Calibration method and performance of a time-of-flight detector to measure absolute beam energy in proton therapy

Background: The beam energy is one of the most significant parameters in particle therapy since it is directly correlated to the particles' penetration depth inside the patient. Nowadays, the range accuracy is guaranteed by offline routine quality control checks mainly performed with water phantoms, 2D detectors with PMMA wedges, or multi-layer ionization chambers. The latter feature low sensitivity, slow collection time, and response dependent on external parameters, which represent limiting factors for the quality controls of beams delivered with fast energy switching modalities, as foreseen in future treatments. In this context, a device based on solid-state detectors technology, able to perform a direct and absolute beam energy measurement, is proposed as a viable alternative for quality assurance measurements and beam commissioning, paving the way for online range monitoring and treatment verification. Purpose: This work follows the proof of concept of an energy monitoring system for clinical proton beams, based on Ultra Fast Silicon Detectors (featuring tenths of ps time resolution in 50 μm active thickness, and single particle detection capability) and time-of-flight techniques. An upgrade of such a system is presented here, together with the description of a dedicated self-calibration method, proving that this second prototype is able to assess the mean particles energy of a monoenergetic beam without any constraint on the beam temporal structure, neither any a priori knowledge of the beam energy for the calibration of the system. Methods: A new detector geometry, consisting of sensors segmented in strips, has been designed and implemented in order to enhance the statistics of coincident protons, thus improving the accuracy of the measured time differences. The prototype was tested on the cyclotron proton beam of the Trento Protontherapy Center (TPC). In addition, a dedicated self-calibration method, exploiting the measurement of monoenergetic beams crossing the two telescope sensors for different flight distances, was introduced to remove the systematic uncertainties independently from any external reference. Results: The novel calibration strategy was applied to the experimental data collected at TPC (Trento) and CNAO (Pavia). Deviations between measured and reference beam energies in the order of a few hundreds of keV with a maximum uncertainty of 0.5 MeV were found, in compliance with the clinically required water range accuracy of 1 mm. Conclusions: The presented version of the telescope system, minimally perturbative of the beam, relies on a few seconds of acquisition time to achieve the required clinical accuracy and therefore represents a feasible solution for beam commission, quality assurance checks, and online beam energy monitoring

Characterization of a modified clinical linear accelerator for ultra-high dose rate electron beam delivery

Irradiations at Ultra High Dose Rate (UHDR) regimes, exceeding 40 Gy/s in single fractions lasting less than 200 ms, have shown an equivalent antitumor effect compared to conventional radio-therapy with reduced harm to normal tissues. This work details the hardware and software modi-fications implemented to deliver 10 MeV UHDR electron beams with a Linear Accelerator Elekta SL 18 MV and the beam characteristics obtained. GafChromic EBT XD films and an Advanced Markus chamber were used for the dosimetry characterization, while a silicon sensor assessed the machine\u27s beam pulses stability and repeatability. Dose per pulse, average dose rate and instantaneous dose rate in the pulse were evaluated for four experimental settings, varying the source-to-surface dis-tance and the beam collimation, i.e. with and without the use of a cylindrical applicator. Results showed dose per pulse from 0.6 Gy to a few tens of Gy and average dose rate up to 300 Gy/s. The obtained results demonstrate the possibility to perform in-vitro radiobiology experiments and test of new technologies for beam monitoring and dosimetry at the upgraded LINAC, thus contributing to the electron UHDR research field

High-redshift post-reionization cosmology with 21cm intensity mapping

We investigate the possibility of performing cosmological studies in the redshift range 2.5<z<5 through suitable extensions of existing and upcoming radio-telescopes like CHIME, HIRAX and FAST. We use the Fisher matrix technique to forecast the bounds that those instruments can place on the growth rate, the BAO distance scale parameters, the sum of the neutrino masses and the number of relativistic degrees of freedom at decoupling, Neff. We point out that quantities that depend on the amplitude of the 21cm power spectrum, like f\u3c38, are completely degenerate with \u3a9HI and bHI, and propose several strategies to independently constrain them through cross-correlations with other probes. Assuming 5% priors on \u3a9HI and bHI, kmax=0.2 h Mpc-1 and the primary beam wedge, we find that a HIRAX extension can constrain, within bins of \u394 z=0.1: 1) the value of f\u3c38 at 4%, 2) the value of DA and H at 1%. In combination with data from Euclid-like galaxy surveys and CMB S4, the sum of the neutrino masses can be constrained with an error equal to 23 meV (1\u3c3), while Neff can be constrained within 0.02 (1\u3c3). We derive similar constraints for the extensions of the other instruments. We study in detail the dependence of our results on the instrument, amplitude of the HI bias, the foreground wedge coverage, the nonlinear scale used in the analysis, uncertainties in the theoretical modeling and the priors on bHI and \u3a9HI. We conclude that 21cm intensity mapping surveys operating in this redshift range can provide extremely competitive constraints on key cosmological parameters

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Development of systems based on silicon detectors for beam monitoring, treatment verification and microdosimetry in Particle Therapy

Charged Particle Therapy (CPT) has gained a signi cant interest for the treatment of solid tumors thanks to the favorable depth-dose deposition which allows for the delivery of a well-conformed dose to the tumour while sparing healthy tissues e ectively. In addition, charged particles, such as carbon ions, exhibit a larger biological effectiveness in comparison to conventional photons, thereby providing the potential to treat radioresistant tumors with a higher success probability. This thesis presents the development and testing of new system based on silicon detectors to further improve the delivery of the dose to the tumor. In particular, this work explores the use of silicon detectors for beam monitoring, particle range verification and treatment quality assurance through microdosimetric measurements.The state-of-the-art of beam monitors in CPT are the gas- lled Ionization Chambers (IC), which measure beam position, shape and particle flux. Even though ICs are widely used in clinics showing good radiation hardness, the slow charge collection time of 100 s and the low sensitivity of 1000 particles prevent ICs from being used for the development of faster and more precise irradiation modalities. The medical physics group of the University of Torino and the Nuclear Institute for Nuclear Physics (INFN) is working on the development of new detectors based on silicon sensors for applications in beam monitoring and range veri cation during the treatment. Thin planar silicon sensors appear to be a promising alternative to ICs, allowing for the direct discrimination of particles, thanks to the short charge collection time of 1 ns and to the sensitivity to the single particle.In this context, an innovative proton and carbon ion counter is presented in this work. The detector exploits strip-segmented planar silicon sensors with an active thickness of a few tens of m read out by a front-end electronics based on a 24-channel ASIC for the discrimination of the particles' signals. The detectors were tested with clinical beams at the Centro Nazionale di Adroterapia Oncologica (CNAO) in Pavia, Italy. The proton counting efficiency shows a dependence on the beam energy because of transversal dimension and pile-up effects whereas an efficiency between 94 and 98 % with lower energy dependence was measured for carbon ion beams. In addition, the particle counter was integrated with the CERN PicoTDC, a Time-to-Digital Converter with a minimum bin size of 3 ps. A measurement of the distribution of the time interval between consecutive crossing particles was performed and was found to be compatible with the accelerator radio-frequency period.The second application investigated in this thesis is a novel range verification system based on the Prompt Gamma Timing (PGT) technique. The PGT method provides the assessment of the particle range by measuring the time of flight between the primary particle transit time and the detection of the Prompt Gamma (PG) photons emitted by the fast de-excitation of nuclei left in an excited state by nuclear interactions. The setup relies on a strip-segmented silicon sensor and a LaBr3(Ce) scintillating crystal coupled with Silicon PhotoMultiplier to detect the primary particles and the PG photons, respectively. The signal readout is based on the PicoTDC. The preliminary measurements were conducted with 398 MeV/u carbon ions at sub-clinical rate in CNAO, showing promising results.Finally, the thesis reports the microdosimetric measurements and simulations performed with a 3D Silicon-On-Insulator (SOI) microdosimeter developed by the Centre for Medical Radiation Physics (CMRP) in Wollongong, Australia. The aim is to compare the Relative Biological Effectiveness (RBE) calculated using the Microdosimetric Kinetic Model (MKM), based on microdosimetric measurements, with the RBE computed by a Treatment Planning System (TPS) using the Local Effect Model (LEM). The 3D SOI microdosimeter was placed in an RW3 phantom and was irradiated with different carbon ion plans at CNAO, acquiring microdosimetric spectra along the beam direction. A good agreement between experiment and Monte Carlo simulation was found, providing RBE10 values ranging between 1.2 and 2.8. The prescribed LEM-based biological dose of 3 GyE in a cubic Spread-Out-Bragg- Peak was found to be 33 % larger than the MKM-based biological dose, consistently with other results found in the literature. This result confirms the reliable use of the 3D SOI microdosimeters as a quality assurance tool for RBE prediction in particle therapy.</p