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Multi-channel magnetic resonance spectroscopy through time domain multiplexing.

Time domain multiplexing (TDM) is presented as a viable approach to increasing the sensitivity and efficiency of magnetic resonance spectroscopic (MRS) experiments through multi-channel signal acquisition. By switching very rapidly between coils of a receive phased array, TDM receiver extensions allow the acquisition of multiple, independent spectra through a single channel magnetic resonance console. A TDM receiver extension designed for imaging and spectroscopy is described, and the impact of this hardware extension on the processing and quantitation of MRS data is addressed. The primary complication involves the use of fixed bandwidth RF band-pass filters that can not be adjusted to match the spectral width of the desired MRS experiment.MRS sequences whose bandwidths are narrower than the bandwidth provided by TDM band-pass filters can be acquired through TDM with minimal loss of SNR as long as two constraints are met. The first constraint requires that the entire bandwidth of the band-pass filters be sampled at or more rapidly than the Nyquist rate associated with their bandwidth, to prevent extra noise from aliasing into the final spectrum. The second requirement is that spectral resolution be held constant to that of the desired experiment. Results from a two-channel multiplexed MRS experiment, conducted according to these guidelines, illustrate that TDM can be used to allow acquisition of multi-channel MRS experiments through single channel console systems with a minimal loss in SNR.

Equipment Design↗

Genes involved in tumor invasion and metastasis are differentially modulated by estradiol and progestin in human breast-cancer cells.

Invasion of basement membranes by cancer cells is a critical step in metastasis, which requires the coordinated expression of specific genes such as laminin receptors and metalloproteinases. Estradiol and progesterone modulate the clinical progression of steroid-sensitive breast cancers; however, little is known about the molecular regulation of the invasive phenotype by these hormones. We therefore examined the effects of 10 nM estradiol and/or 10 nM progestin R5020 on the expression of 2 non-integrin laminin binding proteins, the 67-kDa laminin receptor (67LR) and HLBP31 as well as the 72-kDa type-IV collagenase (MMP-2) and its inhibitor, TIMP-2, in steroid-receptor-positive (T47D and MCF-7) and -negative (MDA-MB 231) human breast-cancer cells. The relative steady-state level of 67LR mRNA was increased 2- to 3-fold by estradiol in both MCF-7 (p < 0.001) and T47D (p < 0.001) cells, also by R5020, alone or in combination with estradiol, in T47D cells (p < 0.001) and to a much less extent in MCF-7 cells. HLBP31 mRNA and protein levels were increased 2- to 3-fold (p < 0.001) by R5020 alone or in combination with estradiol, but not by estradiol alone. None of the steroid treatments affected the expression or activity of MMP-2. Interestingly, however, TIMP-2 mRNA levels and protein expression in MCF-7 and T47D cells were 50% down-regulated (p < 0.001) by treatment with R5020 or R5020 plus estradiol, but not by treatment with estradiol alone. None of these genes were modulated in steroid-independent MDA-MB231 cells. The data suggest that estradiol and progesterone might act as coordinators regulating specific genes in the steroid-sensitive breast-cancer cell, leading to the acquisition of the metastatic phenotype.

Breast Neoplasms↗

Volumetric multishot echo-planar spectroscopic imaging.

Rapid volumetric magnetic resonance spectroscopic imaging (MRSI) is potentially of great relevance to the diagnosis and treatment of focal cerebral diseases such as cancer and epilepsy. A strategy for volumetric multishot echo-planar spectroscopic imaging (MEPSI) is described which allows whole-brain metabolite mapping in approximately 20 min. A multishot trajectory is used in both the spatial and temporal domains which reduces the accumulated phase during each echo train and tolerates conventional Fourier reconstruction without regridding. Also described is a generalized correction for phase discontinuities arising from the multishot acquisition of the time domain, which is independent of the spatial k-space trajectory and is therefore also applicable to multishot spiral MRSI. Whole-brain, lipid-suppressed MEPSI data were acquired from five normal subjects. The mean signal-to-noise ratios (SNRs) (+/-SE) for the n-acetylaspartate (NAA), choline (Cho), and creatine (Cr) maps across all subjects were 21.3 +/- 1.8, 11.7 +/- 0.6, and 9.2 +/- 0.6, respectively, with a computed voxel size of 2.33 ml.

Algorithms↗

A factorial comparison of schedule and bilateral locus of diastolic blood pressure-contingent feedback.

The purpose of this study was twofold: (a) to compare and determine the effects of a partial and a continuous schedule of feedback on the acquisition and subsequent extinction of bidirectional diastolic blood pressure changes in human subjects; and (b) to examine the result of the administration of response-contingent feedback at specific sites on the bilateral axis between left and right arms on diastolic blood pressure changes at those sites. Subjects were 36 normotensive volunteer college students, ages 18-40 years. A 3 X 3 design was used in which three schedules of feedback (0, 25, and 50%) were factorially compared with three sites of feedback (left arm, both arms, and right arm). The results indicated that varying schedules of feedback differentially affected the acquisition and extinction of diastolic blood pressure response changes. The data also suggested that diastolic blood pressure changes could be produced at specific sites on the bilateral axis, although not completely independent of changes at other sites. Extinction was observed to be rapid in most cases, although a number of subjects with partial feedback schedules showed a somewhat greater resistance to extinction.

Adult↗

A quantitative method for the detection and localization of quantum-limited events from radionuclides in cells and tissue sections by computer-enhanced video microscopy.

Cellular dynamics often involve extremely low concentrations of biologically active substances, which can be radiolabeled and detected, localized and quantitated by autoradiography. The latter may require exposures from a few days to many months. The objective of this research was to demonstrate the feasibility of reducing this long period of data collection by one to two orders of magnitude, while maintaining or improving the spatial resolution and localization in tissues and the quantitative characteristics inherent in autoradiography. A mathematical model describing the complete system was generated using energy partition calculations to estimate photon production via scintillant per H3 beta particle emission and to estimate the subsequent photon capture based upon imaging system parameters and microscope geometry. Calculations showed that, typically, a single tritium beta particle produces a maximum of 5.8 X 10(3) photons. A photon-limited camera and microscope imaging system were selected and optimized in conjunction with a specially developed physical scintillation model. Results showed that the number of detected photoevents increases monotonically with both signal integration time and, independently, with the concentration of the radionuclide. Consequently, this work demonstrates that video microscopy imaging methods can spatially and temporally quantify very low concentrations of radiolabeled substances and can reduce data acquisition times.

Beta Particles↗

Noise propagation in SPECT images reconstructed using an iterative maximum-likelihood algorithm.

The effects of photon noise in the emission projection data and uncertainty in the attenuation map on the image noise in attenuation-corrected SPECT images reconstructed using a maximum-likelihood expectation-maximization algorithm were investigated. Emission projection data of a physical Hoffman brain phantom and a thorax-like phantom were acquired from a prototype emission-transmission computed tomography (ETCT) scanner being developed at UCSF. Computer-simulated emission projection data from a head-like phantom and a thorax-like phantom were also obtained using a fan-beam geometry consistent with the ETCT system. The simulation assumed a 99Tcm source, included collimator blurring but ignored photon scatter. For each phantom, a region of interest (ROI) at the centre of the reconstructed image was chosen for the purpose of noise analysis. In all cases, the mean value (m) in the ROI approached a constant value after approximately 20 iterations. The standard deviation (sigma) generally increased with the number of iterations. The ratio (sigma/m) was found to be inversely proportional to the square root of the total detected counts and proportional to the relative uncertainty in the attenuation maps. These two noise components contributed independently towards the noise in the reconstructed image. In the ETCT system employing an x-ray tube for attenuation map acquisition, the uncertainty in the reconstructed radionuclide distribution is limited mainly by photon noise in the emission projection data. Our results are expected to be generally applicable to other emission-transmission systems, including those using external radionuclide sources for the acquisition of attenuation maps.

Algorithms↗

Effects of GABA modulators on the repeated acquisition of response sequences in squirrel monkeys.

The present study investigated the effects of positive and negative GABA(A) modulators under three different baselines of repeated acquisition in squirrel monkeys in which the monkeys acquired a three-response sequence on three keys under a second-order fixed-ratio (FR) schedule of food reinforcement. In two of these baselines, the second-order FR schedule and the discriminative stimuli for the response sequence were manipulated ("chain-strained" and "tandem-strained"). In the third baseline condition, response-independent tail shock was presented during acquisition of the response sequence. All of these baselines maintained high error levels and produced slow rates of acquisition. Under both the chain-strained and tandem-strained conditions, the positive GABA(A) modulator triazolam (0.0032-0.1 mg/kg) and the negative GABA(A) modulators beta-CCE (ethyl-beta-carboline-3-carboxylate; 0.01-1 mg/kg), beta-CCM (methyl-beta-carboline-3-carboxylate; 0.0032-0.1 mg/kg), and FG-7142 (methyl-beta-carboline-3-carboxamide; 0.18-10 mg/kg) dose-dependently decreased overall response rate compared to administration of saline (control). Under the same two conditions, triazolam and the negative GABA(A) modulators also increased the percentage of errors; however, the effects on accuracy frequently depended on the baseline condition and the particular modulator. In contrast, triazolam only decreased errors and enhanced acquisition in the presence of concurrent response-independent tail shock when compared to saline administration under this condition. The neutral GABA(A) modulator, flumazenil (1 mg/kg), had no effect on rate or accuracy of responding when administered alone, but antagonized the rate-decreasing and error-increasing effects produced by the negative GABA(A) modulators. Together, these data suggest that the effects of both the positive and negative GABAA modulators on acquisition can be similar in squirrel monkeys (i.e., both types of modulator may produce rate-decreasing and error-increasing effects) and that their effects on acquisition depend, in part, on the environmental conditions maintaining acquisition.

Animals↗

Three-dimensional localization and optical imaging of objects in turbid media with independent component analysis.

A new approach for optical imaging and localization of objects in turbid media that makes use of the independent component analysis (ICA) from information theory is demonstrated. Experimental arrangement realizes a multisource illumination of a turbid medium with embedded objects and a multidetector acquisition of transmitted light on the medium boundary. The resulting spatial diversity and multiple angular observations provide robust data for three-dimensional localization and characterization of absorbing and scattering inhomogeneities embedded in a turbid medium. ICA of the perturbations in the spatial intensity distribution on the medium boundary sorts out the embedded objects, and their locations are obtained from Green's function analysis based on any appropriate light propagation model. Imaging experiments were carried out on two highly scattering samples of thickness approximately 50 times the transport mean-free path of the respective medium. One turbid medium had two embedded absorptive objects, and the other had four scattering objects. An independent component separation of the signal, in conjunction with diffusive photon migration theory, was used to locate the embedded inhomogeneities. In both cases, improved lateral and axial localizations of the objects over the result obtained by use of common photon migration reconstruction algorithms were achieved. The approach is applicable to different medium geometries, can be used with any suitable photon propagation model, and is amenable to near-real-time imaging applications.

Algorithms↗

Effect of angiotensin II and vasopressin on acquisition and extinction of conditioned avoidance in rats.

The effect of angiotensin II on the acquisition and extinction of a conditioned avoidance response was examined in rats. Angiotensin II, 1 and 2 micrograms, given intracerebroventricularly facilitated acquisition of the conditioned avoidance response but did not influence extinction. [Sar1, Ile8]-angiotensin II (1 microgram), a specific antagonist of angiotensin II receptors, unexpectedly produced an effect quite similar to that of angiotensin II. Vasopressin (1 microgram) did not influence the rate of acquisition of the conditioned avoidance response but it markedly delayed its extinction. The data are discussed in terms of learning and memory facilitating properties of angiotensin II. This action seems to be independent of an interaction of angiotensin II with its known receptors or of release of vasopressin caused by the peptide.

Angiotensin II↗

Subtraction bugs in an acalculic patient.

We report a patient, MT, who presented a specific, though not isolated, deficit in written calculation. Despite a preserved knowledge of simple arithmetic - single-digit addition and subtraction - he failed systematically in multi-digit subtraction. The nature of errors was consistent across problems and reflected the application of a disturbed underlying algorithm. Moreover, the pattern of error observed mimies a very common finding in developmental studies on arithmetical procedure acquisition (Fuson, 1990, 1992, Young and O'Shea, 1981; VanLehn, 1986, 1990). The data suggest that, within calculation skills, syntax may exist as a system of stable, but inappropriate, rules which are independent of any underlying conceptual knowledge.

Aphasia↗

3D tomographic reconstruction of coronary arteries using a precomputed 4D motion field.

In this paper, we present a new method to perform 3D tomographic reconstruction of coronary arteries from cone-beam rotational x-ray angiography acquisitions. We take advantage of the precomputation of the coronary artery motion, modelled as a parametric 4D motion field. Contrary to data gating or data triggering approaches, we homogeneously use all available frames, independently of the cardiac phase. In addition, we artificially subtract angiograms from their background structures. Our method significantly improves the reconstruction, by removing both motion and background artefacts. We have successfully tested it on the datasets from a synthetic phantom and 10 patients.

Algorithms↗

Optical imaging and automated melanoma detection: questions and answers.

Early detection and prompt excision of cutaneous melanoma is of paramount importance to improve patient survival, and the clinician should be aware of the clinical features that suggest the presence of a malignant lesion. The clinical diagnosis is mainly based on observation of the colour and shape of a given skin lesion. Unfortunately, evaluation of a pigmented lesion is to a large extent subjective and is closely related to the experience of the clinician. To overcome this problem, optical imaging techniques using different instrumentation (i.e. colour video camera, epiluminescence microscopy, reflectance spectrophotometry) and computer image analysis have been proposed in an attempt to provide quantitative measurements in an objective and reproducible fashion. The different procedures employed to perform the diagnosis automatically all have a common denominator: mimicking the eye and the brain of the clinician by image processing and computerized analysis programs, respectively. Sensitivity and specificity data reported in the literature suggest that the computer-based diagnosis of melanoma does not greatly differ from the diagnostic capability of an expert clinician, and is independent of the optical acquisition method employed to analyse the lesions. Most of the computer-processed morphometric variables useful in automated diagnosis are not recognizable nor can be objectively evaluated by the human eye, except that of lesion dimension. However, several questions should be answered before assessing the actual usefulness, including the potential and limitations, of computer-based diagnostic procedures. The purpose of this study was to briefly review the different kinds of instrumentation being used to diagnose melanoma, and to raise questions and whenever possible provide answers in an attempt to establish whether there will be a future for these computerized systems.

Automation↗

Variables affecting naming latency for Japanese Kanji: a re-analysis of Yamazaki, et al. (1997).

Yamazaki, Ellis, Morrison, and Lambon Ralph in 1997 demonstrated that written and spoken age-of-acquisitions had a stronger effect on the naming latency of single Kanji words than any other variable including familiarity. The present study was designed to reanalyze Yamazaki, et al.'s data, using the ratings of written and spoken age-of-acquisitions and visual and auditory familiarities taken from the NTT lexical database. This analysis showed that visual familiarity exerted a stronger independent effect on naming latency than two types of age-of-acquisitions.

Adolescent↗

[Stereotaxy, MRI and independent computer. 85 punctures].

After 150 stereotactic biopsy with CT, the team of Val-de-Grâce has made these ones with MRI and simulation of the complete procedure with an independent computer. The result of 85 biopsies is reported. This one imply the acquisition of 3DFT millimetrics slices, the transfer by Ethernet network on a computer where a specific software treat the data and allow to establish the better course for the needle biopsy. The constraints of quality are very important and some test must be executed. The diagnosis are established, avoiding an unless trepanation.

Adult↗

Deprivation state switches the neurobiological substrates mediating opiate reward in the ventral tegmental area.

The population of mesolimbic dopaminergic neurons is believed to be a primary site at which opiates produce their rewarding effects. Using an unbiased, counterbalanced place conditioning paradigm, we reexamined the contribution made by these cells to the rewarding properties of morphine. Rats were conditioned such that distinct environments were paired with an intra-ventral tegmental area (VTA) microinfusion of either 500 ng per 0.5 microl per side morphine or 0. 5 microl per side sterile saline. Furthermore, rats were conditioned either previously drug-naive or while in a motivational state of opiate dependence and withdrawal. We report that pretreatment with the broad-spectrum dopamine antagonist alpha-flupentixol blocked the acquisition of conditioned place preferences for environments paired with morphine microinjections directly into the VTA in opiate-dependent and withdrawn, but not in previously drug-naive, rats. Lesions of the tegmental pedunculopontine nucleus (TPP) produced exactly the opposite pattern of results. TPP lesions blocked the acquisition of conditioned place preferences for environments paired with VTA morphine microinjections in previously drug-naive, but not in opiate-dependent and withdrawn, rats. These data double-dissociate two independent reward substrates within the VTA itself and suggest that deprivation state selects which of these two substrates will be active. Furthermore, these findings are the first to demonstrate a nondopaminergic substrate for reward within the VTA itself.

Animals↗

Ancestral loss of the maxillary sinus in Old World monkeys and independent acquisition in Macaca.

Cercopithecoid monkeys are unique among primates in that all species (except macaques) lack a maxillary sinus, an unusual condition among eutherian mammals. Although this uncommon distribution of cranial pneumatization was noted previously, the phylogenetic ramifications have not been investigated fully. Recently, character state optimization analysis of computed tomography (CT) data from extant Old World monkeys suggested that the loss of the sinus may have occurred at the origin of the group, unlike previous hypotheses positing only a reduction in size of the structure. To critically evaluate the "early loss" hypothesis, a recently recovered complete cranium of Victoriapithecus macinnesi from Maboko Island, Kenya, was examined by CT to determine the extent of its cranial pneumatization. This taxon is crucial for evaluating character state evolution in Old World monkeys, due to its phylogenetic position, preceding the cercopithecine/colobine split. CT analysis reveals only cancellous bone lateral of the nasal cavity, indicating that Victoriapithecus does not possess a maxillary sinus. Phylogenetic evaluation of the fossil with extant catarrhine taxa strongly supports the early loss of the sinus in cercopithecoids. The results suggest that the maxillary sinus found in the genus Macaca is not homologous with that of other eutherians, which may provide insights into the origin and function (if any) of the paranasal pneumatizations.

Animals↗

[Digital selenium radiography: a comparison of the picture quality of thoracic images in normal and reduced image formats based on the structural anatomical details].

PURPOSE: Is there a loss of information when using selenium radiographic images displayed with reduced image format compared to full format? METHOD: Digital selenium radiographic chest images in two planes were obtained in 35 patients for medical reasons. The digital data sets of each patient were separately displayed in full format on two different films and were printed in reduced format on one film. The format was reduced to 61% of the full format using an acquisition matrix of 2166 x 2488 pixels, an image display matrix of 4000 x 5000 pixels and a film format of 43 x 49 cm. All images were anonymously evaluated by four independent readers using a questionnaire concerning anatomic structures. RESULTS: Format reduction did not result in a loss of information in diagnostically relevant anatomic details. CONCLUSIONS: Displaying digital selenium radiographic data sets of thoracic view in two planes on one film presumably does not lead to a loss of diagnostic information. This procedure may help to reduce film costs.

Adult↗

The effects of pH and dissolved organic carbon on the toxicity of cadmium and copper to a freshwater bivalve: further support for the extended free ion activity model.

The extended free ion activity model (FIAM) was developed by integrating concepts from the original FIAM into biological receptor theory, to obtain a conceptual model that more precisely quantifies the interaction of chemical species at biological receptor sites. The extended FIAM was tested by determining the acute (48 h) valve movement behavior (VMB) (measured in terms of the duration of valve opening) of the Australian freshwater bivalve, Hyridella depressa, to increasing concentrations of total Cd or Cu, in a standard synthetic water under conditions of varying pH (6.5-7.5) and/or dissolved organic carbon (as model fulvic acid (FA)) concentrations (0-11.2 mg L(-1)). Valve movement behavior, measured using an automated data acquisition system, was shown to be a quantifiable and rapid, real-time endpoint for assessing the toxic effects of Cd and Cu exposures. The VMB of H. depressa to Cd was independent (p > 0.05) of pH and/or model FA concentration. In contrast, the VMB of H. depressa to Cu was highly dependent (p < 0.001) on pH and/or model FA concentration; individuals were more sensitive to Cu at low pH and model FA concentrations. The VMB of H. depressa was directly proportional to the activity of the free metal ion (Cd2+), for the linear region of the concentration-response curves. In contrast, the VMB of H. depressa was a weighted function of the activities of the free metal ion and the 1:1 metal hydroxide species (i.e. 2.02 x Cu2+ + CuOH+), whereby Cu2+ had a two-fold greater binding affinity than CuOH+ at the cell membrane surface. Moreover, the results for Cd and Cu are consistent with the extended FIAM, as opposed to the original FIAM, where the result for Cu would be regarded as an exception. The extended FIAM explained 98% of the variability in VMB, whereas the original FIAM explained only 63% (i.e. an improvement of 35%). The improved predictability of organism response to Cu is relevant to advancing water quality guidelines for protecting aquatic biota.

Animals↗