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Results for “Spatial heterogeneity”

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PubMed2000

Heterogeneity of cerebral blood flow: a fractal approach.

AIM: We demonstrate the heterogeneity of regional cerebral blood flow using a fractal approach and single-photon emission computed tomography (SPECT). METHOD: Tc-99m-labelled ethylcysteine dimer was injected intravenously in 10 healthy controls and in 10 patients with dementia of frontal lobe type. The head was imaged with a gamma camera and transaxial, sagittal and coronal slices were reconstructed. Two hundred fifty-six symmetrical regions of interest (ROIs) were drawn onto each hemisphere of functioning brain matter. Fractal analysis was used to examine the spatial heterogeneity of blood flow as a function of the number of ROIs. RESULTS: Relative dispersion (= coefficient of variation of the regional flows) was fractal-like in healthy subjects and could be characterized by a fractal dimension of 1.17 +/- 0.05 (mean +/- SD) for the left hemisphere and 1.15 +/- 0.04 for the right hemisphere, respectively. The fractal dimension of 1.0 reflects completely homogeneous blood flow and 1.5 indicates a random blood flow distribution. Patients with dementia of frontal lobe type had a significantly lower fractal dimension of 1.04 +/- 0.03 than in healthy controls. CONCLUSION: Within the limits of spatial resolution of SPECT, the heterogeneity of brain blood flow is well characterized by a fractal dimension. Fractal analysis may help brain scientists to assess age-, sex- and laterality-related anatomic and physiological changes of brain blood flow and possibly to improve precision of diagnostic information available for patient care.

Aged↗

PubMed1993

Spatial features of calcium transients during early and delayed afterdepolarizations.

Although changes in intracellular Ca2+ concentration ([Ca2+]i) are spatially heterogeneous during spontaneous contraction in mammalian cardiac muscle, it has not yet been observed how [Ca2+]i changes spatially within cardiac myocytes during delayed (DADs) and early (EADs) afterdepolarizations. The aim of this study is to characterize the spatial features of the increase in [Ca2+]i during such afterdepolarizations and to understand the ionic mechanisms responsible for them. Myocytes were enzymatically isolated from guinea pig ventricles and loaded with fura 2-acetoxymethylester, the Ca2+ fluorescence indicator dye. Membrane potential was recorded with a conventional microelectrode technique, and spatiotemporal changes in fura 2 fluorescence and cell length were recorded using a digital television system. After superfusion with potassium-free Tyrode solution, DADs and EADs were induced. During DADs, fluorescence transients were heterogeneous within myocytes (n = 11). Furthermore, they often propagated within myocytes as if they were "waves." In contrast, during EADs, fluorescence transients showed no waves within myocytes but rather showed synchronous changes throughout the myocytes (n = 15). The results of this study suggest that the spatial features of the increase in [Ca2+]i differ between the DADs and EADs. We concluded from these differing features that the ionic mechanisms responsible for the two triggered activities are different.

Animals↗

PubMed1986

Efferent projections of nucleus locus coeruleus: topographic organization of cells of origin demonstrated by three-dimensional reconstruction.

The present study examines the spatial distribution within rat locus coeruleus of neurons projecting to particular brain regions. In order to accurately recreate, in digital and pictorial formats, the spatial distribution of neurons for the entire nucleus locus coeruleus, three-dimensional reconstructions were created which specified the location of each individual Nissl-stained locus coeruleus cell in each of five nuclei. Dynamic computerized displays were visually analyzed and statistically compared. The nuclei from different brains were found to be strikingly similar in density and distribution of cells. In order to determine whether the cells of origin for particular locus coeruleus projections were clustered within the nucleus, reconstructions were created of the distributions of cells labeled by injections of a retrograde tracer, horseradish peroxidase, into particular terminal regions. Groups consisting of animals with injections into the same target areas were visually and statistically compared. The cells of origin of most efferent projections were found to be spatially organized within locus coeruleus. Specifically, projections to both the dorsal and ventral hippocampus originated solely from the dorsal segment of the nucleus, while spinal cord projections originated from ventral-posterior locus coeruleus. Cells of origin of cerebral and cerebellar cortical efferents, as well as hypothalamic efferents, exhibited less clustering, although reliable differences in distribution were observed. The most striking example of clustered cells of origin was exhibited by the large norepinephrine-containing cells constituting the anterior pole of locus coeruleus which were labeled only by hypothalamic injections. This analysis of spatial organization within locus coeruleus is unique in its utilization of a defined control group, experimental groups consisting of strictly defined replications, accurate three-dimensional reconstruction, and statistical comparisons. The demonstrated spatial heterogeneity of locus coeruleus neurons with respect to efferent projections can now be compared to the spatial distributions of other cellular characteristics such as soma morphology, colocalized transmitters and physiological properties. Presumably, such spatial segregation reflects the operation of functionally important organizing principles within the nucleus.

Animals↗

PubMed2006

The use of ambient air quality modeling to estimate individual and population exposure for human health research: a case study of ozone in the Northern Georgia Region of the United States.

Ambient monitors are commonly used to estimate exposure for epidemiological studies, and air quality modeling is infrequently applied. However air quality modeling systems have the potential to alleviate some, although not all, of the limitations of monitoring networks. To investigate this application, exposure estimates were generated for a case study high ozone episode in the Northern Georgia Region of the United States based on measurements and concentration estimates from an air quality modeling system. Hourly estimates for 2268 4-km by 4-km gridcells were generated in a domain that includes only eight ozone monitors. Individual and population-based ozone exposures were estimated using multiple approaches, including area-weighted average of modeled estimates, nearest monitor, and spatial interpolation by inverse distance weighting and kriging. Results based on concentration fields from the air quality modeling system revealed spatial heterogeneity that was obscured by approaches based on the monitoring network. With some techniques, such as spatial interpolation, monitoring data alone was insufficient to estimate exposure for certain areas, especially for rural populations. For locations far from ozone monitors, the estimates from the nearest monitor approach tended to overestimate exposure, compared to modeled estimates. Counties in which one or more monitors were present had statistically higher population density and modeled ozone estimates than did counties without monitors (p-value <0.05). This work demonstrates the use of air quality modeling to generate higher spatial and temporal resolution exposure estimates, and compares the advantages of this approach to traditional methods that use monitoring data alone. The air quality modeling method faces its own limitations, such as the need to thoroughly evaluate concentration estimates and the use of ambient levels rather than personal exposure.

Environmental Exposure↗

PubMed2003

Dynamic heterogeneities in the out-of-equilibrium dynamics of simple spherical spin models.

The response of spherical two-spin interaction models, the spherical ferromagnet (s-FM) and the spherical Sherrington-Kirkpatrick (s-SK) model, is calculated for the protocol of the so-called nonresonant hole burning (NHB) experiment for temperatures below the respective critical temperatures. It is shown that it is possible to select dynamic features in the out-of-equilibrium dynamics of both models, one of the hallmarks of dynamic heterogeneities. The behavior of the s-SK model and the s-FM model in three dimensions is very similar, showing dynamic heterogeneities in the long-time behavior, i.e., in the aging regime. The appearance of dynamic heterogeneities in the s-SK model explicitly demonstrates that these are not necessarily related to spatial heterogeneities. For the s-FM model, it is shown that the nature of the dynamic heterogeneities changes as a function of dimensionality. With the increasing dimension, the frequency selectivity of the NHB diminishes and the dynamics in the mean-field limit of the s-FM model becomes homogeneous.

Journal Article↗

PubMed2026

Longitudinal In Vivo Imaging at Single-Lesion Resolution Identifies Allele-Associated Response and Resistance Dynamics in EGFR-Mutant Lung Cancer.

Acquired resistance to targeted therapies is inevitable in EGFR-mutant non-small cell lung cancer (NSCLC), yet the principles governing its emergence in vivo remain incompletely understood. In particular, how lesion-level response patterns vary across distinct EGFR allele contexts during therapy has not been systematically examined at single-lesion resolution. Here, we establish a longitudinal in vivo imaging platform enabling single-lesion resolution tracking of tumor behavior during therapy in genetically engineered mouse models representing clinically relevant EGFR alleles. Using high-resolution micro-computed tomography (micro-CT) and three-dimensional reconstruction, we monitor tumor growth, therapeutic response, and resistance during osimertinib treatment. EGFR genotype is associated with distinct patterns of tumor growth, response kinetics, and resistance timing. Therapeutic response is spatially heterogeneous, with coexisting lesions undergoing complete regression, persistence, or progression within the same lung. During treatment, spatially distinct lesion-level behaviors included persistent growth during therapy and initial regression followed by regrowth. These findings demonstrate the utility of longitudinal micro-CT imaging to investigate allele-associated differences in treatment response and resistance timing at single-lesion resolution in vivo.

Animals↗

PubMed2001

The evolution of dispersal rates in a heterogeneous time-periodic environment.

A reaction-diffusion model for the evolution of dispersal rates is considered in which there is both spatial heterogeneity and temporal periodicity. The model is restricted to two phenotypes because of technical difficulties, but a wide range of mathematical techniques and computational effort are needed to obtain useful answers. We find that the question of selection is a great deal richer than in the autonomous case, where the phenotype with the lowest diffusion is selected for. In the current model either the lower or higher diffuser rate may be selected, or there may be coexistence of phenotypes. The paper raises several open questions and suggests in particular that a mutation-selection multi-phenotypic model would repay study.

Animals↗

PubMed2006

A systematic investigation of the rate laws valid in intracellular environments.

Recently there has been significant interest in deducing the form of the rate laws for chemical reactions occurring in the intracellular environment. This environment is typically characterized by low-dimensionality and a high macromolecular content; this leads to a spatial heterogeneity not typical of the well stirred in vitro environments. For this reason, the classical law of mass action has been presumed to be invalid for modeling intracellular reactions. Using lattice-gas automata models, it has recently been postulated [H. Berry, Monte Carlo simulations of enzyme reactions in two dimensions: Fractal kinetics and spatial segregation, Biophys. J. 83 (2002) 1891-1901; S. Schnell, T.E. Turner, Reaction kinetics in intracellular environments with macromolecular crowding: simulations and rate laws, Prog. Biophys. Mol. Biol. 85 (2004) 235-260] that the reaction kinetics is fractal-like. In this article we systematically investigate for the first time how the rate laws describing intracellular reactions vary as a function of: the geometry and size of the intracellular surface on which the reactions occur, the mobility of the macromolecules responsible for the crowding effects, the initial reactant concentrations and the probability of reaction between two reactant molecules. We also compare the rate laws valid in heterogeneous environments in which there is an underlying spatial lattice, for example crystalline alloys, with the rate laws valid in heterogeneous environments where there is no such natural lattice, for example in intracellular environments. Our simulations indicate that: (i) in intracellular environments both fractal kinetics and mass action can be valid, the major determinant being the probability of reaction, (ii) the geometry and size of the intracellular surface on which reactions are occurring does not significantly affect the rate law, (iii) there are considerable differences between the rate laws valid in heterogeneous non-living structures such as crystals and those valid in intracellular environments. Deviations from mass action are less pronounced in intracellular environments than in a crystalline material of similar heterogeneity.

Fractals↗

PubMed2000

Pollen availability for predaceous mites on apple: spatial and temporal heterogeneity.

It has been suggested that an abundance of alternate food early in the spring may be critical to the ability of generalist predaceous mites to suppress spider mite pests. One alternate food that is typically very abundant in spring is wind-dispersed pollen. Here we investigate, at several spatial scales, the heterogeneity in the availability of pollen to predaceous mites on apple. We found pollen to be abundant on apple leaves very soon after they opened (> 100 grains/cm2), and that the dominant pollen types at this time were wind-dispersed tree pollens (Betulaceae and Pinaceae). We found that most of the spatial variation in pollen abundance occurred at either small spatial scales (within trees) or very large spatial scales (among orchard blocks). Variability among orchards was clearly influenced by the surrounding vegetation, and probably also by the management regime (frequency of mowing). Spatial heterogeneity in pollen availability may affect the build-up of predatory mite populations in the spring, as we found early season abundances of Typhlodromus pyri (Phytoseiidae) and Zetzellia mali (Stigmaeidae) to be better correlated with early season pollen density than with abundance of mite prey (Aculus schlechtendali).

Animals↗

PubMedDate not supplied

Analysis of sampling volume and tissue heterogeneity on the in vivo detection of fluorescence.

The effect of sampling region size and tissue heterogeneity is examined using fluorescence histogram assessment in a rat prostate tumor model with benzoporphyrin derivative fluorophore. Spatial heterogeneity in the fluorescence signal occurs on both macroscopic and microscopic scales. The periphery of the tumor is more fluorescent than the center. Fluorescence is also highest nearest the blood vessels immediately after injection, but over time this fluorescence becomes uniform through the tumor tissue. Using microscopy analysis, the fluorescence intensity histogram distributions follow a normal distribution, yet as the sampling area is increased from the micron scale to the millimeter scale, the variance of the distribution decreases. The mean fluorescence intensity is accurately measured with a millimeter size scale, but this cannot provide accurate measurements of the microscopic variance of drug in tissue. Fiber probe measurements taken in vivo are used to confirm that the variance observed is smaller than would be expected with microscopic sampling, but that the average fluorescence can be measured with fibers. Sampling tissue with fibers smaller than the intercapillary spacing could provide a way to estimate the spatial variance more accurately. In summary, sampling fiber size affects the fluorescence intensities detected and use of multiple region microscopic sampling could provide better information about the distribution of values that occur.

Algorithms↗

PubMedDate not supplied

Annual Plasmodium falciparum entomological inoculation rates (EIR) across Africa: literature survey, Internet access and review.

This paper presents the results of an extensive search of the formal and informal literature on annual Plasmodium falciparum entomological inoculation rates (EIR) across Africa from 1980 onwards. It first describes how the annual EIR data were collated, summarized, geo-referenced and staged for public access on the internet. Problems of data standardization, reporting accuracy and the subsequent publishing of information on the internet follow. The review was conducted primarily to investigate the spatial heterogeneity of malaria exposure in Africa and supports the idea of highly heterogeneous risk at the continental, regional and country levels. The implications for malaria control of the significant spatial (and seasonal) variation in exposure to infected mosquito bites are discussed.

Africa↗

PubMed2005

Dynamical heterogeneity close to the jamming transition in a sheared granular material.

The dynamics of a bidimensional dense granular packing under cyclic shear is experimentally investigated close to the jamming transition. Measurement of multipoint correlation functions are produced. The self-intermediate scattering function, displaying slower than exponential relaxation, suggests dynamic heterogeneity. Further analysis of four point correlation functions reveal that the grain relaxations are strongly correlated and spatially heterogeneous, especially at the time scale of the collective rearrangements. Finally, a dynamical correlation length is extracted from a spatiotemporal pattern of mobility. Our experimental results open the way to a systematic study of dynamic correlation functions in granular materials.

Journal Article↗

PubMed2003

Infrared microspectroscopic imaging maps the spatial distribution of exogenous molecules in skin.

Infrared (IR) microscopic imaging is used, in a series of proof-of-principle experiments to map the spatial distribution of two penetration enhancers, dimethylsulphoxide (DMSO) and propylene glycol, in skin. The current instrumentation utilizes a 64 x 64 array of IR detectors imaged at the focal plane of an IR microscope, each collecting a complete mid-infrared spectrum of the skin section on each pass of the interferometer. The spatial area sampled by each element in the array is approximately 6.3 x 6.3 microm. Any spectral parameter (e.g., arising from lipid or protein vibrational modes of the endogenous tissue or the exogenous component) may be quantitatively analyzed across the entire array of 4096 spectra, thereby generating an IR spectroscopic image of that particular parameter throughout the sample. The images directly reveal the spatial heterogeneity of the protein and lipid distributions. In transverse slices of skin, the depth dependencies of the spatial distribution of triglyceride and protein have been monitored, and compared to those of the exogenous penetration enhancers. Images of both DMSO and propylene glycol suggest that each penetrates the skin to a depth of at least 1 mm (under our experimental protocols), and reveals a spatial distribution that is essentially coincident with the protein constituents of the skin. These results demonstrate that IR microscopic imaging has great potential for mechanistic studies of topical, dermal, and transdermal delivery.

Animals↗

PubMed2005

Adaptive migratory divergence among sympatric brook charr populations.

Ecological processes clearly contribute to population divergence, yet how they interact over complex life cycles remains poorly understood. Notably, the evolutionary consequences of migration between breeding and non-breeding areas have received limited attention. We provide evidence for a negative association between interpopulation differences in migration (between breeding and feeding areas, as well as within each) and the amount of gene flow (m) among three brook charr (Salvelinus fontinalis) populations inhabiting Mistassini Lake, Quebec, Canada. Individuals (n = 1166) captured throughout lake feeding areas over two consecutive sampling years were genotyped (10 microsatellites) and assigned to one of the three populations. Interpopulation differences in migration were compared based on spatial distribution overlap, habitat selection, migration distance within feeding areas, and morphology. We observed a temporally stable, heterogeneous spatial distribution within feeding areas among populations, with the extent of spatial segregation related to differential habitat selection (represented by littoral zone substrate). Spatial segregation was lowest and gene flow highest (m = 0.015) between two populations breeding in separate lake inflows. Segregation was highest and gene flow was lowest (mean m = 0.007) between inflow populations and a third population breeding in the outflow. Compared to outflow migrants, inflow migrants showed longer migration distances within feeding areas (64-70 km vs. 22 km). After entering natal rivers to breed, inflow migrants also migrated longer distances (35-75 km) and at greater elevations (50-150 m) to breeding areas than outflow migrants (0-15 km; -10-0 m). Accordingly, inflow migrants were more streamlined with longer caudal regions, traits known to improve swimming efficiency. There was no association between the geographic distance separating population pairs and the amount of gene flow they exchanged. Collectively, our results are consistent with the hypothesis that reduced gene flow between these brook charr populations results from divergent natural selection leading to interpopulation differences in migration. They also illustrate how phenotypic and genetic differentiation may arise over complex migratory life cycles.

Animal Migration↗

PubMed2001

Heterogeneity of metabolic activity in the canine parasternal intercostals during breathing.

In the dog, the inspiratory mechanical advantage of the parasternal intercostals shows a marked spatial heterogeneity, whereas the expiratory mechanical advantage of the triangularis sterni is relatively uniform. The contribution of a particular respiratory muscle to lung volume expansion during breathing, however, depends both on the mechanical advantage of the muscle and on its neural input. To evaluate the distribution of neural input across the canine parasternal intercostals and triangularis sterni, we have examined the distribution of metabolic activity among these muscles in seven spontaneously breathing animals by measuring the uptake of the glucose tracer analog [(18)F]fluorodeoxyglucose (FDG). FDG uptake in any given parasternal intercostal was greatest in the medial bundles and decreased rapidly toward the costochondral junctions. In addition, FDG uptake in the medial parasternal bundles increased from the first to the second interspace, plateaued in the second through fifth interspaces, and then decreased progressively toward the eighth interspace. In contrast, uptake in the triangularis sterni showed no significant rostrocaudal gradient. These results overall strengthen the idea that the spatial distribution of neural input within a particular set of respiratory muscles is closely matched with the spatial distribution of mechanical advantage.

Animals↗

PubMed2004

[Heterogeneity of small intestinal microcirculation].

INTRODUCTION: Microcirculatory disorders play important roles in the impairment of the mucosal barrier of the small intestine. Circulatory failures may increase the heterogeneity of microvascular perfusion, however, conventional methods are inadequate to describe an evolving heterogeneity in time or space. The authors aims were to examine and characterize the microcirculatory reactions in the mucosa and longitudinal muscle of the small intestine in clinically relevant experimental models of circulatory disorders. METHODS: Intravital videomicroscopy with orthogonal polarization spectral imaging technique was used to visualize the microcirculation. A mathematical approach was applied to describe the temporal variability in perfusion based on the calculation of average red blood cell velocity from the relative time periods of observed velocity, while spatial heterogeneity was calculated as a function of the perfused area. The authors' experiments were performed after 1. sham operation, 2. during hemorrhagic shock and crystalloid resuscitation, 3. during 2-hr endotoxin infusion, 4. in response to nitric oxide synthesis inhibition, and 5. after superior mesenteric artery occlusion and reperfusion. RESULTS: During hemorrhagic shock a fluctuating flow pattern appeared in the mucosa, the average red blood cell velocity decreased by 40% in the villi and by 60% in the muscle. Ischemia caused 20% flow reduction in both layers, while endotoxin caused a temporary 20% decrease in the mucosa, and a persistent, over 25% decrease in the muscle layer. Nitric oxide synthesis inhibition resulted in a 40% decrease in both structures. CONCLUSIONS: Heterogeneity of microcirculatory perfusion may appeared both spatially (between or within anatomical layers) and in time (periodically) after the insults. A redistribution of blood flow favouring the mucosa evolves in the small intestine after systemic circulatory disorders. Heterogenous perfusion-related microcirculatory changes can be characterized with mathematical approaches, and these calculations should be taken into account during the comparison of the consequences of distinct circulatory failures involving the small intestine.

Animals↗

PubMed2006

Tick-borne encephalitis in the Baltic States: identifying risk factors in space and time.

This paper presents preliminary results in our investigations of the biological (abiotic and biotic) and non-biological causes of the spatial heterogeneity and temporal change of tick-borne encephalitis (TBE), both within and between Estonia, Latvia, and Lithuania. Spatial analysis revealed that the land cover and precise seasonal patterns of climatic indices (temperature and normalized difference vegetation index) can explain 55% of the observed spatial variation in TBE incidence over the period 1993-98 across all the Baltic States. Temporal analysis of climatic variables indicates a very specific change in spring temperature conditions from 1993 onwards that could enhance the transmission of TBE virus. Further time series analysis of climate, together with analysis of biotic factors, socio-economic conditions, and human behaviour is being undertaken to explain the epidemiological patterns more fully.

Animals↗

PubMed2002

Heterogeneous hepatic enhancement on CT angiography in idiopathic portal hypertension.

BACKGROUND: Idiopathic portal hypertension is an uncommon condition characterized by presinusoidal portal perfusion disturbance without known causes. METHODS: In the present study, portal and arterial perfusion dynamics were evaluated in two cases with idiopathic portal hypertension using computed tomography during arterial portography and hepatic arteriography. Ten cases with liver cirrhosis were also studied as a reference. RESULTS: In cases with idiopathic portal hypertension, portal perfusion was conspicuously heterogeneous and decreased especially at the periphery of the liver where arterial perfusion was reciprocally increased. When the spatial heterogeneity of an enhancement of the liver was quantified using a densitometric analysis of computed tomography during hepatic arteriography images, the densities at the periphery were higher and varied more than those of the inner areas in cases with idiopathic portal hypertension. In contrast, the densities did not vary between the periphery and the inner areas at the cases with liver cirrhosis. CONCLUSIONS: The heterogeneous increase of arterial perfusion in periphery of the liver may be an important feature of idiopathic portal hypertension.

Adult↗