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A comparison of count rate parameters in gamma cameras.

Pulse pile-up is a fundamental problem that limits the ability of a gamma camera to produce high quality images at high count rates. Pulse pile-up results in loss of events and spatial distortions in the image. The question asked in this study is how well do some of the test procedures for measuring count rate performance in gamma cameras compare. In four gamma cameras we compared measurements of spectral fraction, count-rate curve, pulse-pair resolution, deadtime, maximum count rate, full width at half maximum of the line spread function, and misplaced event count rate. The results indicated that no one technique provides a complete description of the count-rate effects in gamma cameras. The misplaced-event measurements provided the most information.

Evaluation Studies as Topic↗

Three-dimensional correction for spillover and recovery of myocardial PET images.

UNLABELLED: PET permits the quantification of myocardial blood flow, but is hampered by the limited spatial resolution of PET images. METHODS: We evaluated two methods for the correction of resolution effects in PET perfusion 13NH3-ammonia images. In one model, the spillover and recovery coefficients are estimated in the kinetic modeling analysis. The new, second model uses an explicit delineation of the left ventricular wall and a convolution model for the system point spread function to compute the regional values of the spillover and recovery coefficients. RESULTS: The new method is validated with phantom measurements. The two methods are evaluated on animal experiments using 13NH3-ammonia. Both two- and three- compartment models were used to compute absolute flow values. Excellent linear correlations with microsphere data were obtained. The slope of the regression line was lower for corrections based on kinetic modeling as compared to convolution-based correction. In animal experiments, recovery coefficients of 59% for the myocardial wall and 86% for the blood pool were obtained. Spillover from the blood pool into the myocardial was was 14%. CONCLUSION: The new correction method strongly suppresses spillover and recovery effects due to limited resolution.

Algorithms↗

A hypothesis about the decline of fertility: evidence from the United States.

The author examines the relationships among fertility decline, urbanization, and the increase in personal autonomy in the United States during the nineteenth century. "Urbanization was consistently negatively correlated with the level of fertility in 1810, 1860, 1920, and 1940. Urbanization was not significantly correlated with the decline of fertility in the period, i.e. from 1800 to 1860; from 1860 to 1920; and from 1920 to 1940. For the period from 1800 to 1860, however, the decline was closely associated with a proxy variable for what is called the spirit of autonomy, i.e., a feeling of control over one's life. It is hypothesized that this sense of control extended to control over fertility. After 1860 the ideas became so widespread that they were no longer associated with any particular group, region, religion, or class. It was just a matter of time until the ideas spread slowly to all groups." (SUMMARY IN FRE)

Americas↗

Periodic calcium waves cross ascidian eggs after fertilization.

Ascidian eggs respond to fertilization with one to two dozen periodic calcium pulses (J.E. Speksnijder, D.W. Corson, C. Sardet, and L.F. Jaffe, 1989a, Dev. Biol. 135, 182-190). We examined the spatial pattern of these pulses and found that they are initiated in discrete regions from which they propagate as waves. The first few pulses start in the animal hemisphere, whereas the later ones are mostly initiated near the vegetal pole. Such vegetal waves are often followed by a contraction of the egg surface. Since these waves are attenuated as they spread, they repeatedly expose the vegetal pole region to more calcium. The mechanism of these repetitive calcium waves and their possible role in establishing pattern or completing meiosis is discussed.

Animals↗

Visualizing the cortical representation of whisker touch: voltage-sensitive dye imaging in freely moving mice.

Voltage-sensitive dye imaging resolves the spatiotemporal dynamics of supragranular subthreshold cortical activity with millisecond temporal resolution and subcolumnar spatial resolution. We used a flexible fiber optic image bundle to visualize voltage-sensitive dye dynamics in the barrel cortex of freely moving mice while simultaneously filming whisker-related behavior to generate two movies matched frame-by-frame with a temporal resolution of up to 2 ms. Sensory responses evoked by passive whisker stimulation lasted longer and spread further across the barrel cortex in awake mice compared to anesthetized mice. Passively evoked sensory responses were large during behaviorally quiet periods and small during active whisking. However, as an exploring mouse approached an object while whisking, large-amplitude, propagating cortical sensory activity was evoked by active whisker-touch. These experiments demonstrate that fiber optics can be used to image cortical sensory activity with high resolution in freely moving animals. The results demonstrate differential processing of sensory input depending upon behavior.

Anesthesia, General↗

Peripubertal refinement of the intrinsic and associational circuitry in monkey prefrontal cortex.

The peripubertal elimination of axospinous synapses and dendritic spines in monkey prefrontal cortex suggests that this region undergoes substantial reorganization during late postnatal development. Understanding the functional impact of these maturational refinements requires knowledge of the specific presynaptic elements involved in these changes. Two potential sources of these presynaptic terminals are the intrinsic axon collaterals furnished by pyramidal cells within a region and the associational axons that arise from pyramidal neurons in other cortical regions in the same hemisphere. In the adult, both of these types of axon terminals form synapses predominantly with dendritic spines on other pyramidal neurons, and thus they may be preferentially involved in the peripubertal pruning of axospinous synapses and dendritic spines. In order to test this hypothesis, iontophoretic injections of the anterograde tracer biotinylated dextran amine were made into the superficial layers of areas 9 or 46 of the prefrontal cortex of four prepubertal juvenile (14.9-21.5 months old) and three young adult macaque monkeys. Tangential reconstructions revealed a stripe-like pattern of labeled terminals for intrinsic and associational projections in both juvenile and adult animals. During puberty, the intrinsic circuitry underwent extensive topographic refinement, as demonstrated by a 42.7% decrease in stripe area and a 28.0% increase in gap distance between stripes. Furthermore, the mediolateral tangential spread of labeled stripes around the injection site decreased by 27.0%. In contrast, topographic refinement was not evident in the associational circuitry. In both layers 1 and 3, the densities of varicosities and branch points on labeled axons decreased by about 50% in intrinsic stripes during puberty, but only by approximately 30% in associational stripes. These findings suggest that the spatial form and magnitude of peripubertal refinements in prefrontal cortical connectivity may be specific for certain neural elements.

Aging↗

A role for sugar transporters during seed development: molecular characterization of a hexose and a sucrose carrier in fava bean seeds.

To analyze sugar transport processes during seed development of fava bean, we cloned cDNAs encoding one sucrose and one hexose transporter, designated VfSUT1 and VfSTP1, respectively. sugar uptake activity was confirmed after heterologous expression in yeast. Gene expression was studied in relation to seed development. Transcripts were detected in both vegetative and seed tissues. In the embryo, VfSUT1 and VfSTP1 mRNAs were detected only in epidermal cells, but in a different temporal and spatial pattern. VfSTP1 mRNA accumulates during the midcotyledon stage in epidermal cells covering the mitotically active parenchyma, whereas the VfSUT1 transcript was specific to outer epidermal cells showing transfer cell morphology and covering the storage parenchyma. Transfer cells developed at the contact area of the cotyledonary epidermis and the seed coat, starting first at the early cotyledon stage and subsequently spreading to the abaxial region at the late cotyledon stage. Feeding high concentrations of sugars suppressed both VfSUT1 expression and transfer cell differentiation in vitro, suggesting a control by carbohydrate availability.

Carbohydrate Metabolism↗

Spatiotemporally differential inhibition of pyramidal cells in the cat motor cortex.

1. The spatiotemporal pattern of inhibition in the cat motor cortex was studied in in vitro slice preparations in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 2-amino-5-phosphonovaleric acid (APV). 2. After intracortical microstimulation (0.5-6 microA), fast and slow inhibitory postsynaptic potentials (IPSPs) were produced in layers II-VI pyramidal cells and selectively reduced with bicuculline methiodide and phaclofen, respectively. 3. Fast IPSPs were maximally produced by stimulation of the same layer where their cell bodies were located, and they decreased in amplitude as the more superficial layer was stimulated. In contrast, slow IPSPs were maximally produced by stimulation of layer II regardless of the location of the recorded pyramidal cell and decreased in amplitude as the deeper layer was stimulated. 4. The reduction of amplitude of fast IPSPs, in response to a vertical shift of the stimulation site toward more superficial layers, was always correlated with an increase in rise time and with a shift of the reversal potential to a more hyperpolarized level. 5. When the stimulation site was moved horizontally to the more lateral site, fast IPSPs increased in latency and decreased in amplitude gradually without appreciable changes in rise time. Fast IPSPs could be evoked from horizontally remote sites of up to 800-1,200 microns. 6. Inhibitory interneurons, which are responsible for evoking fast IPSPs, appear to be distributed through almost all layers to send horizontally spreading parallel axons making synaptic contacts at different electrotonic distances along apical dendrites of single pyramidal cells. 7. Horizontal spreads were much less in slow IPSPs (< 340-680 microns). The time-to-peak of slow IPSPs produced in layer V pyramidal cells (159.5 +/- 6.8 ms, mean +/- SD, n = 10) was significantly (P < 0.0001) longer than that in layers II and III pyramidal cells (128.5 +/- 7.5 ms, n = 7). Asymmetric reversal properties of slow IPSPs were seen, suggesting the spatial dispersion of synaptic inputs along apical dendrites of pyramidal cells. 8. In layer V pyramidal cells, the time-to-peak of slow IPSPs decreased with increasing membrane hyperpolarization, indicating that the later portion of slow IPSPs was more sensitive to the membrane-potential change than the early portion. This further indicates that the late portion of slow IPSPs is generated at synapses on the more proximal dendrite of pyramidal cells than the early portion, contrary to that expected from the Rall's model of passive dendrite under the condition of synchronous inputs.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗

Three levels of lateral inhibition: A space-time study of the retina of the tiger salamander.

The space-time patterns of activity generated across arrays of retinal neurons can provide a sensitive measurement of the effects of neural interactions underlying retinal activity. We measured the excitatory and inhibitory components associated with these patterns at each cellular level in the retina and further dissected inhibitory components pharmacologically. Using perforated and loose patch recording, we measured the voltages, currents, or spiking at 91 lateral positions covering approximately 2 mm in response to a flashed 300-microm-wide bar. First, we showed how the effect of well known lateral inhibition at the outer retina, mediated by horizontal cells, evolved in time to compress the spatial representation of the stimulus bar at ON and OFF bipolar cell bodies as well as horizontal cells. Second, we showed, for the first time, how GABA(C) receptor mediated amacrine cell feedback to bipolar terminals compresses the spatial representation of the stimulus bar at ON bipolar terminals over time. Third, we showed that a third spatiotemporal compression exists at the ganglion cell layer that is mediated by feedforward amacrine cells via GABA(A) receptors. These three inhibitory mechanisms, via three different receptor types, appear to compensate for the effects of lateral diffusion of activity attributable to dendritic spread and electrical coupling between retinal neurons. As a consequence, the width of the final representation at the ganglion cell level approximates the dimensions of the original stimulus bar.

Action Potentials↗

Dynamic infrared functional mapping of the cerebral cortex.

Although many neuroimaging methods (computer tomography, H+ and isotope clearance, [14C]deoxyglucose utilization, potential-sensitive dyes, electroencephalogram and magnetoencephalogram-mapping, nuclear magnetic resonance tomography, single photon emission computer tomography, and positron emission tomography) are now being used to map brain structure and function, there still exists a need for a new approach that is functional, dynamic, remote, and noninvasive, and that also has reasonable sensitivity and spatial and temporal resolution. Such a method is described here. Thermoencephaloscopy (TES), based on thermovision and digital image processing techniques, is a method of neuroimaging consisting of recording through the intact skull the very weak changes in infrared radiation that are connected with brain activity. The parameters of the method are: temperature sensitivity of 0.002 degrees C, instrumental spatial resolution of 70 microns pixel-1, and instrumental temporal resolution of 40 ms (enabling up to twenty-five maps to be produced per second). The distribution over the rat cerebral cortex of local, multiple, and modally and regionally specific thermoresponses to various sensory stimuli, direct cortical stimulation, and associative learning (conditioning), have been studied, as well as the spreading of thermowaves over the brain cortex. The underlying mechanisms which form the basis of the technique of TES, such as joule heating, local changes in brain metabolism and local cerebral blood flow, as well as the formation of thermodipoles, are discussed.

Animals↗

Asymmetric gap junctional coupling between glial cells in the rat retina.

Gap junctional communication between glial cells is thought to play a role in K+ spatial buffering, in the propagation of inter-astrocytic Ca2+ waves, and in glial-neuronal signaling. In the present study, we characterize dye coupling between astrocytes, and between astrocytes and Müller cells, in the isolated rat retina. Whole-cell patch recordings were obtained from retinal astrocytes and Müller cells and the cells filled with Lucifer Yellow and neurobiotin. Spread of Lucifer Yellow to two to ten neighboring astrocytes occurred in 90% of the astrocyte recordings. After fixation and incubation of the retina with fluorescent conjugated streptavidin, neurobiotin was seen to label clusters of 13-88 astrocytes, as well as > 100 Müller cells. In contrast, when Müller cells were filled with Lucifer Yellow and neurobiotin, both tracers were confined solely to the recorded Müller cell. The uncoupling agents octanol, halothane, and doxyl-stearic acid were tested for their ability to uncouple retinal glia in situ. All three agents eliminated the visible spread of Lucifer Yellow from the injected astrocyte and the spread of neurobiotin into Müller cells. However, only doxyl-stearic acid combined with octanol eliminated the spread of neurobiotin between astrocytes. These results demonstrate that astrocytes in the rat retina are coupled to each other and to Müller cells. The astrocyte-to-Müller cell coupling is asymmetric, allowing transfer of the tracer in the forward direction only. In addition, astrocyte-to-Müller cell coupling is more sensitive to the uncoupling agents tested than is astrocyte-to-astrocyte coupling.

1-Octanol↗

Voltage-sensitive dye imaging of neocortical spatiotemporal dynamics to afferent activation frequency.

The spatial and temporal patterns of neocortex activation are determined not only by the dynamic character of the input but also by the intrinsic dynamics of the cortical circuitry. To study the role of afferent input frequency on cortical activation dynamics, the electrical activity of in vitro neocortex slices was imaged during white-matter electrical stimulation. High-speed optical imaging was implemented using voltage-sensitive dyes in guinea pig visual and somatosensory cortex slices concomitantly with intracellular recordings. Single white-matter electrical stimuli activated well-defined cortical sites with a radially oriented columnar configuration. This configuration was followed, over the next few milliseconds, by a lateral spread of excitation through cortical layers 5 and 6 and layers 2 and 3. Much of the optical response was eliminated in low extracellular calcium, indicating that it was primarily synaptically mediated. Repetitive stimuli at 10 Hz reproduced the spatiotemporal pattern observed for single stimuli. In contrast, repetitive stimulation in the gamma frequency range ( approximately 40 Hz) rapidly restrained the area of excitation to a small columnar site directly above the stimulating electrode. Intracellular recordings from cells lateral to the activated column revealed increased inhibitory synaptic activity and/or decreased excitatory responses during the train at 40 Hz, but not during a 10 Hz stimulation. Localized microinjections of GABA(A) antagonist produced a reorganization of the geometrical activity pattern that was dependent on the position of the microinjection site. These findings indicate that the frequency-dependent spatial organization of neocortex activation is determined by inhibitory sculpting attributable to local network dynamics.

Afferent Pathways↗

Spatial patterns and travelling waves in population genetics.

We consider a reaction-diffusion equation to model a multi-allelic, single locus problem. The population can migrate in a homogeneous region and the diffusion rates depend upon the genotype. It is shown that if there is an equilibrium point with all alleles present and if this polymorphism is stable for the classical reaction system then it is also stable for the reaction-diffusion equation. Also a simplified model is used to investigate which allele will spread in the two-allele case. Alleles which are associated with large fitness and small dispersion do best.

Alleles↗

Optical signals from neurons with internally applied voltage-sensitive dyes.

We carried out experiments to monitor optically the generation and spread of action potentials and subthreshold potentials in the processes of individual neurons in ganglia of the snail, Helix aspersa. The neurons were selectively stained by intracellular pressure injection of voltage-sensitive dyes. Optical signals were detected by a system for fast, multiple-site optical monitoring, utilizing a silicon photodiode array. After testing 30 voltage-sensitive dyes using absorption, we concluded that this mode was probably not sensitive enough to allow monitoring neuronal signals from distal processes. Satisfactory signals were obtained in fluorescence measurements using a newly synthesized styryl dye, JPW1114, specifically designed for intracellular application. There was an improvement in sensitivity (as defined by the signal-to-noise ratio) by a factor of about 50 over previously reported absorption and fluorescence signals from neuronal processes stained by either intra- or extracellular application of dyes. Recordings with good signal-to-noise ratio and adequate spatial and temporal resolution were obtained simultaneously from the cell body and long axonal branches. From this data, the site of action potential initiation was determined. Also, the propagation velocity of the action potential was calculated for different axonal segments; the results suggest that different regions have different velocities ranging from 0.53 m/sec to 0.07 m/sec. The present sensitivity was adequate to allow the recording of a 10 mV hyperpolarizing electrotonic response along axonal branches and to observe directly the decline of this passive response with distance from the site of stimulation. Relatively modest improvements in sensitivity will allow systematic analyses of the spread and summation of synaptic potentials in individual neurons.

Action Potentials↗

Organization of the cytoskeleton in square fibroblasts.

The relationship between the cytoskeleton, stress fiber formation, and cell shape has been difficult to determine in fibroblasts grown in tissue culture. Vagaries in cell shape are complicated, as well, by stochastic cell movements. We dictated the attachment sites and shape of fibroblasts by growing them on square adhesive substrates surrounded by nonadhesive substrates. Cytoskeletal models were made by treating the cells with buffered Triton X-100 and glycerol. The residues were then examined by scanning electron microscopy followed by light microscopy of the same cells. The cytoskeletons of randomly moving cells were examined with whole mount transmission microscopy to confirm images seen with scanning microscopy. The cells thus examined demonstrated definite relationships between ruffling activity and stress fiber terminations, which were limited to the more adhesive, palladium substrate. No stress fibers were seen to end on the lesser adhesive substrate, agarose, and ruffling did not occur across the agarose. Cells too small to fill an entire square tended to extend across one diagonal of the square, and the stress fibers ran parallel to the longest axis of these cells. Larger cells were able to completely fill their squares. The cytoskeletons of these cells were organized in a spatial relation to the square shape of the cells. The cortical meshwork was aligned circularly and diagonally within the cells. Stress fibers appeared to form from the microfilaments of the meshwork and were aligned diagonally across the cells. We conclude that the diagonal arrangement of the stress fibers and cortical meshwork is caused by the same mechanism by which smaller cells spread over the longest axis of a square. Regions of cells where the meshwork was absent or where stress fibers were tightly bundled were occupied by more randomly arranged cytoskeletal components. Regions of tightly bundled stress fibers did not seem to coincide with regions of cortical meshwork as seen by either whole mount transmission or scanning electron microscopy. Stress fibers were revealed in the light microscope to course beneath more randomly oriented cytoskeletal elements. These "lacework-like" elements were found frequently in square cells. Conspicuous structures in this random lacework were focal points of radially arranged filaments. Our observations suggest a continuity between stress fibers and the cortical microfilaments. The orientation of fibers and filaments was, in turn, dependent on cell shape for organization within the cell.

Cell Adhesion↗

Activin mRNA induced during amygdala kindling shows a spatiotemporal progression that tracks the spread of seizures.

The progressive development of seizures in rats by amygdala kindling, which models temporal lobe epilepsy, allows the study of molecular regulators of enduring synaptic changes. Neurotrophins play important roles in synaptic plasticity and neuroprotection. Activin, a member of the transforming growth factor-beta superfamily of growth and differentiation factors, has recently been added to the list of candidate synaptic regulators. We mapped the induction of activin betaA mRNA in amygdala and cortex at several stages of seizure development. Strong induction, measured 2 hours after the first stage 2 (partial) seizure, appeared in neurons of the ipsilateral amygdala (confined to the lateral, basal, and posterior cortical nuclei) and insular, piriform, orbital, and infralimbic cortices. Activin betaA mRNA induction, after the first stage 5 (generalized) seizure, had spread to the contralateral amygdala (same nuclear distribution) and cortex, and the induced labeling covered much of the convexity of neocortex as well as piriform, perirhinal, and entorhinal cortices in a nearly bilaterally symmetrical pattern. This pattern had filled in by the sixth stage 5 seizure. Induced labeling in cortical neurons was confined mainly to layer II. A similar temporal and spatial pattern of increased mRNA expression of brain-derived neurotrophic factor (BDNF) was found in the amygdala and cortex. Activin betaA and BDNF expression patterns were similar at 1, 2, and 6 hours after the last seizure, subsiding at 24 hours; in contrast, c-fos mRNA induction appeared only at 1 hour throughout cortex and then subsided. In double-label studies, activin betaA mRNA-positive neurons were also BDNF mRNA positive, and they did not colocalize with GAD67 mRNA (a marker of gamma-aminobutyric acidergic neurons). The data suggest that activin and BDNF transcriptional activities accurately mark excitatory neurons participating in seizure-induced synaptic alterations and may contribute to the enduring changes that underlie the kindled state.

Activins↗

Three-dimensional radial ultrashort echo-time imaging with T2 adapted sampling.

The application of 3D radial sampling of the free-induction decay to proton ultrashort echo-time (UTE) imaging is reported. The effects of T2 decay during signal acquisition on the 3D radial point-spread function are analyzed and compared to 2D radial and 1D sampling. It is found that in addition to the use of ultrashort TE, the proper choice of the acquisition-window duration TAQ is essential for imaging short-T2 components. For 3D radial sampling, a maximal signal-to-noise ratio (SNR) with negligible decay-induced loss in spatial resolution is obtained for an acquisition-window duration of TAQ approximately 0.69 T2. For 2D and 1D sampling, corresponding values are derived as well. Phantom measurements confirm the theoretical findings and demonstrate the impact of different acquisition-window durations on SNR and spatial resolution for a given T2 component. In vivo scans show the potential of 3D UTE imaging with T2-adapted sampling for musculoskeletal imaging using standard MR equipment. The visualization of complex anatomy is demonstrated by extracting curved slices from the isotropically resolved 3D UTE image data.

Algorithms↗

Using paramagnetic particles as repulsive templates for the preparation of membranes of controlled porosity.

Using mixtures of repulsive superparamagnetic polystyrene particles and a photopolymerizable organic liquid (trimethylolpropane trimethacrylate) that are applied to a water surface, it is possible to prepare porous membranes with controlled porosity. The particles were polarized by applying a magnetic field H perpendicular to the interface and spread out over the interface making use of the induced repulsive magnetic dipole interactions. As a consequence, the organic liquid in which the particles were embedded covered the water surface uniformly. Subsequent photo cross linking of the organic liquid and dissolution of the embedded particles gave rise to membranes whose porosities were controlled mainly by the chosen areas per particle. The spatial distribution of the pores and the deviation from a crystalline arrangement were characterized in terms of the 2D pair-correlation function and the mean nearest-neighbor interpore distance.

Journal Article↗