Stability and efficiency of a CMOS sensor as detector of low energy beta and gamma particles

Radio Guided Surgery (RGS) is a nuclear medicine technique allowing the surgeon to identify tumor residuals in real time with a millimetric resolution, thanks to a radiopharmaceutical as tracer and a probe as detector. The use of beta(-) emitters, instead of gamma or beta(+), has been recently proposed with the aim to increase the technique sensitivity and reducing both the administered activity to the patient and the medical exposure. In this paper, the possibility to use the commercial CMOS Image Sensor MT9V115, originally designed for visible light imaging, as beta(-) radiation detector RGS is discussed. Being crucial characteristics in a surgical environment, in particular its stability against time, operating temperature, integration time and gain has been studied on laboratory measurements. Moreover, a full Monte Carlo simulation of the detector has been developed. Its validation against experimental data allowed us to obtain efficiency curves for both beta and gamma particles, and also to evaluate the effect of the covering heavy resin protective layer that is present in the "off the shelf" detector. This study suggests that a dedicated CMOS Image Sensor (i.e. one produced without the covering protective layer) represents the ideal candidate detector for RGS, able to massively increase the amount of application cases and the efficacy of this technique

Localization of anatomical changes in patients during proton therapy with in-beam PET monitoring: a voxel-based morphometry approach exploiting Monte Carlo simulations

Purpose: In-beam positron emission tomography (PET) is one of the modalities that can be used for in vivo noninvasive treatment monitoring in proton therapy. Although PET monitoring has been frequently applied for this purpose, there is still no straightforward method to translate the information obtained from the PET images into easy-to-interpret information for clinical personnel. The purpose of this work is to propose a statistical method for analyzing in-beam PET monitoring images that can be used to locate, quantify, and visualize regions with possible morphological changes occurring over the course of treatment. Methods: We selected a patient treated for squamous cell carcinoma (SCC) with proton therapy, to perform multiple Monte Carlo (MC) simulations of the expected PET signal at the start of treatment, and to study how the PET signal may change along the treatment course due to morphological changes. We performed voxel-wise two-tailed statistical tests of the simulated PET images, resembling the voxel-based morphometry (VBM) method commonly used in neuroimaging data analysis, to locate regions with significant morphological changes and to quantify the change. Results: The VBM resembling method has been successfully applied to the simulated in-beam PET images, despite the fact that such images suffer from image artifacts and limited statistics. Three dimensional probability maps were obtained, that allowed to identify interfractional morphological changes and to visualize them superimposed on the computed tomography (CT) scan. In particular, the characteristic color patterns resulting from the two-tailed statistical tests lend themselves to trigger alarms in case of morphological changes along the course of treatment. Conclusions: The statistical method presented in this work is a promising method to apply to PET monitoring data to reveal interfractional morphological changes in patients, occurring over the course of treatment. Based on simulated in-beam PET treatment monitoring images, we showed that with our method it was possible to correctly identify the regions that changed. Moreover we could quantify the changes, and visualize them superimposed on the CT scan. The proposed method can possibly help clinical personnel in the replanning procedure in adaptive proton therapy treatments

In-vivo range verification analysis with in-beam PET data for patients treated with proton therapy at CNAO

Morphological changes that may arise through a treatment course are probably one of the most significant sources of range uncertainty in proton therapy. Non-invasive in-vivo treatment monitoring is useful to increase treatment quality. The INSIDE in-beam Positron Emission Tomography (PET) scanner performs in-vivo range monitoring in proton and carbon therapy treatments at the National Center of Oncological Hadrontherapy (CNAO). It is currently in a clinical trial (ID: NCT03662373) and has acquired in-beam PET data during the treatment of various patients. In this work we analyze the in-beam PET (IB-PET) data of eight patients treated with proton therapy at CNAO. The goal of the analysis is twofold. First, we assess the level of experimental fluctuations in inter-fractional range differences (sensitivity) of the INSIDE PET system by studying patients without morphological changes. Second, we use the obtained results to see whether we can observe anomalously large range variations in patients where morphological changes have occurred. The sensitivity of the INSIDE IB-PET scanner was quantified as the standard deviation of the range difference distributions observed for six patients that did not show morphological changes. Inter-fractional range variations with respect to a reference distribution were estimated using the Most-Likely-Shift (MLS) method. To establish the efficacy of this method, we made a comparison with the Beam's Eye View (BEV) method. For patients showing no morphological changes in the control CT the average range variation standard deviation was found to be 2.5 mm with the MLS method and 2.3 mm with the BEV method. On the other hand, for patients where some small anatomical changes occurred, we found larger standard deviation values. In these patients we evaluated where anomalous range differences were found and compared them with the CT. We found that the identified regions were mostly in agreement with the morphological changes seen in the CT scan

Monitoring Carbon Ion Beams Transverse Position Detecting Charged Secondary Fragments: Results From Patient Treatment Performed at CNAO

Particle therapy in which deep seated tumours are treated using 12C ions (Carbon Ions RadioTherapy or CIRT) exploits the high conformity in the dose release, the high relative biological effectiveness and low oxygen enhancement ratio of such projectiles. The advantages of CIRT are driving a rapid increase in the number of centres that are trying to implement such technique. To fully profit from the ballistic precision achievable in delivering the dose to the target volume an online range verification system would be needed, but currently missing. The 12C ions beams range could only be monitored by looking at the secondary radiation emitted by the primary beam interaction with the patient tissues and no technical solution capable of the needed precision has been adopted in the clinical centres yet. The detection of charged secondary fragments, mainly protons, emitted by the patient is a promising approach, and is currently being explored in clinical trials at CNAO. Charged particles are easy to detect and can be back-tracked to the emission point with high efficiency in an almost background-free environment. These fragments are the product of projectiles fragmentation, and are hence mainly produced along the beam path inside the patient. This experimental signature can be used to monitor the beam position in the plane orthogonal to its flight direction, providing an online feedback to the beam transverse position monitor chambers used in the clinical centres. This information could be used to cross-check, validate and calibrate, whenever needed, the information provided by the ion chambers already implemented in most clinical centres as beam control detectors. In this paper we study the feasibility of such strategy in the clinical routine, analysing the data collected during the clinical trial performed at the CNAO facility on patients treated using 12C ions and monitored using the Dose Profiler (DP) detector developed within the INSIDE project. On the basis of the data collected monitoring three patients, the technique potential and limitations will be discussed

The Gaia-ESO Survey::the present-day radial metallicity distribution of the Galactic disc probed by pre-main-sequence clusters

Context. The radial metallicity distribution in the Galactic thin disc represents a crucial constraint for modelling disc formation and evolution. Open star clusters allow us to derive both the radial metallicity distribution and its evolution over time. Aims. In this paper we perform the first investigation of the present-day radial metallicity distribution based on [Fe/H] determinations in late type members of pre-main-sequence clusters. Because of their youth, these clusters are therefore essential for tracing the current interstellar medium metallicity. Methods. We used the products of the Gaia-ESO Survey analysis of 12 young regions (age < 100 Myr), covering Galactocentric distances from 6.67 to 8.70 kpc. For the first time, we derived the metal content of star forming regions farther than 500 pc from the Sun. Median metallicities were determined through samples of reliable cluster members. For ten clusters the membership analysis is discussed in the present paper, while for other two clusters (i.e. Chamaeleon I and Gamma Velorum) we adopted the members identified in our previous works. Results. All the pre-main-sequence clusters considered in this paper have close-to-solar or slightly sub-solar metallicities. The radial metallicity distribution traced by these clusters is almost flat, with the innermost star forming regions having [Fe/H] values that are 0.10−0.15 dex lower than the majority of the older clusters located at similar Galactocentric radii. Conclusions. This homogeneous study of the present-day radial metallicity distribution in the Galactic thin disc favours models that predict a flattening of the radial gradient over time. On the other hand, the decrease of the average [Fe/H] at young ages is not easily explained by the models. Our results reveal a complex interplay of several processes (e.g. star formation activity, initial mass function, supernova yields, gas flows) that controlled the recent evolution of the Milky Way

Characterization of Ultra-High-Dose Rate Electron Beams with ElectronFlash Linac

Purpose: The electron linac ElectronFlash installed at Institut Curie (Orsay, France) is entirely dedicated to FLASH irradiation for radiobiological and pre-clinical studies. The system was designed to deliver an ultra-high-dose rate per pulse (UHDR) (above 106 Gy/s) and a very high average dose rate at different energies and pulse durations. A campaign of tests and measurements was performed to obtain a full reliable characterizations of the electron beam and of the delivered dose, which are necessary to the radiobiological experiments. Methods: A Faraday cup was used to measure the electron charges in a single RF pulse. The percentage depth dose (PDD) and the transverse dose profiles, at the energies of 5 MeV and 7 MeV, were evaluated employing Gafchromic films EBT-XD for two Poly-methylmethacrylate (PMMA) applicators with irradiation sizes of 30 mm and 120 mm, normally used for in vivo and in vitro experiments, respectively. The results were compared with Monte Carlo (MC) simulations. Results: The measurements were performed during a period of a few months in which the experimental set up was adapted and tuned in order to characterize the electron beam parameters and the values of delivered doses before the radiobiological experiments. The measurements showed that the dose parameters, obtained at the energy of 5 MeV and 7 MeV with different applicators, fulfill the FLASH regime, with a maximum value of an average dose rate of 4750 Gy/s, a maximum dose per pulse of 19 Gy and an instantaneous dose rate up to 4.75 ×106 Gy/s. By means of the PMMA applicators, a very good flatness of the dose profiles was obtained at the cost of a reduced total current. The flatness of the large field is reliable and reproducible in radiobiological experiments. The measured PDD and dose profiles are in good agreement with Monte Carlo simulations with more than 95% of the gamma-index under the thresholds of 3 mm/3%. Conclusions: The results show that the system can provide UHDR pulses totally satisfying the FLASH requirements with very good performances in terms of beam profile flatness for any size of the fields. The monitoring of electron beams and the measurement of the dose parameters played an important role in the in vivo and in vitro irradiation experiments performed at the Institut Curie laboratory

GPU-accelerated Monte Carlo simulation of electron and photon interactions for radiotherapy applications

The Monte Carlo simulation software is a valuable tool in radiation therapy, in particular to achieve the needed accuracy in the dose evaluation for the treatment plans optimisation. The current challenge in this field is the time reduction to open the way to many clinical applications for which the computational time is an issue. In this manuscript we present an innovative GPU-accelerated Monte Carlo software for dose valuation in electron and photon based radiotherapy, developed as an update of the FRED (Fast paRticle thErapy Dose evaluator) software

Deep seated tumour treatments with electrons of high energy delivered at FLASH rates: the example of prostate cancer

Different therapies are adopted for the treatment of deep seated tumours in combination or as an alternative to surgical removal or chemotherapy: radiotherapy with photons (RT), particle therapy (PT) with protons or even heavier ions like 12C, are now available in clinical centres. In addition to these irradiation modalities, the use of Very High Energy Electron (VHEE) beams (100–200 MeV) has been suggested in the past, but the diffusion of that technique was delayed due to the needed space and budget, with respect to standard photon devices. These disadvantages were not paired by an increased therapeutic efficacy, at least when comparing to proton or carbon ion beams. In this contribution we investigate how recent developments in electron beam therapy could reshape the treatments of deep seated tumours. In this respect we carefully explored the application of VHEE beams to the prostate cancer, a well-known and studied example of deep seated tumour currently treated with high efficacy both using RT and PT. The VHEE Treatment Planning System was obtained by means of an accurate Monte Carlo (MC) simulation of the electrons interactions with the patient body. A simple model of the FLASH effect (healthy tissues sparing at ultra-high dose rates), has been introduced and the results have been compared with conventional RT. The study demonstrates that VHEE beams, even in absence of a significant FLASH effect and with a reduced energy range (70–130 MeV) with respect to implementations already explored in literature, could be a good alternative to standard RT, even in the framework of technological developments that are nowadays affordable