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PubMed2002

Dosimetric verification of inverse planned step and shoot multileaf collimator fields from a commercial treatment planning system.

An inverse treatment planning (ITP) module on a commercial treatment planning system (TPS) (Helax AB, Uppsala, Sweden) is being used for an in-house clinical trial for treatment of nasopharyngeal cancer with contralateral parotid sparing. Intensity modulated radiation therapy (IMRT) fields are delivered by step and shoot multileaf collimator (MLC) with a DMLC enabled Varian 2300 CD (Varian Associates, Palo Alto, CA). A series of testing procedures have been devised to quantify the modeling and delivery accuracy of routine clinical inverse planned IMRT using Helax TMS and the Varian step and shoot MLC delivery option. Testing was done on specific aspects of the TPS modeling germane to DMLC. Measured relative dose factors (head scatter plus phantom scatter) for small MLC fields, normalized to a 10x10 cm2 non-MLC field, were found to differ by 2-3% from the TPS values for the smallest of the fields tested. Relative distributions for small off axis fields were found to be in good agreement. A process for the routine clinical verification of IMRT fields has been implemented. Each IMRT field in an inverse plan is imported into a flat water tank plan and a "beam's eye view" (BEV) dose distribution is generated. This is compared to the corresponding measured BEV dose distribution. The IMRT verification process has also been performed using an anthropomorphic phantom. Large clinical fields (i.e., greater than 14.5 cm in the leaf direction) caused difficulties due to a vendor specific machine restriction, and several techniques for dealing with these were examined. These techniques were (i) the use of static stepping of closed junctions, (ii) the use of two separate IMRT fields for a given gantry angle, and (iii) restricting the overall maximum field size used. The overall process has allowed implementation of an in-house protocol for IMRT use on an initial clinical site. Results of the verification measurements for the first ten patients treated at this center reveal an average maximum dose per IMRT field delivered of 71.0 cGy, with a mean local deviation from the planned dose of -1.2 cGy, and a standard deviation of 2.4 cGy.

Algorithms↗
PubMed2002

A phase regulated back wave propagation technique for geoacoustic inversion.

An inversion method based on the concept of back wave propagation (BWP) is described in this paper for estimation of geoacoustic parameters from acoustic field data. A phase-regulation technique is introduced to increase the sensitivity of the method for geoacoustic model parameters having low sensitivity. The case of data consisting of signal plus additive noise is also addressed. It is shown theoretically that the sensitivity can be increased by a factor alpha using the phase regulation procedure, and that the spatial resolution of signal energy that is concentrated by BWP at the known source position is increased when a increases. This result suggests an effective criterion for use in the inversion, based on the spatial distribution of signal energy around the true source location. The basis for the criterion is the spatial variance of the back-propagated pressure field in a window around the known source location. A multistep search process is proposed to avoid using a complicated multidimensional search process. Inversion results from both simulations and experimental data are given. The real data were taken from the Pacific Shelf experiment carried out in shallow water off the West Coast of Vancouver Island in the Northeast Pacific Ocean.

Acoustics↗
PubMed2002

Range-dependent seabed characterization by inversion of acoustic data from a towed receiver array.

The MAPEX2000 experiments were conducted in the Mediterranean Sea in March, 2000 to determine seabed properties using a towed acoustic source and receiver array. Towed systems are advantageous because they are easy to deploy from a ship and the moving platform offers the possibility for estimating spatially variable (range-dependent) seabed properties. In this paper, seabed parameters are determined using a matched-field geoacoustic inversion approach with measured, towed array data. Previous research has successfully applied matched-field geoacoustic inversion techniques to measured acoustic data. However, in nearly all cases the inverted data were collected on moored, vertical receiver arrays. Results here show that seabed parameters can also be extracted by inverting acoustic measurements from a towed array of receivers, and these agree with those inverted using data received simultaneously on a vertical array. These findings imply that a practical technique could be developed to map range-dependent seabed parameters over large areas using a towed acoustic system. An example of such a range-dependent inversion is given using measurements from the MAPEX2000 experiments.

Acoustics↗
PubMed2002

Effects of incoherent and coherent source spectral information in geoacoustic inversion.

This paper examines the effect on matched-field geoacoustic inversion of including source spectral information, as can be available in controlled-source acoustic surveys. Source information can consist of relative or absolute knowledge of the source amplitude and/or phase spectra, and can allow frequency-coherent processing of spatial acoustic-field data. A number of multi-frequency acoustic processors, appropriate for specific types of source information, are defined based on the likelihood function for complex acoustic-field data with Gaussian noise. The information content of the various processors is quantified in terms of marginal probability distributions and highest-probability density intervals for the unknown geoacoustic and geometric parameters, which define the accuracy expected in inversion. Marginal distributions are estimated using a fast Gibbs sampler approach to Bayesian inversion, which provides an efficient, unbiased sampling of the multi-dimensional posterior probability density. The analysis is illustrated for incoherent and coherent processors corresponding to several types of source knowledge ranging from complete information to no information, and the results are considered as a function of the spatial and frequency sampling of the acoustic fields.

Acoustics↗
PubMed2003

Broadband sound propagation in shallow water and geoacoustic inversion.

Part of an experiment to test a measurement package in a shallow water region in the Gulf of Mexico was designed to gather broadband acoustic data suitable for inversion to estimate seabed geoacoustic parameters. Continuous wave tow acoustic signals at multiple frequencies and broadband impulsive source signals were recorded on a horizontal line array in a high-noise environment. Simulated annealing with a normal mode forward propagation model is utilized to invert for a geoacoustic representation of the seabed. Several inversions are made from different data samples of two light bulb implosions, the measured sound speed profiles at the HLA and at the positions of the light bulb deployments, and for two different cost functions. The different cost functions, measured sound speed profiles, and measured time series result in different inverted geoacoustic profiles from which transmission loss is generated for comparison with measurements. On the basis of physical consistency and from the comparison of the transmission loss and time series, a best estimate geoacoustic profile is selected and compared to those obtained from previously reported inversions. Uncertainties in the sound speed profile are shown to affect the uncertainties of the estimated seabed parameters.

Journal Article↗
PubMed2003

Sound source reconstruction using inverse boundary element calculations.

Whereas standard boundary element calculations focus on the forward problem of computing the radiated acoustic field from a vibrating structure, the aim in this work is to reverse the process, i.e., to determine vibration from acoustic field data. This inverse problem is brought on a form suited for solution by means of an inverse boundary element method. Since the numerical treatment of the inverse source reconstruction results in a discrete ill-posed problem, regularization is imposed to avoid unstable solutions dominated by errors. In the present work the emphasis is on Tikhonov regularization and parameter-choice methods not requiring an error-norm estimate for choosing the right amount of regularization. Several parameter-choice strategies have been presented lately, but it still remains to be seen how well these can handle industrial applications with real measurement data. In the present work it is demonstrated that the L-curve criterion is robust with respect to the errors in a real measurement situation. In particular, it is shown that the L-curve criterion is superior to the more conventional generalized cross-validation (GCV) approach for the present tire noise studies.

Journal Article↗
PubMed2003

Contrast source inversion methods in elastodynamics.

In this paper a nonlinear inversion method is presented for determining the mass density of an elastic inclusion from the knowledge of how the inclusion scatters known incident elastic waves. The algorithm employed is an extension of the multiplicative regularized contrast source inversion method (MR-CSI) to elasticity. This method involves alternate determination of the mass density contrast and the contrast sources (the product of the contrast and the fields) in each iterative step. The simple updating schemes of the method allow the introduction of an extra regularization term to the cost functional as a multiplicative constraint. This so-called MR-CSI method (MR-CSI) has been proven to be very effective for the acoustic and electromagnetic inverse scattering problems. Numerical examples demonstrate that the MR-CSI method shows excellent edge preserving properties by robustly handling noisy data very well, even for more complicated elastodynamic problems.

Journal Article↗
PubMed2004

Measuring of viscoelastic properties of homogeneous soft solid using transient elastography: an inverse problem approach.

Two main questions are at the center of this paper. The first one concerns the choice of a rheological model in the frequency range of transient elastography, sonoelasticity or NMR elastography for soft solids (20-1000 Hz). Transient elastography experiments based on plane shear waves that propagate in an Agar-gelatin phantom or in bovine muscles enable one to quantify their viscoelastic properties. The comparison of these experimental results to the prediction of the two simplest rheological models indicate clearly that Voigt's model is the better. The second question studied in the paper deals with the feasibility of quantitative viscosity mapping using inverse problem algorithm. In the ideal situation where plane shear waves propagate in a sample, a simple inverse problem based on the Helmholtz equation correctly retrieves both elasticity and viscosity. In a more realistic situation with nonplane shear waves, this simple approach fails. Nevertheless, it is shown that quantitative viscosity mapping is still possible if one uses an appropriate inverse problem that fully takes into account diffraction in solids.

Algorithms↗
PubMed2005

Hilbert space inverse wave imaging in a planar multilayer environment.

Most diffraction tomography (DT) algorithms use a homogeneous Green function (GF) regardless of the medium being imaged. This choice is usually motivated by practical considerations: analytic inversions in standard geometries (Cartesian, spherical, etc.) are significantly simplified by the use of a homogeneous GF, estimating a nonhomogeneous GF can be very difficult, as can incorporating a nonhomogeneous GF into standard DT algorithms. Devaney has circumvented these issues by developing a purely numerical DT inversion algorithm [A. J. Devaney and M. Dennison, Inverse Probl. 19, 855-870 (2003)] that is independent of measurement system geometry, number of frequencies used in the reconstruction, and GF. A planar multilayer GF has been developed for use in Devaney's "Hilbert space" algorithm and used in a proof-of-principle nondestructive evaluation (NDE) experiment to image noninvasively a flaw in an aluminum/copper planar multilayer medium using data collected from an ultrasonic measurement system. The data were collected in a multistatic method with no beamforming: all focusing through the multilayer was performed mathematically "after-the-fact," that is, after the data were collected.

Acoustics↗
PubMed2006

Ultrasonic characterization of human cancellous bone using the Biot theory: inverse problem.

This paper concerns the ultrasonic characterization of human cancellous bone samples by solving the inverse problem using experimental transmitted signals. The ultrasonic propagation in cancellous bone is modeled using the Biot theory modified by the Johnson et al. model for viscous exchange between fluid and structure. The sensitivity of the Young modulus and the Poisson ratio of the skeletal frame is studied showing their effect on the fast and slow wave forms. The inverse problem is solved numerically by the least squares method. Five parameters are inverted: the porosity, tortuosity, viscous characteristic length, Young modulus, and Poisson ratio of the skeletal frame. The minimization of the discrepancy between experiment and theory is made in the time domain. The inverse problem is shown to be well posed, and its solution to be unique. Experimental results for slow and fast waves transmitted through human cancellous bone samples are given and compared with theoretical predictions.

Bone and Bones↗
PubMed1995

The "inverse problem" solved for a three-dimensional model of the cochlea. I. Analysis.

With nonactive cochlear models of the "classical" type, it is impossible to stimulate the characteristic type of frequency selectivity that is revealed by modern mechanical measurements of the motion of the basilar membrane (BM). Locally active models of the cochlea have been proposed to alleviate this problem but it remains uncertain whether the real cochlea is active in this sense. The present study was undertaken to investigate this subject in a more general and systematic way than has hitherto been done. The "inverse" problem is solved for a three-dimensional (3-D) model and a procedure is developed for recovering the BM impedance needed to stimulate the given BM response function. In the present paper the theoretical basis of the procedure is presented, and an analysis is given of the validity of the method and the errors involved. It is shown why the inverse problem is "ill-posed" and why the results of our procedure are more accurate in the region of the response peak than in the more basal region of the model. The latter finding serves to delimit the domain within which results of an inverse procedure (for instance, in the short- or long-wave approximation) are to be judged. In a subsequent paper the technique developed will be applied to actual data sets from the literature on mechanical BM measurements.

Auditory Perception↗
PubMed1998

Ultrasonic focusing through inhomogeneous media by application of the inverse scattering problem.

A new approach is introduced for self-focusing phased arrays through inhomogeneous media for therapeutic and imaging applications. This algorithm utilizes solutions to the inverse scattering problem to estimate the impulse response (Green's function) of the desired focal point(s) at the elements of the array. This approach is a two-stage procedure, where in the first stage the Green's functions is estimated from measurements of the scattered field taken outside the region of interest. In the second stage, these estimates are used in the pseudoinverse method to compute excitation weights satisfying predefined set of constraints on the structure of the field at the focus points. These scalar, complex valued excitation weights are used to modulate the incident field for retransmission. The pseudoinverse pattern synthesis method requires knowing the Green's function between the focus points and the array, which is difficult to attain for an unknown inhomogeneous medium. However, the solution to the inverse scattering problem, the scattering function, can be used directly to compute the required inhomogeneous Green's function. This inverse scattering based self-focusing is noninvasive and does not require a strong point scatterer at or near the desired focus point. It simply requires measurements of the scattered field outside the region of interest. It can be used for high resolution imaging and enhanced therapeutic effects through inhomogeneous media without making any assumptions on the shape, size, or location of the inhomogeneity. This technique is outlined and numerical simulations are shown which validate this technique for single and multiple focusing using a circular array.

Acoustics↗
PubMed2000

Inversion of penetrable obstacles from far-field data on narrow angular apertures

Reported in this paper are reconstructions of shape and material parameters of two-dimensional, homogeneous, acoustic, penetrable obstacles of arbitrary cross-sections which are immersed in an infinite, homogeneous ambience. Reconstructions are based on the far-field scattering patterns of multiple incident plane acoustic waves. For remotely acquired data, practical necessities require not only that the entire data collection region be less than 2 pi, but also that each received "sees" the object over as narrow an angular aperture as possible. The inversions presented here were obtained under such conditions. Two types of data were used for each incidence namely, "near-monostatic" fields of narrow angular apertures (the narrowest aperture reported is 2 degrees), and a "duostatic" geometry consisting of backscatter plus one other receiver angle. These data sets were acquired for a series of incident angles. The theoretical formalism for inversion is algebraic in nature, requires no integral equation, and possesses a number of advantages for the implementation of a Gauss-Newton type of inversion that was used in this study. Moreover, the algorithm is shown to be inheritently parallelizable.

Journal Article↗
PubMed2000

High-resolution geoacoustic inversion in shallow water: a joint time- and frequency-domain technique

High-resolution geoacoustic data are required for accurate predictions of acoustic propagation and scattering in shallow water. Since direct measurement of geoacoustic data is difficult, time-consuming, and expensive, inversion of acoustic data is a promising alternative. However, the main problem encountered in geoacoustic inversion is the problem of uniqueness, i.e., many diverse geoacoustic models can be made to fit the same data set. A key, and perhaps unique, aspect of this approach is the combination of data analysis in both the space-time and the space-frequency domains. This combination attempts to ameliorate the uniqueness problem by exploiting as much independent data as possible. In order to meet the stringent requirements of high spatial resolution and uniqueness, an entire method has been developed including a new measurement technique, processing/analysis technique, and inversion strategy. These techniques are described and then illustrated with a shallow-water data set. Sound-speed gradients in the upper few meters of the sub-bottom appear to be much higher (one order of magnitude) than generally assumed. And, although often ignored, a large density gradient was observed in the top layer that played an acoustically significant role.

Journal Article↗
PubMed2000

Inverse problem solution techniques as applied to indirect in situ estimation of fish target strength.

In situ indirect methods of fish target strength (TS) estimation are analyzed in terms of the inverse techniques recently applied to the problem in question. The solution of this problem requires finding the unknown probability density function (pdf) of fish target strength from acoustic echoes, which can be estimated by solving the integral equation, relating pdf's of echo variable, target strength, and beam pattern of the echosounder transducer. In the first part of the paper the review of existing indirect in situ TS-estimation methods is presented. The second part introduces the novel TS-estimation methods, viz.: Expectation, Maximization, and Smoothing (EMS), Windowed Singular Value Decomposition (WSVD), Regularization and Wavelet Decomposition, which are compared using simulations as well as actual data from acoustic surveys. The survey data, acquired by the dual-beam digital echosounder, were thoroughly analyzed by numerical algorithms and the target strength and acoustical backscattering length pdf's estimates were calculated from fish echoes received in the narrow beam channel of the echosounder. Simultaneously, the estimates obtained directly from the dual-beam system were used as a reference for comparison of the estimates calculated by the newly introduced inverse techniques. The TS estimates analyzed in the paper are superior to those obtained from deconvolution or other conventional techniques, as the newly introduced methods partly avoid the problem of ill-conditioned equations and matrix inversion.

Acoustics↗
PubMed2006

BF2.649 [1-{3-[3-(4-Chlorophenyl)propoxy]propyl}piperidine, hydrochloride], a nonimidazole inverse agonist/antagonist at the human histamine H3 receptor: Preclinical pharmacology.

Histamine H3 receptor inverse agonists are known to enhance the activity of histaminergic neurons in brain and thereby promote vigilance and cognition. 1-{3-[3-(4-Chlorophenyl)propoxy]propyl}piperidine, hydrochloride (BF2.649) is a novel, potent, and selective nonimidazole inverse agonist at the recombinant human H3 receptor. On the stimulation of guanosine 5'-O-(3-[35S]thio)triphosphate binding to this receptor, BF2.649 behaved as a competitive antagonist with a Ki value of 0.16 nM and as an inverse agonist with an EC50 value of 1.5 nM and an intrinsic activity approximately 50% higher than that of ciproxifan. Its in vitro potency was approximately 6 times lower at the rodent receptor. In mice, the oral bioavailability coefficient, i.e., the ratio of plasma areas under the curve after oral and i.v. administrations, respectively, was 84%. BF2.649 dose dependently enhanced tele-methylhistamine levels in mouse brain, an index of histaminergic neuron activity, with an ED50 value of 1.6 mg/kg p.o., a response that persisted after repeated administrations for 17 days. In rats, the drug enhanced dopamine and acetylcholine levels in microdialysates of the prefrontal cortex. In cats, it markedly enhanced wakefulness at the expense of sleep states and also enhanced fast cortical rhythms of the electroencephalogram, known to be associated with improved vigilance. On the two-trial object recognition test in mice, a promnesiant effect was shown regarding either scopolamine-induced or natural forgetting. These preclinical data suggest that BF2.649 is a valuable drug candidate to be developed in wakefulness or memory deficits and other cognitive disorders.

Acetylcholine↗
PubMed2002

Enhanced detection of receptor constitutive activity in the presence of regulators of G protein signaling: applications to the detection and analysis of inverse agonists and low-efficacy partial agonists.

Fusion proteins between the human 5-hydroxytryptamine (5-HT)(1A) receptor and either wild type or certain pertussis toxin-resistant forms of G(o1)alpha and G(i1)alpha display constitutive GTPase activity that can be inhibited by the inverse agonist spiperone. Addition of recombinant regulator of G protein signaling (RGS) 1 or RGS16 to membranes expressing these fusion proteins resulted in elevation of this constitutive GTPase activity without significantly altering the binding affinity of antagonist/inverse agonist ligands. For a 5-HT(1A) receptor-(Cys(351)Ile)G(o1)alpha fusion protein the increase in basal GTPase activity was greater than 4-fold. Enzyme kinetic analysis demonstrated that the effect of RGS1 was as a GTPase-activating protein for the fusion construct. In the presence of the RGS proteins, both agonists and inverse agonists produced much more robust regulation of high-affinity GTPase activity than in their absence. This allowed detection of the partial agonist nature of WAY100635, which has been described previously as a neutral antagonist at the 5-HT(1A) receptor. Of a range of ligands studied, only haloperidol functioned as a neutral ligand in the presence of RGS1. These studies show that addition of a recombinant RGS protein provides a simple and novel means to elevate the fraction of basal membrane GTPase activity contributed by the constitutive activity of a receptor. By so doing, it also greatly enhances the ability to detect and analyze the effects of inverse agonists and to discriminate between neutral ligands and those with low levels of positive intrinsic efficacy.

Cells, Cultured↗
PubMed2003

Tiotidine, a histamine H2 receptor inverse agonist that binds with high affinity to an inactive G-protein-coupled form of the receptor. Experimental support for the cubic ternary complex model.

Knowing the importance for research and pharmacological uses of proper ligand classification into agonists, inverse agonists, and antagonists, the aim of this work was to study the behavior of tiotidine, a controversial histamine H2 receptor ligand. We found that tiotidine, described previously as an H2 antagonist, actually behaves as an inverse agonist in U-937 cells, diminishing basal cAMP levels. [3H]Tiotidine showed two binding sites, one with high affinity and low capacity and the other with low affinity and high capacity. The former site disappeared in the presence of guanosine 5'-O-(3-thio)triphosphate, indicating that it belongs to a subset of receptors coupled to G-protein, showing the classic binding profile for an agonist. Considering the occupancy models developed up to now, the only one that explains tiotidine dual behavior is the cubic ternary complex (CTC) model. This model allows G-protein to interact with the receptor even in the inactive state. We showed by theoretical simulations based on the CTC model of dose-response and binding experiments that tiotidine biases the system to a G-protein-coupled form of the receptor that is unable to evoke a response. This theoretical approach was supported by experimental results in which an unrelated G-protein-coupled receptor that also signals through Galphas-protein (beta2-adrenoreceptor) was impeded by tiotidine. This interference clearly implies that tiotidine biases the system to Galphas-coupled form of the H2 receptor and turns Galphas-protein less available to interact with beta2-adrenoreceptor. These findings not only show that tiotidine is an H2 inverse agonist in U-937 cells but also provide experimental support for the CTC model.

Animals↗