RESUMEN
BACKGROUND AND OBJECTIVE: Embolotherapy has been increasingly used to disrupt tumor growth. Despite its success in the occlusion of microvessels, it has drawbacks such as limited access to the target location, limited control of the blocker size, and inattention to the tumor characteristics, especially high interstitial fluid pressure. The present work introduces a novel numerical method of gas embolotherapy for cancer treatment through tumor vessel occlusion. METHODS: The gas microbubbles are generated from Levovist bolus injection into the tumor microvessel. The microbubble movement in the blood flow is innovatively controlled by an electric field applied to the tumor-feeding vessel. The interaction between the Levovist microbubbles and the electric field is resolved by developing a fully coupled model using the phase-field model, Carreau model for non-Newtonian blood, Navier-Stokes equations and Maxwell stress tensor. Additionally, the critical effect of high interstitial fluid pressure as a characteristic of solid tumors is included. RESULTS: The findings of this study indicate that the rates of microbubble deformation and displacement increase with the applied potential intensity to the microvessel wall. Accordingly, the required time for a microbubble to join the upper microvessel wall reduces from 1.97ms to 22â µs with an increase of the electric potential from 3.5V to 12.5V. Additionally, an electric potential of 12.5V causes the microbubbles coalescence and formation of a gas column against the bloodstream. CONCLUSIONS: Clinically, our novel embolization procedure can be considered a non-invasive targeted therapy, and under a controlled electric field, the blocker size can be precisely controlled. Also, the proposed method has the potential to be used as a gradual treatment in advanced cancers as tumors develop resistance and relapse.
Asunto(s)
Embolización Terapéutica , Neoplasias , Enfermedades Vasculares , Humanos , Microburbujas , Embolización Terapéutica/métodos , Microvasos , Neoplasias/terapia , Medios de ContrasteRESUMEN
Gas embolotherapy (GE) is a developing medical method which can be utilized either as an autonomous therapeutic method to treat vascularized solid tumors, or it can be combined with other medical procedures-such as high-intensity focused ultrasound-to improve their efficiency. This paper is dedicated to investigating the different parameters which influence bubble lodging inside human vasculature via 2D-modeling of bubble dynamics in arteries' and arterioles' bifurcations which are potential sticking positions. Values used in the simulations are in accordance with the non-dimensional physiological numbers. It is found out that inlet pressure plays a decisive role in bubble lodging; the lower the value, the higher the possibility of bubble sticking. On the other hand, gravity has a counteracting effect on bubble lodging in arteries, but not on arterioles. The initial length of the bubble is not a determining factor in sticking behavior, even though it affects the flow rate behavior. Surface tension, another critical factor, has a semi-linear impact on bubble resisting power; lowering the surface tension will reduce bubble resistance to the flow, diminishing the possibility of bubble lodging. Finally, it is shown that lower values for the static contact angle impose higher resistance to the flow.
Asunto(s)
Arterias , Embolización Terapéutica , HumanosRESUMEN
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.
Asunto(s)
Microburbujas , Modelos Teóricos , Arterias/fisiología , Embolización Terapéutica , Fricción , Humanos , Análisis Numérico Asistido por Computador , Piel , Estrés MecánicoRESUMEN
Gas embolotherapy is achieved by locally vaporizing microdroplets through acoustic droplet vaporization, which results in bubbles that are large enough to occlude blood flow directed to tumors. Endothelial cells, lining blood vessels, can be affected by these vaporization events, resulting in cell injury and cell death. An idealized monolayer of endothelial cells was subjected to acoustic droplet vaporization using a 3.5-MHz transducer and dodecafluoropentane droplets. Treatments included insonation pressures that varied from 2 to 8 MPa (rarefactional) and pulse lengths that varied from 4 to 16 input cycles. The bubble cloud generated was directly dependent on pressure, but not on pulse length. Cellular damage increased with increasing bubble cloud size, but was limited to the bubble cloud area. These results suggest that vaporization near the endothelium may impact the vessel wall, an effect that could be either deleterious or beneficial depending on the intended overall therapeutic application.