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Research Papers

Enhanced Targeted Drug Delivery Through Controlled Release in a Three-Dimensional Vascular Tree

[+] Author and Article Information
Shuang J. Zhu

Mechanical Engineering,
The University of Melbourne,
Parkville,
Victoria 3010, Australia
e-mail: sjzhu@unimelb.edu.au

Eric K. W. Poon, Andrew S. H. Ooi

Mechanical Engineering,
The University of Melbourne,
Parkville,
Victoria 3010, Australia

Stephen Moore

IBM Research Collaboratory,
Victoria Life Sciences Computation Initiative,
The University of Melbourne,
Parkville,
Victoria 3010, Australia

Manuscript received September 4, 2013; final manuscript received October 29, 2014; published online January 29, 2015. Assoc. Editor: Francis Loth.

J Biomech Eng 137(3), 031002 (Mar 01, 2015) (8 pages) Paper No: BIO-13-1410; doi: 10.1115/1.4028965 History: Received September 04, 2013; Revised October 29, 2014; Online January 29, 2015

“Controlled particle release and targeting” is a technique using particle release score map (PRSM) and transient particle release score map (TPRSM) via backtracking to determine optimal drug injection locations for achieving an enhanced target efficiency (TE). This paper investigates the possibility of targeting desired locations through an idealized but complex three-dimensional (3D) vascular tree geometry under realistic hemodynamic conditions by imposing a Poiseuille velocity profile and a Womersley velocity profile derived from cine phase contrast magnetic resonance imaging (MRI) data for steady and pulsatile simulations, respectively. The shear thinning non-Newtonian behavior of blood was accounted for by the Carreau–Yasuda model. One-way coupled Eulerian–Lagrangian particle tracking method was used to record individual drug particle trajectories. Particle size and density showed negligible influence on the particle fates. With the proposed optimal release scoring algorithm, multiple optimal release locations were determined under steady flow conditions, whereas there was one unique optimal release location under pulsatile flow conditions. The initial in silico results appear promising, showing on average 66% TE in the pulsatile simulations, warranting further studies to improve the mathematical model and experimental validation.

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Figures

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Fig. 1

The idealized 3D vascular tree geometry used in the present study showing the definition of the anatomical positions, the origin of the Cartesian coordinate system and key design parameters in the root branch of the tree. The naming convention for the 32 outlet branches is shown in the inferior view for clarity.

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Fig. 2

The mean flowrate and flowrate waveforms used in the steady and pulsatile simulations, respectively. Illustrated are 11 key times within the cardiac cycle where planar particles were released.

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Fig. 3

The schematic diagram of the 3D vascular tree geometry viewed from the inlet (see Fig. 1), where branch 12 is the target branch and its direct neighbor is branch 11: (a) left half of the tree branches and (b) right half of the tree branches

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Fig. 4

Instantaneous particle locations throughout the course of a generic steady state simulation at (a) t = 0.01 s, (b) t = 0.08 s, the approximate time at which the fastest moving particles reach the first bifurcation, (c) t = 0.6 s, the approximate time at which the fastest particles exit the domain, and (d) t = 2 s, the end of the simulation at which all particles traveling at the average velocity through the tree should have exited the domain

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Fig. 5

PRM of the 65 nm particles, where the gray color represents the particles that remain in the domain at the end of simulations

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Fig. 8

TPRSMs for branch outlet 9–16 as the targets with normalized PDF values between 0 and 1

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Fig. 7

PRMs of the 65 nm particles over one cardiac cycle. Color codes used to indicate individual outlets and particles remain in the domain at the end of simulations are the same as those used in Fig. 5.

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Fig. 6

PRSMs for branch outlet 9–16 as the targets with normalized PDF values between 0 and 1

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