Gas Embolotherapy: Vascular Microbubbles for Cancer Treatment Joseph L. Bull, Brijesh Eshpuniyani, Andres J. Calderon, Tao Ye, and J. Brian Fowlkes Department of Biomedical Engineering The University of Michigan [email protected] http://www.umich.edu/~joebull. Introduction.
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Gas Embolotherapy: Vascular Microbubbles for Cancer Treatment
Joseph L. Bull, Brijesh Eshpuniyani, Andres J. Calderon, Tao Ye, and J. Brian Fowlkes
Department of Biomedical Engineering
The University of Michigan
Acoustic Droplet Vaporization
Transport of Emboli
For more details, see: Bull J.L. Critical Reviews in Biomedical Engineering 33(4): 299-346, 2005.
Rigid Tube Wall
Flexible Tube Wall
t (dimensionless) = 0, 0.4, 0.8, 1.2, 1.6, 2, time scale = 10.5 μs
Objective: determine effects of flow rate, bubble size, and gravity on splitting ratio of the bubble in a single bifurcation
Calderón A.J., Fowlkes J.B., and Bull J.L. Bubble splitting in bifurcating tubes: a model study of cardiovascular gas emboli transport. Journal of Applied Physiology, 99: 479-487, 2005.
Experiments θ = 0° □, θ = 15° Δ, θ = 30° ○, θ = 45° ◊, θ = 60° , θ = 90° . Theory θ = 0° ―――, θ = 15° ―― ――, θ = 30° ―― – ―― , θ = 45° …, θ = 60° ――― ―――, θ = 90° ―― – – ――.
Experiments θ = 0° □, θ = 5° Δ, θ = 10° , θ = 15° , θ = 20° ◊, θ = 30° . Theory θ = 0° ―――, θ = 5° ―― ――, θ = 10° ―― – ―― , θ = 15° …, θ = 20° ――― ―――, θ = 30° ―― – – ――.
Higher flow rates will improve homogeneity and there is a critical flow rate below which bubbles will not split
Bubble size relative to vessel size affects splitting behavior
Theory captures behavior of experiments
Resolved apparent paradox between Chang et al. and Souders et al. studies
Acoustic droplet vaporization in small vessels could potentially lead to even distribution of microbubbles
Inertial, viscous, and surface tension forces are important—gravity doesn’t tell the whole story!
Bubble Lodging: Experiments and Theory
Calderón A.J., Heo Y.S., Huh D., Futai N., Takayama S., Fowlkes J.B., and Bull J.L. A microfluidic model of bubble lodging in microvessel bifurcations. Applied Physics Letters, 89(24): Art. No. 244103, 2006.
Bubble Lodging and Dislodging Pressures
Dimensionless Bubble Lodging Pressure vs. Diameter Ratio
Blood Flow Occlusion In Vivo
Kripfgans OD, et al., IEEE Transactions on Ultrasonics Ferroelectrics and Frequency Control. 52(7): 1101-1110, 2005.