Evaluation of MRI-only based online adaptive radiotherapy of abdominal region on MR-linac

Purpose A hybrid magnetic resonance linear accelerator (MRL) can perform magnetic resonance imaging (MRI) with high soft-tissue contrast to be used for online adaptive radiotherapy (oART). To obtain electron densities needed for the oART dose calculation, a computed tomography (CT) is often deformably registered to MRI. Our aim was to evaluate an MRI-only based synthetic CT (sCT) generation as an alternative to the deformed CT (dCT)-based oART in the abdominal region. Methods The study data consisted of 57 patients who were treated on a 0.35 T MRL system mainly for abdominal tumors. Simulation MRI-CT pairs of 43 patients were used for training and validation of a prototype convolutional neural network sCT-generation algorithm, based on HighRes3DNet, for the abdominal region. For remaining test patients, sCT images were produced from simulation MRIs and daily MRIs. The dCT-based plans were re-calculated on sCT with identical calculation parameters. The sCT and dCT were compared in terms of geometric agreement and calculated dose. Results The mean and one standard deviation of the geometric agreement metrics over dCT-sCT-pairs were: mean error of 8 +/- 10 HU, mean absolute error of 49 +/- 10 HU, and Dice similarity coefficient of 55 +/- 12%, 60 +/- 5%, and 82 +/- 15% for bone, fat, and lung tissues, respectively. The dose differences between the sCT and dCT-based dose for planning target volumes were 0.5 +/- 0.9%, 0.6 +/- 0.8%, and 0.5 +/- 0.8% at D-2%, D-50%, and D-98% in physical dose and 0.8 +/- 1.4%, 0.8 +/- 1.2%, and 0.6 +/- 1.1% in biologically effective dose (BED). For organs-at-risk, the dose differences of all evaluated dose-volume histogram points were within [-4.5%, 7.8%] and [-1.1 Gy, 3.5 Gy] in both physical dose and BED. Conclusions The geometric agreement metrics were within typically reported values and most average relative dose differences were within 1%. Thus, an MRI-only sCT-based approach is a promising alternative to the current clinical practice of the abdominal oART on MRL.Peer reviewe

The Lyman Alpha Reference Sample. VIII. Characterizing Lyman-Alpha Scattering in Nearby Galaxies

We examine the dust geometry and Ly{\alpha} scattering in the galaxies of the Lyman Alpha Reference Sample (LARS), a set of 14 nearby (0.02 < $z$ < 0.2) Ly{\alpha} emitting and starbursting systems with Hubble Space Telescope Ly{\alpha}, H{\alpha}, and H{\beta} imaging. We find that the global dust properties determined by line ratios are consistent with other studies, with some of the LARS galaxies exhibiting clumpy dust media while others of them show significantly lower Ly{\alpha} emission compared to their Balmer decrement. With the LARS imaging, we present Ly{\alpha}/H{\alpha} and H{\alpha}/H{\beta} maps with spatial resolutions as low as $\sim$ 40 pc, and use these data to show that in most galaxies, the dust geometry is best modeled by three distinct regions: a central core where dust acts as a screen, an annulus where dust is distributed in clumps, and an outer envelope where Ly{\alpha} photons only scatter. We show that the dust that affects the escape of Ly{\alpha} is more restricted to the galaxies' central regions, while the larger Ly{\alpha} halos are generated by scattering at large radii. We present an empirical modeling technique to quantify how much Ly{\alpha} scatters in the halo, and find that this "characteristic" scattering distance correlates with the measured size of the Ly{\alpha} halo. We note that there exists a slight anti-correlation between the scattering distance of Ly{\alpha} and global dust properties.Comment: 32 pages, 51 figures, accepted to Ap

The Lyman alpha reference sample. VII. Spatially resolved Hα\alpha kinematics

We present integral field spectroscopic observations with the Potsdam Multi Aperture Spectrophotometer of all 14 galaxies in the $z\sim 0.1$ Lyman Alpha Reference Sample (LARS). We produce 2D line of sight velocity maps and velocity dispersion maps from the Balmer $\alpha$ (H$\alpha$) emission in our data cubes. These maps trace the spectral and spatial properties of the LARS galaxies' intrinsic Ly$\alpha$ radiation field. We show our kinematic maps spatially registered onto the Hubble Space Telescope H$\alpha$ and Lyman $\alpha$ (Ly$\alpha$) images. Only for individual galaxies a causal connection between spatially resolved H$\alpha$ kinematics and Ly$\alpha$ photometry can be conjectured. However, no general trend can be established for the whole sample. Furthermore, we compute non-parametric global kinematical statistics -- intrinsic velocity dispersion $\sigma_0$, shearing velocity $v_\mathrm{shear}$, and the $v_\mathrm{shear}/\sigma_0$ ratio -- from our kinematic maps. In general LARS galaxies are characterised by high intrinsic velocity dispersions (54\,km\,s$^{-1}$ median) and low shearing velocities (65\,km\,s$^{-1}$ median). $v_\mathrm{shear}/\sigma_0$ values range from 0.5 to 3.2 with an average of 1.5. Noteworthy, five galaxies of the sample are dispersion dominated systems with $v_\mathrm{shear}/\sigma_0 <1$ and are thus kinematically similar to turbulent star forming galaxies seen at high redshift. When linking our kinematical statistics to the global LARS Ly$\alpha$ properties, we find that dispersion dominated systems show higher Ly$\alpha$ equivalent widths and higher Ly$\alpha$ escape fractions than systems with $v_\mathrm{shear}/\sigma_0 > 1$. Our result indicates that turbulence in actively star-forming systems is causally connected to interstellar medium conditions that favour an escape of Ly$\alpha$ radiation.Comment: 26 pages, 15 figures, accepted for publication in A&

Decoding the auditory brain with canonical component analysis

The relation between a stimulus and the evoked brain response can shed light on perceptual processes within the brain. Signals derived from this relation can also be harnessed to control external devices for Brain Computer Interface (BCI) applications. While the classic event-related potential (ERP) is appropriate for isolated stimuli, more sophisticated “decoding” strategies are needed to address continuous stimuli such as speech, music or environmental sounds. Here we describe an approach based on Canonical Correlation Analysis (CCA) that finds the optimal transform to apply to both the stimulus and the response to reveal correlations between the two. Compared to prior methods based on forward or backward models for stimulus-response mapping, CCA finds significantly higher correlation scores, thus providing increased sensitivity to relatively small effects, and supports classifier schemes that yield higher classification scores. CCA strips the brain response of variance unrelated to the stimulus, and the stimulus representation of variance that does not affect the response, and thus improves observations of the relation between stimulus and response

Abatacept modulates CD80 and CD86 expression and memory formation in human B-cells

Background: Cytotoxic T lymphocyte antigen-4 (CTLA-4) limits T-cell activation and is expressed on T-regulatory cells. Human CTLA-4 deficiency results in severe immune dysregulation. Abatacept (CTLA-4 Ig) is approved for the treatment of rheumatoid arthritis (RA) and its mechanism of action is attributed to effects on T-cells. It is known that CTLA-4 modulates the expression of its ligands CD80 and CD86 on antigen presenting cells (APC) by transendocytosis. As B-cells express CD80/CD86 and function as APC, we hypothesize that B-cells are a direct target of abatacept. Objectives: To investigate direct effects of abatacept on human B-lymphocytes in vitro and in RA patients. Methods: The effect of abatacept on healthy donor B-cells’ phenotype, activation and CD80/CD86 expression was studied in vitro. Nine abatacept-treated RA patients were studied. Seven of these were followed up to 24 months, and two up to 12 months only and treatment response, immunoglobulins, ACPA, RF concentrations, B-cell phenotype and ACPA-specific switched memory B-cell frequency were assessed. Results: B-cell development was unaffected by abatacept. Abatacept treatment resulted in a dose-dependent decrease of CD80/CD86 expression on B-cells in vitro, which was due to dynamin-dependent internalization. RA patients treated with abatacept showed a progressive decrease in plasmablasts and serum IgG. While ACPA-titers only moderately declined, the frequency of ACPA-specific switched memory B-cells significantly decreased. Conclusions: Abatacept directly targets B-cells by reducing CD80/CD86 expression. Impairment of antigen presentation and T-cell activation may result in altered B-cell selection, providing a new therapeutic mechanism and a base for abatacept use in B-cell mediated autoimmunity.Fil: Lorenzetti, Raquel. Albert Ludwigs University of Freiburg; AlemaniaFil: Janowska, Iga. Albert Ludwigs University of Freiburg; AlemaniaFil: Smulski, Cristian Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; ArgentinaFil: Frede, Natalie. Albert Ludwigs University of Freiburg; AlemaniaFil: Henneberger, Nadine. Albert Ludwigs University of Freiburg; AlemaniaFil: Walter, Lea. Albert Ludwigs University of Freiburg; AlemaniaFil: Schleyer, Marei-Theresa. Albert Ludwigs University of Freiburg; AlemaniaFil: Hüppe, Janika M.. Albert Ludwigs University of Freiburg; AlemaniaFil: Staniek, Julian. Albert Ludwigs University of Freiburg; AlemaniaFil: Salzer, Ulrich. Albert Ludwigs University of Freiburg; AlemaniaFil: Venhoff, Ana. Albert Ludwigs University of Freiburg; AlemaniaFil: Troilo, Arianna. Albert Ludwigs University of Freiburg; AlemaniaFil: Voll, Reinhard Edmund. Albert Ludwigs University of Freiburg; AlemaniaFil: Venhoff, Nils. Albert Ludwigs University of Freiburg; AlemaniaFil: Thiel, Jens. Albert Ludwigs University of Freiburg; AlemaniaFil: Rizzi, Marta. Albert Ludwigs University of Freiburg; Alemani

On the evolution of the size of Lyman alpha halos across cosmic time: no change in the circumgalactic gas distribution when probed by line emission

Lyman $\alpha$ (Ly$\alpha$) is now routinely used as a tool for studying high-redshift galaxies and its resonant nature means it can trace neutral hydrogen around star-forming galaxies. Integral field spectrograph measurements of high-redshift Ly$\alpha$ emitters indicate that significant extended Ly$\alpha$ halo emission is ubiquitous around such objects. We present a sample of redshift 0.23 to 0.31 galaxies observed with the Hubble Space Telescope selected to match the star formation properties of high-$z$ samples while optimizing the observations for detection of low surface brightness Ly$\alpha$ emission. The Ly$\alpha$ escape fractions range between 0.7\% and 37\%, and we detect extended Ly$\alpha$ emission around six out of seven targets. We find Ly$\alpha$ halo to UV scale length ratios around 6:1 which is marginally lower than high-redshift observations, and halo flux fractions between 60\% and 85\% -- consistent with high-redshift observations -- when using comparable methods. However, our targets show additional extended stellar UV emission: we parametrize this with a new double exponential model. We find that this parametrization does not strongly affect the observed Ly$\alpha$ halo fractions. We find that deeper H$\alpha$ data would be required to firmly determine the origin of Ly$\alpha$ halo emission, however, there are indications that H$\alpha$ is more extended than the central FUV profile, potentially indicating conditions favorable for the escape of ionizing radiation. We discuss our results in the context of high-redshift galaxies, cosmological simulations, evolutionary studies of the circumgalactic medium in emission, and the emission of ionizing radiation.Comment: 20 page, 14 figures, 6 tables. Accepted for publication in MNRA

In-sample forecasting: A brief review and new algorithms

Statistical methods often distinguish between in-sample and out-of-sample approaches. In particular this is the case when time is involved. Then often time series methods are proposed that extrapolate past patterns into the future via complicated recursion formulas. Standard statistical inference is on the other hand concerned with estimating parameters within the given sample. This review paper is about a statistical methodology, where all parameters are estimated in-sample while producing a forecast out-of-sample without recursion or extrapolation. A new super-simulation algorithm ensures a faster implementation of the simplest and perhaps most important version of in-sample forecasting