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@ARTICLE{deSaintVictor:837521,
author = {de Saint Victor, M. and Carugo, D. and Barnsley, L. C. and
Owen, J. and Coussios, C-C and Stride, E.},
title = {{M}agnetic targeting to enhance microbubble delivery in an
occluded microarterial bifurcation},
journal = {Physics in medicine and biology},
volume = {62},
number = {18},
issn = {1361-6560},
address = {Bristol},
publisher = {IOP Publ.},
reportid = {FZJ-2017-06416},
pages = {7451 - 7470},
year = {2017},
abstract = {Ultrasound and microbubbles have been shown to accelerate
the breakdown of blood clots both in vitro and in vivo.
Clinical translation of this technology is still limited,
however, in part by inefficient microbubble delivery to the
thrombus. This study examines the obstacles to delivery
posed by fluid dynamic conditions in occluded vasculature
and investigates whether magnetic targeting can improve
microbubble delivery. A 2D computational fluid dynamic model
of a fully occluded Y-shaped microarterial bifurcation was
developed to determine: (i) the fluid dynamic field in the
vessel with inlet velocities from 1–100 mm s−1
(corresponding to Reynolds numbers 0.25–25); (ii) the
transport dynamics of fibrinolytic drugs; and (iii) the flow
behavior of microbubbles with diameters in the
clinically-relevant range (0.6–5 µm). In vitro
experiments were carried out in a custom-built microfluidic
device. The flow field was characterized using tracer
particles, and fibrinolytic drug transport was assessed
using fluorescence microscopy. Lipid-shelled magnetic
microbubbles were fluorescently labelled to determine their
spatial distribution within the microvascular model. In both
the simulations and experiments, the formation of laminar
vortices and an abrupt reduction of fluid velocity were
observed in the occluded branch of the bifurcation, severely
limiting drug transport towards the occlusion. In the
absence of a magnetic field, no microbubbles reached the
occlusion, remaining trapped in the first vortex, within 350
µm from the bifurcation center. The number of microbubbles
trapped within the vortex decreased as the inlet velocity
increased, but was independent of microbubble size.
Application of a magnetic field (magnetic flux density of 76
mT, magnetic flux density gradient of 10.90 T m−1 at the
centre of the bifurcation) enabled delivery of microbubbles
to the occlusion and the number of microbubbles delivered
increased with bubble size and with decreasing inlet
velocity.},
cin = {JCNS (München) ; Jülich Centre for Neutron Science JCNS
(München) ; JCNS-FRM-II / Neutronenstreuung ; JCNS-1},
ddc = {570},
cid = {I:(DE-Juel1)JCNS-FRM-II-20110218 /
I:(DE-Juel1)JCNS-1-20110106},
pnm = {6G15 - FRM II / MLZ (POF3-6G15) / 6G4 - Jülich Centre for
Neutron Research (JCNS) (POF3-623)},
pid = {G:(DE-HGF)POF3-6G15 / G:(DE-HGF)POF3-6G4},
experiment = {EXP:(DE-MLZ)NOSPEC-20140101},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000409379600007},
pubmed = {pmid:28796644},
doi = {10.1088/1361-6560/aa858f},
url = {https://juser.fz-juelich.de/record/837521},
}