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Advances in human cardiac 31P-MR spectroscopy: SLOOP and clinical applications.

Phosphorus magnetic resonance spectroscopy (31P-MRS) has revealed a lot about the biochemistry of physiological and pathological processes in the heart. Nevertheless, until today, cardiac 31P-MRS has not had any clinical impact, albeit some pioneering studies demonstrated that 31P-MRS can indeed provide diagnostic information. In this paper, the development of techniques for human cardiac 31P-MRS over the past decade is reviewed, and the requirements for a reliable clinical measurement protocol are discussed. Spatial localization with optimal pointspread function (SLOOP) is a new method to achieve spatial localization and absolute quantitation. Its properties are detailed, and preliminary findings in patients with dilated cardiomyopathy or myocardial infarction are presented.

Heart Diseases↗

Spatial frequency processing in inferred PC- and MC-pathways.

The goal of this study was to investigate the role of inferred parvocellular (PC) and magnocellular (MC) pathways in spatial contrast sensitivity. Localized, spatially narrow-band patterns (sixth derivatives of Gaussians, D6s) were presented at various peak spatial frequencies. When the D6 appeared on a pulsed luminance pedestal (Pulsed-Pedestal Paradigm), the spatial contrast sensitivity showed a band-pass shape with good contrast sensitivity at medium spatial frequencies. When the D6 appeared on a steady luminance pedestal (Steady-Pedestal Paradigm), the spatial contrast sensitivity showed a low-pass shape with decreased sensitivity at high spatial frequencies. The band-pass CSF was interpreted as reflecting PC-pathway mediation; the lower spatial frequency region of the low-pass CSF as reflecting MC-pathway mediation.

Contrast Sensitivity↗

Inhibitory feedback required for network oscillatory responses to communication but not prey stimuli.

Stimulus-induced oscillations occur in visual, olfactory and somatosensory systems. Several experimental and theoretical studies have shown how such oscillations can be generated by inhibitory connections between neurons. But the effects of realistic spatiotemporal sensory input on oscillatory network dynamics and the overall functional roles of such oscillations in sensory processing are poorly understood. Weakly electric fish must detect electric field modulations produced by both prey (spatially localized) and communication (spatially diffuse) signals. Here we show, through in vivo recordings, that sensory pyramidal neurons in these animals produce an oscillatory response to communication-like stimuli, but not to prey-like stimuli. On the basis of well-characterized circuitry, we construct a network model of pyramidal neurons that predicts that diffuse delayed inhibitory feedback is required to achieve oscillatory behaviour only in response to communication-like stimuli. This prediction is experimentally verified by reversible blockade of feedback inhibition that removes oscillatory behaviour in the presence of communication-like stimuli. Our results show that a sensory system can use inhibitory feedback as a mechanism to 'toggle' between oscillatory and non-oscillatory firing states, each associated with a naturalistic stimulus.

Acoustic Stimulation↗

Comparison of spatial scan statistic and spatial filtering in estimating low birth weight clusters.

BACKGROUND: The purpose of this study is to examine the spatial and population (e.g., socio-economic) characteristics of low birthweight using two different cluster estimation techniques. We compared the results of Kulldorff's Spatial Scan Statistic with the results of Rushton's Spatial filtering technique across increasing sizes of spatial filters (circle). We were able to demonstrate that varying approaches exist to explore spatial variation in patterns of low birth weight. RESULTS: Spatial filtering results did not show any particular area that was not statistically significant based on SaTScan. The high rates, which remain as the filter size increases to 0.4, 0.5 to 0.6 miles, respectively, indicate that these differences are less likely due to chance. The maternal characteristics of births within clusters differed considerably between the two methods. Progressively larger Spatial filters removed local spatial variability, which eventually produced an approximate uniform pattern of low birth weight. CONCLUSION: SaTScan and Spatial filtering cluster estimation methods produced noticeably different results from the same individual level birth data. SaTScan clusters are likely to differ from Spatial filtering clusters in terms of population characteristics and geographic area within clusters. Using the two methods in conjunction could provide more detail about the population and spatial features contained with each type of cluster.

Journal Article↗

Stereological estimation of covariance using linear dipole probes.

Classical stereology is capable of quantifying the total amount or 'density' of a geometrical feature from sampled information, but gives no information about the local spatial arrangement of the feature. However, stereological methods also exist for quantifying the 'local' spatial architecture of a 3D microstructure from sampled information. These methods are capable of quantifying, in a statistical manner, the spatial interaction in a structure over a range of distances. One of the key quantities used in a second-order analysis of a volumetric feature is the set covariance. Previous applications of covariance analysis have been 'model-based' and relied upon computerized image analysis. In this paper we describe a new 'design-based' manual method, known as linear dipole probes, that is suitable for estimating covariance from microscopic images. The approach is illustrated in practice on vertically sectioned lung tissue. We find that only relatively sparse sampling per animal is required to obtain estimates of covariance that have low inter-animal variability.

Animals↗

The relationship of undershooting (anticipation) error in space localization to spatial dimension and spatial category width.

In this study I explored whether the degree of anticipation/habituation (undershooting/overshooting) varies with the dimension to be localized, when the method of adjustment is used in space localization. In this study, undershooting occurred for both the vertical (Group 1) and the horizontal (Group 2) dimensions, but was significant only for verticality. The magnitude of undershooting observed for verticality was significantly greater than that for horizontality. A secondary issue regarding the possible relationship between spatial category width and undershooting/overshooting was examined. It was hypothesized that greater degree of spatial category width would be associated with greater undershooting. The opposite was found: Spatial category width was negatively related to undershooting. Finally, within each group, very high consistency of magnitude of spatial category width was observed (rs greater than .90), despite the fact that spatial category width showed shrinkage over the course of the study.

Cognition↗

The visual space sense.

At the conclusion of this discussion it is important to keep in mind the influences of all the complex processes involved in visual spatial localization, among which stereopsis is only one. The various factors and cues for this spatial localization interact with, complement, reinforce, and perhaps even inhibit one another, depending upon the varying visual surroundings of the moment and upon the physiologic perfection of the visual apparatus. In one's daily work probably no single factor or group of factors dominates at all times. "Any one who knows how pliable our spatial visual perceptions are under the influence of various conditions of observation and under the influence of past experience, taken into account consciously or unconsciously, should not be surprised at the multiplicity of results of observations on different objects and with different observers" (see 18).

Cues↗

Local and spatially coordinated movements in Dictyostelium discoideum amoebae during chemotaxis.

We have studied chemotaxis by individual Dictyostelium discoideum amoebae using strong, local gradients of the chemoattractant cyclic AMP. Gradients were provided by diffusion of cyclic AMP from a microneedle, which could be positioned at various points around the cell. Responses to changes in the gradient indicate how the cell is structurally organized for chemotactic movement. There is a polarity in the responsiveness of the surface to stimulation by cyclic AMP along the length of the amoeba. Furthermore, two aspects of chemotactic movement can be distinguished. The first response to cyclic AMP is a locally generated extension of a hyaline pseudopod from the region of the surface nearest the stimulus. The second response, is coordinated and separate from the first response. The coordination appears to depend on the nucleus or on the microtubule-organizing center.

Cell Membrane↗

From individuals to epidemics.

Heterogeneous mixing fundamentally changes the dynamics of infectious diseases; finding ways to incorporate it into models represents a critical challenge. Phenomenological approaches are deficient in their lack of attention to underlying process; individual-based models, on the other hand, may obscure the essential interactions in a sea of detail. The challenge then is to find ways to bridge these levels of description, starting from individual-based models and deriving macroscopic descriptions from them that retain essential detail, and filter out the rest. In this paper, attempts to achieve this transformation are described for a class of models where nonrandom mixing arises from the spatial localization of interactions. In general, the epidemic threshold is found to be larger owing to spatial localization than for a homogeneously mixing population. An improved estimate of the dynamics is developed by the use of moment equations, and a simple estimate of the threshold in terms of a 'dyad heuristic'. For more general models in which local infection is not described by mass action, the connection with related partial differential equations is investigated.

Communicable Diseases↗

Chromatic adaptation to natural and incandescent illuminants.

A color CRT image display system was used to present adapting backgrounds that were spatially and temporally varied. Three observers adjusted the chromaticity of test stimuli to produce an achromatic appearance under a variety of adapting conditions. The achromatic-appearing chromaticities were used as measures of the observers' states of chromatic adaptation. The spatial configuration of the adapting background was varied to measure the spatial extent of the mechanisms responsible for chromatic adaptation. The temporal configuration of the adapting background was varied to measure the time-course of these mechanisms. The results show that chromatic adaptation is spatially localized with a time-course on the order of 10 sec. Since the mechanisms were shown to be spatially localized, the observed temporal integration across eye movements is required to allow these mechanisms to adjust to the spatially integrated scene chromaticity.

Adaptation, Ocular↗

A technique for detecting GABA in the human brain with PRESS localization and optimized refocusing spectral editing radiofrequency pulses.

A proton magnetic resonance spectral editing technique is presented that uses PRESS excitation to achieve spatially localized measurements of brain gamma-aminobutyric acid (GABA). The homonuclear difference spectroscopy technique employs a frequency selective inversion pulse to suppress the creatine resonance at 3.0 ppm. The timing of this pulse is optimized to maximize the suppression of creatine by minimizing the effect of the editing pulse on the 3.0 ppm resonances. The PRESS excitation achieves three dimensional spatial localization in a single acquisition making it less sensitive to patient motion than multiple acquisition techniques. The performance and utility of this technique were evaluated by phantom experiments and by in vivo measurements of brain GABA concentration in 10 normal subjects.

Brain↗

Localization of subclinical ictal activity by functional magnetic resonance imaging: correlation with invasive monitoring.

Functional magnetic resonance imaging (fMRI) with susceptibility-based contrast was used to detect focal changes in cerebral blood flow and metabolism in a patient with focal epilepsy. The patient presented with frequent partial motor seizures involving his right lower face that spread to produce speech arrest and occasionally right arm jerking. Consciousness was never impaired during these events. A multislice echoplanar technique was used to acquire 16 contiguous axial slices every 4 seconds for 11 minutes. Although no overt seizures were observed or reported by the patient during the scanning, a time series analysis of the functional data revealed focal signal-intensity changes in the posterior left frontal lobe, which correlated well both in duration and spatial localization with ictal activity subsequently recorded by invasive electrophysiological monitoring. The spatial localization of fMRI was more accurate than electroencephalography recorded from a subdural grid in predicting the site of successful surgical therapy. These results illustrate the potential of functional MRI for localizing seizure foci with high spatial and temporal resolution. Such studies can be readily combined with high-resolution anatomical imaging, task-activation studies, and other magnetic resonance techniques.

Adult↗

Gravitational effects on the rearrangement of cytoplasmic components during axial formation in amphibian development.

The spatial positioning of the dorsal-ventral axis in the amphibian, Xenopus laevis, can be experimentally manipulated either by tipping the embryo relative to Earth's gravitational force vector or by centrifugation. Experimental evidence suggests that certain cytoplasmic components are redistributed during the first cell cycle and that these components are, in part, responsible for the establishment of this axis. Further studies indicate that at least some of the cytoplasmic components responsible for establishing this axis may be RNA. Recombinant cDNA and PCR technology are utilized to isolate DNA clones for messenger RNA which becomes spatially localized to the dorsal side of the embryo. These clones are being used to study the mechanisms of spatial localization and the function of the localized RNA transcripts.

Animals↗

Localized real-time velocity spectra determination.

The accurate measurement of flow velocity has long been a subject of NMR research. In the field of medical imaging, a variety of techniques primarily based on the principle of Fourier encoding have been described. Due to time constraints, necessary trade-offs exist between spatial versus velocity spectral resolution. In general, either the average velocity of individual pixels is displayed or velocity spectral determinations are made at the cost of spatial localization. The recent development of multidimensional excitation pulses makes spatial localization possible during the excitation phase of the pulse sequences. This approach, coupled with time varying gradient readout, can be used to obtain single-shot localized velocity spectra. Using these concepts, we have obtained in vivo real-time measurements of localized velocity spectra on our clinical imager.

Aorta↗

Magnetic resonance imaging and magnetic resonance spectroscopy of bone tumors and bone marrow disease.

The authors have made use of an integrated magnetic resonance imaging/spectroscopy (MRI/MRS) examination to study seven patients with a variety of bone tumors. The spatial localization method used in the 31P portion of the examination was surface coil localization and a one-dimensional chemical shift imaging method (3 cases). The authors found that the precision of spatial localization was critical in many of these cases, since most of these bone tumors were surrounded by muscle tissue that contained high concentrations of phosphocreatine (PCr). For this reason, they suggest that the metabolite ratios should be referenced to the adenosine triphosphate (beta-NTP) resonance rather than PCr. The phosphate monoester (PME) to beta-NTP ratio was elevated as compared with normal muscle in all of the bone tumors studied. The authors found that all of these tumors exhibited pHs between 7.0 and 7.2, which are similar to the values found for normal muscle. They also show the feasibility of using a line-selective proton chemical shift imaging sequence with high spatial resolution for investigating changes in the fatty composition of bone marrow. This method is illustrated in an example of a patient with advanced avascular necrosis in the femoral heads.

Adolescent↗

Attending, ignoring, and repetition: on the relation between negative priming and inhibition of return.

A series of spatial localization experiments is reported that addresses the relation between negative priming and inhibition of return. The results of Experiment 1 demonstrate that slowed responses to repeated location stimuli can be obscured by repetition priming effects involving stimulus dimensions other than spatial location. The results of Experiments 2, 3A, and 3B demonstrate that these repetition priming effects may occur only when participants are required to respond to the prime display. Together, these results suggest that differences between attended and ignored repetition effects in selective attention studies of spatial localization do not provide a basis for distinguishing between spatial negative priming and inhibition of return.

Adult↗

Further evidence for the role of proprioception in space perception.

In this paper results are presented of errors in spatial localization found after encircling procedures for retinal detachment both in the operated and in the normal eye. Also changes in spatial localization were found in strabismus patients in which a stretch on the operated muscle was exerted after an adjustable recession. In both groups of patients a manipulation of the eye muscle was performed without inducing an eye muscle imbalance in the retinal detachment patients and without modifying the eye position in the strabismus patients in which a stretch was exerted. These data provide further evidence in favour of the role of proprioceptive information in space perception.

Humans↗

cAMP-dependent protein kinase differentially regulates prestalk and prespore differentiation during Dictyostelium development.

We and others have previously shown that cAMP-dependent protein kinase (PKA) activity is essential for aggregation, induction of prespore gene expression and multicellular development in Dictyostelium. In this manuscript, we further examine this regulatory role. We have overexpressed the Dictyostelium PKA catalytic subunit (PKAcat) in specific cell types during the multicellular stages, using prestalk and prespore cell-type-specific promoters to make PKA activity constitutive in these cells (independent of cAMP concentration). To examine the effects on cell-type differentiation, we cotransformed the PKAcat-expressing vectors with reporter constructs expressing lacZ from four cell-type-specific promoters: ecmA (specific for prestalk A cells); ecmB (specific for prestalk B and anterior-like cells in the slug); ecmB delta 89 (specific for stalk cells); and SP60 (prespore-cell-specific). By staining for beta-galactosidase expression histologically at various stages of development in individual strains, we were able to dissect the morphological changes in these strains, examine the spatial localization of the individual cell types, and understand the possible roles of PKA during multicellular development. Expression of PKAcat from either the ecmA or ecmB prestalk promoters resulted in abnormal development that arrested shortly after the mound stage, producing a mound with a round apical protrusion at the time of tip formation. Prestalk A and prestalk B cells were localized in the central region and the apical mound in the terminal differentiated aggregate, while prespore cells showed an aberrant spatial localization. Consistent with a developmental arrest, these mounds did not form either mature spores or stalk cells and very few cells expressed a stalk-cell-specific marker. Expression of PKAcat from the prespore promoter resulted in abnormal morphogenesis and accelerated spore cell differentiation. When cells were plated on agar, a fruiting body was formed with a very large basal region, containing predominantly spores, and a small, abnormal sorocarp. Mature spore cells were first detected by 14 hours, with maximal levels reached by 18-20 hours, in contrast to 24-26 hours in wild-type strains. When cells were plated on filters, they produced an elongated tip from a large basal region, which continued to elongate as a tubular structure and produce a 'slug-like' structure at the end. The slug was composed predominantly of prestalk cells with a few prespore cells restricted to the junction between the 'slug' and tube. As the slug migrated, these prespore cells were found in the tube, while new prespore cells appeared at the slug/tube junction, suggesting a continual differentiation of new prespore cells at the slug's posterior.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗