多普勒超声对二尖瓣球囊成形术后二尖瓣返流的远期随访分析

应用多普勒超声心动图对74例二尖瓣球囊成形术(PBMV)病人术前、术后1天及4年的二尖瓣返流(MR)进行研究，将MR划分为Ⅳ级，术后1天与术前比较，MP程度不变59例(80％)、加重Ⅰ级12例(16％）、加重Ⅲ级1例(1％)、减轻Ⅰ级2例(3%)，术后4年与术后1天比较．MR程度不变55例(74％)，加重Ⅰ级11例(15％)、加重Ⅲ级1例(1％)、减轻Ⅰ级7例(10％)。表明轻度MR(≥2 )是PBMV木后常见并发症．仅极少数病人出现严重MR(≥3 )，且部分病人随访过程中MR程度减轻。     

Response of Functional Mitral Regurgitation during Dobutamine Infusion in Relation to Changes in Left Ventricular Dyssynchrony and Mitral Valve Geometry

Purpose

Functional mitral regurgitation (FMR) and myocardial dyssynchrony commonly occur in patients with dilated cardiomyopathy (DCM). The aim of this study was to elucidate changes in FMR in relation to those in left ventricular (LV) dyssynchrony as well as geometric parameters of the mitral valve (MV) in DCM patients during dobutamine infusion.

Materials and Methods

Twenty-nine DCM patients (M:F=15:14; age: 62±15 yrs) with FMR underwent echocardiography at baseline and during peak dose (30 or 40 ug/min) of dobutamine infusion. Using 2D echocardiography, LV end-diastolic volume, end-systolic volume (LVESV), ejection fraction (EF), and effective regurgitant orifice area (ERO) were estimated. Dyssynchrony indices (DIs), defined as the standard deviation of time interval-to-peak myocardial systolic contraction of eight LV segments, were measured. Using the multi-planar reconstructive mode from commercially available 3D image analysis software, MV tenting area (MVTa) was measured. All geometrical measurements were corrected (c) by the height of each patient.

Results

During dobutamine infusion, EF (28±8% vs. 39±11%, p=0.001) improved along with significant decrease in cLVESV (80.1±35.2 mm³/m vs. 60.4±31.1 mm³/m, p=0.001); cMVTa (1.28±0.48 cm²/m vs. 0.79±0.33 cm²/m, p=0.001) was significantly reduced; and DI (1.31±0.51 vs. 1.58±0.68, p=0.025) showed significant increase. Despite significant deterioration of LV dyssynchrony during dobutamine infusion, ERO (0.16±0.09 cm² vs. 0.09±0.08 cm², p=0.001) significantly improved. On multivariate analysis, ΔcMVTa and ΔEF were found to be the strongest independent determinants of ΔERO (R²=0.443, p=0.001).

Conclusion

Rather than LV dyssynchrony, MV geometry determined by LV geometry and systolic pressure, which represents the MV closing force, may be the primary determinant of MR severity.     

超声心动图在诊断二尖瓣脱垂中的应用价值

目的 探讨超声心动图在诊断二尖瓣脱垂中的应用价值,特别探讨超声心动图对二尖瓣脱垂疾病的诊断以及二尖瓣脱垂部位的定位。方法 对2010年1月~2015年3月我院52例超声心动图诊断并手术证实的二尖瓣脱垂患者的二维超声、M型超声及彩色多普勒血流显像资料进行回顾性分析,对比术前超声心动图对二尖瓣脱垂的诊断与手术所见。 结果 52例二尖瓣脱垂患者,前叶病变25例,后叶病变20例,双叶病变7例,误诊1例,诊断符合率为98.07%。结论 超声心动图对二尖瓣脱垂疾病的诊断及定位脱垂部位具有很好的应用价值。     

Patient-Specific Three-Dimensional Ultrasound Derived Computational Modeling of the Mitral Valve

Several new techniques to repair the mitral valve affected by functional mitral regurgitation are in development. However, due to the heterogeneity of valve lesions between patients, predicting the outcomes of novel treatment approaches is challenging. We present a patient-specific, 3D ultrasound-derived computational model of the mitral valve for procedure planning, that faithfully mimics the pathological valve dynamics. 3D ultrasound images were obtained in three pigs induced with heart failure and which developed functional mitral regurgitation. For each case, images were segmented, and finite element model of mitral valve was constructed. Annular and papillary muscle dynamics were extracted and imposed as kinematic boundary conditions, and the chordae were pre-strained to induce valve tethering. Valve closure was simulated by applying physiologic transvalvular pressure on the leaflets. Agreement between simulation results and truth datasets was confirmed, with accurate location of regurgitation jets and coaptation defects. Inclusion of kinematic patient-specific boundary conditions was necessary to achieve these results, whereas use of idealized boundary conditions deviated from the truth dataset. Due to the impact of boundary conditions on the model, the effect of repair strategies on valve closure varied as well, indicating that our approach of using patient-specific boundary conditions for mitral valve modeling is valid.

     

A Novel Approach to Improve the Function of FGF21

Background and Objective

Fibroblast growth factor 21 (FGF21) has potent effects on normalizing glucose, lipid, and energy homeostasis, and represents an attractive novel therapy for type 2 diabetes mellitus and obesity. Approaches to improve the pharmacokinetic properties of FGF21, such as conjugation with polyethylene glycol, have been explored for therapeutic development. However, not only is there room for further pharmacokinetic improvements, additional re-engineering approaches to improve the potency and stability of FGF21 have not been reported. Here, we describe a novel approach to modify and improve the function of FGF21 by altering its C-terminal βKlotho interaction domain.

Methods

We first identified Avimer proteins that are capable of binding βKlotho. Then we explored replacing the C-terminal βKlotho interaction domain of FGF21 with a βKlotho-binding Avimer protein.

Results

Such a βKlotho-binding Avimer protein was able to fully complement the C-terminal domain function of FGF21. The resulting FGF21-Avimer fusion is functionally indistinguishable from wild type FGF21, and more tolerant of C-terminal modification.

Conclusion

These results demonstrate a viable strategy to modulate the affinity, potency, and engineering of FGF21, paving the way for further improvements of FGF21 as a therapeutic.     

Combined Experimental and Mathematical Approach for Development of Microfabrication-Based Cancer Migration Assay

Migration of cancer cells is a key determinant of metastasis, which is correlated with poor prognosis in patients. Evidence shows that cancer cell motility is regulated by stromal cell interactions. To quantify the role of homotypic and heterotypic cell–cell interaction in migration, a two-dimensional migration assay has been developed by microfabrication techniques. Two breast cancer cell lines, MDA-MB-231 and MDA-MB-453, were used to develop micropatterns of cancer cells (cell islands) that revealed distinct migration profiles in this assay. Although the individual migration rates of these cells showed only a sevenfold difference, MDA-MB-453 islands migrated significantly lower than MDA-MB-231 islands, indicating differential regulation of migration in isolated cells vs. islands. Island size had the greatest impact on migration, primarily for MDA-MB-231 cells. Migration of MDA-MB-231 islands was decreased by interaction with homotypic cells, and significantly more by heterotypic non-cancer-associated fibroblasts. In addition, a mathematical model of island migration in multi-cellular population has been developed using Stefan–Maxwell’s equation. The model showed qualitative agreement with experimental results and predicted a biphasic relation between cell densities and island sizes. The combined experimental and mathematical model can be used to quantitatively study the impact of cell–cell interactions on migration.     

A Combined Computational and Experimental Study on the Free‐Radical Copolymerization of Styrene and Hydroxyethyl Acrylate

Bulk free‐radical copolymerization of styrene and 2‐hydroxyethyl acrylate (HEA) is investigated experimentally at 50 °C using pulsed‐laser polymerization and computationally using ab initio simulations. Arrhenius parameters for HEA chain‐end homopropagation are A = 1.72 × 10⁷ L mol^?1 s^?1 and E_a = 16.8 kJ mol^?1, based on experiments between 20 and 60 °C. Copolymer composition data are well fitted by the terminal model with reactivity ratios r_ST = 0.44 ± 0.03 and r_HEA = 0.18 ± 0.04, but the variation in the propagation rate coefficient with monomer composition is underpredicted. Results are compared with computational predictions assuming the terminal as well as the penultimate unit effect (PUE) model. Intramolecular H‐bonding is shown to have a significant influence on PUE calculations. Discrepancies between computational predictions and experiment are attributed to the influence of intermolecular H‐bonding.     

Combined Behavioral and EEG Power Analysis in DAI Improve Accuracy in the Assessment of Sustained Attention Deficit

In clinical routine, the evaluation of sustained attention is often performed by analyzing the behavioral data collected during specific tests. Such analyses are rarely accompanied by a detailed examination of the subject’s simultaneous electroencephalographic (EEG) activity, and particularly its frequency content. In this study, a group of healthy volunteers and a group of patients affected by diffuse axonal injury (DAI) were tested while performing a modified version of the Conners’ continuous performance test. A comparative study was carried out between the behavioral and neuropsychological data obtained during the task, to investigate neural activation. Spectral power was calculated for each of the recorded EEG signals, taking account of the frequency bands traditionally considered in literature. Then a compressed spectral array sequence of spectra was plotted to put into evidence the temporal modifications in the signal power spectral density, and, finally, the analysis of the rhythm variability was carried out. Evaluation of the results thus obtained shows that the two groups registered very different cerebral activation dynamics during the ongoing attentional task. Moreover, DAI patients showed mild cortical activation in the prefrontal region, spread equally throughout both brain hemispheres, while controls showed strong predominant activation of the right prefrontal area. Our findings encourage further investigations of the combined employment of tests and EEG recordings during the clinical assessment of sustained attention performance.     

Paradoxical Heart Failure Precipitated by Profound Dehydration: Intraventricular Dynamic Obstruction and Significant Mitral Regurgitation in a Volume-Depleted Heart

Occurrence of dynamic left ventricular outflow tract (LVOT) obstruction is not infrequent in critically ill patients, and it is associated with potential danger. Here, we report a case of transient heart failure with hemodynamic deterioration paradoxically induced by extreme dehydration. This article describes clinical features of the patient and echocardiographic findings of dynamic LVOT obstruction and significant mitral regurgitation caused by systolic anterior motion of the mitral valve in a volume-depleted heart.     

基于实时三维超声图像的二尖瓣环重建及运动分析

二尖瓣环的非平面特性对二尖瓣返流的超声诊断和二尖瓣环成形术的合理设计具有重要意义.基于心脏的实时三维超声图像,我们研究了一种对二尖瓣环三维重建及运动分析的方法.首先通过人机交互方式提取出二尖瓣环的特征点,并根据位置关系对特征点排序,然后利用非均匀有理B样条曲线建立二尖瓣环三维形态模型,并编程实现二尖瓣环的动态显示和运动分析.通过对20组病例分析,初步证明此方法所建模型较准确反映患者的二尖瓣环的运动,能满足二尖瓣环三维可视化和分析研究的需要.     

提高光声成像质量的Renyi熵方法

针对光声成像数据采集系统中获得的超声数据存在杂波问题,提出一种先基于Renyi熵分离超声信号和杂波,再利用分离后的超声数据进行光声成像的方法。光声成像平台实验表明,通过Renyi熵的直方图来选择超声信号和杂波分离的阈值,可以有效地滤除超声信号中的大部分杂波。成像重构的评估结果也验证了该结论。可见,该文提出的方法能有效滤除超声采集数据中的杂波,从而提高光声成像的质量。     

Computational Study of the Dynamics of a Bileaflet Mechanical Heart Valve in the Mitral Position

A computational study of the flow-structure interaction of a bileaflet mechanical heart valve in the mitral position is presented. Flow in a simple model of the left ventricle is simulated using an immersed boundary method, and the dynamics of the valve leaflets are solved in a fully-coupled manner with the flow. Simulations are conducted for two distinct valve orientations and multiple valve hinge locations, and the performance of the valve is compared in terms of metrics associated with leaflet motion, mitral regurgitation, and mechanical energy losses through the valve. Results indicate that a bileaflet mechanical heart valve with a more centrally located hinge, and implanted in the anatomical orientation provides the best overall performance. The fluid and leaflet dynamics, as well as the clinical implications underlying these findings are discussed.     

Computational Approach to Estimating the Effects of Blood Properties on Changes in Intra-stent Flow

In this study various blood rheological assumptions are numerically investigated for the hemodynamic properties of intra-stent flow. Non-newtonian blood properties have never been implemented in blood coronary stented flow investigation, although its effects appear essential for a correct estimation and distribution of wall shear stress (WSS) exerted by the fluid on the internal vessel surface. Our numerical model is based on a full 3D stent mesh. Rigid wall and stationary inflow conditions are applied. Newtonian behavior, non-newtonian model based on Carreau-Yasuda relation and a characteristic newtonian value defined with flow representative parameters are introduced in this research. Non-newtonian flow generates an alteration of near wall viscosity norms compared to newtonian. Maximal WSS values are located in the center part of stent pattern structure and minimal values are focused on the proximal stent wire surface. A flow rate increase emphasizes fluid perturbations, and generates a WSS rise except for interstrut area. Nevertheless, a local quantitative analysis discloses an underestimation of WSS for modelisation using a newtonian blood flow, with clinical consequence of overestimate restenosis risk area. Characteristic viscosity introduction appears to present a useful option compared to rheological modelisation based on experimental data, with computer time gain and relevant results for quantitative and qualitative WSS determination.     

A Computational Approach to Understand Phenotypic Structure and Constitutive Mechanics Relationships of Single Cells

The goal of this study is to construct a representative 3D finite element model (FEM) of individual cells based on their sub-cellular structures that predicts cell mechanical behavior. The FEM simulations replicate atomic force microscopy (AFM) nanoindentation experiments on live vascular smooth muscle cells. Individual cells are characterized mechanically with AFM and then imaged in 3D using a spinning disc confocal microscope. Using these images, geometries for the FEM are automatically generated via image segmentation and linear programming algorithms. The geometries consist of independent structures representing the nucleus, actin stress fiber network, and cytoplasm. These are imported into commercial software for mesh refinement and analysis. The FEM presented here is capable of predicting AFM results well for 500 nm indentations. The FEM results are relatively insensitive to both the exact number and diameter of fibers used. Despite the localized nature of AFM nanoindentation, the model predicts that stresses are distributed in an anisotropic manner throughout the cell body via the actin stress fibers. This pattern of stress distribution is likely a result of the geometric arrangement of the actin network.