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Reblurred deconvolution method for chemical shift removal in F-19 (PFOB) MR imaging.

Perfluorocarbons such as perfluoroctylbromide (PFOB) can be used as contrast agents in the vascular system for fluorine-19 magnetic resonance imaging or as synthetic oxygen carriers. F-19 imaging has been proposed for studying the vascular system, capillary flow, tissue perfusion, and tumor oxygenation. A major difficulty is that F-19 compounds often have complex multipeak spectra. These peaks result in chemical shift artifacts, lower signal-to-noise ratios, and blurred images. Each peak also excites a different section when a section-select gradient is applied. Direct inverse filtering is the simplest deconvolution method for correcting such artifacts; however, two major difficulties present themselves: functional singularity and noise amplification at high frequencies. The use of a new reblurred deconvolution (RED) method appears to overcome these problems. Although this method is based on iterative deconvolution in the spatial domain, the computational overhead is negligible. Since the point spread function and object data are already available in the time domain as FID data, RED appears to be useful for eliminating chemical shift artifacts and suppressing noise amplification while restoring the original image without loss of resolution.

Contrast Media↗

Theoretical and experimental evaluation of phase-dispersion effects caused by brain motion in diffusion and perfusion MR imaging.

We investigated intravoxel phase dispersion caused by pulsatile brain motion in diffusion spin-echo pulse sequences. Mathematical models were used to describe the spatial and temporal velocity distributions of human brain motion. The spatial distribution of brain-tissue velocity introduces a phase spread over one voxel, leading to signal loss. This signal loss was estimated theoretically, and effects on observed diffusion coefficient and perfused capillary fraction were assessed. When parameters from a diffusion pulse sequence without motion compensation were used, and ECG triggering with inappropriate delay times was assumed, the maximal signal loss caused by brain-motion-induced phase dispersion was predicted to be 21%. This corresponds to a 95% overestimation of the diffusion coefficient, and the perfusion-fraction error was small. Corresponding calculations for motion-compensated pulse sequences predicted a 1% to 1.5% signal loss due to undesired phase dispersion, whereas experimental results indicated a signal loss related to brain motion of 4%.

Adult↗

Vibratory detection thresholds following a digital nerve lesion.

Vibratory detection thresholds were measured at a number of frequencies between 5 and 320 Hz following a lesion of the lateral digital nerve innervating the terminal phalanx of the left index finger. Thresholds measurements began approximately 4 weeks after the nerve was repaired. A staircase method was used to determine thresholds on both the injured fingerpad and the intact fingerpad of the opposite hand. There was a large increase in thresholds on the injured fingerpad in the lower range of frequencies (5-40 Hz) while at higher frequencies (80-250 Hz) there was no significant difference between the thresholds on the injured fingerpad and those on the intact fingerpad. It is suggested that the differential effect of the nerve lesion on vibratory thresholds reflects the spread of the vibratory stimulus through the skin and the spatial characteristics of functionally intact receptor/afferent groups innervating neighbouring skin.

Fingers↗

Dynamic population epidemic models.

Most multipopulation epidemic models are of the contact distribution type, in which the locations of successive contacts are chosen independently from appropriate contact distributions. This paper is concerned with an alternative class of models, termed dynamic population epidemic models, in which infectives move among the populations and can infect only within their current population. Both the stochastic and deterministic versions of such models are considered. Their threshold behavior is analyzed in some depth, as are their final outcomes. Velocities of spread of infection are considered when the populations have a spatial structure. A criterion for finding the equivalent contact distribution epidemic for any given dynamic population epidemic is provided, enabling comparisons to be made for the velocities and final outcomes displayed by the two classes of models. The relationship between deterministic and stochastic epidemic models is also discussed briefly.

Disease Outbreaks↗

Ca2+ waves in astrocytes.

The glial cell is the most numerous cell type in the central nervous system and is believed to play an important role in guiding brain development and in supporting adult brain function. One type of glial cell, the astrocyte also may be an integral computational element in the brain since it undergoes neurotransmitter-triggered signalling. Here we review the role of the astrocyte in the central nervous system, emphasizing receptor-mediated Ca2+ physiology. One focus is the recent discovery that the neurotransmitter glutamate induces a variety of intracellular Ca2+ changes in astrocytes. Simple Ca2+ spikes or intracellular Ca2+ oscillations often appear spatially uniform. However, in many instances, the Ca2+ rise has a significant spatial dimension, beginning in one part of the cell it spreads through the rest of the cell in the form of a wave. With high enough agonist concentration an astrocyte syncitium supports intercellular waves which propagate from cell to cell over relatively long distances. We present results of experiments using more specific pharmacological glutamate receptor agonists. In addition to describing the intercellular Ca2+ wave we present evidence for another form of intercellular signalling. Some possible functions of a long-range glial signalling system are also discussed.

Aniline Compounds↗

Ca2+ movement in smooth muscle cells studied with one- and two-dimensional diffusion models.

Although many of the processes involved in the regulation of Ca2+ in smooth muscle have been studied separately, it is still not well known how they are integrated into an overall regulatory system. To examine this question and to study the time course and spatial distribution of Ca2+ in cells after activation, one- and two-dimensional diffusion models of the cell that included the major processes thought to be involved in Ca regulation were developed. The models included terms describing Ca influx, buffering, plasma membrane extrusion, and release and reuptake by the sarcoplasmic reticulum. When possible these processes were described with known parameters. Simulations with the models indicated that the sarcoplasmic reticulum Ca pump is probably primarily responsible for the removal of cytoplasmic Ca2+ after cell activation. The plasma membrane Ca-ATPase and Na/Ca exchange appeared more likely to be involved in the long term regulation of Ca2+. Pumping processes in general had little influence on the rate of rise of Ca transients. The models also showed that spatial inhomogeneities in Ca2+ probably occur in cells during the spread of the Ca signal following activation and during the subsequent return of Ca2+ to its resting level.

Animals↗

Spatial sensing in fibroblasts mediated by 3' phosphoinositides.

The directed movement of fibroblasts towards locally released platelet-derived growth factor (PDGF) is a critical event in wound healing. Although recent studies have implicated polarized activation of phosphoinositide (PI) 3-kinase in G protein-mediated chemotaxis, the role of 3' PI lipids in tyrosine kinase-triggered chemotaxis is not well understood. Using evanescent wave microscopy and green fluorescent protein-tagged Akt pleckstrin homology domain (GFP-AktPH) as a molecular sensor, we show that application of a shallow PDGF gradient triggers a markedly steeper gradient in 3' PI lipids in the adhesion zone of fibroblasts. Polar GFP-AktPH gradients, as well as a new type of radial gradient, were measured from front to rear and from the periphery to the center of the adhesion zone, respectively. A strong spatial correlation between polarized 3' PI production and rapid membrane spreading implicates 3' PI lipids as a direct mediator of polarized migration. Analysis of the temporal changes of 3' PI gradients in the adhesion zone revealed a fast diffusion coefficient (0.5 microm(2)/s) and short lifetime of 3' PIs of <1 min. Together, this study suggests that the tyrosine kinase-coupled directional movement of fibroblasts and their radial membrane activity are controlled by local generation and rapid degradation of 3' PI second messengers.

3T3 Cells↗

Cumulant solution of the elastic boltzmann transport equation in an infinite uniform medium

We consider an analytical solution of the time-dependent elastic Boltzmann transport equation in an infinite uniform isotropic medium with an arbitrary phase function. We obtain (1) the exact distribution in angle, (2) the exact first and second spatial cumulants at any angle, and (3) an approximate combined distribution in position and angle and a spatial distribution whose central position and half-width of spread are always exact. The resulting Gaussian distribution has a center that advances in time, and an ellipsoidal contour that grows and changes shape providing a clear picture of the time evolution of the particle migration from near ballistic, through snakelike and into the final diffusive regime.

Journal Article↗

Generalized Wiener estimation of three-dimensional current distribution from biomagnetic measurements.

This paper proposes a method for estimating three-dimensional (3-D) biocurrent distribution from spatio-temporal biomagnetic data. This method is based on the principle of generalized Wiener estimation, and it is formulated based on the assumption that current sources are uncorrelated. Computer simulation demonstrates that the proposed method can reconstruct a 3-D current distribution where the conventional least-squares minimum-norm method fails. The influence of noise is also simulated, and the results indicate that a signal-to-noise ratio of more than 20 for the uncorrelated sensor noise is needed to implement the proposed method. The calculated point spread function shows that the proposed method has very high spatial resolution compared to the conventional minimum norm method. The results of computer simulation of the distributed current sources are also presented, including cases where current sources are correlated. These results suggest that no serious errors arise if the source correlation is weak.

Artifacts↗

Effect of lamotrigine on EEG paroxysmal abnormalities and background activity: a computerized analysis.

1. Little information is available about the action of lamotrigine (LTG) on EEG paroxysmal abnormalities and background activity. On the contrary, several clinical trials have shown the therapeutic efficacy of the drug in preventing partial and generalized seizures. 2. We performed computerized EEG monitoring in 21 patients suffering from focal and generalized epilepsy before and 4 months after addition of LTG. The anticonvulsant modified the EEG ictal events by reducing their frequency and duration. A statistically significant decrease of the interictal spikes was observed. The decrease involved mainly the spreading component of the interictal events leading to a better spatial definition of the epileptic focus. 3. In the presence of LTG, generalized tonic-clonic attacks were completely controlled, whereas partial seizures were decreased. 4. The EEG background activity was not modified by the addition of the drug. 5. Our findings suggest a specific role for LTG in the generation and propagation processes of epileptiform activity without interfering with the EEG background activity.

Adolescent↗

Evaluation of historical factors influencing the occurrence and distribution of Mycobacterium bovis infection among wildlife in Michigan.

OBJECTIVES: To determine historical events leading to establishment of bovine tuberculosis in the white-tailed deer population in the northeastern corner of the lower peninsula (NELP) of Michigan and describe factors relevant to the present outbreak of bovine tuberculosis in Michigan. SAMPLE POPULATION: Cattle and white-tailed deer in Michigan from 1920 to 1990. PROCEDURES: A search of extant historical documents (eg, scientific journals, books, public reports, and correspondence and internal reports from governmental agencies) was conducted. Factors investigated included the number of cattle and prevalence of tuberculosis, deer population and density levels, and changes in regional environments affecting the population and management of cattle and wild deer. RESULTS: High deer numbers and severe winter feed shortages resulting from habitat destruction in the NELP in 1930 contributed to the transmission of tuberculosis from cattle to deer. Starvation increased the susceptibility of deer to infection and modified behavior such that exposure to infected cattle was increased. Relocation of deer resulted in spread of infection to other sites, including locations at which spatial clusters of tuberculosis presently exist. Ribotyping of Mycobacterium bovis from a human patient suggests that the strain of M. bovis presently infecting white-tailed deer in the region is the same strain that affected cattle farms at that time. CONCLUSIONS AND CLINICAL RELEVANCE: Feeding deer to maintain numbers above the normal carrying capacity of the NELP led to deer depending on consumption of livestock feed for survival during winter and increased contact with domestic cattle. This practice should be avoided.

Animals↗

Understanding Puccinia striiformis West. epidemics on winter wheat.

Yellow rust epidemics, caused by Puccinia striiformis West., often arise in wheat field as infection focus of a few decimetres of diameter, including some sporulating lesions on a few plants. Under appropriate environmental conditions such as high relative humidity and temperatures between 2 and 20 degrees C, those initial foci may grow rapidly and initiate new foci elsewhere in the field. The first aim of this work was to better understand the effects of weather parameters on the focus growth. An experiment was conducted in a wheat field during the 2001 season to measure, from inoculated plants, the disease progression related to climatic conditions (temperature, relative humidity, precipitations and wind). Three plots were inoculated in March and the sporulating lesions around each focus were monitored every week on 8 segments starting from the centre of the plot, by recording the infected leaf layers and the spatial position of every infected plant. Once established, the disease spread not only horizontally, by spore transport from plants to plants, but also vertically, by spore dispersal from lower leaf layers to upper ones. The focus required a build up period, with diseased plants confined to a circle of maximum 3 m diameter around the centre with the inoculated plants, before a widespread expansion. This initial build up period required at least two generations. On base of the changes of the disease status observed every week and the calculation of the latent period, the supposed infection dates and the environmental factors responsible for those infections were determined. This allowed adjustment of an infection forecasting model based on weather data. These results will be integrated into a decision support system to control the disease before the occurrence of large scale inoculum dispersion.

Forecasting↗

Spread of synchronous firing in longitudinal slices from the CA3 region of the hippocampus.

1. Mechanisms underlying the propagation of synchronous epileptiform activity in disinhibited hippocampal slices were examined in experimental and computer simulation studies. 2. Experiments were performed with longitudinal slices of the CA3 region. Synchronous firing was initiated by stimulating stratum radiatum fibers in the presence of picrotoxin. It propagated smoothly and without decrement at velocities close to 0.15 m/s over distances up to 10 mm. 3. In elevated extracellular calcium, neuronal firing threshold was increased and synchronous burst firing did not spread. Monophasic excitatory postsynaptic potentials (EPSPs) were recorded in cells at limited distances from a stimulus in the presence of 10 mM Ca and picrotoxin. Axonal conduction velocity, estimated from EPSP latencies, was several times faster than the spread of synchronous firing. 4. EPSPs recorded in 5-7 mM Ca and picrotoxin could consist of two components. The properties of the first component were similar to those of synaptic events recorded in 10 mM Ca. The second component was of longer latency and unlike the first component was suppressed in responses to paired stimuli at interval 50-300 ms. Recordings from cells at different distances from a stimulus suggested that the second component spread further and more slowly than the first component. 5. In computer simulations the CA3 region was represented by a spatially distributed network of 9,000 excitatory neurons and 900 inhibitory cells. Individual cells and synapses had properties based on experimental data. The effects of varying synaptic strength and connectivity on the spread of activity in the model was examined. 6. When synaptic inhibition was functional in simulations, firing was restricted to a single action potential in model cells close to the stimulus, as in experiments. Synchronous burst firing spread throughout the neuronal array when fast synaptic inhibition was absent. The velocity of propagation was slower than conduction in simulated axons when synaptic contacts made by excitatory cells were spatially limited. Propagation velocity increased with increases in the spatial extent of excitatory connectivity. 7. Increasing the threshold of neurons in a region of the model network reduced the speed at which synchronous firing spread. In experiments focal application of gamma-aminobutyric acid (GABA) elevated neuronal firing threshold and slowed the propagation of synchrony in a local region. 8. As the strength of synaptic inhibition was gradually reduced, neuronal activity spread further and faster through the simulated neuronal network.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

A fractal model of HIV transmission on complex socio-geographic networks. Part 2: spread from a ghettoized 'core group' into a 'general population'.

"Study of the initial stages of HIV transmission along a 'sociogeographic network'--a large, complex, spatially focused social network with possibly fractal geometry--is extended to include interaction between a low-dimensional ghettoized 'core group' within which the disease spreads very rapidly and a higher dimensional, more loosely structured 'general population' in which spread is relatively slow. A mathematical modeling exercise suggests that contextually modulated interaction between them can be highly nonlinear and may greatly increase the initial rate of disease transmission within the general population. This work contributes to a growing body of literature which suggests that programs to control HIV infection within the majority heterosexual population of the United States will fail spectacularly without particular focus on the coupled physical and social stabilization and rehabilitation of the urban ghettoes of marginalized populations which are the present, and rapidly expanding, disease epicenters. Evidence suggests their continued disintegration can both increase disease rates within the epicenters and increase the coupling between core groups and general populations by creating large numbers of spatially or economically displaced refugees."

Americas↗

Spatial effects favour the evolution of niche construction.

We present an individual-based, spatial implementation of an existing two-locus population genetic model of niche construction. Our analysis reveals that, across a broad range of conditions, niche-construction traits can drive themselves to fixation by simultaneously generating selection that favours 'recipient' trait alleles and linkage disequilibrium between niche-construction and recipient trait alleles. The effect of spatiality is key, since it is the local, resource-mediated interaction between recipient and niche-constructing loci which gives rise to gene linkage. Spatial clustering effects point to a possible mechanism by which an initially rare recipient trait whose selection depends on niche construction could establish in an otherwise hostile environment. The same mechanism could also lead to the spread of an established niche-constructing colony. Similar phenomena are observed in the spatial modelling of two species 'engineering webs'. Here, the activities of two niche-constructing species can combine to drive a particular recipient trait to fixation, or in certain circumstances, maintain the presence of polymorphisms through the preservation of otherwise deleterious alleles. This may have some relevance to ecosystem stability and the maintenance of genetic variation, where the frequencies of key resources are affected by the niche-constructing activities of more than one species. Our model suggests that the stability of multi-species webs in natural populations may increase as the complexity of species-environment interactions increases.

Biological Evolution↗

Localized synaptic actions of neurotrophin-4.

Neurotrophins secreted by the postsynaptic target cell may participate in activity-dependent synaptic modification during development and in the mature brain. A fundamental question of how neurotrophins can sculpt synaptic connections is whether neurotrophin-induced synaptic changes are spatially restricted to the site of neurotrophin secretion or whether they can spread to neighboring synapses. Using a model system of nerve-muscle coculture in which neurotrophin-4 (NT-4) is overexpressed in a subpopulation of postsynaptic myocytes, we demonstrated that presynaptic potentiation is restricted to synapses on myocytes overexpressing NT-4 without affecting nearby synapses formed by the same neuron on control myocytes. Likewise, postsynaptic modulation of acetylcholine channels by secreted NT-4 is spatially restricted to <60 micron from the site of NT-4 secretion. Therefore, activity-dependent secretion of neurotrophins can result in highly localized modification of neuronal connections.

Animals↗

Exploring the limits of spatial memory in rats, using very large mazes.

In Experiment 1, rats foraged for food in six successive phases with 8, 16, 24, 32, 40, and 48 arms attached in random locations to a large radial maze. The percentage of novel choices appeared to be determined more by spatial proximity than by number of arms. In Experiment 2, rats foraged for food in four successive phases with 8, 16, 24, and 48 arms attached to the maze in spread-out or tight configurations. Performance was poor in the tight configurations regardless of the number of arms. Performance was excellent in the 8-arm spread-out condition but declined as 16 and, then again, 24 arms were added. Thus, spatial separation, not number of locations, was the chief determinant of performance in the first two experiments. In Experiment 3, in successive phases, 8, 16, 24, 32, 40, 48, 16, and 8 food towers were set in a circle on the floor, with the spatial separation between adjacent towers held constant at 33 cm. The percentage of novel choices declined as 8 towers became 16 and did not change again with 24, 32, 40, or 48 towers in place but then increased again as 16 towers became 8. In Experiment 4, in successive phases, 8, 16, 24, and 32 food towers were set in a circle, with the spatial separation between adjacent towers held constant at 66 cm. The percentage of novel choices declined as 8 towers became 16 and again as 16 towers became 24 but did not decline further. These data were discussed in terms of the fundamental problems posed by variations in the number of food locations in the pursuit of the limit of spatial memory in rats.

Animals↗

Three dimensional reconstruction of a human breast carcinoma using routine laboratory equipment and immunohistochemistry.

AIMS: To establish a three dimensional reconstruction of an invasive breast carcinoma using basic laboratory equipment to evaluate and characterise the spatial arrangement of the parenchymal cells of the breast. METHODS: One hundred and twenty eight sequential 4 microm sections (20 microm apart) of the tumour were stained immunohistochemically with an epithelial specific marker (AE1/AE3) or tumour specific marker (c-erbB-2) to reconstruct two different three dimensional images of the normal and malignant parenchymal cells. Sections were digitally imaged using a microscope, scanner, and digital camera linked to a conventional personal computer. Accurate alignment of the digitalised images was carried out using a semiautomatic graphical method of manual interaction, using the cross correlation coefficient as a goodness of fit measure, and an automatic search algorithm using the Fibonacci search algorithm for automatic alignment. The volume was reconstructed using maximum, minimum point projection and "back to front" opacity blending. RESULTS: The quality of the reconstructed images was distinct and perfect, providing a comprehensive and explicit view of the normal and malignant parenchymal tissues of the breast that is not possible by viewing two dimensional histological sections. Specifically, this approach showed the spatial arrangement of the tumour cells and their relation to the surrounding tissues at a high resolution. CONCLUSION: This simple and reproducible approach enables the spread and infiltration of invasive carcinoma to be understood and could also be used to analyse the spatial relation between atypical hyperplastic and malignant in situ lesions of the breast.

Biomarkers, Tumor↗