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M E Alexander

Publications and source records attributed to M E Alexander.

At least 19 recordsLinked to original sources
PubMed2005

Modelling the effect of a booster vaccination on disease epidemiology.

Despite the effectiveness of vaccines in dramatically decreasing the number of new infectious cases and severity of illnesses, imperfect vaccines may not completely prevent infection. This is because the immunity afforded by these vaccines is not complete and may wane with time, leading to resurgence and epidemic outbreaks notwithstanding high levels of primary vaccination. To prevent an endemic spread of disease, and achieve eradication, several countries have introduced booster vaccination programs. The question of whether this strategy could eventually provide the conditions for global eradication is addressed here by developing a seasonally-forced mathematical model. The analysis of the model provides the threshold condition for disease control in terms of four major parameters: coverage of the primary vaccine; efficacy of the vaccine; waning rate; and the rate of booster administration. The results show that if the vaccine provides only temporary immunity, then the infection typically cannot be eradicated by a single vaccination episode. Furthermore, having a booster program does not necessarily guarantee the control of a disease, though the level of epidemicity may be reduced. In addition, these findings strongly suggest that the high coverage of primary vaccination remains crucial to the success of a booster strategy. Simulations using estimated parameters for measles illustrate model predictions.

Algorithms↗
PubMed2004

Periodicity in an epidemic model with a generalized non-linear incidence.

We develop and analyze a simple SIV epidemic model including susceptible, infected and perfectly vaccinated classes, with a generalized non-linear incidence rate subject only to a few general conditions. These conditions are satisfied by many models appearing in the literature. The detailed dynamics analysis of the model, using the Poincaré index theory, shows that non-linearity of the incidence rate leads to vital dynamics, such as bistability and periodicity, without seasonal forcing or being cyclic. Furthermore, it is shown that the basic reproductive number is independent of the functional form of the non-linear incidence rate. Under certain, well-defined conditions, the model undergoes a Hopf bifurcation. Using the normal form of the model, the first Lyapunov coefficient is computed to determine the various types of Hopf bifurcation the model undergoes. These general results are applied to two examples: unbounded and saturated contact rates; in both cases, forward or backward Hopf bifurcations occur for two distinct values of the contact parameter. It is also shown that the model may undergo a subcritical Hopf bifurcation leading to the appearance of two concentric limit cycles. The results are illustrated by numerical simulations with realistic model parameters estimated for some infectious diseases of childhood.

Algorithms↗
PubMed2001

Electroanatomic mapping of entrained and exit zones in patients with repaired congenital heart disease and intra-atrial reentrant tachycardia.

BACKGROUND: Characterization of reentrant circuits and targeting ablation sites remains difficult for intra-atrial reentrant tachycardias (IART) in congenital heart disease (CHD). METHODS AND RESULTS: Electroanatomic mapping and entrainment pacing were performed before successful ablation of 18 IART circuits in 15 patients with CHD. Principal features of IART circuits were atrial septal defect (4 patients), atriotomy (3 patients), other atrial scar (3 patients), crista terminalis (3 patients), and right atrioventricular valve (5 patients). A median of 176 sites (range, 96 to 317 sites) was mapped for activation and 13 sites (range, 9 to 28 sites) for entrainment response. Postpacing intervals within 20 ms of tachycardia cycle length and stimulus-to-P-wave intervals of 0 to 90 ms (exit zones) were mapped to atrial surfaces generated by electroanatomic mapping. Criteria for entrainment were met over a median of 21 cm2 of atrial surface (range, 2 to 75 cm2), 19% (range, 1% to 81%) of total area tested. Using integrated data, relations between activation sequence and protected corridor of conduction could be inferred for 16 of 17 LARTs. Successful ablation was achieved at a site distant from the putative protected corridor in 9 of 18 (50%) circuits. CONCLUSIONS: The right atrium in CHD supports a variety of IART mechanisms. Fusion of activation and entrainment data provided insight into specific IART mechanisms relevant to ablation.

Adolescent↗
PubMed2001

Minimally invasive cardioverter defibrillator implantation for children: an animal model and pediatric case report.

The smaller venous capacitance in infants and small children may hamper transvenous ICD lead implantation, and epicardial approaches require thoracotomy and have associated complications. The study evaluated the feasibility and performance of subcutaneous arrays and active can ICDs without transvenous shocking coils or epicardial patches. An immature and mature pig were anesthetized and ventilated. A pacing lead was inserted in the right ventricle for fibrillation induction and rate sensing. Subcutaneous arrays were positioned in the right and left chest walls. An ICD emulator was placed in abdominal and prepectoral pockets. Fluoroscopic images were acquired for each electrical vector configuration (array --> can, can --> array, array --> array, array + array --> can). Ventricular fibrillation was induced and DFT testing performed. Defibrillation was achieved in all ten trials in the immature piglet, with DFT < or = 9 J, regardless of vector configuration. Using a single subcutaneous array and active can, the shock impedance ranged from 28-36 ohms. With two arrays, shocking impedance fell to 15-22 ohms. In the adult pig, defibrillation was not accomplished with maximum energy of 40 J, using all vector configurations. Using data garnered from these experiments, this technique was then successfully performed in a 2-year-old child with VT and repaired congenital heart disease, needing an ICD. This study demonstrates the feasibility of leadless ICD implantation in an immature animal and successful implementation in a small child. A single subcutaneous array and active can resulted in excellent implant characteristics and DFTs with a minimally invasive approach. Defibrillation was not possible in a larger animal, possibly due to maximal available energy. This may be of value for small children requiring ICD implantation.

Animals↗
PubMed2001

Supraventricular arrhythmias in children and young adults with implantable cardioverter defibrillators.

INTRODUCTION: Rapidly conducted supraventricular tachycardias (SVTs) can lead to inappropriate device therapy in implantable cardioverter defibrillator (ICD) patients. We sought to determine the incidence of SVTs and the occurrence of inappropriate ICD therapy due to SVT in a pediatric and young adult population. METHODS AND RESULTS: We undertook a retrospective review of clinical course, Holter monitoring, and ICD interrogations of patients receiving ICD follow-up at our institution between March 1992 and December 1999. Of 81 new ICD implantations, 54 eligible patients (median age 16.5 years, range 1 to 48) were identified. Implantation indications included syncope and/or spontaneous/inducible ventricular arrhythmia with congenital heart disease (30), long QT syndrome (9), structurally normal heart (ventricular tachycardia/ventricular fibrillation [VT/VF]) (7), and cardiomyopathies (7). Sixteen patients (30%) received a dual-chamber ICD. SVT was recognized in 16 patients, with 12 of 16 having inducible or spontaneous atrial tachycardias. Eighteen patients (33%) received > or =1 appropriate shock(s) for VT/VF; 8 patients (15%) received inappropriate therapy for SVT. Therapies were altered after an inappropriate shock by increasing the detection time or rate and/or increasing beta-blocker dosage. No single-chamber ICD was initially programmed with detection enhancements, such as sudden onset, rate stability, or QRS discriminators. Only one dual-chamber defibrillator was programmed with an atrial discrimination algorithm. Appropriate ICD therapy was not withheld due to detection parameters or SVT discrimination programming. CONCLUSION: SVT in children and young adults with ICDs is common. Inappropriate shocks due to SVT can be curtailed even without dual-chamber devices or specific SVT discrimination algorithms.

Adolescent↗
PubMed2000

3D image registration using a fast noniterative algorithm.

This note describes the implementation of a three-dimensional (3D) registration algorithm, generalizing a previous 2D version [Alexander, Int J Imaging Systems and Technology 1999;10:242-57]. The algorithm solves an integrated form of linearized image matching equation over a set of 3D rectangular sub-volumes ('patches') in the image domain. This integrated form avoids numerical instabilities due to differentiation of a noisy image over a lattice, and in addition renders the algorithm robustness to noise. Registration is implemented by first convolving the unregistered images with a set of computationally fast [O(N)] filters, providing four bandpass images for each input image, and integrating the image matching equation over the given patch. Each filter and each patch together provide an independent set of constraints on the displacement field derived by solving a set of linear regression equations. Furthermore, the filters are implemented at a variety of spatial scales, enabling registration parameters at one scale to be used as an input approximation for deriving refined values of those parameters at a finer scale of resolution. This hierarchical procedure is necessary to avoid false matches occurring. Both downsampled and oversampled (undecimating) filtering is implemented. Although the former is computationally fast, it lacks the translation invariance of the latter. Oversampling is required for accurate interpolation that is used in intermediate stages of the algorithm to reconstruct the partially registered from the unregistered image. However, downsampling is useful, and computationally efficient, for preliminary stages of registration when large mismatches are present. The 3D registration algorithm was implemented using a 12-parameter affine model for the displacement: u(x) = Ax + b. Linear interpolation was used throughout. Accuracy and timing results for registering various multislice images, obtained by scanning a melon and human volunteers in various stationary positions, is described. The algorithm may be generalized to more general models of the displacement field, and is also well suited to parallel processing.

Algorithms↗
PubMed2000

A wavelet-based method for improving signal-to-noise ratio and contrast in MR images.

Magnetic resonance (MR) images acquired with fast measurement often display poor signal-to-noise ratio (SNR) and contrast. With the advent of high temporal resolution imaging, there is a growing need to remove these noise artifacts. The noise in magnitude MR images is signal-dependent (Rician), whereas most de-noising algorithms assume additive Gaussian (white) noise. However, the Rician distribution only looks Gaussian at high SNR. Some recent work by Nowak employs a wavelet-based method for de-noising the square magnitude images, and explicitly takes into account the Rician nature of the noise distribution. In this article, we apply a wavelet de-noising algorithm directly to the complex image obtained as the Fourier transform of the raw k-space two-channel (real and imaginary) data. By retaining the complex image, we are able to de-noise not only magnitude images but also phase images. A multiscale (complex) wavelet-domain Wiener-type filter is derived. The algorithm preserves edges better when the Haar wavelet rather than smoother wavelets, such as those of Daubechies, are used. The algorithm was tested on a simulated image to which various levels of noise were added, on several EPI image sequences, each of different SNR, and on a pair of low SNR MR micro-images acquired using gradient echo and spin echo sequences. For the simulated data, the original image could be well recovered even for high values of noise (SNR approximately 0 dB), suggesting that the present algorithm may provide better recovery of the contrast than Nowak's method. The mean-square error, bias, and variance are computed for the simulated images. Over a range of amounts of added noise, the present method is shown to give smaller bias than when using a soft threshold, and smaller variance than a hard threshold; in general, it provides a better bias-variance balance than either hard or soft threshold methods. For the EPI (MR) images, contrast improvements of up to 8% (for SNR = 33 dB) were found. In general, the improvement in contrast was greater the lower the original SNR, for example, up to 50% contrast improvement for SNR of about 20 dB in micro-imaging. Applications of the algorithm to the segmentation of medical images, to micro-imaging and angiography (where the correct preservation of phase is important for flow encoding to be possible), as well as to de-noising time series of functional MR images, are discussed.

Algorithms↗
PubMed2000

Estimation of atrial response to entrainment pacing using electrograms recorded from remote sites.

INTRODUCTION: Assessing the entrainment response by measuring postpacing intervals (PPIs) at the pacing site facilitates localization of reentrant circuits, but may be technically difficult. METHODS AND RESULTS: There were 269 right atrial sites entrained in 21 circuits in congenital heart patients left atrial (LA) electrograms were recorded. Entrainment response was measured by two methods: (1) PPI-tachycardia cycle length, and (2) the difference in latencies between the stimulus artifact and the pacing site electrogram, referenced to the LA electrogram. PPI also was measured from the LA as an index of antidromic activation. Among 43 pacing sites with antidromic LA activation, half showed a discrepancy 225 msec between methods 1 and 2. At the other 226 sites, agreement between the two methods was high (mean discrepancy -3+/-8 msec, r = 0.975, 0 sites with discrepancy 225 msec). Correcting all sites by LA antidromicity reduced the mean discrepancy to +1+/-6 msec and improved correlation (r = 0.988). CONCLUSION: LA electrograms can be used to estimate right atrial entrainment response, if antidromic activation of the LA is recognized and taken into account.

Adolescent↗
PubMed1999

Value of programmed ventricular stimulation in patients with congenital heart disease.

INTRODUCTION: The role of programmed ventricular stimulation (VSTIM) for risk stratification in congenital heart disease is unclear. We analyzed the results of VSTIM in selected congenital heart disease survivors at a single center to determine whether it improved the ability to predict a serious outcome. METHODS AND RESULTS: Between July 1985 and September 1996, 140 primary VSTIM studies were performed on 130 patients (median age 18.1 years, range 0 to 51). Tetralogy of Fallot (33 %), d-transposition of the great arteries (25 %), and left ventricular outflow tract obstruction (12%) accounted for the majority of patients. Indications included spontaneous ventricular tachycardia (VT) of > or = 3 beats (72%) and/or symptoms (68%). Sustained VT was induced in 25% of the studies, and nonsustained VT in 12%. Atrial flutter or other supraventricular tachycardia was documented in 32% and bradyarrhythmias in 26%. By univariate analysis, mortality was increased in patients with positive VSTIM versus negative VSTIM (18% vs 7%, P = 0.04). Using multivariate analysis, positive VSTIM was associated with a sixfold increased risk of decreased survival and a threefold increased risk of serious arrhythmic events, allowing up to 87% sensitivity in predicting mortality. However, 7 (33%) of 21 patients with documented clinical VT had false-negative studies. CONCLUSION: VSTIM in a large, selected group of congenital heart disease patients identified a subgroup with significantly increased mortality and sudden arrhythmic events. Failure to induce VT was a favorable prognostic sign, but the frequency of false-negative studies was high. Frequent supraventricular tachycardia further complicated risk stratification. Although VSTIM appears to be a reasonable tool for evaluation of this population, a larger, multicenter trial is recommended to clarify its utility.

Adolescent↗
PubMed1999

Preventing sudden death after repair of tetralogy of Fallot: complex therapy for complex patients.

Sudden arrhythmic death in patients with repaired tetralogy of Fallot or its variants has a variety of causes. Consequently, it can serve as a paradigm for management of potentially malignant arrhythmias in all pediatric patients, particularly with regard to the use of nonpharmacologic therapy for management. Five cases are presented as touchpoints for discussion and demonstrate a number of important issues concerning the assessment and reduction of sudden cardiac death risk in these patients. First, there are no clinical parameters that can be used to accurately assess risk. Second, pharmacologic agents alone rarely are adequate therapy. Third, catheter ablation and antitachycardia devices continue to play an ever increasing role in management of these patients, and, finally, additional data are necessary to establish clear management guidelines in patients with congenital heart disease at risk for arrhythmic death.

Adolescent↗
PubMed1997

An improved robust hierarchical registration algorithm.

This note describes an improvement to an accurate, robust, and fast registration algorithm (Alexander, M.E. and Somorjai, R.L., Mag. Reson. Imaging, 14:453-468, 1996). A computationally inexpensive preregistration method is proposed, consisting of simply aligning the image centroids, from which estimates of the translation shifts are derived. The method has low sensitivity to noise, and provides starting values of sufficient accuracy for the iterative registration algorithm to allow accurate registration of images that have significant levels of noise and/or large misalignments. Also, it requires a smaller computational effort than the Fourier Phase Matching (FPM) preregistration method used previously. The FPM method provides accurate preregistration for low-noise images, but fails when significant noise is present. For testing the various methods, a 256 x 256 pixel T2*-weighted image was translated, rotated, and scaled to produce large misalignments and occlusion at the image boundaries. The two situations of no noise being present in the images and in which Gaussian noise is added, were tested. After preregistration, the images were registered by applying one or several passes of the iterative algorithm at different levels of preblurring of the input images. Results of using the old and new preregistration methods, as well as no preregistration, are compared for the final accuracy of recovery of registration parameters. In addition, the performances of three robust estimators: Least Median of Squares, Least Trimmed Squares, and Least Winsorized Mean, are compared with those of the nonrobust Least Squares and Woods' methods, and found to converge to correct solutions in cases where the nonrobust methods do not.

Algorithms↗
PubMed1996

The registration of MR images using multiscale robust methods.

Acquisition of MR images involves their registration against some prechosen reference image. Motion artifacts and misregistration can seriously flaw their interpretation and analysis. This article provides a global registration method that is robust in the presence of noise and local distortions between pairs of images. It uses a two-stage approach, comprising an optional Fourier phase-matching method to carry out preregistration, followed by an iterative procedure. The iterative stage uses a prescribed set of registration points, defined on the reference image, at which a robust nonlinear regression is computed from the squared residuals at these points. The method can readily accommodate general linear or even nonlinear, registration transformations on the images. The algorithm was tested by recovering the registration transformation parameters when a 256 x 256 pixel T2*-weighted human brain image was scaled, rotated, and translated by prescribed amounts, and to which different amounts of Gaussian noise had been added. The results show subpixel accuracy of recovery when no noise is present, and graceful degradation of accuracy as noise is added. When 40% noise is added to images undergoing small shifts, the recovery errors are less than 3 pixels. The same tests applied to the Woods algorithm gave slightly inferior accuracy for these images, but failed to converge to the correct parameters in some cases of large-scale-shifted images with 10% added noise.

Algorithms↗
PubMed1995

Effects of local connectivity on striatal function: stimulation and analysis of a model.

Neuronal population activity was investigated by computer simulation of a network model based on the neostriatum. Three network topologies were studied, based on different assumptions about the synaptic connectivity among medium spiny neurons. In all networks neurons were interconnected by inhibitory synapses. The connectivity was either symmetric, in which case all connections between cells were reciprocal and equal in strength; or asymmetric. Simulations showed that networks with symmetric connectivity receiving randomly distributed afferent excitation produced stationary spatial activity patterns. In contrast, asymmetric connectivity in homogeneous networks produced slow travelling-wave activity across the network. We suggest that the shape of the medium spiny neurons is an important determinant of synaptic connectivity and that changes in the shape of these neurons caused by Huntington's disease would result in asymmetric connectivity. Slow travelling-wave activity produced by asymmetric connectivity in the neostriatum could explain some aspects of the choreic movement and some electromyographic features seen in Huntington's patients.

Computer Simulation↗
PubMed1993

Analysis of striatal dynamics: the existence of two modes of behaviour.

The qualitative dynamical behaviour of a neural model based on the mammalian neostriatum was analyzed. The neostriatum was modelled as a mutually inhibitory network of physiological neurones, which was driven by excitatory afferents from the cerebral cortex. The analysis defined the conditions under which the system would enter into one of two dynamic modes, competition or co-activation, in terms of the parameters defining receptor-operated and voltage-sensitive channels in the neuronal membrane. We have previously argued that the mode of co-activation in the neostriatum may correspond to the state of muscular rigidity which occurs as a symptom of Parkinson's disease. The present work extends a preliminary analysis of a two-neurone system to a system of arbitrary size. An explicit prediction is made of the conditions under which a transition from co-activation to competition will occur, which is testable experimentally. The wavelength of a non-uniform activity pattern produced by small departures from uniform afferent drive is determined for one- and two-dimensional arrays of neurones. Two mild assumptions about the connectivity of the network were used to simplify the analysis, namely that the network was symmetric and homogeneous. The implications of departures from these assumptions for understanding the disordered movement seen in Huntington's disease are also considered.

Animals↗
PubMed1992

A nuclear magnetic resonance investigation of the upper airways in ferrets. I. Effects of histamine and methacholine.

Alterations induced in the upper airways of ferrets by intranasal provocation with methacholine (MC) and histamine (HS) were monitored using proton magnetic resonance imaging (MRI) and spin-spin relaxation rate (R2) measurements. Both MC and HS cause a significant increase in the MRI signal intensity and a decrease in R2 in the nasal turbinates. A dose-dependent response is observed for 20 to 315 nmol of HS, with a maximum increase in intensity of ca. 50% occurring above 80 nmol. A single unilateral challenge with MC yields a 62 +/- 3% increase in intensity. Control animals (saline-treated) show little change in image intensity. MC and HS cause decreases in the proton R2 by -27.0 +/- 5.5% and -17.2 +/- 4.3%, respectively. These data are indicative of an accumulation of fluid in the nasal airways. MRI provides an effective means to monitor changes in the nasal airways which occur as a result of pharmacological treatment.

Administration, Intranasal↗
PubMed1992

A nuclear magnetic resonance investigation of the upper airways in ferrets. II. Contrast-enhanced imaging to distinguish vascular from other nasal fluids.

Proton magnetic resonance imaging (MRI), used in conjunction with the intravascular contrast agent albumin-(Gd-DTPA), provides a means to distinguish vascular fluids from other nasal fluids in the upper airways. Ferrets were given an intravenous dose of albumin-(Gd-DTPA) followed by an intranasal challenge with either histamine (HS) or methacholine (MC). An observed increase in image intensity indicates that HS and MC both cause an accumulation of fluids in the nasal turbinate region. The MRI data are also influenced by the presence of blood, which contains the contrast agent, and a clear distinction can be made between vascular fluids and other nasal fluids (i.e., cellular and glandular secretions). The results show that HS causes an increase in vascular fluids in the nasal turbinates while MC does not. This methodology represents a new means to investigate airway pharmacology and the pathophysiology associated with various pharmacological agents, allergens, or viral infections.

Administration, Intranasal↗