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Biomedical subjects

S Akselrod

Publications and source records attributed to S Akselrod.

At least 19 recordsLinked to original sources
PubMed2001

Diffusion anisotropy MRI for quantitative assessment of recovery in injured rat spinal cord.

Spinal cord injury and its devastating consequences are the subject of intensive research aimed at reversing or at least minimizing functional loss. Research efforts focus on either attenuating the post-injury spread of damage (secondary degeneration) or inducing some regeneration. In most of these studies, as well as in clinical situations, evaluation of the state of the injured spinal cord poses a serious difficulty. To address this problem, we carried out a diffusion-weighted MRI experiment and developed an objective routine for quantifying anisotropy in injured rat spinal cords. Rats were subjected to a contusive injury of the spinal cord caused by a controlled weight drop. Untreated control rats were compared with rats treated with T cells specific to the central nervous system self-antigen myelin basic protein, a form of therapy recently shown to be neuroprotective. After the rats were killed their excised spinal cords were fixed in formalin and imaged by multislice spin echo MRI, using two orthogonal diffusion gradients. Apparent diffusion coefficient (ADC) values and anisotropy ratio (AI) maps were extracted on a pixel-by-pixel basis. The calculated sum of AI values (SAI) for each slice was defined as a parameter representing the total amount of anisotropy. The mean-AI and SAI values increased gradually with the distance from the site of the lesion. At the site itself, the mean-AI and SAI values were significantly higher in the spinal cords of the treated animals than in the controls (P = 0.047, P = 0.028, respectively). These values were consistent with the score of functional locomotion. The difference was also manifested in the AI maps, which revealed well-organized neural structure in the treated rats but not in the controls. The SAI values, AI histograms, and AI maps proved to be useful parameters for quantifying injury and recovery in an injured spinal cord. These results encourage the development of diffusion anisotropy MRI as a helpful approach for quantifying the extent of secondary degeneration and measuring recovery after spinal cord injury. Magn Reson Med 45:1-9, 2001.

Animals↗
PubMed2001

A model for optimizing normal tissue complication probability in the spinal cord using a generalized incomplete repair scheme.

The purpose of this study was to determine the treatment protocol, in terms of dose fractions and interfraction intervals, which minimizes normal tissue complication probability in the spinal cord for a given total treatment dose and treatment time. We generalize the concept of incomplete repair in the linear-quadratic model, allowing for arbitrary dose fractions and interfraction intervals. This is incorporated into a previously presented model of normal tissue complication probability for the spinal cord. Equations are derived for both mono-exponential and bi-exponential repair schemes, regarding each dose fraction and interfraction interval as an independent parameter, subject to the constraints of fixed total treatment dose and treatment time. When the interfraction intervals are fixed and equal, an exact analytical solution is found. The general problem is nonlinear and is solved numerically using simulated annealing. For constant interfraction intervals and varying dose fractions, we find that optimal normal tissue complication probability is obtained by two large and equal doses at the start and conclusion of the treatment, with the rest of the doses equal to one another and smaller than the two dose spikes. A similar result is obtained for bi-exponential repair. For the general case where the interfraction intervals are discrete and also vary, the pattern of two large dose spikes is maintained, while the interfraction intervals oscillate between the smallest two values. As the minimum interfraction interval is reduced, the normal tissue complication probability decreases, indicating that the global minimum is achieved in the continuum limit, where the dose delivered by the "middle" fractions is given continuously at a low dose rate. Furthermore, for bi-exponential repair, it is seen that as the slow component of repair becomes increasingly dominant as the magnitude of the dose spikes decreases. Continuous low-dose-rate irradiation with dose spikes at the start and end of treatment yields the lowest normal tissue complication probability in the spinal cord, given a fixed total dose and total treatment time, for both mono-exponential and bi-exponential repair. The magnitudes of the dose spikes can be calculated analytically, and are in close agreement with the numerical results.

Algorithms↗
PubMed2000

Passive or active immunization with myelin basic protein promotes recovery from spinal cord contusion.

Partial injury to the spinal cord can propagate itself, sometimes leading to paralysis attributable to degeneration of initially undamaged neurons. We demonstrated recently that autoimmune T cells directed against the CNS antigen myelin basic protein (MBP) reduce degeneration after optic nerve crush injury in rats. Here we show that not only transfer of T cells but also active immunization with MBP promotes recovery from spinal cord injury. Anesthetized adult Lewis rats subjected to spinal cord contusion at T7 or T9, using the New York University impactor, were injected systemically with anti-MBP T cells at the time of contusion or 1 week later. Another group of rats was immunized, 1 week before contusion, with MBP emulsified in incomplete Freund's adjuvant (IFA). Functional recovery was assessed in a randomized, double-blinded manner, using the open-field behavioral test of Basso, Beattie, and Bresnahan. The functional outcome of contusion at T7 differed from that at T9 (2.9+/-0.4, n = 25, compared with 8.3+/-0.4, n = 12; p<0.003). In both cases, a single T cell treatment resulted in significantly better recovery than that observed in control rats treated with T cells directed against the nonself antigen ovalbumin. Delayed treatment with T cells (1 week after contusion) resulted in significantly better recovery (7.0+/-1; n = 6) than that observed in control rats treated with PBS (2.0+/-0.8; n = 6; p<0.01; nonparametric ANOVA). Rats immunized with MBP obtained a recovery score of 6.1+/-0.8 (n = 6) compared with a score of 3.0+/-0.8 (n = 5; p<0.05) in control rats injected with PBS in IFA. Morphometric analysis, immunohistochemical staining, and diffusion anisotropy magnetic resonance imaging showed that the behavioral outcome was correlated with tissue preservation. The results suggest that T cell-mediated immune activity, achieved by either adoptive transfer or active immunization, enhances recovery from spinal cord injury by conferring effective neuroprotection. The autoimmune T cells, once reactivated at the lesion site through recognition of their specific antigen, are a potential source of various protective factors whose production is locally regulated.

Animals↗
PubMed2000

Effect of incomplete repair on normal tissue complication probability in the spinal cord.

PURPOSE: To incorporate the effects of repair into a model for normal tissue complication probability (NTCP) in the spinal cord. METHODS AND MATERIALS: We used an existing model of NTCP for the spinal cord, based on a critical volume concept, into which we incorporated an incomplete repair (IR) scheme. Values for the repair half time were taken from existing experimental data. Repair corrections were expanded to account for the possibility of biphasic repair, namely the existence of long and short components of repair. RESULTS: We found that the model predicts complete repair to occur at approximately 15 hours, consistent with experimental data. The dependence of the model on the value of the dose per fraction was also studied. It was found that there is a sparing effect as the dose per fraction is decreased below 2 Gy. Surface plots of the NTCP as a function of both the interfraction interval (IFI) and the dose per fraction were generated. We investigated "iso-NTCP" curves, which may allow freedom in choice of treatment plans in terms of the optimal IFI and dose per fraction. As for biphasic repair, as the relative weights of the long and short components of repair were varied, the NTCP changed as well. The model showed little difference between mono- and bi-exponential repair in the time to complete repair, due to a dominance of the long component at long IFIs. CONCLUSIONS: Incorporating IR into NTCP modeling of the spinal cord is consistent with current experimental data. The concept of iso-NTCP curves is an approach which may be clinically useful.

Dose Fractionation, Radiation↗
PubMed2000

Is fatigue in patients with multiple sclerosis related to autonomic dysfunction?

Time-dependent frequency decomposition of fluctuations in cardiovascular signals (heart rate [HR], blood pressure, and blood flow) provides noninvasive and quantitative evaluation of autonomic activity during transient and steady-state conditions. This method was applied during a change of position from supine to standing in patients with multiple sclerosis (MS) who experienced unexplained fatigue and in age-matched control subjects. No difference in response to standing, as reflected in the time domain parameters (mean HR, mean blood pressure, and mean blood flow), was observed between patients with MS and control subjects. Moreover, no difference was observed in very-low-frequency and low-frequency (related to sympathetic activity) content of HR, blood pressure, blood flow, or high-frequency content of HR (related to parasympathetic activity). The only spectral estimates that showed a significant difference between groups were the ratio of low-frequency to high-frequency content of HR and low-frequency content of HR normalized to total power. Both these parameters provide an estimate of the sympathovagal balance. A significant increase in these two estimates on standing was observed in control subjects only, indicating possible impairment of the sympathovagal balance response to standing in patients with MS who experienced fatigue. The authors observed a significant age dependence between close age subgroups, which occurred in the MS group only and was observed in some of the investigated spectral estimates that reflect vagal activity. Therefore, the authors assumed that age-related reduction in vagal activity occurred earlier in patients with MS who experienced fatigue. This reduction could also explain the lack of increase in the sympathovagal balance on standing. To validate this enhanced age dependence, further investigation should be performed in a larger group of subjects with a wider age range.

Adult↗
PubMed2000

Spectral analysis of left ventricular area variability as a tool to improve the understanding of cardiac autonomic control.

Spectral analysis of the fluctuations in heart rate (HR) or blood pressure (BP) has been extensively used as a tool for the noninvasive assessment of autonomic control of the heart. The recently developed echocardiographic acoustic quantification allows noninvasive continuous measurement of the left ventricular cross-sectional area (LVA) signal. In this study, we investigated whether the LVA signal, and more specifically its fluctuations, can be reliably subjected to spectral analysis, and whether the results of such analysis may improve the understanding of the cardiovascular control mechanisms. Our results show that the general pattern of power spectra of LVA fluctuations, as well as their reproducibility, is similar to the power spectra of HR and BP fluctuations. Analysis of LVA signals obtained in normal subjects at rest as well as under vagal blockade and under held respiration, and in patients with known autonomic dysfunction, showed significant differences between groups and states. The effects of age, related to the reduction in parasympathetic activity, were not evident in the spectral content of the LVA and BP signals. The high frequency LVA fluctuations are mainly of mechanical origin, since they were eliminated by breath-holding. We observed an increase in the high frequency LVA fluctuations under vagal blockade, indicating that under normal (control) conditions, these high frequency fluctuations are attenuated by parasympathetic activity. The enhancement in high frequency fluctuations in LVA observed in diabetic patients can thus be attributed to reduced parasympathetic activity. The analysis of LVA variability may be used as a tool for basic research and, possibly, as a quantitative clinical measure for specific disease states.

Adolescent↗
PubMed2000

A simulation of the SA node by a phase response curve-based model of a two-dimensional pacemaker cells array.

This paper presents a simulation of the sino-atrial (SA) node by a two-dimensional pacemaker cells array model, based on phase response curve (PRC) interaction. This simple model of the cardiac pacemaker cells, involves only the most basic functional properties, which play a direct role in the determination of the SA node rhythm. The two most relevant functional properties of the pacemaker cells are: The intrinsic cycle length, an "internal" feature of each pacemaker cell, and the PRC, an "overall collective" function. The PRC contains the "information" about the type of interactions of each pacemaker cell with the outside world (i.e., interaction with neighboring cells, external stimulus, etc.), and "strength" of the interaction (strong, weak, etc.). We studied the spatial interaction among a large number of pacemaker cells (15 x 15), as a function of the regional variation of cells properties, the "electrical" coupling between cells (the PRC), and the appearance of regions with abnormal cycle lengths. We investigated the influence of those parameters on the mutual interaction between the pacemaker cells, on the activation pattern and conduction time of the array, and on a pseudo-electrocardioigram (ECG) signal. This study demonstrates that by representing the pacemaker cells in the SA node by only two fundamental features, and by applying a simple physical-mathematical model, we can create a global picture of the SA node system. This enables us to explore physiological phenomena related to the genesis and maintenance of the SA node activity, and to gain insight into the conditions which predispose the SA node instability, and conduction disturbances.

Body Surface Potential Mapping↗
PubMed2000

Bifurcation in a simple model of the cardiovascular system.

A simple nonlinear beat-to-beat model of the human cardiovascular system has been studied. The model, introduced by DeBoer et al. was a simplified linearized version. We present a modified model which allows to investigate the nonlinear dynamics of the cardiovascular system. We found that an increase in the alpha-sympathetic gain, via a Hopf bifurcation, leads to sustained oscillations both in heart rate and blood pressure variables at about 0.1 Hz (Mayer waves). Similar oscillations were observed when increasing the beta-sympathetic gain or decreasing the vagal gain. Further changes of the gains, even beyond reasonable physiological values, did not reveal another bifurcation. The dynamics observed were thus either fixed point or limit cycle. Introducing respiration into the model showed entrainment between the respiration frequency and the Mayer waves.

Blood Pressure↗
PubMed1999

Autonomic cardiovascular control in children with obstructive sleep apnea.

Autonomic cardiorespiratory control changes with sleep-wake states and is influenced by sleep-related breathing disorders. Power spectrum (PS) analysis of instantaneous fluctuations in heart rate (HR) is used to investigate the role of the autonomic nervous system (ANS) in cardiorespiratory control. The two spectral regions of interest are the low frequency component (LF) and high frequency component (HF). The aim of the present study was to investigate the autonomic cardiorespiratory control in children with obstructive sleep apnea (OSA) syndrome. We studied 10 children with OSA versus 10 normal children. All subjects underwent whole night polysomnography. Spectral analysis of the HR and breathing signals was performed for 256 second long, artifact-free epochs in each sleep-wake state. The LF power was higher in the OSA group compared with control subjects for all states, reflecting enhanced sympathetic activity in OSA subjects. The results indicated sympathetic predominance during REM sleep in all subjects and parasympathetic predominance in slow wave sleep only in controls. The autonomic balance (LF/HF) was significantly higher in OSA patients than in control subjects, at all stages during night sleep, and while awake before sleep onset. An index of overall autonomic balance (ABI) was computed for each subject and correlated well with the measured respiratory disturbance index (RDI).

Autonomic Nervous System↗
PubMed1999

Phase response curve based model of the SA node: simulation by two-dimensional array of pacemaker cells with randomly distributed cycle lengths.

A simulation of the SA node is presented, based on a 2D array (15 x 15) model of randomly distributed pacemaker cells, interacting via a phase response curve (PRC). The model involves only the basic properties that play a direct role in the determination of the SA node rhythm: intrinsic cycle length and PRC. The PRC reflects the 'type' of interaction of each pacemaker cell with the outside world (neighbouring cells, external stimulus, etc.). A major outcome of this study is the demonstration that global dynamics and the degree of 'disorder' of the SA node are strongly affected by the cycle length distribution of the model, as well as spatial inhomogeneity in the cell-to-cell 'electrical' coupling (PRC). Those factors also determine the conduction velocity throughout the SA node and may therefore be responsible for anisotropic conduction. For example, lowering the PRC parameters (d and a) by 25% increases the array activation time from 46 to 126 ms. The model also responds appropriately to a perturbation such as a vagal pulse. This pulse produces a shift of the dominant pacemaker to another site in the array and a transient lengthening of the array cycle length, for example from 312 to 355 ms.

Biological Clocks↗
PubMed1999

Simulation of atrial activity by a phase response curve based model of a two-dimensional pacemaker cells array: the transition from a normal activation pattern to atrial fibrillation.

In this paper, we present an original model of the atria, based on our hypothesis that atrial cells have features of pacemaker cells, characterized by their normally longer intrinsic cycle lengths and different type of connection (stronger) than the, sino-atrial (SA) node pacemaker cells. The atrium is simulated by a two-dimensional array of pacemaker cells (25 x 25), composed of a region of SA node pacemaker cells (11 x 11) surrounded by atrial pacemaker cells. All pacemakers cells are characterized by only the most relevant functional properties, those which play the most direct role in the determination of the cardiac rate and in the mechanism of arrhythmias. These properties are: the intrinsic cycle length, tau, an 'internal' feature of each pacemaker cell, and the phase-response curve (PRC), an 'overall collective' function. The PRC embodies the interactions of each pacemaker cell with its neighboring cells, and thus represents the type of connection (strong, weak, etc.) of the pacemaker cell with its surroundings. In our model, the SA node region differs from the atrial region by cycle length distribution and PRCs. We studied the spatial interaction between SA node pacemaker cells and atrial pacemaker cells as a function of the regional variation of cells properties and as a function of the "electrical" coupling between cells (the PRC), in the SA node region, in the atrial region, and in a border zone between them. We investigated the influence of those parameters on the activation pattern, on the conduction time of the array, and on a pseudo-ECG signal. This study demonstrates that by representing the atrial cells as a population of 'pacemaker-like' cells, similar to the SA node pacemaker cells, but differing markedly in their cycle lengths and cell-to-cell interaction (PRC), we can create a global picture of the atrial system by applying a simple physical-mathematical model. This approach enables us to explore physiological phenomena related to the genesis and maintenance of atrial activity. It also reveals the conditions which predispose to atrial arrhythmias and conduction disturbances (e.g. tachycardia, pacemaker shift, re-entry, fibrillation). In particular, it yields insight into the mechanism of transition from normal atrial activity to the disordered state of atrial fibrillation. Therefore, this study suggests a new way of looking at the development of cardiac arrhythmias of atrial origin.

Atrial Fibrillation↗
PubMed1999

Computerized quantification of structures within ovarian cysts using ultrasound images.

Ovarian cysts are a common type of ovarian mass. The morphology of cysts, as it appears in ultrasound images, is currently used for classification of ovarian pathologies. However, this classification process is based on human interpretation of the sonographic image. In this article, a semiautomatic algorithm for the quantification of ovarian cysts is presented. This algorithm categorizes the structures within a cyst and extracts their quantitative geometric properties (width, characteristic diameter). To assess the validity of the technique, its performance was compared to human classification and manual measurements made by an expert. The results show a good match between automatic evaluations made by a computer and those of an experienced observer, indicating a potential for clinical use.

Algorithms↗
PubMed1999

Application of a semiautomatic boundary detection algorithm for the assessment of amniotic fluid quantity from ultrasound images.

The aim of this study was to develop a computer-assisted method to evaluate amniotic fluid volume (AFV). This was done by automatically detecting the boundaries of the amniotic fluid portion in 2-D ultrasonographic images. The study population consisted of 36 low-risk patients that were selected at random from a healthy population undergoing routine pregnancy follow-up. For each patient, images of the four quadrants of the uterus were digitized into a PC. The amniotic fluid portion in each ultrasonographic image was automatically detected, and its area was calculated. Its area was also manually determined by an expert physician (R. T.). The areas automatically detected by the algorithm were highly correlated with the areas manually delimited by the expert: r2 = 0.9722 (p < 0.01). The areas calculated by the program provide a good measure for the areas determined by the expert and may, therefore, be used for calculating the actual amniotic fluid volume.

Algorithms↗
PubMed1999

Correlation dimension estimation: can this nonlinear description contribute to the characterization of blood pressure control in rats?

The application of correlation dimension estimation to the study of cardiovascular control, via the blood pressure (BP) time series was investigated. We chose to calculate the Grassberger-Procaccia (GP) correlation dimension. In order to obtain a reliable estimate of the correlation dimension, we studied impact of various parameters such as the appropriate sampling rate, the time delays, the embedding dimension, the minimal trace length required, and the number of points needed as reference points. We developed a recipe for the reliable treatment of the continuous BP signal in rats, our animal model, and discussed the possible pitfalls which demand special attention. Next, we applied the surrogate data method to a BP time series, looking for the existence of nonlinear components, in order to test whether the nonlinear modeling is necessary for accurately describing the system. We found that, indeed, the correlation dimension does reveal information which cannot be unveiled by the commonly used power spectral technique, thus, making the nonlinear modeling an important approach, providing additional insight into the cardiovascular control system.

Algorithms↗
PubMed1998

The effect of thermal stimulation on the heart-rate variability in neonates.

Thermoregulation in humans can be divided into three broad mechanisms of control, namely: shivering, sweating and vasomotor activity. Previous investigations suggested the presence of an autonomic rhythm, originating in the central nervous system, possibly related to thermal vasomotor control and directly affecting heart rate by reflex changes in cardiac sympathetic and parasympathetic activity. The objective of the present work was to study the maturation process of the thermoregulatory system in newborns. We used peripheral thermal entrainment and focused on the reflections of vasomotor control in the heart-rate (HR) power spectrum (PS). The study included three groups of neonates at three different ages: 10 premature infants, 6 full-terms and 7 older infants (4 to 6 months). Thermal stimulation was achieved by placing a hot and cold surface on the subject's right palm alternately at three different rates: replacing the touching surface every 4 s (0.25 Hz), 7 s (0.14 Hz) and 10 s (0.1 Hz). 'Double period' stimulation was defined as the total duration of each period of hot and cold stimulation at the three rates, namely 8 s (0.125 Hz), 14 s (0.07 Hz), 20 s (0.05 Hz). The ECG of every infant was measured and recorded during the various stages of the experiment. The HR power spectrum from 0.02 Hz up to 2.00 Hz was considered, focusing on narrow ranges around the thermal stimulation frequencies. We found that in most subjects, clear peaks arise in the HR PS at the thermal entrainment frequency and its corresponding half frequency ('double period'). In premature infants, the reaction is best in response to the longest (10 s) stimulus (9 out of 10 prematures reacted positively), in group B (full-term infants) the reaction responds best to the 7-s stimulus (6 out of 6 reacted) and in older infants the reaction is slightly better at the 4-s stimulus. Since sympathetic control is slower, this ability to entrain the control system at increasing frequencies, might be related to the gradual maturation of parasympathetic control after birth. The different reaction of the three groups may help to understand the maturation process of the thermoregulation system.

Adaptation, Biological↗
PubMed1998

A phase response curve based model: effect of vagal and sympathetic stimulation and interaction on a pacemaker cell.

This study introduces a simple mathematical model for a pacemaker cell affected by an external parasympathetic and/or sympathetic input. The model presented is based on the two most important functional properties of the cardiac pacemaker cells. The first property is the intrinsic pacemaker cycle length, an "internal" parameter of the cell. The second basic property is the phase response curve (PRC), a function which reflects the various interactions of the pacemaker cell with the outside world (i.e. interaction with surrounding cells, external stimulus). The vagal stimulus is simulated as affecting the pacemaker cycle length via a PRC, while the sympathetic input is expressed in the model as a continuous reduction in the pacemaker cycle length. When combined vagal and sympathetic activation is allowed, our model shows that autonomic systems are also capable of interacting. First, we studied the entrainment phenomena resulting from a repetitively applied vagal stimulus. Various complex patterns of dynamic interaction between the pacemaker cell and the vagal input were simulated. The PRC parameters appear to be an important factor in the prediction of the entrainment phenomena. Specifically, they permit a quantitative description of the limits of a 1:1 synchronization zone. Next, we apply this model to qualitatively investigate the phenomenon of "accentuated antagonism" between parasympathetic and sympathetic autonomic branches. We examined the various options for this interaction in regulating the pacemaker periodicity. Although this model is a simplified reflection of the biological system, we conclude that it can mimic many aspects of the dynamic autonomic control and of the possible interactions between vagal and sympathetic stimulation of a pacemaker cell.

Animals↗