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Imaging performance of amorphous selenium based flat-panel detectors for digital mammography: characterization of a small area prototype detector.

Our work is to investigate and understand the factors affecting the imaging performance of amorphous selenium (a-Se) flat-panel detectors for digital mammography. Both theoretical and experimental methods were developed to investigate the spatial frequency dependent detective quantum efficiency [DQE(f)] of a-Se flat-panel detectors for digital mammography. Since the K edge of a-Se is 12.66 keV and within the energy range of a mammographic spectrum, a theoretical model was developed based on cascaded linear system analysis with parallel processes to take into account the effect of K fluorescence on the modulation transfer function (MTF), noise power spectrum (NPS), and DQE(f) of the detector. This model was used to understand the performance of a small-area prototype detector with 85 microm pixel size. The presampling MTF, NPS, and DQE(f) of the prototype were measured, and compared to the theoretical calculation of the model. The calculation showed that K fluorescence accounted for a 15% reduction in the MTF at the Nyquist frequency (fNy) of the prototype detector, and the NPS at fNy was reduced to 89% of that at zero spatial frequency. The measurement of presampling MTF of the prototype detector revealed an additional source of blurring, which was attributed to charge trapping in the blocking layer at the interface between a-Se and the active matrix. This introduced a drop in both presampling MTF and NPS at high spatial frequency, and reduced aliasing in the NPS. As a result, the DQE(f) of the prototype detector at fNy approached 40% of that at zero spatial frequency. The measured and calculated DQE(f) using the linear system model have reasonable agreement, indicating that the factors controlling image quality in a-Se based mammographic detectors are fully understood, and the model can be used to further optimize detector imaging performance.

Artifacts↗

Mapping the MRI voxel volume in which thermal noise matches physiological noise--implications for fMRI.

This work addresses the choice of the imaging voxel volume in blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI). Noise of physiological origin that is present in the voxel time course is a prohibitive factor in the detection of small activation-induced BOLD signal changes. If the physiological noise contribution dominates over the temporal fluctuation contribution in the imaging voxel, further increases in the voxel signal-to-noise ratio (SNR) will have diminished corresponding increases in temporal signal-to-noise (TSNR), resulting in reduced corresponding increases in the ability to detect activation induced signal changes. On the other hand, if the thermal and system noise dominate (suggesting a relatively low SNR) further decreases in SNR can prohibit detection of activation-induced signal changes. Here we have proposed and called the "suggested" voxel volume for fMRI the volume where thermal plus system-related and physiological noise variances are equal. Based on this condition we have created maps of fMRI suggested voxel volume from our experimental data at 3T, since this value will spatially vary depending on the contribution of physiologic noise in each voxel. Based on our fast EPI segmentation technique we have found that for gray matter (GM), white matter (WM), and cerebral spinal fluid (CSF) brain compartments the mean suggested cubical voxel volume is: (1.8 mm)3, (2.1 mm)3 and (1.4 mm)3, respectively. Serendipitously, (1.8 mm)3 cubical voxel volume for GM approximately matches the cortical thickness, thus optimizing BOLD contrast by minimizing partial volume averaging. The introduced suggested fMRI voxel volume can be a useful parameter for choice of imaging volume for functional studies.

Artifacts↗

Temporal spatial differences observed by functional MRI and human intraoperative optical imaging.

Pre-operative functional magnetic resonance imaging (fMRI), cortical evoked potentials (EPs) and intraoperative optical imaging of intrinsic signals (iOIS) were employed to relate the temporal-spatial characteristics of sensorimotor responses in human brain. Peripheral somasthetic stimulation (2 s) was provided either by a 110 Hz finger vibrator or transcutaneous median nerve stimulation in eight patients undergoing neurosurgical procedures. Each technique provided unique spatial patterns and temporal response profiles. EPs and iOIS activities were observed over the surface of pre- and post-central gyri (at the level of the superior genu) with very similar spatial distributions. In contrast, fMRI spatial distributions depended upon the model used for statistical correlation analysis. Using a monophasic response model, fMRI primarily localized within the central sulcus and did not demonstrate large signal changes over the pre- and post-central gyri (areas with iOIS/EP activity). However, as initial negative responses were incorporated into the response model, fMRI progressively localized closer to the iOIS and somatosensory EP maps. Temporally, responses to single stimuli differed between the fMRI and iOIS techniques. Using a monophasic model for fMRI analysis, the total fMRI response was delayed by 2--3 s relative to iOIS. As initial negative responses were incorporated in the analysis, the fMRI time course developed temporal characteristics similar to iOIS. Ultimately, when fMRI time courses were examined over pixels co-localizing with iOIS activation (without using statistical correlation analysis), the fMRI temporal profile included an initial decrease in signal (an initial dip) that closely resembled the time course of iOIS response. This is the first study to experimentally co-localize (temporally and spatially) iOIS and fMRI signals in human subjects. The spatial/temporal differences in this study likely reflect the capillary versus venous contributions of iOIS and fMRI, respectively. The temporal/spatial co-localization of the iOIS signal and the fMRI initial dip suggests the initial fMRI dip and the iOIS signal may result from similar physiologic events.

Algorithms↗

A diffusion theory model of spatially resolved fluorescence from depth-dependent fluorophore concentrations.

A photon diffusion model has been developed to calculate the steady-state spatially resolved fluorescence from pencil beam excitation in layered tissue. The model allows the calculation of both the excitation reflectance and the fluorescence escape for an arbitrary continuous depth distribution of tissue optical properties and fluorophore concentration. The validity of this model was verified by comparison with Monte Carlo simulations and experimental measurements using phantoms with tissue-like optical properties. The potential usefulness of the spatially resolved fluorescence was explored using the model and simulations of realistic drug distributions. It was shown that using this technique it may be possible to quantify the diffusion of a topically administered drug into the skin, or the photobleaching of a sensitizer during photodynamic therapy.

Algorithms↗

Separate spatial scales determine neural activity-dependent changes in tissue oxygen within central visual pathways.

The relationship between oxygen levels and neural activity in the brain is fundamental to functional neuroimaging techniques. We have examined this relationship on a fine spatial scale in the lateral geniculate nucleus (LGN) and visual cortex of the cat using a microelectrode sensor that provides simultaneous colocalized measurements of oxygen partial pressure in tissue (tissue oxygen) and multiunit neural activity. In previous work with this sensor, we found that changes in tissue oxygen depend strongly on the location and spatial extent of neural activation. Specifically, focal neural activity near the microelectrode elicited decreases in tissue oxygen, whereas spatially extended activation, outside the field of view of our sensor, yielded mainly increases. In the current study, we report an expanded set of measurements to quantify the spatiotemporal relationship between neural responses and changes in tissue oxygen. For the purpose of data analysis, we develop a quantitative model that assumes that changes in tissue oxygen are composed of two response components (one positive and one negative) with magnitudes determined by neural activity on separate spatial scales. Our measurements from visual cortex and the LGN are consistent with this model and suggest that the positive response spreads over a distance of 1-2 mm, whereas the negative component is confined to a few hundred micrometers. These results are directly relevant to the mechanisms that generate functional brain imaging signals and place limits on their spatial properties.

Animals↗

Two-dimensional spatiotemporal coding of linear acceleration in vestibular nuclei neurons.

Response properties of vertical (VC) and horizontal (HC) canal/otolith-convergent vestibular nuclei neurons were studied in decerebrate rats during stimulation with sinusoidal linear accelerations (0.2-1.4 Hz) along different directions in the head horizontal plane. A novel characteristic of the majority of tested neurons was the nonzero response often elicited during stimulation along the "null" direction (i.e., the direction perpendicular to the maximum sensitivity vector, Smax). The tuning ratio (Smin gain/Smax gain), a measure of the two-dimensional spatial sensitivity, depended on stimulus frequency. For most vestibular nuclei neurons, the tuning ratio was small at the lowest stimulus frequencies and progressively increased with frequency. Specifically, HC neurons were characterized by a flat Smax gain and an approximately 10-fold increase of Smin gain per frequency decade. Thus, these neurons encode linear acceleration when stimulated along their maximum sensitivity direction, and the rate of change of linear acceleration (jerk) when stimulated along their minimum sensitivity direction. While the Smax vectors were distributed throughout the horizontal plane, the Smin vectors were concentrated mainly ipsilaterally with respect to head acceleration and clustered around the naso-occipital head axis. The properties of VC neurons were distinctly different from those of HC cells. The majority of VC cells showed decreasing Smax gains and small, relatively flat, Smin gains as a function of frequency. The Smax vectors were distributed ipsilaterally relative to the induced (apparent) head tilt. In type I anterior or posterior VC neurons, Smax vectors were clustered around the projection of the respective ipsilateral canal plane onto the horizontal head plane. These distinct spatial and temporal properties of HC and VC neurons during linear acceleration are compatible with the spatiotemporal organization of the horizontal and the vertical/torsional ocular responses, respectively, elicited in the rat during linear translation in the horizontal head plane. In addition, the data suggest a spatially and temporally specific and selective otolith/canal convergence. We propose that the central otolith system is organized in canal coordinates such that there is a close alignment between the plane of angular acceleration (canal) sensitivity and the plane of linear acceleration (otolith) sensitivity in otolith/canal-convergent vestibular nuclei neurons.

Acceleration↗

5-Aminolaevulinate synthase gene promoter contains two cAMP-response element (CRE)-like sites that confer positive and negative responsiveness to CRE-binding protein (CREB).

The first and rate-controlling step of the haem biosynthetic pathway in mammals and fungi is catalysed by the mitochondrial-matrix enzyme 5-aminolaevulinate synthase (ALAS). The purpose of this work was to explore the molecular mechanisms involved in the cAMP regulation of rat housekeeping ALAS gene expression. Thus we have examined the ALAS promoter for putative transcription-factor-binding sites that may regulate transcription in a cAMP-dependent protein kinase (PKA)-induced context. Applying both transient transfection assays with a chloramphenicol acetyltransferase reporter gene driven by progressive ALAS promoter deletions in HepG2, and electrophoresis mobility-shift assays we have identified two putative cAMP-response elements (CREs) at positions -38 and -142. Functional analysis showed that both CRE-like sites were necessary for complete PKA induction, but only one for basal expression. Co-transfection with a CRE-binding protein (CREB) expression vector increased PKA-mediated induction of ALAS promoter transcriptional activity. However, in the absence of co-transfected PKA, CREB worked as a specific repressor for ALAS promoter activity. A CREB mutant deficient in a PKA phosphorylation site was unable to induce expression of the ALAS gene but could inhibit non-stimulated promoter activity. Furthermore, a DNA-binding mutant of CREB did not interfere with ALAS promoter basal activity. Site-directed-mutagenesis studies showed that only the nearest element to the transcription start site was able to inhibit the activity of the promoter. Therefore, we conclude that CREB, through its binding to CRE-like sites, mediates the effect of cAMP on ALAS gene expression. Moreover, we propose that CREB could also act as a repressor of ALAS transcription, but is able to reverse its role after PKA activation. Dephosphorylated CREB would interfere in a spatial-disposition-dependent manner with the transcriptional machinery driving inhibition of gene expression.

5-Aminolevulinate Synthetase↗

Recall of two visual targets embedded in RSVP streams of distractors depends on their temporal and spatial relationship.

In the present study, I examined how the temporal and spatial relationship between two visual targets (T1 and T2) affects the recall of both targets when they are embedded in rapidly displayed distractors. Presented on a trial were two synchronized streams of characters, one to the left and the other to the right of the fixation. Independent of their spatial relationship, a U-shaped curve described the recall of the second target (T2) as a function of stimulus onset asynchrony (SOA) between T1 and T2. It indicated the presence of the attentional blink with a T2 deficit sparing up to about 150- to 200-msec SOA. However, T2 deficit was greater at short SOAs (up to about 250 msec) when T1 and T2 occurred at different locations than when they occurred at a common location. When SOA was short (100 msec or so), recall of T1 was impaired when T1 and T2 occurred at a common location, but not when they were at different locations. The present findings can be reconciled with existing models (e.g., the interference model and the two-stage model) by distinguishing automatic and controlled attention gating processes at the transfer of perceptual representations to a more durable storage (e.g., visual short-term memory).

Adult↗

Spatial restriction of alpha4 integrin phosphorylation regulates lamellipodial stability and alpha4beta1-dependent cell migration.

Integrins coordinate spatial signaling events essential for cell polarity and directed migration. Such signals from alpha4 integrins regulate cell migration in development and in leukocyte trafficking. Here, we report that efficient alpha4-mediated migration requires spatial control of alpha4 phosphorylation by protein kinase A, and hence localized inhibition of binding of the signaling adaptor, paxillin, to the integrin. In migrating cells, phosphorylated alpha4 accumulated along the leading edge. Blocking alpha4 phosphorylation by mutagenesis or by inhibition of protein kinase A drastically reduced alpha4-dependent migration and lamellipodial stability. alpha4 phosphorylation blocks paxillin binding in vitro; we now find that paxillin and phospho-alpha4 were in distinct clusters at the leading edge of migrating cells, whereas unphosphorylated alpha4 and paxillin colocalized along the lateral edges of those cells. Furthermore, enforced paxillin association with alpha4 inhibits migration and reduced lamellipodial stability. These results show that topographically specific integrin phosphorylation can control cell migration and polarization by spatial segregation of adaptor protein binding.

Animals↗

Inadequacy of motion correction algorithms in functional MRI: role of susceptibility-induced artifacts.

Functional MR (fMR) has been useful in providing insight into the localization and detection of neural cortical activity. However, patient head motion is inevitable over the course of most fMR experiments. Although methods to align the control and activation fMR images may correct for some of this motional error, they will be incomplete in correcting for those that depend on spatial orientation. MR signal amplitude of structures that lie along air-tissue interfaces, for example, are sensitive to susceptibility errors introduced by their reorientation with respect to the main magnetic field. This analysis, using phantoms, cadaver brain, and volunteers, has shown that this reorientation between control and activation images can create regions of "false activation" that increase in area with rotation. Anatomic regions that are expected to be most affected by these susceptibility-induced magnetic field homogeneity variations are those adjacent to bone or air, such as the mesial and inferior temporal lobes and the inferior and anterior frontal lobes. Interpretation of "activation" in these areas on fMR studies must be performed with careful consideration of this important source of error.

Algorithms↗

Fate of the anterior neural ridge and the morphogenesis of the Xenopus forebrain.

The fate of the anterior neural ridge was studied by following the relative movements of simultaneous spot applications of DiI and DiO from stage 15 through stage 45. These dye movements were mapped onto the neuroepithelium of the developing brain whose shape was gleaned from whole-mount in situs to neural cell adhesion molecule and dissections of the developing nervous system. The result is a model of the cell movements that drive the morphogenesis of the forebrain. The midanterior ridge moves inside and drops down along the most anterior wall of the neural tube. It then pushes forward a bit, rotates ventrally during forebrain flexing, and gives rise to the chiasmatic ridge and anterior hypothalamus. The midanterior plate drops, forming the floor of the forebrain ventricle, and, keeping its place behind the ridge, it gives rise to the posterior hypothalamus or infundibulum. The midlateral anterior ridge slides into the lateral anterior wall of the neural tube and stretches laterally into the optic stalk and retina, and then rotates into a ventral position. The lateral anterior ridge converges to the most anterior part of the dorsal midline during neural tube closure, then rotates anteriorly, and gives rise to telencephalic structures. Whole-mount bromodeoxyuridine labeling at these stages showed that cell division is widespread and relatively uniform throughout the brain during the late neurula and early tailbud stages, but that during late tailbud stages cell division becomes restricted to specific proliferative zones. We conclude that the early morphogenesis of the brain is carried out largely by choreographed cell movements and that later morphogenesis depends on spatially restricted patterns of cell division.

Animals↗

Sources of flexibility in human cognition: dual-task studies of space and language.

Under many circumstances, children and adult rats reorient themselves through a process which operates only on information about the shape of the environment (e.g., Cheng, 1986; Hermer & Spelke, 1996). In contrast, human adults relocate themselves more flexibly, by conjoining geometric and nongeometric information to specify their position (Hermer & Spelke, 1994). The present experiments used a dual-task method to investigate the processes that underlie the flexible conjunction of information. In Experiment 1, subjects reoriented themselves flexibly when they performed no secondary task, but they reoriented themselves like children and adult rats when they engaged in verbal shadowing of continuous speech. In Experiment 2, subjects who engaged in nonverbal shadowing of a continuous rhythm reoriented like nonshadowing subjects, suggesting that the interference effect in Experiment 1 did not stem from general limits on working memory or attention but from processes more specific to language. In further experiments, verbally shadowing subjects detected and remembered both nongeometric information (Experiment 3) and geometric information (Experiments 1, 2, and 4), but they failed to conjoin the two types of information to specify the positions of objects (Experiment 4). Together, the experiments suggest that humans' flexible spatial memory depends on the ability to combine diverse information sources rapidly into unitary representations and that this ability, in turn, depends on natural language.

Adolescent↗

Dynamics of the cytoskeleton in Amoeba proteus. I. Redistribution of microinjected fluorescein-labeled actin during locomotion, immobilization and phagocytosis.

Fluorescein-labeled muscle actin was microinjected into Amoeba proteus and followed during intracellular redistribution by means of the image-intensification technique. The fully polymerization-competent protein becomes part of the endogenous actomyosin system undergoing dynamic changes over time periods of several hours. Single-frame analysis of long-term sequences enabled the direct demonstration of both the contractile activities and morphological transformations of microfilaments in normally locomoting, immobilized and phagocytozing specimens. In normally locomoting cells the filament layer undergoes continuous changes in spatial distribution depending on the actual pattern of cytoplasmic streaming and cell shape. The highest degree of differentiation is always maintained in the intermediate region between the front and the uroid, thus indicating this segment of the cortex to be the most important site in generating motive force for pseudopodium formation and ameboid movement. In immobilized cells contracted by the application of ruthenium red or relaxed by different anesthetics, the filament layer forms a continuous thick sheath beneath the cell surface or becomes completely disintegrated. In phagocytozing cells the local polymerization of actin at the tip of pseudopodia forming the food-cup and around the nascent phagosome points to a significant participation of the actomyosin system in the process of capturing and constricting prey organisms. Although our results provide clear evidence for the overall importance of motive force generation according to the hydraulic pressure theory, some motile phenomena exist in Amoeba proteus that cannot exclusively be explained by this mechanism.

Actins↗

Measurement of resolution and recovery in recent generation positron tomographs.

In positron tomographic images, the ability to differentiate closely lying structures, the spillover of activity from a region into adjacent regions and the reduction in apparent isotope concentration in small structures are all dependent on spatial resolution. Resolution in the reconstructed image is affected by (i) detector size, (ii) the spatial sampling used (e.g. stationary, wobble), (iii) the amount of smoothing in the reconstruction process (or subsequent to reconstruction) and (iv) the image pixel size. Under ideal conditions, modern commercial tomographs can produce a reconstructed spatial resolution of 5 mm or less. However, this is rarely realizable in a clinical study due to the inadequacy of counting statistics and the amplification of statistical noise. In practice, a smoother filter has to be used. This paper presents a summary of practical measurements of spatial resolution, and the related count recovery, performed on recent generation positron tomographs. It is intended to contribute to the definition of methods of measuring these parameters which is part of an on going concerted action in positron tomography supported by the European Commission.

Image Processing, Computer-Assisted↗

Effects of spatial attention on directional manual and ocular responses.

The aim of the present study was to investigate how spatial attention influences directional manual and saccadic reaction times. Two experiments were carried out. In experiment 1 subjects were instructed to perform pointing responses toward targets that were located either in the same or the opposite hemifield with respect to the hemifield in which an imperative stimulus was presented. In experiment 2, they were instructed to make saccadic or pointing responses. The direction of the responses was indicated by the shape of the imperative stimulus. Reaction time (RT), movement time, and, in experiment 2, saccadic trajectory were measured. The imperative stimulus location was either cued (endogenous attention) or uncued. In the latter case the imperative stimulus presentation attracted attention (exogenous attention). The main results of the experiments were the following: First, exogenous attention markedly decreased the RTs when the required movement was directed toward the imperative stimulus location. This directional effect was much stronger for pointing than for ocular responses. Second, endogenously allocated attention did not influence differentially RTs of pointing responses directed toward or away the attended hemifield. In contrast, endogenous attention markedly favored the saccadic responses when made away from the cued hemifield. Third, regardless of cueing, the direction of movement affected both pointing and saccadic reaction times. Saccadic reaction times were faster when the required movement was directed upward, while manual reaction times were faster when the movement was directed downward. Fourth, lateralized spatial attention deviated the trajectory of the saccades contralateral to the attention location. This pattern of results supports the notion that spatial attention depends on the activation of the same sensorimotor circuits that program actions in space.

Adult↗

Local responses to inundation and de-farming in the reservoir region of the three gorges project (China).

Large-scale infrastructural developments in rural areas often impose significant direct and indirect impacts on environment and people. The Three Gorges Project to dam the Yangtze River in China will create a huge reservoir, inundate farmlands and villages, and incur large-scale resettlement. The concurrent de-farming program to reforest marginal farmlands on steep slopes imposes additional stresses on local people. This study evaluates the ecological and economic adjustments in rural areas affected by both projects, and explores villagers' knowledge, attitudes, perceptions, and expectations vis-à-vis the drastic changes. Eleven villages in Yunyang County in Sichuan Province, stratified into three zones based on topography and agriculture, were assessed by field studies, questionnaire surveys, maps, satellite imagery, and census and government reports. Multiple regressions identified predictors for 17 dependent variables. Spatial variations in the difficult terrain imposed zone-differentiated agricultural constraints, ecological impacts, and human responses. The dominant farming population--mainly young adults working as migrant laborers in cities--has adopted some nonagricultural work to supplement incomes. Expected per-capita standardized farmland (SF) exceeded threshold SF, which surpasses existing SF. Motivations to reclaim more farmlands, de-farm marginal lands, and become migrant laborers were explained by different multiple-regression predictors. Reduction in farmland stock by inundation and de-farming, aggravated by unwillingness towards nonlocal resettlement, would impose ecological pressures and stimulate demands for nonfarming incomes. Common anticipation of better future income and occupation has been subdued by unfavorable feedbacks from early relocatees. Future environmental and landscape changes are hinged upon changing human responses. Government policies could be informed by research findings to match economic, ecological, and social realities.

Agriculture↗

A structured-population model of Proteus mirabilis swarm-colony development.

In this paper we present continuous age- and space-structured models and numerical computations of Proteus mirabilis swarm-colony development. We base the mathematical representation of the cell-cycle dynamics of Proteus mirabilis on those developed by Esipov and Shapiro, which are the best understood aspects of the system, and we make minimum assumptions about less-understood mechanisms, such as precise forms of the spatial diffusion. The models in this paper have explicit age-structure and, when solved numerically, display both the temporal and spatial regularity seen in experiments, whereas the Esipov and Shapiro model, when solved accurately, shows only the temporal regularity. The composite hyperbolic-parabolic partial differential equations used to model Proteus mirabilis swarm-colony development are relevant to other biological systems where the spatial dynamics depend on local physiological structure. We use computational methods designed for such systems, with known convergence properties, to obtain the numerical results presented in this paper.

Agar↗