Numerical simulation of unsteady generalized Newtonian blood flow through differently shaped distensible arterial stenoses

An updated numerical simulation of unsteady generalized Newtonian blood flow through differently shaped distensible arterial stenoses is developed. A shear-thinning fluid modelling the deformation dependent viscosity of blood is considered for the characterization of generalized Newtonian behaviour of blood. The arterial model is treated as two-dimensional and axisymmetric with an outline of the stenosis obtained from a three-dimensional casting of a mildly stenosed artery. The full Navier-Stokes equations governing blood flow are written in the dimensionless form and the solution is accomplished by finite time-step advancement through their finite difference staggered grid representations. The marker and cell (MAC) method comprising the use of a set of marker particles moving with the fluid is used for the purpose. Results are obtained for three differently shaped stenoses – irregular, smooth and cosine curve representations. The present results do agree well with those of existing investigations in the steady state, but contrary to their conclusions the present findings demonstrate that the excess pressure drop across the cosine and the smooth stenoses is caused by neither their smoothness nor their higher degree of symmetry relative to the irregular stenosis, but is rather an effect of area cover with respect to the irregular stenosis. This effect clearly prevails throughout the entire physiological range of Reynolds numbers. Further the in-depth study in flow patterns reveals the development of flow separation zones in the diverging part of the stenosis towards the arterial wall, and they are influenced by non-Newtonian blood rheology, distensibility of the wall and flow unsteadiness in order to validate the applicability of the present model.     

Numerical simulation of unsteady generalized Newtonian blood flow through differently shaped distensible arterial stenoses

An updated numerical simulation of unsteady generalized Newtonian blood flow through differently shaped distensible arterial stenoses is developed. A shear-thinning fluid modelling the deformation dependent viscosity of blood is considered for the characterization of generalized Newtonian behaviour of blood. The arterial model is treated as two-dimensional and axisymmetric with an outline of the stenosis obtained from a three-dimensional casting of a mildly stenosed artery. The full Navier-Stokes equations governing blood flow are written in the dimensionless form and the solution is accomplished by finite time-step advancement through their finite difference staggered grid representations. The marker and cell (MAC) method comprising the use of a set of marker particles moving with the fluid is used for the purpose. Results are obtained for three differently shaped stenoses - irregular, smooth and cosine curve representations. The present results do agree well with those of existing investigations in the steady state, but contrary to their conclusions the present findings demonstrate that the excess pressure drop across the cosine and the smooth stenoses is caused by neither their smoothness nor their higher degree of symmetry relative to the irregular stenosis, but is rather an effect of area cover with respect to the irregular stenosis. This effect clearly prevails throughout the entire physiological range of Reynolds numbers. Further the in-depth study in flow patterns reveals the development of flow separation zones in the diverging part of the stenosis towards the arterial wall, and they are influenced by non-Newtonian blood rheology, distensibility of the wall and flow unsteadiness in order to validate the applicability of the present model.     

Vacuolar cytoplasmic phase separation in cultured mammalian cells involves the microfilament network and reduces motional properties of intracellular water

Hep-2, human epithelial carcinoma cells, and human foreskin fibroblasts (FF9 and FF13) were exposed to either an ultrafiltrate (< 50 kD) of human sera or the weak base, procaine hydrochloride, to induce reversible cytoplasmic vacuolization. The formation of vacuoles was shown not to be due to imbibition of medium. Ultrastructural details obtained from various stages of vacuole formation were compared. In both cases of induction vacuoles were irregular and often appeared membraneless, with little in the way of electron-dense content. They started to form in the perinuclear cytoplasm and progressed towards the periphery. Osmotic stress was not involved since mitochondria remained normal throughout a vacuolization episode.
Vacuoles were often seen in close contact with filamentous structures, and this association remained detectable at late stages of the phenomenon. Fluorescent visualization of F-actin confirmed that the vacuoles were frequently bordered by microfilaments. No major metabolic impairment was apparent in vacuolized cells as judged by protein synthesis measurements, but nuclear fluorescence (DNA content) and forward light scatter (nuclear volume) by flow cytometric analysis suggested late S phase and G2 retardation. ¹H-nmr relaxation measurements indicated intracellular water restricted in motional characteristics in vacuolized cells. The possibility of a restricted cytoplasmic phase separation as part of a transient adaptation response is raised, and a hypothesis to explain the findings is discussed.     

Doppler ultrasound wall removal based on the spatial correlation of wavelet coefficients

In medical Doppler ultrasound systems, a high-pass filter is commonly used to reject echoes from the vessel wall. However, this leads to the loss of the information from the low velocity blood flow. Here a spatially selective noise filtration algorithm cooperating with a threshold denoising based on wavelets coefficients is applied to estimate the wall clutter. Then the blood flow signal is extracted by subtracting the wall clutter from the mixed signal. Experiments on computer simulated signals with various clutter-to-blood power ratios indicate that this method achieves a lower mean relative error of spectrum than the high-pass filtering and other two previously published separation methods based on the recursive principle component analysis and the irregular sampling and iterative reconstruction, respectively. The method also performs well when applied to in vivo carotid signals. All results suggest that this approach can be implemented as a clutter rejection filter in Doppler ultrasound instruments.     

Influence of optical properties and fiber separation on laser doppler flowmetry

Microcirculatory blood flow can be measured using a laser Doppler flowmetry (LDF) probe. However, the readings are affected by the tissue's optical properties (absorption and scattering coefficients, mu(a) and mu(s)) and probe geometry. In this study the influence of optical properties [mu(a)in(0.053,0.23) mm-1,mu(s)in(14.7,45.7) mm-1] on LDF perfusion and LDF sampling depth was evaluated for different fiber separations. In vitro measurements were made on a sophisticated tissue phantom with known optical properties that mimicked blood flow at different depths. Monte Carlo simulations were carried out to extend the geometry of the tissue phantom. A good correlation between measured and simulated data was found. The simulations showed that, for fixed flow at a discrete depth, the influence of mu(s) or mu(a) on LDF perfusion increased with an increase in flow depth and decreased with an increase in fiber separation. For a homogeneous flow distribution, however, the perfusion varied 40% due to variations in the optical properties, almost independent of the fiber separation (0.23-1.61 mm). Therefore, the effect in real tissue is likely to vary due to the unknown heterogeneous blood flow distribution. Further, the LDF sampling depth increased with a decrease in mu(s) or mu(a) and an increase in fiber separation. For fiber separation of 0.46 mm, the e-1 sampling depth ranged from 0.21 to 0.39 mm.     

Arterial flow characterization with a photodiode array based imaging system

An x-ray imaging system is described that can be used for obtaining arterial blood flow information. The system consists of a linear photodiode array image detector, simple optical and mechanical components, and a data acquisition microcomputer that connect to a conventional x-ray image intensifier based fluorography system. Flow information is obtained by detecting the movement of a small, locally injected bolus of radio-opaque contrast agent. This is done by determining the bolus mass, integrated over the cross-sectional area, at each of 1024 positions along the length of the artery with a sampling rate of up to 200 samples per s. It is shown in a phantom study that the peak flow velocity can be measured with an accuracy of +/- 5% by detecting the bolus arrival times at each of the 1024 positions. The mean velocity is obtained with similar accuracy using a cross-correlation technique and a modified form of the Stewart-Hamilton principle. In addition, it is shown that the separation and reattachment points resulting from flow separation near a stenosis can be determined from the bolus clearance times. The locations of these points are consistent with theoretical values for the cosine shaped symmetric 89% stenosis used in this study.     

On empirical methods to determine scatter factors for irregular MLC shaped beams

Multileaf collimators (MLCs) are in clinical use for more than a decade and are a well accepted tool in radiotherapy. For almost each MLC design different empirical or semianalytical methods have been presented for calculating output ratios in air for irregularly shaped beams. However, until now no clear recommendations have been given on how to handle irregular fields shaped by multileaf collimators for independent monitor unit (MU) verification. The present article compares different empirical methods, which have been proposed for independent MU verification, to determine (1) output ratios in air (Sc) and (2) phantom scatter factors (Sp) for irregular MLC shaped fields. Ten dedicated field shapes were applied to five different types of MLCs (Elekta, Siemens, Varian, Scanditronix, General Electric). All calculations based on empirical relations were compared with measurements and with calculations performed by a treatment planning system with a fluence based algorithm. For most irregular MLC shaped beams output ratios in air could be adequately modeled with an accuracy of about 1%-1.5% applying a method based on the open field aperture defined by the leaf and jaw setting combined with the equivalent square formula suggested by Vadash and Bj?rngard [P. Vadash and B. E. Bj?rngard, Med. Phys. 20, 733-734 (1993)]. The accuracy of this approach strongly depends on the inherent head scatter characteristics of the accelerator in use and on the irregular field under consideration. Deviations of up to 3% were obtained for fields where leaves obscure central parts of the flattening filter. Simple equivalent square methods for Sp calculations in irregular fields did not provide acceptable results (deviations mostly >3%). Sp values derived from Clarkson integration, based on published tables of phantom scatter correction factors, showed the same accuracy level as calculations performed using a pencil beam algorithm of a treatment planning system (in a homogeneous media). The separation of head scatter and phantom scatter contributions is strongly recommended for irregular MLC shaped beams as both contributions have different factors of influence. With rather simple methods Sc and Sp can be determined for independent MU calculation with an accuracy better than 1.5% for most clinical situations encountered in conformal radiotherapy.     

高频脉冲弱磁场检测技术的研究

生物医学领域中通常涉及高频瞬态弱磁场的应用,目前通用的磁感应强度探头无法满足MHz脉冲磁场的测量需求,为了准确测量MHz脉冲弱磁场,研究设计了对0.1~1 MHz脉冲磁场进行测量及标定的技术。设计一套由非铁磁性材料制成的脉冲磁场测量与标定装置,通过装置将磁场发生线圈与磁场检测线圈的相对位置精确固定。选用正弦脉冲施加于磁场发生线圈,采集检测线圈产生的感应电动势,根据法拉第电磁感应定律在Matlab平台编写算法,仿真计算得到MHz脉冲磁场强度并标定。实现了频率分别为0.5、1.0、1.5 MHz强度为μT量级磁场的准确测量,测量结果通过标定,与真实值的相对误差约为2.5%,保持较好的稳定性和一致性。     

Centrifugal and Electric Field Forces Dual-Pumping CD-Like Microfluidic Platform for Biomedical Separation

In this article, we propose a versatile CD-like multi-channel electrophoresis-based biomedical separation system that is driven by the interactive forces between the centrifugal force and the electric field force. The centrifugal force control of this system is realized through the velocity control of a DC servo motor, while the electric field is governed through the concentric conducting circuits, which are suitably designed and fabricated by sputtering on metal mask method, and can be adjusted to provide multi-stage voltages. Experimental results demonstrate that the electro-osmotic flow (EOF) effect can be effectively reduced when the electric field force and centrifugal force are in the opposite direction. Benefits from this are that the electrophoresis separation time can be prolonged and the length of the microfluidic channels can be shortened; therefore, more effective separation efficiency can be obtained. Moreover, other advantages, such as lower joule-heat generation, low-chemistry reaction, and no variation on the ion concentration during processes, make this biomedical separation system more useful.     

Involvement of upper-airway muscles in extrapyramidal disorders. A cause of airflow limitation

To identify the site and cause of airflow limitation in patients with parkinsonism, we tested pulmonary function in 27 patients with extrapyramidal disorders. In 24 patients, an abnormal flow-volume loop contour, showing either regular (18 patients) or irregular (6 patients) flow oscillations, was found. On direct fiberoptic visualization of the upper airway, these oscillations corresponded to either rhythmic (4 to 8 Hz) or irregular involuntary movements of glottic and supraglottic structures. Ten patients had physiologic evidence of upper-airway obstruction, which was symptomatic in four. We conclude that the upper-airway musculature is frequently involved in extrapyramidal disorders. This causes upper-airway dysfunction that can be severe enough to limit airflow.     

Broadband ultrasound attenuation imaging: algorithm development and clinical assessment of a region growing technique

This paper presents a computerized method for the selection of an irregular region of interest (ROI) in broadband ultrasound attenuation (BUA) images. A region growing algorithm searches an initial region in the posterior part of the calcaneus until the pixel with the lowest attenuation value is found; this is the starting seed. Then, the algorithm evaluates the values of the eight pixels neighbouring the starting seed. Pixels that have the closest value to the starting seed are accepted. This procedure is the first processing level. The procedure is repeated for the group of pixels neighbouring those accepted from the previous processing level. The algorithm ceases when the number of accepted pixels reaches a user-specified number. The clinical part of this study compares measurements of BUA at an automatic ROI implemented on a quantitative ultrasound imaging device, defined as the circular region of lowest attenuation in the posterior part of the calcaneus, and at irregular ROIs of various sizes generated by the algorithm developed in this study. The algorithm was applied to BUA images obtained from 24 post-menopausal women with hip fractures and 26 age-matched healthy female subjects. The use of the irregular ROI with a size of 2400 pixels is proposed because that region yielded better clinical results compared to irregular ROIs with different size and the circular automatic ROI.     

Predicting sleep latency from the three-process model of alertness regulation

This paper presents a modification of the quantitative “three-process model of alertness regulation” to predict sleep latency in connection with irregular sleep/wake patterns. This model uses a circadian and a homeostatic component(sleep loss) that are summed to yield predicted alertness (on a scale of 1 to 20) across a specified time span. The timing of sleep from two studies of irregular sleep were used as input to the model. The predicted alertness at bedtime was regressed on empirical sleep latency from two studies. The maximum R² (0.88) was reached for an exponential function, with the model acrophase set to 2048. The predictions were cross validated on another set of sleep latency data from an irregular sleep study and a maximum R² of 0.65 was obtained. In both studies, the prediction from the model explained more variance that did self-rated alertness at bedtime. Cross validation was also carried out sucessfully with published data from two studies of shift work. It was concluded that sleep latency on irregular schedules may be predicted with accuracy from knowledge of the prior sleep/wake pattern. This may have practical consequences for rest/actvity management.     

Scaling of prediction error does not confirm chaotic dynamics underlying irregular firing using interspike intervals from midbrain dopamine neurons

Dopamine neurons in the substantia nigra pars compacta often fire in an irregular, single spike mode in vivo, and a similar firing pattern can be observed in vitro when small conductance calcium-activated potassium channel blockers are applied to the bath. It is not clear whether the irregular firing is due to stochastic processes or nonlinear deterministic processes. A previous study [Neuroscience 104 (2001) 829] used nonlinear forecasting methods applied to a continuous function derived from the interspike interval (ISI) data from irregularly firing dopamine neurons to show that the predictability scaled exponentially with forecast horizon and was consistent with nonlinear deterministic chaos. However, we show here that the observed exponential scaling is also consistent with a stochastic process, because it did not differ significantly from that of shuffled surrogate data. On the other hand, nonlinear forecasting directly from the ISI data using the package TISEAN provided some evidence for nonlinear deterministic structure in four of five records obtained in vitro and in two of nine records obtained in vivo. Although we cannot rule out a role for nonlinear chaotic dynamics in structuring the firing pattern, we suggest an alternate hypothesis that includes a mechanism by which the firing pattern can become more variable in the presence of a constant level of background noise.     

Simple and rapid chromatographic separation of IgM using microcolumns and stained sera

By adding two different stains to samples of serum it was possible to monitor visually the chromatographic separation of the IgM antibody-containing fraction from other serum components and to collect this fraction manually. The use of microcolumns filled with a medium of very low resistance of flow reduced drastically the time for the separation. A simple apparatus is described which allows to run up to 10 columns in periods of 3 min. Using this technique, IgM antibody-containing fractions from 20 sera can be obtained in 2 h. The efficiency of the method was demonstrated using sera from 55 patients with hepatitis A infection.     

Blood plasma separation in elevated dimension T-shaped microchannel

In recent years, microfluidic chips have proven ideal tools for biochemical analysis, which, however, demands a unique and compatible plasma separation scheme. Various research groups have established continuous flow separation methods in microfluidic devices; however, they have worked with relatively small dimension microchannels (similar to the blood cell diameter). The present work demonstrates separation of plasma by utilizing the hydrodynamic separation techniques in microchannels with size of the order of mm. The separation process exploits the phenomenon, which is very similar to that of plasma skimming explained under Zweifach-Fung bifurcation law. The present experiments demonstrates for, the first time, that applicability of the Zweifach-Fung bifurcation law can be extended to dimensions much higher than the suspended particle size. The T-microchannel device (comprising perpendicularly connected blood and plasma channels) were micro-fabricated using conventional PDMS micro-molding techniques. Three variables (feed hematocrit, main channel width, and flow rate distributions) were identified as the important parameters which define the device’s efficiency for the blood plasma separation. A plasma separation efficiency of 99.7 % was achieved at a high flow ratio. Novel concepts of 2-stage or multiple plasma channel designs are also proposed to yield high separation efficiency with undiluted blood. The possible underlying principle causing plasma separation (viz. aggregation and shear thinning) are investigated in detail as part of this work. The results are significant because they show nearly 100 % separations in microchannels which are much easier to fabricate than previously designed devices.     

A flow cytometric method for determination of absolute counts of myeloid precursor dendritic cells in peripheral blood

Circulating precursor dendritic cells (pDCs) constitute a rare population in peripheral blood. They have a typical immunophenotypic profile, yet, they cannot be identified by pDC-specific immunophenotypic markers and therefore, their accurate and absolute enumeration poses a challenge. Here, we report a method for the evaluation of absolute counts of myeloid pDC in minimally manipulated blood samples on a flow cytometer as a single platform. Three-color flow cytometry was done to identify myeloid pDC as CD33+ HLA-DR+ CD14/CD16(dim/negative) cells in commercially available TruCount trade mark tubes that contain a defined number of brightly fluorescent polystyrene beads. The normal range in peripheral blood of 41 healthy adults, as determined by this single-platform method, was 17.0+/-5.7 x 10(6)/l, or 0.64+/-0.23% of mononuclear cells (MNCs). In parallel experiments, we have compared our procedure with two published 'dual-platform' methods that derive the absolute pDC count from a relative number obtained by flow cytometry, and from absolute counts obtained from a haematological analyser. Regression analysis showed an excellent correlation between results obtained with our single-platform protocol and these double-platform procedures (R2 > or = 0.90). However, the values obtained by the single-platform method were significantly higher than those obtained by the dual-platform methods. The higher myeloid pDC numbers in this single-platform procedure are likely due to reduced cell loss in this 'lyse-no-wash' protocol compared with the other methods which include density gradient separation and centrifugation steps. The intra- and interassay variability were 4.4% (range, 2.04-8.96%) and 5.8% (range, 2.59-9.65%), respectively. Thus, the single-platform method described here allows accurate, rapid and simple measurement of circulating blood myeloid pDC and is suitable for routine enumeration of circulating myeloid pDC.     

Monoclonal antibody reveals heterogeneity in human aortic intima: detection of a ganglioside antigen associated with a subpopulation of intimal cells.

The cells of the arterial wall are heterogeneous. To study the functions and peculiarities of various subpopulations of arterial cells the authors have generated an IgM mouse monoclonal antibody, designated 3-Lena, which interacts with human aortic cells (demonstrated by RIA and flow cytofluorometry). The cellular antigens interacting with monoclonal antibody 3-Lena are gangliosides GM3, GD3, GD1a, and GT1b. Presumably, the epitope is represented by the structure -NeuAc alpha 2----3Gal beta 1, a component of the oligosaccharide moiety of the ganglioside molecule. In addition to aortic cells, those dissociated from other large human vessels as well as cells of the myometrium and lung parenchyma interact with 3-Lena. Cells dissociated from the spleen and renal cortex exhibit a substantially weaker interaction, while liver and myocardial cells do not react. Compared with human aortic cells, aortic cells of other mammalian species stain less effectively (dog, swine) or do not stain at all (bovine, ram). Flow cytofluorometric analysis demonstrates that practically all human aorta medial cells interact with antibody 3-Lena, whereas a certain portion of cells in the intimal population do not. In the outer intimal sublayer adjoining the media, the cells reacting with monoclonal antibody 3-Lena make up the bulk of the cell population, and the inner sublayers are characterized by a prevalence of nonreactive cells. After separation of reactive and nonreactive human aortic intimal cells by a cytofluorometer-cell sorter, 3-Lena+ cells were found to have an elongated bipolar shape, whereas most 3-Lena- cells have multiple processes and variable elongated, stellate, or irregular shapes.(ABSTRACT TRUNCATED AT 250 WORDS)     

应用CFD对人工血泵流场进行数值仿真

发展人工心脏以便在某些情况下代替心脏进行供血已成为医学界的普遍要求。血泵研制和改进中所面临的主要难点之一是血液在血泵中的流动分离等复杂流动情况 ,对人工血泵中血液的流体动力分析是发展先进人工血泵的前提。本文应用计算机求解三维Navier Stokes方程 ,对某型血泵叶片通道间内部流场进行了数值仿真。研究分析结果表明 ,血泵中流体具有非常复杂的流动情况。为避免流动中分离造成流体升压比下降和血细胞破坏 ,对通道的进口和小叶片的安放位置以及叶片高度的变化都提出了很高的要求。充分应用计算流体力学的发展来推动人工血泵的研究具有非常广阔的前景     

Microfluidic particle sorting utilizing inertial lift force

A simple passive microfluidic device that continuously separates microparticles is presented. Its development is motivated by the need for specific size micro perfluorocarbon (PFC) droplets to be used for a novel gas embolotherapy method. The device consists of a rectangular channel in which inertial lift forces are utilized to separate particles in lateral distance. At the entrance of the channel, particles are introduced at the center by focusing the flow from a center channel with flow from two side channels. Downstream, large particles will occupy a lateral equilibrium position in shorter axial distance than small particles. At the exit of the channel, flow containing large particles is separated from flow containing small particles. It is shown that 10.2-μm diameter microspheres can be separated from 3.0-μm diameter microspheres with a separation efficiency of 69–78% and a throughput in the order of 2 ·10⁴ particles per minute. Computational Fluid Dynamics (CFD) calculations were done to calculate flow fields and verify theoretical particle trajectories. Theory underlying this research shows that higher separation efficiencies for very specific diameter cut-off are possible. This microfluidic channel design has a simple structure and can operate without external forces which makes it feasible for lab-on-a-chip (LOC) applications.