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PubMed2006

Sensorineural hearing loss: potential therapies and gene targets for drug development.

Recent advances in the developmental biology, genetics and cell biology of the inner ear are guiding research to novel therapeutic modalities - a market currently estimated to be at least US Dollars 10 billion. This article highlights prospects to manipulate the mammalian hearing organ with gene and stem cell delivery to the inner ear to protect, repair or regenerate the hair cells, supporting cells and associated nerves.

Aging↗
PubMed2005

New techniques for the reconstruction of complex vascular anatomies from MRI images.

The accurate representation of two-dimensional images in three dimensions has become important for many medical imaging applications and for cardiac magnetic resonance imaging (MRI) in particular. Reconstruction methods applied after data acquisition can produce three-dimensional information from two-dimensional data and make applications such as surgical planning more effective. Current reconstruction techniques usually demand contrast agents, and can suffer due to poor segmentation and sampling constraints that cause surface irregularities and distort dimensions. The novel technique presented here for anatomical modeling uses adaptive control grid interpolation (ACGI) to approximate data not captured by scanning, and a progressive shape-element segmentation technique to complete reconstruction. Quantitative validations conducted on models of pediatric cardiac malformations have confirmed the theoretical advantages of this technique, and that higher quality is achieved than with competing methods based on geometric parameters. Vascular diameters from reconstructions showed errors of less than 1% for a known geometry as compared to over 9% for competing methods. Qualitatively, models produced with the new methodology displayed substantial improvement over alternatives. Approximately 50 rare cardiac structures, including surgically altered Fontan and atypical aortic anatomies, have been reconstructed. All data used to create these reconstructions were acquired using standard pulse sequences and without contrast agents. Benefits of the new technique are particularly evident when complex vascular configurations complicate reconstruction. The proposed methodology enables a powerful tool allowing physicians to analyze and manipulate highly accurate and clearly presented vascular structures in an interactive medium.

Child↗
PubMed1999

Golgi structure in three dimensions: functional insights from the normal rat kidney cell.

Three-dimensional reconstructions of portions of the Golgi complex from cryofixed, freeze-substituted normal rat kidney cells have been made by dual-axis, high-voltage EM tomography at approximately 7-nm resolution. The reconstruction shown here ( approximately 1 x 1 x 4 microm3) contains two stacks of seven cisternae separated by a noncompact region across which bridges connect some cisternae at equivalent levels, but none at nonequivalent levels. The rest of the noncompact region is filled with both vesicles and polymorphic membranous elements. All cisternae are fenestrated and display coated buds. They all have about the same surface area, but they differ in volume by as much as 50%. The trans-most cisterna produces exclusively clathrin-coated buds, whereas the others display only nonclathrin coated buds. This finding challenges traditional views of where sorting occurs within the Golgi complex. Tubules with budding profiles extend from the margins of both cis and trans cisternae. They pass beyond neighboring cisternae, suggesting that these tubules contribute to traffic to and/or from the Golgi. Vesicle-filled "wells" open to both the cis and lateral sides of the stacks. The stacks of cisternae are positioned between two types of ER, cis and trans. The cis ER lies adjacent to the ER-Golgi intermediate compartment, which consists of discrete polymorphic membranous elements layered in front of the cis-most Golgi cisterna. The extensive trans ER forms close contacts with the two trans-most cisternae; this apposition may permit direct transfer of lipids between ER and Golgi membranes. Within 0.2 microm of the cisternae studied, there are 394 vesicles (8 clathrin coated, 190 nonclathrin coated, and 196 noncoated), indicating considerable vesicular traffic in this Golgi region. Our data place structural constraints on models of trafficking to, through, and from the Golgi complex.

Animals↗
PubMed1987

Inverse solutions based on MEG and EEG applied to volume conductor analysis.

An inverse solution computer program, using a single current dipole in a selected volume conductor, calculates an equivalent dipole from a magneto- or electroencephalographic distribution. The program is used to evaluate several volume conductor models of the head by using one model when generating the distribution and another when calculating the equivalent dipole. Sources of errors in the equivalent dipole, namely uncertainties in the model parameters (e.g. conductivities) and noise in the MEG or EEG distribution, are investigated in the same way. A realistically shaped model of the head is introduced to investigate the extent to which sphere-shaped models can be used.

Adult↗
PubMed1987

Analysis of magnetoencephalographic data using the homogeneous sphere model: empirical tests.

The external magnetic fields produced by artificial current dipoles placed in conducting-gel filled spheres, partial spheres and human skulls have been measured. Using a homogeneously conducting sphere model, the dipole parameters have been estimated. Although good quality data fitting is obtainable for a range of positions of the centre of the sphere used in the modelling, the predictions for the dipole obtained with those different assumed positions differ considerably. It is found that the most reliable method of obtaining accurate estimates of the dipole parameters is by taking an average of the predictions of several of the best-fit analyses. The information about the accuracy of the predictions that is obtainable from the fitting routine's residual error parameter is discussed.

Brain↗
PubMed1987

Improved procedure for neuromagnetic localisation.

We describe an improved algorithm for localising equivalent sources of biomagnetic fields in the human brain. The algorithm is an improvement over the sphere model in that it considers two distinct surfaces: an ellipsoid, to model the region of the skull on which the sensors are placed, and a sphere as the medium in which the current dipole model is considered. This allows us to easily correct the formula of the magnetic field in order to take better account of the true position of the sensor with respect to the subject's head.

Algorithms↗
PubMed1987

Development of an agar phantom adaptable for simulation of various tissues in the range 5-40 MHz.

A phantom, electrically adaptable for simulation of various tissues, was developed using agar as the jelly. This phantom has the following features: the dielectric property is specified in the range 5-40 MHz, the conductivity can be varied between 0.02 and 1.23 S m-1, the permittivity can be varied between 35 and 80, preparation and handling are readily facilitated; the original shape is retained for over one year, and it is free from deterioration caused by mould for at least one year.

Agar↗
PubMed1994

Non-invasive bone biopsy: a new method to analyse and display the three-dimensional structure of trabecular bone.

Three-dimensional structure is one of the main factors influencing the mechanical behaviour of cancellous bone. To analyse the trabecular bone structure non-destructively we used a peripheral QCT system and applied a special thin-slice technique to create high-resolution volumetric data sets serving as a basis for something we would like to call non-invasive bone biopsy. In order to obtain binary data sets, the mineralized bone in the CT volume was separated from bone marrow and muscle tissue with the help of a sophisticated three-dimensional segmentation algorithm based on the analysis of directional derivatives, which are computed from a locally approximated fit function of the original CT volume. Binary volumes including either a solid representation of trabecular plates and rods or a topological representation of the cancellous bone architecture were acquired. Such volumes can be processed non-destructively and, even more important, repetitively. By using a surface reconstruction algorithm based on interpolating triangulation it was possible to visualize the three-dimensional surface of the trabecular bone structure. The results showed that surface representation and visualization in combination with a multiple thin-slice measuring technique are valuable tools in studying three-dimensional bone architecture. In the future, the non-invasive bone biopsies will be evaluated by means of three-dimensional mechanical analysis incorporating finite element modelling and direct morphological investigations of the cancellous bone architecture for a better prediction of bone strength as an index for fracture risk or osteoporosis.

Biopsy↗
PubMed1994

Modelling the effect of charge on selective deposition of particles in a diseased lung using aerosol boli.

The technique of using a charged bolus of aerosol to deliver a drug or other agent is advantageous since sites of interest within the lung can be selectively targeted. Ideally, the volume of the bolus should match that of the targeted region allowing the aerosol bolus particles to be confined to the selected area during the pause period after inhalation. Our existing computer model for predicting the deposition of charged aerosol particles has been developed to encompass aerosol boli, some diseased lung morphologies and drug dose administered per breathing cycle. Aerosol deposition in the targeted region is found to be enhanced by increasing particle charge, pause period and particle size. For particles in the size range 1-2.5 microm, aerosol deposition in the region affected by bronchoconstriction does not alter significantly with flow rate variation (range 250-1000 ml s(-1)) for a targeted charged bolus of matched volume. The technique may enable the optimal delivery of therapeutic or other agents to diseased or normal lungs.

Administration, Inhalation↗
PubMed1997

Monte Carlo modelling of angular radiance in tissue phantoms and human prostate: PDT light dosimetry.

Photodynamic therapy (PDT) is a promising technique for destroying tumours. Photosensitizing drugs presently available are not sufficiently tumour specific; hence, light dosimetry is required in order to control light exposure and thereby restrict cell kill to the target tissue to avoid damage to healthy tissue. Current light dosimetry methods rely on tissue optical characterization by fluence measurements at several points. Fluence-based tissue characterization is impractical for tumours in organs such as prostate where access by optical probes is limited and the tumours are highly optically inhomogeneous. This paper explores the potential of radiance-based light dosimetry as an alternative. Correlation is found between Monte Carlo simulation of radiance in a tissue phantom and radiance measurements made using a new radiance probe. Radiance is sensitive to variations in the tissue optical parameters, absorption coefficient mu(a), scattering coefficient mu(s), and anisotropy factor g, and therefore is potentially useful for tissue characterization. Radiance measurements have several advantages over fluence measurements. Radiance measurements provide more information from a single location, better spatial resolution of the tissue optical parameters, and higher sensitivity in discriminating between different media. However, the Monte Carlo method is too slow to be of practical value for tissue characterization by correlation of measured and simulated radiance. An analytical solution to the transport equation for radiance would be desirable as this would facilitate and increase the speed of tissue characterization.

Anisotropy↗
PubMed1997

Performance of a light applicator for photodynamic therapy in the oral cavity: calculations and measurements.

Photodynamic therapy (PDT) is an experimental therapy for the treatment of superficial cancer using laser light. In PDT a uniform light distribution is usually required for an optimal therapeutic effect. To irradiate part of the oral cavity uniformly for PDT, two prototype applicators were built, each for a different lower jaw. The applicators made use of the light transmitted through the wall of a cavity of diffusely reflecting material. The radiant exitance of the applicators was measured at 632.8 nm. For the radiant exitance of M of the two applicators, a uniformity ratio, UR = Mmax/Mmin < 2 was found, which was considered reasonable for clinical applications. Calculations predict that the UR can be improved by decreasing the thickness of the cavity wall.

Biophysical Phenomena↗
PubMed1997

Image segmentation by a deformable contour model incorporating region analysis.

Deformable contour models are useful tools for image segmentation. However, many fields depend mainly on local edge-based image features to guide the convergence of the contour. This makes the models sensitive to noise and the initial estimate. Our model incorporates region-based image features to improve its convergence and to reduce its dependence on initial estimation. Computational efficiency is achieved by an optimization strategy, modified from the greedy algorithm of Williams and Shah. The model allows a simultaneous optimization of multiple contours, making it useful for a large variety of segmentation problems.

Algorithms↗
PubMed1998

Measurement of dielectric properties of subcutaneous fat with open-ended coaxial sensors.

A three-layer model of stratum corneum, epidermis/dermis and subcutaneous fat has been developed for the capacitance of an open-ended coaxial line in contact with human skin. Applying the model, the electrical properties of subcutaneous fat can be calculated from skin dielectric measurements with three probes of different sizes. The three-layer model is based on a variational formula for the capacitance of the coaxial probe. An accurate approximation for the dielectric constant of the multilayer cutaneous structure is presented for the inverse problem of solving the dielectric constants of various layers. The method was tested at 300 MHz with breast cancer patients who often have radiotherapy-induced late alterations in the structure of subcutaneous fat due to the development of subcutaneous fibrosis. Measurements from 206 sites yielded a good agreement between the dielectric constant of subcutaneous fat and the clinical score for subcutaneous fibrosis.

Adipose Tissue↗
PubMed1998

Feldkamp and circle-and-line cone-beam reconstruction for 3D micro-CT of vascular networks.

Detailed morphometric knowledge of the microvascular network is needed for studies relating structure to haemodynamic function in organs like the lung. Clinical volumetric CT is limited to millimetre-order spatial resolution. Since evidence suggests that small arterioles (50 to 300 micrometres) dominate pulmonary haemodynamics, we built a micro-CT scanner, capable of imaging excised lungs in 3D with 100 microm resolution, for basic physiology research. The scanner incorporates a micro-focal (3 microm) x-ray source, an xyz theta stage and a CCD-coupled image intensifier detector. We imaged phantoms and contrast-enhanced rat lungs, reconstructing the data with either the Feldkamp or the circle-and-line cone-beam reconstruction algorithm. We present reconstructions using 180 views over 360 degrees for the circular trajectory, augmented with views from a linear scan for the circle-and-line algorithm. Especially for platelike features perpendicular to the rotation axis and remote from the midplane, the circle-and-line algorithm produces superior reconstructions compared with Feldkamp's algorithm. We conclude that the use of nonplanar source trajectories to perform micro-CT on contrast-enhanced, excised lungs can provide data useful for morphometric analysis of vascular trees, currently down to the 130 microm level.

Algorithms↗
PubMed1999

Resistivity and phase in localized BIA.

We describe a system for highly reproducible non-invasive rf impedance measurements as a function of position along body segments such as the thigh. Results are reported for mainly healthy male and female subjects ranging in age from 19 to 65 and in body-mass index from 15 to 40. A principal conclusion is that the phase of the impedance falls monotonically with increasing distance from the knee, with average values substantially above what is found using standard, whole-body bioelectrical impedance analysis (BIA). To compensate for thigh shape, the data are further analysed using an anatomical model based on reasonable approximations for the distributions of muscle, fat and bone, yielding values of the effective resistivity for current flow parallel to the muscle fibres. The phase and resistivity results are discussed with reference to the whole-body BIA study of maintenance haemodialysis patients by Chertow et al, and in regard to possible physiological correlations observed in this work.

Adult↗