ORIGAMIX, a CdTe-based spectro-imager development for nuclear applications

The Astrophysics Division of CEA Saclay has a long history in the development of CdTe based pixelated detection planes for X and gamma-ray astronomy, with time-resolved imaging and spectrometric capabilities. The last generation, named Caliste HD, is an all-in-one modular instrument that fulfills requirements for space applications. Its full-custom front-end electronics is designed to work over a large energy range from 2 keV to 1 MeV with excellent spectroscopic performances, in particular between 10 and 100 keV (0.56 keV FWHM and 0.67 keV FWHM at 13.9 and 59.5 keV). In the frame of the ORIGAMIX project, a consortium based on research laboratories and industrials has been settled in order to develop a new generation of gamma camera. The aim is to develop a system based on the Caliste architecture for post-accidental interventions or homeland security, but integrating new properties (advanced spectrometry, hybrid working mode) and suitable for industry. A first prototype was designed and tested to acquire feedback for further developments. In this study, we particularly focused on spectrometric performances with high energies and high fluxes. Therefore, our device was exposed to energies up to 700 keV (133Ba, 137Cs) and we measured the evolution of energy resolution (0.96 keV at 80 keV, 2.18 keV at 356 keV, 3.33 keV at 662 keV). Detection efficiency decreases after 150 keV, as Compton effect becomes dominant. However, CALISTE is also designed to handle multiple events, enabling Compton scattering reconstruction, which can drastically improve detection efficiencies and dynamic range for higher energies up to 1408 keV (22Na, 60Co, 152Eu) within a 1-mm thick detector. In particular, such spectrometric performances obtained with 152Eu and 60Co were never measured before with this kind of detector.Comment: Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. Available online 9 January 2015, ISSN 0168-9002 (http://www.sciencedirect.com/science/article/pii/S0168900215000133). Keywords: CdTe; X-ray; Gamma-ray; Spectrometry; Charge-sharing; Astrophysics Instrumentation; Nuclear Instrumentation; Gamma-ray camera

In vitro expansion of U87-MG human glioblastoma cells under hypoxic conditions affects glucose metabolism and subsequent in vivo growth

Hypoxia is a characteristic feature of solid tumors leading to the over expression of hypoxia-inducible factor (HIF)-1α protein and therefore to a specific cellular behavior. However, even though the oxygen tension in tumors is low (<5 %), most of the cell lines used in cancer studies are grown under 21 % oxygen tension. This work focuses on the impact of oxygen conditions during in vitro cell culture on glucose metabolism using 1-13C-glucose. Growing U87-MG glioma cells under hypoxic conditions leads to a two- to threefold reduction of labeled glutamine and an accumulation of fructose. However, under both hypoxic and normoxic conditions, glucose is used for de novo synthesis of pyrimidine since the 13C label is found both in the uracil and ribose moieties. Labeling of the ribose ring demonstrates that U87-MG glioma cells use the reversible branch of the non-oxidative pentose phosphate pathway. Interestingly, stereotactic implantation of U87-MG cells grown under normoxia or mild hypoxia within the striatum of nude mice led to differential growth; the cells grown under hypoxia retaining an imprint of the oxygen adaptation as their development is then slowed down

Susceptibility gradient quantization by MRI signal response mapping (SIRMA) to dephaser

Purpose: Susceptibility effects are a very efficient source of contrast in magnetic resonance imaging. However, detection is hampered by the fact the induced contrast is negative. In this work, the SIgnal Response MApping (SIRMA) to dephaser method is proposed to map susceptibility gradient to improve visualization. Methods: In conventional gradient echo acquisitions, the echo formation of susceptibility affected spins is shifted in k -space, the shift being proportional to the susceptibility gradient. Susceptibility gradients map can be produced by measuring this induced shifts. The SIRMA method measures these shifts from a series of dephased images collected with additional incremental dephasers. These additional dephasers correspond either to a slice refocusing gradient offset or to a reconstruction window off-centering. The signal intensity profile as a function of the additional dephaser was determined on a pixel-by-pixel basis from the ensemble of dephased images. Susceptibility affected voxels presented a signal response profile maximum shifted compared to nonaffected voxels ones. Shift magnitude and sign were measured for each pixel to determine susceptibility gradients and produce a susceptibility gradient map. Results: In vitro experiments demonstrated the ability of the method to map gradient inhomogeneities induced by a cylinder. Quantization accuracy was evaluated comparing SIRMA images and simulations performed on the well-characterized air filled cylinder model. Performances of the SIRMA method, evaluated in vitro on cylinders filled with various superparamagnetic iron oxide SPIO concentrations, showed limited influence of acquisition parameters. Robustness of the method was then assessed in vivo after an infusion of SPIO-loaded nanocapsules into the rat brain using a convection-enhanced drug delivery approach. The region of massive susceptibility gradient induced by the SPIO-loaded nanocapsules was clearly delineated on SIRMA maps and images were compared to T 2 weighted images, Susceptibility Gradient Map (SGM), and histological Perl\u27s staining slice. The potential for quantitative evaluation of SPIO distribution volume was demonstrated. Conclusions: The proposed method is a promising technique for a wide range of applications especially in molecular or cellular imaging with respect to its quantitative nature and its computational simplicity

Magic traits drive the emergence of pathogens

An important branch of evolutionary biology strives to understand how divergent selection for an ecologically important trait can foster the emergence of new species specialized on different niches. Such ecological speciation is usually difficult to achieve because recombination between different subsets of a population that are adapting to different environments counteracts selection for locally adapted gene combinations. Traits pleiotropically controlling adaptation to different environments and reproductive isolation are therefore the most favourable for ecological speciation, and are thus called “magic traits”. We used genetic markers and cross-inoculations to show that pathogenicity-related loci are responsible for both host adaptation and reproductive isolation in emerging populations of Venturia inaequalis, the fungus causing apple scab disease. Because the fungus mates within its host and because the pathogenicity-related loci prevent infection of the non-host trees, host adaptation pleiotropically maintains genetic differentiation and adaptive allelic combinations between sympatric populations specific to different apple varieties. Such “magic traits” are likely frequent in fungal pathogens, and likely drive the emergence of new diseases.

Emergence of novel fungal pathogens by ecological speciation: importance of the reduced viability of immigrants

Expanding global trade and the domestication of ecosystems have greatly accelerated the rate of emerging infectious fungal diseases, and host-shift speciation appears to be a major route for disease emergence. There is therefore an increased interest in identifying the factors that drive the evolution of reproductive isolation between populations adapting to different hosts. Here, we used genetic markers and cross-inoculations to assess the level of gene flow and investigate barriers responsible for reproductive isolation between two sympatric populations of Venturia inaequalis, the fungal pathogen causing apple scab disease, one of the fungal populations causing a recent emerging disease on resistant varieties. Our results showed the maintenance over several years of strong and stable differentiation between the two populations in the same orchards, suggesting ongoing ecological divergence following a host shift. We identified strong selection against immigrants (i.e. host specificity) from different host varieties as the strongest and likely most efficient barrier to gene flow between local and emerging populations. Cross-variety disease transmission events were indeed rare in the field and cross-inoculation tests confirmed high host specificity. Because the fungus mates within its host after successful infection and because pathogenicity-related loci prevent infection of nonhost trees, adaptation to specific hosts may alone maintain both genetic differentiation between and adaptive allelic combinations within sympatric populations parasitizing different apple varieties, thus acting as a ‘magic trait’. Additional intrinsic and extrinsic postzygotic barriers might complete reproductive isolation and explain why the rare migrants and F1 hybrids detected do not lead to pervasive gene flow across years

Assessment of myocardial viability in rats: Evaluation of a new method using superparamagnetic iron oxide nanoparticles and Gd-DOTA at high magnetic field

The aim of this study was to detect salvageable peri-infarction myocardium by MRI in rats after infarction, using with a double contrast agent (CA) protocol at 7 Tesla. Intravascular superparamagnetic iron oxide (SPIO) nanoparticles and an extracellular paramagnetic CA (Gd-DOTA) were used to characterize the peri-infarction zone, which may recover function after reperfusion occurs. Infarcted areas measured from T1-weighted (T1-w) images post Gd-DOTA administration were overestimated compared to histological TTC staining (52% +/- 3% of LV surface area vs. 40% +/- 3%, P=0.03) or to T2-w images post SPIO administration (41% +/- 4%, P=0.04), whereas areas measured from T2-w images post SPIO administration were not significantly different from those measured histologically (P=0.7). Viable and nonviable myocardium portions of ischemically injured myocardium were enhanced after diffusive Gd-DOTA injection. The subsequent injection of vascular SPIO nanoparticles enables the discrimination of viable peri-infarction regions by specifically altering the signal of the still-vascularized myocardium