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J T Ratnanather

Publications and source records attributed to J T Ratnanather.

9 recordsLinked to original sources

Electromechanical models of the outer hair cell composite membrane.

The outer hair cell (OHC) is an extremely specialized cell and its proper functioning is essential for normal mammalian hearing. This article reviews recent developments in theoretical modeling that have increased our knowledge of the operation of this fascinating cell. The earliest models aimed at capturing experimental observations on voltage-induced cellular length changes and capacitance were based on isotropic elasticity and a two-state Boltzmann function. Recent advances in modeling based on the thermodynamics of orthotropic electroelastic materials better capture the cell's voltage-dependent stiffness, capacitance, interaction with its environment and ability to generate force at high frequencies. While complete models are crucial, simpler continuum models can be derived that retain fidelity over small changes in transmembrane voltage and strains occurring in vivo. By its function in the cochlea, the OHC behaves like a piezoelectric-like actuator, and the main cellular features can be described by piezoelectric models. However, a finer characterization of the cell's composite wall requires understanding the local mechanical and electrical fields. One of the key questions is the relative contribution of the in-plane and bending modes of electromechanical strains and forces (moments). The latter mode is associated with the flexoelectric effect in curved membranes. New data, including a novel experiment with tethers pulled from the cell membrane, can help in estimating the role of different modes of electromechanical coupling. Despite considerable progress, many problems still confound modelers. Thus, this article will conclude with a discussion of unanswered questions and highlight directions for future research.

Animals↗

Labeled cortical mantle distance maps of the cingulate quantify differences between dementia of the Alzheimer type and healthy aging.

The cingulate gyri in 37 subjects with and without early dementia of the Alzheimer type (DAT) were studied by using MRI at 1.0 mm3 isotropic resolution. Groups were segregated into young controls (n = 10), age-matched normal controls (n = 10), very mild DAT (n = 8), and mild DAT (n = 9). By using automated Bayesian segmentation of the cortex and gray matter/white matter (GM/WM) isosurface generation, tissue compartments were labeled into gray, white, and cerebrospinal fluid as a function of distance from the GM/WM isosurface. Cortical mantle distance maps are generated profiling the GM volume and cortical mantle distribution as a function of distance from the cortical surface. Probabilistic tests based on generalizations of Wilcoxon-Mann-Whitney tests were applied to quantify cortical mantle distribution changes with normal and abnormal aging. We find no significant change between young controls and healthy aging as measured by the GM volume and cortical mantle distribution as a function of distance in both anterior and posterior regions of the cingulate. Significant progression of GM loss is seen in the very mild DAT and mild DAT groups in all areas of the cingulate. Posterior regions show both GM volume loss as well as significant cortical mantle distribution decrease with the onset of mild DAT. The "shape of the cortical mantle" as measured by the cortical mantle distance profiles manifests a pronounced increase in variability with mild DAT.

Adult↗

Dynamic programming generation of boundaries of local coordinatized submanifolds in the neocortex: application to the planum temporale.

Dynamic programming is used to define boundaries of cortical submanifolds with focus on the planum temporale (PT) of the superior temporal gyrus (STG), which has been implicated in a variety of neuropsychiatric disorders. To this end, automated methods are used to generate the PT manifold from 10 high-resolution MRI subvolumes ROI masks encompassing the STG. A procedure to define the subvolume ROI masks from original MRI brain scans is developed. Bayesian segmentation is then used to segment the subvolumes into cerebrospinal fluid, gray matter (GM), and white matter (WM). 3D isocontouring using the intensity value at which there is equal probability of GM and WM is used to reconstruct the triangulated graph representing the STG cortical surface, enabling principal curvature at each point on the graph to be computed. Dynamic programming is used to delineate the PT manifold by tracking principal curves from the retro-insular end of the Heschl's gyrus (HG) to the STG, along the posterior STG up to the start of the ramus and back to the retro-insular end of the HG. A coordinate system is then defined on the PT manifold. The origin is defined by the retro-insular end of the HG and the y-axis passes through the point on the posterior STG where the ramus begins. Automated labeling of GM in the STG is robust with L(1) distances between Bayesian and manual segmentation in the range 0.001-0.12 (n = 20). PT reconstruction is also robust with 90% of the vertices of the reconstructed PT within about 1 voxel (n = 20) from semiautomated contours. Finally, the reliability index (based on interrater intraclass correlation) for the surface area derived from repeated reconstructions is 0.96 for the left PT and 0.94 for the right PT, thus demonstrating the robustness of dynamic programming in defining a coordinate system on the PT. It provides a method with potential significance in the study of neuropsychiatric disorders.

Algorithms↗

Validating cortical surface analysis of medial prefrontal cortex.

This paper describes cortical analysis of 19 high resolution MRI subvolumes of medial prefrontal cortex (MPFC), a region that has been implicated in major depressive disorder. An automated Bayesian segmentation is used to delineate the MRI subvolumes into cerebrospinal fluid (CSF), gray matter (GM), white matter (WM), and partial volumes of either CSF/GM or GM/WM. The intensity value at which there is equal probability of GM and GM/WM partial volume is used to reconstruct MPFC cortical surfaces based on a 3-D isocontouring algorithm. The segmented data and the generated surfaces are validated by comparison with hand segmented data and semiautomated contours, respectively. The L(1) distances between Bayesian and hand segmented data are 0.05-0.10 (n = 5). Fifty percent of the voxels of the reconstructed surface lie within 0.12-0.28 mm (n = 14) from the semiautomated contours. Cortical thickness metrics are generated in the form of frequency of occurrence histograms for GM and WM labelled voxels as a function of their position from the cortical surface. An algorithm to compute the surface area of the GM/WM interface of the MPFC subvolume is described. These methods represent a novel approach to morphometric chacterization of regional cortex features which may be important in the study of psychiatric disorders such as major depression.

Adult↗

Bayesian construction of geometrically based cortical thickness metrics.

This paper describes the construction of cortical metrics quantifying the probabilistic occurrence of gray matter, white matter, and cerebrospinal fluid compartments in their correlation to the geometry of the neocortex as measured in 0.5-1.0 mm magnetic resonance imagery. These cortical profiles represent the density of the tissue types as a function of distance to the cortical surface. These metrics are consistent when generated across multiple brains indicating a fundamental property of the neocortex. Methods are proposed for incorporating such metrics into automated Bayes segmentation.

Anthropometry↗

An analysis of the hydraulic conductivity of the extracisternal space of the cochlear outer hair cell.

The cylindrically shaped cochlear outer hair cell (OHC) plays an important role in the transduction of acoustic energy into electrical energy in the cochlea. The extracisternal space (ECiS) of the lateral wall of the OHC is the fluid-filled space between the plasma membrane (PM) and the intracellular subsurface cisterna (SSC). In the ECiS, an array of cylindrical micropillars extends from the SSC to the PM. We obtain equations for the pressure, osmotic concentration and fluid velocity in the ECiS from the Brinkman-Stokes equations for steady incompressible flow in a plane channel that encloses an array of cylinders and whose upper wall, i.e. the plasma membrane, has a hydraulic conductivity of P(PM). From these equations we obtain an estimate for the hydraulic conductivity of the ECiS, P(ECiS). We show that the ECiS geometry accounts for P(ECiS) being several orders of magnitude larger than P(PM) and that P(ECiS) increases with the width of the ECiS and decreases with the length of the ECiS.

Cochlea↗

Measurements and a model of the outer hair cell hydraulic conductivity.

The hydraulic conductivity of the cochlear outer hair cell (OHC) is central to the maintenance of the positive intracellular pressure necessary for its function as the cochlear amplifier. A mathematical model of osmotic water transport across the OHC membrane is formulated. The model relates the OHC hydraulic conductivity, Lp, to the rate of volume change in response to osmotic stimuli. Lp is evaluated from osmotic experiments in which isolated OHCs are exposed to an hypotonic solution. The rate of volume increase in response to the hypotonic challenge was determined by a morphometric analysis of video images of cells. Lp was found to be about 10(-14) m s-1 Pa-1 or equivalently, Pf approximately 10(-4) cm s-1. This is on the low side of values reported for different lipid bilayers and is 2 orders of magnitude lower than the hydraulic conductivity of red blood cells. The relation of the low OHC hydraulic conductivity to the composition and morphology of its membranes is discussed.

Animals↗

The ratio of elastic moduli of cochlear outer hair cells derived from osmotic experiments.

Outer hair cells (OHCs) were subjected to three different hypo-osmotic challenges which induced shape changes in OHCs. The longitudinal and circumferential strains, epsilon z and epsilon c, respectively, were extracted from a morphometric analysis of video images of the cells. A value of epsilon z/epsilon c = -0.72 was obtained and was found to be independent of the applied osmotic gradient. Using an elastic isotropic membrane model for the OHC lateral wall, the ratio of the elastic shear modulus mu to the elastic area expansion modulus K was calculated yielding a value of 0.054. The contribution of this ratio to OHC mechanics is discussed.

Animals↗