Hemodynamics analyses in treated and untreated carotid arteries of the same patient: A preliminary study based on three patient cases

Carotid atherosclerotic disease is highly related to cerebrovascular events. Carotid endarterectomy is the common operation method to treat this disease. In this study, hemodynamics analyses are performed on the carotid arteries in three patients, whose right carotid artery had been treated by carotid endarterectomy and the left carotid artery remained untreated. Flow and loading conditions are compared between these treated and untreated carotid arteries and evaluation of the operative results is discussed. Patient-specific models are reconstructed from MDCT data. Intraoperative ultrasound flow measurements are performed on the treated carotid arteries and the obtained data are used as the boundary conditions of the models and the validations of the computational results. Finite volume method is employed to solve the transport equations and the flow and loading conditions of the models are reported. The results indicate that: (i) in two of the three patients, the internal-to-external flow rate ratio in the untreated carotid artery is larger than that in the treated one, and the average overall flow split ratio by summing up the data of both the left and right carotid arteries is about 2.15; (ii) in the carotid bulb, high wall shear stress occurs at the bifurcation near the external carotid artery in all of the cases without hard plaques; (iii) the operated arteries present low time-averaged wall shear stress at the carotid bulb, especially for the treated arteries with patch technique, indicating the possibility of the recurrence of stenosis; (iv) high temporal gradient of wall shear stress (>35 Pa/s) is shown in the narrowing regions along the vessels; and (v) in the carotid arteries without serious stenosis, the maximum velocity magnitude during mid-diastole is 32~37% of that at systolic peak, however, in the carotid artery with 50% stenosis by hard plaques, this value is nearly doubled (64%). The computational work quantifies flow and loading distributions in the treated and untreated carotid arteries of the same patient, contributing to evaluation of the operative results and indicating the recurrent sites of potential atheromatous plaques.

Pharmacological Modulation of Hemodynamics in Adult Zebrafish In Vivo

INTRODUCTION: Hemodynamic parameters in zebrafish receive increasing attention because of their important role in cardiovascular processes such as atherosclerosis, hematopoiesis, sprouting and intussusceptive angiogenesis. To study underlying mechanisms, the precise modulation of parameters like blood flow velocity or shear stress is centrally important. Questions related to blood flow have been addressed in the past in either embryonic or ex vivo-zebrafish models but little information is available for adult animals. Here we describe a pharmacological approach to modulate cardiac and hemodynamic parameters in adult zebrafish in vivo. MATERIALS AND METHODS: Adult zebrafish were paralyzed and orally perfused with salt water. The drugs isoprenaline and sodium nitroprusside were directly applied with the perfusate, thus closely resembling the preferred method for drug delivery in zebrafish, namely within the water. Drug effects on the heart and on blood flow in the submental vein were studied using electrocardiograms, in vivo-microscopy and mathematical flow simulations. RESULTS: Under control conditions, heart rate, blood flow velocity and shear stress varied less than ± 5%. Maximal chronotropic effects of isoprenaline were achieved at a concentration of 50 μmol/L, where it increased the heart rate by 22.6 ± 1.3% (n = 4; p < 0.0001). Blood flow velocity and shear stress in the submental vein were not significantly increased. Sodium nitroprusside at 1 mmol/L did not alter the heart rate but increased blood flow velocity by 110.46 ± 19.64% (p = 0.01) and shear stress by 117.96 ± 23.65% (n = 9; p = 0.03). DISCUSSION: In this study, we demonstrate that cardiac and hemodynamic parameters in adult zebrafish can be efficiently modulated by isoprenaline and sodium nitroprusside. Together with the suitability of the zebrafish for in vivo-microscopy and genetic modifications, the methodology described permits studying biological processes that are dependent on hemodynamic alterations.

Seismic anisotropy in the Morcles nappe shear zone: Implications for seismic imaging of crustal scale shear zones

Microstructures and textures of calcite mylonites from the Morcles nappe large-scale shear zone in southwestern Switzerland develop principally as a function of 1) extrinsic physical parameters including temperature, stress, strain, strain rate and 2) intrinsic parameters, such as mineral composition. We collected rock samples at a single location from this shear zone, on which laboratory ultrasonic velocities, texture and microstructures were investigated and quantified. The samples had different concentration of secondary mineral phases (< 5 up to 40 vol.%). Measured seismic P wave anisotropy ranges from 6.5% for polyphase mylonites (~ 40 vol.%) to 18.4% in mylonites with < 5 vol.% secondary phases. Texture strength of calcite is the main factor governing the seismic P wave anisotropy. Measured S wave splitting is generally highest in the foliation plane, but its origin is more difficult to explain solely by calcite texture. Additional texture measurements were made on calcite mylonites with low concentration of secondary phases (≤ 10 vol.%) along the metamorphic gradient of the shear zone (15 km distance). A systematic increase in texture strength is observed moving from the frontal part of the shear zone (anchimetamorphism; 280 °C) to the higher temperature, basal part (greenschist facies; 350–400 °C). Calculated P wave velocities become increasingly anisotropic towards the high-strain part of the nappe, from an average of 5.8% in the frontal part to 13.2% in the root of the basal part. Secondary phases raise an additional complexity, and may act either to increase or decrease seismic anisotropy of shear zone mylonites. In light of our findings we reinterpret the origin of some seismically reflective layers in the Grône–Zweisimmen line in southwestern Switzerland (PNR20 Swiss National Research Program). We hypothesize that reflections originate in part from the lateral variation in textural and microstructural arrangement of calcite mylonites in shear zones.

Specimen specific parameter identification of ovine lumbar intervertebral discs: On the influence of fibre-matrix and fibre-fibre shear interactions.

Numerical models of the intervertebral disc, which address mechanical questions commonly make use of the difference in water content between annulus and nucleus, and thus fluid and solid parts are separated. Despite this simplification, models remain complex due to the anisotropy and nonlinearity of the annulus and regional variations of the collagen fibre density. Additionally, it has been shown that cross-links make a large contribution to the stiffness of the annulus. Because of this complex composite structure, it is difficult to reproduce several sets of experimental data with one single set of material parameters. This study addresses the question to which extent the ultrastructure of the intervertebral disc should be modelled so that its moment-angle behaviour can be adequately described. Therefore, a hyperelastic constitutive law, based on continuum mechanical principles was derived, which does not only consider the anisotropy from the collagen fibres, but also interactions among the fibres and between the fibres and the ground substance. Eight ovine lumbar intervertebral discs were tested on a custom made spinal loading simulator in flexion/extension, lateral bending and axial rotation. Specimen-specific geometrical models were generated using CT images and T2 maps to distinguish between annulus fibrosus and nucleus pulposus. For the identification of the material parameters the annulus fibrosus was described with two scenarios: with and without fibre-matrix and fibre-fibre interactions. Both scenarios showed a similar behaviour on a load displacement level. Comparing model predictions to the experimental data, the mean RMS of all specimens and all load cases was 0.54±0.15° without the interaction and 0.54±0.19° when the fibre-matrix and fibre-fibre interactions were included. However, due to the increased stiffness when cross-links effects were included, this scenario showed more physiological stress-strain relations in uniaxial and biaxial stress states. Thus, the present study suggests that fibre-matrix and fibre-fibre interactions should be considered in the constitutive law when the model addresses questions concerning the stress field of the annulus fibrosus.

Small quantity but large effect — How minor phases control strain localization in upper mantle shear zones

Low viscosity domains such as localized shear zones exert an important control on the geodynamics of the uppermost mantle. Grain size reduction and subsequent strain localization related to a switch from dislocation to diffusion creep is one mechanism to form low viscosity domains. To sustain strain localization, the grain size of mantle minerals needs to be kept small over geological timescales. One way to keep olivine grain sizes small is by pinning of mobile grain boundaries during grain growth by other minerals (second phases). Detailed microstructural studies based on natural samples from three shear zones formed at different geodynamic settings, allowed the derivation of the olivine grain-size dependence on the second-phase content. The polymineralic olivine grain-size evolution with increasing strain is similar in the three shear zones. If the second phases are to pin the mobile olivine grain boundary the phases need to be well mixed before grain growth. We suggest that melt-rock and metamorphic reactions are crucial for the initial phase mixing in mantle rocks. With ongoing deformation and increasing strain, grain boundary sliding combined with mass transfer processes and nucleation of grains promotes phase mixing resulting in fine-grained polymineralic mixtures that deform by diffusion creep. Strain localization due to the presence of volumetrically minor minerals in polymineralic mantle rocks is only important at high strain deformation (ultramylonites) at low temperatures (<~800°C). At smaller strain and stress conditions and/or higher temperatures other parameters like overall energy available to deform a given rock volume, the inheritance of mechanical anisotropies or the presence of water or melts needs to be considered to explain strain localization in the upper mantle.

Interpretation of fluid inclusions in quartz deformed by weak ductile shearing: reconstruction of differential stress magnitudes and pre-deformation fluid properties

A well developed theoretical framework is available in which paleofluid properties, such as chemical composition and density, can be reconstructed from fluid inclusions in minerals that have undergone no ductile deformation. The present study extends this framework to encompass fluid inclusions hosted by quartz that has undergone weak ductile deformation following fluid entrapment. Recent experiments have shown that such deformation causes inclusions to become dismembered into clusters of irregularly shaped relict inclusions surrounded by planar arrays of tiny, new-formed (neonate) inclusions. Comparison of the experimental samples with a naturally sheared quartz vein from Grimsel Pass, Aar Massif, Central Alps, Switzerland, reveals striking similarities. This strong concordance justifies applying the experimentally derived rules of fluid inclusion behaviour to nature. Thus, planar arrays of dismembered inclusions defining cleavage planes in quartz may be taken as diagnostic of small amounts of intracrystalline strain. Deformed inclusions preserve their pre-deformation concentration ratios of gases to electrolytes, but their H2O contents typically have changed. Morphologically intact inclusions, in contrast, preserve the pre-deformation composition and density of their originally trapped fluid. The orientation of the maximum principal compressive stress (σ1σ1) at the time of shear deformation can be derived from the pole to the cleavage plane within which the dismembered inclusions are aligned. Finally, the density of neonate inclusions is commensurate with the pressure value of σ1σ1 at the temperature and time of deformation. This last rule offers a means to estimate magnitudes of shear stresses from fluid inclusion studies. Application of this new paleopiezometer approach to the Grimsel vein yields a differential stress (σ1–σ3σ1–σ3) of ∼300 MPa∼300 MPa at View the MathML source390±30°C during late Miocene NNW–SSE orogenic shortening and regional uplift of the Aar Massif. This differential stress resulted in strain-hardening of the quartz at very low total strain (<5%<5%) while nearby shear zones were accommodating significant displacements. Further implementation of these experimentally derived rules should provide new insight into processes of fluid–rock interaction in the ductile regime within the Earth's crust.

The Initial Slope of the Variogram, Foundation of the Trabecular Bone Score, Is Not or Poorly Associated With Vertebral Strength

Trabecular bone score (TBS) rests on the textural analysis of DXA to reflect the decay in trabecular structure characterising osteoporosis. Yet, its discriminative power in fracture studies remains incomprehensible as prior biomechanical tests found no correlation with vertebral strength. To verify this result possibly due to an unrealistic set-up and to cover a wide range of loading scenarios, the data from three previous biomechanical studies using different experimental settings was used. They involved the compressive failure of 62 human lumbar vertebrae loaded 1) via intervertebral discs to mimic the in vivo situation (“full vertebra”), 2) via the classical endplate embedding (“vertebral body”) or 3) via a ball joint to induce anterior wedge failure (“vertebral section”). HR-pQCT scans acquired prior testing were used to simulate anterior-posterior DXA from which areal bone mineral density (aBMD) and the initial slope of the variogram (ISV), the early definition of TBS, were evaluated. Finally, the relation of aBMD and ISV with failure load (Fexp) and apparent failure stress (σexp) was assessed and their relative contribution to a multi-linear model was quantified via ANOVA. We found that, unlike aBMD, ISV did not significantly correlate with Fexp and σexp, except for the “vertebral body” case (r2 = 0.396, p = 0.028). Aside from the “vertebra section” set-up where it explained only 6.4% of σexp (p = 0.037), it brought no significant improvement to aBMD. These results indicate that ISV, a replica of TBS, is a poor surrogate for vertebral strength no matter the testing set-up, which supports the prior observations and raises a fortiori the question of the deterministic factors underlying the statistical relationship between TBS and vertebral fracture risk.

Comparison of Mixed and Kinematic Uniform Boundary Conditions in Homogenized Elasticity of Femoral Trabecular Bone Using Microfinite Element Analyses

Mechanical properties of human trabecular bone play an important role in age-related bone fragility and implant stability. Micro-finite element (microFE) analysis allows computing the apparent elastic properties of trabecular bone biopsies, but the results depend on the type of applied boundary conditions (BCs). In this study, 167 femoral trabecular cubic biopsies with a side length of 5.3 mm were analyzed using microFE analysis to compare their stiffness systematically with kinematic uniform boundary conditions (KUBCs) and periodicity-compatible mixed uniform boundary conditions (PMUBCs). The obtained elastic constants were then used in the volume fraction and fabric-based orthotropic Zysset-Curnier model to identify their respective model parameters. As expected, PMUBCs lead to more compliant apparent elastic properties than KUBCs, especially in shear. The differences in stiffness decreased with bone volume fraction and mean intercept length. Unlike KUBCs, PMUBCs were sensitive to heterogeneity of the biopsies. The Zysset-Curnier model predicted apparent elastic constants successfully in both cases with adjusted coefficients of determination of 0.986 for KUBCs and 0.975 for PMUBCs. The role of these boundary conditions in finite element analyses of whole bones and bone-implant systems will need to be investigated in future work.

Effect of boundary conditions on yield properties of human femoral trabecular bone

Trabecular bone plays an important mechanical role in bone fractures and implant stability. Homogenized nonlinear finite element (FE) analysis of whole bones can deliver improved fracture risk and implant loosening assessment. Such simulations require the knowledge of mechanical properties such as an appropriate yield behavior and criterion for trabecular bone. Identification of a complete yield surface is extremely difficult experimentally but can be achieved in silico by using micro-FE analysis on cubical trabecular volume elements. Nevertheless, the influence of the boundary conditions (BCs), which are applied to such volume elements, on the obtained yield properties remains unknown. Therefore, this study compared homogenized yield properties along 17 load cases of 126 human femoral trabecular cubic specimens computed with classical kinematic uniform BCs (KUBCs) and a new set of mixed uniform BCs, namely periodicity-compatible mixed uniform BCs (PMUBCs). In stress space, PMUBCs lead to 7–72 % lower yield stresses compared to KUBCs. The yield surfaces obtained with both KUBCs and PMUBCs demonstrate a pressure-sensitive ellipsoidal shape. A volume fraction and fabric-based quadric yield function successfully fitted the yield surfaces of both BCs with a correlation coefficient R2≥0.93. As expected, yield strains show only a weak dependency on bone volume fraction and fabric. The role of the two BCs in homogenized FE analysis of whole bones will need to be investigated and validated with experimental results at the whole bone level in future studies.

Fault development and interaction in distributed strike-slip shear zones: an experimental approach

Analogue model experiments using both brittle and viscous materials were performed to investigate the development and interaction of strike-slip faults in zones of distributed shear deformation. At low strain, bulk dextral shear deformation of an initial rectangular model is dominantly accommodated by left-stepping, en echelon strike-slip faults (Riedel shears, R) that form in response to the regional (bulk) stress field. Push-up zones form in the area of interaction between adjacent left-stepping Riedel shears. In cross sections, faults bounding push-up zones have an arcuate shape or merge at depth. Adjacent left-stepping R shears merge by sideways propagation or link by short synthetic shears that strike subparallel to the bulk shear direction. Coalescence of en echelon R shears results in major, through-going faults zones (master faults). Several parallel master faults develop due to the distributed nature of deformation. Spacing between master faults is related to the thickness of the brittle layers overlying the basal viscous layer. Master faults control to a large extent the subsequent fault pattern. With increasing strain, relatively short antithetic and synthetic faults develop mostly between old, but still active master faults. The orientation and evolution of the new faults indicate local modifications of the stress field. In experiments lacking lateral borders, closely spaced parallel antithetic faults (cross faults) define blocks that undergo clockwise rotation about a vertical axis with continuing deformation. Fault development and fault interaction at different stages of shear strain in our models show similarities with natural examples that have undergone distributed shear.