Three-sided pyramid wavefront sensor. II. Preliminary demonstration on the new CACTI testbed

The next generation of giant ground and space telescopes will have the light-collecting power to detect and characterize potentially habitable terrestrial exoplanets using high-contrast imaging for the first time. This will only be achievable if the performance of Giant Segmented Mirror Telescopes (GSMTs) extreme adaptive optics (ExAO) systems are optimized to their full potential. A key component of an ExAO system is the wavefront sensor (WFS), which measures aberrations from atmospheric turbulence. A common choice in current and next-generation instruments is the pyramid wavefront sensor (PWFS). ExAO systems require high spatial and temporal sampling of wavefronts to optimize performance, and as a result, require large detectors for the WFS. We present a closed-loop testbed demonstration of a three-sided pyramid wavefront sensor (3PWFS) as an alternative to the conventional four-sided pyramid wavefront (4PWFS) sensor for GSMT-ExAO applications on the new Comprehensive Adaptive Optics and Coronagraph Test Instrument (CACTI). The 3PWFS is less sensitive to read noise than the 4PWFS because it uses fewer detector pixels. The 3PWFS has further benefits: a high-quality three-sided pyramid optic is easier to manufacture than a four-sided pyramid. We detail the design of the two components of the CACTI system, the adaptive optics simulator and the PWFS testbed that includes both a 3PWFS and 4PWFS. A preliminary experiment was performed on CACTI to study the performance of the 3PWFS to the 4PWFS in varying strengths of turbulence using both the Raw Intensity and Slopes Map signal processing methods. This experiment was repeated for a modulation radius of 1.6 lambda/D and 3.25 lambda/D. We found that the performance of the two wavefront sensors is comparable if modal loop gains are tuned.Comment: 28 Pages, 15 Figures, and 4 Table

Etude des mécanismes moléculaires responsables de la fonction anti-tumorale de la semaphorine SEMA3F dans le cancer broncho-pulmonaire

La sémaphorine SEMA3F est une protéine de guidage axonal également impliquée dans l'angiogenèse. Le gène SEMA3F est situé dans une région de perte d'hétérozygotie dans les tumeurs pulmonaires chez l'homme, suggérant un rôle anti-tumoral. Nous avons tout d'abord développé un modèle animal de cancer pulmonaire chez le rat en injectant des cellules tumorales pulmonaires transfectées avec SEMA3F. Ce modèle a permis de démontrer un pouvoir anti-tumoral de SEMA3F. De plus, nous avons analysé les mécanismes moléculaires qui expliqueraient le pouvoir anti-tumoral de SEMA3F. Nos résultats, basés sur une lignée cellulaire cancéreurese pulmonaire (H157), indiquent que SEMA3F inhibe l'activation de l'intégrine alphaV beta3, de la voie ILK-ERK1/2, de AKT et de STAT3. SEMA3F inhibe aussi l'expression de HIF-1 alpha et du VEGF, ce qui pourrait être à l'origine des effets anti-angiogéniques que nous avons observés dans un modèle de tumorigenèse sous-cutanée chez la souris ainsi que dans un modèle d'angiogenèse chez le poulet in ovo. Nos résultats montrent que SEMA3F bloque le développement tumoral pulmonaire, probablement en affectant des voies de signalisation intracellulaire participant à l'angiogenèse tumorale.POITIERS-BU Sciences (861942102) / SudocSudocFranceF

Interaction Between Modern Radiotherapy and Immunotherapy for Metastatic Prostate Cancer

International audienceProstate cancer is the most frequently diagnosed cancer in men and a leading cause of cancer-related death. In recent decades, the development of immunotherapies has resulted in great promise to cure metastatic disease. However, prostate cancer has failed to show any significant response, presumably due to its immunosuppressive microenvironment. There is therefore growing interest in combining immunotherapy with other therapies able to relieve the immunosuppressive microenvironment. Radiation therapy remains the mainstay treatment for prostate cancer patients, is known to exhibit immunomodulatory effects, depending on the dose, and is a potent inducer of immunogenic tumor cell death. Optimal doses of radiotherapy are thus expected to unleash the full potential of immunotherapy, improving primary target destruction with further hope of inducing immune-cell-mediated elimination of metastases at distance from the irradiated site. In this review, we summarize the current knowledge on both the tumor immune microenvironment in prostate cancer and the effects of radiotherapy on it, as well as on the use of immunotherapy. In addition, we discuss the utility to combine immunotherapy and radiotherapy to treat oligometastatic metastatic prostate cancer

A new tissue segmentation method to calculate 3D dose in small animal radiation therapy

International audienceBackground: In pre-clinical animal experiments, radiation delivery is usually delivered with kV photon beams, in contrast to the MV beams used in clinical irradiation, because of the small size of the animals. At this medium energy range, however, the contribution of the photoelectric effect to absorbed dose is significant. Accurate dose calculation therefore requires a more detailed tissue definition because both density (ρ) and elemental composition (Z[eff]) affect the dose distribution. Moreover, when applied to cone beam CT (CBCT) acquisitions, the stoichiometric calibration of HU becomes inefficient as it is designed for highly collimated fan beam CT acquisitions. In this study, we propose an automatic tissue segmentation method of CBCT imaging that assigns both density (ρ) and elemental composition (Z[eff]) in small animal dose calculation. Methods: The method is based on the relationship found between CBCT number and ρ*Z[eff] product computed from known materials. Monte Carlo calculations were performed to evaluate the impact of ρZ[eff] variation on the absorbed dose in tissues. These results led to the creation of a tissue database composed of artificial tissues interpolated from tissue values published by the ICRU. The ρZ[eff] method was validated by measuring transmitted doses through tissue substitute cylinders and a mouse with EBT3 film. Measurements were compared to the results of the Monte Carlo calculations.Results: The study of the impact of ρZ(eff] variation over the range of materials, from ρZ[eff] = 2 g.cm[− 3] (lung) to 27 g.cm[− 3] (cortical bone) led to the creation of 125 artificial tissues. For tissue substitute cylinders, the use of ρZ[eff] method led to maximal and average relative differences between the Monte Carlo results and the EBT3 measurements of 3.6% and 1.6%. Equivalent comparison for the mouse gave maximal and average relative differences of 4.4% and 1.2%, inside the 80% isodose area. Gamma analysis led to a 94.9% success rate in the 10% isodose area with 4% and 0.3 mm criteria in dose and distance.Conclusions: Our new tissue segmentation method was developed for 40kVp CBCT images. Both density and elemental composition are assigned to each voxel by using a relationship between HU and the product ρZ[eff]. The method, validated by comparing measurements and calculations, enables more accurate small animal dose distribution calculated on low energy CBCT images

microRNAs identified in prostate cancer: Correlative studies on response to ionizing radiation

International audienceAs the most frequently diagnosed non-skin cancer in men and a leading cause of cancer-related death, understanding the molecular mechanisms that drive treatment resistance in prostate cancer poses a significant clinical need. Radiotherapy is one of the most widely used treatments for prostate cancer, along with surgery, hormone therapy, and chemotherapy. However, inherent radioresistance of tumor cells can reduce local control and ultimately lead to poor patient outcomes, such as recurrence, metastasis and death. The underlying mechanisms of radioresistance have not been fully elucidated, but it has been suggested that miRNAs play a critical role. miRNAs are small non-coding RNAs that regulate gene expression in every signaling pathway of the cell, with one miRNA often having multiple targets. By fine-tuning gene expression, miRNAs are important players in modulating DNA damage response, cell death, tumor aggression and the tumor microenvironment, and can ultimately affect a tumor's response to radiotherapy. Furthermore, much interest has focused on miRNAs found in biofluids and their potential utility in various clinical applications. In this review, we summarize the current knowledge on miRNA deregulation after irradiation and the associated functional outcomes, with a focus on prostate cancer. In addition, we discuss the utility of circulating miRNAs as non-invasive biomarkers to diagnose, predict response to treatment, and prognosticate patient outcomes

Optimizing radiotherapy protocols using computer automata to model tumour cell death as a function of oxygen diffusion processes

International audienceThe concept of hypofractionation is gaining momentum in radiation oncology centres, enabled by recent advances in radiotherapy apparatus. The gain of efficacy of this innovative treatment must be defined. We present a computer model based on translational murine data for in silico testing and optimization of various radiotherapy protocols with respect to tumour resistance and the microenvironment heterogeneity. This model combines automata approaches with image processing algorithms to simulate the cellular response of tumours exposed to ionizing radiation, modelling the alteration of oxygen permeabilization in blood vessels against repeated doses, and introducing mitotic catastrophe (as opposed to arbitrary delayed cell-death) as a means of modelling radiation-induced cell death. Published data describing cell death in vitro as well as tumour oxygenation in vivo are used to inform parameters. Our model is validated by comparing simulations to in vivo data obtained from the radiation treatment of mice transplanted with human prostate tumours. We then predict the efficacy of untested hypofractionation protocols, hypothesizing that tumour control can be optimized by adjusting daily radiation dosage as a function of the degree of hypoxia in the tumour environment. Further biological refinement of this tool will permit the rapid development of more sophisticated strategies for radiotherapy

Response characterization of a new radiochromic film to ultra high dose rates for light ions beams

International audienc

Response characterization of a new radiochromic film to ultra high dose rates for light ions beams

International audienc