Biomedical subjects

John W Clark

Publications and source records attributed to John W Clark.

12 recordsLinked to original sources

PubMed2006

A motion-incorporated reconstruction method for gated PET studies.

Cardiac and respiratory motion artefacts in PET imaging have been traditionally resolved by acquiring the data in gated mode. However, gated PET images are usually characterized by high noise content due to their low photon statistics. In this paper, we present a novel 4D model for the PET imaging system, which can incorporate motion information to generate a motion-free image with all acquired data. A computer simulation and a phantom study were conducted to test the performance of this approach. The computer simulation was based on a digital phantom that was continuously scaled during data acquisition. The phantom study, on the other hand, used two spheres in a tank of water, all of which were filled with (18)F water. One of the spheres was stationary while the other moved in a sinusoidal fashion to simulate tumour motion in the thorax. Data were acquired using both 4D CT and gated PET. Motion information was derived from the 4D CT images and then used in the 4D PET model. Both studies showed that this 4D PET model had a good motion-compensating capability. In the phantom study, this approach reduced quantification error of the radioactivity concentration by 95% when compared to a corresponding static acquisition, while signal-to-noise ratio was improved by 210% when compared to a corresponding gated image.

Algorithms↗

PubMed2006

Hemodynamic analysis and design of a paracorporeal artificial lung device.

We have extended our model of the ovine pulmonary circulation to include a model of a paracorporeal artificial lung (AL) and its attachments to the natural pulmonary circulation in two configurations: in series and in parallel. Our model of the natural lung (NL) circulation is first shown to be in agreement with hemodynamic and input impedance data from the open literature. We then study design efficacy of the AL in terms of its housing and attachments. A sensitivity analysis of the modified pulmonary circulation model reveals that there are three key parameters: inlet graft length (IGL) and the compliances of the inlet compliance chamber (CC) and housing of the artificial lung. Based on literature reports, we assume the right ventricle is well-matched to the impedance of the natural pulmonary circulation and adjust the parameters of the modeled AL circuit to achieve the best least-squares fit to natural pulmonary input impedance data. Best-fit parameters produce impedance curves that fit natural impedance well, particularly below 3 Hz, where both compliance and graft length have their largest effects. Of these parameters, the impedance profile is most sensitive to IGL. However, the compliances are important, as well, particularly at low frequencies.

Animals↗

PubMed2006

Nonlinear multiscale wavelet diffusion for speckle suppression and edge enhancement in ultrasound images.

This paper introduces a novel nonlinear multiscale wavelet diffusion method for ultrasound speckle suppression and edge enhancement. This method is designed to utilize the favorable denoising properties of two frequently used techniques: the sparsity and multiresolution properties of the wavelet, and the iterative edge enhancement feature of nonlinear diffusion. With fully exploited knowledge of speckle image models, the edges of images are detected using normalized wavelet modulus. Relying on this feature, both the envelope-detected speckle image and the log-compressed ultrasonic image can be directly processed by the algorithm without need for additional preprocessing. Speckle is suppressed by employing the iterative multiscale diffusion on the wavelet coefficients. With a tuning diffusion threshold strategy, the proposed method can improve the image quality for both visualization and auto-segmentation applications. We validate our method using synthetic speckle images and real ultrasonic images. Performance improvement over other despeckling filters is quantified in terms of noise suppression and edge preservation indices.

Algorithms↗

PubMed2005

Mathematical modeling of the nitric oxide/cGMP pathway in the vascular smooth muscle cell.

The nitric oxide (NO)/cGMP pathway in the vascular smooth muscle cell (VSMC) is an important cellular signaling system for the regulation of VSMC relaxation. We present a mathematical model to investigate the underlying mechanisms of this pathway. The model describes the flow of NO-driven signal transduction: NO activation of soluble guanylate cyclase (sGC), sGC- and phosphodiesterase-catalyzed cGMP production and degradation, cGMP-mediated regulation of protein targets including the Ca2+-activated K+ (KCa) channel, and the myosin contractile system. Model simulations reproduce major NO/cGMP-induced VSMC relaxation effects, including intracellular Ca2+ concentration reduction and Ca2+ desensitization of myosin phosphorylation and force generation. Using the model, we examine several testable principles. 1) Rapid sGC desensitization is caused by end-product cGMP feedback inhibition; a large fraction of the steady-state sGC population is in an inactivated intermediate state, and cGMP production is limited well below maximum. 2) NO activates the K(Ca) channel with both cGMP-dependent and -independent mechanisms; moderate NO concentration affects the K(Ca) via the cGMP-dependent pathway, whereas higher NO concentration is accommodated by a cGMP-independent mechanism. 3) Chronic NO synthase inhibition may cause underexpressions of K+ channels including inward rectifier and K(Ca) channels. 4) Ca2+ desensitization of the contractile system is distinguished from Ca2+ sensitivity of myosin phosphorylation. The model integrates these interactions among the heterogeneous components of the NO signaling system and can serve as a general modeling framework for studying NO-mediated VSMC relaxation under various physiological and pathological conditions. New data can be readily incorporated into this framework for interpretation and possible modification and improvement of the model.

Animals↗

PubMed2005

A model of the pacemaking neuron of the respiratory central pattern generator.

We have developed a model of the mammalian respiratory central pattern generator (rCPG) to mimic the salient characteristics of its constituent medullary neurons. This model is designed as a network of Hodgkin-Huxley-type medullary neurons driven by a pacemaking neuron from the pre-Bötzinger complex. Here, we present the results of our model of this pacemaking neuron, based on available voltage clamp data. Implications for the behavior of the rCPG are discussed.

Action Potentials↗

PubMed2004

Multimodal behavior in a four neuron ring circuit: mode switching.

We study a four-neuron ring circuit comprised of oscillating burst-type neurons unidirectionally coupled via inhibitory synapses. Simple circuits of this type have been used previously to study gait patterns. The ring circuit itself is a variant of the basic reciprocal inhibition network, and it exhibits the property of multistability (multiple stable modes of behavior). That is, different gait modes can be achieved via appropriate initialization of and parameterization of this self-excited oscillatory network. We demonstrate three common gait modes with this circuit: the walk, the bound, and a slightly rotated trot mode. Attention is focused mainly on the mechanisms of rapidly and effectively switching between these modes. Our simulations suggest that neuron membrane dynamics, as well as synaptic junctional properties, strongly influence phase sensitivity in the network; each synapse is a combination of both and can be characterized by a transient phase response curve (PRC). We use the same bursting neuron model to characterize all network neurons, and shape different transient PRCs by using different synaptic properties. The characteristics of these PRCs determine the gait modes sustained in any network configuration, as well as, the ability to switch between modes. The mechanisms explored in this simple circuit, may find application in the switching of more complicated gait pattern networks, as well as, in the design of neuromorphic gait pattern circuits.

Action Potentials↗

PubMed2004

A model of the rat phrenic motor neuron.

We have developed a model for the rat phrenic motor neuron (PMN) that robustly replicates many experimentally observed behaviors of PMNs in response to pharmacological, ionic, and electrical perturbations using a single set of parameters. Our model suggests that the after-depolarization (ADP) response seen in action potentials is a result of the slow deactivation of the fast sodium channel in the range of the ADP coupled with the activation of the L-type calcium channel (I(CaL)). This current and its interactions with the small and large conductance calcium-activated potassium currents (I(KCaSK) and I(KCaBK), respectively) is also important in the generation of spike frequency adaptation in the repetitive firing mode of activity. Other aspects of the model conform very well to experimental observations in both the action potential and repetitive firing mode of activity, including the role of I(KCaSK) in the medium after-hyperpolarization (AHP) and the role of I(KCaBK) in the fast AHP. We have made a number of predictions using the model, including the characterization of two putative sodium currents (fast and persistent), as well as functional roles for the N- and T-type calcium currents.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed2004

A simplified model for V-ATPase H+ extrusion.

An analytical model of V-type H+-translocating ATPase (V-ATPase) was developed based on an approximation to the mechanochemical model of Grabe et al. (Biophys. J., pp. 2798-2813, vol. 78, 2000). Grabe's work utilizes structural information and physiological assumptions to construct a detailed mechanochemical model of the V-ATPase. Due to the complexity of their model, it does not give a readily usable mathematical expression for the V-ATPase current. Based on their analysis of the structure of the proton pump, we develop a two-compartment model of the V-ATPase, which contains a membrane "half-channel" for proton translocation separated by a hydrophilic strip and a hydrophobic wall from the cytoplasm. Using the Langevin equation to describe proton transport across the membrane, we simplify the model based on their assumptions on the molecular structure of the pump and arrive at a general form of solution to the proton pump flux driven by ATP hydrolysis based on assumptions on the physiological properties of the strip and the wall, as well as the two fluid compartments. In this process of simplification, we explicitly relate V-ATPase structure, stoichiometry, pump efficiency, and ATP hydrolysis energy to the active pump current. The simplified model is used to provide model-generated approximations to measured data from a variety of laboratories. In addition, it provides a very compact characterization of V-ATPase, which can be used as a proton extruder in a variety of different cell membranes, as well as in the membranes of intracellular organelles. Index Terms-Electrophysiology, mechanochemstry, molecular motors, proton extrusion

Biological Transport, Active↗

PubMed2003

The myogenic response in isolated rat cerebrovascular arteries: smooth muscle cell model.

Previous models of the cerebrovascular smooth muscle cell have not addressed the interaction between the electrical, chemical, and mechanical components of cell function during the development of active tension. These models are primarily electrical, biochemical or mechanical in their orientation, and do not permit a full exploration of how the smooth muscle responds to electrical or mechanical forcing. To address this issue, we have developed a new model that consists of two major components: electrochemical and chemomechanical subsystem models of the smooth muscle cell. Included in the electrochemical model are models of the electrophysiological behavior of the cell membrane, fluid compartments, Ca2+ release and uptake by the sarcoplasmic reticulum (SR), and cytosolic Ca2+ buffering, particularly by calmodulin (CM). With this subsystem model, we can study the mechanics of the production of intracellular Ca2+ transient in response to membrane voltage clamp pulses. The chemomechanical model includes models of: (a) the chemical kinetics of myosin phosphorylation, and the formation of phosphorylated (cycling) myosin cross-bridges with actin, as well as attached (non-cycling) latch-type cross-bridges; and (b) a model of force generation and mechanical coupling to the contractile filaments and their attachments to protein structures and the skeletal framework of the cell. The two subsystem models are tested independently and compared with data. Likewise, the complete (combined) cell model responses to voltage pulse stimulation under isometric and isotonic conditions are calculated and compared with measured single cell length-force and force-velocity data obtained from literature. This integrated cell model provides biophysically based explanations of electrical, chemical, and mechanical phenomena in cerebrovascular smooth muscle, and has considerable utility as an adjunct to laboratory research and experimental design.

Animals↗

PubMed2003

The myogenic response in isolated rat cerebrovascular arteries: vessel model.

We develop an integrated model of isolated rat arterial resistance vessel (RV), which can simulate its major property of myogenic response. The vascular smooth muscle cell is an important component of the wall of this vessel, and serves as a vasomotor organ providing the active tension generation that underlies the myogenic response of the wall to stretch. In the previous study, we focused on the development of a smooth muscle cell model that can mimic the strain-sensing and force-generating features of the myogenic mechanism. In the current model, we embed this cell model in a larger vessel wall configuration, and couple the time course of cellular contractile activation to macroscopic changes in vessel diameter. The integrated model is used to mimic published pressure-vessel diameter data obtained from isolated RVs that are mounted in a hydraulic test apparatus. The model provides biophysically based insights into the myogenic mechanism as it responds to changes in transmural pressure, in the presence and absence of Ca2+ blockers applied to the bathing fluid.It mimics measured data very well and provides a model that is able to link events at subcellular level to macroscopic changes in vessel diameter. The model initiates a mechanistic approach to investigate myogenic response, which has not been taken previously by any other models.

Animals↗

PubMed2002

Threshold disorder as a source of diverse and complex behavior in random nets.

We study the diversity of complex spatio-temporal patterns in the behavior of random synchronous asymmetric neural networks (RSANNs). Special attention is given to the impact of disordered threshold values on limit-cycle diversity and limit-cycle complexity in RSANNs which have 'normal' thresholds by default. Surprisingly, RSANNs exhibit only a small repertoire of rather complex limit-cycle patterns when all parameters are fixed. This repertoire of complex patterns is also rather stable with respect to small parameter changes. These two unexpected results may generalize to the study of other complex systems. In order to reach beyond this seemingly disabling 'stable and small' aspect of the limit-cycle repertoire of RSANNs, we have found that if an RSANN has threshold disorder above a critical level, then there is a rapid increase of the size of the repertoire of patterns. The repertoire size initially follows a power-law function of the magnitude of the threshold disorder. As the disorder increases further, the limit-cycle patterns themselves become simpler until at a second critical level most of the limit cycles become simple fixed points. Nonetheless, for moderate changes in the threshold parameters, RSANNs are found to display specific features of behavior desired for rapidly responding processing systems: accessibility to a large set of complex patterns.

Algorithms↗

PubMedDate not supplied

Computing relative motion with complex cells.

Contextual influences shape our perception of local visual stimuli. Relative-motion stimuli represent an important contextual influence, yet the mechanism subserving relative-motion computation remains largely unknown. In the present work, we investigated the responses of an established model for simple and complex cells to relative-motion stimuli. A straightforward mathematical analysis showed that relative-motion computation is inherent in the nonlinear transformation of the complex-cell model. Tuning to relative velocity is achieved by applying a temporal filter to the complex-cell response. The mathematical inference is supported by simulations that quantitatively reproduce measured complex-cell responses in both cat and monkey to a variety of relative-motion stimuli. Importantly, the posited mechanism for cortical computation of relative motion does not require an intermediate neural representation of local velocities and does not require lateral or feedback interactions within a network.

Animals↗