompt gamma imaging system suitable for the use in clinical condition and the optimization of a gamma-ray detector for PGI is still ongoing. The Gammarad project works in this direction and aims to develop an high-performance and solid-state gamma ray detection module (GDM) with a slit camera design. The project is based on a collaboration among Fondazione Bruno Kessler (FBK, Trento, Italy), Politecnico di Milano (Milano, Italy), the Trento Institute for Fundamental Physics and Applications (TIFPA, Trento, Italy ), and the Proton Therapy Center of Trento (Italy). The project is divided into two parts. The first part focuses on the technological development of a gamma-ray imaging module. This module is composed by a gamma-ray detector, based on a solid-state silicon sensor, and an integrated circuit. They are assembled into a compact module with data and control systems. The second part of the project will be dedicated to the experimental validation of the system both in laboratory with radioactive sources and in a real environment, that of proton therapy. The most innovative part of the gamma-ray detector developed for the project is the photo-sensor used for the scintillation light readout. In traditional applications it is a photomultiplier tube (PMT). However, in recent years, Silicon Photomultiplier (SiPM) has become increasingly popular in a variety of applications for its promising characteristics. Among them, current-generation SiPMs offer high gain, high Photon Detection Efficiency (PDE), excellent timing performance, high count-rate capability and good radiation hardness. Due to these characteristics they are used as PMTs replacement in several applications, such as in nuclear medicine (PET), in high-energy physics (calorimeters), astrophysics (Cherenkov telescopes) and in others single-photon or few-photon applications. For its characteristics, the SiPM is also very promising for the scintillator readout in prompt gamma imaging and in high energy gamma-ray spectroscopy. Detectors for these applications must be compact, robust, and insensitive to the magnetic field. They have to provide high performance in terms of spatial, temporal, and energy resolution. SiPMs can satisfy all these requirements but typically they have been used with relatively low energy gamma rays and low photon flux, so manufacturers have optimized them for these conditions. Because of the limited number of micro-cells in a standard SiPM, 625 cells/mm^2 with 40 µm cells, the detector response is non-linear in high energies condition. Increasing the cell density is extremely important to improve the linearity of the SiPM and to avoid the compression of the energy spectrum at high energies, which worsens the energy resolution and makes difficult the calibration of the detector. On the other hand, small cells provide a lower Photon Detection Efficiency (PDE) because of the lower Fill Factor (FF) and as a consequence a lower energy resolution. Summarizing, the energy resolution at high energies is a trade-off between the excess noise factor (ENF) caused by the non-linearity of the SiPM and the PDE of the detector. Moreover, the small cell size provides an ultra-fast recovery time, in the order of a few of nanosecond for the smallest cells. A short recovery time together with a fast scintillator such a LYSO, reduces pile-up in high-rate applications, such as PGI. Based on the above considerations, the aim of this thesis is to develop an optimized gamma-ray detector composed of SiPMs for high-dynamic-range application, such as the scintillation light readout in prompt gamma imaging and in high-energy gamma-ray spectroscopy. SiPMs evaluated for the detector are High-Density (HD) and Ultra-High-Density (UHD) SiPM technologies recently produced at Fondazione Bruno Kessler (FBK). Instead of standard SiPMs, HD and UHD SiPMs have a very small micro-cell pitch, from 30 µm down to 5 µm with a cell density from 1600 cells/mm^2 to 46190 cells/mm^2, respectively. HD SiPMs are produced using a lithography technology with smaller critical dimensions and designed with trenches among SPADs. Small cells have a lower gain which helps to reduce correlated noise, such as After-Pulse and Cross-Talk. Trenches provide an optical and electrical cell isolation, and a smaller dead border around cells which increase the FF limiting PDE losses. UHD SiPMs push the limits of the HD technology even further, by reducing all the feature sizes, such as contacts, resistors and border region around cells. UHD SiPMs have hexagonal cells in a honeycomb configuration which generate a circular active area and a dead border around cells lower than 1 µm. The reduction of this dead boarder can improve the FF in smaller cells although it usually decrease with cell sizes. It is necessary understand how these significant layout changes affect the optical properties of SiPMs to evaluate which SiPM technology provides best performance in high-energy gamma-ray applications. In the first part of the thesis, I presents the characterization of HD and UHD SiPM technologies in terms of PDE, gain, Dark Count Rate, and correlated noise for the cell sizes between 30 and 7.5 µm. The most important markers of SiPMs performance in gamma-ray spectroscopy are however the energy resolution and the linearity when coupled to the scintillator for the detection of high-energy gamma-rays. A typical characterization of the energy resolution of SiPMs, coupled to scintillator crystals, is performed with radioactive source up to 1.5 MeV. However, PGI features gamma ray-energies up to 15 MeV which are not easily provided by the usual laboratory calibration sources. Extrapolating the behaviour of the detector from the "low" energy data is not correct and leads to unreliable data for calibration and performance estimation. Therefore, I developed a novel setup that simulates the LYSO light emission in response to gamma photons up to 30 MeV. A LED (emitting at 420 nm) is driven by a pulse generator, emulating the light emitted by a LYSO scintillator when excited by gamma rays. The pulse generator parameters (amplitude, duration, rise and fall time constants) are adjusted so that the LED emitted photons match the intensity and time distribution of the LYSO emission. The photon number in each light pulse is calibrated from the measurements at 511 keV obtained with a ^(22)Na source and a LYSO crystal coupled to the SiPMs. Using this LED setup I characterized the energy resolution and non-linearity of HD and UHD SiPMs in high-energy gamma-ray conditions. The second part of the thesis provides a detailed description of the scintillator setup and of the setup for the simulation of high-energy gamma-ray response, followed by the results of the characterization performing with these setups. Summarizing the results, the lowest non-linearity is provided by the technology with highest cell density, the RGB-UHD. For the 10 and 12.5 µm-cells we obtained values of 4.5% and 5% respectively at 5 MeV and 6 V over-voltage. On the other hand, we measured the best energy resolution of 2.6% and 2.3% at 5 MeV for the largest SiPM cells of 20 and 25 µm respectively, without the intrinsic term of the scintillator crystal and at 6 V over-voltage. This is due to the dependence of the energy resolution on the photon detection efficiency, which increases with the size of the SiPM cell. The optimal performance of the detector in high-dynamic-range applications, which depends on the several SiPM parameters, such as excess noise factor, photon detection efficiency, and cell sizes of the SiPM, is a trade off between non-linearity and energy resolution. At 5 MeV, the best trade-off for prompt gamma imaging application is reached by the 15 µm-cell. At 10 MeV the 12.5 µm-cell provides the best trade-off, because of the higher number of photons emitted by the scintillator. Furthermore, I distinguish the different components of the energy resolution (intrinsic, statistical, detector and electronic noise) as a function of cell sizes, over-voltage and energy, thanks to the combination of the scintillator and LED setups. The estimation of the intrinsic contribution of the scintillator crystal, coupled to the HD SiPMs, getting consistent results among the several cell sizes. On the basis of previous characterization, HD SiPMs with dimensions of 4x4 mm^2 and 15 µm-cell were chosen to produce the photo-detector module of the gamma camera, optimized for an energy range between 2 and 8 MeV. This module is a 8x8 array of SiPMs which is called tile. The production of the tile requires research on packaging techniques to solve two main challenges: the maximization of the photo-sensitive area and the application of a protective resin, transparent in the near UV to maximize light collection from the LYSO. After some R&D on packaging, I obtained a fully functional tile with 64 SiPMs with a fill factor, ratio between the photo-sensitive area and the total area, of about 86%. This fill factor is comparable to the values obtained when a Through Silicon Vias (TSVs) technique is used to connect SiPMs but without the high production cost and the additional fabrication process complexity of the TSV. It should be highlighted that packaging operations is very critical because it is necessary to produce a tile with all working SiPMs, since defective items can not be replaced in the tile. The last part of the thesis presents the packaging procedure that I have defined to produce photo-detector modules and the characterization of the photo-detector array in terms of energy resolution, position sensitive and non-linearity. The measurements on the tile were carried out jointly with the Gammarad partner of Politecnico di Milano, which provided the ASIC and DAQ for the readout. In conclusion, the R&D activity carried out during this thesis has provided to Gammarad project the final photo-detection module with state of the art performance for high-energy gamma-ray spectroscopy. The characterization of the module shows also a position sensitivity that matches with the SiPM dimensions, and a proper acquisition of high-energy gamma-ray events from 800 keV to 13 MeV. This module will be tested on beam in an experimental treatment room at the Proton therapy facility in Trento by the Gammarad project partners.