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Indirect MR arthrography: optimization and clinical applications.

PURPOSE: To evaluate and optimize a method for producing magnetic resonance (MR) images similar to MR arthrograms of multiple synovial joints with intravenous gadopentetate dimeglumine injection. MATERIALS AND METHODS: The authors examined the effects of joint motion, dose of gadopentetate dimeglumine (0.1, 0.2, and 0.4 mmol/kg), and fat saturation on the enhancement rate of the joint cavity and the degree of image contrast generated among articular structures on MR images in 14 healthy volunteers. Shoulder, elbow, wrist, hip, knee, and ankle joints of 10 volunteers were imaged with optimized parameters. Indirect MR arthrographic findings in 17 patients with joint disorders (eg, rotator-cuff tears, meniscal tears, and osteoarthritis) were compared with arthroscopic findings. RESULTS: Fat-saturated images obtained after 10 minutes of exercise and administration of 0.1 mmol/kg gadopentetate dimeglumine were similar to those obtained after intraarticular injection of contrast medium. Exercising the joint yielded the strongest joint-cavity enhancement. Increasing the dose of contrast medium in the unexercised joint did not statistically significantly improve the contrast-to-noise ratio. Rotator cuff tears, meniscal tears, and cartilage defects were better delineated with this method than with unenhanced MR imaging and showed good correlation with arthroscopic results. CONCLUSION: Indirect MR arthrography of an exercised joint provides homogeneous enhancement and improved delineation of soft-tissue structures.

Adult↗

Tracheobronchial tree: assessment with volume rendering--technical aspects.

A volume-rendering technique was applied at the level of normal airways. Two spiral computed tomographic data sets (central and peripheral bronchi) were selected to evaluate the influence of the technique parameters. Optimal bronchogram-like images were obtained with a continuous rim of peripheral voxels, a 70% opacity value, and the unshaded algorithm. Volume rendering allows creation of airway reconstructions that are very similar to conventional bronchograms.

Algorithms↗

Measurement of total pulmonary arterial compliance using invasive pressure monitoring and MR flow quantification during MR-guided cardiac catheterization.

Pulmonary hypertensive disease is assessed by quantification of pulmonary vascular resistance. Pulmonary total arterial compliance is also an indicator of pulmonary hypertensive disease. However, because of difficulties in measuring compliance, it is rarely used. We describe a method of measuring pulmonary arterial compliance utilizing magnetic resonance (MR) flow data and invasive pressure measurements. Seventeen patients with suspected pulmonary hypertension or congenital heart disease requiring preoperative assessment underwent MR-guided cardiac catheterization. Invasive manometry was used to measure pulmonary arterial pressure, and phase-contrast MR was used to measure flow at baseline and at 20 ppm nitric oxide (NO). Total arterial compliance was calculated using the pulse pressure method (parameter optimization of the 2-element windkessel model) and the ratio of stroke volume to pulse pressure. There was good agreement between the two estimates of compliance (r = 0.98, P < 0.001). However, there was a systematic bias between the ratio of stroke volume to pulse pressure and the pulse pressure method (bias = 61%, upper level of agreement = 84%, lower level of agreement = 38%). In response to 20 ppm NO, there was a statistically significant fall in resistance, systolic pressure, and pulse pressure. In seven patients, total arterial compliance increased >10% in response to 20 ppm NO. As a population, the increase did not reach statistical significance. There was an inverse relation between compliance and resistance (r = 0.89, P < 0.001) and between compliance and mean pulmonary arterial pressure (r = 0.72, P < 0.001). We have demonstrated the feasibility of quantifying total arterial compliance using an MR method.

Adolescent↗

Fetal whole-body interstitial compliance, vascular compliance, and capillary filtration coefficient.

Fluid movements across the capillary wall were studied in chronically catheterized, near-term fetal sheep. We hemorrhaged 15 fetuses and infused isotonic saline in seven fetuses. The average experimental changes in arterial pressure, venous pressure, and blood volume were then analyzed by using mathematical modeling and parameter optimization techniques to estimate mean values for the average whole-body interstitial and vascular compliances of the fetus and for the average whole-body fetal capillary filtration coefficient. After fetal hemorrhage, interstitial compliance averaged 45 ml X mmHg-1 X kg-1 of fetal weight and vascular compliance averaged 3.0 ml X mmHg-1 X kg-1, whereas the capillary filtration coefficient averaged 0.4 ml X min-1 X mmHg-1 X kg-1. For intravenous saline infusions, interstitial compliance averaged 45 ml X mmHg-1 X kg-1, and vascular compliance averaged 3.5 ml X mmHg-1 X kg-1, whereas the capillary filtration coefficient averaged 0.8 ml X min-1 X mmHg-1 X kg-1. These data suggest that the fetus has a high whole-body interstitial compliance and a high capillary filtration coefficient compared with the adult. In addition, it appears that the fetus has the ability to decrease its vascular compliance and capillary surface area after a fetal hemorrhage.

Animals↗

Heat transfer pathways between fetal lamb and ewe.

Heat produced by the fetus exists to the mother by one of two principal routes: by fetal-maternal exchange in the placenta or through the fetal skin to the amniotic fluid and uterine wall. We measured heat conductances along each pathway to estimate the fraction of total heat exiting each route. Thermistors were placed in the fetal aorta, two different sites in the amniotic fluid, and in a maternal artery. Five days after surgery we injected a total of 280 ml of ice-cold saline into the two separate amniotic fluid sites during a 45-s interval and measured the temperature response for the next hour. After one or two such injections the fetus was killed to cut off umbilical blood flow, and the experiment was repeated to measure the heat fluxes in the absence of placental heat exchange. Experimentally obtained temperature curves were compared with the predictions of a mathematical model. Heat conductances of the skin and uterine wall, as well as the fetal heat production, were estimated in the model using least-squares parameter optimization. In 10 fetal lambs, weighing 3.73 +/- 0.40 (SE) kg, total fetal heat production averaged 3.75 +/- 0.33 W X kg-1. The heat conductance of the uterine wall, 6.6 +/- 0.8 W X degrees C-1, was lower than that of the fetal skin, 10.2 +/- 1.0, and of the placenta, 25.7 +/- 2.9 W X degrees C-1, temperature gradient. We estimated that 84.5% of total fetal heat production exists by fetal-maternal exchange in the placenta with the remaining 15.5% exiting through the fetal skin.

Amniotic Fluid↗

Characteristics and mechanisms of locomotion induced by intraspinal microstimulation and dorsal root stimulation in spinal cats.

Intraspinal microstimulation (ISMS) through a single microelectrode can induce locomotion in cats spinalized at T(13) 1 wk before (untrained) or after 3-5 wk of treadmill training. Here we study the optimal parameters of ISMS and the characteristics of locomotion evoked. ISMS was applied in the dorsal region of segments L(3)-S(1) at different lateralities (midline to 2.5 mm) and after an intravenous injection of clonidine (noradrenergic agonist). Kinematics and electromyographic recordings were used to characterize locomotion. ISMS could induce a bilateral locomotor pattern similar to that obtained with perineal stimulation, and the characteristics of locomotion varied according to the spinal segment stimulated. Mechanisms by which ISMS could evoke locomotion were then investigated by stimulating, inactivating, or lesioning different spinal structures. Dorsal root stimulation (DRS), just like ISMS, could evoke a variety of ipsi- and bilateral nonlocomotor movements as well as locomotor responses. This suggests that sensory afferent pathways are involved in the production of locomotion by ISMS. Microinjections of yohimbine (noradrenergic antagonist) in L(3) and L(4) segments or a complete second spinal lesion at L(3)-L(4) abolished all locomotor activity evoked by ISMS applied at more caudal segments. Progressive dorsoventral spinal lesions at L(3) or L(4) and restricted ventral lesions at L(4) further suggest that the integrity of the ventral or ventrolateral funiculi as well as the L(3)-L(4) segments are critical for the induction of locomotion by ISMS at L(5) to S(1) or by DRS at these caudal segments.

Adrenergic alpha-Antagonists↗

Spatial and temporal properties of neurons of the lateral suprasylvian cortex of the cat.

Neurons in the posteromedial lateral suprasylvian cortex (PMLS) of cats were recorded extracellularly to investigate their response to stimulation by bars and by sinusoidal gratings. Two general types of cells were identified: those that modulated in synchrony with the passage of drifting bars and gratings and those that responded with an unmodulated increase in discharge. Both types responded to contrast reversed gratings with a modulation of activity: the cells that modulated to drifting gratings modulated to the first harmonic of contrast reversed gratings (at appropriate spatial phase and frequency), whereas those that did not modulate to drifting gratings always modulated to the second harmonic of contrast reversed gratings. No cell had a clear null point. Nearly all cells were selective for spatial frequency. The preferred frequency ranged from 0.1 to 1 cycles per degree (cpd), and selectivity bandwidths (full width at half height) were around two octaves. Preferred spatial frequency was not correlated with receptive field size, but bandwidth and receptive field size were positively correlated. Preferred spatial frequency decreased with eccentricity, at about 0.05 octaves/deg. The response of all cells increased as a function of grating contrast up to a saturation level. The contrast threshold for response to a grating of optimal parameters was approximately 1% for most cells and the saturation contrast approximately 10%. The contrast gain was approximately 25 spikes/s per log unit of contrast. All cells were tuned for temporal frequency, preferring frequencies from approximately 3 to 10 Hz, with a selectivity bandwidth approximately 2 octaves. For some cells, the spatial selectivity did not depend on the temporal frequency and vice versa. Others were spatiotemporally coupled, with the preferred temporal frequency being lower at high than at low spatial frequencies, and the preferred spatial frequency lower at high than at low temporal frequencies. Previous results showing broad velocity tuning to a bar were replicated and found to be predictable from the combined spatial and temporal tuning of PMLS cells and the Fourier spectrum of a bar. Preferred temporal frequency steadily decreased with eccentricity, at 0.025 octaves/deg. The results for PMLS cells are compared with those of other visual areas. Acuity and spatial preference and selectivity bandwidth is comparable to all areas except area 17, where they are a factor of about two higher. Temporal selectivity in PMLS is as fine as observed in other areas. The possibility that PMLS cells may be involved with motion detection and detection of motion in depth is discussed.

Animals↗

Modulation of cortical evoked potentials by stimulation of nucleus raphe magnus in rats.

1. In pentobarbital sodium-anesthetized rats, we evaluated changes in cortical evoked potentials (EPs) associated with electrical and chemical stimulation of nucleus raphe magnus (NRM). A condition-test (C-T) paradigm was used. Cortical EPs were produced by test stimuli delivered to a hindpaw or the thalamic ventral posterior lateral nucleus (VPL; electrical stimulation), or by photic stimulation of the eyes or electrical stimulation of contralateral homotopical cortex (transcallosal EPs). These test stimuli were then preceded by electrical or chemical conditioning stimulation (CS) delivered to NRM through a stereotaxically implanted electrode or injection cannula, respectively. Effects of CS on EPs produced by the test stimuli were characterized. 2. Electrical CS preceding a test stimulus delivered to the foot reduced the amplitude of EPs at thresholds as low as 10-25 microA. The magnitude of EP reduction was dependent on CS intensity, frequency, and the C-T interval. Optimal parameters were trains of 10 pulses (400 Hz) delivered at a C-T interval of 5-10 ms. Injection of glutamate and lidocaine into NRM demonstrated that these effects were due to activation of NRM neurons and not to current spread to medial lemniscus (ML). NRM CS also reduced cortical EPs produced by test stimulation in VPL but did not alter EPs from visual stimulation or from electrical stimulation of contralateral homotopical cortex. 3. These findings suggest that NRM CS attenuates EPs by inhibiting thalamic or thalamocortical afferent activity. Because NRM CS affected all components of the cortical EPs, the effect appears to involve alteration of general sensory activity and is not nociception specific.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Characteristics of electrically evoked somatodendritic dopamine release in substantia nigra and ventral tegmental area in vitro.

Somatodendritic dopamine (DA) release from neurons of the midbrain represents a nonclassical form of neuronal signaling. We assessed characteristics of DA release during electrical stimulation of the substantia nigra pars compacta (SNc) in guinea pig midbrain slices. With the use of parameters optimized for this region, we compared stimulus-induced increases in extracellular DA concentration ([DA]o) in medial and lateral SNc, ventral tegmental area (VTA), and dorsal striatum in vitro. DA release was monitored directly with carbon-fiber microelectrodes and fast-scan cyclic voltammetry. Detection of DA in SNc was confirmed by electrochemical, pharmacological, and anatomic criteria. Voltammograms of the released substance had the same peak potentials as those of DA obtained during in vitro calibration, but different from those of the indoleamine 5-hydroxytryptamine. Similar voltammograms were also obtained in the DA-rich striatum during local electrical stimulation. Contribution from the DA metabolite 3,4-dihydroxyphenylacetic acid to somatodendritic release was negligible, as indicated by the lack of effect of the monoamine oxidase inhibitor pargyline (20 microM) on the signal. Lastly, DA voltammograms could only be elicited in regions that were subsequently determined to be positive for tyrosine hydroxylase immunoreactivity (TH-ir). The frequency dependence of stimulated DA release in SNc was determined over a range of 1-50 Hz, with a constant duration of 10 s. Release was frequency dependent up to 10 Hz, with no further increase at higher frequencies. Stimulation at 10 Hz was used in all subsequent experiments. With this paradigm, DA release in SNc was tetrodotoxin insensitive, but strongly Ca2+ dependent. Stimulated [DA]o in the midbrain was also site specific. At the midcaudal level examined, DA efflux was significantly greater in VTA (1.04 +/- 0.05 microM, mean +/- SE) than in medial SNc (0.52 +/- 0.05 microM), which in turn was higher than in lateral SNc (0.35 +/- 0.03 microM). This pattern followed the apparent density of TH-ir, which was also VTA > medial SNc > lateral SNc. This report has introduced a new paradigm for the study of somatodendritic DA release. Voltammetric recording with electrodes of 2-4 microns tip diameter permitted highly localized, direct detection of endogenous DA. The Ca2+ dependence of stimulated release indicated that the process was physiologically relevant. Moreover, the findings that somatodendritic release was frequency dependent across a range characteristic of DA cell firing rates and that stimulated [DA]o varied markedly among DA cell body regions have important implications for how dendritically released DA may function in the physiology and pathophysiology of substantia nigra and VTA.

Animals↗

A system for deriving revertants of oncogene-transformed human cells.

We have previously shown that some transformed derivatives of the human osteosarcoma-derived cell line HOS are killed by treatment with 1 microM ouabain at pH 8.2, whereas their nontransformed counterparts are relatively unharmed by the same conditions. HOS cells transformed by v-Ki-ras and RAS, v-fms, or MET are susceptible to 1 microM ouabain while those transformed by v-fes are not. Here we describe the adaptation of this differentially cytotoxic effect as a method to enrich for cells which revert to a nontransformed phenotype. We have optimized parameters which increase the differential cytotoxicity, including pH and potassium concentration during and subsequent to ouabain treatment. The efficiency of this procedure was tested in mixed cell experiments where model populations were constructed consisting of HOS cells mixed with an excess of v-Ki-ras-transformed HOS cells. Two successive OAK treatments (ouabain/alkaline/K+-free) were sufficient to recover nontransformed cells free of ras-transformants as indicated by genetic markers and morphology. This HOS/ouabain system is currently being used to derive revertants of ras-transformed human cells and could facilitate the isolation of genes interacting in the pathways by which these cells are transformed.

Cell Line, Transformed↗

Rapid determination of five coagulation parameters in one sample with a centrifugal analyzer.

Spectrophotometric clotting assays using chromogenic substrates were adapted for use in a routine laboratory batch analyzer. Contrary to another described method the same plasma dilution can be used for each of the different coagulation parameters. Optimal assay conditions were determined. The within- and between-assay variation, the intraindividual variation during 1 day and from month-to-month were determined; the chromogenic assay was compared to a clotting assay. No significant difference (p less than 0.01) between manual and automated methods was found.

Antithrombin III↗

Bounds on error expectation for support vector machines.

We introduce the concept of span of support vectors (SV) and show that the generalization ability of support vector machines (SVM) depends on this new geometrical concept. We prove that the value of the span is always smaller (and can be much smaller) than the diameter of the smallest sphere containing the support vectors, used in previous bounds (Vapnik, 1998). We also demonstrate experimentally that the prediction of the test error given by the span is very accurate and has direct application in model selection (choice of the optimal parameters of the SVM).

Learning↗

Properties of gray and binary representations.

Representations are formalized as encodings that map the search space to the vertex set of a graph. We define the notion of bit equivalent encodings and show that for such encodings the corresponding Walsh coefficients are also conserved. We focus on Gray codes as particular types of encoding and present a review of properties related to the use of Gray codes. Gray codes are widely used in conjunction with genetic algorithms and bit-climbing algorithms for parameter optimization problems. We present new convergence proofs for a special class of unimodal functions; the proofs show that a steepest ascent bit climber using any reflected Gray code representation reaches the global optimum in a number of steps that is linear with respect to the encoding size. There are in fact many different Gray codes. Shifting is defined as a mechanism for dynamically switching from one Gray code representation to another in order to escape local optima. Theoretical results that substantially improve our understanding of the Gray codes and the shifting mechanism are presented. New proofs also shed light on the number of unique Gray code neighborhoods accessible via shifting and on how neighborhood structure changes during shifting. We show that shifting can improve the performance of both a local search algorithm as well as one of the best genetic algorithms currently available.

Algorithms↗

Optimal, unsupervised learning in invariant object recognition.

A means for establishing transformation-invariant representations of objects is proposed and analyzed, in which different views are associated on the basis of the temporal order of the presentation of these views, as well as their spatial similarity. Assuming knowledge of the distribution of presentation times, an optimal linear learning rule is derived. Simulations of a competitive network trained on a character recognition task are then used t highlight the success of this learning rule in relation to simple Hebbian learning and to show that the theory can give accurate quantitative predictions for the optimal parameters for such networks.

Animals↗

Estimation of coupled assist flows in a moving-actuator bi-ventricular assist device using interventricular pressure.

An assist flow estimation scheme for a moving-actuator biventricular assist device (MA-BVAD) using interventricular pressure (IVP) has been developed. The scheme uses a waveform feature parameter of IVP, peak IVP time (PIT), for estimation of the filling volumes of both left and right blood sacs simultaneously. In a regression analysis on data from an in vivo test in an 85 Kg male calf for 20 days, the PIT was found to have high correlation with the blood sac filling volume (R=0.883: left filling volume, R=0.967: right filling volume). A conceptual equation hypothesizing this correlation between PIT and filling volume was established based on the observation and the unknown parameters were identified using least squares parameter optimization. The estimation equation identified proved highly accurate (R=0.916 for left flow, R=0.970 for right flow). The accuracy of the estimation scheme promises very good practical applicability.

Animals↗

Research on the utilisation of waste chromic materials in the sodium chromate production process.

The results of investigations on the utilisation of waste chromic materials for the production of sodium chromate have been presented. The optimal parameters of the sodium chromate production, which make it possible to select the best technological solutions, have been determined. A mathematical model based on a system of equations describing the process of sodium chromate production as a function of selected process parameters has been devised. This allows the values useful for a practical estimation of the process, such as mass balances, technological indicators and especially the quantity of the produced chromic waste, to be determined.

Chemical Industry↗

Application of clinical scanners in rats: experimental carotid imaging using magnetic resonance imaging, spiral computed tomography, and color duplex ultrasound.

BACKGROUND AND PURPOSE: Noninvasive small animal imaging allows for reduction of the required numbers of animals in research by providing the possibility of long-term follow-up at various time points. Additionally, correlation to the investigated respective human disease is possible as equivalent equipment is employed. The authors therefore evaluate feasibility and potential of color duplex sonography, computed tomography angiography (CTA), and magnetic resonance angiography (MRA) by the use of clinical scanners for carotid artery imaging in rats. METHODS: Male Wistar rats (n = 17) were subjected to color duplex sonography, CTA, and MRA of the common carotid artery (CCA) and the carotid bifurcation. Clinical scanners were used for the experiments and optimal parameter settings evaluated accounting for the different size of the animals. The applied imaging methods were analyzed in regard to image quality and practicability in laboratory settings. RESULTS: The CCA could be clearly displayed by all imaging modalities in all rats. Duplex sonography provided distinct images and reproducible basic functional information. CTA and MRA provided distinct images of the CCA and the carotid bifurcation in both axial and reconstructed 3-dimensional images. The authors further describe different indications for these imaging methods regarding spatial resolution, acquisition times, possible scanning range, and application of contrast agent. CONCLUSIONS: Color duplex sonography, CTA, and MRA are all feasible methods for imaging of the carotid arteries in rats. Images of sufficient clarity and resolution could be obtained by the use of clinical scanners, yielding information about vessel size, direction of blood flow, and adjacent structures. Further studies need to be performed that address investigations of pathological conditions such as flow disturbances or vessel stenosis.

Animals↗

Data-driven computer simulation of human cancer cell.

Using the Diagrammatic Cell Language trade mark, Gene Network Sciences (GNS) has created a network model of interconnected signal transduction pathways and gene expression networks that control human cell proliferation and apoptosis. It includes receptor activation and mitogenic signaling, initiation of cell cycle, and passage of checkpoints and apoptosis. Time-course experiments measuring mRNA abundance and protein activity are conducted on Caco-2 and HCT 116 colon cell lines. These data were used to constrain unknown regulatory interactions and kinetic parameters via sensitivity analysis and parameter optimization methods contained in the DigitalCell computer simulation platform. FACS, RNA knockdown, cell growth, and apoptosis data are also used to constrain the model and to identify unknown pathways, and cross talk between known pathways will also be discussed. Using the cell simulation, GNS tested the efficacy of various drug targets and performed validation experiments to test computer simulation predictions. The simulation is a powerful tool that can in principle incorporate patient-specific data on the DNA, RNA, and protein levels for assessing efficacy of therapeutics in specific patient populations and can greatly impact success of a given therapeutic strategy.

Apoptosis↗