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Some physical factors influencing the accuracy of convolution scatter correction in SPECT.

Some important physical factors influencing the accuracy of convolution scatter correction techniques in SPECT are presented. In these techniques scatter correction in the projection relies on filter functions, QF, evaluated by Fourier transforms, from measured scatter functions, Qp, obtained from point spread functions. The spatial resolution has a marginal effect on Qp. Thus a single QF can be used in the scatter correction of SPECT measurements acquired with the low energy high resolution or the low energy general purpose collimators and over a wide range of patient-collimator distances. However, it is necessary to examine the details of the shape of point spread functions during evaluation of Qp. QF is completely described by scatter amplitude AF, slope BF and filter sum SF. SF is obtained by summation of the values of QF occupying a 31 x 31 pixels matrix. Regardless of differences in amplitude and slope, two filter functions are shown to be equivalent in terms of scatter correction ability, whenever their sums are equal. On the basis of filter sum, the observed small influence of ellipticity on QF implies that an average function can be used in scatter correcting SPECT measurements conducted with elliptic objects. SF is shown to increase with a decrease in photon energy and with an increase in window size. Thus, scatter correction by convolution may be severely hampered by photon statistics when SPECT imaging is done with low-energy photons. It is pointless to use unnecessarily large discriminator windows, in the hope of improving photon statistics, since most of the extra events acquired will eventually be subtracted during scatter correction. Regardless of the observed moderate reduction in SF when a lung-equivalent material replaces a portion of a water phantom, further studies are needed to develop a technique that is capable of handling attenuation and scatter corrections simultaneously. Whenever superficial and inner radioactive distributions coexist the observed reduction of SF close to the phantom surface indicates that scatter correction of such distributions has to rely on two distinct filter functions. Corrections based on a surface function produce accurate results in the superficial region, while the central distributions are substantially overestimated. Surface radioactive distributions introduce appreciable errors in the determination of central distributions when corrections are based on central filter function. This function introduces a reduction of about 40% in the measured surface concentration.

Humans↗

In vivo tracing of pathways and spatio-temporal activity patterns in rat visual cortex using voltage sensitive dyes.

We monitored optical signals from cortex stained with a voltage sensitive dye to study activity evoked by intracortical electrical stimulation. The objectives were to study the spatial and temporal spread of activity from intrinsic connections near the stimulating electrode and to develop a new technique to study extrinsic projections from striate cortex to extrastriate target areas. Various measures were made of the time course of the optical signal (latency, rise time, decay time, temporal summation, facilitation versus depression, and presence or absence of a slow undershoot); in general, these measures were found to vary significantly across different response positions, different experiments, and even different runs within the same experiment. The spatial distribution of responses near the stimulating electrode in striate cortex was usually elliptical and was most often elongated along the anterior-posterior axis, with a typical size (full width at 75% max) of 1.3 mm (anterior-posterior axis) by 0.75 mm (medio-lateral axis). In some cases, complex spatio-temporal patterns were observed, in which the position of the maximum optical signal shifted with time or split into multiple peaks. In eight experiments, a response focus was found in extrastriate cortex at an expected location within the lateromedial area (LM). The response focus in LM was typically about half the size of that in striate cortex. In some experiments we observed additional focal responses in the anterolateral visual area (AL). The extrastriate responses showed a significant delay (3-10 ms) in onset and time to peak relative to the striate response. The validity of this technique for determining extrinsic projections was tested in two types of experiments. In the first, stimulation from two electrodes in striate cortex generated response foci consistent with the known topographic organization of area LM. In the second, the optically measured response focus was shown to correlate with the histologically reconstructed projection of a chemical tracer injected near the site of stimulation. We discuss the chain of neurophysiological events that occur during and after focal electrical stimulation and how they relate to the observed optical signal. We conclude that direct passive responses were a small component of our signal, that the component due to action potentials in directly stimulated neurons should have occurred in the first 1-2 ms post stimulus and is small compared to the peak signal, and that overall our signals were probably dominated by a combination of asynchronously occurring action potentials and excitatory and inhibitory synaptic potentials.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Color appearance: the effects of illumination and spatial pattern.

The color we perceive at each point in an image depends on information spread across the three spatial arrays of cone photoreceptors. I describe experiments aimed at clarifying how information is integrated across the spatial arrays to yield a color experience. We have found that changes of color appearance due to changes of the ambient illumination and the pattern's spatial frequency can be described by using a simple set of optical and neural transformations. Each transformation can be thought of as having two parts. First, the transformation converts the color representation into a new coordinate frame that is independent of the image contents. Second, the transformation scales the neural responses in the new coordinate frame by a gain factor that depends on the image contents.

Color↗

A modelling framework to describe the spread of scrapie between sheep flocks in Great Britain.

My aim was to develop a stochastic, spatial model describing the spread of scrapie between sheep flocks in Great Britain; I wanted a model, which could subsequently be used to assess the efficacy of different control strategies. The structure of the model reflects the demography of the British sheep flock, including a description of the contact structure between flocks. The dynamics of scrapie were incorporated through two probabilities associated with each flock: of acquiring infection and of experiencing a within-flock outbreak following exposure. The acquisition of infection depends on whether or not a flock buys-in sheep and, if it does, whether or not it trades with an affected flock. Once a flock is exposed, the probability of a within-flock outbreak occurring and its duration depend on the basic reproductive number, the prion-protein (PrP) genotype profile and the flock size. The model was validated using regional data from two postal surveys conducted in 1998 and 2002, which demonstrated that the model captures the spatial dynamics of scrapie (at least at a regional level). Moreover, the predicted distribution for the duration of a within-flock outbreak reflects the duration of outbreaks reported in the literature. Using the model to predict long-term trends in the proportion of affected flocks suggested that, even without control measures beyond the removal of animals with clinical signs, scrapie ultimately will disappear from the national flock, though it is likely to be decades before the disease is eliminated. However, there were scenarios consistent with the available data which suggested that scrapie could remain endemic within the British sheep flock. Consequently, it is essential to take this uncertainty in the long-term dynamics of scrapie into account when considering the efficacy of control strategies. Although control strategies were not explicitly examined, the model suggests two aspects important for control: larger flocks remain affected for longer and provide infection for other, smaller flocks and animal movements must be traceable.

Animals↗

Spatial patterns of protein expression in focal infections of human cytomegalovirus.

Human cytomegalovirus (HCMV) is a medically significant human pathogen that infects a wide range of cell and tissue types. During infection, HCMV activates a variety of signal transduction pathways that induce profound changes in cellular processes and dramatically affect cellular gene expression patterns. To better define how these virus-host interactions affect the local microenvironment and influence the spatial and temporal spread of HCMV, we initiated HCMV focal infections on normal human dermal fibroblast monolayers and monitored viral gene expression patterns and infection spread over 45 days. To establish baseline temporal measurements of HCMV infection and spread in cell monolayers, we characterized the influence of three experimental variables on viral gene expression: cell plating density, the presence of serum, and neutralization of cellular antiviral responses with an antibody against interferon-beta. We found that high cell plating density or the inclusion of serum correlated with enhanced HCMV infection spread. Dramatic differences in the expression pattern of the viral immediate early 2 (IE2) gene were observed under these conditions as compared to low plating density or the absence of serum. In the latter case round, uniform foci were observed with a clear wave of IE2 expression visible in advance of a late stage viral protein, envelope glycoprotein B. By contrast, larger irregular foci with arms of IE2 expression were observed in the presence of serum. Addition of the antibody had little effect on the rate of spread, which is consistent with the knowledge that HCMV represses antiviral responses during infection. This experimental system provides a useful means to visualize and quantify complex virus-host interactions.

Antibodies↗

Rapid measurement of time-averaged blood flow using ungated spiral phase-contrast.

A novel ungated spiral phase-contrast (USPC) imaging method was developed for rapid measurement of time-averaged blood-flow rates in the presence of pulsatility. The spatial point-spread function was analyzed to provide an intuitive understanding of how spiral trajectories, which sample the k-space origin at every excitation, can mitigate the effects of pulsatility. Pulsatile flow phantom experiments were performed to validate the accuracy and repeatability of the USPC method. The measurement of flow in the renal and femoral arteries of normal volunteers were also performed. The phantom results (error < or = +9%, SD(phantom) < or = 2%, time-averaged pulsatile-flow rates = 3-15 ml/s) and in vivo results (SD(renal) < or = 8%, SD(femoral) < or = 14%) demonstrate the potential of the USPC method for rapidly and repeatedly measuring accurate time-averaged blood flow even in relatively small arteries and in the presence of strong pulsatility.

Blood Flow Velocity↗

Different patterns of the L-histidine decarboxylase (HDC) gene expression in mice resistant and susceptible to experimental cutaneous leishmaniasis.

OBJECTIVE AND DESIGN: In the present study the experimental murine Leishmania major ( L. major) infection model was used to investigate the role of histamine biosynthesis in cutaneous leishmaniasis. SUBJECTS, TREATMENT AND METHODS: A novel RNase Protection Assay (RPA) was developed and applied for the assessment of L-histidine decarboxylase (HDC) gene expression in organs of resistant C57BL/6 and susceptible BALB/c mice after infection with L. major. RESULTS: In the acute phase of infection a rapid but transient induction of HDC expression was observed in the infected lymph nodes of both strains correlating both temporally and spatially with parasite spread. The signal was present in the draining popliteal lymph nodes of both hosts, however, only susceptible mice known to be unable to control parasite dissemination showed induction of HDC in their distant periaortic lymph nodes as well. During the chronic phase of infection only the heavily parasitized organs of BALB/c mice showed high HDC gene expression. CONCLUSIONS: These data suggest that expression of the histamine-producing enzyme HDC in the decisive acute phase of leishmaniasis is not coupled with development of either appropriate Th1 or inadequate Th2 responses to L. major. We hypothesize, however, that during the chronic phase of infection elevated HDC levels, possibly of mast cell origin, are associated with Th2-dominated responses and serious disease development.

Acute Disease↗

A prototype high-resolution animal positron tomograph with avalanche photodiode arrays and LSO crystals.

To fully utilize positron emission tomography (PET) as a non-invasive tool for tissue characterization, dedicated instrumentation is being developed which is specially suited for imaging mice and rats. Semiconductor detectors, such as avalanche photodiodes (APDs), may offer an alternative to photomultiplier tubes for the readout of scintillation crystals. Since the scintillation characteristics of lutetium oxyorthosilicate (LSO) are well matched to APDs, the combination of LSO and APDs seems favourable, and the goal of this study was to build a positron tomograph with LSO-APD modules to prove the feasibility of such an approach. A prototype PET scanner based on APD readout of small, individual LSO crystals was developed for tracer studies in mice and rats. The tomograph consists of two sectors (86 mm distance), each comprising three LSO-APD modules, which can be rotated for the acquisition of complete projections. In each module, small LSO crystals (3.7 x 3.7 x 12 mm3) are individually coupled to one channel within matrices containing 2x8 square APDs (2.6 x 2.6 mm2 sensitive area per channel). The list-mode data are reconstructed with a penalized weighted least squares algorithm which includes the spatially dependent line spread function of the tomograph. Basic performance parameters were measured with phantoms and first experiments with rats and mice were conducted to introduce this methodology for biomedical imaging. The reconstructed field of view covers 68 mm, which is 80% of the total detector diameter. Image resolution was shown to be 2.4 mm within the whole reconstructed field of view. Using a lower energy threshold of 450 keV, the system sensitivity was 350 Hz/MBq for a line source in air in the centre of the field of view. In a water-filled cylinder of 4.6 cm diameter, the scatter fraction at the centre of the field of view was 16% (450 keV threshold). The count rate was linear up to 700 coincidence counts per second. In vivo studies of anaesthetized rats and mice showed the feasibility of in vivo imaging using this PET scanner. The first LSO-APD prototype tomograph has been successfully introduced for in vivo animal imaging. APD arrays in combination with LSO crystals offer new design possibilities for positron tomographs with finely granulated detector channels.

Animals↗

Three-dimensional endoluminal ultrasound: a new method for the evaluation of gastrointestinal tumors.

BACKGROUND: The purpose of the present study was to evaluate the feasibility of three-dimensional endoluminal ultrasound of gastrointestinal tumors. METHODS: Sixteen patients with esophageal, gastric, or colorectal tumors underwent endoscopic ultrasound. Three-dimensional ultrasound data were obtained from multiple serial images of a miniprobe (360 degrees, 12.5 MHz) and processed on a PC-based 3D workstation. RESULTS: Adequate three-dimensional ultrasound scans were obtained in eight patients with esophageal cancer and five patients with colorectal cancer. Three-dimensional image processing enabled visualization of the data as a multiplanar display or as a life-like three-dimensional view. The availability of arbitrary scan planes improved the assessment of local tumor spread and the spatial relation of the tumor to relevant adjacent structures (e.g., major vessels). Three-dimensional presentations provided realistic views of the anatomy and facilitated the interpretation of the ultrasound images. CONCLUSIONS: Three-dimensional display and the ability to review endoluminal ultrasound data interactively may improve the staging of gastrointestinal tumors. These preliminary data encourage further evaluation of this technique.

Artifacts↗

Seed, dispersal, microsite, habitat and recruitment limitation: identification of terms and concepts in studies of limitations.

Recently, there is an increase in number of studies concerned with the effect of various types of limitations on species local population size and distribution pattern at the landscape scale. The terminology used to describe these limitations is, however, very inconsistent. Since the different terms often appear in conclusions of the papers, the inconsistency in their use obscures the message of these papers. In this study, we review the current uses of these terms, identify the basic concepts involved in the discussion of a limitation and link the concepts with the currently used terms. Finally, we discuss the experimental approaches used to assess the different types of limitations. We differentiated four basic concepts resulting from the combination of limitation by environment versus ability to grow and spread, and two spatial scales (local and regional scale). The two concepts at each spatial scale are expected to form a gradient of all possible combinations of the two respective types of limitations. In the considerations of various experimental approaches used to assess these limitations, we conclude that sowing experiments, i.e. seed addition into existing populations or seed introduction into unoccupied habitats, are the only reliable types of evidence for the different types of limitations.

Biodiversity↗

Autoimmune epitopes: autoepitopes.

The identity of reactants for autoantibodies has been successively refined from whole cellular organelles (immunofluorescence), identified molecules (immunoblot; gene expression libraries), epitope regions (truncated cDNAs; peptide scanning) to contact residues, as described here. Most autoantibodies react with conformational epitopes, in which amino acids distant in the linear sequence come into contiguity by protein folding. Identification of contact sites with the antibody paratope requires particular technologies, crystallography, or antibody screening of phage-displayed random peptide libraries. The latter is illustrated by our studies on the autoepitope for anti-PDC-E2 (AMA) in primary biliary cirrhosis (PBC), anti-GAD65 in type 1 diabetes, and anti-C1 of type II collagen in collagen-induced arthritis. More precise definition of the structure of conformational autoepitopes could (a) clarify controversial aspects of autoimmunity including epitope mimicry, epitope spreading, and molecular spatial relationships between B and T cell autoepitopes, and (b) impact on novel diagnostic and therapeutic (vaccine) molecules.

Animals↗

Quarantine in a multi-species epidemic model with spatial dynamics.

Motivation is provided for the development of infectious disease models that incorporate the movement of individuals over a range of spatial scales. A general model is formulated for a disease that can be transmitted between different species and multiple patches, and the behavior of the system is investigated in the case in which the spatial component consists of a ring of patches. The influence of various parameters on the spatial and temporal spread of the disease is studied numerically, with particular focus on the role of quarantine in the form of travel restriction.

Algorithms↗

Combinatorial decomposition of an outbreak signature.

We use mathematically rigorous definitions of epidemiological concepts in order to derive a sequential combinatorial model of disease outbreak decomposition. We define the idea of a population specific 'disease signature' and use this in order to decompose and further understand outbreaks as incidents of spatial and temporal spread of disease exposure both in, and across, populations. This allows us to differentiate between different disease spread scenarios with a level of sensitivity that previous models were unable to provide. This perspective leads us to propose a new practical definition for 'outbreak'. In addition, we are able to use this model to understand, estimate, and, in some cases, correct for, the likely instances of reporting error inherent in disease surveillance. We demonstrate our model first with a hypothetical outbreak scenario and then in an analysis of suspected outbreaks of waterborne diseases in Massachusetts (MA) in 1995.

Adult↗

Receptors, second messengers and protein kinases required for heterosynaptic cerebellar long-term depression.

Raising the frequency and intensity of stimulation to one of two sets of parallel fibre synaptic inputs to cerebellar Purkinje cells results in a localised calcium influx and a long-term depression (LTD) of parallel fibre-Purkinje cell responses. Although the calcium influx remains spatially constrained, depression spreads heterosynaptically to distant sites. Inhibition of the synthetic enzyme for cGMP, guanylate cyclase, did not significantly affect the overall level of calcium-dependent synaptic depression observed at the site of raised stimulation (test site), but it entirely prevented synaptic depression at the distant (control) site. Inhibition of protein kinase G produced identical results. In contrast, protein kinase A inhibition had no effect. Selective inhibition of either metabotropic glutamate receptors (mGluRs), protein kinase C (PKC) or tyrosine protein kinase (PTK) blocked depression at both sites equally effectively. These data reveal that two, inter-dependent cellular pathways capable of inducing cerebellar LTD exist. The levels of PF stimulation required to induce heterosynaptic depression were similar to those used routinely in more widely accepted models of LTD. The data predict that cerebellar long-term depression will not be input specific at the single cell level under those conditions of PF-activation that give rise to NO/cGMP production.

Animals↗

Separation of the glucose-stimulated cytoplasmic and mitochondrial NAD(P)H responses in pancreatic islet beta cells.

Two-photon excitation microscopy was used to image and quantify NAD(P)H autofluorescence from intact pancreatic islets under glucose stimulation. At maximal glucose stimulation, the rise in whole-cell NAD(P)H levels was estimated to be approximately 30 microM. However, because glucose-stimulated insulin secretion involves both glycolytic and Kreb's cycle metabolism, islets were cultured on extracellular matrix that promotes cell spreading and allows spatial resolution of the NAD(P)H signals from the cytoplasm and mitochondria. The metabolic responses in these two compartments are shown to be differentially stimulated by various nutrient applications. The glucose-stimulated increase of NAD(P)H fluorescence within the cytoplasmic domain is estimated to be approximately 7 microM. Likewise, the NAD(P)H increase of the mitochondrial domain is approximately 60 microM and is delayed with respect to the change in cytoplasmic NAD(P)H by approximately 20 sec. The large mitochondrial change in glucose-stimulated NAD(P)H thus dominates the total signal but may depend on the smaller but more rapid cytoplasmic increase.

Animals↗

Visual attention to surfaces in three-dimensional space.

Although attention plays a significant role in vision, its spatial deployment and spread in the third dimension is not well understood. In visual search experiments we show that we cannot easily focus attention across isodepth loci unless they are part of a well-formed surface with locally coplanar elements. Yet we can easily spread our attention selectively across well-formed surfaces that span an extreme range of stereoscopic depths. In cueing experiments, we show that this spread of attention is, in part, obligatory. Attentional selectivity is reduced when targets and distractors are coplanar with or rest on a common receding stereoscopic plane. We conclude that attention cannot be efficiently allocated to arbitrary depths and extents in space but is linked to and spreads automatically across perceived surfaces.

Attention↗

Axonal injury in children after motor vehicle crashes: extent, distribution, and size of axonal swellings using beta-APP immunohistochemistry.

The brains of 32 children (3 months to 16 years) who died as a result of motor vehicle collisions were examined for axonal injury using beta-APP immunohistochemistry. The extent and distribution of axonal injury was assessed and quantified throughout the forebrain, brainstem and cerebellum. The mean diameter of immunoreactive axons in the corpus callosum was measured for this pediatric group and, for comparison, a small adult sample. beta-APP immunoreactivity was seen in 14 pediatric cases (survival 35 mins to 87 h), most frequently in the parasagittal white matter (12/14), the corpus callosum (11/14), the brainstem (10/14) and cerebellum (9/14). In 2 cases, axon swelling was visualized in the internal capsule after only 35-45-min survival, earlier than has previously been reported. No immunoreactivity was seen in the remaining 18 cases who died within 1 h. The extent and distribution of axonal injury throughout the brain showed a rapid early increase with increasing survival time and then a slower progression. The diameter of individual callosal axons increased with increasing survival times, rapidly over the first 24 h and then more slowly. There was no statistical difference (p < 0.05) for callosal axon diameters at different survival times between the children and the adults sampled here. The extent and distribution of axonal injury throughout the brain appears to be similar in children to that previously reported in adults. The spatial and temporal spread of axonal damage suggests there may be therapeutic potential for the process to be arrested or slowed in its early stages.

Accidents, Traffic↗

Wavelet tree quantization for copyright protection watermarking.

This paper proposes a wavelet-tree-based blind watermarking scheme for copyright protection. The wavelet coefficients of the host image are grouped into so-called super trees. The watermark is embedded by quantizing super trees. The trees are so quantized that they exhibit a large enough statistical difference, which will later be used for watermark extraction. Each watermark bit is embedded in perceptually important frequency bands, which renders the mark more resistant to frequency based attacks. Also, the watermark is spread throughout large spatial regions. This yields more robustness against time domain geometric attacks. Examples of various attacks will be given to demonstrate the robustness of the proposed technique.

Algorithms↗