A current and significant limitation to metabolomics is the large-scale, high-throughput conversion of raw chromatographically coupled mass spectrometry datasets into organized data matrices necessary for further statistical processing and data visualization. This article describes a new data extraction tool, MET-IDEA (Metabolomics Ion-based Data Extraction Algorithm) which surmounts this void. MET-IDEA is compatible with a diversity of chromatographically coupled mass spectrometry systems, generates an output similar to traditional quantification methods, utilizes the sensitivity and selectivity associated with selected ion quantification, and greatly reduces the time and effort necessary to obtain large-scale organized datasets by several orders of magnitude. The functionality of MET-IDEA is illustrated using metabolomics data obtained for elicited cell culture exudates from the model legume, Medicago truncatula. The results indicate that MET-IDEA is capable of rapidly extracting semiquantitative data from raw data files, which allows for more rapid biological insight. MET-IDEA is freely available to academic users upon request.

The mechanical loading-deformation relation of elastin and collagen fibril bundles is fundamental to understanding the microstructural properties of tissue. Here, we use multiphoton microscopy to obtain quantitative data of elastin and collagen fiber bundles under in situ loading of coronary adventitia. Simultaneous loading-imaging experiments on unstained fresh coronary adventitia allowed morphometric measurements of collagen and elastin fibril bundles and their individual deformation. Fiber data were analyzed at five different distension loading points (circumferential stretch ratio λ(θ) = 1.0, 1.2, 1.4, 1.6, and 1.8) at a physiological axial stretch ratio of λ(axial) = 1.3. Four fiber geometrical parameters were used to quantify the fibers: orientation angle, waviness, width, and area fraction. The results show that elastin and collagen fibers in inner adventitia form concentric densely packed fiber sheets, and the fiber orientation angle, width, and area fraction vary transmurally. The extent of fiber deformation depends on the initial orientation angle at no-distension state (λ(θ) = 1.0 and λ(axial) = 1.3). At higher distension loading, the orientation angle and waviness of fibers decrease linearly, but the width of collagen fiber is relatively constant at λ(θ) = 1.0-1.4 and then decrease linearly for λ(θ) ≥ 1.4. A decrease of the relative dispersion (SD/mean) of collagen fiber waviness suggests a heterogeneous mechanical response to loads. This study provides fundamental microstructural data for coronary artery biomechanics and we consider it seminal for structural models.

The microstructural deformation-mechanical loading relation of the blood vessel wall is essential for understanding the overall mechanical behavior of vascular tissue in health and disease. We employed simultaneous mechanical loading-imaging to quantify in situ deformation of individual collagen and elastin fibers on unstained fresh porcine coronary adventitia under a combination of vessel inflation and axial extension loading. Specifically, the specimens were imaged under biaxial loads to study microscopic deformation-loading behavior of fibers in conjunction with morphometric measurements at the zero-stress state. Collagen fibers largely orientate in the longitudinal direction, while elastin fibers have major orientation parallel to collagen, but with additional orientation angles in each sublayer of the adventitia. With an increase of biaxial load, collagen fibers were uniformly stretched to the loading direction, while elastin fibers gradually formed a network in sublayers, which strongly depended on the initial arrangement. The waviness of collagen decreased more rapidly at a circumferential stretch ratio of λθ = 1.0 than at λθ = 1.5, while most collagen became straightened at λθ = 1.8. These microscopic deformations imply that the longitudinally stiffer adventitia is a direct result of initial fiber alignment, and the overall mechanical behavior of the tissue is highly dependent on the corresponding microscopic deformation of fibers. The microstructural deformation-loading relation will serve as a foundation for micromechanical models of the vessel wall.

Although vascular smooth muscle cells (VSMCs) are pivotal in physiology and pathology, there is a lack of detailed morphological data on these cells. The objective of this study was to determine dimensions (width and length) and orientation of swine coronary VSMCs and to develop a microstructural constitutive model of active media. The dimensions, spatial aspect ratio and orientation angle of VSMCs measured at zero-stress state were found to follow continuous normal (or bimodal normal) distributions. The VSMCs aligned off circumferential direction of blood vessels with symmetrical polar angles 18.7°±10.9°, and the local VSMC deformation was affine with tissue-level deformation. A microstructure-based active constitutive model was developed to predict the biaxial vasoactivity of coronary media, based on experimental measurements of geometrical and deformation features of VSMCs. The results revealed that the axial active response of blood vessels is associated with multi-axial contraction as well as oblique VSMC arrangement. The present morphological data base is essential for developing accurate structural models and is seminal for understanding the biomechanics of muscular vessels.

ObjectiveTo compare foam bubble size and bubble size distribution, stability, and degradation rate of commercially available polidocanol endovenous microfoam (Varithena®) and physician-compounded foams using a number of laboratory tests.MethodsFoam properties of polidocanol endovenous microfoam and physician-compounded foams were measured and compared using a glass-plate method and a Sympatec QICPIC image analysis method to measure bubble size and bubble size distribution, Turbiscan™ LAB for foam half time and drainage and a novel biomimetic vein model to measure foam stability. Physician-compounded foams composed of polidocanol and room air, CO2, or mixtures of oxygen and carbon dioxide (O2:CO2) were generated by different methods.ResultsPolidocanol endovenous microfoam was found to have a narrow bubble size distribution with no large (>500 µm) bubbles. Physician-compounded foams made with the Tessari method had broader bubble size distribution and large bubbles, which have an impact on foam stability. Polidocanol endovenous microfoam had a lower degradation rate than any physician-compounded foams, including foams made using room air (p < 0.035). The same result was obtained at different liquid to gas ratios (1:4 and 1:7) for physician-compounded foams. In all tests performed, CO2 foams were the least stable and different O2:CO2 mixtures had intermediate performance. In the biomimetic vein model, polidocanol endovenous microfoam had the slowest degradation rate and longest calculated dwell time, which represents the length of time the foam is in contact with the vein, almost twice that of physician-compounded foams using room air and eight times better than physician-compounded foams prepared using equivalent gas mixes.ConclusionBubble size, bubble size distribution and stability of various sclerosing foam formulations show that polidocanol endovenous microfoam results in better overall performance compared with physician-compounded foams. Polidocanol endovenous microfoam offers better stability and cohesive properties in a biomimetic vein model compared to physician-compounded foams. Polidocanol endovenous microfoam, which is indicated in the United States for treatment of great saphenous vein system incompetence, provides clinicians with a consistent product with enhanced handling properties.

Even when entirely unloaded, biological structures are not stress-free, as shown by Y.C. Fung’s seminal opening angle experiment on arteries and the left ventricle. As a result of this prestrain, subject-specific geometries extracted from medical imaging do not represent an unloaded reference configuration necessary for mechanical analysis, even if the structure is externally unloaded. Here we propose a new computational method to create physiological residual stress fields in subject-specific left ventricular geometries using the continuum theory of fictitious configurations combined with a fixed-point iteration. We also reproduced the opening angle experiment on four swine models, to characterize the range of normal opening angle values. The proposed method generates residual stress fields which can reliably reproduce the range of opening angles between 8.7±1.8 and 16.6 ± 13.7 as measured experimentally. We demonstrate that including the effects of prestrain reduces the left ventricular stiffness by up to 40%, thus facilitating the ventricular filling, which has a significant impact on cardiac function. This method can improve the fidelity of subject-specific models to improve our understanding of cardiac diseases and to optimize treatment options.

Double-J stenting is the most common clinical method employed to restore the upper urinary tract drainage, in the presence of a ureteric obstruction. After implant, stents provide an immediate pain relief by decreasing the pressure in the renal pelvis (P). However, their long-term usage can cause infections and encrustations, due to bacterial colonization and crystal deposition on the stent surface, respectively. The performance of double-J stents - and in general of all ureteric stents - is thought to depend significantly on urine flow field within the stented ureter. However very little fundamental research about the role played by fluid dynamic parameters on stent functionality has been conducted so far. These parameters are often difficult to assess in-vivo, requiring the implementation of laborious and expensive experimental protocols. The aim of the present work was therefore to develop an artificial model of the ureter (i.e. ureter model, UM) to mimic the fluid dynamic environment in a stented ureter. The UM was designed to reflect the geometry of pig ureters, and to investigate the values of fluid dynamic viscosity (μ), volumetric flow rate (Q) and severity of ureteric obstruction (OB%) which may cause critical pressures in the renal pelvis. The distributed obstruction derived by the sole stent insertion was also quantified. In addition, flow visualisation experiments and computational simulations were performed in order to further characterise the flow field in the UM. Unique characteristics of the flow dynamics in the obstructed and stented ureter have been revealed with using the developed UM.

The passive mechanical properties of blood vessel mainly stem from the interaction of collagen and elastin fibers, but vessel constriction is attributed to smooth muscle cell (SMC) contraction. Although the passive properties of coronary arteries have been well characterized, the active biaxial stress-strain relationship is not known. Here, we carry out biaxial (inflation and axial extension) mechanical tests in right coronary arteries that provide the active coronary stress-strain relationship in circumferential and axial directions. Based on the measurements, a biaxial active strain energy function is proposed to quantify the constitutive stress-strain relationship in the physiological range of loading. The strain energy is expressed as a Gauss error function in the physiological pressure range. In K ϩ -induced vasoconstriction, the mean Ϯ SE values of outer diameters at transmural pressure of 80 mmHg were 3.41 Ϯ 0.17 and 3.28 Ϯ 0.24 mm at axial stretch ratios of 1.3 and 1.5, respectively, which were significantly smaller than those in Ca 2ϩ -free-induced vasodilated state (i.e., 4.01 Ϯ 0.16 and 3.75 Ϯ 0.20 mm, respectively). The mean Ϯ SE values of the inner and outer diameters in no-load state and the opening angles in zero-stress state were 1.69 Ϯ 0.04 mm and 2.25 Ϯ 0.08 mm and 126 Ϯ 22°, respectively. The active stresses have a maximal value at the passive pressure of 80 -100 mmHg and at the active pressure of 140 -160 mmHg. Moreover, a mechanical analysis shows a significant reduction of mean stress and strain (averaged through the vessel wall). These findings have important implications for understanding SMC mechanics.contraction; constitutive equation; stress-strain relation; vessel mechanics VASOACTIVITY OF LARGE EPICARDIAL coronary arteries is affected by cardiovascular diseases such as diabetes (14, 15), hypertension (14, 20), atherosclerosis (11), vasospasm (10, 32), and aneurysm (26), which are major risk factors for angina pectoris or myocardial infarction in patients. The constitutive passive and active stress-strain relationships can characterize the vasoactivity and are fundamental for understanding the mechanical behaviors of vascular smooth muscle cell (SMC) in health and disease (5). The strain energy function has been widely used to characterize the passive mechanical properties of blood vessels (5,8). For large epicardial coronary arteries, extensive mechanical measurements and analysis were carried out in the passive state (18,19,23,30,33,34).The active mechanical properties of coronary arteries are much known. To date, there are only uniaxial active constitutive length-tension relationships in the circumferential direction of coronary arteries (1, 2, 24, 31). Although some multi-axial active models have been proposed, those have been of theoretical forms not rooted in experimental measurements (25, 36). Clearly, there is a need for multi-axial active mechanical measurements and experimentally determined multi-dimensional active strain energy functions for coronary arteries.The objective ...