Carbon fragmentation measurements and validation of the GEANT4 nuclear reaction models for hadrontherapy

Nuclear fragmentation measurements are necessary when using heavy-ion beams in hadrontherapy to predict the effects of the ion nuclear interactions within the human body. Moreover, they are also fundamental to validate and improve the Monte Carlo codes for their use in planning tumor treatments. Nowadays, a very limited set of carbon fragmentation cross sections are being measured, and in particular, to our knowledge, no double-differential fragmentation cross sections at intermediate energies are available in the literature. In this work, we have measured the double-differential cross sections and the angular distributions of the secondary fragments produced in the C-12 fragmentation at 62 A MeV on a thin carbon target. The experimental data have been used to benchmark the prediction capability of the GEANT4 Monte Carlo code at intermediate energies, where it was never tested before. In particular, we have compared the experimental data with the predictions of two GEANT4 nuclear reaction models: the Binary Light Ions Cascade and the Quantum Molecular Dynamic. From the comparison, it has been observed that the Binary Light Ions Cascade approximates the angular distributions of the fragment production cross sections better than the Quantum Molecular Dynamic model. However, the discrepancies observed between the experimental data and the Monte Carlo simulations lead to the conclusion that the prediction capability of both models needs to be improved at intermediate energies

Microdosimetric measurements of a monoenergetic and modulated Bragg Peaks of 62 MeV therapeutic proton beam with a synthetic single crystal diamond microdosimeter

Purpose The purpose of this study was to investigate for the first time the performance of a synthetic single crystal diamond detector for the microdosimetric characterization of clinical 62 MeV ocular therapy proton beams. Methods A novel diamond microdosimeter with a well-defined sensitive volume was fabricated and tested with a monoenergetic and spread-out Bragg peak (SOBP) of the CATANA therapeutic proton beam in Catania, Italy. The whole sensitive volume of the detector has an active planar-sectional area of 100 mu m x 100 mu m and a thickness of approximately 6.3 um. Microdosimetric measurements were performed at several water equivalent depths, corresponding to positions of clinical relevance. From the measured spectra, microdosimetric quantities such as the frequency mean lineal energy (y over bar F), dose mean lineal energy (y over bar D) as well as microdosimetric relative biological effectiveness (RBE mu) values were derived for each depth along both a pristine Bragg curve and SOBP. Finally, Geant4 Monte Carlo simulations were performed modeling the detector geometry and CATANA beamline in order to calculate the average linear energy transfer (LET) values in the diamond active layer and water. Results The microdosimetric spectra acquired by the diamond microdosimeter show different shapes as a function of the water equivalent depths. No spectral distortion, due to pile-up events and polarization effects, was observed. The experimental spectra have a very low detection threshold due to the electronic noise during the irradiation of about 1 keV/mu m. They over bar Fandy over bar Dvalues were in agreement with expected trends, showing a sharp increase in mean lineal energy at the distal edge of the Bragg peak. In addition, a good agreement between the mean lineal energy values and the calculated average LET ones was also observed. Finally, the RBE values evaluated with the diamond microdosimeter were in excellent agreement with those obtained with a mini tissue equivalent proportional counter as well as with radiobiological measurements in the same proton beam field. Conclusions The microdosimetric performance of the tested synthetic single crystal diamond microdosimeter clearly indicates its suitability for quality assurance in clinical proton therapy beam

Radiation-induced telomere length variations in normal and in Nijmegen Breakage Syndrome cells

Purpose: The meiotic recombination protein 11 (MRE11), radiation sensitive 50 (RAD50) and nibrin (NBN) are members of the MRE11/RAD50/NBN (MRN) complex which plays a fundamental role in the double-strand break damage response, including DNA damage sensing, signalling and repair after exposure to ionizing radiations. In addition the MRN complex is involved in the mechanisms regulating telomere length maintenance. Based on our previous results indicating that, in contrast to X-rays, high linear energy transfer (LET) radiations were able to elongate telomeres, we investigated the behavior of cells mutated in components of the MRN complex after exposure either to 62 MeV carbon-ions (50 keV/mm, at cell surface) or X-rays. Materials and methods: Epstein Barr Virus (EBV)-transformed lymphoblastoid cell lines (LCL) established from normal, heterozygous for the NBN gene, homozygous for either mutant/deleted NBN, RAD50 or ataxia telangiectasia mutated (ATM) genes were irradiated with 4 Gy, with telomere length being evaluated 24 h later or in time course-experiments up to 15 days later. The induction of telomeric sister chromatid exchanges (T-SCE) was measured as a hallmark of homologous directed recombinational repair. Results: NBN and RAD50 mutated cells failed to elongate telomeres that instead occurred in the remaining cell lines as a response only to high-LET irradiation. Also, a kinetic study with 0.5-4 Gy up to 15 days from irradiation confirmed that NBN gene was indispensable for telomere elongation. Furthermore, such an elongation, was accompanied by an increased frequency of sister chromatid exchanges at telomeres (T-SCE). In contrast, the induction of genomic sister chromatid exchanges (G-SCE) occurred for carbon-ions irrespective of NBN gene status. Conclusions: We speculate that the MRN is necessary to process a subclass of high-LET radiation-induced complex DNA damage through a recombinational-repair mediated mechanism which in turn is responsible for telomere elongatio

Characterization of an in-beam PET prototype for proton therapy with different target composition

Positron emission tomography is a valuable method for in situ and non invasive monitoring of the accuracy of the treatment in hadron therapy. It takes advantage of short lived β +- emitters spontaneously produced in the biological tissues during irradiation, by means of projectile and/or target nuclei fragmentations. Although β + - emitter production cross-sections and hadron stopping power exhibit a different dependence on the hadron energy, it is' still possible to extract non invasively in vivo information about dose localization reconstructing the distribution of positron annihilation points. Our research within the DoPET (Dosimetry with a Positron Emission Tomograph) project aim to develop and characterize an ad hoc in beam dual-head PET scanner for the quality control in proton therapy. The realized prototype has been already tested on homogeneous poly-methyl methacrylate (PMMA) phantoms by measuring the β + - activation induced by 62 MeV proton beam at Catana facility (LNS, Catania, Italy). The experimental nvestigation has shown the feasibility of this system for detecting small range variations along the beam direction, with an accuracy less than one millimeter. In this paper we extend the previous analysis by reporting and discussing the results we obtained on several inhomogeneous targets, so as to investigate the sensitivity and accuracy of the PET prototype depending on target geometrical arrangements and chemical composition

Experimental validation of the filtering approach for dose monitoring in proton therapy at low energy

The higher physical. selectivity of proton therapy demands higher accuracy in monitoring of the delivered dose, especially when the target volume is Located next to critical, organs and a fractionated therapy is applied. A method to verify a treatment plan and to ensure the high quality of the hadrontherapy is to use Positron Emission Tomography (PET), which takes advantage of the nuclear reactions between protons and nuclei in the tissue during irradiation producing beta(+)-emitting isotopes. Unfortunately, the PET image is not directly proportional. to the delivered radiation dose distribution; this is the reason why, at the present time, the verification of depth dose profiles with PET techniques is limited to a comparison between the measured activity and the one predicted for the planned treatment by a Monte Carlo model. In this paper we test the feasibility of a different scheme, which permits to reconstruct the expected PET signal from the planned radiation dose distribution along beam direction in a simpler and more direct way. The considered filter model, based on the description of the PET image as a convolution of the dose distribution with a filter function, has already demonstrated its potential applicability to beam energies above 70 MeV. Our experimental. investigation provides support to the possibility of extending the same approach to the Lower energy range ([40, 70] MeV), in the perspective of its clinical. application in eye proton therapy. (C) 2008 Published by Elsevier Ltd on behalf of Associazione Italiana di Fisica Medica

Preliminary results of an in-beam PET prototype for proton therapy

Proton therapy can overcome the limitations of conventional radiotherapy due to the more selective energy deposition in depth and to the increased biological effectiveness. Verification of the delivered dose is desirable, but the complete stopping of the protons in patient prevents the application of electronic portal imaging methods that are used in conventional radiotherapy During proton therapy beta(+) emitters like C-11, O-15, C-10 are generated in irradiated tissues by nuclear reactions. The measurement of the spatial distribution of this activity, immediately after patient irradiation, can lead to information on the effective delivered dose. First, results of a feasibility study 2 of an in-beam PET for proton therapy are reported. The prototype is based on two planar heads with an active area of about 5 x 5 cm Each head is made up of a position sensitive photomultiplier coupled to a square matrix of same size of LYSO scintillating crystals (2 x 2 x 18 mm(3) pixel dimensions). Four signals from each head are acquired through a dedicated electronic board that performs signal amplification and digitization. A 3D reconstruction of the activity distribution is calculated using an expectation maximization algorithm. To characterize the PET prototype, the detection efficiency and the spatial resolution were measured using a point-like radioactive source. The validation of the prototype was performed using 62 MeV protons at the CATANA beam line of INFN LNS and PMMA phantoms. Using the full energy proton beam and various range shifters, a good correlation between the position of the activity distal edge and the thickness of the beam range shifter was found along the axial direction

Monte Carlo implementation of new algorithms for the evaluation of averaged-dose and -track linear energy transfers in 62 MeV clinical proton beams

We exploited the power of the Geant4 Monte Carlo toolkit to study and validate new approaches for the averaged linear energy transfer (LET) calculation in 62 MeV clinical proton beams. The definitions of the averaged LET dose and LET track were extended, so as to fully account for the contribution of secondary particles generated by target fragmentation, thereby leading to a more general formulation of the LET total. Moreover, in the proposed new strategies for the LET calculation, we minimised the dependencies in respect to the transport parameters adopted during the Monte Carlo simulations (such as the production cut of secondary particles, voxel size and the maximum steplength). The new proposed approach was compared against microdosimetric experimental spectra of clinical proton beams, acquired at the Italian eye proton therapy facility of the Laboratori Nazionali del Sud, Istituto Nazionale di Fisica Nucleare (INFN-LNS, Catania, I) from two different detectors: A mini-tissue equivalent proportional chamber (TEPC), developed at the Legnaro National Laboratories of the National Institute for Nuclear Physics (LNL-INFN) and a silicon-on-insulator (SOI) microdosimeter with 3D sensitive volumes developed by the Centre for Medical Radiation Physics of Wollongong University (CMRP-UoW). A significant increase of the LET in the entrance region of the spread out Bragg peak (SOBP) was observed, when the contribution of the generated secondary particles was included in the calculation. This was consistent with the experimental results obtained

Characterization of an In-Beam PET Prototype for Proton Therapy With Different Target Compositions

At the University of Pisa, the DoPET (Dosimetry with a Positron Emission Tomograph) project has focused on the development and characterization of an ad hoc, scalable, dual-head PET prototype for in-beam treatment planning verification of the proton therapy. In this paper we report the first results obtained with our current prototype, consisting of two opposing lutetium yttrium orthosilicate (LYSO) detectors, each one covering an area of 4.5x4.5 cm(2). We measured the beta(+)-activation induced by 62 MeV proton beams at Catana facility (LNS, Catania, Italy) in several plastic phantoms. Experiments were performed to evaluate the possibility to extract accurate phantom geometrical information from the reconstructed PET images. The PET prototype proved its capability of locating small air cavities in homogeneous PMMA phantoms with a submillimetric accuracy and of distinguishing materials with different (16)O and (12)O content by back mapping phantom geometry through the separation of the isotope contributions. This could be very useful in the clinical practice as a tool to highlight anatomical or physiological organ variations among different treatment sessions and to discriminate different tissue types, thus providing feedbacks for the accuracy of dose deposition