Mast cells and exosomes in hyperoxia-induced neonatal lung disease.

Chronic lung disease of prematurity (CLD) is a frequent sequela of premature birth and oxygen toxicity is a major associated risk factor. Impaired alveolarization, scarring, and inflammation are hallmarks of CLD. Mast cell hyperplasia is a feature of CLD but the role of mast cells in its pathogenesis is unknown. We hypothesized that mast cell hyperplasia is a consequence of neonatal hyperoxia and contributes to CLD. Additionally, mast cell products may have diagnostic and prognostic value in preterm infants predisposed to CLD. To model CLD, neonatal wild-type and mast cell-deficient mice were placed in an O2 chamber delivering hyperoxic gas mixture [inspired O2 fraction (FiO2 ) of 0.8] (HO) for 2 wk and then returned to room air (RA) for an additional 3 wk. Age-matched controls were kept in RA (FiO2 of 0.21). Lungs from HO mice had increased numbers of mast cells, alveolar simplification and enlargement, and increased lung compliance. Mast cell deficiency proved protective by preserving air space integrity and lung compliance. The mast cell mediators ß-hexosaminidase (ß-hex), histamine, and elastase increased in the bronchoalveolar lavage fluid of HO wild-type mice. Tracheal aspirate fluids (TAs) from oxygenated and mechanically ventilated preterm infants were analyzed for mast cell products. In TAs from infants with confirmed cases of CLD, ß-hex was elevated over time and correlated with FiO2 Mast cell exosomes were also present in the TAs. Collectively, these data show that mast cells play a significant role in hyperoxia-induced lung injury and their products could serve as potential biomarkers in evolving CLD.

A performance comparison of flat-panel imager-based MV and kV cone-beam CT.

The use of cone-beam computed tomography (CBCT) has been proposed for guiding the delivery of radiation therapy, and investigators have examined the use of both kilovoltage (kV) and megavoltage (MV) x-ray beams in the development of such CBCT systems. In this paper, the inherent contrast and signal-to-noise ratio (SNR) performance for a variety of existing and hypothetical detectors for CBCT are investigated analytically as a function of imaging dose and object size. Theoretical predictions are compared to the results of experimental investigations employing largearea flat-panel imagers (FPIs) at kV and MV energies. Measurements were performed on two different FPI-based CBCT systems: a bench-top prototype incorporating an FPI and kV x-ray source (100 kVp x rays), and a system incorporating an FPI mounted on the gantry of a medical linear accelerator (6 MV x rays). The SNR in volume reconstructions was measured as a function of dose and found to agree reasonably with theoretical predictions. These results confirm the theoretically predicted advantages of employing kV energy x rays in imaging soft-tissue structures found in the human body. While MV CBCT may provide a valuable means of correcting 3D setup errors and may offer an advantage in terms of simplicity of mechanical integration with a linear accelerator (e.g., implementation in place of a portal imager), kV CBCT offers significant performance advantages in terms of image contrast and SNR per unit dose for visualization of soft-tissue structures. The relatively poor SNR performance at MV energies is primarily a result of the low x-ray quantum efficiencies (approximately a few percent or less) that are currently achieved with FPIs at high energies. Furthermore, kV CBCT with an FPI offers the potential of combined volumetric and radiographic/fluoroscopic imaging using the same device.

An iterative algorithm for reconstructing incident beam distributions from transmission measurements using electronic portal imaging.

The problem of reconstructing incident radiotherapy beam profiles from electronic portal images recorded behind a phantom is addressed. To this end an iterative algorithm is presented, which is able to extract the input beam profile from a portal image by compensating for the attenuation of the beam and subtracting the amount of scatter emitted by the phantom. The algorithm requires only a thickness map of the phantom. Scatter is estimated using a superposition method based on precalculated Monte Carlo scatter kernels. The method is tested for a homogeneous water-equivalent slab phantom for simple rectangular and complex multileaf collimated fields. It is shown that the method produces a stable result within four iterations yielding an accuracy for the incident beam distribution of better than 3%.

Crystal structures and freezing of dipolar fluids.

We investigate the crystal structure of classical systems of spherical particles with an embedded point dipole at T=0. The ferroelectric ground state energy is calculated using generalizations of the Ewald summation technique. Due to the reduced symmetry compared to the nonpolar case the crystals are never strictly cubic. For the Stockmayer (i.e., Lennard-Jones plus dipolar) interaction three phases are found upon increasing the dipole moment: hexagonal, body-centered orthorhombic, and body-centered tetragonal. An even richer phase diagram arises for dipolar soft spheres with a purely repulsive inverse power law potential approximately r(-n). A crossover between qualitatively different sequences of phases occurs near the exponent n=12. The results are applicable to electro- and magnetorheological fluids. In addition to the exact ground state analysis we study freezing of the Stockmayer fluid by density-functional theory.

Correction of scatter in megavoltage cone-beam CT.

The role of scatter in a cone-beam computed tomography system using the therapeutic beam of a medical linear accelerator and a commercial electronic portal imaging device (EPID) is investigated. A scatter correction method is presented which is based on a superposition of Monte Carlo generated scatter kernels. The kernels are adapted to both the spectral response of the EPID and the dimensions of the phantom being scanned. The method is part of a calibration procedure which converts the measured transmission data acquired for each projection angle into water-equivalent thicknesses. Tomographic reconstruction of the projections then yields an estimate of the electron density distribution of the phantom. It is found that scatter produces cupping artefacts in the reconstructed tomograms. Furthermore, reconstructed electron densities deviate greatly (by about 30%) from their expected values. The scatter correction method removes the cupping artefacts and decreases the deviations from 30% down to about 8%.

Hard-sphere solids near close packing: testing theories for crystallization

The freezing transition of hard spheres has been well described by various versions of density-functional theory (DFT). These theories should possess the close-packed crystal as a special limit, which represents an extreme testing ground for the quality of such liquid-state based theories. We therefore study the predictions of DFT for the structure and thermodynamics of the hard-sphere crystal in this limit. We examine the Ramakrishnan-Yussouff (RY) approximation and two variants of the fundamental-measure theory (FMT) developed by Rosenfeld and co-workers. We allow for general shapes of the density peaks, going beyond the common Gaussian approximation. In all cases we find that upon approaching close packing, the peak width vanishes proportionally to the free distance a between the particles and the free energy depends logarithmically on a. However, different peak shapes and next-to-leading contributions to the free energy result from the different approximate functionals. For the RY theory, within the Gaussian approximation, we establish that the crystalline solutions form a closed loop with a stable and an unstable branch both connected to the close-packing point at a=0, consistent with the absence of a liquid-solid spinodal. That version of FMT that has previously been applied to freezing, predicts asymptotically steplike density profiles confined to the cells of self-consistent cell theory. But a recently suggested improved version which employs tensor weighted densities yields wider and almost Gaussian peaks that are shown to be in very good agreement with computer simulations.

Density-functional theory for vacancies in hard-sphere crystals

The equilibrium vacancy concentration in solids can be computed from density-functional theory (DFT) if allowance is made for density profiles with less than one particle per lattice site. For the fundamental-measure theory (FMT), this approach predicts reasonably small vacancy concentrations in hard sphere crystals, in contrast to earlier DFTs. Using an asymptotic analysis of the FMT functional, it is shown that the number of vacancies depends exponentially on the distance to the close packing density, as expected from heuristic arguments. The prefactor of the exponential is calculated for three recently suggested variants of the theory, using density profiles obtained from a quasifree minimization. Extrapolation of the asymptotic behavior to the melting density yields good agreement with other estimates and computer simulation results.

Vesicles in solutions of hard rods.

The surface free energy of ideal hard rods near curved hard surfaces is determined to second order in curvature for surfaces of general shapes. In accordance with previous results for spherical and cylindrical surfaces it is found that this quantity is nonanalytical when one of the principal curvatures changes signs. This prohibits writing it in the common Helfrich form. It is shown that the nonanalytical terms are the same for any aspect ratio of the rods. These results are used to find the equilibrium shape of vesicles immersed in solutions of rodlike (colloidal) particles. The presence of the particles induces a change in the equilibrium shape and a shift of the prolate-oblate transition in the vesicle phase diagram, which are calculated within the framework of the spontaneous curvature model. As a consequence of the special form of the energy contribution due to the rods, these changes cannot be accounted for by a simple rescaling of the elastic constants of the vesicle as for solutions of spherical colloids or polymers.

Why all crystals need not be bcc: symmetry breaking at the liquid-solid transition revisited.

Alexander and McTague [Phys.Rev. Lett. 41, 702 (1978)] argued that if there is a spinodal point associated with the liquid-solid transition in a fluid of spherically symmetric particles, the bcc phase will be uniquely favored as the only accessible symmetry breaking structure that forms a regular three-dimensional lattice. By reconsidering their analysis in the framework of density-functional theory, we show that at a liquid-solid spinodal in fact many other solid stuctures also are simultaneously accessible, among them the fcc structure. Nevertheless, the bcc structure is still shown to be special, as, independent of the details of the interaction, the free energy of the unstable bcc phase close to the spinodal is always lower than that of the other solidlike structures. We illustrate our general results by explicit calculations on a toy model, the "Onsager solid." This simple model also indicates that the ultimately stable crystal phase, which, as usual for sufficiently steep repulsive forces, turns out to be fcc, is dictated by properties of the free energy that cannot be obtained perturbatively starting from the spinodal point.

Tomotherapeutic portal imaging for radiation treatment verification.

In their tomotherapy concept Mackie and co-workers proposed not only a new technique for IMRT but also an appropriate and satisfactory method of treatment verification. This method allows both monitoring of the portal dose distribution and imaging of the patient anatomy during treatment by means of online CT. This would enable the detection of inaccuracies in dose delivery and patient set-up errors. In this paper results are presented showing that a single electronic portal imaging device (EPID) could deliver all data necessary to establish such a complete verification system for tomotherapy and even other IMRT techniques. Consequently it has to be shown that it is able to record both the low-intensity photon fluences encountered in tomographic imaging and the intense photon transmission of each treatment field. The detector under investigation is a video-based EPID, the BIS 710 (manufactured by Wellhöfer Dosimetrie, Schwarzenbruck, Germany). To examine the suitability of the BIS for CT at 6 MV beam quality, different phantoms were scanned and reconstructed. The agreement between a diamond detector and BIS responses is quantitative. Tomographic reconstruction of a complete set of these transmission profiles resulted in images which resolve 3 cm large objects having a (theoretical) contrast to water of less than 9%. Three millimetre objects with a 100% contrast are clearly visible. The BIS signal was shown to measure photon fluence distributions. The reconstructed images possess a spatial and contrast resolution sufficient for accurate imaging of the patient anatomy, needed for treatment verification in many clinical cases.