Microbubble expansion in a flexible tube

We have utilized a computational model of the expansion of a microbubble in a liquid-filled flexible tube to investigate the potential for acoustic vaporization of perfluorocarbon droplets to damage blood vessels during a novel gas embolotherapy technique for the potential treatment of tumors. This model uses a fixed grid, multi-domain, interface tracking, direct numerical simulation method that treats all interfaces and boundaries as sharp discontinuities for high accuracy. In the current work, we examined effects of initial bubble size on the flows and wall stresses that result from droplet vaporization. The remaining dimensionless parameters that govern the system response (Reynolds, Weber, and Strouhal numbers, initial bubble pressure, and wall stiffness and tension) were selected to model an arteriole. The results for a flexible tube are significantly different from those for a rigid tube. Two major flow regimes occur due to the combined effect of bubble and tube deformation: in flow at the tube ends and out flow near the bubble surface. The flexibility of the tube largely dissipates the extreme pressure that develops in the rigid tube model. Both the magnitude and the overall expansion time of the rapidly changing pressure are greatly reduced in the flexible tube. Smaller initial bubble diameters, relative to the vessel diameter, result in lower wall stresses. This study indicates that wall flexibility can significantly influence the wall stresses that result from acoustic vaporization of intravascular perfluorocarbon droplets, and suggests that acoustic activation of droplets in larger, more flexible vessels may be less likely to damage or rupture vessels than activation in smaller and stiffer vessels.     

Evolution of acoustically vaporized microdroplets in gas embolotherapy

Acoustic vaporization dynamics of a superheated dodecafluoropentane (DDFP) microdroplet inside a microtube and the resulting bubble evolution is investigated in the present work. This work is motivated by a developmental gas embolotherapy technique that is intended to treat cancers by infarcting tumors using gas bubbles. A combined theoretical and computational approach is utilized and compared with the experiments to understand the evolution process and to estimate the resulting stress distribution associated with vaporization event. The transient bubble growth is first studied by ultra-high speed imaging and then theoretical and computational modeling is used to predict the entire bubble evolution process. The evolution process consists of three regimes: an initial linear rapid spherical growth followed by a linear compressed oval shaped growth and finally a slow asymptotic nonlinear spherical bubble growth. Although the droplets are small compared to the tube diameter, the bubble evolution is influenced by the tube wall. The final bubble radius is found to scale linearly with the initial droplet radius and is approximately five times the initial droplet radius. A short pressure pulse with amplitude almost twice as that of ambient conditions is observed. The width of this pressure pulse increases with increasing droplet size whereas the amplitude is weakly dependent. Although the rise in shear stress along the tube wall is found to be under peak physiological limits, the shear stress amplitude is found to be more prominently influenced by the initial droplet size. The role of viscous dissipation along the tube wall and ambient bulk fluid pressure is found to be significant in bubble evolution dynamics.     

Acoustic emission analysis and experiments with physical model systems reveal a peculiar nature of the xylem tension

Advanced acoustic emission analysis, special microscopic examinations and experiments with physical model systems give reasons for the assumption that the tension in the water conducting system of vascular plants is caused by countless minute gas bubbles strongly adhering to the hydrophobic lignin domains of the xylem vessel walls. We ascertained these bubbles for several species of temperate deciduous trees and conifers. It is our hypothesis that the coherent bubble system of the xylem conduits operates as a force-transmitting medium that is capable of transporting water in traveling peristaltic waves. By virtue of the high elasticity of the gas bubbles, the hydro-pneumatic bubble system is capable of cyclic storing and releasing of energy. We consider the abrupt regrouping of the wall adherent bubble system to be the origin of acoustic emissions from plants. For Ulmus glabra, we recorded violent acoustic activity during both transpiration and re-hydration. The frequency spectrum and the waveforms of the detected acoustic emissions contradict traditional assumptions according to which acoustic emissions are caused by cavitation disruption of the stressed water column. We consider negative pressure in terms of the cohesion theory to be mimicked by the tension of the wall adherent bubble system.     

Small-bubble transport and splitting dynamics in a symmetric bifurcation

Simulations of small bubbles traveling through symmetric bifurcations are conducted to garner information pertinent to gas embolotherapy, a potential cancer treatment. Gas embolotherapy procedures use intra-arterial bubbles to occlude tumor blood supply. As bubbles pass through bifurcations in the blood stream nonhomogeneous splitting and undesirable bioeffects may occur. To aid development of gas embolotherapy techniques, a volume of fluid method is used to model the splitting process of gas bubbles passing through artery and arteriole bifurcations. The model reproduces the variety of splitting behaviors observed experimentally, including the bubble reversal phenomenon. Splitting homogeneity and maximum shear stress along the vessel walls is predicted over a variety of physical parameters. Small bubbles, having initial length less than twice the vessel diameter, were found unlikely to split in the presence of gravitational asymmetry. Maximum shear stresses were found to decrease exponentially with increasing Reynolds number. Vortex-induced shearing near the bifurcation is identified as a possible mechanism for endothelial cell damage.     

Effects of bubble–liquid two‐phase turbulent hydrodynamics on cell damage in sparged bioreactor

According to recent experimental studies on sparged bioreactors, significant cell damage may occur at the gas inlet region near the sparger. Although shear stress was proposed to be one of the potential causes for cell damage, detailed hydrodynamic studies at the gas inlet region of gas–liquid bioreactors have not been performed to date. In this work, a second‐order moment (SOM) bubble–liquid two‐phase turbulent model based on the two‐fluid continuum approach is used to investigate the gas–liquid hydrodynamics in the bubble column reactor and their potential impacts on cell viability, especially at the gas inlet region. By establishing fluctuation velocity and bubble–liquid two‐phase fluctuation velocities correlation transport equations, the anisotropy of two‐phase stresses and the bubble–liquid interactions are fully considered. Simulation results from the SOM model indicate that shear and normal stresses, turbulent energy dissipation rate, and the turbulent kinetic energy are generally smaller at the gas inlet region when compared with those in the fully developed region. In comparison, a newly proposed correlation expression, stress‐induced turbulent energy production (STEP), is found to correlate well with the unusually high cell death rate at the gas inlet region. Therefore, STEP, which represents turbulent energy transfer to a controlled volume induced by a combination of shear and normal stresses, has the potential to provide better explanation for increased cell death at the sparger region. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 30:48–58, 2014     

Some unusual considerations about vessel walls and wall stresses

The "zero-stress state" of blood vessels is usually defined with respect to the atmospheric pressure p(a) ( approximately 750 mmHg). As a consequence, circumferential and axial wall stresses due to a positive transmural pressure can only be positive and thus, by definition, only tensile. If the zero-stress state were defined with respect to vacuum pressure (0 mmHg), the compressive stress -p(a) generated by p(a) everywhere in the wall would, however, be included so that negative (=compressive) wall stresses would formally become possible. In order to examine the consequences this alternative definition would have for arteries, we have compared radial, circumferential, and axial stresses calculated "conventionally" to the values they take when the zero-stress state is defined "correctly" by reference to the vacuum pressure. It turns out that, under normal physiologic conditions, axial stress and perhaps also circumferential stress might well be compressive in many elastic and conductance arteries, contrary to the intuitive conviction of many people. Since the type of stresses a vessel wall is submitted to may be highly relevant for its structure and mechanical properties, this unconventional way of considering wall stresses may reveal unsuspected relationships between wall stresses on one side, and wall structure, vessel growth, adaptation and repair processes, atherosclerosis, angioplasty or stenting on the other side. Similar considerations might also prove useful with regard to cardiac hypertrophy.     

In vivo spectroscopic photoacoustic imaging and laser-induced nanoparticle vaporization for anti-HER2 breast cancer

This study reports on the development and application of theragnostic agents targeting the HER2 receptors in breast tumors. The agent was constructed by loading silica-coated gold nanorods (GNRs) and a perfluorohexane liquid into PLGA-PEG nanoparticles, followed by surface conjugation with antibody Herceptin. The particle uptake in human breast cancer MDA-MB-231 (HER2-negative) and BT474 (HER2-positive) cell lines was tested. A proof of principle in vivo study was also performed using a xenograft mouse bilateral tumor model (16 mice, 32 tumors). Photoacoustic imaging was performed using a VevoLAZR device at 720/750/850 nm illuminations and 21 MHz central frequency. The relative concentrations of GNRs in the tumor were quantified using a linear spectral unmixing technique. The therapeutic efficacy of these nanoparticles was evaluated through optical droplet vaporization, and cell damage was confirmed using tissue immunofluorescence and histology. Our results demonstrate the potential of PLGA-GNRs as theragnostic agents for anti-HER2 breast cancer therapy.     

On the influence of vessel planarity on local hemodynamics at the human carotid bifurcation

The human carotid artery bifurcation is a complex, three-dimensional structure exhibiting non-planarity and both in- and out-of-plane curvature. The aim of this study was to determine the relative importance of vessel planarity, a potential geometric risk factor for atherogenesis, in determining the local hemodynamics. A combination of computational fluid dynamics and magnetic resonance imaging was used to reconstruct the subject-specific hemodynamics for three subjects. Planar models were then constructed by translating the centroids of the lumen contours onto a plane defined by the centroids of the vessel branches near the bifurcation apex. A novel "patching" technique was used to convert the continuous arterial surfaces into contiguous but discrete patches according to an objective scheme, making it possible to compare the original and planar models without the need for registration and warping. Results suggest that the planarity of the vessel has a relatively minor effect on the spatial distribution of mean and oscillatory wall shear stress. Out-of-plane curvature was, however, found to have a marked influence on the extent and magnitude of these hemodynamic variables. We conclude that vessel curvature - whether in- or out-of-plane - rather than planarity may deserve further scrutiny as a potential geometric risk for atherogenesis.     

Flow-tissue interaction with compliance mismatch in a model stented artery

The insertion of an endovascular prosthesis is known to have a thrombogenic effect that is also a consequence of the interaction between the flowing blood and the stented arterial segment; in fact the prosthesis induces a compliance mismatch and a possible small expansion along the vessel that eventually gives rise to an anomalous distribution of wall shear stresses. The fluid dynamics inside a rectilinear elastic vessel with compliance and section variation is studied here numerically. A recently introduced perturbative approach is employed to model the interaction between the fluid and the elastic tissue; this approximate technique is first validated by comparison with a complete solution within a simple one-dimensional model of the same system. Then it is applied to an axisymmetric model in order to evaluate the flow dynamics and the distribution of wall shear stress in the stented vessel. Compliance mismatch is shown to produce more intense negative wall shear stresses in the stented segment while rapid variations of wall shear stress are found at the stent ends. These effects are enhanced when the prosthesis is accompanied by a small increase of the vessel lumen.     

A Novel Tram Stent Method in the Treatment of Coronary Bifurcation Lesions – Finite Element Study

A novel stent was designed for the treatment of coronary bifurcation lesion, and it was investigated for its performance by finite element analysis. This study was performed in search of a novel method of treatment of bifurcation lesion with provisional stenting. A bifurcation model was created with the proximal vessel of 3.2 mm diameter, and the distal vessel after the side branch (2.3 mm) was 2.7 mm. A novel stent was designed with connection links that had a profile of a tram. Laser cutting and shape setting of the stent was performed, and thereafter it was crimped and deployed over a balloon. The contact pressure, stresses on the arterial wall, stresses on the stent, the maximal principal log strain of the main artery and the side-branch were studied. The study was performed in Abaqus, Simulia. The stresses on the main branch and the distal branch were minimally increased after deployment of this novel stent. The side branch was preserved, and the stresses on the side branch were lesser; and at the confluence of bifurcation on either side of the side branch origin the von-Mises stress was marginally increased. The stresses and strain at the bifurcation were significantly lesser than the stresses and strain of the currently existing techniques used in the treatment of bifurcation lesions though the study was primarily focused only on the utility of the new technology. There is a potential for a novel Tram-stent method in the treatment of coronary bifurcation lesions.     

Controllable microfluidic synthesis of multiphase drug‐carrying lipospheres for site‐targeted therapy

We report the production of micrometer‐sized gas‐filled lipospheres using digital (droplet‐based) microfluidics technology for chemotherapeutic drug delivery. Advantages of on‐chip synthesis include a monodisperse size distribution (polydispersity index (σ) values of <5%) with consistent stability and uniform drug loading. Photolithography techniques are applied to fabricate novel PDMS‐based microfluidic devices that feature a combined dual hydrodynamic flow‐focusing region and expanding nozzle geometry with a narrow orifice. Spherical vehicles are formed through flow‐focusing by the self‐assembly of phospholipids to a lipid layer around the gas core, followed by a shear‐induced break off at the orifice. The encapsulation of an extra oil layer between the outer lipid shell and inner bubble gaseous core allows the transport of highly hydrophobic and toxic drugs at high concentrations. Doxorubicin (Dox) entrapment is estimated at 15 mg mL^?1 of particles packed in a single ordered layer. In addition, the attachment of targeting ligands to the lipid shell allows for direct vehicle binding to cancer cells. Preliminary acoustic studies of these monodisperse gas lipospheres reveal a highly uniform echo correlation of greater than 95%. The potential exists for localized drug concentration and release with ultrasound energy. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009     

Investigation of the structure of two-phase flows. Model media in bubble-column bioreactors

Summary The following two-phase properties were evaluated in bubble column reactors with porous plate (5 m pore diameter) or perforated plate (1 mm and/or 3 mm hole diameter) gas distributors using distilled water or a 1% methanol solution: transverse profiles of the mean and Sauter bubble diameters, local gas holdups, true mean liquid and bubble velocities. Furthermore, swarm bubble velocity distributions were evaluted and compared with calculated values.     

A methodology for in silico endovascular repair of abdominal aortic aneurysms

Endovascular aneurysm repair (EVAR) can involve some unfavorable complications such as endoleaks or stent-graft (SG) migration. Such complications, resulting from the complex mechanical interaction of vascular tissue, SG and blood flow or incompatibility of SG design and vessel geometry, are difficult to predict. Computational vascular mechanics models can be a predictive tool for the selection, sizing and placement process of SGs depending on the patient-specific vessel geometry and hence reduce the risk of potential complications after EVAR. In this contribution, we present a new in silico EVAR methodology to predict the final state of the deployed SG after intervention and evaluate the mechanical state of vessel and SG, such as contact forces and wall stresses. A novel method to account for residual strains and stresses in SGs, resulting from the precompression of stents during the assembly process of SGs, is presented. We suggest a parameter continuation approach to model various different sizes of SGs within one in silico EVAR simulation which can be a valuable tool when investigating the issue of SG oversizing. The applicability and robustness of the proposed methods are demonstrated on the example of a synthetic abdominal aortic aneurysm geometry.     

Damage mechanisms of suspended animal cells in agitated bioreactors with and without bubble entrainment

We show that when freely suspended hybridoma cells are cultured in an agitated bioreactor, two fluid-mechanical mechanisms can cause cell damage and growth retardation. The first is present only when there is a gas phase, and is associated with vortex formation accompanied by bubble entrainment and breakup. In the absence of a vortex and bubble entrainment, cells can be damaged only at very high agitation rates, above approximately 700 rpm, by stresses in the bulk turbulent liquid. Cell damage then correlates with Kolmogorov eddy sizes similar to or smaller than the cell size. In the absence of a vortex, the entrainment and motion of very fine bubbles cause no growth retardation even at agitation rates as high as 600 rpm.     

Local gas hydrodynamics in an external-loop airlift reactor: newtonian and non-newtonian fluids

Measurements of local gas phase characteristics are obtained in an external-loop airlift reactor filled with newtonian or viscous non-newtonian liquids. A double-optical fiber probe technique is used. It allows the determination of the axial and radial profiles of gas hold-up, bubbling frequency, bubble size and velocity. In the case of air-water system, the results show a strong effect of radial liquid velocity variation on the gas flow characteristics at the bottom of the riser. In the case of highly viscous non-newtonian solution, the gas flow is strongly affected by the gas distribution just above the gas sparger. This study also points out the bubble coalescence and the break-up phenomena in different liquids and levels in the reactor. Furthermore, the local measurements of bubble size and velocity allows to gain more detailed information on the dynamics of the bubble-flow and shows a tendency of large bubbles to circulate in the column center.     

Design of a novel rotating wall bioreactor for the in vitro simulation of the mechanical environment of the endothelial function

Endothelial cells (ECs), besides being a permeability barrier between the blood and vessel wall, perform many important functions, e.g., cell migration, remodeling, proliferation, and the production, secretion and metabolism of biochemical substances, as well as the regulation of contractility of vascular smooth muscle cells (SMCs). Their function is modulated by chemical ligands as well as mechanical factors. The mechanical stresses acting on the vessel wall include the normal and circumferential stresses that result from the action of blood pressure, the shear stress that acts parallel to the luminal surface of the vessel due to blood flow and the magnitude and orientation of the gravitation field. The aim of this work was to design and construct a novel bioreactor for the stimulation of endothelial cells in vitro with a combination of mechanical factors that simulates their in vivo environment.     

Investigation of the structure of two-phase flow fermentation model media in bubble-column bioreactors

Summary Electrical conductivity microprobes have been used to estimate the transverse variation of bubble size, local gas holdup and local specific gas/liquid interfacial area in bench scale bubble column bioreactors containing fermentation model media. Inserted O₂-electrodes and plane parallel windows alter the structure of the two phase flow. Even slight tilting of the column strongly influences the transverse profiles of the bubble size and local gas holdup. The larger bubbles are collected at the wall, where they can be redispersed. These observations open up new possibilities for the construction of bubble column bioreactors.     

Fluid–structure interaction in aortic cross-clamping: Implications for vessel injury

Vascular cross-clamping is applied in many cardiovascular surgeries such as coronary bypass, aorta repair and valve procedures. Experimental studies have found that clamping of various degrees caused damage to arteries. This study examines the effects of popular clamps on vessel wall. Models of the aorta and clamp were created in Computer Assisted Design and Finite Element Analysis packages. The vessel wall was considered as a non-linear anisotropic material while the fluid was simulated as Newtonian with pulsatile flow. The clamp was applied through displacement time function. Fully coupled two-way solid–fluid interaction models were developed. It was found that the clamp design significantly affected the stresses in vessel wall. The clamp with a protrusion feature increased the overall Von Mises stress by about 60% and the compressive stress by more than 200%. Interestingly, when the protrusion clamp was applied, the Von Mises stress at the lumen (endothelium) side of artery wall was about twice that of the outer wall. This ratio was much higher than that of the plate-like clamp which was about 1.3. The flow reversal process was demonstrated during clamping. Vibrations, flow and wall shear stress oscillations were detected immediately before total vessel occlusion. The commonly used protrusion clamp increased stresses in vessel wall, especially the compressive stress. This design also significantly increased the stresses on endothelium, detrimental to vessel health. The present findings are relevant to surgical clamp design as well as the transient mechanical loading on the endothelium and potential injury. The deformation and stress analysis may provide valuable insights into the mode of tissue injury during cross-clamping.     

A molecular dynamics analysis of homogeneous bubble nucleation with a noncondensable gas in cryogenic cavitation inception

In this paper, homogeneous bubble nucleation in liquid oxygen (as one of the cryogenic fluids) with a noncondensable gas of nitrogen or that of helium was investigated using molecular dynamics method employing a fitted Lennard-Jones potential. We evaluated the influence of nitrogen gas and helium gas on the SATuration line (SAT) and the spinodal line as the thermodynamic limit of stability (TLS), and on the kinetic limit of stability (KLS) defined from a bubble nucleation rate. As a result, it was obtained that the influence of the noncondensable gases on the SAT and the TLS was negligible at molar fraction less than 1% although helium gas had several times stronger action to decrease the KLS compared with nitrogen gas. On the other hand, it was also indicated that the actual influence of both noncondensable gases on the cavitation inception in liquid oxygen might be negligible at least at standard conditions where the fluid starts to flow around or less than the atmospheric pressure.