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Spline surface interpolation for calculating 3-D ventricular strains from MRI tissue tagging.

A method is developed and validated for approximating continuous smooth distributions of finite strains in the ventricles from the deformations of magnetic resonance imaging (MRI) tissue tagging "tag lines" or "tag surfaces." Tag lines and intersections of orthogonal tag lines are determined using a semiautomated algorithm. Three-dimensional (3-D) reconstruction of the displacement field on tag surfaces is performed using two orthogonal sets of MRI images and employing spline surface interpolation. The 3-D regional ventricular wall strains are computed from an initial reference image to a deformed image in diastole or systole by defining a mapping or transformation of space between the two states. The resultant mapping is termed the measurement analysis solution and is defined by determining a set of coefficients for the approximating functions that best fit the measured tag surface displacements. Validation of the method is performed by simulating tag line or surface deformations with a finite element (FE) elasticity solution of the heart and incorporating the measured root-mean-square (rms) errors of tag line detection into the simulations. The FE-computed strains are compared with strains calculated by the proposed procedure. The average difference between two-dimensional (2-D) FE-computed strains and strains calculated by the measurement analysis was 0.022 +/- 0.009 or 14.2 +/- 3.6% of the average FE elasticity strain solution. The 3-D displacement reconstruction errors averaged 0.087 +/- 0.002 mm or 2.4 +/- 0.1% of the average FE solution, and 3-D strain fitting errors averaged 0.024 +/- 0.011 or 15.9 +/- 2.8% of the average 3-D FE elasticity solution. When the rms errors in tag line detection were included in the 2-D simulations, the agreement between FE solution and fitted solution was 24.7% for the 2-D simulations and 19.2% for the 3-D simulations. We conclude that the 3-D displacements of MRI tag lines may be reconstructed accurately; however, the strain solution magnifies the small errors in locating tag lines and reconstructing 3-D displacements.

Animals↗

Pulmonary blood flow determined by continuous analysis of pulmonary N2O exchange.

Measurement of mean pulmonary blood flow (Qp) as a function of pulmonary inert gas (N2O) uptake was studied with the aid of a mathematical model, fast response measurement of gas flow and gas concentrations at the mouth, and digital computer analysis of the data. The model treats the total pulmonary inert gas uptake as the sum of dead space, alveolar, lung tissue, and pulmonary blood flow uptakes. Analysis of any two breaths during breathing of a gas mixture (39 percent N2O, 21 percent O2, 40 percent N2 or He) in terms of the soluble (N2O) and the insoluble (N2 or He) inert gas yields two simultaneous equations with two unknowns which can be solved for Qp. No assumptions are required about the magnitude of the alveloar, dead space, or lung tissue volumes and constant FRC is not a requirement. The validity of the mathematical model and its sensitivity to known measurement errors was studied by computer simulation of respiratory gas exchange for N2O and N2. Comparison of Qp (N2O) with the direct Fick method (O2) in five anesthetized dogs showed agreement within plus or minus 20 percent. The proposed method has promise as a clinical method for determination of cardiac output on a breath-to-breath basis during regular breathing at rest or during exercise.

Animals↗

Parameter space structure of continuous-time recurrent neural networks.

A fundamental challenge for any general theory of neural circuits is how to characterize the structure of the space of all possible circuits over a given model neuron. As a first step in this direction, this letter begins a systematic study of the global parameter space structure of continuous-time recurrent neural networks (CTRNNs), a class of neural models that is simple but dynamically universal. First, we explicitly compute the local bifurcation manifolds of CTRNNs. We then visualize the structure of these manifolds in net input space for small circuits. These visualizations reveal a set of extremal saddle node bifurcation manifolds that divide CTRNN parameter space into regions of dynamics with different effective dimensionality. Next, we completely characterize the combinatorics and geometry of an asymptotically exact approximation to these regions for circuits of arbitrary size. Finally, we show how these regions can be used to calculate estimates of the probability of encountering different kinds of dynamics in CTRNN parameter space.

Animals↗

Temporal surveillance using scan statistics.

We describe two classes of statistics for testing an arbitrary model of disease incidence over time against an alternative model involving a spike (pulse) superimposed on this background. The statistics are each based on taking the maximum of some function comparing observed and expected numbers of events in a window of width w. One approach applies p-values for scan statistics calculated for a constant background rate to this more general problem. For a fixed window, w, the approach gives a simple formula to determine p-values for retrospective analysis, or to sound an alarm for either continuous or grouped prospective data. The latter application involves a new approximation for the distribution of the maximum number of cases in w consecutive intervals. The second approach based on generalized likelihood ratio tests (GLRTs), sounds an alarm for a higher than anticipated rate of events in a scanning window of fixed length, or for window sizes that lie in a region. GLRTs are constructed for continuous observations, for grouped data, or for a sequence of trials. As for GLRTs used in retrospective evaluations, simulation is required to implement the prospective procedure. For grouped surveillance data, we compare by simulation, operating characteristics of the P-scan with fixed windows (both correctly specified and not), the fixed-window GLRT, the variable-window GLRT, and a variant of the CUSUM. The simulations demonstrate a very high correlation between the P-scan and corresponding fixed-window GLRT.

Adult↗

A software simulation of tibial fracture reduction with external fixator.

In modern orthopaedic practice, circular external fixators are frequently preferred to plaster cast for various reasons. The realignment of the two fractured bone segments is usually performed under a continuous fluoroscopy checking which involves a long radiation exposure time for both patients and surgeon. In order to overcome this problem, a computer controlled external fixator is under development. One relevant problem which this project faced in its initial stage was the difficulty to define in geometrical terms the manual reduction trajectory normally adopted by the surgeon. Basically it was a typical problem of empirical knowledge transfer from the surgeon to the engineer. Thus, it was necessary to create a common ground where the two experts could carry out the necessary analyses in order to define an empirical algorithm capable of suggesting a correction trajectory. The problem was solved by developing a simulation program called S.E.R.F. (Simulation Environment of a Robotic Fixator) provided with an extremely powerful graphic output, able to visualize the whole reduction trajectory from any viewpoint in space. The authors suggest the use of this kind of tool every time the techno-clinical information exchange is a critical issue.

Algorithms↗

Exercise load index and changes in body weight during long-duration confinement in an isolated environment.

PURPOSE: The objectives of this project were to investigate exercise load and body weight related to long-duration confinement in a closed environment simulating ISS flight conditions, and to evaluate subjects' motivation to continue the experiment and their adaptation to isolation. METHODS: Four Russian male subjects participated in a 240-d experiment (Group I), and four subjects (three male subjects and one female subject) from Austria, Canada, Japan, and Russia participated in a 110-d experiment (Group II). Exercise load was estimated during confinement using a modified Rating of Perceived Exertion scale. Free reports were used to determine subjects' motivation. Body weight was measured before, during, and after confinement. RESULTS: Group I achieved their lowest exercise loads during their first month of isolation; problems with adaptation to the isolation environment were also reported during this first month. Group II exercise load was significantly lower in the second month due to crewmember problems; loss of motivation could be noted from their free reports. The subject with the lowest exercise load retired from the isolation experiment earlier than scheduled. Exercise load was not correlated with prior exercise habits. Significant differences in body weight was observed between group I and II and between Russian and non-Russian subjects. One subject in Group I experienced a significant increase in his body weight. CONCLUSION: Exercise load may be a good indicator for adaptation problems and motivation changes in closed environments. Immobility, lack of space, and smoking cessation in general did not induce significant body weight changes.

Adaptation, Physiological↗

In vivo estimation of cardiac transmembrane current.

The ionic currents that cross the myocardial membrane during cardiac activation have a corresponding return path in the extracellular space. The transmembrane current (Im) during activation of cardiac cells in situ has previously been envisioned only in mathematical models. We have developed a remarkably simple in vivo technique that incorporates an electrode array with cellular dimensions to continuously estimate the extracellular counterparts of cardiac Ims. Mathematical modeling was performed for uniform plane wave propagation to clarify the biophysical basis and underlying assumptions inherent in this approach. Five-element electrode arrays incorporating 75-microns-diameter silver electrodes with center-to-center distances of 210 microns were experimentally verified to provide spatially sufficient samples for voltage gradient determinations of myocardial activation. Similar results were obtained with 25-microns-diameter electrodes at a center-to-center spacing of 65 microns. An estimate of Im was obtained from the derivative of the magnitude of the voltage gradient of the measured interstitial potentials. The inward component of Im generated by normal Na+ channel activation at 37 degrees C was measured in vivo to be less than 1 msec in duration, consistent with previously known voltage-clamp and simulation results. Intravenous KCl bolus injection was used to demonstrate the voltage-dependent depression of Na(+)-mediated Im in vivo, culminating in either severely depressed Na(+)-mediated or Ca(2+)-mediated activations. Normal Na(+)-, depressed Na(+)-, and possibly Ca(2+)-mediated currents can be recorded in vivo using this technique.

Animals↗

Dynamical control of the dialysis process. Part II: An improved algorithm for the solution of a tracking problem.

An efficient algorithm for the optimization of process parameters during dialysis has been developed. By solving a tracking-problem for prescribed time courses of distinguished variables, it is possible to compute optimal concentrations of electrolytes in dialysate as well as an optimal rate of ultrafiltration. These variables are indirectly influencing the status of the patient and can be directly modelled. They are describing the important exchange processes between blood and dialysate as well as between the different distribution spaces within the patient during dialysis. Their time courses are determined by an individually identifiable patient model. The tracking problem was treated as a dynamic optimization problem, and a continuous descent procedure which is usually employed for solving unconstrained static optimization problems has been adapted in such a manner that it is applicable for the solution of this problem. The used method is characterized by its simple mode of application, short solution time and moderate storage need. Especially in cases of contradictional requirements for desired time courses of model outputs the used optimization method performs well.

Algorithms↗

Deterministic and stochastic models for the seasonal variability of measles transmission.

Fine and Clarkson used a discrete-time epidemic model with variable transmission parameter to analyze measles data for England and Wales for 1950-1965, during the time of biennial epidemics. Their model seems to provide a convincing fit when its parameters are estimated from these data. In particular, they obtained nearly equal estimates for the variable transmission parameter from the widely different data for epidemic and nonepidemic years. They did not, however, study the dynamics of their model. In this paper we make such a study, and find that the model is unsatisfactory in some important respects. It has a unique equilibrium (to be exact, a solution showing only seasonal variation), and neutrally stable oscillations around this equilibrium are possible, but with period approximately 3 years, not 2. (The model also has an exact 3-year cycle, while for intermediate initial values it shows unstable "chaotic" behavior.) If we vary the amount of variation in the transmission parameter, from no variation to 2.5 times the observed amount, the main periodicity remains approximately 3 years, though the complexity of behavior changes, increasing as the amount of variation increases. A continuous-time version of the model also has an equilibrium and a 3-year cycle, the main difference being that these are stable rather than neutrally stable. A stochastic version shows that simulations starting close to either the equilibrium or the 3-year cycle have a high probability of remaining close to the corresponding deterministic solutions for at least 20-30 years. The oscillatory features of the model are thus reasonably robust against stochastic fluctuations. We conclude that the simple homogeneous mixing model cannot be adapted to provide an adequate fit to the data, especially in explaining the observed biennial cycles. It seems likely that the pattern of seasonal variation found by Fine and Clarkson is essentially correct, but for accurate modeling of measles we need also to take into account heterogeneities of mixing in the population, especially those due to age and space.

Age Factors↗

Three-dimensional spatial grouping affects estimates of the illuminant.

The brightnesses (i.e., perceived luminance) of surfaces within a three-dimensional scene are contingent on both the luminances and the spatial arrangement of the surfaces. Observers viewed a CRT through a haploscope that presented simulated achromatic surfaces in three dimensions. They set a test patch to be approximately 33% more intense than a comparison patch to match the comparison patch in brightness, which is consistent with viewing a real scene with a simple lightning interpretation from which to estimate a different level of illumination in each depth plane. Randomly positioning each surface in either depth plane minimized any simple lighting interpretation, concomitantly reducing brightness differences to approximately 8.5%, although the immediate surrounds of the test and comparison patches continued to differ by a 5:1 luminance ratio.

Adult↗

A possible role for gap junctions in generation of very fast EEG oscillations preceding the onset of, and perhaps initiating, seizures.

PURPOSE: We propose an experimentally and clinically testable hypothesis, concerning the origin of very fast (> approximately 70 Hz) EEG oscillations that sometimes precede the onset of focal seizures. These oscillations are important, as they may play a causal role in the initiation of seizures. METHODS: Subdural EEG recordings were obtained from children with focal cortical dysplasias and intractable seizures. Intra- and extracellular recordings were performed in rat hippocampal slices, with induction of population activity, as follows: (a) bath-applied tetramethylamine (an intracellular alkalinizing agent, that opens gap junctions); (b) bath-applied carbachol, a cholinergic agonist; and (c) focal pressure ejection of hypertonic K+ solution. Detailed network simulations were performed, the better to understand the cellular mechanisms underlying oscillations. A major feature of the simulations was inclusion of axon-axon gap junctions between principal neurons, as supported by recent experimental data. RESULTS: Very fast oscillations were found in children before seizure onset, but also superimposed on bursts during the seizure, and on interictal bursts. In slice experiments, very fast oscillations had previously been seen on interictal-like bursts; we now show such oscillations before, between, and after epileptiform bursts. Very fast oscillations were also seen superimposed on gamma (30-70 Hz) oscillations induced by carbachol or hypertonic K+, and in the latter case, very fast oscillations became continuous when chemical synapses were blocked. Simulations replicate these data, when axonal gap junctions are included. CONCLUSIONS: Electrical coupling between principal neurons, perhaps via axonal gap junctions, could underlie very fast population oscillations, in seizure-prone brain, but possibly also in normal brain. The anticonvulsant potential of gap-junction blockers such as carbenoxolone, now in clinical use for treatment of ulcer disease, should be considered.

Animals↗

Cardiovascular function during sustained +Gz stress.

The development of aerospace systems capable of very high levels of positive (+Gz) stress, has created a need for a better understanding of the cardiovascular responses to acceleration. Using a canine model, the heart and cardiovascular system were instrumented to continuously measure coronary blood flow, cardiac output, left ventricular and aortic root pressure, and oxygen saturation in the aorta, coronary sinus, and right ventricle. The animals were exposed to acceleration profiles up to +6 Gz, 120 s at peak G; a seatback angle of 45 degrees was simulated in some experiments. Radiopaque contrast medium was injected to visualize the left ventricular chamber, coronary vasculature, aorta, and branches of the aorta. The results suggest mechanisms responsible for arrhythmias which may occur, and subendocardial hemorrhage which has been reported in other animals.

Blood Pressure↗

Three-dimensional imaging and display of the temporomandibular joint.

Despite recent advances in diagnostic radiology, current techniques for radiographic evaluation of the temporomandibular joint continue to present the clinician with difficult problems in interpretation and diagnosis. The use of three-dimensional images reconstructed from computed tomographic (CT) data improves the diagnostic value of conventional CT at no additional risk to the patient and may provide new insights into this complex anatomic structure. A sequence of 1.5 mm CT sections is made with a slice-to-slice spacing of 1.0 mm. These are used to construct a new sequence of slices by mathematical interpolation in which the new slice spacing equals the size of the pixels. Structures to be imaged separately are then masked in the interpolated sections prior to "windowing" for the appropriate tissue density. A special algorithm detects the boundary surface of the selected structure. The surface pixels are assigned gray levels on the basis of their distance and attitude from the observer. When displayed, this produces a simulated three-dimensional image. The image can be rotated and sectioned. Rotations permit otherwise hidden surfaces to be examined. Images of a human temporomandibular joint in vitro are presented to demonstrate (1) the bony components of the joint and their relationships within the joint; (2) the bony components separated to display hidden surfaces; and (3) the joint meniscus in situ and as a separate component.

Cadaver↗

Comparison of cross-talk effects between colloidal quantum dot and conventional waveguides.

We present cross-talk calculations for a subdiffraction nanophotonic waveguide that consists of a colloidal quantum dot (QD) array 10 nm in diameter and compare the results with conventional continuous dielectric waveguides, assuming the same 10 nm size as well as a 200 nm cutoff diameter for guided mode. We find that the QD cascade has much lower cross talk than 10 nm dielectric waveguides at an identical separation >30 nm. Moreover, results for 200 nm dielectric waveguides at a 280 nm gap are comparable with those of QD structures spaced 110 nm apart. Hence the proposed QD device is potentially superior to conventional waveguides in achieving lower cross talk in the subdiffraction regime and provides a new route to achieving high-density photonic integrated circuits.

Artifacts↗

Massive retroperitoneal hemorrhage from an asymptomatic adrenal cortical adenoma. Report of a case.

A 52-year-old man was admitted to the General Surgical Service, with acute onset of left back and flank pain. Two weeks prior to admission he had been subjected to a 3G to 4G acceleration in an ejection seat training simulator. On the day of admission, he had performed a 100 yard swim in flight gear following a seven foot jump into water. He denied any injury during the above exercises or any other trauma. A falling hematocrit was demonstrated by serial determinations and a computerized tomography scan revealed a left retroperitoneal hematoma with normal bilateral renal function and no obvious renal injury. Continued hemorrhage resulted in laparotomy, which showed an 11 cm left adrenal tumor with massive hemorrhage into the retroperitoneum. Histologically the tumor was a benign non-functioning adrenal cortical adenoma.

Adenoma↗

Numerical simulation of a child restraint system in an aircraft crash-test.

Studies conducted at the FAA Civil Aeromedical Institute have shown that when used in aircraft, automotive child restraint devices do not always provide the level of safety desired. Various factors that contribute to poor performance, such as seat belt anchor location, cushion stiffness, and child restraint device design features, were evaluated by a dynamic impact test program. To efficiently continue the research, a computer model was developed using MADYMO. Results of two of the impact tests were used to validate the model. Both test configurations utilized a typical commercial transport airplane passenger seat and a popular automotive child restraint device. These tests were considered representative of the extremes of child restraint device and occupant kinematics due to variance in seat belt anchor location. Details are presented of the test parameters and geometry, as well as cushion and restraint system properties. Test and modelling results for these two impact conditions are summarized and compared. Parametric studies were then conducted that used the model to investigate the effect of cushion stiffness, belt anchor spacing, and initial belt tension.

Accidents, Aviation↗

Effect of intra-tracheal instillation and inhalation of silicon dioxide on some biochemical variables in broncho-alveolar lavage fluid and lung histopathology in rats.

In the present study, the bronchial alveolar lavage fluid (BALF) biochemical and lung histopathological changes occurring in response to single large intra-tracheal exposure to silica have been compared to the changes seen after continued chronic exposure via inhalation. Male albino rats (200-250gms) were exposed to silicon dioxide via intratracheal instillation (8mg/0.05ml saline) and whole body inhalation (200mg/m3, 6 hours/day for 2 and 4 weeks) in separate groups . The respective control animals were instilled with normal saline (0.05ml) or exposed to fresh air in simulation chamber for the same duration. BALF was analyzed for total protein, elastase, malondialdehyde (MDA) levels and catalase activity and histopathology of right lung was carried out after 4 weeks post-exposure in intra-tracheal model and after 2 and 4 weeks of exposure in the inhalation model. The levels of total protein, elastase and malondialdehyde (MDA) were significantly elevated, while catalase activity was significantly decreased in the BALF of exposed animals as compared to controls. The histopathological studies of lungs, showed exudates of inflammatory cells, chiefly of macrophages in the alveolar spaces and interstitial septa with multifocal nodular granulomatous lesions. The biochemical findings in BALF of both the models indicate inflammatory changes, lipid peroxidation and fibrosis. However, comparatively lower catalase activity and higher elastase levels in the 4 week inhalationally exposed group than the 4 week post intratracheally exposed group, suggests that these parameters may be affected by acute and chronic exposure and require further confirmation.

Animals↗

Three-dimensional lattice-Boltzmann simulations of critical spinodal decomposition in binary immiscible fluids.

We use a modified Shan-Chen, noiseless lattice-BGK model for binary immiscible, incompressible, athermal fluids in three dimensions to simulate the coarsening of domains following a deep quench below the spinodal point from a symmetric and homogeneous mixture into a two-phase configuration. The model is derivable from a continuous-time Boltzmann-BGK equation in the presence of an intercomponent body force. We find the average domain size grows with time as t(gamma), where gamma increases in the range 0.545+/-0.014 q(4) crossover in the scaled structure function, which disappears when the dynamical scaling reasonably improves at later stages (Re=37). This excludes noise as the cause for a q(2) behavior, as analytically derived from Yeung and proposed by Appert et al. and Love et al. on the basis of their lattice-gas simulations. We also observe exponential temporal growth of the structure function during the initial stages of the dynamics and for wave numbers less than a threshold value, in accordance with the diffusive Cahn-Hilliard Model B. However, this exponential growth is also present in regimes proscribed by that model. There is no evidence that regions of parameter space for which the scheme is numerically stable become unstable as the simulations proceed, in agreement with finite-difference relaxational models and in contradistinction with an unconditionally unstable lattice-BGK free-energy model previously reported. Those numerical instabilities that do arise in this model are the result of large intercomponent forces which turn the equilibrium distribution negative.

Journal Article↗