Experimental validation of an analytical microdosimetric model based on Geant4-DNA simulations by using a silicon-based microdosimeter.

PURPOSE: To study the agreement between proton microdosimetric distributions measured with a silicon-based cylindrical microdosimeter and a previously published analytical microdosimetric model based on Geant4-DNA in-water Monte Carlo simulations for low energy proton beams. METHODS AND MATERIAL: Distributions for lineal energy (y) are measured for four proton monoenergetic beams with nominal energies from 2.0 MeV to 4.5 MeV, with a tissue equivalent proportional counter (TEPC) and a silicon-based microdosimeter. The actual energy for protons traversing the silicon-based microdosimeter is simulated with SRIM. Monoenergetic beams with these energies are simulated with Geant4-DNA code by simulating a water cylinder site of dimensions equal to those of the microdosimeter. The microdosimeter response is calibrated by using the distribution peaks obtained from the TEPC. Analytical calculations for y ¯ F and y ¯ D using our methodology based on spherical sites are also performed choosing the equivalent sphere to be checked against experimental results. RESULTS: Distributions for y at silicon are converted into tissue equivalent and compared to the Geant4-DNA simulated, yielding maximum deviations of 1.03% for y ¯ F and 1.17% for y ¯ D . Our analytical method generates maximum deviations of 1.29% and 3.33%, respectively, with respect to experimental results. CONCLUSION: Simulations in Geant4-DNA with ideal cylindrical sites in liquid water produce similar results to the measurements in an actual silicon-based cylindrical microdosimeter properly calibrated. The found agreement suggests the possibility to experimentally verify the calculated clinical y ¯ D with our analytical method.

New opto-electro-mechanical sensor for two-dimensions dosimetry based on radiochromic films.

This work presents the validation of a new Opto‒Electro-Mechanical (MOEM) system consisting of a matrix of photodetectors for two-dimensional dosimetry evaluation with radiochromic films. The proposed system is based on a 5 × 10 matrix of photodetectors controlled by both in-house electronic circuit and graphical user interface, which enables optical measurements directly. We present the first tests performed in an X-ray machine and 137Cs source with that array by using Gafchromic EBT3 films. We obtained similar results than with a standard method (e.g. flat-bed scanner). Results were compared with Monte Carlo simulations and very good agreement was found. Results show the feasibility of using this system for dose evaluations. To the best of our knowledge, this is the first MOEM sensor for radiotherapy. Further developments are ongoing to create an advanced 16 × 16 LDRs system covering 1.6 cm × 1.6 cm with a 1 mm of spatial resolution. We point to develop a portable dosimetry tool delivering dose maps in real time to improve the clinical application of radiochromic films.

Dosimetry with gafchromic films based on a new micro-opto-electro-mechanical system.

This work presents the first tests performed with radiochromic films and a new Micro‒Opto‒Electro-Mechanical system (MOEMS) for in situ dosimetry evaluation in radiotherapy in real time. We present a new device and methodology that overcomes the traditional limitation of time-delay in radiochromic film analysis by turning a passive detector into an active sensor. The proposed system consists mainly of an optical sensor based on light emitting diodes and photodetectors controlled by both customized electronic circuit and graphical user interface, which enables optical measurements directly. We show the first trials performed in a low‒energy proton cyclotron with this MOEMS by using gafchromic EBT3 films. Results show the feasibility of using this system for in situ dose evaluations. Further adaptation is ongoing to develop a full real‒time active detector by integrating MOEM multi‒arrays and films in flexible printed circuits. Hence, we point to improve the clinical application of radiochromic films with the aim to optimize radiotherapy treatment verifications.

Microdosimetry in low energy proton beam at therapeutic-equivalent fluence rate with silicon 3D-cylindrical microdetectors.

In this work we show the first microdosimetry measurements on a low energy proton beam with therapeutic-equivalent fluence rates by using the second generation of 3D-cylindrical microdetectors. The sensors belong to an improved version of a novel silicon-based 3D-microdetector design with electrodes etched inside silicon, which were manufactured at the National Microelectronics Centre (IMB-CNM, CSIC) in Spain. A new microtechnology has been employed using quasi-toroid electrodes of 25µm diameter and a depth of 20µm within the silicon bulk, resulting in a well-defined cylindrical radiation sensitive volume. These detectors were tested at the 18 MeV proton beamline of the cyclotron at the National Accelerator Centre (CNA, Spain). They were assembled into an in-house low-noise readout electronics to assess their performance at a therapeutic-equivalent fluence rate. Microdosimetry spectra of lineal energy were recorded at several proton energies starting from 18 MeV by adding 50µm thick tungsten foils gradually at the exit-window of the cyclotron external beamline, which corresponds to different depths along the Bragg curve. The experimentalyF¯values in silicon cover from (5.7 ± 0.9) to (8.5 ± 0.4) keV µm-1in the entrance to (27.4 ± 2.3) keV µm-1in the distal edge. Pulse height energy spectra were crosschecked with Monte Carlo simulations and an excellent agreement was obtained. This work demonstrates the capability of the second generation 3D-microdetectors to assess accurate microdosimetric distributions at fluence rates as high as those used in clinical centers in proton therapy.

Minibeam radiation therapy at a conventional irradiator: Dose-calculation engine and first tumor-bearing animals irradiation.

PURPOSE: Minibeam radiation therapy (MBRT) is a novel therapeutic strategy, whose exploration was hindered due to its restriction to large synchrotrons. Our recent implementation of MBRT in a wide-spread small animal irradiator offers the possibility of performing systematic radiobiological studies. The aim of this research was to develop a set of dosimetric tools to reliably guide biological experiments in the irradiator. METHODS: A Monte Carlo (Geant4)-based dose calculation engine was developed. It was then benchmarked against a series of dosimetric measurements performed with gafchromic films. Two voxelized rat phantoms (ROBY, computer tomography) were used to evaluate the treatment plan of F98 tumor-bearing rats. The response of a group of 7 animals receiving a unilateral irradiation of 58 Gy was compared to a group of non-irradiated controls. RESULTS: The good agreement between calculations and the experimental data allowed the validation of the dose-calculation engine. The latter was first used to compare the dose distributions in computer tomography images of a rat's head and in a digital model of a rat's head (ROBY), obtaining a good general agreement. Finally, with respect to the in vivo experiment, the increase of mean survival time of the treated group with respect to the controls was modest but statistically significant. CONCLUSIONS: The developed dosimetric tools were used to reliably guide the first MBRT treatments of intracranial glioma-bearing rats outside synchrotrons. The significant tumor response obtained with respect to the non-irradiated controls, despite the heterogenous dose coverage of the target, might indicate the participation of non-targeted effects.

Impact of charge collection efficiency and electronic noise on the performance of solid-state 3D microdetectors.

Microdosimetry has been traditionally performed through gaseous proportional counters, although in recent years different solid-state microdosimeters have been proposed and constructed for this task. In this paper, we analyze the response of solid-state devices of micrometric size with no intrinsic gain developed by CNM-CSIC (Spain). There are two major aspects of the operation of these devices that affect the reconstruction of the probability distributions and momenta of stochastic quantities related to microdosimetry. For micrometric volumes, the drift and diffusion of the charge carriers gives rise to a partial charge collection efficiency in the peripheral region of the depleted volume. This effect produces a perturbation of the reconstructed pulse height (i.e. imparted energy) distributions with respect to the actual microdosimetric distributions. The relevance of this deviation depends on the size, geometry and operating conditions of the device. On the other hand, the electronic noise from the single-event readout set-up poses a limit on the minimum detectable lineal energy when the microdosimeter size is reduced. This article addresses these issues to provide a framework on the physical constraints for the design and operation of solid-state microdosimeters.

Spatial fractionation of the dose in proton therapy: Proton minibeam radiation therapy.

In radiation therapy, a renewed interest is emerging for the study of spatially fractionated irradiation. In this article, a few applications using spatial fractionation of the dose will be discussed with a focus on proton minibeam radiation therapy. Examples of calculated dose (1D profiles and 2D dose distributions) and biological evidence obtained so far will be presented for various spatially fractionated techniques GRID, micro- and minibeam radiation therapy. Recent results demonstrating that proton minibeam radiation therapy leads to an increase in normal tissues sparing will be discussed, which opens the door to a dose escalation in the tumour and a possibly efficient treatment of very radioresistant tumours.

Transfer of Minibeam Radiation Therapy into a cost-effective equipment for radiobiological studies: a proof of concept.

Minibeam radiation therapy (MBRT) is an innovative synchrotron radiotherapy technique able to shift the normal tissue complication probability curves to significantly higher doses. However, its exploration was hindered due to the limited and expensive beamtime at synchrotrons. The aim of this work was to develop a cost-effective equipment to perform systematic radiobiological studies in view of MBRT. Tumor control for various tumor entities will be addressable as well as studies to unravel the distinct biological mechanisms involved in normal and tumor tissues responses when applying MBRT. With that aim, a series of modifications of a small animal irradiator were performed to make it suitable for MBRT experiments. In addition, the brains of two groups of rats were irradiated. Half of the animals received a standard irradiation, the other half, MBRT. The animals were followed-up for 6.5 months. Substantial brain damage was observed in the group receiving standard RT, in contrast to the MBRT group, where no significant lesions were observed. This work proves the feasibility of the transfer of MBRT outside synchrotron sources towards a small animal irradiator.

AIR KERMA TO Hp(3) CONVERSION COEFFICIENTS FOR IEC 61267 RQR X-RAY RADIATION QUALITIES: APPLICATION TO DOSE MONITORING OF THE LENS OF THE EYE IN MEDICAL DIAGNOSTICS.

Recent studies highlight the fact that the new eye lens dose limit can be exceeded in interventional radiology procedures and that eye lens monitoring could be required for these workers. The recommended operational quantity for monitoring of eye lens exposure is the personal dose equivalent at 3 mm depth Hp(3) (ICRU 51). However, there are no available conversion coefficients in international standards, while in the literature coefficients have only been calculated for monoenergetic beams and for ISO 4037-1 X-ray qualities. The aim of this article is to provide air kerma to Hp(3) conversion coefficients for a cylindrical phantom made of ICRU-4 elements tissue-equivalent material for RQR radiation qualities (IEC-61267) from 40 to 120 kV and for angles of incidence from 0 to 180°, which are characteristic of medical workplace. Analytic calculations using interpolation techniques and Monte Carlo modelling have been compared.

Measurement of carbon ion microdosimetric distributions with ultrathin 3D silicon diodes.

The commissioning of an ion beam for hadrontherapy requires the evaluation of the biologically weighted effective dose that results from the microdosimetric properties of the therapy beam. The spectra of the energy imparted at cellular and sub-cellular scales are fundamental to the determination of the biological effect of the beam. These magnitudes are related to the microdosimetric distributions of the ion beam at different points along the beam path. This work is dedicated to the measurement of microdosimetric spectra at several depths in the central axis of a (12)C beam with an energy of 94.98 AMeV using a novel 3D ultrathin silicon diode detector. Data is compared with Monte Carlo calculations providing an excellent agreement (deviations are less than 2% for the most probable lineal energy value) up to the Bragg peak. The results show the feasibility to determine with high precision the lineal energy transfer spectrum of a hadrontherapy beam with these silicon devices.

Neutron measurements with ultra-thin 3D silicon sensors in a radiotherapy treatment room using a Siemens PRIMUS linac.

The accurate detection and dosimetry of neutrons in mixed and pulsed radiation fields is a demanding instrumental issue with great interest both for the industrial and medical communities. In recent studies of neutron contamination around medical linacs, there is a growing concern about the secondary cancer risk for radiotherapy patients undergoing treatment in photon modalities at energies greater than 6 MV. In this work we present a promising alternative to standard detectors with an active method to measure neutrons around a medical linac using a novel ultra-thin silicon detector with 3D electrodes adapted for neutron detection. The active volume of this planar device is only 10 µm thick, allowing a high gamma rejection, which is necessary to discriminate the neutron signal in the radiotherapy peripheral radiation field with a high gamma background. Different tests have been performed in a clinical facility using a Siemens PRIMUS linac at 6 and 15 MV. The results show a good thermal neutron detection efficiency around 2% and a high gamma rejection factor.