Joseph L. Bull

Tear size and location impacts false lumen pressure in an ex vivo model of chronic type B aortic dissection.

BACKGROUND Follow-up mortality is high in patients with type B aortic dissection (TB-AD) approaching one in four patients at 3 years. A predictor of increased mortality is partial thrombosis of the false lumen which may occlude distal tears. The hemodynamic consequences of differing tear size, location, and patency within the false lumen is largely unknown. We examined the impact of intimal tear size, tear number, and location on false lumen pressure. METHODS In an ex-vivo model of chronic type B aortic dissection connected to a pulsatile pump, simultaneous pressures were measured within the true and false lumen. Experiments were performed in different dissection models with tear sizes of 6.4 mm and 3.2 mm in the following configurations; model A: proximal and distal tear simulating the most common hemodynamic state in patients with TB-AD; model B: proximal tear only simulating patients with partial thrombosis and occlusion of distal tear; and model C: distal tear only simulating patients sealed proximally via a stent graft with persistent distal communication. To compare false lumen diastolic pressure between models, a false lumen pressure index (FPI%) was calculated for all simulations as FPI% = (false lumen diastolic pressure/true lumen diastolic pressure) x 100. RESULTS In model A, the systolic pressure was slightly lower in the false lumen compared with the true lumen while the diastolic pressure (DP) was slightly higher in the false lumen (DP 66.45 +/- 0.16 mm Hg vs 66.20 +/- 0.12 mm Hg, P < .001, FPI% = 100.4%). In the absence of a distal tear (model B), diastolic pressure was elevated within the false lumen compared with the true lumen (58.95 +/- 0.10 vs 54.66 +/- 0.17, P < .001, FPI% = 107.9%). The absence of a proximal tear in the presence of a distal tear (model C) diastolic pressure was also elevated within the false lumen versus the true lumen (58.72 +/- 0.24 vs 56.15 +/- 0.16, P < .001, FPI% 104.6%). The difference in diastolic pressure was greatest with a smaller tear (3.2 mm) in model B. In model B, DBP increased by 13.9% (P < .001, R(2) 0.69) per 10 beat per minute increase in heart rate (P < .001) independent of systolic pressure. CONCLUSIONS In this model of chronic type B aortic dissection, diastolic false lumen pressure was the highest in the setting of smaller proximal tear size and the lack of a distal tear. These determinants of inflow and outflow may impact false lumen expansion and rupture during the follow-up period.

The application of microbubbles for targeted drug delivery

Interest in microbubbles as vehicles for drug delivery has grown in recent years, due in part to characteristics that make them well suited for this role and in part to the need the for localized delivery of drugs in a number of applications. Microbubbles are inherently small, allowing transvascular passage, they can be functionalized for targeted adhesion, and can be acoustically driven, which facilitates ultrasound detection, production of bioeffects and controlled release of the cargo. This article provides an overview of related microbubble biofluid mechanics and reviews recent developments in the application of microbubbles for targeted drug delivery. Additionally, related advances in non-bubble microparticles for drug delivery are briefly described in the context of targeted adhesion.

Bubble evolution in acoustic droplet vaporization at physiological temperature via ultra-high speed imaging

Acoustic droplet vaporization in a rigid tube at body temperature was investigated experimentally using an ultra-high speed camera. This study was motivated by gas embolotherapy, a developmental cancer treatment in which gas microbubbles that are selectively formed by acoustically vaporizing liquid droplets in vivo are used to occlude tumor blood flow. The evolution of microbubbles formed by acoustic droplet vaporization was analyzed and a four-stage empirical curve was fit to the growth. Viscous resistance from the tube was shown to dampen oscillations of the microbubbles even though the bubble diameter was smaller than the tube diameter. The results suggest that, for some parameter values, vaporization may still be occurring when the bubble expansion starts and indicate the importance of this in modeling the growth of bubbles formed by acoustic droplet vaporization.

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.

Dynamics of acoustic droplet vaporization in gas embolotherapy

Acoustic droplet vaporization is investigated in a theoretical model. This work is motivated by gas embolotherapy, a developmental cancer treatment involving tumor infarction with gas microbubbles that are selectively formed from liquid droplets. The results indicate that there exists a threshold value for initial droplet size below which the bubble evolution is oscillatory and above which it is smooth and asymptotic, and show that the vaporization process affects the subsequent microbubble expansion. Dampening of the bubble expansion is observed for higher viscosity and surface tension, with effects more pronounced for droplet size less than 6 mum in radius.

Microfluidic particle sorting utilizing inertial lift force

A simple passive microfluidic device that continuously separates microparticles is presented. Its development is motivated by the need for specific size micro perfluorocarbon (PFC) droplets to be used for a novel gas embolotherapy method. The device consists of a rectangular channel in which inertial lift forces are utilized to separate particles in lateral distance. At the entrance of the channel, particles are introduced at the center by focusing the flow from a center channel with flow from two side channels. Downstream, large particles will occupy a lateral equilibrium position in shorter axial distance than small particles. At the exit of the channel, flow containing large particles is separated from flow containing small particles. It is shown that 10.2-μm diameter microspheres can be separated from 3.0-μm diameter microspheres with a separation efficiency of 69–78% and a throughput in the order of 2 ·104 particles per minute. Computational Fluid Dynamics (CFD) calculations were done to calculate flow fields and verify theoretical particle trajectories. Theory underlying this research shows that higher separation efficiencies for very specific diameter cut-off are possible. This microfluidic channel design has a simple structure and can operate without external forces which makes it feasible for lab-on-a-chip (LOC) applications.

Surfactant-spreading and surface-compression disturbance on a thin viscous film

Spreading of a new surfactant in the presence of a pre-existing surfactant distribution is investigated both experimentally and theoretically for a thin viscous substrate. The experiments are designed to provide a better understanding of the fundamental interfacial and fluid dynamics for spreading of surfactants instilled into the lung. Quantitative measurements of spreading rates were conducted using a fluorescent new surfactant that was excited by argon laser light as it spread on an air-glycerin interface in a petri dish. It is found that pre-existing surfactant impedes surfactant spreading. However, fluorescent microspheres used as surface markers show that pre-existing surfactant facilitates the propagation of a surface-compression disturbance, which travels faster than the leading edge of the new surfactant. The experimental results compare well with the theory developed using lubrication approximations. An effective diffusivity of the thin film system is found to be Deff = (E*gamma)/(mu/H), which indicates that the surface-compression disturbance propagates faster for larger background surfactant concentration, gamma, larger constant slope of the sigma*-gamma* relation, -E*, and smaller viscous resistance, mu/H. Note that sigma* and gamma* are the dimensional surface tension and concentration, respectively, mu is fluid viscosity, and H is the unperturbed film thickness.

An Ex Vivo Study of the Correlation between Acoustic Emission and Microvascular Damage

The objective of this study was to conduct an ex vivo examination of correlation between acoustic emission and tissue damage. Intravital microscopy was employed in conjunction with ultrasound exposure in cremaster muscle of male Wistar rats. Definity microbubbles were administered intravenously through the tail vein (80microL.kg(-1).min(-1)infusion rate) with the aid of a syringe pump. For the pulse repetition frequency (PRF) study, exposures were performed at four locations of the cremaster at a PRF of 1000, 500, 100 and 10Hz (one location per PRF per rat). The 100-pulse exposures were implemented at a peak rarefactional pressure (P(r)) of 2MPa, frequency of 2.25MHz with 46 cycle pulses. For the pressure amplitude threshold study, 100-pulse exposures (46 cycle pulses) were conducted at various peak rarefactional pressures from 0.5MPa to 2MPa at a frequency of 2.25MHz and PRF of 100Hz. Photomicrographs were captured before and 2-min postexposure. On a pulse-to-pulse basis, the 10Hz acoustic emission was considerably higher and more sustained than those at other PRFs (1000, 500, and 100Hz) (p<0.05). Damage, measured as area of extravasation of red blood cells (RBCs), was also significantly higher at 10Hz PRF than at 1000, 500 and 100Hz (p<0.01). The correlation of acoustic emission to tissue damage showed a trend of increasing damage with increasing cumulative function of the relative integrated power spectrum (CRIPS; R(2)=0.75). No visible damage was present at P(r)< or =0.85MPa. Damage, however, was observed at P(r)> or =1.0MPa and it increased with increasing acoustic pressure.

Microfluidic model of bubble lodging in microvessel bifurcations

The lodging mechanisms and dynamics of cardiovascular gas bubbles are investigated in microfluidic model bifurcations made of poly(dimethylsiloxane). This work is motivated by gas embolotherapy for the potential treatment of cancer by tumor infarction. The results show that the critical driving pressure below which a bubble will lodge in a bifurcation is significantly less than the driving pressure required to dislodge it. From the results the authors estimate that gas bubbles from embolotherapy can lodge in vessels 20μm or smaller in diameter, and conclude that bubbles may potentially be used to reduce blood flow to tumor microcirculation.

A prototype of a liquid ventilator using a novel hollow-fiber oxygenator in a rabbit model

Objective:A functional total liquid ventilator should be simple in design to minimize operating errors and have a low priming volume to minimize the amount of perfluorocarbon needed. Closed system circuits using a membrane oxygenator have partially met these requirements but have high resistance to perfluorocarbon flow and high priming volume. To further this goal, a single piston prototype ventilator with a low priming volume and a new high-efficiency hollow-fiber oxygenator in a circuit with a check valve flow control system was developed. Design:Prospective, controlled animal laboratory study. Setting:Research facility at a university medical center. Subjects:Seven anesthetized, paralyzed, normal New Zealand rabbits Interventions:The prototype oxygenator, consisting of cross-wound silicone hollow fibers with a surface area of 1.5 m2 with a priming volume of 190 mL, was tested in a bench-top model followed by an in vivo rabbit model. Total liquid ventilation was performed for 3 hrs with 20 mL·kg−1 initial fill volume, 17.5–20 mL·kg−1 tidal volume, respiratory rate of 5 breaths/min, inspiratory/expiratory ratio 1:2, and countercurrent sweep gas of 100% oxygen. Measurements and Main Results:Bench top experiments demonstrated 66–81% elimination of Co2 and 0.64–0.76 mL·min−1 loss of perfluorocarbon across the fibers. No significant changes in Paco2 and Pao2 were observed. Dynamic airway pressures were in a safe range in which ventilator lung injury or airway closure was unlikely (3.6 ± 0.5 and −7.8 ± 0.3 cm H2O, respectively, for mean peak inspiratory pressure and mean end expiratory pressure). No leakage of perfluorocarbon was noted in the new silicone fiber gas exchange device. Estimated in vivo perfluorocarbon loss from the device was 1.2 mL·min−1. Conclusions:These data demonstrate the ability of this novel single-piston, nonporous hollow silicone fiber oxygenator to adequately support gas exchange, allowing successful performance of total liquid ventilation.