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PubMed2006

Tomographic reconstruction using an adaptive tetrahedral mesh defined by a point cloud.

Medical images in nuclear medicine are commonly represented in three dimensions as a stack of two-dimensional images that are reconstructed from tomographic projections. Although natural and straightforward, this may not be an optimal visual representation for performing various diagnostic tasks. A method for three-dimensional (3-D) tomographic reconstruction is developed using a point cloud image representation. A point cloud is a set of points (nodes) in space, where each node of the point cloud is characterized by its position and intensity. The density of the nodes determines the local resolution allowing for the modeling of different parts of the image with different resolution. The reconstructed volume, which in general could be of any resolution, size, shape, and topology, is represented by a set of nonoverlapping tetrahedra defined by the nodes. The intensity at any point within the volume is defined by linearly interpolating inside a tetrahedron from the values at the four nodes that define the tetrahedron. This approach creates a continuous piecewise linear intensity over the reconstruction domain. The reconstruction provides a distinct multiresolution representation, which is designed to accurately and efficiently represent the 3-D image. The method is applicable to the acquisition of any tomographic geometry, such as parallel-, fan-, and cone-beam; and the reconstruction procedure can also model the physics of the image detection process. An efficient method for evaluating the system projection matrix is presented. The system matrix is used in an iterative algorithm to reconstruct both the intensity and location of the distribution of points in the point cloud. Examples of the reconstruction of projection data generated by computer simulations and projection data experimentally acquired using a Jaszczak cardiac torso phantom are presented. This work creates a framework for voxel-less multiresolution representation of images in nuclear medicine.

Algorithms↗
PubMedDate not supplied

A new algorithm for learning in piecewise-linear neural networks.

Piecewise-linear (PWL) neural networks are widely known for their amenability to digital implementation. This paper presents a new algorithm for learning in PWL networks consisting of a single hidden layer. The approach adopted is based upon constructing a continuous PWL error function and developing an efficient algorithm to minimize it. The algorithm consists of two basic stages in searching the weight space. The first stage of the optimization algorithm is used to locate a point in the weight space representing the intersection of N linearly independent hyperplanes, with N being the number of weights in the network. The second stage is then called to use this point as a starting point in order to continue searching by moving along the single-dimension boundaries between the different linear regions of the error function, hopping from one point (representing the intersection of N hyperplanes) to another. The proposed algorithm exhibits significantly accelerated convergence, as compared to standard algorithms such as back-propagation and improved versions of it, such as the conjugate gradient algorithm. In addition, it has the distinct advantage that there are no parameters to adjust, and therefore there is no time-consuming parameters tuning step. The new algorithm is expected to find applications in function approximation, time series prediction and binary classification problems.

Algorithms↗
PubMed1997

Simulation of the onset of neuromuscular block based on the early oscillations in the arterial plasma concentrations.

OBJECTIVE: The aim of the study was to describe by simulation the true plasma concentrations of non-depolarizing muscle relaxants (NDMRs) as a continuous function of time. In contrast to standard pharmacokinetic analysis of the time course of action via extrapolated plasma concentrations, the derived curve was to reflect zero plasma concentration initially and one or more cycles of peaks and troughs subsequently. We desired to study the influence of the initial delay and the early oscillations in the plasma concentrations on the time to onset of peak but submaximal neuromuscular block (NMB). Hypothetical NDMRs were postulated to display in humans a pattern of early arterial plasma concentrations similar to the reported pattern of indocyanine green plasma concentrations in dogs (an initial delay period and subsequent peaks and troughs). METHODS: Two hypothetical NDMRs with either a very rapid or a slow decay in plasma concentrations were used for the simulations. A delay and oscillations were imposed on a multiexponential function for the plasma concentrations of the NDMRs by an additional, biexponentially dampened sinusoid function. The time between intravenous bolus administration of the NDMRs and the first rise in plasma concentrations was fixed at 0.2 min. As experimentally observed with indocyanine green in dogs, the oscillations were limited to the first minute after injection. The NDMRs were simulated to diffuse from plasma into and out of the interstitial space of muscles according to a rate constant and the concentration gradient. The NDMRs were postulated to have free access from the interstitial space to the receptors, and the neuromuscular block was calculated using the Hill equation. RESULTS: The delay and the peak and trough plasma concentrations during the first minute after bolus injection of the NDMRs were simulated well by the postulated dampened sinusoidal function. The times to peak submaximal NMB and the equieffective doses were similar whether calculated on the basis of oscillatory or extrapolated multiexponential functions. Both simulations demonstrated that a rapid initial decay of the plasma concentrations is associated with a slightly faster onset of peak NMB and a slightly higher equieffective dose. CONCLUSION: Consideration of early oscillations in the plasma concentrations of a NDMR barely alters the simulated time course of action from that simulated by an extrapolated multiexponential function.

Animals↗
PubMed2000

Model study of vector-loop morphology during electrical mapping of microscopic conduction in cardiac tissue.

The large variety in loop morphology of potential differences recorded at the cardiac surface has been generally attributed to structural discontinuities of the tissue. The aim of this work was to examine if the diversity of vector loops of the electric field E found experimentally may also arise during continuous anisotrope conduction. For this purpose a monodomain computer model was used, consisting of a two-dimensional sheet of excitable tissue surrounded with an unbounded volume conductor. Close to the tissue surface our computations predicted a narrow biphasic course of phi(e) with peak-to-peak separation of less than 400 microm. We examined how accurately E could be reconstructed from measurements recorded with four-element electrode arrays and how activation sequence, interelectrode spacing, and probe orientation affects the results. We found "closed" vector loops of E in planar, and at the apex of elliptical wave fronts, whereas outside of these regions vector loops were "open." Varying probe orientation and size resulted in substantial changes of vector-loop morphology. We concluded that close to the cardiac current sources accurate measurement of E would require interelectrode distances of less than 100 microm.

Animals↗
PubMedDate not supplied

Bistability dynamics in simulations of neural activity in high-extracellular-potassium conditions.

Modulation of extracellular potassium concentration ([K](o)) has a profound impact on the excitability of neurons and neuronal networks. In the CA3 region of the rat hippocampus synchronized epileptiform bursts occur in conditions of increased [K](o). The dynamic nature of spontaneous neuronal firing in high [K](o) is therefore of interest. One particular interest is the potential presence of bistable behaviors such as the coexistence of stable repetitive firing and fixed rest potential states generated in individual cells by the elevation of [K](o). The dynamics of repetitive activity generated by increased [K](o) is investigated in a 19-compartment hippocampal pyramidal cell (HPC) model and a related two-compartment reduced HPC model. Results are compared with those for the Hodgkin-Huxley equations in similar conditions. For neural models, [K](o) changes are simulated as a shift in the potassium reversal potential (E(K)). Using phase resetting and bifurcation analysis techniques, all three models are shown to have specific regions of E(K) that result in bistability. For activity in bistable parameter regions, stimulus parameters are identified that switch high-potassium model behavior from repetitive firing to a quiescent state. Bistability in the HPC models is limited to a very small parameter region. Consequently, our results suggest that it is likely some HPCs in networks exposed to high [K](o) continue to burst such that a stable, quiescent network state does not exist. In [K](o) ranges where HPCs are not bistable, the population may still exhibit bistable behaviors where synchronous population events are reversibly annihilated by phase resetting pulses, suggesting the existence of a nonsynchronous network attractor.

Action Potentials↗
PubMed2002

Adaptive spatiotemporal receptive field estimation in the visual pathway.

The encoding properties of the visual pathway are under constant control from mechanisms of adaptation and systems-level plasticity. In all but the most artificial experimental conditions, these mechanisms serve to continuously modulate the spatial and temporal receptive field (RF) dynamics. Conventional reverse-correlation techniques designed to capture spatiotemporal RF properties assume invariant stimulus-response relationships over experimental trials and are thus limited in their applicability to more natural experimental conditions. Presented here is an approach to tracking time-varying encoding dynamics in the early visual pathway based on adaptive estimation of the spatiotemporal RF in the time domain. Simulations and experimental data from the lateral geniculate nucleus reveal that subtle features of encoding properties can be captured by the adaptive approach that would otherwise be undetected. Capturing the role of dynamically varying encoding mechanisms is vital to our understanding of vision on the natural setting, where there is absence of a true steady state.

Adaptation, Physiological↗
PubMed2005

Morphodynamic profiling of protrusion phenotypes.

We propose a framework for tracking arbitrary complex cell boundary movements, relying on a unique definition of protrusion and retraction as the pathlength a virtual edge marker traverses when moving continuously perpendicular to the cell boundary. We introduce the level set method as a numerical scheme to reconstruct continuous boundary movement in time-lapse image sequences with finite time sampling. For moderately complex movements, we describe a numerically less expensive method that satisfactorily approximates the definition. Densely sampled protrusion and retraction rates were accumulated in space-time charts revealing distinct morphodynamic states. Applying this technique to the profiling of epithelial cell protrusion we identified three different states. In the I-state, long cell edge sectors are synchronized in cycles of protrusion and retraction. In the V-state random bursts of protrusion initiate protrusion waves propagating transversally in both directions. Cells switch between both states dependent on the Rac1 activation level. Furthermore, the persistence of transversal waves in the V-state depends on Arp2/3 concentration. Inhibition of PAK shifts cells into a lambda-state where continuous protrusion is occasionally interrupted by self-propagating ruffles. Our data support a model where activation of Rac1 mediates the propagation of protrusion waves, whose persistence depends on the relative abundance of activated Arp2/3 and polymerizable G-actin.

Actin-Related Protein 2-3 Complex↗
PubMed2001

Time to learn: the outlook for renewal of patient-centred education in the digital age.

BACKGROUND: Major forces in society and within health systems are fragmenting patient care and clinical learning. The distancing of physician and trainee from the patient undermines learning about the patient-doctor relationship. The disconnection of care and learning from one successive venue to another impedes the ability of trainees to learn about illness longitudinally. METHODS: As a conceptual piece, our methods have been those of witnessing the experiences of patients, practitioners, and students over time and observing the impact of fragmented systems and changing expectations on care and learning. We have reflected on the opportunities created by digital information systems and interactive telemedicine to help renew essential relationships. RESULTS: Although there is, as yet, little in the literature on educational or health outcomes of this kind of technological enablement, we anticipate opportunities for a renewed focus on the patient in that patient's own space and time. Multimedia applications can achieve not only real-time connections, but can help construct a "virtual patient" as a platform for supervision and assessment, permitting preceptors to evaluate trainee-patient interactions, utilization of Web-based data and human resources, and on-line professionalism. CONCLUSIONS: Just as diverse elements in society are capitalizing upon digital technology to create advantageous relationships, all of the elements in the complex systems of health care and medical training can be better connected, so as to put the patient back in the centre of care and the trainee's ongoing relationship to the patient back in the centre of education.

Clinical Competence↗
PubMed2005

Development and characterization of an animal model of dental sinusitis.

CONCLUSION: The results of this study confirm that the present rabbit model of dental maxillary sinusitis (dMxS) is reproducible and simulates human dental sinusitis with respect to initiation, progression and inflammation. It is applicable to further studies of sinusitis of odontogenic origin. OBJECTIVES: To induce acute dMxS in rabbits by using their own oral microflora to create a periapical infection and to follow morphological, radiographic, bacteriological and histological changes to the sinus mucosa. MATERIAL AND METHODS: The experimental animals comprised 26 New Zealand White rabbits. Maxillary premolar root canals were identified bilaterally and the continuously growing germs of the roots were severed by diathermy. The animals were randomized into 2 groups: in Group 1 (n=20) the teeth were left open for the entire study period; in Group 2 (n=6) the root canals were sealed 1 week after the initial intervention. The animals in Group 1 were sacrificed at intervals ranging from 2 h to 9 months after intervention. All animals in Group 2 were sacrificed 6 months after intervention. After macroscopic and radiographic examination, post-mortem inspection of the paranasal sinus cavity and maxillary complex and microbiological sampling, the entire nasal sinus complex with the hard palate in situ was resected and processed for serial coronal sectioning. RESULTS: In Group 1, after 3 months, the radiographic changes ranged from widening of the periodontal space to bone reaction. At sacrifice, changes in the sinus mucosa ranged from signs of mucosal inflammation to purulent dMxS. Microbial growth, predominantly Gram-negative aerobes, increased over time. In Group 2, the findings were generally more pronounced. Anaerobic microorganisms were predominant. In both groups the findings were consistent with dMxS.

Animals↗
PubMed1998

Effects of sustained low-level elevations of carbon dioxide on cerebral blood flow and autoregulation of the intracerebral arteries in humans.

Cerebral blood flow velocity (CBFv) was measured by insonating the middle cerebral arteries of four subjects using a 2 Mhz transcranial Doppler. Ambient CO2 was elevated to 0.7% for 23 d in the first study and to 1.2% for 23 d in the same subjects in the second study. By non-parametric testing CBFv was elevated significantly by +35% above pre-exposure levels during the first 1-3 d at both exposure levels, after which CBFv progressively readjusted to pre-exposure levels. Despite similar CBFv responses, headache was only reported during the initial phase of exposure to 1.2% CO2. Vascular reactivity to CO2 assessed by rebreathing showed a similar pattern with the CBFv increases early in the exposures being greater than those elicited later. An increase in metabolic rate of the visual cortex was evoked by having the subjects open and close their eyes during a visual stimulus. Evoked CBFv responses measured in the posterior cerebral artery were also elevated in the first 1-3 d of both studies returning to pre-exposure levels as hypercapnia continued. Cerebral vascular autoregulation assessed by raising head pressure during 10 degrees head-down tilt both during the low-level exposures and during rebreathing was unaltered. There were no changes in the retinal microcirculation during serial fundoscopy studies. The time-dependent changes in CO2 vascular reactivity might be due either to retention of bicarbonate in brain extracellular fluid or to progressive increases in ventilation, or both. Cerebral vascular autoregulation appears preserved during chronic exposure to these low levels of ambient CO2.

Adult↗
PubMed2003

Random walk through fractal environments.

We analyze random walk through fractal environments, embedded in three-dimensional, permeable space. Particles travel freely and are scattered off into random directions when they hit the fractal. The statistical distribution of the flight increments (i.e., of the displacements between two consecutive hittings) is analytically derived from a common, practical definition of fractal dimension, and it turns out to approximate quite well a power-law in the case where the dimension D(F) of the fractal is less than 2, there is though, always a finite rate of unaffected escape. Random walks through fractal sets with D(F)< or =2 can thus be considered as defective Levy walks. The distribution of jump increments for D(F)>2 is decaying exponentially. The diffusive behavior of the random walk is analyzed in the frame of continuous time random walk, which we generalize to include the case of defective distributions of walk increments. It is shown that the particles undergo anomalous, enhanced diffusion for D(F)<2, the diffusion is dominated by the finite escape rate. Diffusion for D(F)>2 is normal for large times, enhanced though for small and intermediate times. In particular, it follows that fractals generated by a particular class of self-organized criticality models give rise to enhanced diffusion. The analytical results are illustrated by Monte Carlo simulations.

Journal Article↗
PubMed2006

State-space analysis of joint angle kinematics in normal treadmill walking.

By restricting analysis to single averaged strides considered to be characteristic for the individual under investigation, current methods in gait analysis do not exploit the full dynamics of continuous locomotion. Therefore, a novel approach is presented that is based on long-term measurements of kinematic data during treadmill walking. The method consists of reconstructing the system attractor in the embedding space and then analyzing its geometric structure. Estimating the dimension of movement trajectories correlates well with the notion of controlling multiple degrees of freedom during performance of complex movement tasks such as walking. The influence of walking speed on the complexity of physiologic walking was investigated in 10 healthy subjects walking on a treadmill at seven fixed speeds. The results suggest that human walking becomes more complex at slower speeds. This may be associated with results from EMG studies demonstrating more irregular EMG patterns at very slow walking speeds. This study emphasizes that tools from non-linear dynamics are well suited for providing more insight into motor control in humans.

Algorithms↗
PubMedDate not supplied

[Effect of continuous gamma-radiation at low doses on clonogenic hemopoietic (CFU-S) and stromal (CFU-F) bone marrow cells ].

We studied the effects of low doses of continuous gamma-irradiation (Co60, 10 days, mean daily dose power 1.5-2.0 mGy, total dose 15 mGy) on hemopoietic and stromal progenitor cells of murine bone marrow. The content of hemopoietic clonogenic cells representing a "younger" (CFU-S-11) and more "mature" (CFU-S-7) categories in the compartment of stem cells was determined in the bone marrow. The state of bone marrow stroma was estimated by the method of in vitro cloning according to the number of progenitor cells that form colonies of fibroblasts (CFU-F) and by the method of ectopic transplantation according to the capacity of stroma of organizing and building new hemopoietic territories. Continuous gamma-irradiation at low doses, that were by one order of magnitude lower than those inducing hermesis, exerted a stimulating effect on both hemopoietic (CFU-S) and stromal (CFU-F) progenitor cells. The number of CFU-S in the compartment of stem cells of the bone marrow markedly increased and they formed larger hemopoietic territories but these cells appeared to create a qualitatively different microenvironment, which stimulated the proliferation of CFU-S.

Animals↗
PubMed2002

Physiological ecology of Mesozoic polar forests in a high CO2 environment.

Fossils show that coniferous forests extended into polar regions during the Mesozoic, a time when models and independent paleo-CO2 indicators suggest that the atmospheric CO2 concentration was at least double that of the present day. Consequently, such polar forests would have experienced high CO2 interacting with an extreme variation in light. Here we describe an experiment investigating this plant-environment interaction for extant tree species that were important components of polar forests, and give results from the first year of treatment. Specifically, we tested the hypotheses that growth in elevated CO2 (1) stimulates photosynthesis; (2) reduces photoinhibition during the polar summer; and (3) reduces respiration of above- and below-ground plant organs. Our results indicate that CO2 fertilization generally does not affect photosynthesis under continuous daylight characteristic of the polar summer but does increase it when the period of illumination is shorter. Growth in elevated CO2 did not alter the potential for photoinhibition. CO2 enrichment significantly reduced leaf and root respiration rates by 50 and 25 %, respectively, in a range of evergreen taxa. Incorporating these observed CO2 effects into numerical simulations using a process-based model of coniferous forest growth indicates that a high paleo-CO2 concentration would have increased the productivity of Cretaceous conifer forests in northern Alaska. This results from decreased respiratory costs that more than compensate for the absence of high CO2-high temperature interactions during the polar summer. The longer-term effects of CO2 enrichment on seasonal changes in the above- and below-ground carbon balance of trees are discussed.

Atmosphere↗
PubMed2002

Automated breath detection on long-duration signals using feedforward backpropagation artificial neural networks.

A new breath-detection algorithm is presented, intended to automate the analysis of respiratory data acquired during sleep. The algorithm is based on two independent artificial neural networks (ANN(insp) and ANN(expi)) that recognize, in the original signal, windows of interest where the onset of inspiration and expiration occurs. Postprocessing consists in finding inside each of these windows of interest minimum and maximum corresponding to each inspiration and expiration. The ANN(insp) and ANN(expi) correctly determine respectively 98.0% and 98.7% of the desired windows, when compared with 29,820 inspirations and 29,819 expirations detected by a human expert, obtained from three entire-night recordings. Postprocessing allowed determination of inspiration and expiration onsets with a mean difference with respect to the same human expert of (mean +/- SD) 34 +/- 71 ms for inspiration and 5 +/- 46 ms for expiration. The method proved to be effective in detecting the onset of inspiration and expiration in full night continuous recordings. A comparison of five human experts performing the same classification task yielded that the automated algorithm was undifferentiable from these human experts, falling within the distribution of human expert results. Besides being applicable to adult respiratory volume data, the presented algorithm was also successfully applied to infant sleep data, consisting of uncalibrated rib cage and abdominal movement recordings. A comparison with two previously published algorithms for breath detection in respiratory volume signal shows that the presented algorithm has a higher specificity, while presenting similar or higher positive predictive values.

Adult↗
PubMed2006

A theoretical formulation of the electrophysiological inverse problem on the sphere.

The construction of three-dimensional images of the primary current density (PCD) produced by neuronal activity is a problem of great current interest in the neuroimaging community, though being initially formulated in the 1970s. There exist even now enthusiastic debates about the authenticity of most of the inverse solutions proposed in the literature, in which low resolution electrical tomography (LORETA) is a focus of attention. However, in our opinion, the capabilities and limitations of the electro and magneto encephalographic techniques to determine PCD configurations have not been extensively explored from a theoretical framework, even for simple volume conductor models of the head. In this paper, the electrophysiological inverse problem for the spherical head model is cast in terms of reproducing kernel Hilbert spaces (RKHS) formalism, which allows us to identify the null spaces of the implicated linear integral operators and also to define their representers. The PCD are described in terms of a continuous basis for the RKHS, which explicitly separates the harmonic and non-harmonic components. The RKHS concept permits us to bring LORETA into the scope of the general smoothing splines theory. A particular way of calculating the general smoothing splines is illustrated, avoiding a brute force discretization prematurely. The Bayes information criterion is used to handle dissimilarities in the signal/noise ratios and physical dimensions of the measurement modalities, which could affect the estimation of the amount of smoothness required for that class of inverse solution to be well specified. In order to validate the proposed method, we have estimated the 3D spherical smoothing splines from two data sets: electric potentials obtained from a skull phantom and magnetic fields recorded from subjects performing an experiment of human faces recognition.

Algorithms↗
PubMed1998

Structure determination of the phiX174 closed procapsid.

The structure of a procapsid of the single-stranded DNA bacteriophage ++phiX174 was determined to 3.5 A resolution. The crystal space group was I213 with a unit-cell length of 774 A. The unit cell contained 16 icosahedral virus particles, each situated on a crystallographic threefold axis. Thus, there are two independent one-thirds of a particle per asymmetric unit, and a total of 40-fold non-crystallographic redundancy. To aid in the interpretation of the packing arrangement, crystals were prepared for thin sectioning and analyzed by electron microscopy. Oscillation X-ray diffraction data was collected on image plates using synchrotron radiation and oscillation angles of either 0.25 or 0.30 degrees. A low-resolution 6.5 A data set collected from a single frozen crystal was particularly helpful in the structure determination, because of its completeness and internal consistency. The initial particle orientations were determined using self-rotation functions, while the initial position of one particle was determined from a Patterson map. The structure was solved by molecular replacement real-space averaging using a model based on a cryo-electron microscopy reconstruction as a starting point for the phase determination. The initial structure determination used the data between 20 and 13 A resolution, which was then extended one reciprocal lattice point at a time to 6.5 A resolution. At this point, a 3.5 A resolution data set compiled from a number of crystals collected at 277 K was introduced. Phase extension and averaging continued to 3.5 A resolution after re-determining the particle positions and orientations. The amino-acid sequences of most of the D, F and G proteins and part of the B protein could be unambiguously built into the 3.5 A electron-density map. Partial crystallographic refinement yielded an R factor of 31.6%, consistent with the relatively low resolution and lack of completeness of the data.

Bacteriophage phi X 174↗
PubMed2004

Models of the mechanism underlying perceived location of a perisaccadic flash.

A variety of experiments have shown that subjects tend to perceive a target flash as mislocalized when the flash is presented just before, during or shortly after the occurrence of a saccade. The characteristics of this mislocalization suggest that it arises from an anticipatory, slow extraretinal signal, i.e., the signal starts to change before a saccade and continues to change during and after the saccade. However, a target flash creates a visual signal that can persist for as long as 300 ms. Interaction of this visual persistence with the extraretinal signal could have a significant influence on the perceived location of the target flash, and thus on features of the extraretinal signal as inferred from the perceived location. In this study, several different types of models were used to explore how retinal signal persistence together with an extraretinal signal might affect perception. According to these models, the anticipatory, slow extraretinal signal may be an artifact of using a target flash, and the actual extraretinal signal may begin to change only after saccade onset and relatively quickly.

Computer Simulation↗