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International audience; Current preclinical dosimetric models often fail to take account of the complex nature of absorbed dose distribution typical of in vitro clonogenic experiments in targeted radionuclide therapy. For this reason, clonogenic survival is often expressed as a function of added activity rather than the absorbed dose delivered to cells/cell nuclei. We designed a multi-cellular dosimetry model that takes into account the realistic distributions of cells in the Petri dish, for the establishment of survival curves as a function of the absorbed dose. General-purpose software tools were used for the generation of realistic, randomised 3D cell culture geometries based on experimentally determined parameters (cell size, cell density, cluster density, average cluster size, cell cumulated activity). A mixture of Monte Carlo and analytical approaches was implemented in order to achieve as accurate as possible results while reducing calculation time. The model was here applied to clonogenic survival experiments carried out to compare the efficacy of Betalutin®, a novel 177Lu-labelled antibody radionuclide conjugate for the treatment of non-Hodgkin lymphoma, to that of 177Lu-labelled CD20-specific (rituximab) and non-specific antibodies (Erbitux) on lymphocyte B cells. The 3D cellular model developed allowed a better understanding of the radiative and non-radiative processes associated with cellular death. Our approach is generic and can also be applied to other radiopharmaceuticals and cell distributions.

Elevated blood CXCL10/IP-10 levels during primary HIV-1 infection (PHI) were described as an independent marker of rapid disease onset, more robust than peak viremia or CD4 cell nadir. IP-10 enhances the recruitment of CXCR3+ cells, which include major HIV-target cells, raising the question if it promotes the establishment of viral reservoirs. We analyzed data from four cohorts of HIV+ patients, allowing us to study IP-10 levels before infection (Amsterdam cohort), as well as during controlled and uncontrolled viremia (ANRS cohorts). We also addressed IP-10 expression levels with regards to lymphoid tissues (LT) and blood viral reservoirs in patients and non-human primates. Pre-existing elevated IP-10 levels but not sCD63 associated with rapid CD4 T-cell loss upon HIV-1 infection. During PHI, IP-10 levels and to a lesser level IL-18 correlated with cell-associated HIV DNA, while 26 other inflammatory soluble markers did not. IP-10 levels tended to differ between HIV controllers with detectable and undetectable viremia. IP-10 was increased in SIV-exposed aviremic macaques with detectable SIV DNA in tissues. IP-10 mRNA was produced at higher levels in the small intestine than in colon or rectum. Jejunal IP-10+ cells corresponded to numerous small and round CD68neg cells as well as to macrophages. Blood IP-10 response negatively correlated with RORC (Th17 marker) gene expression in the small intestine. CXCR3 expression was higher on memory CD4+ T cells than any other immune cells. CD4 T cells from chronically infected animals expressed extremely high levels of intra-cellular CXCR3 suggesting internalization after ligand recognition. Elevated systemic IP-10 levels before infection associated with rapid disease progression. Systemic IP-10 during PHI correlated with HIV DNA. IP-10 production was regionalized in the intestine during early SIV infection and CD68+ and CD68neg haematopoietic cells in the small intestine appeared to be the major source of IP-10., Author Summary Chronic immune activation is a hallmark of HIV infection and contributes in multiple ways to HIV persistence. Here, we gained insights on the association between a pro-inflammatory chemokine, CXCL10/IP-10 and HIV infection in four cohorts of HIV+ individuals, studied at distinct stages of infection (before, primary and chronic stage with spontaneous- and treatment-controlled infection). We further analyzed pathogenic and non-pathogenic SIV infections to address IP-10 levels and the presence of infected cells in tissues (lymph nodes, small and large intestine). We found that elevated systemic IP-10 levels before HIV-1 infection associate with a more rapid disease progression. During primary infection, IP-10 in blood strongly correlated with the amount of infected cells in blood. The animal model showed that IP-10 expression was regionalized in the intestine and highest in the small intestine. Studies of aviremic animals suggest that high IP-10 is indicative of viral replication in lymphoid tissues. Haematopoietic cells rather than epithelial/endothelial cells mainly contributed to the IP-10 production in small intestine (jejunum). The receptor of IP-10 was highly expressed on memory CD4+ T cells, i.e. major target cells for the virus. This study contributes to our understanding of the establishment of HIV reservoirs and why IP-10 associates with HIV/AIDS.

International audience; The aim was to analyze arc therapy techniques according to the number and position of the brain lesions reported by comparing dynamic noncoplanar conformal arcs (DCA), two coplanar full arcs (RAC) with volumetric-modulated arc therapy (VMAT), multiple noncoplanar partial arcs with VMAT (RANC), and two full arcs with VMAT and 10° table rotation (RAT). Patients with a single lesion (n= 10), multiple lesions (n = 10) or a single lesion close to organs at risk (n = 5) and previously treated with DCA were selected. For each patient, the DCA treatment was replanned with all VMAT techniques. All DCA plans were compared with VMAT plans and evaluated in regard to the different quality indices and dosimetric parameters. For single lesion, homogeneity index (HI) better results were found for the RANC technique (0.17 ± 0.05) compared with DCA procedure (0.27± 0.05). Concerning conformity index (CI), the RAT technique gave higher and better values (0.85 ± 0.04) compared with those obtained with the DCA technique (0.77 ± 0.05). DCA improved healthy brain protection (8.35 ± 5.61 cc vs. 10.52 ± 6.40 cc for RANC) and reduced monitor unit numbers (3046 ± 374 MU vs. 4651 ± 736 for RANC), even if global room occupation was higher. For multiple lesions, VMAT techniques provided better HI (0.16) than DCA (0.24 ± 0.07). The CI was improved with RAT (0.8 ± 0.08 for RAT vs. 0.71 ± 0.08 for DCA). The V10Gy healthy brain was better protected with DCA (9.27 ± 4.57 cc). Regarding the MU numbers: RANC < RAT< RAC < DCA. For a single lesion close to OAR, RAT achieved high degrees of homogeneity (0.27 ± 0.03 vs. 0.53 ± 0.2 for DCA) and conformity (0.72± 0.06vs. 0.56 ± 0.13 for DCA) while sparing organs at risk (Dmax = 12.36 ± 1.05Gyvs. 14.12 ± 0.59 Gy for DCA, and Dmean = 3.96 ± 3.57Gyvs. 4.72 ± 3.28Gy for DCA). On the other hand, MU numbers were lower with DCA (2254 ± 190 MUvs. 3438 ± 457 MU for RANC) even if overall time was inferior with RAC. For a single lesion, DCA provide better plan considering low doses to healthy brain even if quality indexes are better for the others techniques. For multiple lesions, RANC seems to be the best compromise, due to the ability to deliver a good conformity and homogeneity plan while sparing healthy brain tissue. For a single lesion close to organs at risk, RAT is the most appropriate technique.

International audience; UNLABELLED: Radioembolization of liver cancers using (90)Y-loaded microspheres is experiencing more widespread use. However, few data are available concerning the doses delivered to the tumors and the healthy liver. This retrospective study was conducted to calculate the tumor dosimetry (planned tumor dose [T(plan) D]) and nontumor dosimetry in patients treated by (90)Y-loaded glass microspheres and determine whether tumor dosimetry could predict response and survival. METHODS: Thirty-six patients with hepatocellular carcinoma (HCC), including 16 with portal vein thrombosis (PVT), were treated with (90)Y-loaded glass microspheres. The T(plan) D and the dose delivered to the injected healthy liver were calculated using a quantitative analysis of the (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) SPECT/CT exam. Responses were assessed after 3 mo, using the criteria of the European Association for the Study of the Liver. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier tests. RESULTS: The response rate was 69% for the overall population and 75% for the PVT patients. The dose delivered to the tumor was the only parameter associated with response with multivariate analysis (P = 0.019). A threshold T(plan) D value of 205 Gy was predictive of response, with a sensitivity of 100% and an accuracy of 91%. Quantitative (99m)Tc-MAA SPECT/CT allowed us to increase the injected activity for 4 patients with large lesions. PFS was only 5.2 mo and OS 9 mo when using a T(plan) D of less than 205 Gy versus 14 mo (P = 0.0003) and 18 mo (P = 0.0322), respectively, with a T(plan) D of 205 Gy or more. CONCLUSION: Quantitative (99m)Tc-MAA SPECT/CT is predictive of response, PFS, and OS. Dosimetry based on (99m)Tc-MAA SPECT/CT can be used for the selection of patients and for an adaptation of treatment planning, especially in selected patients (particularly in the case of large tumors). These results also confirm the efficacy and safety of (90)Y-loaded microspheres in treating HCC, even in the presence of PVT (and especially when (99m)Tc-MAA uptake is seen inside the PVT).

International audience; UNLABELLED: Several treatment strategies are used for selective internal radiation therapy with (90)Y-microspheres. The diversity of approaches does not favor the standardization of the prescribed activity calculation. To this aim, a fast 3-dimensional (3D) dosimetry method was developed for (90)Y-microsphere treatment planning and was clinically evaluated retrospectively. METHODS: Our 3D approach is based on voxel S values (VSVs) and has been implemented in the software tool VoxelDose. VSVs were previously calculated at a fine voxel size. The time-integrated activity (TIA) map is derived from pretherapeutic (99m)Tc-macroaggregated-albumin SPECT/CT. The fine VSV map is resampled at the voxel size of the TIA map. Then, the TIA map is convolved with the resampled VSV map to construct the 3D dose map. Data for 10 patients with 12 tumor sites treated by (90)Y-microspheres for hepatocellular carcinoma were collected retrospectively. 3D dose maps were computed for each patient, and tumoral liver and nontumoral liver (TL and NTL, respectively) were delineated, allowing the computation of descriptive statistics (i.e., mean absorbed dose, minimum absorbed dose, and maximum absorbed dose) and dose-volume histograms. Mean absorbed doses in TL and NTL from VoxelDose were compared with those calculated with the standard partition model. RESULTS: The estimated processing time for a complete 3D dosimetry calculation is on the order of 15 min, including 10 s for the dose calculation (i.e., VSV resampling and convolution). An additional 45 min was needed for the semiautomatic and manual segmentation of TL and NTL. The mean absorbed dose (±SD) was 422 ± 263 Gy for TL and 50.1 ± 36.0 Gy for NTL. The comparison between VoxelDose and partition model shows a mean relative difference of 1.5% for TL and 4.4% for NTL. Results show a wide spread of voxel-dose values around mean absorbed dose. The minimum absorbed dose within TL ranges from 32 to 267 Gy (n = 12). The fraction of NTL volume irradiated with at least 80 Gy ranges from 4% to 70% (n = 10), and the absorbed dose from which 25% of NTL was the least irradiated ranges from 14 to 178 Gy. CONCLUSION: This article demonstrates the feasibility of a fast 3D dosimetry method for (90)Y-microspheres and highlights the potential value of a 3D treatment planning strategy.

International audience; An experimental binary radiotherapy proposes the concomitant use of a high-Z compound and synchrotron X rays for enhancing radiation dose selectively in tumours by a photoelectric effect. This study aimed at measuring the resulting dose enhancement in irradiated material. A doped Fricke gel dosemeter model was manufactured with 10 mg ml(-1) of iodine (Telebrix) or barium (Micropaque). Samples were irradiated with a monochromatic synchrotron beam at 33.5, 50, 65 and 80 keV. The ensuing enhancement of the sensitivity of the dosemeter was derived from the nuclear magnetic resonance relaxation rates measured at different X-ray doses. Our results demonstrate (1) the preservation of a linear relationship between relaxation rates and X-ray doses for dosemeters doped with high-Z atoms and (2) a clear energy-dependent sensitivity enhancement for barium-doped Fricke gels. This enhancement was neither reproducible with iodinated compounds nor clearly related to the expected dose enhancement factor. However 1% barium sulphate in the gel could significantly improve the gel's response when it was irradiated by low-energy X rays.

International audience; Due to the expected mass deployment of millimeter-wave wireless technologies, thresholds of potential millimeter-wave-induced biological and health effects should be carefully assessed. The main purpose of this study is to propose, optimize, and characterize a near-field exposure configuration allowing illumination of cells in vitro at 60 GHz with power densities up to several tens of mW/cm(2) . Positioning of a tissue culture plate containing cells has been optimized in the near-field of a standard horn antenna operating at 60 GHz. The optimal position corresponds to the maximal mean-to-peak specific absorption rate (SAR) ratio over the cell monolayer, allowing the achievement of power densities up to 50 mW/cm(2) at least. Three complementary parameters have been determined and analyzed for the exposed cells, namely the power density, SAR, and temperature dynamics. The incident power density and SAR have been computed using the finite-difference time-domain (FDTD) method. The temperature dynamics at different locations inside the culture medium are measured and analyzed for various power densities. Local SAR, determined based on the initial rate of temperature rise, is in a good agreement with the computed SAR (maximal difference of 5%). For the optimized exposure setup configuration, 73% of cells are located within the ±3 dB region with respect to the average SAR. It is shown that under the considered exposure conditions, the maximal power density, local SAR, and temperature increments equal 57 mW/cm(2) , 1.4 kW/kg, and 6 °C, respectively, for the radiated power of 425 mW.

We assessed the efficiency and toxicity of brief intraperitoneal radioimmunotherapy using high activities of 125I-labeled monoclonal antibody (mAb) in the treatment of small-volume peritoneal carcinomatosis. Methods: Brief intraperitoneal radioimmunotherapy consisted of a 185-MBq (740 MBq/mg) intraperitoneal injection of 125I-35A7 (an anti–carcinoembryonic antigen mAb) into athymic nude mice 4 d after peritoneal tumor xenografting and, after 1 h, abundant washing of the peritoneal cavity with saline solution to remove unbound radioactivity. Another group of mice received this treatment plus a 37-MBq intravenous injection of 125I-35A7 on day 7 or 11 after grafting. Control groups received a brief treatment followed by an additional intravenous injection on day 7 of either saline solution or irrelevant 125I-PX. Tumor growth was monitored by bioluminescence imaging and SPECT/CT, and hematologic toxicity was evaluated by complete blood counts. Survival time was reported, and the mice were sacrificed when the bioluminescence signal reached 4.5 × 107 photons/s. The biodistribution of 125I-35A7 mAb after intravenous or brief treatment was assessed, and the mean absorbed irradiation dose by organs and tumors was calculated using the MIRD formalism. Results: Mild, transient hematologic toxicity was observed after the brief treatment plus intravenous 125I-mAb, with no weight loss. Median survival increased from 32 d in the control groups, to 46 d in the brief treatment group, to 66 d in the group additionally receiving intravenous treatment on day 11, to 73 d in the group additionally receiving intravenous treatment on day 7. The brief treatment alone resulted in a 3-fold higher tumor-to-blood uptake ratio than did the standard intravenous treatment, and the mean absorbed irradiation doses by tumors were 11.6 Gy for the brief treatment and 16.7 Gy for the additional intravenous treatment. For healthy tissues other than blood, the mean absorbed irradiation dose did not exceed 1 Gy after brief treatment and 4.2 Gy after intravenous treatment. Conclusion: The efficiency, low toxicity, and high tumor–to–healthy tissue uptake ratio associated with brief intraperitoneal 125I-35A7 radioimmunotherapy suggest that this method can be used in combination with radiation-synergistic drugs in the therapy of small-volume peritoneal carcinomatosis after cytoreductive surgery.

International audience; Microbeam radiation therapy (MRT) uses highly collimated, quasi-parallel arrays of X-ray microbeams of 50-600keV, produced by third generation synchrotron sources, such as the European Synchrotron Radiation Facility (ESRF), in France. The main advantages of highly brilliant synchrotron sources are an extremely high dose rate and very small beam divergence. High dose rates are necessary to deliver therapeutic doses in microscopic volumes, to avoid spreading of the microbeams by cardiosynchronous movement of the tissues. The minimal beam divergence results in the advantage of steeper dose gradients delivered to a tumor target, thus achieving a higher dose deposition in the target volume in fractions of seconds, with a sharper penumbra than that produced in conventional radiotherapy. MRT research over the past 20 years has yielded many results from preclinical trials based on different animal models, including mice, rats, piglets and rabbits. Typically, MRT uses arrays of narrow ( approximately 25-100 microm wide) microplanar beams separated by wider (100-400 microm centre-to-centre) microplanar spaces. The height of these microbeams typically varies from 1 to 100 mm, depending on the target and the desired preselected field size to be irradiated. Peak entrance doses of several hundreds of Gy are surprisingly well tolerated by normal tissues, up to approximately 2 yr after irradiation, and at the same time show a preferential damage of malignant tumor tissues; these effects of MRT have now been extensively studied over nearly two decades. More recently, some biological in vivo effects of synchrotron X-ray beams in the millimeter range (0.68-0.95 mm, centre-to-centre distances 1.2-4 mm), which may differ to some extent from those of microscopic beams, have been followed up to approximately 7 months after irradiation. Comparisons between broad-beam irradiation and MRT indicate a higher tumor control for the same sparing of normal tissue in the latter, even if a substantial fraction of tumor cells are not receiving a radiotoxic level of radiation. The hypothesis of a selective radiovulnerability of the tumor vasculature versus normal blood vessels by MRT, and of the cellular and molecular mechanisms involved remains under investigation. The paper highlights the history of MRT including salient biological findings after microbeam irradiation with emphasis on the vascular components and the tolerance of the central nervous system. Details on experimental and theoretical dosimetry of microbeams, core issues and possible therapeutic applications of MRT are presented.

International audience; The quality insurance in radiotherapy in the frame of highly complex technical process as Intensity modulated radiotherapy (IMRT) needs independent control of the delivered dose to the patient. Actually, up to now, most of the radiotherapy treatments rely only on computed dosimetry through a rather complicated series of linked simulation tool. This dosimetry approach requires also qualified treatment means based on cautious quality insurance procedures. However, erroneous parameters could be difficult to detect and systematical errors could happen leading to radiotherapy accidents. In this context, in vivo dosimetry has a critical role of final control of the delivered dose. As many beam incidences and ports are used for any photontherapy treatment, external control could be very tedious and time consuming. Therefore, innovations are needed for in vivo dosimetry to provide ergonomic and efficient tools for these controls. This paper presents a review of technologies and products that can be used for in vivo dosimetry. It proposes also a reflection on the concepts to develop future devices suitable for this purpose. The technical means with their physical principles are reviewed, the clinical experiences demonstrating the feasibility of new techniques are then summarized and finally, the early clinical use and its impact on clinical practice is review.

International audience; PURPOSE: We propose a new method for efficient particle transportation in voxelized geometry for Monte Carlo simulations. We describe its use for calculating dose distribution in CT images for radiation therapy. MATERIAL AND METHODS: The proposed approach, based on an implicit volume representation named segmented volume, coupled with an adapted segmentation procedure and a distance map, allows us to minimize the number of boundary crossings, which slows down simulation. The method was implemented with the GEANT4 toolkit and compared to four other methods: One box per voxel, parameterized volumes, octree-based volumes, and nested parameterized volumes. For each representation, we compared dose distribution, time, and memory consumption. RESULTS: The proposed method allows us to decrease computational time by up to a factor of 15, while keeping memory consumption low, and without any modification of the transportation engine. Speeding up is related to the geometry complexity and the number of different materials used. We obtained an optimal number of steps with removal of all unnecessary steps between adjacent voxels sharing a similar material. However, the cost of each step is increased. When the number of steps cannot be decreased enough, due for example, to the large number of material boundaries, such a method is not considered suitable. CONCLUSION: This feasibility study shows that optimizing the representation of an image in memory potentially increases computing efficiency. We used the GEANT4 toolkit, but we could potentially use other Monte Carlo simulation codes. The method introduces a tradeoff between speed and geometry accuracy, allowing computational time gain. However, simulations with GEANT4 remain slow and further work is needed to speed up the procedure while preserving the desired accuracy.

International audience; Synchrotron stereotactic radiotherapy (SSR) is a radiotherapy technique that makes use of the interactions of monochromatic low energy x-rays with high atomic number (Z) elements. An important dose-enhancement can be obtained if the target volume has been loaded with a sufficient amount of a high-Z element, such as iodine. In this study, we compare experimental dose measurements, obtained with normoxic polymer gel (nPAG), with Monte Carlo computations. Gels were irradiated within an anthropomorphic head phantom and were read out by magnetic resonance imaging. The dose-enhancement due to the presence of iodine in the gel (iodine concentration: 5 and 10 mg ml(-1)) was measured at two radiation energies (35 and 80 keV) and was compared to the calculated factors. nPAG dosimetry was shown to be efficient for measuring the sharp dose gradients produced by SSR. The agreement between 3D gel dosimetry and calculated dose distributions was found to be within 4% of the dose difference criterion and a distance to agreement of 2.1 mm for 80% of the voxels. Polymer gel doped with iodine exhibited higher sensitivity, in good agreement with the calculated iodine-dose enhancement. We demonstrate in this preliminary study that iodine-doped nPAG could be used for measuring in situ dose distributions for iodine-enhanced SSR treatment.

International audience; The present study investigated the possible influence of the earthworm Aporrectodea tuberculata on the transfer of cesium-137 ((137)Cs) from a contaminated (130 Bq/kg) deciduous forest soil to the lettuce Lactuca sativa and to the snail Cantareus aspersus (formerly Helix aspersa) in two laboratory experiments. In the first experiment, the International Organization for Standardization 15952 test was used to expose snails for five weeks to contaminated soil with or without earthworms. In these conditions, the presence of earthworms caused a two- to threefold increase in (137)Cs concentrations in snails. Transfer was low in earthworms as well as in snails, with transfer factors (TFs) lower than 3.7 x 10(-2). Activity concentrations were higher in earthworms (2.8- 4.8 Bq/kg dry mass) than in snails (

International audience; PURPOSE: To evaluate direct intracerebral and intratumoral iodine delivery as means to improve iodine distribution for synchrotron stereotactic radiotherapy (SSR) and to evaluate the corresponding X-ray dose distribution. METHODS AND MATERIALS: Healthy rats and F98 glioma-bearing rats received an iodinated contrast agent (iopamidol) intracerebrally either by bolus injection (5 microL over approximately 1 min) or by convection-enhanced delivery (infusion volumes of 5, 10, and 20 microL at a rate of 0.5 microL/min). We used synchrotron computed tomography (CT) to determine the iodine distribution after completion of infusion and a Monte Carlo code to compute the resulting radiation dose in SSR. RESULTS: Post-infusion CT imaging revealed high iodine concentrations in the perfused area with both injection methods. The iodine concentration remained elevated, with an exponential decay time constant of approximately 50 min, well suited for SSR treatment. Convection-enhanced delivery was shown to provide more uniform and controlled volumes of distribution than bolus injection and was chosen to evaluate the corresponding X-ray dose distribution. Sharp dose gradients around the target and excellent sparing of the contralateral brain were achievable with low iodine concentrations in the surrounding healthy brain tissues and blood vessels. CONCLUSIONS: Convection-enhanced delivery is an effective method to deliver high iodine concentrations and could improve the outcome of iodine-enhanced SSR.

International audience; We comprehensively study the least-squares Gaussian approximations of the diffraction-limited 2D-3D paraxial-nonparaxial point-spread functions (PSFs) of the wide field fluorescence microscope (WFFM), the laser scanning confocal microscope (LSCM), and the disk scanning confocal microscope (DSCM). The PSFs are expressed using the Debye integral. Under an L(infinity) constraint imposing peak matching, optimal and near-optimal Gaussian parameters are derived for the PSFs. With an L1 constraint imposing energy conservation, an optimal Gaussian parameter is derived for the 2D paraxial WFFM PSF. We found that (1) the 2D approximations are all very accurate; (2) no accurate Gaussian approximation exists for 3D WFFM PSFs; and (3) with typical pinhole sizes, the 3D approximations are accurate for the DSCM and nearly perfect for the LSCM. All the Gaussian parameters derived in this study are in explicit analytical form, allowing their direct use in practical applications.

International audience; AIM: Segmentation of computed tomography (CT) images is an important step in three-dimensional (3D) internal dosimetry. To this end, a semiautomated method was developed to delineate organs, using the belief functions theory. MATERIALS AND METHODS: The membership degree of each voxel to each volume of interest is estimated by computing a basic belief assignment (bba). For each voxel V, bbas corresponding to each neighbor are aggregated to obtain a unique bba, using a merging procedure. Before aggregating information, a 3D filter is applied, in order to take into account the fact that the more the voxel V(i) is close to V, the more the information coming from V(i) is reliable. The aim is to weaken the contribution of voxels according to their distance with respect to the voxel to be classified. The algorithm was applied on 10 CT scans (pixel size, 0.98 x 0.98 mm2, slice thickness 3 mm, 120 kV). For each organ (i.e., the lung, liver, kidney, and spleen), the algorithm was applied on a part of the CT volume. First, the lung was segmented using two classes with characteristic values, C, defined by the K-means clustering algorithm. Second, the liver and kidneys were segmented using three classes with C-values defined by local mean Hounsfield Unit (HU) measurements, corresponding to fat, liver, and kidney. Third, the spleen was segmented using three classes corresponding to fat, kidney, and spleen, using local mean HU measurements. The semiautomated segmentation was compared with manual segmentation using the volume difference and the agreement (overlap) index. RESULTS: For organ segmentation, the computation duration was between 5 and 20 minutes (2.5 GHz, RAM of 1 GByte), depending on the number of classes and the volume size to classify. On the 10 patients, manual correction was needed for none on the lung, 1 on the spleen, 2 on the kidneys, and 7 on the liver, mostly owing to intercostal structures. The mean relative volume difference (+/-1 standard deviation [SD]) between manual and automated segmentation was 5.0% +/- 3.7%, 5.7% +/- 3.6%, 6.2% +/- 3.3%, and 7.5% +/- 6.5% for the lung, liver, kidney, and spleen, respectively. The corresponding mean agreement index (+/-1 SD) was 0.94 +/- 0.03, 0.90 +/- 0.01, 0.88 +/- 0.03, and 0.84 +/- 0.04. CONCLUSIONS: The algorithm allows for the delineating of organs on thoracic and abdominal CT images, and will be integrated in a 3D internal dosimetry dedicated software.

International audience; BACKGROUND AND PURPOSE: The goal of our study was to quantify the limits of the EUD models for use in score functions in inverse planning software, and for clinical application. MATERIALS AND METHODS: We focused on oesophagus cancer irradiation. Our evaluation was based on theoretical dose volume histograms (DVH), and we analyzed them using volumetric and linear quadratic EUD models, average and maximum dose concepts, the linear quadratic model and the differential area between each DVH. RESULTS: We evaluated our models using theoretical and more complex DVHs for the above regions of interest. We studied three types of DVH for the target volume: the first followed the ICRU dose homogeneity recommendations; the second was built out of the first requirements and the same average dose was built in for all cases; the third was truncated by a small dose hole. We also built theoretical DVHs for the organs at risk, in order to evaluate the limits of, and the ways to use both EUD(1) and EUD/LQ models, comparing them to the traditional ways of scoring a treatment plan. For each volume of interest we built theoretical treatment plans with differences in the fractionation. CONCLUSION: We concluded that both volumetric and linear quadratic EUDs should be used. Volumetric EUD(1) takes into account neither hot-cold spot compensation nor the differences in fractionation, but it is more sensitive to the increase of the irradiated volume. With linear quadratic EUD/LQ, a volumetric analysis of fractionation variation effort can be performed.

International audience; Solar ultraviolet (UV) radiation has hazardous effects on human health that are, in part, associated with its immunosuppressive effects via the induction of interleukin (IL)-10 production. Although IL-10 is produced by both T helper type 2 (Th2) cells and T-regulatory type 1 (Tr1) cells, the relative contribution of either subset in UV radiation-induced immunosuppression has not been established. Here, we show that T cells isolated from non-treated allergic contact dermatitis (ACD) reactions, 48 h following nickel challenge and propagated for 7-10 days in the presence of IL-2, were mainly CD4(+) and produced IL-10, but little interferon-gamma. A single sub-erythematous solar-simulated radiation (SSR) prior to antigen challenge exposure resulted in a clinical attenuation of the intensity of ACD reactions which was associated with a significant increase in both the magnitude of IL-10 production by skin-infiltrating T cells and the frequency of IL-10-producing Tr1 cells. Skin-infiltrating T cells in SSR-exposed, as well as non-exposed, ACD reactions showed a perturbed T-cell receptor (TCR)-Vbeta repertoire, without overexpression of a particular TCR-Vbeta gene product, indicating the presence of high frequencies of nickel non-specific T cells in ACD reactions. These results show that a single sub-erythematous SSR induces immunosuppression via the cutaneous infiltration of IL-10-producing Tr1, and to a lesser extent, Th2 cells.

International audience; A radiation dose enhancement can be obtained in brain tumours after infusion of an iodinated contrast agent and irradiation with kilovoltage x-rays in tomography mode. The aim of this study was to assess dosimetric properties of the synchrotron stereotactic radiotherapy technique applied to humans (SSR) for preparing clinical trials. We designed an interface for dose computation based on a Monte Carlo code (MCNPX). A patient head was constructed from computed tomography (CT) data and a tumour volume was modelled. Dose distributions were calculated in SSR configuration for various energy beam and iodine content in the target volume. From the calculations, it appears that the iodine-filled target (10 mg ml(-1)) can be efficiently irradiated by a monochromatic beam of energy ranging from 50 to 85 keV. This paper demonstrates the feasibility of stereotactic radiotherapy for treating deep-seated brain tumours with monoenergetic x-rays from a synchrotron.

International audience; Synchrotron stereotactic radiotherapy (SSR) consists in loading the tumour with a high atomic number element (Z), and exposing it to monochromatic x-rays from a synchrotron source (50-100 keV), in stereotactic conditions. The dose distribution results from both the stereotactic monochromatic x-ray irradiation and the presence of the high Z element. The purpose of this preliminary study was to evaluate the two-dimensional dose distribution resulting solely from the irradiation geometry, using Monte Carlo simulations and a Fricke gel dosimeter. The verification of a Monte Carlo-based dosimetry was first assessed by depth dose measurements in a water tank. We thereafter used a Fricke dosimeter to compare Monte Carlo simulations with dose measurements. The Fricke dosimeter is a solution containing ferrous ions which are oxidized to ferric ions under ionizing radiation, proportionally to the absorbed dose. A cylindrical phantom filled with Fricke gel was irradiated in stereotactic conditions over several slices with a continuous beam (beam section = 0.1 x 1 cm2). The phantom and calibration vessels were then imaged by nuclear magnetic resonance. The measured doses were fairly consistent with those predicted by Monte Carlo simulations. However, the measured maximum absolute dose was 10% underestimated regarding calculation. The loss of information in the higher region of dose is explained by the diffusion of ferric ions. Monte Carlo simulation is the most accurate tool for dosimetry including complex geometries made of heterogeneous materials. Although the technique requires improvements, gel dosimetry remains an essential tool for the experimental verification of dose distribution in SSR with millimetre precision.

International audience; A sparse phased array is specially designed for non-invasive ultrasound transskull brain therapy. The array is made of 200 single elements corresponding to a new generation of high power transducers developed in collaboration with Imasonic (Besançon, France). Each element has a surface of 0.5 cm2 and works at 0.9 MHz central frequency with a maximum 20 W cm(-2) intensity on the transducer surface. In order to optimize the steering capabilities of the array, several transducer distributions on a spherical surface are simulated: hexagonal, annular and quasi-random distributions. Using a quasi-random distribution significantly reduces the grating lobes. Furthermore, the simulations show the capability of the quasi-random array to electronically move the focal spot in the vicinity of the geometrical focus (up to +/- 15 mm). Based on the simulation study, the array is constructed and tested. The skull aberrations are corrected by using a time reversal mirror with amplitude correction achieved thanks to an implantable hydrophone, and a sharp focus is obtained through a human skull. Several lesions are induced in fresh liver and brain samples through human skulls, demonstrating the accuracy and the steering capabilities of the system.

International audience; Flow radioactivity counters coupled to liquid chromatography devices cause a systematic bias to the separation by broadening peaks within the radiochromatogram. Such signal smearing may be evaluated on standardization runs with a single peak, using the ratio between Fourier transforms of whole chromatographic data for the measured radioactivity time series (radioactivity channel) and for the concentration time series (optical density channel). This ratio constitutes a kernel suitable to perform the deconvolution of any radiochromatogram performed under similar conditions. Through deconvolution, the signal smearing is removed, reverting to peaks with the same geometry as in the concentration chromatogram: same retention time, peak width, and shape. The deconvolution method in processing radiochromatograms allows an easier interpretation and gives more reliable radioactivity quantification (improved linearity of the measured response). Fourier transformation of the radiochromatogram also allows the removal of transitory events (noise) through the correlation procedure. This method may provide substantial gain in sensitivity, depending upon the residence time of the sample in the counting cell.

International audience; The antimycobacterial spectrum of roxithromycin, a semisynthetic 14-membered ring macrolide, was determined against 28 strains belonging to 16 species of atypical mycobacteria by measuring radiometric MICs by BACTEC methodology at two different pH values, i.e., 6.8 and 7.4. The MICs obtained at pH 7.4 were 1 to 2 dilutions lower or more than those obtained at pH 6.8 for some of the species. Roxithromycin possessed promising MICs against such potential pathogens as the Mycobacterium avium complex, M. scrofulaceum, M. szulgai, M. malmoense, M. xenopi, M. marinum, M. kansasii, and rare pathogens like M. chelonei subsp. chelonei and M. chelonei subsp. abscessus but not against M. simiae. Roxithromycin showed lower MICs against M. fortuitum var. peregrinum than M. fortuitum var. fortuitum.