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PubMed1991

A microcomputer method for continuous system simulation in health care.

A method for continuous system simulation in biomedicine and health care intended for use with personal computers is described. The method is applicable to multistate deterministic models and based on the use of standard spreadsheet programs used with such computers. It includes features such as model implementation, changes of simulation parameters, execution of simulation experiments as well as tabular and graphic presentation of simulation results. The method can be used for simulation of systems in epidemiology, health-care organization and other biomedical fields where deterministic models are suitable tools for studying phenomena connected with live systems.

Communicable Diseases↗
PubMed1995

Evaluation on blood platelets by the image analysis system VIDAS 2.5.

This paper introduces a program written on the image analysis system VIDAS 2.5. It enables the automatic quantification of high numbers of adhesion areas of vital human platelets, thus allowing statistical analysis. These adhesion areas were observed by reflection contrast microscopy (RCM), which generates images of an intense contrast and serves as a prerequisite for an evaluation by image analysis. However, RCM-photographs of the observed platelets have highly varying mean greyvalues and greyranges. These common problems for self-operating identification are excluded by two procedures within the program: 1. calibration of the scanning process for an optimal use of the available greyvalues provided by the negative, camera, and the image analysis system; and 2. relation of the threshold for discrimination of adhesion areas to the statistic parameters of the histogram within each individual digitized image. Images processed according to these prerequisites were transferred to the VIDAS implemented routines for identification and measurement of areas. Thus, image analysis combined with RCM offers a tool for basic and clinical platelet research, which is shown by an example of stimulation and inhibited stimulation of platelet activation.

Blood Platelets↗
PubMed1993

Non-discrete biomolecular computing: an approach to computational complexity.

General principles of information processing at the molecular level inherent in simple biological and biomolecular entities can be used to elaborate essentially new non-discrete information-processing devices. These principles are: giant parallelism of information processing; processing mechanisms based on complicated non-linear dynamics; high efficiency of information transformations; considerable behavioral complexity of computational (pseudoelementary) primitives; and the possibility of variation and evolution of the molecular components of information-processing devices, including the possibility of evolutionary learning. Problems of high computational complexity are currently of great practical importance. Non-discrete biomolecular information-processing devices seem to be able to solve effectively some classes of problems of high computational complexity.

Biomedical Engineering↗
PubMed1994

The use of generalized cell-survival data in a physiologically based objective function for hyperthermia treatment planning: a sensitivity study with a simple tissue model implanted with an array of ferromagnetic thermoseeds.

PURPOSE: A physiologically based objective function for identifying a combination of ferromagnetic seed temperatures and locations that maximizes the fraction of tumor cells killed in pretreatment planning of local hyperthermia. METHODS AND MATERIALS: An objective-function is developed and coupled to finite element software that solves the bioheat transfer equation. The sensitivity of the objective function is studied in the optimization of a ferromagnetic hyperthermia treatment. The objective function has several salient features including (a) a physiological basis that considers increasing the fraction of cells killed with increasing temperatures above a minimum therapeutic temperature (Tmin,thera), (b) a term to penalize for heating of normal tissues above Tmin,thera, and (c) a scalar weighting factor (gamma) that has treatment implications. Reasonable estimates for gamma are provided and their influence on the objective function is demonstrated. The cell-kill algorithm formulated in the objective function is based empirically upon the behavior of published hyperthermic cell-survival data. The objective function is shown to be independent of normal tissue size and shape when subjected to a known outer-surface, thermal boundary condition. Therefore, fractions of cells killed in tumors of different shapes and sizes can be compared to determine the relative performance of thermoseed arrays to heat different tumors. RESULTS: In simulations with an idealized tissue model perfused by blood at various rates, maxima of the objective function are unique and identify seed spacings and Curie-point temperatures that maximize the fraction of tumor cells killed. In ferromagnetic hyperthermia treatment planning, seed spacing can be based on maximizing the minimum tumor temperature and minimizing the maximum normal tissue temperature. It is shown that this treatment plan is less effective than a plan based on seed spacings that maximize the objective function. CONCLUSIONS: It is shown that under the assumptions of the model and based on a desired therapeutic goal, the objective function identifies a combination of thermoseed temperatures and locations that maximizes the fraction of tumor cells killed.

Cell Survival↗
PubMed2006

SCEW: a Microsoft Excel add-in for easy creation of survival curves.

Survival curves are frequently used for reporting survival or mortality outcomes of experimental pharmacological/toxicological studies and of clinical trials. Microsoft Excel is a simple and widely used tool for creation of numerous types of graphic presentations however it is difficult to create step-wise survival curves in Excel. Considering the familiarity of clinicians and biomedical scientists with Excel, an algorithm survival curves in Excel worksheet (SCEW) has been developed for easy creation of survival curves directly in Excel worksheets. The algorithm has been integrated in the form of Excel add-in for easy installation and usage. The program is based on modification of frequency data for binary break-up using the spreadsheet formula functions whereas a macro subroutine automates the creation of survival curves. The advantages of this program are simple data input, minimal procedural steps and the creation of survival curves in the familiar confines of Excel.

Algorithms↗
PubMed2006

Generalized training subset selection for statistical estimation of epicardial activation maps from intravenous catheter measurements.

Catheter-based electrophysiological studies of the epicardium are limited to regions near the coronary vessels or require transthoracic access. We have developed a statistical approach by which to estimate high-resolution maps of epicardial activation from very low-resolution multi-electrode venous catheter measurements. This technique uses a linear estimation model that derives a relationship between venous catheter measurements and unmeasured epicardial sites from a set of previously recorded, high-resolution epicardial activation-time maps used as a training data set based on the spatial covariance of the measurement sites. We performed 14 dog experiments with various interventions to create an epicardial activation-time map database. This database included a total of 592 epicardial activation maps which were recorded using a sock array placed on the ventricles of dog hearts. We present five approaches, which examined sequential addition and removal of maps to select a generalized training set for the estimation technique. The selection consisted of choosing a subset of epicardial ectopic activation-time maps from the database of beats which resulted in estimation accuracy levels better than or at least similar to using all the maps in database. Our aim was to minimize the redundancy in the database and to be able to guide the eventual procedures required to obtain training data from open-chest surgery patients. The results from this study illustrated this redundancy and suggested that by including an optimal subset (around 100 maps) of the full database the estimation technique was able to perform as well as and even in some cases better than including all the maps in the database. The results also suggest that such an approach is feasible for providing accurate reconstruction of complete epicardial activation-time maps in a clinical setting and with fewer maps we can obtain similar reconstruction accuracy levels.

Animals↗
PubMed2006

A novel method for analysis of single ion channel signal based on wavelet transform.

A single ion channel signal was analysed by the power distribution fraction constructed by a discrete wavelet transform. Average opening time and energy distribution of the signal can be obtained directly by this method. The method can also be used when the signal is corrupted by noise. By contrast, the conventional frequency domain analysis method--power spectral density--is less effective. Power distribution fraction will therefore give more useful information in analysis of experimental ion channel signals, principally by giving values of the mean channel opening time. The method may be applied to distinguish different ion channels more efficiently and to find their reactions to drugs.

Algorithms↗
PubMed2006

Long-term signal detection, segmentation and summarization using wavelets and fractal dimension: a bioacoustics application in gastrointestinal-motility monitoring.

The current paper describes a wavelet-based method for long-term processing and analysis of gastrointestinal sounds (GIS). Windowing techniques are used to select sequential blocks of the prolonged multi-channel recordings and proceed to various wavelet-domain processing stages. De-noising, significant-activity detection, automated segmentation and extraction of summary curves are applied in an integrated mode, allowing for enhanced content manipulation and analysis. The proposed analysis scheme combines flexible long-term graphical representation tools, while maintaining the ability of quick browsing via visualization and auralization of the detected short-term events. This work is part of a project aiming to implement non-invasive diagnosis over gastrointestinal-motility (GIM) physiology. However, the proposed techniques might be applied to any study of long-term bioacoustics time series.

Algorithms↗
PubMed2006

Three-dimensional US volume analysis of gastric pseudotumors in a porcine model.

BACKGROUND: Tumor burden is difficult to estimate by endoscopy and conventional EUS. OBJECTIVE: The purpose of this study was to determine the accuracy and the reliability of a new 3-dimensional (3D) EUS system in a pseudotumor model (Olympus EUS EXERA EU-M60). DESIGN: A pseudotumor model was developed in a porcine stomach. Pseudotumors were created by injecting various volumes of US gel (0.3, 0.5, 0.7, and 1 mL) into porcine stomach specimens, and then the volume was measured in vitro. Two investigators made volume measurements by outlining the cross-sectional area of the pseudotumor at different radial planes. The instrument then automatically calculated the volume based on the outlined cross-sectional areas. The measured volume was compared with the actual volume of the pseudotumor by using a Bland-Altman analysis. Every second, third, fourth, fifth, sixth, and tenth image was measured to calculate the tumor volume and to determine the optimum number of images required for accurate volume determination. Inter- and intraobserver variability, percentage error, Bland-Altman analysis, analysis of variance (ANOVA), and kappa statistic were performed. SETTING: This study was performed in an in vitro animal model. PATIENTS: There were no patients involved in this study. MAIN OUTCOME MEASUREMENTS: Accuracy and reliability of pseudotumor volume measurement. RESULTS: When averaging across all measurements, the overall average mean error was 3.25%. The overall inter-rater reliability as measured by intraclass correlation coefficient was 0.78. The overall intra-rater reliability as measured by intraclass correlation coefficient was 0.99. Bland-Altman analysis and ANOVA showed similar low variability for measured volumes based on image frequencies for volume calculations between every other and every sixth image but greater variability for measured volumes based on every tenth image. Larger pseudotumors were measured with a slight decrease in mean percentage error. The kappa statistic for interobserver variability was .61, which demonstrated substantial agreement among observers. LIMITATIONS: The major limitation of this technology is the penetration of the US beam to evaluate large tumors, because the US transducer is high frequency (20 MHz) and, therefore, has a limited penetration. CONCLUSIONS: In conclusion, the new Olympus EUS EXERA EU-M60 3D US probe allowed for accurate volume measurements of small pseudotumors in porcine stomach model in vitro. There was substantial evaluator agreement, with a low interobserver variability. Larger pseudotumors were measured with a slightly lower percentage error than smaller pseudotumors. Volumes measured with a greater number of radial images were measured slightly more accurately. We plan to test this device in patients with GI tumors in the near future.

Animals↗
PubMed2005

Broad-beam spectral Doppler sonification of the vena contracta using matrix-array technology: A new solution for semi-automated quantification of mitral regurgitant flow volume and orifice area.

OBJECTIVES: The objective of this study was to evaluate broad-beam spectral Doppler sonification of the vena contracta using a matrix-array transducer for quantification of mitral regurgitation (MR). BACKGROUND: Noninvasive assessment of the severity of valvular regurgitation remains challenging. A recent technique measures regurgitant flow directly at the vena contracta based on the product of velocity times backscattered Doppler power (proportional to orifice area). That approach, however, has been limited by relatively narrow conventional beamwidths. Matrix-array transducers, recently developed for three-dimensional imaging, can potentially provide broader beams. Therefore, we addressed the hypothesis that deliberate broadening of the Doppler beam can encompass larger regurgitant cross-sectional areas to capture a broader range of regurgitant flows. METHODS: A matrix-array transducer system was modified to provide a three-dimensionally expanded spectral Doppler sample volume. Calculations of orifice area, flow rate, and regurgitant stroke volume (RSV) from Doppler power were automated on board a routinely used echocardiographic scanner and tested in vitro. In 24 patients with isolated MR, RSV was compared with magnetic resonance imaging (MRI) mitral inflow minus aortic outflow from phase-velocity maps. RESULTS: The calculated flow rate and RSV correlated and agreed well with reference values in vitro (r = 0.98 to 0.99) and in patients (r = 0.93, mean difference 0.4 +/- 3.2 ml, p = NS vs. 0), with sufficient sonification to measure flow orifices up to 0.85 cm in diameter. Agreement with MRI was comparable in 17 patients with central and seven with eccentric jets (p = NS vs. 0). CONCLUSIONS: The broad-beam spectral Doppler technique provides accurate, largely automated quantification of regurgitant flow rate and integrated RSV directly at the lesion. The accuracy related to broader sonification is made possible by the new matrix-array transducer design.

Adult↗
PubMed2005

Detection of peripheral vascular stenosis by assessing skeletal muscle flow reserve.

OBJECTIVES: We sought to determine whether the severity of peripheral arterial disease (PAD) can be assessed by measuring blood flow reserve in limb skeletal muscle with contrast-enhanced ultrasound (CEU). BACKGROUND: Noninvasive imaging of distal limb perfusion could improve management of patients with PAD by evaluating the impact of large and small vessel disease, and collateral flow. METHODS: In 12 dogs, blood flow in the quadriceps femoris was measured by CEU at rest and during either electrostimulated contractile exercise or adenosine infusion. Femoral artery blood flow was measured by Doppler ultrasound. Studies were performed in the absence and presence of either moderate or severe stenosis (pressure gradient of 10 to 20 mm Hg and >20 mm Hg, respectively). RESULTS: Resting femoral artery blood flow progressively decreased with stenosis severity, while resting skeletal muscle flow was reduced only with severe stenosis (52 +/- 21% of baseline, p < 0.05), indicating the presence of collateral flow. Skeletal muscle flow reserve during contractile exercise or adenosine decreased incrementally with increasing stenosis severity (p < 0.01). The stenotic pressure gradient correlated with skeletal muscle flow reserve for exercise and adenosine (r = 0.70 for both, p < 0.01). CONCLUSIONS: Contrast-enhanced ultrasound of limb skeletal muscle can be used to assess the severity of PAD by measuring muscle flow reserve during either contractile exercise or pharmacologic vasodilation. Unlike currently used methods, this technique may provide a measure of the physiologic effects of large- and small-vessel PAD, and the influence of collateral perfusion.

Adenosine↗
PubMed2006

Updated hazard rate equations for dual safeguard systems.

A previous paper by this author [M.J. Rothschild, Updated hazard rate equation for single safeguards, J. Hazard. Mater. 130 (1-2) (2006) 15-20] showed that commonly used analytical methods for quantifying failure rates overestimates the risk in some circumstances. This can lead the analyst to mistakenly believe that a given operation presents an unacceptable risk. For a single safeguard system, a formula was presented in that paper that accurately evaluates the risk over a wide range of conditions. This paper expands on that analysis by evaluating the failure rate for dual safeguard systems. The safeguards can be activated at the same time or at staggered times, and the safeguard may provide an indication whether it was successful upon a challenge, or its status may go undetected. These combinations were evaluated using a Monte Carlo simulation. Empirical formulas for evaluating the hazard rate were developed from this analysis. It is shown that having the safeguards activate at the same time while providing positive feedback of their individual actions is the most effective arrangement in reducing the hazard rate. The hazard rate can also be reduced by staggering the testing schedules of the safeguards.

Computer Simulation↗
PubMed2004

Myelin characterization of fetal brain with mono-point estimated T1-maps.

Magnetic resonance imaging (MRI) allows non-invasive assessment of fetus brain maturation at the beginning of the third trimester because of its high sensitivity for fat and water content changes accompanying the myelin formation. In this article we propose a new ultra-fast mono point T(1)-map method based on simplified optimized Gradient Echo (GE) two-point method. Results are compared between the two methods and the precision discussed. This quantitative method can be used in clinical routine, as sedation is not needed for patients.

Adult↗
PubMed2004

Neural predictive error signal correlates with depressive illness severity in a game paradigm.

Considerable experimental evidence supports the existence of predictive error signals in various brain regions during associative learning in animals and humans. These regions include the prefrontal cortex, temporal lobe, cerebellum and monoamine systems. Various quantitative theories have been developed to describe behaviour during learning, including Rescorla-Wagner, Temporal Difference and Kalman filter models. These theories may also account for neural error signals. Reviews of imaging studies of depressive illness have consistently implicated the prefrontal and temporal lobes as having abnormal function, and sometimes structure, whilst the monoamine systems are directly influenced by antidepressant medication. It was hypothesised that such abnormalities may be associated with a dysfunction of associative learning that would be reflected by different predictive error signals in depressed patients when compared with healthy controls. This was tested with 30 subjects, 15 with a major depressive illness, using a gambling paradigm and fMRI. Consistent with the hypothesis, depressed patients differed from controls in having an increased error signal. Additionally, for some brain regions, the magnitude of the error signal correlated with Hamilton depression rating of illness severity. Structural equation modelling was used to investigate hypothesised change in effective connectivity between prespecified regions of interest in the limbic and paralimbic system. Again, differences were found that in some cases correlated with illness severity. These results are discussed in the context of quantitative theories of brain function, clinical features of depressive illness and treatments.

Adult↗
PubMed2004

Combining voxel intensity and cluster extent with permutation test framework.

In a massively univariate analysis of brain image data, statistical inference is typically based on intensity or spatial extent of signals. Voxel intensity-based tests provide great sensitivity for high intensity signals, whereas cluster extent-based tests are sensitive to spatially extended signals. To benefit from the strength of both, the intensity and extent information needs to be combined. Various ways of combining voxel intensity and cluster extent are possible, and a few such combining methods have been proposed. Poline et al.'s [NeuroImage 16 (1997) 83] minimum P value approach is sensitive to signals whose either intensity or extent is significant. Bullmore et al.'s [IEEE Trans. Med. Imag. 18 (1999) 32] cluster mass method can detect signals whose intensity and extent are sufficiently large, even when they are not significant by intensity or extent alone. In this work, we study such combined inference methods using combining functions (Pesarin, F., 2001. Multivariate Permutation Tests. Wiley, New York) and permutation framework [Holmes et al., J. Cereb. Blood Flow Metab. 16 (1996) 7], which allow us to examine different ways of combining voxel intensity and cluster extent information without knowing their distribution. We also attempt to calibrate combined inference by using weighted combining functions, which adjust the test according to signals of interest. Furthermore, we propose meta-combining, a combining function of combining functions, which integrates strengths of multiple combining functions into a single statistic. We found that combined tests are able to detect signals that are not detected by voxel or cluster size test alone. We also found that the weighted combining functions can calibrate the combined test according to the signals of interest, emphasizing either intensity or extent as appropriate. Though not necessarily more sensitive than individual combining functions, the meta-combining function is sensitive to all types of signals and thus can be used as a single test summarizing all the combining functions.

Artifacts↗
PubMed2004

New methods for the computer-assisted 3-D reconstruction of neurons from confocal image stacks.

Exact geometrical reconstructions of neuronal architecture are indispensable for the investigation of neuronal function. Neuronal shape is important for the wiring of networks, and dendritic architecture strongly affects neuronal integration and firing properties as demonstrated by modeling approaches. Confocal microscopy allows to scan neurons with submicron resolution. However, it is still a tedious task to reconstruct complex dendritic trees with fine structures just above voxel resolution. We present a framework assisting the reconstruction. User time investment is strongly reduced by automatic methods, which fit a skeleton and a surface to the data, while the user can interact and thus keeps full control to ensure a high quality reconstruction. The reconstruction process composes a successive gain of metric parameters. First, a structural description of the neuron is built, including the topology and the exact dendritic lengths and diameters. We use generalized cylinders with circular cross sections. The user provides a rough initialization by marking the branching points. The axes and radii are fitted to the data by minimizing an energy functional, which is regularized by a smoothness constraint. The investigation of proximity to other structures throughout dendritic trees requires a precise surface reconstruction. In order to achieve accuracy of 0.1 microm and below, we additionally implemented a segmentation algorithm based on geodesic active contours that allow for arbitrary cross sections and uses locally adapted thresholds. In summary, this new reconstruction tool saves time and increases quality as compared to other methods, which have previously been applied to real neurons.

Algorithms↗
PubMed2005

Cortical thickness analysis examined through power analysis and a population simulation.

We have previously developed a procedure for measuring the thickness of cerebral cortex over the whole brain using 3-D MRI data and a fully automated surface-extraction (ASP) algorithm. This paper examines the precision of this algorithm, its optimal performance parameters, and the sensitivity of the method to subtle, focal changes in cortical thickness. The precision of cortical thickness measurements was studied using a simulated population study and single subject reproducibility metrics. Cortical thickness was shown to be a reliable method, reaching a sensitivity (probability of a true-positive) of 0.93. Six different cortical thickness metrics were compared. The simplest and most precise method measures the distance between corresponding vertices from the white matter to the gray matter surface. Given two groups of 25 subjects, a 0.6-mm (15%) change in thickness can be recovered after blurring with a 3-D Gaussian kernel (full-width half max = 30 mm). Smoothing across the 2-D surface manifold also improves precision; in this experiment, the optimal kernel size was 30 mm.

Algorithms↗