A unified model for the speed of sound in cranial bone based on genetic algorithm optimization

The density and structure of bone is highly heterogeneous, causing wide variations in the reported speed of sound for ultrasound propagation. Current research on the propagation of high intensity focused ultrasound through an intact human skull for non-invasive therapeutic action on brain tissue requires a detailed model for the acoustic velocity in cranial bone. Such models have been difficult to derive empirically due to the aforementioned heterogeneity of bone itself. We propose a single unified model for the speed of sound in cranial bone based upon the apparent density of bone by CT scan. This model is based upon the coupling of empirical measurement, theoretical acoustic simulation and genetic algorithm optimization. The phase distortion caused by the presence of skull in an acoustic path is empirically measured. The ability of a theoretical acoustic simulation coupled with a particular speed-of-sound model to predict this phase distortion is compared against the empirical data, thus providing the fitness function needed to perform genetic algorithm optimization. By performing genetic algorithm optimization over an initial population of candidate speed-of-sound models, an ultimate single unified model for the speed of sound in both the cortical and trabecular regions of cranial bone is produced. The final model produced by genetic algorithm optimization has a nonlinear dependency of speed of sound upon local bone density. This model is shown by statistical significance to be a suitable model of the speed of sound in bone. Furthermore, using a skull that was not part of the optimization process, this model is also tested against a published homogeneous speed-of-sound model and shown to return an improved prediction of transcranial ultrasound propagation.     

Owl's behavior and neural representation predicted by Bayesian inference

The owl captures prey using sound localization. In the classical model, the owl infers sound direction from the position of greatest activity in a brain map of auditory space. However, this model fails to describe the actual behavior. Although owls accurately localize sources near the center of gaze, they systematically underestimate peripheral source directions. We found that this behavior is predicted by statistical inference, formulated as a Bayesian model that emphasizes central directions. We propose that there is a bias in the neural coding of auditory space, which, at the expense of inducing errors in the periphery, achieves high behavioral accuracy at the ethologically relevant range. We found that the owl's map of auditory space decoded by a population vector is consistent with the behavioral model. Thus, a probabilistic model describes both how the map of auditory space supports behavior and why this representation is optimal.     

Encoding of virtual acoustic space stimuli by neurons in ferret primary auditory cortex

Recent studies from our laboratory have indicated that the spatial response fields (SRFs) of neurons in the ferret primary auditory cortex (A1) with best frequencies > or =4 kHz may arise from a largely linear processing of binaural level and spectral localization cues. Here we extend this analysis to investigate how well the linear model can predict the SRFs of neurons with different binaural response properties and the manner in which SRFs change with increases in sound level. We also consider whether temporal features of the response (e.g., response latency) vary with sound direction and whether such variations can be explained by linear processing. In keeping with previous studies, we show that A1 SRFs, which we measured with individualized virtual acoustic space stimuli, expand and shift in direction with increasing sound level. We found that these changes are, in most cases, in good agreement with predictions from a linear threshold model. However, changes in spatial tuning with increasing sound level were generally less well predicted for neurons whose binaural frequency-time receptive field (FTRF) exhibited strong excitatory inputs from both ears than for those in which the binaural FTRF revealed either a predominantly inhibitory effect or no clear contribution from the ipsilateral ear. Finally, we found (in agreement with other authors) that many A1 neurons exhibit systematic response latency shifts as a function of sound-source direction, although these temporal details could usually not be predicted from the neuron's binaural FTRF.     

On the structure-property relationship of sound and hypomineralized enamel

Developmental defects in dental enamel pose significant clinical challenges which have highlighted our limited understanding of the structure and properties of this tissue. In this study, we first investigated the contact-size dependence of the physical properties of sound and hypomineralized enamel, and then examined the microstructure to establish a structural basis for their differing properties. Depth-sensing indentation tests were carried out over a wide range of peak loads in a direction perpendicular to the enamel prisms. Hypomineralized enamel demonstrated stronger penetration dependence for measured hardness and elastic modulus than sound enamel. The microstructure of sound and hypomineralized enamel was observed using field emission scanning electron microscopy and transmission electron microscopy with support of a focused ion beam milling system. Images of sound enamel showed barely distinguishable sheath regions with minimal organic presence. In contrast, hypomineralized enamel showed thicker sheath structures surrounding the prisms and higher levels of organic content within both the prisms and the sheath regions. It is argued that the higher organic content within prism structure was responsible for an initial lower hardness and elastic modulus of hypomineralized enamel under low-load indentation. As the indentation depth increased, the thicker organic-rich sheath regions played a more important role in reducing the mechanical properties of the hypomineralized enamel. On the basis of Spears finite element model [Spears IR. A three-dimensional finite element model of prismatic enamel: a re-appraisal of the data on the Young’s modulus of enamel. J Dental Res 1997; 76(10):1690–97], elastic moduli of sound and hypomineralized enamel were predicted, which matched experimental results.     

The Role of Phase Changes in Sound Signals in Localization of Sound Sources

The auditory system in humans and animals makes virtually no discrimination of phase changes in the structure of monaurally presented sound signals. However, electrophysiological studies have demonstrated marked changes in the responses of the central parts of the auditory system when the phase structure of the signal changes during presentation of the same type of stimulation. We have suggested that this inconsistency is due to the preparative role of phase effects during monaural stimulation for subsequent operations in the auditory system involved in determining the location of a sound source in space. This report presents experimental data on defined changes (increases in amplitude) in the electrical responses of the midbrain center of the auditory system (inferior colliculus) in antiphase binaural presentation of series of sound impulses (comparison with synphase presentation). These changes may be part of the mechanism underlying the interference resistance of the auditory system during determination of the location of a sound source (binaural release from masking). Neuronal cortical activity is sensitive and selective to dynamic interaural changes in the phase spectrum of the signal, which may provide the basis of the mechanism for locating a moving sound source. Auditory evoked potentials in humans demonstrate memorizing of the direction of movement of a sound image, as shown by the changes in parameters on presentation of stimuli of different locations (deviant stimuli) differing from the standard parameters of mismatch negativity.     

Beam orientation optimization in intensity-modulated radiation treatment planning

Beam direction optimization is an important problem in radiation therapy. In intensity modulated radiation therapy (IMRT), the difficulty for computer optimization of the beam directions arises from the fact that they are coupled with the intensity profiles of the incident beams. In order to obtain the optimal incident beam directions using iterative or stochastic methods, the beam profiles ought to be optimized after every change of beam configuration. In this paper we report an effective algorithm to optimize gantry angles for IMRT. In our calculation the gantry angles and the beam profiles (beamlet weights) were treated as two separate groups of variables. The gantry angles were sampled according to a simulated annealing algorithm. For each sampled beam configuration, beam profile calculation was done using a fast filtered backprojection (FBP) method. Simulated annealing was also used for beam profile optimization to examine the performance of the FBP for beam orientation optimization. Relative importance factors were incorporated into the objective function to control the relative importance of the target and the sensitive structures. Minimization of the objective function resulted in the best possible beam orientations and beam profiles judged by the given objective function. The algorithm was applied to several model problems and the results showed that the approach has potential for IMRT applications.     

A comparison of tracheal breath sounds, airflow, and impedance pneumography in the detection of childhood apnea

Impedance respiratory monitoring is not capable of detecting obstructive apneas. We compared a microphone breath sound detector, coupled to the chest wall, with a standard impedance device in 10 sleeping infants and children in order to determine the ability of the breath sound detector to detect normal respirations and central and obstructive apneas. Airflow was used as a standard for all measurements. No difference was found between the breath sound detector and impedance device techniques in the detection rate of either normal respirations or central apneic intervals. There was no statistically significant difference between breath sounds and airflow in the ability of either technique to detect obstructive apnea. The use of a breath sound detector avoids unnecessary stimulation of a sleeping child, whose monitoring would otherwise require that two or three airflow sensing devices be taped on the face. Breath sound monitoring may represent an alternative to impedance and airflow techniques for evaluation of apnea in closely observed infants and children.     

Coding of sound direction in the auditory periphery of the lake sturgeon, Acipenser fulvescens

The lake sturgeon, Acipenser fulvescens, belongs to one of the few extant nonteleost ray-finned fishes and diverged from the main vertebrate lineage about 250 million years ago. The aim of this study was to use this species to explore the peripheral neural coding strategies for sound direction and compare these results to modern bony fishes (teleosts). Extracellular recordings were made from afferent neurons innervating the saccule and lagena of the inner ear while the fish was stimulated using a shaker system. Afferents were highly directional and strongly phase locked to the stimulus. Directional response profiles resembled cosine functions, and directional preferences occurred at a wide range of stimulus intensities (spanning at least 60 dB re 1 nm displacement). Seventy-six percent of afferents were directionally selective for stimuli in the vertical plane near 90° (up down) and did not respond to horizontal stimulation. Sixty-two percent of afferents responsive to horizontal stimulation had their best axis in azimuths near 0° (front back). These findings suggest that in the lake sturgeon, in contrast to teleosts, the saccule and lagena may convey more limited information about the direction of a sound source, raising the possibility that this species uses a different mechanism for localizing sound. For azimuth, a mechanism could involve the utricle or perhaps the computation of arrival time differences. For elevation, behavioral strategies such as directing the head to maximize input to the area of best sensitivity may be used. Alternatively, the lake sturgeon may have a more limited ability for sound source localization compared with teleosts.     

A quasi-brittle continuum damage finite element model of the human proximal femur based on element deletion

In this paper, a simple and practical finite element (FE) model coupled to a quasi-brittle damage law to describe the initiation and progressive propagation of multiple cracks based on element deletion is developed to predict the complete force–displacement curve and the fracture pattern of a human proximal femur under quasi-static load. The motivation of this work was to propose a FE model for possible clinical use with a good compromise between complexity and capability of the simulation. The model considers a limited number of parameters that can predict proximal femur fracture in more adequate physical terms than criteria-based fracture models. Based on experimental results, different damage laws for cortical and trabecular bone are proposed to describe inelastic damage accumulation under excessive load. When the damage parameter reaches its critical value inside an element of the mesh, its stiffness matrix is set to zero, leading to the redistribution of the stress state in the vicinity of the damaged zone (crack initiation). Once a crack is initiated, the propagation direction is simulated by the propagation of the broken elements of the mesh. To illustrate the potential of the proposed approach, the left femur of a male (age 61) previously investigated by Keyak and Falkinstein [37] (Model B: male, age 61) was simulated till complete fracture under one-legged stance quasi-static load. The proposed finite element model leads to more physical results concerning the shape of the force–displacement curve (yielding and fracturing) and the profile of the fractured edge.     

Biocomputing: numerical simulation of glioblastoma growth using diffusion tensor imaging

Glioblastoma multiforma (GBM) is one of the most aggressive tumors of the central nervous system. It can be represented by two components: a proliferative component with a mass effect on brain structures and an invasive component. GBM has a distinct pattern of spread showing a preferential growth in the white fiber direction for the invasive component. By using the architecture of white matter fibers, we propose a new model to simulate the growth of GBM. This architecture is estimated by diffusion tensor imaging in order to determine the preferred direction for the diffusion component. It is then coupled with a mechanical component. To set up our growth model, we make a brain atlas including brain structures with a distinct response to tumor aggressiveness, white fiber diffusion tensor information and elasticity. In this atlas, we introduce a virtual GBM with a mechanical component coupled with a diffusion component. These two components are complementary, and can be tuned independently. Then, we tune the parameter set of our model with an MRI patient. We have compared simulated growth (initialized with the MRI patient) with observed growth six months later. The average and the odd ratio of image difference between observed and simulated images are computed. Displacements of reference points are compared to those simulated by the model. The results of our simulation have shown a good correlation with tumor growth, as observed on an MRI patient. Different tumor aggressiveness can also be simulated by tuning additional parameters. This work has demonstrated that modeling the complex behavior of brain tumors is feasible and will account for further validation of this new conceptual approach.     

Mechanical behaviour of aortic tissue as a function of collagen orientation

X-ray diffraction techniques have been used to investigate the orientation under stress of collagen fibres in pig's descending aortic wall. The variation of the limit value of the incremental modulus as a function of the collagen content seems to suggest that the extra amount of collagen going from the aortic arch downwards is deposited in a preferred orientation corresponding to the circumferential direction. The results have been used to describe the uniaxial mechanical behaviour of this tissue taking into account its composite structure.     

Tactile recalibration of auditory spatial representations

In the well-known spatial ventriloquism effect, auditory stimuli are mislocalized towards the location of synchronous but spatially disparate visual stimuli. Recent studies have demonstrated a similar influence of tactile stimuli on auditory localization, which predominantly operates in an external coordinate system. Here, we investigated whether this audio-tactile ventriloquist illusion leads to comparable aftereffects in the perception of auditory space as have been observed previously for audiovisual stimulation. Participants performed a relative sound localization task in which they had to judge whether a brief sound was perceived at the same or a different location as a preceding tactile stimulus (“Experiment 1”) or to the left or right of a preceding visual stimulus (“Experiment 2”). Sound localization ability was measured before and after exposure to synchronous audio-tactile stimuli with a constant spatial disparity. After audio-tactile adaptation, unimodal sound localization was shifted in the direction of the tactile stimuli during the preceding adaptation phase in both tasks. This finding provides evidence for the existence of an audio-tactile ventriloquism aftereffect and suggests that auditory space (rather than specific audio-tactile connections) can be rapidly recalibrated to compensate for audio-tactile spatial disparities.     

Coupled radiative transfer equation and diffusion approximation model for photon migration in turbid medium with low-scattering and non-scattering regions

In this paper, a coupled radiative transfer equation and diffusion approximation model is extended for light propagation in turbid medium with low-scattering and non-scattering regions. The light propagation is modelled with the radiative transfer equation in sub-domains in which the assumptions of the diffusion approximation are not valid. The diffusion approximation is used elsewhere in the domain. The two equations are coupled through their boundary conditions and they are solved simultaneously using the finite element method. The streamline diffusion modification is used to avoid the ray-effect problem in the finite element solution of the radiative transfer equation. The proposed method is tested with simulations. The results of the coupled model are compared with the finite element solutions of the radiative transfer equation and the diffusion approximation and with results of Monte Carlo simulation. The results show that the coupled model can be used to describe photon migration in turbid medium with low-scattering and non-scattering regions more accurately than the conventional diffusion model.     

Absorption and noise in cesium iodide x-ray image intensifiers

The measured and theoretically predicted values of detective quantum efficiency (DQE) for a CsI x-ray image intensifier are compared for nine monoenergetic beams of x rays. The agreement between measurement and theory of better than +/- 5% indicates that we have a sound understanding of the physical parameters controlling the DQE. It is shown that the fraction of K-fluorescent x rays escaping from the input phosphor is independent of incident energy. The number of electrons released within the x-ray image intensifier (XRII) by an incident x ray has been measured. The mechanism for energy broadening within the XRII is shown to be predominantly the limited number of electrons and not light absorption.     

Acoustic rhinometry measurements in stepped-tube models of the nasal cavity

Stepped-tube models with a constriction in the anterior section were used to evaluate the effects that nasal valve passage area and nasal cavity shape have on acoustic rhinometry (AR) measurements. The AR-determined cross-sectional areas beyond a constriction of small passage area were consistently underestimated, and the corresponding area-distance curves showed pronounced oscillations. Also, the AR technique did not accurately reproduce abrupt changes in passage area. The results suggest that, regardless of the particular shape of the nasal cavity model, AR does not provide reliable information about cross-sectional areas posterior to a severe constriction. The experimental results are discussed in terms of theoretically calculated acoustic input impedance for the models studied, the physical limitations of AR, and assumptions made in AR algorithms. The study demonstrated that energy losses and sound wave attenuation due to air viscosity do not significantly affect AR measurements. It was also shown that passage area beyond a severe constriction is underestimated because the barrier created by the constriction reflects most of the incident sound power. The results also indicate that the oscillations in area-distance curves are due to low-frequency acoustic resonances in the nasal cavity model.     

Control analysis of the Rose-Hindmarsh model for neural activity

It is well known that vasopressin cells fire action potentialsin bursts, but also have the ability to continuously dischargeor have long periods of silence. Experimentally, various externalstimuli can be applied to the vasopressin cell in order tomanipulate the patterns of discharge observed. In this paper, the Rose–Hindmarsh model is used to describe the dischargingof a single vasopressin cell. The range of parameter valueswhich makes the model display the various patterns observedin vivo are described. It is shown that the model can be controlledto follow desired patterns of discharge and thus mimic externalstimulation.     

A comparison of two boundary conditions used with the bidomain model of cardiac tissue

In the bidomain model, two alternative sets of boundary conditions at the interface between cardiac tissue and a saline bath have been used. It is shown that these boundary conditions are equivalent if the length constant of the tissue in the direction transverse to the fibers is much larger than the radius of the individual cardiac cells. If this is not the case, the relative merits of the two boundary conditions are closely related to the question of the applicability of a continuum model, such as the bidomain model, to describe a discrete multicellular tissue.     

The effect of topographic characteristics on cell migration velocity

The migration of cells on structured surfaces is known to be affected by its surface topography. Although the effects of topography have been extensively investigated the crucial parameters determining the cell-surface reaction are largely unknown. The present study was performed to describe and to define the role of groove/elevation (ridge) dimensions at the micrometre scale on fibroblast cell migration by correlating cell shape, migration angle alpha, cell orientation beta and velocity with these dimensions. For this a quantitative method was developed. We could show that the surface structures significantly influenced migration direction alpha, cell orientation beta and mean velocity, as well as migration speed in the directions parallel and perpendicular to the grooves/elevations in a surface structure dependant way. Cell migration velocity parallel, respectively, perpendicular to the structures was significantly affected by the geometries and dimensions of the substratum. Surface structures were not able to significantly affect distribution patterns of cell shapes. Overall, it could be shown that differently structured surfaces influenced the cells but no crucial feature could be clearly identified, suggesting that the reaction of the surface structure might be far more complex than generally is assumed.     

Early development of the myotome in the mouse.

The structure and development of the myotome has been extensively studied in birds and amphibians but few studies have systematically addressed its development in mammals. We have used a transgenic mouse carrying an nLacZ marker coupled to a myosin light chain 3F promoter to describe the structure of the developing mammalian myotome. Through studies of transgene expression pattern, coupled with immunohistochemistry for the muscle structural proteins desmin and slow myosin heavy chain we describe a gradient of maturity for the cells within the developing myotome. Our results show that the earliest myocytes of the mammalian myotome span the rostrocaudal extent of the somite and have single large nuclei which localise centrally within the myotome. Throughout the period of study the myotome is more mature ventrally than dorsally and cells comprising the medial aspect of the myotome are younger than those lying laterally. Immunohistochemistry for the earliest expressed muscle regulatory factor (myf-5) is used to define areas of the myotome contributing new myogenic cells. In the early myotome small, round, myf-5-expressing cells are found extensively within the dorsomedial aspect of the dermamyotome and also within the entire rostral and caudal dermamyotomal lips. They subsequently appear within the central zone of the myotome, adjacent to the medially curled rostral and caudal dermamyotomal lips, and there begin to elongate symmetrically. As the myotome enlarges, myf-5 expression is always restricted to the most medial aspect of the myotome, adjacent to the least mature myocytes, marking the site of addition of new myogenic cells. Together, these results allow development of a model of mammalian myotome formation where growth occurs medially by addition of new cells from both rostral and caudal dermamyotome lips, while more mature myocytes are displaced laterally. Furthermore, early myotomal myocytes differentiate in the absence of MyoD expression, unlike later myotomal myocytes. This, along with their distinct morphology, suggests these cells may form a separate lineage of pioneer myogenic cells.     

Light dosimetry in optical phantoms and in tissues: I. Multiple flux and transport theory

This is the first of two papers on the quantitative measurement of light energy fluence rates in optical phantoms and in tissues, in vitro and in vivo. The theory discussed in the present paper will be used in a forthcoming experimental paper to quantitatively check measurements of light energy fluence rates. A simple multiple flux model, which is equivalent to the diffusion approximation, is derived from the equation of transfer in a plane as well as in a spherical geometry. The equations obtained are similar to those of the Kubelka-Munk and related heuristic models. This permits conclusions regarding the limitations of these models and the values of their constants. The heuristic models are equivalent to diffusion theory for diffuse incident light, but not for collimated incident light. We also present a simple calculation of the radiance as a function of direction in the diffusion domain. This, together with the effective attenuation coefficient, permits indirect experimental determination of both the albedo and the anisotropy factor (g) of the scattering function. Similarity relations are discussed, as they result from the so called delta-Eddington approximation, leading to the conclusion that far from boundaries and sources light propagation characteristics do not change very much when g and omega s are varied, provided omega s (1-g) is kept constant (omega s = scattering coefficient). Therefore, only two optical constants are required to approximately describe light propagation in homogeneous and isotropic media in the diffusion approximation.