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PubMed2004

Quantitative phase microscopy: a new tool for measurement of cell culture growth and confluency in situ.

Quantitative phase microscopy (QPM) is a recently developed computational approach that provides quantitative phase measurements of specimen images obtained under bright-field conditions without phase- or interference-contrast optics. To perform QPM, an in-focus bright-field image is acquired, together with one positive and one negative de-focus image. An algorithm is then applied to produce a specimen phase map. In this investigation we demonstrate that manipulation of the phase map intensity histogram using novel, non-subjective thresholding and segmentation methods provides enhanced delineation of cells in culture. QPM was utilised to measure the growth behaviour of cultured airway smooth muscle cells over a 92-h period. There was a high degree of correlation between parallel QPM-derived confluency measurements and haemocytometry-derived counts of airway smooth muscle cells over this time period. Using QPM, translucent cells can be visualised with improved cell boundary definition allowing precise and reproducible measurements of cell culture confluency. Quantitative phase imaging provides a rapid, optically simple and non-destructive approach for measurement of cellular morphology. Further development of the QPM-based analysis methodology has the potential to provide even more refined measures of cellular growth.

Algorithms↗
PubMed1991

Solid state 2H-NMR as a method for determining the orientation of cannabinoid analogs in membranes.

In order to investigate the correlation between the pharmacological activities of cannabinoids and the geometric features of their interactions with membranes, we have calculated the molecular orientations of five analogs in model membrane bilayers. The studies involved the stereospecific 2H-labeling of each analog in different positions and the use of solid state 2H-NMR. The cannabinoids included in our study are (-)-delta 9-tetrahydrocannabinol (THC), (-)-delta 8-THC and its methylated ether analog (-)-O-methyl-delta 8-THC, as well as two hexahydrocannabinols (HHC) having an additional hydroxyl in the 11-position, (-)-11-OH-9 alpha-HHC and (-)-11-OH-9 beta-HHC. A new algorithm is used to circumvent the problem of deuterium quadrupolar splitting signs. The method has general applicability for calculating the orientation of a molecule in a anisotropic environment. Our calculations show that the biological inactive O-methyl-delta 8-THC orients with its long axis parallel to the lipid acyl chains, whereas the psychoactive cannabinoids assume "awkward" orientations in which the hydroxyl groups are pointing towards the bilayer interface, presumably to maximize the amphipathic interaction with the membrane. To produce their biological effects, cannabinoids may need to acquire an appropriate location and orientation in the membrane bilayer so that, through lateral diffusion, they can reach their sites of action and interact productively with these sites.

Cannabinoids↗
PubMed1995

A parallel neural network simulator on the connection machine CM-5.

We here present a parallel implementation of artificial neural networks on the connection machine CM-5 and compare it with other parallel implementations on SIMD and MIMD architectures. This parallel implementation was developed with the goal of efficiently training large neural networks with huge training pattern sets for applications in molecular biology, in particular the prediction of coding regions in DNA sequences. The implementation uses training pattern parallelism and makes use of the parallel I/O facilities of the CM-5 and its efficient reduction operations available within the control network to achieve a high scalability. The parallel simulator obtains a maximum speed of 149.25 MCUPS for training feedforward networks with backpropagation on a 512 processor CM-5 system without using the CM-5 vector facility. The implementation poses no restriction on the type of network topology and works with different batch training algorithms like BP. Quickprop and Rprop.

Algorithms↗
PubMed2006

BOLD contrast sensitivity enhancement and artifact reduction with multiecho EPI: parallel-acquired inhomogeneity-desensitized fMRI.

Functional MRI (fMRI) generally employs gradient-echo echo-planar imaging (GE-EPI) to measure blood oxygen level-dependent (BOLD) signal changes that result from changes in tissue relaxation time T(*) (2) between activation and rest. Since T(*) (2) strongly varies across the brain and BOLD contrast is maximal only where the echo time (TE) equals the local T(*) (2), imaging at a single TE is a compromise in terms of overall sensitivity. Furthermore, the long echo train makes EPI very sensitive to main field inhomogeneities, causing strong image distortion. A method is presented that uses accelerated parallel imaging to reduce image artifacts and acquire images at multiple TEs following a single excitation, with no need to increase TR. Sensitivity gains from the broadened T(*) (2) coverage are optimized by pixelwise weighted echo summation based on local T(*) (2) or contrast-to-noise ratio (CNR) measurements. The method was evaluated using an approach that allows differential BOLD CNR to be calculated without stimulation, as well as with a Stroop experiment. Results obtained at 3 T showed that BOLD sensitivity improved by 11% or more in all brain regions, with larger gains in areas typically affected by strong susceptibility artifacts. The use of parallel imaging markedly reduces image distortion, and hence the method should find widespread application in functional brain imaging.

Adult↗
PubMed1999

The incipient stage in thrombin-induced fibrin polymerization detected by FCS at the single molecule level.

We used fluorescence correlation spectroscopy (FCS) to study the activation of fibrinogen by thrombin and the subsequent aggregation of fibrin monomers into fibrin polymers at a very low and at physiological fibrinogen concentrations. In the labeling procedure used the fibrinogen was randomly labeled and the label was bound to the fibrinopeptide A and/or to the part of fibrinogen which after activation takes part in fibrin formation. We measured a diffusion coefficient for fibrinogen of 2.48 x 10(-7) +/- 0.10 x 10(-7) cm2/s. After activation with thrombin both fibrinopeptide A and fibrin polymerization products could be demonstrated. From our findings we suggest a model for the formation of a three-dimensional network as two parallel processes, elongation and branching and that fibrin oligomers are not only intermediates in the polymerization process but also are substrates for branching.

Algorithms↗
PubMed2005

Protein structure prediction by tempering spatial constraints.

The probability to predict correctly a protein structure can be enhanced through introduction of spatial constraints - either from NMR experiments or from homologous structures. However, the additional constraints lead often to new local energy minima and worse sampling efficiency in simulations. In this work, we present a new parallel tempering variant that alleviates the energy barriers resulting from spatial constraints and therefore yields to an enhanced sampling in structure prediction simulations.

Algorithms↗
PubMed2000

Forecasts using neural network versus Box-Jenkins methodology for ambient air quality monitoring data.

This study explores ambient air quality forecasts using the conventional time-series approach and a neural network. Sulfur dioxide and ozone monitoring data collected from two background stations and an industrial station are used. Various learning methods and varied numbers of hidden layer processing units of the neural network model are tested. Results obtained from the time-series and neural network models are discussed and compared on the basis of their performance for 1-step-ahead and 24-step-ahead forecasts. Although both models perform well for 1-step-ahead prediction, some neural network results reveal a slightly better forecast without manually adjusting model parameters, according to the results. For a 24-step-ahead forecast, most neural network results are as good as or superior to those of the time-series model. With the advantages of self-learning, self-adaptation, and parallel processing, the neural network approach is a promising technique for developing an automated short-term ambient air quality forecast system.

Air Pollution, Indoor↗
PubMed1988

Interaction of carotid chemoreceptor and baroreceptor reflexes in anesthetized dogs.

Interaction between baroreceptors and chemoreceptors during simultaneous activation of the reflexes was studied in eight pentobarbital sodium-anesthetized vagotomized dogs. The carotid sinus reflexogenic area was isolated and perfused at controlled carotid sinus pressure (CSP), PO2, and PCO2. Random combinations of CSP, PO2, and PCO2 were delivered to the carotid sinus. Results were analyzed by multiple linear regression. For the arterial pressure response, increasing CO2 resulted in an upward shift of the baroreceptor reflex response curve and an increased slope of the linear portion of the curve. The heart rate-CSP curve was also shifted upward by CO2, with the effect being greatest at high levels of CSP. The respiratory frequency-CO2 relationship had an increased slope and was shifted upward when CSP was decreased. The responses of tidal volume and ventilation (VE) depended on all three inputs. At any level of PO2, decreasing CSP resulted in a parallel shift of the VE-CO2 relationship. The results indicate that there is a significant interaction between chemoreceptor and baroreceptor reflex sensitivities.

Algorithms↗
PubMed2005

A design of multiagent-based framework for volume image construction and analysis.

This paper describes a design of a multiagent-based system that can be used to manage the acquisition and analysis of ultrasonograph images. The major concept is to design a management framework consisting of multiple intelligent agents to direct the ultrasonograph image acquisition and analysis operations carried out using a high-speed bit-parallel architecture efficiently as well as to allow for the construction of 3D images from 2D ones. Volume image operations need reactivity, autonomy, and intelligence of software. Therefore, agents can play an important role in enhancing the overall operation of medical image analysis. The system suggests a set of image analysis operations including smoothing, noise removal, and enhancing techniques. These operations will be implemented using parallel processing architectures while the management framework will consist of different agent types such as: simple reflex agents, agents that keep track of the world, goal-based agents, and utility-based agents. These agents interact with each other and exchange data among themselves in order to achieve a comprehensive speed in performing the volume image construction operations. Guided with the fact that the agent consists of program and architecture, the system deploys parallel processing architectures to implement the image analysis operations. The system is considered a step towards a complete multiagent-based framework for medical image acquisition and analysis.

Algorithms↗
PubMed2001

Detection of motion in hybrid PET/SPECT imaging based on the correlation of partial sinograms.

This paper describes a motion detection method specific to hybrid positron emission tomography/single photon emission computed tomography systems. The method relies on temporal fractionation of the acquisition into three data sets followed by an algorithm based on the cross correlation (CC) of partial sinograms from successive sets at different rotations of the camera. Spatial inconsistencies due to motion are detected by decreases in the CC between two sets. This permits to separate data into premotion and postmotion sets of consistent data that are reconstructed independently then registered and summed. Rigid motions greater than 1-cm translation or 10 degrees rotation were detected with this method from experimental data obtained by manually moving phantoms made of radioactive spheres as well as from a patient lung study corrupted by artificial motion. The different motion studies showed that the image contrast does not seem to be a limiting factor and that the motion is best detected when the gantry is parallel to the direction of motion. The registration and fusion of the reconstructed premotion and postmotion sets lead in all cases to a reduction of the motion artifacts and an increase in signal-to-noise ratio.

Algorithms↗
PubMed1990

Image analysis techniques for automatic evaluation of two-dimensional electrophoresis.

Techniques for automatic analysis of two-dimensional electrophoresis gels by computer-aided image analysis are described. Original gels or photographic films are scanned using a laser scanner and the files are transferred to a microcomputer. The program package first performs a compression and preevaluation of the files. Spot identification and quantification is performed by the chain code algorithm after appropriate zooming and cutting. Labeling facilitates spot identification and quantification in numerical and graphical (pseudocolor) representation on peripheral devices for camera ready output. Interpolation between measured basepoints is performed by cubic spline algorithms which are automatically switched on and off, depending on the need by the program. High speed analysis and graphic representation is achieved using fast Assembler language routines rather than high level languages. One-dimensional gels can be analyzed using the same software. Spot matching between parallel two-dimensional gels has not yet been implemented.

Electrophoresis, Gel, Two-Dimensional↗
PubMed1996

On-line laser-photometric monitoring of aerosol deposition in ventilated rabbit lungs.

A photometric technique was developed for on-line measurement of aerosol deposition in isolated, ventilated, and perfused rabbit lungs. A jet nebulizer was used for aerosolization of saline (hygroscopic particles) and di(2-ethylhexyl) sebacate (nonhygroscopic particles). Aerosol concentration (laser photometer, constructed for measurements in rabbit lungs) and flow rate (commercial pneumotachograph) were continuously monitored at the inlet of the tracheal cannula. Computer-assisted data processing allowed the breath-by-breath calculation of inhaled and exhaled aerosol mass, thus providing the deposition fraction. With the use of hygroscopic particles, however, this approach was hampered by the humidity-induced particle growth in the airways, leading to an overestimation of the aerosol concentration in exhaled air. This effect was corrected by an algorithm using a "particle growth factor" derived breath by breath from the photometer signal. To test the reliability of this approach, saline particles carrying technetium-99m label were aerosolized into rabbit lungs with the use of various ventilator settings, and the aerosol deposition was assessed in parallel by photometry and by radioactivity detection over the lung and over a trap in the exhaled-air circuit. Superimposable curves of cumulative aerosol deposition, with changes in kinetics dependent on the ventilator mode, were obtained. For a given ventilator setting, absolute values of the deposition fraction were 0.32 +/- 0.04 (radiotracer quantification) and 0.36 +/- 0.04 (photometry; means +/- SD; n = 4). We conclude that the presented laser-photometric technique allows reliable on-line monitoring of the deposition of both nonhygroscopic and hygroscopic aerosol particles in ventilated lungs.

Aerosols↗
PubMed1994

[Pathogenetic rationale and diagnostic methods in allergic tuberculous synovitis of the knee joint].

The pathogenesis of tuberculous allergic synovitis was specified in the experiments on 44 rabbits by applying original simulation methods, including bivalent sensibilization, parallel study of the synovial fluid and serum of laboratory animals. A role of the synovial layer as an organ of immunogenesis and its impact on antibody titers were defined. A new diagnostic test, involving a diagnostic parameter and an equation for its calculation was developed. An algorithm was proposed for examining patients with synovitis (arthritis) of unknown etiology, which includes a set of significant clinical and laboratory parameters. Its testing in 64 patients enabled the tuberculous nature of the disease to be identified in 30% of cases.

Algorithms↗
PubMed2000

Enhanced 3D PET OSEM reconstruction using inter-update Metz filtering.

We present an enhancement of the OSEM (ordered set expectation maximization) algorithm for 3D PET reconstruction, which we call the inter-update Metz filtered OSEM (IMF-OSEM). The IMF-OSEM algorithm incorporates filtering action into the image updating process in order to improve the quality of the reconstruction. With this technique, the multiplicative correction image--ordinarily used to update image estimates in plain OSEM--is applied to a Metz-filtered version of the image estimate at certain intervals. In addition, we present a software implementation that employs several high-speed features to accelerate reconstruction. These features include, firstly, forward and back projection functions which make full use of symmetry as well as a fast incremental computation technique. Secondly, the software has the capability of running in parallel mode on several processors. The parallelization approach employed yields a significant speed-up, which is nearly independent of the amount of data. Together, these features lead to reasonable reconstruction times even when using large image arrays and non-axially compressed projection data. The performance of IMF-OSEM was tested on phantom data acquired on the GE Advance scanner. Our results demonstrate that an appropriate choice of Metz filter parameters can improve the contrast-noise balance of certain regions of interest relative to both plain and post-filtered OSEM, and to the GE commercial reprojection algorithm software.

Algorithms↗
PubMed2004

A stochastic limit cycle oscillator model of the EEG.

We present an empirical model of the electroencephalogram (EEG) signal based on the construction of a stochastic limit cycle oscillator using Ito calculus. This formulation, where the noise influences actually interact with the dynamics, is substantially different from the usual definition of measurement noise. Analysis of model data is compared with actual EEG data using both traditional methods and modern techniques from nonlinear time series analysis. The model demonstrates visually displayed patterns and statistics that are similar to actual EEG data. In addition, the nonlinear mechanisms underlying the dynamics of the model do not manifest themselves in nonlinear time series analysis, paralleling the situation with real, non-pathological EEG data. This modeling exercise suggests that the EEG is optimally described by stochastic limit cycle behavior.

Algorithms↗
PubMed2004

Extracellular matrix dynamics during vertebrate axis formation.

The first evidence for the dynamics of in vivo extracellular matrix (ECM) pattern formation during embryogenesis is presented below. Fibrillin 2 filaments were tracked for 12 h throughout the avian intraembryonic mesoderm using automated light microscopy and algorithms of our design. The data show that these ECM filaments have a reproducible morphogenic destiny that is characterized by directed transport. Fibrillin 2 particles initially deposited in the segmental plate mesoderm are translocated along an unexpected trajectory where they eventually polymerize into an intricate scaffold of cables parallel to the anterior-posterior axis. The cables coalesce near the midline before the appearance of the next-formed somite. Moreover, the ECM filaments define global tissue movements with high precision because the filaments act as passive motion tracers. Quantification of individual and collective filament "behaviors" establish fate maps, trajectories, and velocities. These data reveal a caudally propagating traveling wave pattern in the morphogenetic movements of early axis formation. We conjecture that within vertebrate embryos, long-range mechanical tension fields are coupled to both large-scale patterning and local organization of the ECM. Thus, physical forces or stress fields are essential requirements for executing an emergent developmental pattern-in this case, paraxial fibrillin cable assembly.

Animals↗
PubMed2004

In silico simulation of biological network dynamics.

Realistic simulation of biological networks requires stochastic simulation approaches because of the small numbers of molecules per cell. The high computational cost of stochastic simulation on conventional microprocessor-based computers arises from the intrinsic disparity between the sequential steps executed by a microprocessor program and the highly parallel nature of information flow within biochemical networks. This disparity is reduced with the Field Programmable Gate Array (FPGA)-based approach presented here. The parallel architecture of FPGAs, which can simulate the basic reaction steps of biological networks, attains simulation rates at least an order of magnitude greater than currently available microprocessors.

Algorithms↗
PubMed1995

Estimation of shape characteristics of surface muscle signal spectra from time domain data.

Myoelectric manifestations of muscle fatigue have been described by monitoring the first-order moment (mean frequency) of the power spectral density function during voluntary or electrically elicited sustained contractions. Higher order central moments provide additional information about the width, skewness, and kurtosis of the spectrum and its shape changes, thereby providing a description of slow nonstationarities more accurate than that allowed by the mean frequency alone. In 1986, B. Saltzberg introduced a method of representing the moments of the power spectral density function of band limited signals, without computing the Fourier transform, as weighted sums of samples of the autocorrelation function. If we allow for oversampling of the signal (and therefore of its autocorrelation function), more efficient weighted sums can be found which give Saltzberg's formula as a limiting case. The faster rate of decay of the weights implies a faster convergence of the estimates and the need to compute fewer samples of the autocorrelation function. The algorithm is particularly suitable for: 1) analysis of evoked potentials (M-waves), because it does not need zero padding to increase resolution and operates on any number of samples, and 2) on-line implementation by dedicated microprocessors performing simultaneous spectral moment analysis on a number of parallel channels.

Electrophysiology↗