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Brain tumor evaluation and segmentation by in vivo proton spectroscopy and relaxometry.

A new methodology has been developed for the evaluation and segmentation of brain tumors using information obtained by different magnetic resonance techniques such as in vivo proton magnetic resonance spectroscopy (1HMRS) and relaxometry. In vivo 1HMRS may be used as a preoperative technique that allows noninvasive monitoring of metabolites to identify the different tissue types present in the lesion (active tumor, necrotic tissue, edema, and normal or non-affected tissue). Spatial resolution for treatment consideration may be improved by using 1HMRS combined or fused with images obtained by relaxometry which exhibit excellent spatial resolution. Some segmentation schemes are presented and discussed. The results show that segmentation performed in this way efficiently determines the spatial localization of the tumor both qualitatively and quantitatively. It provides appropriate information for therapy planning and application of therapies such as radiosurgery or radiotherapy and future control of patient evolution.

Brain Neoplasms↗

Effects of high-potassium solutions and caffeine on synaptic vesicle exoendocytosis processes in the frog neuromuscular junction.

Studies on frog skin-pectoris muscle preparations using vital fluorescent microscopy showed that stimulation of transmitter secretion using high-potassium solutions with the endocytosis marker FM 1-43 induced bright spots in all motor nerve terminals, these representing accumulations of vesicles undergoing the exoendocytic cycle in the active zones of nerve endings. Stimulation of transmitter secretion with caffeine evoked bright spots only in some nerve terminals and only in some parts of the terminals. In summer, the number of bright spots on stimulation of transmitter secretion by caffeine increased sharply. Extracellular recording of spontaneous synaptic signals showed that high-potassium solutions, like caffeine, produced dose-dependent increases in the frequency of miniature endplate currents. However, while high-potassium solutions always increased the frequency, this occurred with caffeine in only a proportion of experiments. This leads to the conclusion that exoendocytosis processes can occur both because of the influx of Ca(2+) ions into nerve endings as a result of depolarization (high-potassium solutions) and because of the release of Ca(2+) ions from the endoplasmic reticulum (caffeine). The possible spatial localization of the endoplasmic reticulum in nerve endings is discussed. The endoplasmic reticulum is suggested to have a role in synapse remodeling processes.

Animals↗

Effects of dobutamine on myocardial blood flow, contractile function, and bioenergetic responses distal to coronary stenosis: implications with regard to dobutamine stress testing.

To determine the effects of dobutamine stimulation on myocardium distal to a coronary stenosis, transmural spatially localized phosphorus 31 nuclear magnetic resonance measurements of myocardial high-energy phosphate compounds (adenosine triphosphate and phosphocreatine), inorganic phosphate, and blood flow and systolic wall thickening were made in 8 open-chested dogs. Data were collected under (1) control conditions, (2) after the application of a moderate coronary stenosis, (3) during infusion of dobutamine with continuing stenosis, and (4) after the release of the stenosis with continuing dobutamine. Stenosis was associated with concordant reductions of subendocardial blood flow, wall thickening, and high-energy phosphate, and mild elevation of inorganic phosphate; subepicardial measurements were essentially unchanged. During dobutamine infusion, blood flow increased in all myocardial layers. Wall thickening returned to control values in the subendocardium and increased nonsignificantly in the subepicardium. Additional loss of high-energy phosphate occurred only in the subepicardium. The data suggest that improved contractile function associated with dobutamine infusion resulted from the inotropic effects of dobutamine and was made possible by the improved blood flow it produced. The data indicate that measurements of blood flow and contractile function do not reliably predict the transmural myocardial metabolic responses to inotropic perturbations in the hypoperfused heart. Taken together, the present findings yield insights with regard to the interpretation of diagnostic dobutamine stimulation testing with single photon emission tomography, radionuclide angiography, and echocardiography.

Animals↗

Monte Carlo studies of the lateral organization of molecules in two-component lipid bilayers.

The lateral organization of two-component phosphatidylcholine bilayers has been investigated using Monte Carlo calculations based upon non-ideality parameters deduced from the phase diagrams of these mixtures. The results are used to develop a quantitative description of the distribution and spatial localization of compositional regions along the bilayer plane in both the gel and liquid crystalline phases. In particular, a detailed analysis of the physical extension (lateral connectivity) and compactness of the compositional clusters is made. It is concluded that the chemical composition of the membrane, the physical state of the bilayer and the interaction energies between molecules greatly influence the lateral connectivity and compactness of compositional regions and that these parameters might play an important role in the formation of diffusional pathways along the membrane plane.

Computers↗

Eye-head coordination in labyrinthine-defective human beings.

(1) Eye-head coordination was studied in three human beings with absent labyrinthine function. Each subject adopted a unique pattern of adaptive responses to achieve optimal gaze stability. (2) One subject used saccades (even in darkness) to help stabilize gaze. In addition, during rotation of the body with the head stationary in darkness, he made slow and quick phases of nystagmus in the same direction. This subject apparently used quick phases to help stabilize gaze rather than to redirect the center of visual attention. (3) One subject, to help prevent gaze overshoot, showed a decrease in the saccadic amplitude-retinal error relationship selectively during active combined eye-head movements. (4) One subject showed a significant amount of preprogramming of compensatory slow phases independent of actual head motion. (5) In all subjects, the passively induced cervico-ocular reflex was moderately potentiated, accounting for about 25% of compensation for head motion during active target seeking. (6) In all subjects, 'effort of spatial localization', as shown by imagining targets in total darkness, increased the velocity of compensatory slow phases to near that of head movements during both active and passively induced head rotations. (7) In all subjects, gaze stability was enhanced during tracking of targets jumping in a predictable fashion. (8) The choice of strategies used by each subject may depend, in part, upon the latency of the cervico-ocular reflex during active head movements.

Adaptation, Physiological↗

Effects of kainic acid and radiofrequency lesions of the pulvinar on visual discrimination in the monkey.

Monkeys with thermocoagulation or kainic acid lesions of the pulvinar and unoperated control monkeys were tested in two tasks: pattern discrimination retention and color discrimination learning in which the stimuli were located at the response sites or were separated spatially from them (S-R separation). The monkeys with kainic acid pulvinar lesions were mildly impaired in retention of the pattern discrimination, but were unimpaired in the color discrimination tasks with or without the S-R separation. The monkeys with thermocoagulation lesions, like monkeys with superior colliculus lesions in a prior study, were severely impaired in performing one of the color discrimination tasks with S-R separation. These findings suggest that: (a) the inferior pulvinar, unlike the superior colliculus, does not contribute to the performance of discriminations involving S-R separation; and (b) corticotectal projections traversing the pulvinar and destroyed by the thermocoagulation lesions are crucial to the performance of discriminations involving S-R separation. The results of an earlier experiment also suggested that interruption of corticotectal fibers passing through the pulvinar impairs performance in another task sensitive to superior colliculus lesions--spatial localization of light flashes. Thus, corticotectal projections may be crucial for the contribution of the colliculus to performance in a variety of visual tasks.

Animals↗

Characteristics of memory impairment following lesioning of the basal forebrain and medial septal nucleus in rats.

Memory impairment in rats with lesions of the basal forebrain (BF) and medial septal nucleus (MS) including cell bodies of the cortical and septohippocampal cholinergic systems, respectively, were compared in order to evaluate the functional contribution of the two cholinergic systems to memory. Biochemical assay revealed that lesioning of the BF and MS resulted in marked and selective decreases in both choline acetyltransferase and acetylcholinesterase activities in the cerebral cortex and hippocampus, respectively. Rats with BF lesions exhibited a severe deficit in a passive avoidance task; acquisition of passive avoidance by repeated training was sluggish, and the acquired response was rapidly eliminated in a subsequent extinction test. However, only slight impairment of passive avoidance was observed in rats with MS lesions. Memory impairment in rats with BF or MS lesions was also investigated using two spatial localization tasks, the Morris water task and the 8-arm radial maze task. Both BF and MS lesions elicited a significant impairment in the Morris water task that required reference memory, as demonstrated by an apparent increase in the latency to escape onto a hidden platform in a large water tank. The impairment was much more obvious in the BF-lesioned rats. In contrast, in the radial maze task primarily requiring working memory, rats with lesions of the MS showed severe disruption, exhibiting a marked increase in total errors, a decrease in the number of initial correct responses, and an apparent change in the strategy pattern. However, corresponding changes in the rats with BF lesions were slight. These results suggest that BF lesions may lead to substantial long-term memory impairment while MS lesions may primarily produce short-term or working memory impairment, indicating a qualitatively different contribution of the two cholinergic systems to memory. It is also suggested that these two experimental animal models may be useful for evaluation of therapeutic drugs for senile dementia of the Alzheimer type.

Acetylcholinesterase↗

On a neural mechanism for cortical processing of taste quality in the rat.

The responses of 31 chorda tympani fibers and 47 cortical neurons were recorded in response to 6 concentrations of NaCl, and single concentrations of sucrose, HCl, and quinine hydrochloride solutions applied to the anterior portion of the tongue in rats. The neural responses were analyzed in terms of the two hypotheses of quality coding: across-neuron response pattern and across-region response pattern notions. In a behavioral experiment, animals were given a conditioned taste aversion to one of 5 concentrations of NaCl solution by pairing it with a gastrointestinal illness caused by i.p. injection of 0.15 M LiCl. Behavioral taste profiles were constructed for each stimulus from the suppression of drinking, which indicates the extent of generalization of aversion to each of the 4 basic taste stimuli. Among the two neural analyses employed for the chorda tympani and cortical units, across-region correlation coefficients for cortical neurons that were derived from the across-region response pattern theory showed the highest correlation (r = 0.89) with the behavioral suppression rates. Across-neuron correlation coefficients in the chorda tympani fibers also showed a good correlation (r = 0.81) with the behavioral data. However, the taste profile for 1.0 M NaCl in chorda tympani fibers was very similar to that for the lower concentrations of NaCl, in spite of the suggestion from the behavioral experiment and the neural analyses of cortical responses that 1.0 M NaCl has HCl and quinine components besides the NaCl component. The present result confirmed the idea that processing of taste information in the cortex involves differences in both response magnitude across neurons and the spatial localization of those neurons.

Animals↗

The effects of A- and C-fiber stimulation on patterns of neuropeptide immunostaining in the rat superficial dorsal horn.

The present study determines the effects of sciatic nerve stimulation at intensities that activate A-fibers alone or both A- and C-fibers on immunostaining for substance P (SP), cholecystokinin-octapeptide (CCK-8), galanin (GAL), dynorphin (DYN) and vasoactive intestinal polypeptide (VIP) in the superficial dorsal horn of the rat spinal cord. The goal of this study is to provide a more precise spatial localization of the sites of release or accumulation of these compounds in relation to specific types of stimuli. Following A-fiber stimulation, there was no significant change in immunostaining for any of these compounds. However, A- and C-fiber stimulation resulted in major changes. For SP, CCK-8, GAL and DYN there was a large and significant loss of immunostaining in medial regions of the dorsal horn. This is the area where sciatic nerve primary afferent fibers terminate and the depletion is probably correlated with activity in these fibers. By contrast, VIP immunostaining is increased in the lateral part of the superficial cord, which is outside of the central sciatic afferent fiber terminations. This indicates that the increase is not in the fine sciatic sensory axons that are directly stimulated. As a final point, the fact that C-fiber but not A-fiber stimulation causes marked changes in the immunocytochemical distribution of all these compounds is further evidence, albeit indirect, that they are involved in nociceptive information processing.

Animals↗

Histamine-modulated transdifferentiation of dermal microvascular endothelial cells.

Homeostatic and inflammatory functions of skin microvessels are tightly regulated by vasoactive amines. Following stimulation with histamine, dermal microvascular endothelial cells (MEC) undergo a rapid change in phenotype (transdifferentiation) and subsequently exhibit an enhanced rate of growth. To elucidate mechanisms regulating MEC transdifferentiation, this study investigated the functional relationships among vimentin, Ca2+, and protein kinase C (PKC) in histamine-modulated dermal MEC in vitro. Distribution of vimentin and PKC in foreskin-derived MEC cultivated in a modified Iscove's medium was assessed with immunocytochemistry. Calcium ion kinetics in histamine-treated MEC were analyzed using the Ca2+ probe Fluo-3 in conjunction with interactive laser cytometry. Histamine, acting through H-1 receptors, produces a rapid (less than 100 ms) and differential elevation of free calcium in each of three cytological compartments defined by the vimentin cytoskeleton in epithelial MEC. A distinctive compartmentalized and nonuniform distribution of PKC precisely coincides with that observed for free-Ca2+ released in response to histamine. The studies reveal that histamine modulation of the MEC phenotype is associated with a rapid patterned reorganization of the vimentin skeleton. It is hypothesized that histamine induces vimentin post-translational modifications by activating a spatially localized interaction among cytoplasmic free Ca2+, PKC, and the vimentin matrix. The results further suggest that vimentin, in addition to its structural role, may participate in signal transduction and gene regulation processes in effecting MEC transdifferentiation.

Calcium↗

The effects of time-varying curvature on velocity profiles in a model of the coronary arteries.

Blood flow patterns in the coronary arteries are of interest due to their possible involvement in atherosclerosis localization. Spatial variations in hemodynamic flow patterns are predominantly determined by the vessel geometry. The coronary arteries represent a unique situation in the cardiovascular system because their geometry undergoes large dynamic variations during each cardiac cycle due to the contraction of the heart. This study was initiated to analyze the effects of time-varying curvature on flow velocity profiles in a curved tube model of the coronary arteries. An in vitro flow model was constructed, which consisted of a flexible curved tube through which fluid flowed under a steady imposed pressure gradient. The radius of curvature of the tube was varied in time using a stepper motor and carriage. Two different deformation configurations were used to determine if variations in center of curvature displacement affected the velocity profiles. It was found in both cases that the skewing of the axial velocity profile depended on the instantaneous dynamic vessel movement, with maximal skewing occurring when the radius of curvature was in transition from the minimum to the maximum value. The change in skewing was greater for the case where carriage moved obliquely to the main direction of flow than when the carriage moved perpendicularly. Although this study was limited to relatively low values of the radius of curvature and change in curvature, an initial understanding of this flow situation was obtained which may lead to the development of more physiologic models.

Animals↗

A comparison of the psychopharmacological profiles of phencyclidine, ketamine and (+) SKF 10,047 in the trimethyltin rat model.

The potential neuroprotective effects of phencyclidine, ketamine and (+) SKF 10,047 were investigated in the trimethyltin (TMT)-treated rat. Of the three drugs used in this study, only phencyclidine (5 mg/kg i.p.) reversed the behavioral hyperactivity and deficits in spatial localization of TMT-treated rats. Neurochemically, phencyclidine and (+) SKF 10,047 were without effect on the neurotransmitters (e.g. noradrenaline, dopamine, serotonin and 5-hydroxindole 3-acetic acid), examined in the amygdaloid cortex and hippocampal regions, while ketamine increased the steady state concentrations of 5-HIAA in the amygdaloid cortex. These results suggest the involvement of the phencyclidine receptor in reversal of the behavioural impairments produced by TMT in rats. The significance of these results with respect to phencyclidine and sigma receptors is discussed. The lack of effect of (+) SKF 10,047 in this model may reflect behavioural differences between phencyclidine and sigma ligands. It may be concluded that the TMT model can be exploited for studying the mechanism of action of molecules liable to have an effect at the phencyclidine receptor site, as opposed to the sigma receptor.

Animals↗

"McGurk illusion" to bilateral administration of sensory stimuli in patients with hemispatial neglect.

The illusion of McGurk (Nature 264, 746-748, 1976) refers to the blending of conflicting audio-visual messages. By taking advantage of this phenomenon the study explored whether visual cues (i.e. manner of articulation) in ipsilesional (right) space would help a patient with auditory neglect to mentally reconstruct syllabic sounds voiced in contralesional (left) space. We examined seven patients with clinically detectable visual neglect following right hemisphere damage. All had signs of auditory neglect as documented by the inferior identification of syllables delivered through a loudspeaker on the left side. In contrast, syllabic sounds delivered contralesionally together with visual stimuli in the ipsilesional space significantly increased identification of "neglected" syllabic sounds. Of the increased responses, 23% were classified as illusory blends, thereby suggesting that manner of articulation provides a valuable clue as to the possible "best fit" for a consonant. The susceptibility to the blend illusion was identical in patients and controls. Results indicate that neglected auditory stimuli are retrieved in patients with right hemisphere lesion by the mechanism of the ventriloquist illusion in the presence of a carefully timed sequence of comparisons of auditory signals in the neglected space with visual signals in the attended space. The possibility that neuronal mechanisms that serve audio-visual merger in spatial localization are also utilized for processing speech distinctions is discussed.

Acoustic Stimulation↗

Prescribing cylinders: the problem of distortion.

Astigmatic spectacle corrections produce distortion of retinal images. Under binocular conditions, small amounts of monocular distortion may significantly alter the sense of spatial localization, producing symptomatic binocular distortion. From examination of the nature and sources of monocular distortion, a rational basis may be developed for methods to minimize distortion when necessary. Adaptation to distortion occurs both by interpretive and physiological mechanisms, with the physiological mechanism appearing to be a type of rotational anomalous retinal correspondence. Through better knowledge of distortion and adaptive mechanisms, a revised set of practical guidelines for prescribing cylinders is presented.

Adaptation, Ocular↗

The responses of single cells in the lateral geniculate nucleus of the rhesus monkey to color and luminance contrast.

The responses of parvocellular and magnocellular cells in the monkey lateral geniculate nucleus (LGN) were assessed to red-green color substitution at various luminance ratios. Parvocellular LGN cells lacking well defined color selectivity could be rendered unresponsive to red-green light exchange at specific luminance ratios. By contrast, magnocellular LGN cells could not be silenced at any luminance ratio. The difference between these two types of cells is attributable to the greater sensitivity of magnocellular cells. The results suggest that magnocellular cells are well suited for the detection of any spatially localized change, be it the result of luminance or wavelength change.

Action Potentials↗

Receptive-field-like functions inferred from large-area psychophysical measurements.

By means of quasi-sinusoidal, circular stimulus patterns, frequency modulated to correct for the radial component of retinal inhomogeneity, we attempt to make all eccentricities within a 16-deg field contribute equally to the threshold response. Wide-field contrast-sensitivity data obtained with these frequency-modulated stimuli are modeled using a canonical form of local contrast sensitivity function (CSF), scaled linearly with eccentricity. Calculating Fourier transforms of the constant-velocity, local CSF, we obtain line-spread and point-spread functions that can also be interpreted as receptive-field responses at various eccentricities. These results are compared to other data on local spatial processing in the retina.

Fovea Centralis↗

Selectivity of the evoked potential for vernier offset.

Hyperacuity thresholds of a few arc seconds can be achieved psychophysically for a variety of spatial localization tasks. The present experiments show that evoked potentials can be elicited in response to the introduction of vernier offsets, but not by the introduction of other cues to hyperacuity such as bisection or relative pattern motion, although each of these cues is equally salient psychophysically. Moreover, vernier acuity measurements and the evoked potentials elicited in response to vernier offsets are strongly degraded by the introduction of flanking stimuli 2-4 min from the vernier target. This suggests that the hyperacuity VEP is a cortical correlate of a very specific type of hyperacuity, that produced by vernier offsets (colinearity failure).

Adult↗

The effect of spatial parameters on oscillatory movement displacement thresholds.

Earlier work has established that oscillatory movement displacement thresholds (OMDT) are a form of hyperacuity. There is speculation that the mechanism determining OMDT, like motion perception in general, involves direct motion sensing at high temporal frequencies of oscillation and spatial localization processes (from which motion is inferred) at low temporal frequencies, which are both hyperacuities in their own right. OMDT were determined, for three experienced observers, over the temporal frequency range 1-15 Hz, for three stimulus lengths and three stimulus widths. Both decreasing stimulus length and decreasing stimulus width increased OMDT at all temporal frequencies. Furthermore, the resulting functions consistently exhibit a "kink" in the temporal frequency midrange. The results are interpreted as evidence that there are two subsystems involved in the analysis of visual motion with the kink indicating the transition where one system begins to predominate over the other.

Humans↗