Contribution au contrôle de l’hadronthérapie et à la modélisation de la dose biologique

L’hadronthérapie est une technique de traitement des tumeurs cancéreuses par faisceau d’ions (essentiellement proton et carbone, jusqu’à présent). Le principal avantage physique des ions par rapport aux rayons de la radiothérapie conventionnelle est qu’ils présentent un dépôt d’énergie maximum en fin de parcours avec une dispersion latérale relativement faible. De plus, dans le cas des ions plus lourds que le proton (ions carbone par exemple), l’efficacité biologique du dépôt d’énergie est maximale dans la tumeur et proche de celle des photons dans les tissus sains. L’hadronthérapie est donc particulièrement indiquée pour les tumeurs radiorésistantes proches d’organes à risques.Il existe actuellement dans le monde une bonne trentaine de centres de protonthérapie et six centres de traitements par ion carbone : HIMAC (Chiba, 1994), HIBMC (Hyogo, 2002), (Gunma, 2010), Lanzhou (2006), HIT (Heidelberg, 2010), CNAO (Pavia, 2012). À la fin de l’année 2011, près de 100 000 patients avaient été traités avec des faisceaux de particules 1 : ~ 80 000 par protons, ~ 10 000 par ions carbone, ~ 2 000 par ions hélium, ~ 1 000 par pions et ~ 400 avec d’autres types d’ions. Ces chiffres sont à comparer par exemple aux 200 000 nouveaux cancers diagnostiqués par an en France dont la moitié sont traités par radiothérapie conventionnelle (éventuellement couplée à de la chirurgie ou de la chimiothérapie). Malgré un développement considérable lors des 10 dernières années, l’hadronthérapie reste donc une technique émergente qui réclame des efforts de recherche et de développement soutenus, principalement sur les thématiques suivantes : l’accélération des ions, le contrôle de la dose, la modélisation des organes en mouvement, la modélisation de l’effet biologique et les études cliniques

Biological systems: from water radiolysis to carbon ion radiotherapy

International audienceHadron therapy is an innovative cancer treatment method based on the acceleration of light ions at high energy. In addition to their interesting profile of dose deposition, which ensures accurate targeting of localized tumors, carbon ions offer biological properties that lead to an efficient treatment for radio-and chemo-resistant tumors and to provide a boost for tumors in hypoxia. This paper is a short review of the progress in theoretical, experimental, fundamental and applied research, aiming at understanding the origin of the biological benefits of light ions better. As a limit of such a vast and multidisciplinary domain, this review adopts the point of view of the physicists, leaning on results obtained in connection with CIMAP's IRRABAT platform. 1. Introduction Interaction of fast ions with biological systems constitutes one aspect of the interdisciplinary researches performed with ion-beam facilities. This domain is as rich as it is complex since it encompasses several orders of magnitude in both space and time. The shortest space and time scale corresponds to atomic collisions, which may be as short as 10 −18 s for the interaction of fast ions with individual atoms. At the opposite end of this domain, late effects – like cancer induction, chromosomal instability or organ dysfunctions – may appear or remain several years after irradiations. While irradiations may be limited to a very localized region, the whole behavior of an organ may be affected, possibly leading to human death, in particular when the irradiation dose and spatial extension are high. Between these two extreme scales, stands a great number of mechanisms, including for instance: the transport of the primary ejected electrons, the relaxation of the ionized and excited molecules, which may lead to direct damage in biological targets and to radical species and associated biochemical reactions. These early physical and chemical stages are followed by numerous and complex cell responses, such as the triggering of mechanisms to check DNA, to repair its damage, to manage the oxidative stress or to induce cell death. The numerous biological endpoints that have been studied reveal the complexity and the diversity of this biological response. These endpoints may involve particular structures of cells at the molecular scale (tracking of protein activities, damage in DNA, protein or lipid) or at the sub-cellular scale (chromosomes, nucleus, membranes, mitochondria.. .) and may concern cell organization (3D cell culture, tissues, organs, body). The domain of low dose

Assessment of Geant4 Prompt-Gamma Emission Yields in the Context of Proton Therapy Monitoring

International audienceMonte Carlo tools have been long used to assist the research and development of solutions for proton therapy monitoring. The present work focuses on the prompt-gamma emission yields by comparing experimental data with the outcomes of the current version of Geant4 using all applicable proton inelastic models. For the case in study and using the binary cascade model, it was found that Geant4 overestimates the prompt-gamma emission yields by 40.2 ± 0.3%, even though it predicts the prompt-gamma profile length of the experimental profile accurately. In addition, the default implementations of all proton inelastic models show an overestimation in the number of prompt gammas emitted. Finally, a set of built-in options and physically sound Geant4 source code changes have been tested in order to try to improve the discrepancy observed. A satisfactory agreement was found when using the QMD model with a wave packet width equal to 1.3 fm 2

Development of an in Vitro Rat Intestine Segmental Perfusion Model to Investigate Permeability and Predict Oral Fraction Absorbed

Purpose: The aims of the study are to develop and evaluate an in vitro rat intestine segmental perfusion model for the prediction of the oral fraction absorbed of compounds and to assess the ability of the model to study intestinal metabolism. Methods: The system consisted of a perfusion cell with a rat intestinal segment and three perfusion circulations (donor, receiver, and rinsing circulation). Lucifer yellow (LY) was applied as internal standard together with test compounds in the donor circulation. To validate the model, the permeability of eight noncongeneric passively absorbed drugs was determined. Intestinal N-demethylation of verapamil into norverapamil was followed in the donor and receiver circulations by high-performance liquid chromatography analysis. Results: The in vitro model allowed ranking of the tested compounds according to their in vivo absorption potential. The Spearman's correlation coefficient between the oral fraction absorbed in humans and the ratio of permeation coefficient of test compound to the permeation coefficient of LY within the same experiment was 0.98 (P < 0.01). Moreover, intestinal N-demethylation of verapamil, its permeation, and the permeation of its metabolite norverapamil could be assessed in parallel. Conclusions: Up to six permeation kinetics can be obtained per rat, and the method has shown to be a valuable tool to estimate human oral absorptio

Contribution of high energy physics techniques to the medical imaging field

The purpose of this study was to show how advanced concepts of compact, lossless and "Time Of Flight" (TOF) capable electronics similar to those foreseen for the LHC and ILC experiments could be fairly and easily transferred to the medical imaging field through Positron Emission Tomography (PET). As a wish of explanation, the two overriding weaknesses of PET camera readout electronics, namely dead-time and timing resolution, were investigated analytically and with a Monte-Carlo simulator presently dedicated to this task. Results have shown there was room left for count rate enhancement through a huge decrease of the timing resolution well below the nanosecond. The novel electronics scheme suggested for PET in this paper has been partly inspired by the long experience led in High Energy Physics where the latter requirement is compulsory. Its structure entirely pipelined combined to a pixelation of the whole detector should allow dead-times to be suppressed, while the absence of devoted timing channel would remove the preponderant contributions to the timing resolution. To the common solution for timing would substitute an optimal filtering method witch clearly appears as a good candidate as timing resolution of a few tens of picoseconds may be achieved provided the shape of the signal is known and sufficient samples are available with enough accuracy. First investigations have yield encouraging results as a sampling frequency of 50 MHz with a 7 bits precision appears sufficient to ensure the 500ps coincidence timing resolution planed. At this point, there will be a baby step ahead to draw benefice from a TOF implementation to the design and the enormous noise variance enhancement that would come with.Comment: presented at EuroMedIm 2006 : 1st European Conference on Molecular Imaging Technology, Marseille 9-12 May 2006, 6 pp, 4 figures, submitted to NI

The On-Site Analysis of the Cherenkov Telescope Array

The Cherenkov Telescope Array (CTA) observatory will be one of the largest ground-based very high-energy gamma-ray observatories. The On-Site Analysis will be the first CTA scientific analysis of data acquired from the array of telescopes, in both northern and southern sites. The On-Site Analysis will have two pipelines: the Level-A pipeline (also known as Real-Time Analysis, RTA) and the level-B one. The RTA performs data quality monitoring and must be able to issue automated alerts on variable and transient astrophysical sources within 30 seconds from the last acquired Cherenkov event that contributes to the alert, with a sensitivity not worse than the one achieved by the final pipeline by more than a factor of 3. The Level-B Analysis has a better sensitivity (not be worse than the final one by a factor of 2) and the results should be available within 10 hours from the acquisition of the data: for this reason this analysis could be performed at the end of an observation or next morning. The latency (in particular for the RTA) and the sensitivity requirements are challenging because of the large data rate, a few GByte/s. The remote connection to the CTA candidate site with a rather limited network bandwidth makes the issue of the exported data size extremely critical and prevents any kind of processing in real-time of the data outside the site of the telescopes. For these reasons the analysis will be performed on-site with infrastructures co-located with the telescopes, with limited electrical power availability and with a reduced possibility of human intervention. This means, for example, that the on-site hardware infrastructure should have low-power consumption. A substantial effort towards the optimization of high-throughput computing service is envisioned to provide hardware and software solutions with high-throughput, low-power consumption at a low-cost.Comment: In Proceedings of the 34th International Cosmic Ray Conference (ICRC2015), The Hague, The Netherlands. All CTA contributions at arXiv:1508.0589

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}$and correspond to an integrated luminosity of$4.6\;{\rm f}{{{\rm b}}^{-1}}$. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum${{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}$and pseudorapidity$|\eta |\lt 1.9$, is measured to be${{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT