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Spreading of vascular endothelial cells in culture: spatial reorganization of cytoplasmic fibers and organelles.

The three-dimensional organization and fine structure of cytoplasmic components within whole non-embedded bovine aortic endothelial cells were examined during their attachment and spreading in tissue culture. Cells were cultured directly on Formvar-coated gold grids, fixed in glutaraldehyde and osmium tetroxide, critical point dried and examined by transmission electron microscopy (TEM) using stereoscopic methods, and by scanning electron microscopy (SEM). Reorganization of cytoplasmic structures during cell spreading occurred in four sequential stages: (1) spreading of the plasma membrane and unstructured cytoplasmic matrix; (2) spreading of cytoplasmic fiber systems (microtubules, microfilament bundles and microtrabecular system); (3) alignment of microfilament bundles and formation of radial tracts of microtubules; and (4) centripetal movement of organelles along radial tracts. These stages observed by TEM correlated with progressive degrees of cell flattening as visualized by SEM. These studies demonstrate that a characteristic reorganization of intracellular fiber systems and organelles accompanies the spreading of endothelial cells in culture.

Animals↗

Computer analysis of the shape of spread of epidemics on a grid.

Models concerned with the spatial features of epidemic spread are often defined in terms of a nearest-neighbor grid network. It has been strongly conjectured, and can be proved in certain cases, that the infected area has an asymptotically well-defined shape. The present work concerns computer analysis of the shape of spread of a discrete-time single-parameter infection process on an eight-neighbor lattice. Results of extensive simulation are displayed using up-to-date exploratory data analysis software, and various attempts at fitting functions to the probability surfaces are considered.

Computer Simulation↗

Epidemic thresholds and vaccination in a lattice model of disease spread.

We use a lattice-based epidemic model to study the spatial and temporal rates of disease spread in a spatially distributed host population. The prevalence of the disease in the population is studied as well as the spread of infection about a point source of infection. In particular, two distinct critical population densities are identified. The first relates to the minimum population density for a epidemic to occur, whilst the second is the minimum population density for long-term persistence to occur. Vaccination regimes are introduced that are used to measure the impact of spatially and nonspatially dependent intervention strategies. Specifically we show how a ring of vaccinated susceptibles, of sufficient thickness, can halt the spread of infection across space.

Animals↗

Particle selection for laser-accelerated proton therapy feasibility study.

In this paper we present calculations for the design of a particle selection system for laser-accelerated proton therapy. Laser-accelerated protons coming from a thin high-density foil have broad energy and angular spectra leading to dose distributions that cannot be directly used for therapeutic applications. Our solution to this problem is a compact particle selection and collimation device that delivers small pencil beams of protons with desired energy spectra. We propose a spectrometer-like particle selection and beam modulation system in which the magnetic field will be used to spread the protons spatially according to their energies and emitting angles. Subsequently, an aperture will be used to select the protons within a therapeutic window of energy (energy modulation). It will be shown that for the effective proton spatial differentiation, the primary collimation device should be used, which will collimate protons to the desired angular distribution and limit the spatial mixing of different energy protons once they have traveled through the magnetic system. Due to the angular proton distribution, the spatial mixing of protons of different energies will always be present and it will result in a proton energy spread with the width depending on the energy. For 250 MeV protons, the width (from the maximum to the minimum energy) is found to be 50 MeV for the magnetic field configuration used in our calculations. As the proton energy decreases, its energy width decreases as well, and for 80 MeV protons it equals 9 MeV. The presence of the energy width in the proton energy distribution will modify the depth dose curves needed for the energy modulation calculation. The matching magnetic field setup will ensure the refocusing of the selected protons and the final beam will be collimated by the secondary collimator. The calculations presented in this article show that the dose rate that the selection system can yield is on the order of D=260 Gy/min for a field size of 1 x 1 cm2.

Equipment Design↗

Measurement of the point spread function in MRI using constant time imaging.

The point spread function is a fundamental property of magnetic resonance imaging methods that affects image quality and spatial resolution. The point spread function is difficult to measure precisely in magnetic resonance even with the use of carefully designed phantoms, and it is difficult to calculate this function for complex sequences such as echo-planar imaging. This report describes a method that measures the point spread function with high spatial resolution at each pixel in samples of uniform intensity distribution. This method uses additional phase encoding gradients before the echo-planar acquisition that are constant in length but vary in amplitude. The additional gradients are applied to image the contents within each individual voxel. This method has been used to measure the point spread function for echo-planar imaging to demonstrate the effects of limited k-space sampling and transverse relaxation, as well as the effects of object motion. By considering the displacement of the point spread function, local distortions due to susceptibility and chemical shift effects have been quantified and corrected. The method allows rapid assessment of the point spread function in echo-planar imaging, in vivo, and may also be applied to other rapid imaging sequences that can be modified to include these additional phase encoding gradients.

Brain↗

[Dynamic thermomapping of the brain of the rat during sensory stimulation and spreading depression].

Dynamics of spatial distribution of temperature over the dorsal surface of white rat cerebral cortex was studied through the skull with the thermovision technics. Visual, somatosensory and acoustic stimulation revealed both diffuse and regionally specific thermoreactions of the brain as well as multiple local termoresponses. After injection of KCl into the cortex temperature waves spreading over the cortex were obtained. Mechanisms of brain patterned thermoreactions dealing with blood flow and neuronal metabolic thermoproduction are discussed.

Animals↗

The spread of excitation in neocortical columns visualized with infrared-darkfield videomicroscopy.

A combination of darkfield techniques and infrared videomicroscopy was used to measure the intrinsic optical signal (IOS) in slices of adult rat neocortex. The IOS, which reflects changes in light transmittance and scattering, provides a means of studying the spread of neuronal excitation and its modulation with high sensitivity and spatial resolution. The column-like IOS elicited by orthodromic stimulation is in accordance with models of neocortical circuitry. Blockade of synaptic transmission by the glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and D-2-amino-5-phosphovaleric acid (D-APV) reduced the IOS. The GABAA agonist muscimol and the neuroactive steroid 5 alpha-tetrahydrodeoxy-corticosterone (5 alpha-THDOC) decreased the spread of excitation, whereas the GABAA antagonist bicuculline increased it. The present data suggest that the spatial spread of excitation in different neocortical layers is delimited by GABAergic inhibition mediated by the activation of GABAA receptors.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

[Nosocomial epidemic outbreak of acute gastroenteritis by Norwalk-like virus].

BACKGROUND: From the notification of an acute gastroenteritis outbreak in a nursing home, an epidemiological study was started to determine the characteristics of the outbreak and its spreading pattern and to identify determining factors. PATIENTS AND METHOD: A study of historic cohorts was performed and the case was defined by the presence of diarrhea and vomiting. Spatial aggregation in double rooms was analyzed by a binomial distribution and temporal aggregation was analyzed by a relative risks model. The variables in the study allowed us to calculate the adjusted relative risk; the odds ratio was calculated in relation to the meal on day January 30. RESULTS: We studied 95.9% residents. The total attack rate was 28.7% (31.8% employees, 30.1% permanent residents and 15.2% day residents). The attack rate in rotation health personnel was 45.2%. Spatial and temporal spread in double rooms was negative. There was a significant association with the disease in rotator employees (RR = 3.22; CI 95%, 1.30-7.99; p = 0.02). No association was found between eating and disease (OR = 1.5; CI 95%, 0.4-6.1; p = 0.46). Norwalk-like virus was isolated in four faecal samples. CONCLUSIONS: This epidemic outbreak had the characteristic of a nosocomial infection with a likely person-to-person transmission mechanism. The main factor contributing to the spread of the infection was the existence of employees in permanent contact with residents with an important physical and mental impairment, hence highly dependent on the care provided by these health workers.

Acute Disease↗

Analysis of information transmission in the Schaffer collaterals.

Hippocampal region CA1 seems from comparative studies to be particularly important in the primate brain, in addition to being crucial to memory function. Thus, it is an extremely appropriate place to begin a quantitative investigation of the information representation and transmission capabilities of cerebral neural networks. In this study, a mathematical model of the Schaffer collateral projection from CA3 to CA1 is described. From the model, the amount of information that can be conveyed by the Schaffer collaterals is calculated, i.e., the information that a pattern of firing in CA1 conveys about a pattern of firing in CA3, because of the connections between them. The calculation is performed analytically for an arbitrary probability distribution describing the pattern of CA3 firing and then solved numerically for particular input distributions. The effect of a number of issues on the information conveyed is examined. Consideration of the effect of the amount of analog resolution of firing rates in the patterns of activity in CA3 confirmed information transmission to be most efficient for binary codes, to a degree that depends on the sparseness of activity. For very sparse codes, a binary code allows more information to be received even in absolute terms, but for more distributed codes, slightly more information can be received by CA1 by making use of analog resolution. The pattern of convergence of connections from CA3 to CA1 is examined, i.e., the spatial distribution of the number of connections each CA1 neuron receives. It is found that the effect of the difference between a uniform convergence model and a proposed real convergence pattern (Bernard and Wheal, Hippocampus 1994;4:497-529) is minimal. The effect of the ratio of expansion between CA3 and CA1 due to the relative numbers of neurons in these two areas is studied. The Schaffer collaterals in all mammalian species reported in the literature seem to operate in a regime in which there is at least the scope for efficient transfer of information. In addition, the effect of topography (with respect to the transverse hippocampal axis) in the Schaffer collateral connectivity is examined. In the absence of spatial correlations, topography is found to have essentially no effect on information transmission. If spatial correlations in firing were present in CA3 (which, however, would be less efficient for memory storage in the recurrent collaterals), information transmission would be maximized by matching the topographic spread to the spatial scale of correlation.

Animals↗

Optical monitoring of neuronal activity during spontaneous sharp waves in chronically epileptic human neocortical tissue.

Functional changes in neuronal circuitry reflected in spontaneously occurring synchronous sharp field potentials (SSFP) have been reported to occur in human brain suffering from chronic epileptogenicity but not in primary nonepileptic tissue from peritumoral resectates. Voltage sensitive dyes and fast imaging were used to visualize spontaneously occurring rhythmic depolarizations correlated to SSFP in chronically epileptic human neocortical slices obtained during epilepsy surgery. Localized and spatially inhomogeneous neuronal depolarizations were found to underlie spontaneous SSFP, which remained unchanged and spatially restricted to foci <750 micrometer diam even under epileptogenic (low-Mg(2+)) conditions. In cases where ictaform paroxysmal activity occurred in low-Mg(2+) medium, neuronal depolarizations were wide-spread but still spatially inhomogeneous, and the events were preferentially initiated at distinct foci. The findings suggest that small neuronal networks are able to establish and maintain synchronous rhythmic and epileptiform activity.

Action Potentials↗

Iterative three-dimensional expectation maximization restoration of single photon emission computed tomography images: application in striatal imaging.

Single photon emission computed tomography imaging suffers from poor spatial resolution and high statistical noise. Consequently, the contrast of small structures is reduced, the visual detection of defects is limited and precise quantification is difficult. To improve the contrast, it is possible to include the spatially variant point spread function of the detection system into the iterative reconstruction algorithm. This kind of method is well known to be effective, but time consuming. We have developed a faster method to account for the spatial resolution loss in three dimensions, based on a postreconstruction restoration method. The method uses two steps. First, a noncorrected iterative ordered subsets expectation maximization (OSEM) reconstruction is performed and, in the second step, a three-dimensional (3D) iterative maximum likelihood expectation maximization (ML-EM) a posteriori spatial restoration of the reconstructed volume is done. In this paper, we compare to the standard OSEM-3D method, in three studies (two in simulation and one from experimental data). In the two first studies, contrast, noise, and visual detection of defects are studied. In the third study, a quantitative analysis is performed from data obtained with an anthropomorphic striatal phantom filled with 123-I. From the simulations, we demonstrate that contrast as a function of noise and lesion detectability are very similar for both OSEM-3D and OSEM-R methods. In the experimental study, we obtained very similar values of activity-quantification ratios for different regions in the brain. The advantage of OSEM-R compared to OSEM-3D is a substantial gain of processing time. This gain depends on several factors. In a typical situation, for a 128 x 128 acquisition of 120 projections, OSEM-R is 13 or 25 times faster than OSEM-3D, depending on the calculation method used in the iterative restoration. In this paper, the OSEM-R method is tested with the approximation of depth independent resolution. For the striatum this approximation is appropriate, but for other clinical situations we will need to include a spatially varying response. Such a response is already included in OSEM-3D.

Algorithms↗

Predicting the spatial dynamics of rabies epidemics on heterogeneous landscapes.

Often as an epidemic spreads, the leading front is irregular, reflecting spatial variation in local transmission rates. We developed a methodology for quantifying spatial variation in rates of disease spread across heterogeneous landscapes. Based on data for epidemic raccoon rabies in Connecticut, we developed a stochastic spatial model of rabies spread through the state's 169 townships. We quantified spatial variation in transmission rates associated with human demography and key habitat features. We found that large rivers act as semipermeable barriers, leading to a 7-fold reduction in the local rates of propagation. By combining the spatial distribution of major rivers with long-distance dispersal we were able to account for the observed irregular pattern of disease spread across the state without recourse to direct assessment of host-pathogen populations.

Animals↗

Spatial parasite transmission, drug resistance, and the spread of rare genes.

The transmission of many parasitic worms involves aggregated movement between hosts of "packets" of infectious larvae. We use a generic metapopulation model to show that this aggregation naturally promotes the preferential spread of rare recessive genes, compared with the expectations of traditional nonspatial models. A more biologically realistic model also demonstrates that this effect could explain the rapid observed spread of recessive or weakly dominant drug-resistant genotypes in nematode parasites of sheep. This promotion of a recessive trait arises from a novel mechanism of inbreeding arising from the metapopulation dynamics of transmission.

Animals↗

Iterative reconstruction with correction of the spatially variant fan-beam collimator response in neurotransmission SPET imaging.

The dopamine transporter (DAT) has been shown to be a sensitive indicator of nigrostriatal dopamine function. Although visual inspection is often sufficient to assess DAT imaging, quantification could improve the diagnostic accuracy of single-photon emission tomography (SPET) studies of the dopaminergic system. The aim of this study was to assess the accuracy of quantification of the striatal/background uptake ratio when correction for attenuation, scatter and spatially variant fan-beam collimator response is performed in technetium-99m and iodine-123 SPET imaging. A numerical striatal phantom was implemented, and simulated projections of low-energy photons were obtained by using the SimSET Monte Carlo code. High-energy contamination in 123I studies was modelled from experimental measurements with 99mTc and 123I. The ordered subsets expectation maximisation (OSEM) algorithm was employed in reconstruction. Mean improvements of 8% and 16% were obtained in the calculated striatal/background uptake ratio in the putamen and the caudate, respectively, when the spatially variant point spread function was included in the transition matrix. Ideal scatter correction resulted in improvements in the putamen and caudate of 9% for 99mTc agents and 19% for 123I agents. Improvements averaged 31% in the putamen and 43% in the caudate when correction for attenuation, scatter and spatially variant collimator response was included in the reconstruction.

Algorithms↗

The spread of attention and learning in feature search: effects of target distribution and task difficulty.

We examined the roles of two determinants of spatial attention in governing the spread of perceptual learning, namely, stimulus location distribution and task difficulty. Subjects were trained on detection of a target element with an odd orientation imbedded in an array of light bars with otherwise uniform orientation. To assess the effects of target distribution on attention and learning, target positions were distributed so that attention was allocated not only to the target positions themselves, but also to intermediate positions where the target was not presented. Target detection performance substantially improved and improvement spread to match the induced window of spatial attention rather than only the actual target locations. To assess the effect of task difficulty on the spread of attention and learning, the target-distractor orientation difference and the time interval available for processing were manipulated. In addition, we compared performance of subjects with more versus with less detection difficulty. A consistent pattern emerged: When the task becomes more difficult, the window of attention shrinks, and learning becomes more localized. We conclude that task-specific spatial attention is both necessary and sufficient to induce learning. The spread of spatial attention, and thus of learning, is determined by the integrated effects of target distribution and task difficulty. We propose a theoretical framework whereby these factors combine to determine the cortical level of the focus of attention, which in turn enables learning modifications.

Adult↗

Real time monitoring of laser-induced thermal changes in cartilage in vitro by using snapshot FLASH.

Snapshot FLASH imaging has been applied to study the spatial and temporal spreading of thermal changes caused by a Holmium:YAG laser in patella cartilage in vitro at 7 T. The temperature dependence of the proton resonance frequency was used to demonstrate the thermal energy deposition. A series of cartilage images, with a time resolution of 512 ms and a spatial resolution of 400 x 200 microm, showed dynamic changes of the temperature-related image phase in the regions irradiated by the laser.

Cartilage, Articular↗

Nonlinear X waves in second-harmonic generation: experimental results.

X waves, spatiotemporal generalization of the monochromatic Bessel- (or Durnin-) type beams, are known in linear acoustic, microwave and optics for their unique property of defeating both spatial and temporal spreadings. Recently, we brought to the attention that X-type waves are also the key to understand the spatiotemporal dynamics observed in the nonlinear (high intensity) regime. Indeed, X waves represent the normal-propagation mode for a wide class of parametric interactions described by hyperbolic nonlinear models featuring spatial self-focusing and temporal self-broadening. Here, we provide a complete and detailed description of the experiment in which the spontaneous appearance of X waves has been observed. The experiment concerns frequency doubling of a 170-fs, 50-microm standard laser wave packet in a 22-mm lithium triborate crystal, tuned for second-harmonic generation with positive phase mismatch, positive group-velocity dispersion, and large group-velocity mismatch. Conventional beam-profile and autocorrelation measurements at the crystal output face show evidence of spatiotemporal self-trapping. The characterization of the free-space propagation reveals sub-Gaussian diffraction and pulse broadening, consistent with the presence of angular dispersion. Space-resolved autocorrelations indicate the generation of an X-type profile.

Journal Article↗