Analysis on Motion Characteristics of Red Blood Cells in Capillaries / 医用生物力学

Objective To study the motion and deformation of red blood cells ( RBCs) with different mechanical properties in capillaries,and make analysis on the associated hemorheological parameters. Methods The RBC was modeled as a hyper elastic membrane using Skalak model. The fluid was solved using a two-order difference scheme with the membrane mechanics treated by the immersed method. The pathological viscosity ratio λ= 5 was considered. Results The steady deformation of RBCs with different membrane stiffness in the capillary was obtained. With membrane stiffness increasing, the cell transformed from axisymmetric shapes to non-axisymmetric shapes. With capillary number increasing, the deformability of RBCs weakened and the flow resistance increased. Conclusions With stiffening of cell membrane, the non-axisymmetric cell shape appears and the flow resistance increases. Therefore, in diseases involved stiffening RBCs, the stiffened RBCs can cause the blockage of capillaries and hypoxia in surrounding tissues.

Effects of Physical Heterogeneity Variation on Differentiation Potential of Mesenchymal Stem Cells During Senescence / 医用生物力学

With the multi-directional differentiation potential such as osteogenic differentiation, chondrogenic differentiation and adipogenic differentiation, mesenchymal stem cells (MSCs) have been widely used in basic research and clinical applications. The differentiation potential of MSCs is altered during senescence. Osteogenic differentiation potential decreases, while the lipogenic differentiation potential increases in aging MSCs. Changes in differentiation potential of MSCs during senescence are accompanied with cell physical heterogeneity variation (cell size, cell stiffness and nucleoplasmic ratio). Studies have shown that changes in physical heterogeneity of stem cells may be a key factor leading to the differences in differentiation potential of MSCs. Therefore, studies on physical heterogeneity variation of MSCs during senescence will provide a new research direction in fate prediction of stem cell. In this review, the effects of physical heterogeneity variation on differentiation potential of MSCs were summarized, and the corresponding mechanism was also discussed.

Comparative Experiment on Physical Properties of Red Blood Cells in Newborn Infants and Elderly People / 医用生物力学

Objective By comparing the physical properties (cell area, volume and elastic modulus) of red blood cells (RBCs) between newborn infants and the elderly over 80 years old, and correlation with the physiological and biochemical parameters such as total cholesterol and glycosylated hemoglobin, the effects of different ages and biochemical parameters on RBC physical properties were analyzed. Methods The mcropipette aspiration was used to measure the surface area, volume and elastic modulus of erythrocytes in newborn infants and the elderly over 80 years old, and the data were analyzed by statistical distribution analysis, correlation analysis and regression analysis. Results The mean values of RBC volume, surface area and elastic modulus in the elderly over 80 years old were smaller than those in newborn infants, and the mean values of RBC mechanical parameters in the same age group were not significantly different. The erythrocytes geometric parameter distribution of newborn infants was more concentrated than that of the elderly, while the elastic modulus distribution of newborn infants was more dispersed than that of the elderly. The mechanical properties of RBCs in newborn infants were highly correlated with the total cholesterol and gestational week; the mechanical properties of RBCs in the elderly were highly correlated with diastolic blood pressure and glycated hemoglobin. Conclusions There are significant differences in physical properties of RBCs between newborn infants and the elderly over 80 years old, and the biochemical parameters that affect physical properties of RBCs at different ages are also different.

Experimental Study on Separation of Fetal Nucleated Red Blood Cell from the Whole Blood Using Microfluidic Chip / 医用生物力学

Objective To seperate fetal nucleated red blood cells (fNRBCs) from the whole maternal peripheral blood effectively by designing a circular channel microfluidic chip. Methods A microfluidic chip is designed by utilizing the margination in blood flow and the specific adhesion characteristics of immuno-agent anti-CD147. With the whole umbilical cord blood, the effects of different shear forces on the enrichment of fNRBCs was studied by immunofluorescence counting. Results Increasing shear rate in microfluidic chip could improve the number of captured fNRBCs compared with the static adhesion. With the increase of shear rate of blood flow, the number of the captured cells increased at first, and then decreased. Conclusions The use of microfluid chip can effectively seperate fNRBCs from the whole blood. The results provide an experimental reference for the non-invasive prenatal diagnosis research and the exploration on the mechanism of fetal cell migration.

In vivo Mechanical Niches of Vascular Cells / 医用生物力学

The elastic stress and viscous shear stress experienced by the vessel wall under pulse blood pressure and blood flow and the mechanical properties of the substrate constitute the in vivo mechanical niches of vascular cells, and these mechanical stimuli are involved in regulating the biological responses of vascular cells and inducing the remodeling and pathological changes of vascular tissues. Although many experimental studies on vascular mechanobiology have been reported, the quantitative correlation between the mechanical stimuli of in vitro experiments and the physiological and pathological conditions of blood vessels remains to be elucidated. This paper summarized the quantitative evaluation method of in vivo mechanical niches of vascular cells from the viewpoint of biomechanics, and then focused on effects of the physiological locations and aging on mechanical behaviors of the vessel wall. This paper also explored the physiological and pathological characteristics of the cellular mechanical niches and their implications for current vascular mechanobiological studies.

Microfluidic Chip Separation and Physical Property Measurement of Circulating Tumor Cells / 医用生物力学

Objective To establish a new method to measure the elastic modulus of living circulating tumor cells (CTCs) by micropipette aspiration. Methods Living CTCs were enriched by commercial microfluidic chips and identified individually using EpCAM antibody under fluorescence microscope. The elastic modulus of CTCs was measured using micropipette aspiration and compared with cancer cell lines. Results For the elastic modulus of different cancer cell lines, heterogeneity was found not only between the different types of cancer cell lines but also inside the same cell line. The CTCs in breast cancer had a smaller elasticity modulus compared with MCF-7 cancer cell line. Conclusions This method can measure the elastic modulus of living CTCs, which provides cell mechanics data for studying the relationship between physical properties of CTCs and diagnosis of cancers, as well as developing the physical biomarkers of tumor cells.

In Vivo Stress Analysis of an Atherosclerotic Plaque at Carotid Bifurcation / 医用生物力学

Objective To investigate the in vivo stress distribution of the atherosclerotic plaque at carotid bifurcation, so as to provide references for the mechanical mechanisms of plaque rupture at carotid bifurcation and the design for further medical treatment. Methods The three-dimensional geometric model of carotid bifurcation and plaque were established according to average geometric parameters of human carotid bifurcation. Residual stress of the carotid bifurcation and plague was reestablished with “thermal-structure” coupling method, and in vivo stresses of vessels with the plaque at carotid bifurcation under blood pressure and blood flow were calculated. Results Both the maximum principal stress and elastic shear stress concentrated on the shoulder of the plaque. Elastic shear stress increased with the increase of stenosis ratio and blood pressure. Wall shear stress in the upstream of the plaque was considerably higher than that of the downstream. The distribution of oscillatory shear index(OSI) was quite the opposite. The changing patterns of the elastic shear stress and flow shear stress were quite different with the change of stenosis ratios. Conclusions Tension grew gradually from the centrality to shoulder surface of the plaque. The centrality of the plaque might bear compression when the stenosis was very severe. The periodic variation of the structural stress might cause structural fatigue of the plaque, thus increasing the rupture risk. Distinction of the component and vulnerability of the plaque between upstream and downstream might be caused by differences in hemodynamic parameters of the plaque between upstream and downstream.

Application of plasma neutrophil gelatinase-associated lipocalin as an emerging biomarker in the early diagnosis of acute renal injury following renal transplantation / 中华器官移植杂志

Objective To study the prognostic role of plasma neutrophil gelatinase-associated lipocalin (NGAL) early after renal transplantation.Methods A total of 37 kidney recipients were enrolled from Department of Organ Transplantation,Guangdong Second Provincial General Hospital within a 12-month period of time.Plasma NGAL was measured immediately before and at 6 and 12 h post-transplantation.Changes of serum creatinine were documented daily within the first week postoperation.Acute kidney injury (AKI)/graft rejection during the first week after transplantation was the outcome variable.Results The levels of serum NGAL in the 37 patients were (311.14 ± 102.69),(317.81 ± 107.28) and (312.16 ± 134.80) μg/L respectively immediately before and at 6 and 12 h post-transplantation.There was no significant difference in serum NGAL levels before and 6 h or 12 h after operation (P =0.70,and P =0.96).There were no significant differences in gender and age between the two groups (P =0.29,and P =0.20).There was significant difference in creatinine levels between the AKI group and the non-AKI group (P =0.002) and between pre-operation and 6 or 12 h postoperation.The preoperative levels of serum NGAL in AKI group and non-AKI group were (333.58 ± 116.30) and (300.36 ± 96.15) μg/L (P =0.36),and those were (383.3 ± 147.16) and (286.32 ± 65.97) μg/L (P＜0.01) at 6 h,and (437.33 ± 164.16) and (252.08 ± 57.53) μg/L (P＜ 0.001) at 12 h after operation.The sensitivity and specificity of serumNGAL (317μg/L at 12 h after operation as the cutoff value) predicting AKI was 100％ and 92％ respectively,which was much better than that of serum creatinine at the corresponding time point (sensitivity =66.7％,and specificity =61.9％).Conclusion Plasma NGAL,particularly at 12 h after transplantation,is a very sensitive and specific biomarker for predicting AKI.

Research on thermal dose for high intensity focused ultrasound treatment based on the temperature-map of magnetic resonance imaging / 生物医学工程学杂志

<p><b>UNLABELLED</b>Based on the T-map of MRI, this research sought to address the relationship between the simulated threshold thermal dose of coagulation and actual the coagulation on histological slides. The MR imaging guided HIFU system was used, the parameters of therapeutic transducer were: frequency--1 MHz, diameter--150 mm, and focal length--150 mm. In fresh beef liver tissue in vitro, sonications were delivered at a fixed depth of 20 mm and at varying powers. The temperature-sensitive MR images obtained during the sonications were used to estimate the temperature, and the thermal dosage of each voxel in the target region was calculated. The thermal dosage of each voxel was compared with the reference threshold thermal dosage, so as to calculate the boundary and area of the coagulated tissue. After the exposure, the tissue was dissected along the maximal section of the coagulation necrosis, and the area of the biological focal region was measured.</p><p><b>RESULTS</b>The occurrence of tissue damage correlated well with the equivalent thermal dose calculation based on the T-mapping of MRI, and they share the same variation tendency.</p><p><b>CONCLUSION</b>The equivalent thermal dose calculation based on the T-Map of MRI correlates well with the actual tissue damage, and so an index to predict the threshold for tissue damage in vivo is provided. This index offers improved online control over minimally invasive thermal treatments and increases the security of the therapy.</p>

In vitro study on dosage level of HIFU for formation of line-shaped lesion in bovine liver / 生物医学工程学杂志

The dot-shaped coagulative necrosis induced by a single HIFU exposure can be considered as a basis for HIFU ablation of tumour. For complete ablation of tumour mass with HIFU, the crucial point is to create a complete line-shaped lesion by way of dot-shaped coagulative necrosis. At the beginning of this in vitro study, a dot-shaped coagulative necrosis with focal width (W) 3mm was induced in ox liver by HIFU (acoustical intensity (I(SAL)) 6500W/cm2; exposure time 1s) at focal depth 2cm. And then, we investigated the formation of line-shaped lesion under two different modes, namely, multiple dot-shaped coagulative necrosis overlapping and linear scanning. Under multiple dot-shaped coagulative necrosis overlapping mode, line-shaped lesion is formed by the combination of multiple dot-shaped coagulative necroses. With acoustical intensity (I(SAL)) 6500W/cm2 and exposure time is for each single exposure, different intervals (D) between two successive single exposures (1mm, 2mm, 2.5mm, 3mm, 4.5mm, 5mm) were applied to obtain line-shaped lesion. Under linear scanning mode, the intensity (I(SAL)) 6500W/cm2 and cycle 1 were set constant, and various scanning speeds (V) 1mm/s, 3mm/s, 6mm/s, 7mm/s were adopted to create line-shaped lesion. After the procedures, the tissues were dissected to obtain the maximum section of the line-shaped lesion. The results were as follows: under multiple dot-shaped coagulative necrosis overlapping mode, a complete line-shaped lesion could be formed when D < or = W, while an incomplete line-shape lesion was formed when D > W; under linear scanning mode, a complete line-shaped lesion could be formed using the scanning speed 3mm/s and cycle 1. The results validate that the complete line-shaped lesion can be created with the dosage and exposure parameters optimized for the dimension of a single dot-shaped coagulative necrosis as shown in this study.

Research of the therapeutic enhancement by high intensity focused ultrasound combined with SonoVue on goats livers in vivo / 中华超声影像学杂志

Objective To investigate the feasibility of enhancing therapeutic effects on goats' liver in vivo treated by high intensity focused ultrasound(HIFU)combined with microbubble contrast agent SonoVue.Methods Fifteen Nanjiang goats were adopted,own control was adopted in this study.One group received purely HIFU therapy(control group),another one was radiated with HIFU combined with SonoVue contrast agent(SonoVue group).The HIFU irradiating mode was dotted with 30 mm focal length and 150 W,250 W,350 W acoustic power respectively,and the exposure time was 15 s.Animals were sacrificed and dissected 24h later,and the sizes of necrotic region were measured.Specimens were collected for histological inspection.Results Under the same parameter of exposure,the maximum length,width,depth,and the mean volume of the tissue coagulated by HIFU in the SonoVue group were all significantly greater than those in control group(P＜0.05),the change of volume coagulated tissue was much more significant with the increase of the acoustic power.The energy effciency factor (EEF)of SonoVue group was significantly smaller than that of control group(P＜0.05).The demarcation line between the necrosis and normal region was clear and the necrosis was complete,no living cell.The boundary exist amount of bubbles.Conclusions The therapy of HIFU combined with microbubble eontrast agent can substantially enhance the biological effects of the treatment and improve the efficiency of HIFU therapy on goats liver.