Calculation of dose distribution near an innovative concentric balloon catheter for endovascular brachytherapy

Purpose: Using a radioactive solution-filled catheter for intravascular irradiation has the potential problem of chemical and radiological toxicity in the case of a balloon rupture. In order to reduce this risk, an innovative concentric balloon catheter was developed.Methods and Materials: The concentric balloon was made by inner and outer balloons filled with saline and radioactive solution, respectively. The optimal inner radius was determined by comparing the dose rate reduction vs. the volume reduction for various inner and outer radii for 188Re, 32P, and 90Y solutions.Results: For a balloon with an outer radius of 1.5 mm, there was no advantage of a concentric balloon. For balloons with outer radii of 3.0 and 5 mm, the optimal inner radius was 1.5 and 3 mm, respectively.Conclusions: With the newly designed concentric balloon, the risk of toxicity can be reduced while keeping the dose rate high enough so that the treatment times within tolerable limits are still maintained.     

Repeatability of surface EMG parameters at various isometric contraction levels and during fatigue using bipolar and Laplacian electrode configurations.

The objective of this work was to assess the repeatability of two surface electromyographic (sEMG) recording techniques, the classical bipolar configuration and a Laplacian configuration to document their ability to provide reliable information during follow-up studies. The signals were recorded on 10 healthy subjects during voluntary isometric contractions of the biceps brachii muscle at different constant contraction levels. Slopes, area ratios (at 60% of the maximal voluntary contraction (MVC)) and initial values (at 20%, 40%, 60%, 80% and 100% MVC) of the root mean square (RMS), the mean power frequency (MPF) and the muscle fibre conduction velocity (CV) were estimated. Experimental sessions were repeated on three different days with both electrode sets to evaluate the repeatability of sEMG parameter estimates. Classical results were observed, such as an increase in the RMS and the CV with the contraction level. Only initial values of RMS and MPF were shown to be dependent on electrode type. These two parameters presented intra-class correlation coefficient values higher than .80 for high contraction levels. On the whole, the repeatability of the measures was good; however it was better for all sEMG parameter estimates with bipolar electrodes than Laplacian electrodes. Because a bipolar configuration is less selective than a Laplacian one, it provides a global view of muscular activity, which is more repeatable, hence more suitable for follow-up studies.     

Local estimate of surface Laplacian derivation on a realistically shaped scalp surface and its performance on noisy data

A new implementation of the surface Laplacian derivation (SLD) method is desribed which reconstructs a realistically shaped, local scalp surface geometry using measured electrode positions, generates a local spectral-interpolated potential distribution function, and estimates the surface Laplacian values through a local planar parametric space using a stable numerical method combining Taylor expansions with the least-squares technique. The implementation is modified for efficient repeated SLD operations on a time series. Examples are shown of applications to evoked potential data. The resolving power of the SLD is examined as a function of the spatial signal-to-noise (SNR) ratio. The analysis suggests that the Laplacian is effective when the spatial SNR is greater than 3. It is shown that spatial low-pass filtering with a Gaussian filter can be used to reduce the effect of noise and recover useful signal if the noise is spatially incoherent.     

Stepwise reduction of functional spinal structures increase disc bulge and surface strains

Previous studies postulated that an axial compression of lumbar intervertebral discs causes a complex strain pattern on the annulus. This pattern is not fully understood, since most studies measured only the uniaxial ultimate tensile strain of the annulus. The aim of this study was to investigate surface strains and their relation to disc bulging. This work was extended to study some defects that are relevant for the intermediate process of finite element modeling. Six specimens (L2-3) with a median age of 51 years were utilized for this in vitro study. Specimens were loaded with pure moments (2.5-7.5Nm) in the principal directions. The anatomy was subsequently reduced in three steps: (1) ligamentous and bony posterior structures, (2) anterior and posterior ligaments and (3) nucleus. Measured were ranges of motion, three-dimensional disc bulging and surface strains of the outer annulus. Lateral bending showed the largest axial strains (9.7%) for intact specimens, which increased to 15.1% after the removal of posterior structures. Disc bulging was largest in flexion with 1.56mm, which increased to 2.06mm after step (1). Defect (2) caused that flexion yielded the largest axial strains with 22.6% and 2.17mm of bulging. We could also determine a constriction effect of these ligaments. Nucleotomy did not essentially increase anterior disc bulging in flexion, but inward disc bulging increased by 0.55mm, in extension. Due to the increase in the complexity of finite element models, it is difficult to obtain data from the literature for validation purposes. This study presents new data, which assist in the development of such models.     

Localized strain measurements of the intervertebral disc annulus during biaxial tensile testing

Both inter-lamellar and intra-lamellar failures of the annulus have been described as potential modes of disc herniation. Attempts to characterize initial lamellar failure of the annulus have involved tensile testing of small tissue samples. The purpose of this study was to evaluate a method of measuring local surface strains through image analysis of a tensile test conducted on an isolated sample of annular tissue in order to enhance future studies of intervertebral disc failure. An annulus tissue sample was biaxial strained to 10%. High-resolution images captured the tissue surface throughout testing. Three test conditions were evaluated: submerged, non-submerged and marker. Surface strains were calculated for the two non-marker conditions based on motion of virtual tracking points. Tracking algorithm parameters (grid resolution and template size) were varied to determine the effect on estimated strains. Accuracy of point tracking was assessed through a comparison of the non-marker conditions to a condition involving markers placed on tissue surface. Grid resolution had a larger effect on local strain than template size. Average local strain error ranged from 3% to 9.25% and 0.1% to 2.0%, for the non-submerged and submerged conditions, respectively. Local strain estimation has a relatively high potential for error. Submerging the tissue provided superior strain estimates.     

Immunolocalization of MMP-19 in the human intervertebral disc: implications for disc aging and degeneration.

Matrix metalloproteinases (MMPs) degrade components of the extracellular matrix of the disc, but the presence of MMP-19 has not been explored. In other tissues, MMP-19 is known to act in proteolysis of the insulin-like growth factor (IGF) binding protein-3, thereby exposing this protein to make it available to influence cell behavior. MMP-19 also has been shown to inhibit capillary-like formation and thus play a role in the avascular nature of the disc. Using immunohistochemistry, normal discs from six subjects aged newborn through 10 years and 20 disc specimens from control donors or surgical patients aged 15-76 (mean age 40.2 years) were examined for immunolocalization of MMP-19; six Thompson grade I discs, five Thompson grade II, eight Thompson grade III, five Thompson grade IV, and one Thompson grade V discs were analyzed. The results indicate that in discs from young subjects, MMP-19 was uniformly localized in the outer annulus. In discs from adult donors and surgical patients, outer and inner annulus cells only occasionally showed MMP-19 localization. The greatest expression of MMP-19 was observed in young discs, and little expression was seen in older or degenerating discs. Because MMP-19 has been shown to regulate IGF-mediated proliferation in other tissues, its decline in the aging/degenerating disc may contribute to the age-related decrease in disc cell numbers.     

Immunolocalization of MMP-19 in the human intervertebral disc: implications for disc aging and degeneration

Matrix metalloproteinases (MMPs) degrade components of the extracellular matrix of the disc, but the presence of MMP-19 has not been explored. In other tissues, MMP-19 is known to act in proteolysis of the insulin-like growth factor (IGF) binding protein-3, thereby exposing this protein to make it available to influence cell behavior. MMP-19 also has been shown to inhibit capillary-like formation and thus play a role in the avascular nature of the disc. Using immunohistochemistry, normal discs from six subjects aged newborn through 10 years and 20 disc specimens from control donors or surgical patients aged 15-76 (mean age 40.2 years) were examined for immunolocalization of MMP-19; six Thompson grade I discs, five Thompson grade II, eight Thompson grade III, five Thompson grade IV, and one Thompson grade V discs were analyzed. The results indicate that in discs from young subjects, MMP-19 was uniformly localized in the outer annulus. In discs from adult donors and surgical patients, outer and inner annulus cells only occasionally showed MMP-19 localization. The greatest expression of MMP-19 was observed in young discs, and little expression was seen in older or degenerating discs. Because MMP-19 has been shown to regulate IGF-mediated proliferation in other tissues, its decline in the aging/degenerating disc may contribute to the age-related decrease in disc cell numbers.     

A novel concentric double-barrelled calcium-selective microelectrode for small cells

A novel concentric design of double-barrelled Ca2+-selective microelectrode, with an inner pipette tip that protrudes beyond an outer one, has recently been developed and is described. This configuration of pipettes was produced from concentric capillaries in one step using a horizontal pipette puller. For the tip of the inner barrel to protrude, Corning 1724 aluminosilicate glass was selected, as it has a higher melting point than the 1723 glass which is used for the outer barrel. To reduce electrode resistance the inner capillary was best made with a triangular shape. It was preferentially silanized in a dry box by injection of methyltrichlorosilane into only the inner barrel. The Ca2+ neutral carrier-based liquid membrane (ETH 1001) was back-filled from the tip to the shank of the inner pipette and above this CaCl2 solution was added. KCl, which contained EGTA and was buffered to pCa 7, was used to fill the reference barrel. These Ca2+ electrodes showed linear response with slope approximately equal to 30 mV for changes in Ca2+ concentration between 10(-3) and 10(-7) M in the presence of constant [K+]. They offer a number of advantages including a low noise level achieved by the presence of the external concentric KCl electrode, and a simple mechanical structure that allows applications to a variety of small cells.     

The response of foetal annulus fibrosus cells to growth factors: modulation of matrix synthesis by TGF-β1 and IGF-1

The annulus fibrosus of the intervertebral disc is a complex radial-ply tissue that derives initially from segmental condensations of axial mesenchyme surrounding the notochord. These mesenchymal condensations differentiate into the early annulus fibrosus during foetal development—their outer part becoming fibrous, containing collagen type I; and their inner part cartilaginous, containing type II collagen and aggrecan. With post-natal growth and ageing, there is a switch from type I to type II collagen and an increase in proteoglycan synthesis in the outer annulus. This fibrocartilaginous metaplasia appears to occur in response to compressive loading of the tissue as occurs in tendons that wrap around bony pulleys, and driven by growth factors, such as TGF-β. In this study, using high-density micromass cultures, we have assessed the response of foetal outer annulus cells to growth factor stimulation with TGF-β1 and IGF-1, growth factors known to occur within the developing disc. We qualitatively and quantitatively describe the stimulatory effects of these growth factors, both alone and in combination, on the synthesis of sulphated glycosaminoglycan, and collagen types I and II by annulus cells. We show a potential role for TGF-β1 in pushing cells towards a fibrocartilaginous phenotype, with possible complementary effects of IGF-1.     

Measurement of surface deformation of soft tissue

A method is described for measuring the surface shape and deformations of soft tissue in three dimensions. The method uses close range stereophotogrammetry to record the three-dimensional locations of miniature optical targets applied to the tissue surface. This has been applied to study of human lumbar intervertebral disc. Measurements of the strain along surface annular fibers have been made under varying loads. In this case the maximum expected errors are about 0.15 mm, which corresponds to a strain of less than 1%. Preliminary findings have differed from predictions made in published mathematical models for the disc in that they show very little strain of the annulus in compression loading, but confirm axial torsional loading as liable to produce mechanical disruption of the disc annulus.     

Improving spatial and temporal resolution in evoked EEG responses using surface Laplacians

Spline generated surface Laplacian temporal wave forms are presented as a method to improve both spatial and temporal resolution of evoked EEG responses. Middle latency and the N1 components of the auditory evoked response were used to compare potential-based methods with surface Laplacian methods in the time domain. Results indicate that surface Laplacians provide better estimates of underlying cortical activity than do potential wave forms. Spatial discrimination among electrode sites was markedly better with surface Laplacian than with potential wave forms. Differences in the number and latencies of peaks, and their topographic distributions, were observed for surface Laplacian, particularly during the time period encompassing the middle latency responses. Focal activities were observed in surface Laplacian wave forms and topographic maps which were in agreement with previous findings from auditory evoked response studies. Methodological issues surrounding the application of spline methods to the time domain are also discussed. Surface Laplacian methods in the time domain appear to provide an improved way for studying evoked EEG responses by increasing temporal and spatial resolution of component characteristics.     

Topographical variation in the distributions of versican,aggrecan and perlecan in the foetal human spine reflects their diverse functional roles in spinal development

We evaluated the immunohistochemical distribution of three major proteoglycans of cartilage, i.e., aggrecan, versican and perlecan vis-a-vis collagens I and II in the developing human spine of first-trimester foetuses. Aggrecan and perlecan were prominently immunolocalised in the cartilaginous vertebral body rudiments and to a lesser extent within the foetal intervertebral disc. In contrast, versican was only expressed in the developing intervertebral disc interspace. Using domain-specific monoclonal antibodies against the various modules of versican, we discovered the V0 isoform as the predominant form present. Versican immunolocalisations conducted with antibodies directed to epitopes in its N and C termini and GAG-α and GAG-β core protein domains provided evidence that versican in the nucleus pulposus was either synthesised devoid of a G3 domain or this domain was proteolytically removed in situ. The V0 versican isoform was localised with prominent fibrillar components in the annular lamellae of the outer annulus fibrosus. Perlecan was a notable pericellular proteoglycan in the annulus fibrosus and nucleus pulposus but poorly immunolocalised in the marginal tissues of the developing intervertebral disc, apparently delineating the intervertebral disc–vertebral body interface region destined to become the cartilaginous endplate in the mature intervertebral disc. The distribution of collagens I and II in the foetal spine was mutually exclusive with type I present in the outer annulus fibrosus, marginal tissues around the vertebral body rudiment and throughout the developing intervertebral disc, and type II prominent in the vertebral rudiment, absent in the outer annulus fibrosus and diffusely distributed in the inner annulus fibrosus and nucleus pulposus. Collectively, our findings suggest the existence of an intricate and finely balanced interplay between various proteoglycans and collagens and the spinal cell populations which synthesise and assemble these components during spinal development.     

Computation of coupled diffusion of oxygen, glucose and lactic acid in an intervertebral disc

The present numerical study aims to investigate the disc nutrition and factors affecting it by evaluating the concentrations of oxygen, glucose and lactic acid in the disc while accounting for the coupling between these species via the pH level in the tissue and the nonlinear concentration-consumption (for glucose and oxygen) and concentration-production (for lactate) relations. The effects of changes in the endplate exchange area (EA) adjacent to the nucleus or the inner annulus for the transport of nutrients and in the disc geometry as well as tissue diffusivities under static compression loading on species concentrations are also studied. Moreover, alterations in solute diffusion following a central endplate fracture are investigated. An axisymmetric geometry with four distinct regions is considered. Supply sources are assumed at the outer annulus periphery and disc endplates. Coupling between different solutes, pH level, endplate disruptions (calcifications and fractures) and mechanical loads substantially influenced the distribution of nutrients throughout the disc as well as the magnitude and location of critical concentrations; maximum for the lactic acid and minimum for oxygen and glucose. In cases with loss of endplate permeability and/or disruptions therein, as well as changes in geometry and fall in diffusivity associated with fluid expression, the nutrient concentrations could fall to levels inadequate to maintain cellular activity or viability, thus initiating or accelerating disc degeneration.     

Measuring surface potential components necessary for transmembrane current computation using microfabricated arrays

This study was designed to test the feasibility of using microfabricated electrodes to record surface potentials with sufficiently fine spatial resolution to measure the potential gradients necessary for improved computation of transmembrane current density. To assess that feasibility, we recorded unipolar electrograms from perfused rabbit right ventricular free wall epicardium (n = 6) using electrode arrays that included 25-microm sensors fabricated onto a flexible substrate with 75-microm interelectrode spacing. Electrode spacing was therefore on the size scale of an individual myocyte. Signal conditioning adjacent to the sensors to control lead noise was achieved by routing traces from the electrodes to the back side of the substrate where buffer amplifiers were located. For comparison, recordings were also made using arrays built from chloridized silver wire electrodes of either 50-microm (fine wire) or 250-microm (coarse wire) diameters. Electrode separations were necessarily wider than with microfabricated arrays. Comparable signal-to-noise ratios (SNRs) of 21.2 +/- 2.2, 32.5 +/- 4.1, and 22.9 +/- 0.7 for electrograms recorded using microfabricated sensors (n = 78), fine wires (n = 78), and coarse wires (n = 78), respectively, were found. High SNRs were maintained in bipolar electrograms assembled using spatial combinations of the unipolar electrograms necessary for the potential gradient measurements and in second-difference electrograms assembled using spatial combinations of the bipolar electrograms necessary for surface Laplacian (SL) measurements. Simulations incorporating a bidomain representation of tissue structure and a two-dimensional network of guinea pig myocytes prescribed following the Luo and Rudy dynamic membrane equations were completed using 12.5-microm spatial resolution to assess contributions of electrode spacing to the potential gradient and SL measurements. In those simulations, increases in electrode separation from 12.5 to 75.0, 237.5, and 875.0 microm, which were separations comparable to the finest available with our microfabricated, fine wire, and coarse wire arrays, led to 10%, 42%, and 81% reductions in maximum potential gradients and 33%, 76%, and 96% reductions in peak-to-peak SLs. Maintenance of comparable SNRs for source electrograms was therefore important because microfabrication provides a highly attractive methods to achieve spatial resolutions necessary for improved computation of transmembrane current density.     

正常椎间盘胶原的研究

腰椎间盘突出症是引起腰腿痛常见的原因。胶原作为椎间盘结构的主要成分,构成椎间盘的纤维框架,其类型与分布直接决定着椎间盘结构的强度和功能的稳定。本文利用溴化氰消化椎间盘胶原产生多肽,借助于梯度层析。SDS-PAGE及光密度定量扫描等对正常人椎间盘胶原进行了研究。结果表明:正常人椎间盘含Ⅰ型及Ⅱ型两种胶原,它们的分布呈明显而特征性的移行性变化:纤维环外层边缘以Ⅰ型胶原为主(83％),由外向内Ⅰ型胶原逐渐移行为Ⅱ型胶原,靠近髓核处以Ⅱ型胶原为主(72％);髓核中心含有Ⅱ型胶原。此为椎间盘的一个结构特性,以满足椎间盘的特殊功能的需要。     

Structure of the nuclear pore complex in mammalian cells. Two annular components

The ultrastructure of the nuclear pore complex has been investigated in isolated nuclei of an in vitro cultured bovine liver cell line. In shadow-cast replicas of the surface of nuclei isolated in Tris buffer containing low K⁺ and Mg²⁺ concentrations (RSB) the rims of the pores appeared as annular projections with an outer diameter of 100 to 120 nm. When the nuclei were isolated in Tris buffer containing 0.1% Triton the projections were essentially lost, together with the outer membrane of the nuclear envelope. In electron micrographs of whole-mount preparations the Triton-Tris nuclei—but not the RSB nuclei—were surrounded by numerous circular structures, which obviously had been detached from the nuclear surface during the preparation. They consisted of eight granules of about 20 nm diameter which were connected in a circular fashion by fibrous material. The circular structures had an inside diameter close to 65 nm. In broken nuclei many of these circular structures contained a second, smaller circular component and a central granule. From these observations it is concluded that the annulus of the nuclear pore consists of two components and that the outer component is located in the perinuclear space in intimate association with the membrane limiting the pore. A modified model of the nuclear pore complex which accounts for this location is proposed.     

Study of low-temperature plasma between rotating electrodes

Results are presented from experimental studies of the electrophysical and spatiotemporal characteristics of a dielectric barrier discharge operating in atmospheric-pressure air in a discharge cell with a dielectric barrier in the form of a rotating disc. One of the electrodes of the discharge cell was stationary and placed at a certain distance from the dielectric surface, and the following two versions of the second electrode were used: (i) a metal disc electrode was attached to the surface of the rotating dielectric disc, while on the opposite surface of the disc, there was a rectangular strip electrode that was at the same potential as a metal disc electrode and had a sliding contact with the dielectric; (ii) only the strip electrode with the sliding contact was connected to the high-voltage source, while the metal disc electrode was disconnected. Due to barrier rotation, the discharge operated in a pulse mode, although it was supplied from a dc voltage source. The current-voltage characteristic of such a dielectric barrier discharge was measured and analyzed. The number of microdischarge channels arising at the stationary electrode, the geometrical parameters of the microdischarge channels, and the discharge current were studied as functions of the supplied voltage, the distance between the stationary electrode and the dielectric surface, and the rotation velocity of the barrier disc.