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PubMed2003

Implementation of non-invasive brain physiological monitoring concepts.

The paper presents innovative methods and technology for non-invasive intracranial hemodynamics monitoring based on the measurement of brain parenchyma acoustic properties. The clinical investigation of new technology shows the similarity between the invasively recorded intracranial pressure (ICP) and non-invasively recorded intracranial blood volume (IBV) pulse waves, slow waves and slow trends under intensive care unit (ICU) conditions. Also, the applicability of the non-invasive IBV slow wave monitoring technique for cerebrovascular autoregulation non-invasive long-term monitoring is demonstrated by theoretical and experimental studies.

Adult↗
PubMed2003

Particle-hemodynamics modeling of the distal end-to-side femoral bypass: effects of graft caliber and graft-end cut.

Late-stage occlusions of peripheral synthetic bypass grafts are frequently due to intimal hyperplasia and/or thrombosis at the distal anastomosis, resulting in unacceptably high failure rates. It has been widely established that hemodynamic and blood particle interactions with the vascular surface as well as surgical injury and compliance mismatch are inciting mechanisms capable of eliciting various cellular level responses associated with distal anastomotic intimal hyperplasia (IH) formation. Primary geometric factors influencing anastomotic hemodynamics include the graft-to-artery diameter ratio and graft-hood shape, which are determined by the graft caliber and initial graft-end cut selected by the vascular surgeon. In this study, the particle-hemodynamic effects of graft-end cuts (straight, curved, and S-shaped) and graft-to-artery diameter ratios (2:1 vs. 1.5:1) have been numerically assessed in four common unexpanded anastomotic configurations with respect to vortical flow patterns, wall shear stress based parameters, and platelet interactions with the vascular surface. Sites of significant platelet-wall interactions have been identified by a novel near-wall residence time (NWRT) model, which includes shear stress based factors for platelet activation and endothelial cell expression of anti-thrombogenic compounds. Of the configurations evaluated, straight and curved graft-end cuts with a graft-to-artery diameter ratio of 1.5:1 were found to reduce the particle-hemodynamic potential for IH development at locations critical to flow delivery. Nevertheless, the potential for significant IH occurrence via platelet and/or endothelial response pathways was highly evident in all conventional anastomoses considered, such that a decisively superior configuration was not determined. These results illustrate the need for alternative anastomotic designs with the intent of reducing critical hemodynamic wall parameters and mitigating regions of significant particle-wall interactions.

Anastomosis, Surgical↗
PubMed2000

Two-dimensional spatial and temporal displacement and deformation field fitting from cardiac magnetic resonance tagging.

Tagged magnetic resonance imaging is a specially developed technique to noninvasively assess contractile function of the heart. Several methods have been developed to estimate myocardial deformation from tagged image data. Most of these methods do not explicitly impose a continuity constraint through time although myocardial motion is a continuous physical phenomenon. In this paper, we propose to model the spatio-temporal myocardial displacement field by a cosine series model fitted to the entire tagged dataset. The method has been implemented in two dimensions (2D)+time. Its accuracy was successively evaluated on actual tagged data and on a simulated two-dimensional (2D) moving heart model. The simulations show that an overall theoretical mean accuracy of 0.1 mm can be attained with adequate model orders. The influence of the tagging pattern was evaluated and computing time is provided as a function of the model complexity and data size. This method provides an analytical and hierarchical model of the 2D+time deformation inside the myocardium. It was applied to actual tagged data from a healthy subject and from a patient with ischemia. The results demonstrate the adequacy of the proposed model for this evaluation.

Computer Simulation↗
PubMed2003

In vivo strain and stress estimation of the heart left and right ventricles from MRI images.

Mechanical properties of the myocardium have been investigated intensively in the last four decades. Many complex strain energy functions have been used to estimate the stress-strain relationship of myocardium because the heart muscle is an inhomogeneous, anisotropic, and nearly incompressible material, which undergoes large deformations. These functions can be effective for fitting in vitro experimental data from myocardial stretch testing. However, it is difficult to model in vivo myocardium using these strain energy functions. Moreover, such estimates have so far been carried out almost exclusively on the left ventricle, because of the relative thinness and complex geometry of the right ventricle. Previous work from our research group has successful estimated the motion and deformation of both the left and the right ventricles, using data from noninvasive tagged magnetic resonance imaging. In this paper, we present a novel statistical model to estimate the in vivo material properties and strain and stress distribution in both ventricles, using such data. Two normal hearts and two hearts with right-ventricular hypertrophy (RVH) were studied and noticeable differences were found between the strain and stress distributions for normal volunteers and RVH patients. Compared to the strain energy function approach, our model is more intuitively understandable.

Humans↗
PubMed1998

Definition of a four-dimensional continuous planispheric transformation for the tracking and the analysis of left-ventricle motion.

Cardiologists assume that analysis of the motion of the heart (especially the left ventricle) can provide useful information about the health of the myocardium. A 4-D polar transformation is defined to describe the left-ventricle (LV) motion and a method is presented to estimate it from sequences of 3-D images. The transformation is defined in 3-D planispheric coordinates (3PC) by a small number of parameters involved in a set of simple linear equations. It is continuous and regular in time and space, and periodicity in time can be imposed. The local motion can be easily decomposed into a few canonical motions (radial motion, rotation around the long-axis, elevation). To recover the motion from original data, the 4-D polar transformation is calculated using an adaptation of the iterative closest-point algorithm. We present the mathematical framework and a demonstration of its feasability on a series of gated SPECT sequences.

Humans↗
PubMed2002

The network vs. pacemaker theory of the activity of RVL presympathetic neurons--a comparison with another putative pacemaker system.

Intracellular studies previously conducted in our laboratory on adult rats indicate that the activity of spinally projecting RVL neurons (neurons located in the Rostral Ventrolateral Medulla) results from synaptic inputs. The data obtained by others in medullary slices suggest that the firing of these neurons (RVL C1 and/or non-C1 type, depending on experimental conditions) is mainly determined by their 'beating' pacemaker properties. Interestingly, there is an analogy between the contrasting views on the role of the network vs. pacemakers in the generation of sympathetic tone, and a debate regarding the relative role of such mechanisms in other types of 'spontaneously' active neurons, including dopaminergic neurons of the Substantia Nigra/Ventral Tegmental Area (in ventral mesencephalon). This short review discusses our previous in vivo studies and more recent data obtained in vitro after acute cell isolation, showing that under both experimental conditions, the RVL neurons display no clear pacemaker-like properties. Interestingly, pacemaker activity of dopaminergic mesencephalic neurons can be easily demonstrated in brain slices and after acute isolation, but not in vivo. These findings strongly suggest that under normal in vivo conditions, individual neurons belonging to these two neural systems function as elements of networks.

Animals↗
PubMed2004

A mathematical model for prediction of drug molecule diffusion across the blood-brain barrier.

BACKGROUND: Predicting the ability of drugs to enter the brain is a longstanding problem in neuropharmacology. The first step in creating a much-needed computational algorithm for predicting whether a drug will enter brain is to devise a rigorous mathematical model. METHODS: Employing two experimental measures of blood-brain barrier (BBB) penetrability (brain/plasma ratio and the brain-uptake index) and 14 theoretically derived biophysical predictors, a mathematical model was developed to quantitatively correlate molecular structure with ability to traverse the BBB. RESULTS: This mathematical model employs Stein's hydrogen bonding number and Randic's topological descriptors to correlate structure with ability to cross the BBB. The final model accurately predicts the ability of test molecules to cross the BBB. CONCLUSIONS: A mathematical method to predict blood-brain barrier penetrability of drug molecules has been successfully devised. As a result of bioinformatics, chemoinformatics and other informatics-based technologies, the number of small molecules being developed as potential therapeutics is increasing exponentially. A biophysically rigorous method to predict BBB penetrability will be a much-needed tool for the evaluation of these molecules.

Algorithms↗
PubMed1997

Theoretical study of cardiac transient conduction blocks on reentries induction. Applications to antiarrhythmic drugs.

Limitations of antiarrhythmic drugs on cardiac sudden death prevention appeared since the early 80's. The "Cardiac Arrhythmia Suppression Trial" (CAST) showed more recently that mortality was significantly higher in patients treated with some particular antiarrhythmic drugs than in non-treated patients. In this field, our group recently demonstrated that a bolus of a Class 1 B antiarrhythmic drug was able to trigger a ventricular fibrillation due to transient blocks induction. The aim of the present work was to systematically study, by use of the van Capelle and Durrer (VCD) model which allows to simulate ventricular activation wave propagation, the link between arrhythmogenic effects and the ability of transient blocks to possibly degenerate in severe arrhythmias. A fragment of the ventricular wall is represented by an array of 16384 elements electrically coupled. Effects of induction of one or several transient blocks, as the effects of their size and duration on possible induction of reentries have been studied. Results obtained show that various combinations between these different parameters may trigger reentries, ventricular tachycardia and/or more complex patterns assimilable to ventricular fibrillation. These results clearly evidence the fact that possible induction of transient blocks may directly be related to risk factor associated to arrhythmogenic effects of antiarrhythmic drugs.

Animals↗
PubMed1998

An echocardiographic and magnetic resonance imaging comparative study of right ventricular volume determination.

Assessment of right ventricular volume and function is important in many clinical settings involving heart or lung disease. However, the complexity of the right ventricular anatomy has prevented accurate volume determination by two-dimensional echocardiography. In the present study, 5 models incorporating standard echocardiographic views, were used to determine right ventricular volume in 10 human subjects. Two models were contingent on the true crescentic appearance of the right ventricle, whereas the remaining 3 calculated the right ventricular volume as a pyramid, an ellipsoid or other tapering geometrical figures, respectively. Subsequently, echocardiographic right ventricular volumes were compared to magnetic resonance imaging derived volumes. Correlation analysis and agreement measurement between the echocardiographic and magnetic resonance end-diastolic volume were performed in 10 out of 10 subjects and in 9 out of 10 subjects for the end-systolic volume. The 2 crescentic models resulted in the most reliable estimation of right ventricular volume. Those findings suggest that models based on right ventricular anatomical landmarks are feasible and should be preferred in echocardiographic studies.

Adult↗
PubMedDate not supplied

A model of a segmental oscillator in the leech heartbeat neuronal network.

We modeled a segmental oscillator of the timing network that paces the heartbeat of the leech. This model represents a network of six heart interneurons that comprise the basic rhythm-generating network within a single ganglion. This model builds on a previous two cell model (Nadim et al., 1995) by incorporating modifications of intrinsic and synaptic currents based on the results of a realistic waveform voltage-clamp study (Olsen and Calabrese, 1996). Due to these modifications, the new model behaves more similarly to the biological system than the previous model. For example, the slow-wave oscillation of membrane potential that underlies bursting is similar in form and amplitude to that of the biological system. Furthermore, the new model with its expanded architecture demonstrates how coordinating interneurons contribute to the oscillations within a single ganglion, in addition to their role of intersegmental coordination.

Animals↗
PubMed2004

Increased nonstationarity of neonatal heart rate before the clinical diagnosis of sepsis.

The clinical diagnosis of neonatal sepsis is preceded by abnormal heart rate (HR) characteristics of transient decelerations and reduced variability, which intuitively appear to be more nonstationary than normal HR variability. Our goals were to investigate stationarity of HR, and to devise measures useful for early diagnosis of neonatal sepsis. In this context, we define non-stationarity to be present when the observed data differ from surrogate data generated by stationary Gaussian noise with arbitrary linear correlations. We devised statistical methods for determining stationarity of HR data based on the two-sample Kolmogorov-Smirnov (KS) test. We compared distributions of KS distances between small sample epochs from clinical data with those of isospectral surrogates and of surrogates generated using the amplitude-adjusted Fourier transform technique, reasoning that they should differ significantly for nonstationary data. We found significant evidence of non-stationarity for records longer than 1 min. We developed new HR measures based on the empirical cumulative distribution function (ECDF) that are highly significantly associated with sepsis, but are not correlated with HR measures such as moments or sample entropy. We conclude that neonatal HR data cannot be assumed to be stationary, and become even less stationary prior to sepsis.

Algorithms↗
PubMed2004

Activation dynamics in anisotropic cardiac tissue via decoupling.

Bidomain theory for cardiac tissue assumes two interpenetrating anisotropic media--intracellular (i) and extracellular (e)--connected everywhere via a cell membrane; four local parameters sigma(i,e)(l,t) specify conductivities in the longitudinal (l) and transverse (t) directions with respect to cardiac muscle fibers. The full bidomain model for the propagation of electrical activation consists of coupled elliptic-parabolic partial differential equations for the transmembrane potential upsilon(m) and extracellular potential phi(e), together with quasistatic equations for the flow of current in the extracardiac regions. In this work we develop a preliminary assessment of the consequences of neglecting the effect of the passive extracardiac tissue and intracardiac blood masses on wave propagation in isolated whole heart models and describe a decoupling procedure, which requires no assumptions on the anisotropic conductivities and which yields a single reaction-diffusion equation for simulating the propagation of activation. This reduction to a decoupled model is justified in terms of the dimensionless parameter epsilon = (sigma(i)(l)sigma(e)(t) - sigma(i)(t)sigma(e)(l))/(sigma(i)(l) + sigma(e)(l))(sigma(i)(t) + sigma(e)(t)). Numerical simulations are generated which compare propagation in a sheet H of cardiac tissue using the full bidomain model, an isolated bidomain model, and the decoupled model. Preliminary results suggest that the decoupled model may be adequate for studying general properties of cardiac dynamics in isolated whole heart models.

Action Potentials↗
PubMed1999

Linking a genetic defect to its cellular phenotype in a cardiac arrhythmia.

Advances in genetics and molecular biology have provided an extensive body of information on the structure and function of the elementary building blocks of living systems. Genetic defects in membrane ion channels can disrupt the delicate balance of dynamic interactions between the ion channels and the cellular environment, leading to altered cell function. As ion-channel defects are typically studied in isolated expression systems, away from the cellular environment where they function physiologically, a connection between molecular findings and the physiology and pathophysiology of the cell is rarely established. Here we describe a single-channel-based Markovian modelling approach that bridges this gap. We achieve this by determining the cellular arrhythmogenic consequences of a mutation in the cardiac sodium channel that can lead to a clinical arrhythmogenic disorder (the long-QT syndrome) and sudden cardiac death.

Action Potentials↗
PubMed1996

Scaling behaviour of heartbeat intervals obtained by wavelet-based time-series analysis.

Biological time-series analysis is used to identify hidden dynamical patterns which could yield important insights into underlying physiological mechanisms. Such analysis is complicated by the fact that biological signals are typically both highly irregular and non-stationary, that is, their statistical character changes slowly or intermittently as a result of variations in background influences. Previous statistical analyses of heartbeat dynamics have identified long-range correlations and power-law scaling in the normal heartbeat, but not the phase interactions between the different frequency components of the signal. Here we introduce a new approach, based on the wavelet transform and an analytic signal approach, which can characterize non-stationary behaviour and elucidate such phase interactions. We find that, when suitably rescaled, the distributions of the variations in the beat-to-beat intervals for all healthy subjects are described by a single function stable over a wide range of timescales. However, a similar scaling function does not exist for a group with cardiopulmonary instability caused by sleep apnoea. We attribute the functional form of the scaling observed in the healthy subjects to underlying nonlinear dynamics, which seem to be essential to normal heart function. The approach introduced here should be useful in the analysis of other nonstationary biological signals.

Adult↗
PubMed1987

Tracer disposition kinetics in the determination of local cerebral blood flow by a venous equilibrium model, tube model, and distributed model.

Tracer distribution kinetics in the determination of local cerebral blood flow (LCBF) were examined by using three models, i.e., venous equilibrium, tube, and distributed models. The technique most commonly used for measuring LCBF is the tissue uptake method, which was first developed and applied by Kety (1951). The measurement of LCBF with the 14C-iodoantipyrine (IAP) method is calculated by using an equation derived by Kety based on the Fick's principle and a two-compartment model of blood-tissue exchange and tissue concentration at a single data point (Sakurada et al., 1978). The procedure, in which the tissue is to be in equilibrium with venous blood, will be referred to as the tissue equilibration model. In this article, effects of the concentration gradient of tracer along the length of the capillary (tube model) and the transverse heterogeneity in the capillary transit time (distributed model) on the determination of LCBF were theoretically analyzed for the tissue sampling method. Similarities and differences among these models are explored. The rank order of the LCBF calculated by using arterial blood concentration time courses and the tissue concentration of tracer based on each model were tube model (model II) less than distributed model (model III) less than venous equilibrium model (model I). Data on 14C-IAP kinetics reported by Ohno et al. (1979) were employed. The LCBFs calculated based on model I were 45-260% larger than those in models II or III. To discriminate among three models, we propose to examine the effect of altering the venous infusion time of tracer on the apparent tissue-to-blood concentration ratio (lambda app). A range of the ratio of the predicted lambda app in models II or III to that in model I was from 0.6 to 1.3. In the future, there may be a need to determine which model should be used to calculate the LCBF based on this discriminator and to develop another discriminator by using multiple data points based on positron emission tomography.

Animals↗
PubMed1987

Tracer-kinetic models for measuring cerebral blood flow using externally detected radiotracers.

All tracer-kinetic models currently employed with positron-emission tomography (PET) are based on compartmental assumptions. Our first indication that a compartmental model might suffer from severe limitations in certain circumstances when used with PET occurred when we implemented the Kety tissue-autoradiography technique for measuring CBF and observed that the resulting CBF estimates, rather than remaining constant (to within predictable statistical uncertainty) as expected, fell with increasing scan duration T when T greater than 1 min. After ruling out other explanations, we concluded that a one-compartment model does not possess sufficient realism for adequately describing the movement of labeled water in brain. This article recounts our search for more realistic substitute models. We give our derivations and results for the residue-detection impulse responses for unit capillary-tissue systems of our two candidate distributed-parameter models. In a sequence of trials beginning with the simplest, we tested four progressively more detailed candidate models against data from appropriate residue-detection experiments. In these, we generated high-temporal-resolution counting-rate data reflecting the history of radiolabeled-water uptake and washout in the brains of rhesus monkeys. We describe our treatment of the data to yield model-independent empirical values of CBF and of other parameters. By substituting these into our trial-model functions, we were able to make direct comparisons of the model predictions with the experimental dynamic counting-rate histories, confirming that our reservations concerning the one-compartment model were well founded and obliging us to reject two others. We conclude that a two-barrier distributed-parameter model has the potential of serving as a substitute for the Kety model in PET measurements of CBF in patients, especially when scan durations for T greater than 1 min are desired.

Animals↗
PubMed1989

Evaluation of the 11CO2 positron emission tomographic method for measuring brain pH. II. Quantitative pH mapping in patients with ischemic cerebrovascular diseases.

A practical method has been developed that, using 11CO2 and positron emission tomography (PET), computes and maps (a) "effective pH" (pHt), a weighted average of intra- and extracellular pH, and (b) "clearance" (K1), product of blood flow and 11CO2 extraction. This method, together with measurements of cerebral blood flow (CBF) and oxygen extraction fraction (OEF), was applied to 12 patients with cerebral ischemia or stroke. The regional K1 was positively correlated with CBF (n = +0.78). The k1/CBF ratio, representing the extraction fraction ratio of 11CO2 to H2 15O, was negatively correlated with CBF (r = -0.54), suggesting that 11CO2 extraction decreases as flow increases. In five acute stroke patients within 2 days of onset, the injured cortex had lower CBF (20.6 ml/min/100 g), higher OEF (78.1%), and lower pHt (6.96) than the contralateral cortex (CBF = 41.4 ml/min/100 g, OEF = 53.3%, pHt = 7.00), suggesting intracellular acidosis with intact cell membranes. In three stroke patients 5-8 days after onset, the injured cortex had higher CBF (60.9 ml/min/100 g), lower OEF (32.0%), and higher pHt (7.12) than the contralateral cortex (CBF = 45.3 ml/min/100 g, OEF = 58.0%, pHt = 7.06), which suggested an increase in extracellular volume compartment reflecting loss of cell membrane integrity. This method provides information on the regional tissue acid-base status and cell membrane integrity, which may be prognostic of tissue viability.

Adult↗
PubMed1994

Effects of timing and duration of cognitive activation in [15O]water PET studies.

The multiple injection [15O]water method offers unique opportunities for studying cognitive processing by the human brain. The influence of the duration and temporal placement of an activation task, in relation to the arrival of the radiotracer in the brain, is a fundamental methodologic question for cognitive activation studies. A quantitative positron emission tomography (PET) study of five normal volunteers was performed in which the stimulation consisted of a visual activation task (alternating checkerboard pattern) superimposed on an auditory baseline task (syllable monitoring). Ten injection conditions, with varying duration and timing of the visual activation, were used. Regional CBF (rCBF) in visual cortex was measured quantitatively using the autoradiographic method. A 20-s stimulation, centered on the bolus arrival in the brain, produced significant changes in rCBF. Because varying the duration and timing of the activation task technically violates the temporal homogeneity assumption of the autoradiographic model, a mathematical simulation was formulated to evaluate the potential influence of these variations. Results of the simulation are consistent with the PET data and suggest that activation can be limited to a narrow temporal window centered on the radiotracer uptake. The ability to observe significant changes in rCBF with short stimulation intervals is of particular interest in the use of [15O]water PET for studies of cognitive processes with a short time course.

Adult↗