Magnetic targeting to enhance microbubble delivery in an occluded microarterial bifurcation
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 flu...
| Hoofdauteurs: | , , , , , |
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| Formaat: | Journal article |
| Taal: | English |
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IOP Publishing
2017
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| _version_ | 1826269317276106752 |
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| author | de Saint Victor, M Carugo, D Barnsley, L Owen, J Coussios, C Stride, E |
| author_facet | de Saint Victor, M Carugo, D Barnsley, L Owen, J Coussios, C Stride, E |
| author_sort | de Saint Victor, M |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T21:23:11Z |
| format | Journal article |
| id | oxford-uuid:422f18d3-f734-4a2c-ac9e-394ae40b33d3 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:23:11Z |
| publishDate | 2017 |
| publisher | IOP Publishing |
| record_format | dspace |
| spelling | oxford-uuid:422f18d3-f734-4a2c-ac9e-394ae40b33d32022-03-26T14:47:59ZMagnetic targeting to enhance microbubble delivery in an occluded microarterial bifurcationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:422f18d3-f734-4a2c-ac9e-394ae40b33d3EnglishSymplectic Elements at OxfordIOP Publishing2017de Saint Victor, MCarugo, DBarnsley, LOwen, JCoussios, CStride, EUltrasound 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. |
| spellingShingle | de Saint Victor, M Carugo, D Barnsley, L Owen, J Coussios, C Stride, E Magnetic targeting to enhance microbubble delivery in an occluded microarterial bifurcation |
| title | Magnetic targeting to enhance microbubble delivery in an occluded microarterial bifurcation |
| title_full | Magnetic targeting to enhance microbubble delivery in an occluded microarterial bifurcation |
| title_fullStr | Magnetic targeting to enhance microbubble delivery in an occluded microarterial bifurcation |
| title_full_unstemmed | Magnetic targeting to enhance microbubble delivery in an occluded microarterial bifurcation |
| title_short | Magnetic targeting to enhance microbubble delivery in an occluded microarterial bifurcation |
| title_sort | magnetic targeting to enhance microbubble delivery in an occluded microarterial bifurcation |
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