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PubMed2006

Signal decay correction in 2D ultra-short echo time imaging.

OBJECTIVES: In ultra-short echo time (UTE) imaging, the transverse magnetization experiences significant decay during data acquisition, which gives rise to a loss of signal intensity and spatial resolution in conventionally reconstructed images. The present work proposes an iterative algorithm to correct these adverse effects. MATERIALS AND METHODS: The algorithm involves solving a large linear system of equations and requires a separate reference scan to map the spatially variant transverse relaxation time. It was implemented and applied to simulations and to experiments with custom-built resolution phantoms. The evaluation focused on its ability to improve the actual point-spread function (PSF) and on its influence upon the local signal-to-noise ratio (SNR). RESULTS: The algorithm is demonstrated to virtually restore the ideal PSF of the acquisition. It proves to provide images with better signal intensity and spatial resolution but reduced SNR, if the transverse relaxation time is known with sufficient accuracy. CONCLUSIONS: The present work shows the basic feasibility of correcting signal decay effects in UTE imaging.

Algorithms↗
PubMed2005

Distribution of rare earth elements in an alluvial aquifer affected by acid mine drainage: the Guadiamar aquifer (SW Spain).

This work analyses the spatial distribution, the origin, and the shale-normalised fractionation patterns of the rare earth elements (REE) in the alluvial aquifer of the Guadiamar River (south-western Spain). This river received notoriety in April 1998 for a spill that spread a great amount of slurry (mainly pyrites) and acid waters in a narrow strip along the river course. Groundwaters and surface waters were sampled to analyse, among other elements, the REEs. Their spatial distribution shows a peak close to the mining region, in an area with low values of pH and high concentrations of sulphates and other metals such as Zn, Cu, Co, Ni, Pb, and Cd. The patterns of shale-normalised fractionation at the most-contaminated points show an enrichment in the middle rare earth elements (MREE) with respect to the light (LREE) and heavy (HREE) ones, typical of acid waters. The Ce-anomaly becomes more negative as pH increases, due to the preferential fractionation of Ce in oxyhydroxides of Fe.

Environmental Monitoring↗
PubMed1997

Transneuronal degeneration in the spread of Alzheimer's disease pathology: immunohistochemical evidence for the transmission of tau hyperphosphorylation.

Neurofibrillary tangles and dystrophic neurites appear to develop in a highly characteristic spatial and temporal sequence in AD. In order to examine the nature of the cellular progression we have studied the trisynaptic entorhinal, dentate gyrus, CA3/4 circuit, using an antibody to hyperphosphorylated tau which is a biochemical marker for tangle formation. In early AD cases, we found numerous ATB-stained boutons in the outer molecular layer of the dentate gyrus, the termination field of neurons from the entorhinal cortex. These AT8-stained boutons co-labeled with synaptophysin, indicating that they represent synaptic boutons in an early state of degeneration. Since the labeled boutons were apposed to or clustered around dendrites or soma that lacked or had less intense staining for AT8 or PHF-1, it appeared that presynaptic events preceded postsynaptic neurofibrillary tangle formation. Furthermore, as a function of disease progression, the pattern of degeneration moved through the circuit. In this progression tau, which is normally localized to axons, becomes redistributed into dendrites and hyperphosphorylated. These observations support the hypothesis that the presynaptic terminal changes may promote the formation of initial neurofibrillary pathology in the postsynaptic neurons via anterograde transneuronal mechanisms and that this initiates a breakdown of routing and sorting mechanisms for the cytoskeletal protein tau.

Aged↗
PubMed2001

Dynamic imaging of cerebral blood flow using laser speckle.

A method for dynamic, high-resolution cerebral blood flow (CBF) imaging is presented in this article. By illuminating the cortex with laser light and imaging the resulting speckle pattern, relative CBF images with tens of microns spatial and millisecond temporal resolution are obtained. The regional CBF changes measured with the speckle technique are validated through direct comparison with conventional laser-Doppler measurements. Using this method, dynamic images of the relative CBF changes during focal cerebral ischemia and cortical spreading depression were obtained along with electrophysiologic recordings. Upon middle cerebral artery (MCA) occlusion, the speckle technique yielded high-resolution images of the residual CBF gradient encompassing the ischemic core, penumbra, oligemic, and normally perfused tissues over a 6 x 4 mm cortical area. Successive speckle images demonstrated a further decrease in residual CBF indicating an expansion of the ischemic zone with finely delineated borders. Dynamic CBF images during cortical spreading depression revealed a 2 to 3 mm area of increased CBF (160% to 250%) that propagated with a velocity of 2 to 3 mm/min. This technique is easy to implement and can be used to monitor the spatial and temporal evolution of CBF changes with high resolution in studies of cerebral pathophysiology.

Animals↗
PubMed2002

Long-term voltage-sensitive dye imaging reveals cortical dynamics in behaving monkeys.

A novel method of chronic optical imaging based on new voltage-sensitive dyes (VSDs) was developed to facilitate the explorations of the spatial and temporal patterns underlying higher cognitive functions in the neocortex of behaving monkeys. Using this system, we were able to explore cortical dynamics, with high spatial and temporal resolution, over period of <or=1 yr from the same patch of cortex. The visual cortices of trained macaques were stained one to three times a week, and immediately after each staining session, the monkey started to perform the behavioral task, while the primary and secondary visual areas (V1 and V2) were imaged with a fast optical imaging system. Long-term repeated VSD imaging (VSDI) from the same cortical area did not disrupt the normal cortical architecture as confirmed repeatedly by optical imaging based on intrinsic signals. The spatial patterns of functional maps obtained by VSDI were essentially identical to those obtained from the same patch of cortex by imaging based on intrinsic signals. On comparing the relative amplitudes of the evoked signals and differential map obtained using these two different imaging methodologies, we found that VSDI emphasizes subthreshold activity more than imaging based on intrinsic signals, that emphasized more spiking activity. The latency of the VSD-evoked response in V1 ranged from 46 to 68 ms in the different monkeys. The amplitude of the V2 response was only 20-60% of that in V1. As expected from the anatomy, the retinotopic responses to local visual stimuli spread laterally across the cortical surface at a spreading velocity of 0.15-0.19 m/s over a larger area than that expected by the classical magnification factor, reaching its maximal anisotropic spatial extent within approximately 40 ms. We correlated the observed dynamics of cortical activation patterns with the monkey's saccadic eye movements and found that due to the slow offset of the cortical response relative to its onset, there was a short period of simultaneous activation of two distinct patches of cortex following a saccade to the visual stimulus. We also found that a saccade to a small stimulus was followed by direct transient activation of a cortical region in areas of V1 and V2, located retinotopically within the saccadic trajectory.

Animals↗
PubMed1995

Dynamics of fibroblast spreading.

A new technique of microinterferometry permits cellular growth and motile dynamics to be studied simultaneously in living cells. In isolated chick heart fibroblasts, we have found that the non-aqueous mass of each cell tends to increase steadily, with minor fluctuations, throughout the cell cycle. The spread area of each cell also tends to increase during interphase but fluctuates between wide limits. These limits are dependent on the cell's mass and the upper limit is particularly sharp and directly proportional to mass. From a dynamical point of view, the spread area of a cell is determined by the balance between the rates of two antagonistic processes: protrusion of cellular material into new territory and retraction of material from previously occupied territory. The spatial asymmetry of these processes determines the translocation of the cell. We have found with the chick fibroblasts that the rates of the two processes are generally closely matched to each other and appear to be dependent on the cell's area of spreading. Both continue incessantly in well spread cells, even when there is no net translocation of the cell, and the lower limit of each activity is directly proportional to spread area. The two processes show different behaviour, however, during changes in the spread area of the cell. Both increases and decreases in area appear to be brought about by changes in the rate of retraction, the rate of protrusion remaining relatively constant. A simple stochastic model based on a limited supply of adhesion molecules can simulate all our observations including the mass-limited spreading, the strong correlation between protrusion and retraction and the retraction-dominated changes in area. We conclude that the spread area of the cell is actively regulated, possibly by a simple automatic mechanism that adjusts the area of spreading in relation to the mass of the cell and controls the rate of protrusion to compensate rapidly for spontaneous fluctuations in retraction.

Animals↗
PubMed2001

Functionally independent columns of rat somatosensory barrel cortex revealed with voltage-sensitive dye imaging.

Whisker movement is somatotopically represented in rodent neocortex by electrical activity in clearly defined barrels, which can be visualized in living brain slices. The functional architecture of this part of the cortex can thus be mapped in vitro with respect to its physiological input and compared with its anatomical architecture. The spatial extent of excitation was measured at high temporal resolution by imaging optical signals from voltage-sensitive dye evoked by stimulation of individual barrels in layer 4. The optical signals correlated closely with subthreshold EPSPs recorded simultaneously from excitatory neurons in layer 4 and layer 2/3, respectively. Excitation was initially (<2 msec) limited to the stimulated barrel and subsequently (>3 msec) spread in a columnar manner into layer 2/3 and then subsided in both layers after approximately 50 msec. The lateral extent of the response was limited to the cortical column defined structurally by the barrel in layer 4. Two experimental interventions increased the spread of excitation. First, blocking GABA(A) receptor-mediated synaptic inhibition caused excitation to spread laterally throughout wide regions of layer 2/3 and layer 5 but not into neighboring barrels, suggesting that the local excitatory connections within layer 4 are restricted to single barrels and that inhibitory neurons control spread in supragranular and infragranular layers. Second, NMDA receptor-dependent increase of the spread of excitation was induced by pairing repetitive stimulation of a barrel column with coincident stimulation of layer 2/3 in a neighboring column. Such plasticity in the spatial extent of excitation in a barrel column could underlie changes in cortical map structure induced by alterations of sensory experience.

Animals↗
PubMed2000

Protein adsorption and cell attachment to patterned surfaces.

To better understand the events involved in the generation of defined tissue architectures on biomaterials, we have examined the mechanism of attachment of human bone-derived cells (HBDC) to surfaces with patterned surface chemistry in vitro. Photolithography was used to generate alternating domains of N-(2-aminoethyl)-3-aminopropyl-trimethoxysilane (EDS) and dimethyldichlorosilane (DMS). At 90 min after seeding, HBDC were localized preferentially to the EDS regions of the pattern. Using sera specifically depleted of adhesive glycoproteins, this spatial organization was found to be mediated by adsorption of vitronectin (Vn) from serum onto the EDS domains. In contrast, fibronectin (Fn) was unable to adsorb in the face of competition from other serum components. These results were confirmed by immunostaining, which also revealed that both Vn and Fn were able to adsorb to EDS and DMS regions when coated from pure solution, i.e., in the absence of competition. In this situation, each protein was able to mediate cell adhesion across a range of surface densities. Cell spreading was constrained on the EDS domains, as indicated by cell morphology and the lack of integrin receptor clustering and focal adhesion formation. This spatial constraint may have implications for the subsequent expression of differentiated function.

Animals↗
PubMed1986

Ionic changes and alterations in the size of the extracellular space during epileptic activity.

Experiments with ion-selective microelectrodes revealed that a considerable activity of K ions appears temporarily in the extracellular space (ES) during enhanced neuronal activity and is removed from the ES by diffusion, active uptake, and entry into glial cells. The glial uptake results from the preferential glial K permeability and spatial glial K buffering. The glia responds to the local extracellular accumulation by a depolarization of the exposed part of its membrane. This depolarization will spread along the glial syncytium or extended glial cells. At sites where the extracellular K concentration has not yet increased, the membrane potential will thus be depolarized with respect to the K diffusion potential. Here K will move from the intra- into the extracellular space, in order to restore the electrochemical equilibrium. This induces a current that carries K into glial cells at sites of maximal K accumulation and that transports K out of glial cells at remote areas. In this way K is spatially redistributed. The corresponding current loop in the ES is predominantly carried by Na and Cl, the majority ions. Thus, Na and Ca are transported to the site of K accumulation while Cl moves away. The Cl and K ions are only partially replaced by Na. Hence, a decrease of extracellular osmolarity results, which leads to a water flux from the ES into the cells, inducing a shrinkage of the ES at sites of maximal K accumulation. At remote sites, the opposite effect is expected due to K flow out of glia and Cl transport to these sites. Thus, remote from the area of maximal neuronal activity, an increase of the ES is expected. This mechanism can explain the measured depth profile of the changes in the ES. At sites of maximal neuronal activity, the extracellular space undergoes a reduction by more than 30%. The ionic changes are accompanied by slow negative potential shifts. An increase in intracellular osmolarity due to enhanced metabolic activity and possibly KCl uptake mechanisms contributes to the changes in volume and ionic concentration. Model calculations of the after-effects of the loss of positive charges from the extracellular space and the K-specific glial buffering could predict size and time course of these changes. Experimental tests of this view include observations during epileptiform activity in gliotic scar foci as well as in hippocampal slices with depressed synaptic transmission. The extra- and intracellular ionic changes influence the generation, spread, and termination of seizure activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1982

Topography between the entorhinal cortex and the dentate septotemporal axis in rats: I. Medial and intermediate entorhinal projecting cells.

Retrograde tracing experiments were performed to clarify the topographic projection from medial (area 28m) and intermediate (area 28i) divisions of the entorhinal cortex to the dentate gyrus. Pipets filled with horseradish peroxidase (HRP) were positioned by electrophysiologic guidance at one of several septotemporal (S-T) levels in the dentate molecular layer of anesthetized rats; the tracer was expelled iontrophoretically to minimize its spread. Retrograde labeling of neurons within areas 28m and 28i was analyzed in relation to cytoarchitectonic as well as spatial features of the region (obtained by histologic reconstruction). Regardless of the S-T level, ejections of HRP which were confined to the dentate gyrus labeled only layer II neurons of each area. Following septal pole ejections, labeled neurons were located in the posterolateral, extreme posterior, and posteromedial parts of both areas 28m and 28i. Mid S-T ejections produced not only a ventral, but also an anteromedial, shift in the location of entorhinal projection cells; no cells were labeled posterolaterally. After temporal dentate ejections labeled neurons occupied the most anteromedial part of these entorhinal areas. For both areas, but especially for area 28i, convergence of entorhinal efferents upon a single S-T level in the dentate gyrus occurred from neurons which lay in a dorsoventral (i.e., frontal), and to a lesser extent a rostrocaudal, plane. The efferent axes of both areas 28m and 28i thus appear to be curved and are therefore best described in three dimensions. The entorhinal axes begin in a posterodorsolateral location, wrap around the posterior cortical convexity, and end in an anteroventromedial position. The results provide a useful map for in situ exploration of entorhinodentate connections in the rat, emphasize the parallel innervation of the dentate gyrus by distinct entorhinal fiber systems, and reflect the importance of the S-T axis as a framework for interpreting hippocampal organization.

Animals↗
PubMed1997

Functional MRI BOLD signal coincides with electrical activity in the rat whisker barrels.

Functional MRI (fMRI) provides a noninvasive method for mapping brain functional activity based on blood oxygenation level dependent (BOLD) image contrast that is primarily due to localized increases in perfusion. Recently, Malonek and Grinvald (Science 272:551-554, 1996) suggested that during sustained functional activation, the increases in perfusion were spread over a much larger area than the localized electrical activity. In this study, it is demonstrated that the spatial distribution of the BOLD fMRI signal during sustained stimulation of rat whiskers has the same spatial pattern and dimension as that of neuronal electrical activity in the rat whisker barrels.

Animals↗
PubMed2006

Effects of altered gravity on the actin and microtubule cytoskeleton of human SH-SY5Y neuroblastoma cells.

Human SH-SY5Y neuroblastoma cells were used to study the effects of altered gravity on the actin and microtubule cytoskeleton dynamics. A cholinergic stimulation of the cells during a 6 min period of changing gravity (3 parabolas) resulted in an enhanced actin-driven protrusion of evoked lamellipodia. Likewise, the spontaneous protrusive activity of nonactivated cells was promoted during exposure to changing gravity (6 up to 31 parabolas). Ground-based experiments revealed a similar enhancement of the spontaneous and evoked lamellar protrusive activity when the cells were kept at 2 g hypergravity for at least 6 min. This gravity response was independent of the direction of the acceleration vector in respect to the cells. Exposure of the cells to "simulated weightlessness" (clinorotation) had no obvious influence on this type of lamellar actin cytoskeleton dynamics. A 20 min exposure of the cells to simulated weightlessness or to changing gravity (6 to 31 parabolas) - but not to 2 g (hypergravity, centrifugation) - resulted in an altered arrangement of microtubules indicated by bending, turning, and loop formation. A similar altered arrangement was shown by microtubules which had polymerized into lamellipodia after release from a taxol block at simulated weightlessness (clinorotation) or during changing gravity (5 parabolas). Our data suggest that in human SH-SY5Y neuroblastoma cells, microgravity affects the dynamics and spatial arrangement of microtubules but has no influence on the Rac-controlled lamellar actin cytoskeleton dynamics and cell spreading. The latter, however, seems to be promoted at hypergravity.

Acetylcholine↗
PubMed2004

Assessing cortical functional connectivity by linear inverse estimation and directed transfer function: simulations and application to real data.

OBJECTIVE: To test a technique called Directed Transfer Function (DTF) for the estimation of human cortical connectivity, by means of simulation study and human study, using high resolution EEG recordings related to finger movements. METHODS: The method of the Directed Transfer Function (DTF) is a frequency-domain approach, based on a multivariate autoregressive modeling of time series and on the concept of Granger causality. Since the spreading of the potential from the cortex to the sensors makes it difficult to infer the relation between the spatial patterns on the sensor space and those on the cortical sites, we propose the use of the DTF method on cortical signals estimated from high resolution EEG recordings, which exhibit a higher spatial resolution than conventional cerebral electromagnetic measures. The simulation study was followed by an analysis of variance (ANOVA) of the results obtained for different levels of Signal to Noise Ratio (SNR) and temporal length, as they have been systematically imposed on simulated signals. The whole methodology was then applied to high resolution EEG data recorded during a visually paced finger movement. RESULTS: The statistical analysis performed returns that during simulations, DTF is able to estimate correctly the imposed connectivity patterns under reasonable operative conditions, i.e. when data exhibit a SNR of at least 3 and a length of at least 75 s of non-consecutive recordings at 64 Hz of sampling rate, equivalent, more generally, to 4800 data samples. CONCLUSIONS: Functional connectivity patterns of cortical activity can be effectively estimated under general conditions met in any practical EEG recordings, by combining high resolution EEG techniques, linear inverse estimation and the DTF method. SIGNIFICANCE: The estimation of cortical connectivity can be performed not only with hemodynamic measurements, by using functional MRI recordings, but also with modern EEG recordings treated with advanced computational techniques.

Analysis of Variance↗
PubMed1995

Large secretory structures at the cell surface imaged with scanning force microscopy.

Scanning force microscopy was used to image rat basophilic leukemia (RBL-2H3) cell surfaces under different stimulation conditions that either permit or inhibit secretion. Cross-linking the surface IgE receptors with dinitrophenol-conjugated bovine serum albumin initiates secretion in RBL cells with concomitant spreading of the cell body. Structures at the cell surface approximately 1.5 microns in diameter relate to secretion both spatially and temporally. The position of these surface pits and their sizes suggest that they may be related to the dense-core granules positioned along the cytoskeletal filaments in detergent-extracted, unactivated RBL cell processes. Topographic scanning force microscopy images of RBL cell surfaces at 2, 5, and 35 min after activation show that these structures persist and change in cross-sectional profile with time after activation. These structures may be related to the membrane retrieval mechanism of cells after intense stimulation.

Animals↗
PubMed2002

Analysis of gentamicin kinetics in fluids of the inner ear with round window administration.

HYPOTHESIS: That a theoretical basis for quantifying drug distribution in the inner ear with local applications can be established. BACKGROUND: As methods of local drug delivery to the inner ear gain wider clinical acceptance it becomes important to establish how drugs are distributed in the ear as a function of time and for different delivery methods. METHODS: The time course of gentamicin concentration in the inner ear fluids was simulated with a program that considered general pharmacokinetic principles and incorporated inner ear dimensions and drug dispersal processes, including diffusion, clearance, and intercompartmental exchange. RESULTS: Cochlear fluid space dimensions of the chinchilla were derived from three-dimensional magnetic resonance images and were incorporated into the simulator. The published time course of gentamicin in vestibular perilymph of chinchillas was closely approximated by the adjustment of parameters defining round window membrane permeability, clearance, and interscala exchange. To simulate the time course, it was necessary for drug entry into the vestibule to be dominated by interscala exchange rather than longitudinal spread through the helicotrema. The effects of different round window delivery methods were also calculated. Perilymph drug levels and spatial distribution in the ear were shown to be markedly influenced by the time the applied drug remained in the middle ear. CONCLUSION: The development of local inner ear drug application strategies requires consideration of inner ear pharmacokinetic characteristics, delivery methods, and therapeutic range of the drug.

Animals↗
PubMed1996

A new abnormality of human vision provides evidence of interactions between cortical mechanisms sensitive to movement and those sensitive to colour.

We present the results of a psychophysical study on a human observer, MW, which describe his abnormal visual responses to moving stimuli. It has been shown previously that this subject has normal vision for stationary, achromatic patterns, but responds highly abnormally to saturated chromatic, and especially red stimuli. We now report that like chromatic stimuli, moving black and white patterns elicit an inhibitory response which extends beyond the visual field area covered by the moving stimulus itself, and suppresses detection of stationary, achromatic patterns. Although both chromatic and moving stimuli generate similar percepts in association with their inhibitory activities, these latter differ in several respects, and we conclude that they have different neural origins. We show that in addition to their separate inhibitory actions on detection of achromatic patterns, movement and colour exert mutually inhibitory effects. Movement is markedly effective in limiting the inhibitory spread associated with colour, regardless of the positions in the visual field of the moving and coloured stimuli. Such spatially diffuse activity is characteristic of higher visual processing in pre-occipital cortical visual areas.

Color Perception↗
PubMed1978

Merging of modalities in the optic tectum: infrared and visual integration in rattlesnakes.

The optic tectum of pit vipers (Crotalinae) contains a layer of infrared-sensitive neurons subjacent to the visual layer; these indirectly receive input from the facial pit organs. They respond transiently to the appearance or motion of warm objects within their 25 degrees to 70 degrees excitatory receptive fields (some have inhibitory regions) and presumably allow the snake to orient or strike toward prey. The infrared and visual spatiotopic tectal maps have similar but not identical axes; the infrared magnification is greater than that for vision. Bimodal neurons have receptive fields for each modality that reflect the disparity of the two maps. This finding suggests that (i) during development the infrared and visual fibers spread out independently to fill available tectal sites and (ii) bimodal neurons form local connections without regard to establishing spatial correspondence between the two modalities.

Animals↗
PubMed1999

Emerging concepts in the neurobiology of chronic pain: evidence of abnormal sensory processing in fibromyalgia.

Chronic pain often differs from acute pain. The correlation between tissue pathology and the perceived severity of the chronic pain experience is poor or even absent. Furthermore, the sharp spatial localization of acute pain is not a feature of chronic pain; chronic pain is more diffuse and often spreads to areas beyond the original site. Of importance, chronic pain seldom responds to the therapeutic measures that are successful in treating acute pain. Physicians who are unaware of these differences may label the patient with chronic pain as being neurotic or even a malingerer. During the past decade, an exponential growth has occurred in the scientific underpinnings of chronic pain states. In particular, the concept of nonnociceptive pain has been refined at a physiologic, structural, and molecular level. This review focuses on this new body of knowledge, with particular reference to the chronic pain state termed "fibromyalgia."

Animals↗