Statistical effects of dose deposition in track-structure modelling of radiobiology efficiency

Ion-induced cell killing has been reported to depend on the irradiation dose but also on the projectile parameters. In this paper we focus on two approaches developed and extensively used to predict cell survival in response to ion irradiation: the Local Effect Model and the Katz Model. These models are based on a track-structure description summarized in the concept of radial dose. This latter is sensitive to ion characteristics parameters and gives to both models the ability to predict some important radiobiological features for ion irradiations. Radial dose is however an average quantity, which does not include stochastic effects. These radiation-intrinsic effects are investigated by means of a Monte-Carlo simulation of dose deposition. We show that both models are not fully consistent with the nanometric and microscopic dose deposition statistics.Comment: 32 pages ; 8 figure

2012 Activity Report of the Regional Research Programme on Hadrontherapy for the ETOILE Center

2012 is the penultimate year of financial support by the CPER 2007-2013 for ETOILE's research program, sustained by the PRRH at the University Claude Bernard. As with each edition we make the annual review of the research in this group, so active for over 12 years now. Over the difficulties in the decision-making process for the implementation of the ETOILE Center, towards which all our efforts are focussed, some "themes" (work packages) were strengthened, others have progressed, or have been dropped. This is the case of the eighth theme (technological developments), centered around the technology for rotative beam distribution heads (gantries) and, after being synchronized with the developments of ULICE's WP6, remained so by ceasing its activities, coinciding also with the retirement of its historic leader at IPNL, Marcel Bajard. Topic number 5 ("In silico simulations") has suffered the departure of its leader, Benjamin Ribba, although the work has still been provided by Branka Bernard, a former postdoctoral fellow in Lyon Sud, and now back home in Croatia, still in contract with UCBL for the ULICE project. Aside from these two issues (and the fact that the theme "Medico-economical simulations" is now directly linked to the first one ("Medical Project"), the rest of the teams are growing, as evidenced by the publication statistics at the beginning of this report. This is obviously due to the financial support of our always faithful regional institutions, but also to the synergy that the previous years, the European projects, the arrival of the PRIMES LabEx, and the national France Hadron infrastructure have managed to impulse. The Rhone-Alpes hadron team, which naturally includes the researchers of LPC at Clermont, should also see its influence result in a strong presence in France Hadron's regional node, which is being organized. The future of this regional research is not yet fully guaranteed, especially in the still uncertain context of ETOILE, but the tracks are beginning to emerge to allow past and present efforts translate into a long future that we all want to see established. Each of the researchers in PRRH is aware that 2013 will be (and already is) the year of great challenge : for ETOILE, for the PRRH, for hadron therapy in France, for French hadrontherapy in Europe (after the opening and beginning of treatments in the German [HIT Heidelberg, Marburg], Italian [CNAO, Pavia] and Austrian [MedAustron, Wien Neuerstadt]) centers. Let us meet again in early 2014 for a comprehensive review of the past and a perspective for the future ..

Nanodosimetry as a tool to optimize ion beam therapy

National audienceHadrontherapy with carbon ions is an innovative technique to efficiently treat local tumors that resist to more conventional radiotherapy. It takes advantages of the specific response of biological cells to ion irradiation, which depends not only on the dose, but also on the ion atomic number and energy. With the aim of optimizing these treatments and fully benefiting from these biological properties, biophysics models have been developed to calculate quantities as relative biological efficiency (RBE), biological equivalent dose or cell survival. Our recent analysis of some of these models [1-2] leads us to the conclusion that taking into account for nanodosimetry, and more generally nanoscopic processes, should help to improve models dedicated to the planning of treatments by ion-beam therapy. References: [1] M. Beuve. radiation Research 172(3) 394-402 (2009) [2] M. Beuve, A. Colliaux, D. Dabli, D. Dauvergne, B. Gervais, G. Montarou and E. Testa. Nuclear Instruments and Methods in Physics Research Section B 267(6) 983-988 (2009) This work is supported by the Rhône-Alpes Regional Program for Hadrontherapy Research, the MI2B GDR, and the LabEx PRIMES

Brain image quality according to beam collimation width and image reconstruction algorithm: A phantom study.

To compare quantitatively and qualitatively brain image quality acquired in helical and axial modes on two wide collimation CT systems according to the dose level and algorithm used. Acquisitions were performed on an image quality and an anthropomorphic phantoms at three dose levels (CTDI <sub>vol</sub> : 45/35/25 mGy) on two wide collimation CT systems (GE Healthcare and Canon Medical Systems) in axial and helical modes. Raw data were reconstructed using iterative reconstruction (IR) and deep-learning image reconstruction (DLR) algorithms. The noise power spectrum (NPS) was computed on both phantoms and the task-based transfer function (TTF) on the image quality phantom. The subjective quality of images from an anthropomorphic brain phantom was evaluated by two radiologists including overall image quality. For the GE system, noise magnitude and noise texture (average NPS spatial frequency) were lower with DLR than with IR. For the Canon system, noise magnitude values were lower with DLR than with IR for similar noise texture but the opposite was true for spatial resolution. For both CT systems, noise magnitude was lower with the axial mode than with the helical mode for similar noise texture and spatial resolution. Radiologists rated the overall quality of all brain images as "satisfactory for clinical use", whatever the dose level, algorithm or acquisition mode. Using 16-cm axial acquisition reduces image noise without changing the spatial resolution and image texture compared to helical acquisitions. Axial acquisition can be used in clinical routine for brain CT examinations with an explored length of less than 16 cm

Performance of four dual-energy CT platforms for abdominal imaging: a task-based image quality assessment based on phantom data

International audienceTo compare the spectral performance of dual-energy CT (DECT) platforms using task-based image quality assessment based on phantom data.Materials and methods: Two CT phantoms were scanned on four DECT platforms: fast kV-switching CT (KVSCT), split filter CT (SFCT), dual-source CT (DSCT), and dual-layer CT (DLCT). Acquisitions on each phantom were performed using classical parameters of abdomen-pelvic examination and a CTDIvol at 10 mGy. Noise power spectrum (NPS) and task-based transfer function (TTF) were evaluated from 40 to 140 keV of virtual monoenergetic images. A detectability index (d') was computed to model the detection task of two contrast-enhanced lesions as function of keV.Results: The noise magnitude decreased from 40 to 70 keV for all DECT platforms, and the highest noise magnitude values were found for KVSCT and SFCT and the lowest for DSCT and DLCT. The average NPS spatial frequency shifted towards lower frequencies as the energy level increased for all DECT platforms, smoothing the image texture. TTF values decreased with the increase of keV deteriorating the spatial resolution. For both simulated lesions, higher detectability (d' value) was obtained at 40 keV for DLCT, DSCT, and SFCT but at 70 keV for KVSCT. The detectability of both simulated lesions was highest for DLCT and DSCT.Conclusion: Highest detectability was found for DLCT for the lowest energy levels. The task-based image quality assessment used for the first time for DECT acquisitions showed the benefit of using low keV for the detection of contrast-enhanced lesions

Escalade de dose et efficacité des nanocapsules chargées en 188Re dans un modèle d'adénocarcinome de l'endomètre chez la souris

Objectifs Évaluation de l’efficacité de l’administration intratumorale par convection enhanced delivery (CED) de nanocapsules chargées en 188Re (NCL-188Re) sur un modèle hétérotopique d’adénocarcinome de l’endomètre (Ishikawa) selon un schéma d’escalade de dose. Matériels et méthodes Les souris (n = 40) ont été traitées lorsque le grand axe tumoral a atteint 8 mm. Les animaux ont été séparés en 2 groupes témoins : injection intratumorale par CED de NaCl (groupe 1 ; n = 8) et de NCL blanches (groupe 2 ; n = 8), et 3 groupes traités par injection intratumorale en CED de NCL-188Re (groupe 3 ; 3 MBq ; n = 8/groupe 4 ; 6 MBq ; n = 8 et groupe 5 ; 12 MBq ; n = 8). La réponse thérapeutique a été évaluée en mesurant cliniquement et par μIRM (BioSpec 70/20 USR 7 Tesla Bruker) l’évolution du volume tumoral (VT). Le point limite choisi a été le doublement du VT ou un VT > 2150 μL. Résultats La radiothérapie vectorisée par NCL-188Re a significativement augmenté la médiane de survie des animaux traités des groupes 3, 4 et 5, de 290 %, 290 % et 570 %, respectivement, par rapport au groupe 1 (p = 0,021 ; p = 0,031 ; p < 0,001, respectivement). Le VT moyen du groupe 5 a été significativement réduit par rapport au groupe 1 de j16 (159,6 ± 134,1 μL vs 449,7 ± 169,9 μL ; p = 0,014) à j33 (158,3 ± 197,2 μL vs 803,9 ± 499,4 μL ; p = 0,006). Pour le groupe 4 seule la valeur à j16 a été significative (185,1 ± 149,8 μL vs 449,7 ± 169,9 μL ; p = 0,026). De plus, nous avons observé une différence significative entre le groupe 5 et le groupe 3 de j23 (97,9 ± 115,3 μL vs 568,5 ± 641,9 μL ; p = 0,049) à j33 (158,3 ± 197,2 μL vs 636,2 ± 618,8 μL ; p = 0,041). Conclusions L’injection intratumorale unique par CED de NCL-188Re sur modèle hétérotopique murin de cancer de l’endomètre hormono-dépendant a permis d’obtenir un régression tumorale spectaculaire pour les animaux traités avec une activité de 12 MBq. Ces bons résultats seront à confirmer lors d’études dosimétriques et de fractionnement de dose

Nanovectorized radiotherapy by convection-enhanced delivery (CED), a promising strategy that demonstrates high efficacy in a murine model of human endometrial adenocarcinoma

International audienceAim: To evaluate the biodistribution, the toxicity, the dosimetry and the antitumor efficacy of intra-tumoral injection of rhenium-188 loaded nanoparticles (LNC-188Re-SSS) by CED. Materials and methods: Ishikawa endometrial carcinoma cell lines were implanted subcutaneously in nude mice (n=70). For biodistribution and efficacy studies CED procedure was realized at D28 after tumour implantation. CED was performed using an osmotic pump (0.5μL/min for 20 minutes) after immobilisation of anaesthetized mice on a stereotactic frame. For biodistribution studies, animals (n=30) were injected by CED either with 3MBq of 188ReO4- (n=15) or LNC-188Re-SSS (n=15) and sacrificed at 1h (n=10), 24h (n=10) or 72h (n=10). For efficacy studies, control group mice were injected by CED with saline (n=8) or blank LNC (n=8) and treated group mice were injected with escalating dose of LNC-188Re-SSS: 3MBq (n=8), 6 MBq (n=8) or 12 MBq (n=8). Efficacy on tumour growth was assessed by clinical palpation and μMRI. The time for the tumour volume doubling was chosen as endpoint, leading to the euthanasia of the animal. The physical dose deposited in the tumour for each treated animal was estimated by Monte Carlo simulation (Geant4) using measured biodistribution and μMRI tumour volumes,. Haematological toxicity in mice was evaluated using blood sampling of 50μL (retro-orbital sinus) at D2, D7, D14 and D21 after treatment with saline (n=4) and after treatment with LNC-188Re-SSS, 3MBq (n=4), 6 MBq (n=4) or 12 MBq (n=4). Results: Nanovectorization of 188Re combined with CED allowed the confinement of more than 30 % of ID in the tumour limiting therefore urinary excretion of 188Re since 0,1% versus 81,9% of ID were excreted in urine 24h after CED of LNC-188Re-SSS and 188ReO4- respectively (p=0.016). Nanovectorized radiotherapy has drastically increased the median survival time compared with control group. Animals whose tumor received a dose higher than 69 Gy (69-340 Gy) showed an ISTmedian of + 933%, whereas animals whose tumor received a dose lower than 69 Gy (21-67Gy) showed an ISTmedian of + 391%. Complete response with eradication of the tumor was observed in 4/12 (33.3%) animals of the former group. Depletion of platelets was observed following LNC-188Re-SSS injection with a time to nadir between D14-D21 whereas transient lymphocyte depletion was only observed at D7 for the highest administered activities (12MBq).Conclusion: CED of LNC-188Re-SSS demonstrates interesting biodistribution properties and high efficacy in a model of human endometrial carcinoma.</p