Inside-out Ultraviolet-C Sterilization of Pseudomonas aeruginosa Biofilm In Vitro.

Biofilms are difficult to eradicate due to a protective architecture and create major challenges in patient care by diminishing both host immune response and therapeutic approaches. This study investigated a new strategy for treating surface-attached biofilms by delivering germicidal UV through a material surface in a process referred to as "inside-out sterilization" (IOS). Mature Pseudomonas aeruginosa (ATCC® 27853™ ) biofilms were irradiated with up to 1400 mJ cm-2 of germicidal UV from both ambient and IOS configurations. The lethal dose for the ambient exposure group was 461 mJ cm-2 95% CI [292, 728] compared to the IOS treatment group of 247 mJ cm-2 95% CI [187, 325], corresponding to 47% less UV dosage for the IOS group (P < 0.05). This study demonstrated that with IOS, a lower quantal dosage of UV energy is required to eradicate biofilm than with ambient exposure by leveraging the organizational structure of the biofilm.

Biplane angiography for experimental validation of computational fluid dynamic models of blood flow in artificial lungs.

This article presents an investigation into the validation of velocity fields obtained from computational fluid dynamic (CFD) models of flow through the membrane oxygenators using x-ray digital subtraction angiography (DSA). Computational fluid dynamic is a useful tool in characterizing artificial lung devices, but numerical results must be experimentally validated. We used DSA to visualize flow through a membrane oxygenator at 2 L/min using 37% glycerin at 22°C. A Siemens Artis Zee system acquired biplane x-ray images at 7.5 frames per second, after infusion of an iodinated contrast agent at a rate of 33 ml/s. A maximum cross-correlation (MCC) method was used to track the contrast perfusion through the fiber bundle. For the CFD simulations, the fiber bundle was treated as a single momentum sink according to the Ergun equation. Blood was modeled as a Newtonian fluid, with constant viscosity (3.3 cP) and density (1050 kg/m3). Although CFD results and experimental pressure measurements were in general agreement, the simulated 2 L/min perfusion did not reproduce the flow behavior seen in vitro. Simulated velocities in the fiber bundle were on average 42% lower than experimental values. These results indicate that it is insufficient to use only pressure measurements for validation of the flow field because pressure-validated CFD results can still significantly miscalculate the physical velocity field. We have shown that a clinical x-ray modality, together with a MCC tracking algorithm, can provide a nondestructive technique for acquiring experimental data useful for validation of the velocity field inside membrane oxygenators.

Improved computational fluid dynamic simulations of blood flow in membrane oxygenators from X-ray imaging.

Computational fluid dynamics (CFD) is a useful tool in characterizing artificial lung designs by providing predictions of device performance through analyses of pressure distribution, perfusion dynamics, and gas transport properties. Validation of numerical results in membrane oxygenators has been predominantly based on experimental pressure measurements with little emphasis placed on confirmation of the velocity fields due to opacity of the fiber membrane and limitations of optical velocimetric methods. Biplane X-ray digital subtraction angiography was used to visualize flow of a blood analogue through a commercial membrane oxygenator at 1-4.5 L/min. Permeability and inertial coefficients of the Ergun equation were experimentally determined to be 180 and 2.4, respectively. Numerical simulations treating the fiber bundle as a single momentum sink according to the Ergun equation accurately predicted pressure losses across the fiber membrane, but significantly underestimated velocity magnitudes in the fiber bundle. A scaling constant was incorporated into the numerical porosity and reduced the average difference between experimental and numerical values in the porous media regions from 44 ± 4% to 6 ± 5%.

Numerical and experimental flow analysis of the Wang-Zwische double-lumen cannula.

An experimental and numerical analysis was performed for the Wang-Zwische double-lumen cannula (DLC) (Avalon Elite). The aim of this work was to provide insight for future improvement by characterizing the fluid dynamic behavior of the novel catheter with metrics often associated with blood trauma. Pressure and flow distributions were measured on a steady-flow rig using a 50% glycerol-water mixture by imposing a 2 L/min flow rate across the drainage and infusion lumens. The fluid was modeled as Newtonian with density of 1050 kg/m³ and dynamic viscosity of 0.0035 kg/m·s. Reynolds numbers typical for transitional flow (Re = 2000-2500) were computed within the lumens because of the changing cross-sections of the cannula geometry. Numerical computations were performed using the steady three-dimensional Reynolds-averaged Navier-Stokes (RANS) equations and the low-Reynolds k-ω turbulence model. Discretization of governing equations was based on a cell-centered finite volume method. Numerical results correlated well with global performance of the cannula, allowing evaluation of the geometry toward potential blood trauma. Peak wall shear stress (WSS) in the drainage lumen was higher than that of infusion lumen, mainly due to the presence of side holes. Furthermore, recirculation regions were predicted in transition tubing to connectors of both the drainage and the infusion lumens because of adverse pressure gradients caused by the sudden enlargement of the cannula geometry. In this three-dimensional computational fluid dynamics (CFD) study, we observed higher peak WSS values for the drainage lumen, which may potentially cause blood trauma. Furthermore, recirculation regions were predicted in the proximity of the exit sections of both the infusion and drainage lumens, which may contribute to thrombosis formation. This study provides insight for future DLC modifications in minimizing cannula-induced blood trauma and thrombogenicity in long-term applications.

Noninvasive assessment of tumor vasculature response to radiation-mediated, vasculature-targeted therapy using quantified power Doppler sonography: implications for improvement of therapy schedules.

OBJECTIVE: Stereotactic radiotherapy (ablative radiation) is a modality that holds considerable promise for effective treatment of intracranial and extracranial malignancies. Although tumor vasculature is relatively resistant to small fractionated doses of ionizing radiation, large ablative doses of ionizing radiation lead to effective demise of the tumor vasculature. The purpose of this study was (1) to noninvasively monitor and compare tumor physiologic parameters in response to ablative radiation treatments and (2) to use these noninvasive parameters to optimize the schedule of administration of radiation therapy. METHODS: Lewis lung carcinoma tumors were implanted into C57BL/6 mice and treated with ablative radiation. The kinetics of change in physiologic parameters of a response to single-dose 20-Gy treatments was measured. Parameters studied included tumor blood flow, apoptosis, and proliferation rates. Serial tumor sections were stained to correlate noninvasive Doppler assessment of tumor blood flow with microvasculature histologic findings. RESULTS: A single administration of 20 Gy led to an incomplete tumor vascular response, with subsequent recovery of tumor blood flow within 4 days after treatment. Sustained reduction of tumor blood flow by administering the successive ablative radiation treatment before tumor blood flow recovery led to a 3-fold tumor growth delay. The difference in tumor volumes at each measurement time point (every 2 days) was statistically significant (P=.016). CONCLUSIONS: This study suggests a rational design of schedule optimization for radiation-mediated, vasculature-directed treatments guided by noninvasive assessment of tumor blood flow levels to ultimately improve the tumor response.