On-demand degradable embolic microspheres for immediate restoration of blood flow during image-guided embolization procedures

Hyunjun Choi; Bongseo Choi; Bo Yu; Weiguo Li; Monica M. Matsumoto; Kathleen R. Harris; Robert J. Lewandowski; Andrew C. Larson; Samdeep K. Mouli; Dong Hyun Kim

doi:10.1016/j.biomaterials.2020.120408

On-demand degradable embolic microspheres for immediate restoration of blood flow during image-guided embolization procedures

Hyunjun Choi, Bongseo Choi, Bo Yu, Weiguo Li, Monica M. Matsumoto, Kathleen R. Harris, Robert J. Lewandowski, Andrew C. Larson, Samdeep K. Mouli, Dong Hyun Kim^*

^*Corresponding author for this work

Radiology

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

Abstract

Degradable embolic agents that provide transient arterial occlusion during embolization procedures have been of interest for many years. Ideally, embolic agents are visible with standard imaging modalities and offer on-demand degradability, permitting physicians to achieve desired arterial occlusion tailored to patient and procedure indication. Subsequent arterial recanalization potentially enhances the overall safety and efficacy of embolization procedures. Here, we report on-demand degradable and MRI-visible microspheres for embolotherapy. Embolic microspheres composed of calcium alginate and USPIO nanoclusters were synthesized with an air spray atomization and coagulation reservoir equipped with a vacuum suction. An optimized distance between spray nozzle and reservoir allowed uniform size and narrow size distribution of microspheres. The fabricated alginate embolic microspheres crosslinked with Ca²⁺ demonstrated highly responsive on-demand degradation properties in vitro and in vivo. Finally, the feasibility of using the microspheres for clinical embolization and recanalization procedures was evaluated with interventional radiologists in rabbits. Digital subtraction angiography (DSA) guided embolization of hepatic arteries with these embolic microspheres was successfully performed and the occlusion of artery was confirmed with DSA images and contrast enhanced MRI. T2 MRI visibility of the microspheres allowed to monitor the distribution of intra-arterial (IA) infused embolic microspheres. Subsequent on-demand image-guided recanalization procedures were also successfully performed with rapid degradation of microspheres upon intra-arterial infusion of an ion chelating agent. These instant degradable embolic microspheres will permit effective on-demand embolization/recanalization procedures offering great promise to overcome limitations of currently available permanent and biodegradable embolic agents.

Original language	English (US)
Article number	120408
Journal	Biomaterials
Volume	265
DOIs	https://doi.org/10.1016/j.biomaterials.2020.120408
State	Published - Jan 2021

Funding

This work was mainly supported by grants R01CA218659 and R01EB026207 from the National Cancer Institute and National Institute of Biomedical Imaging and Bioengineering . This work was also supported by the Center for Translational Imaging and Mouse Histology and Phenotyping Laboratory at Northwestern University .

Keywords

Embolic agents
Embolization
Embolotherapy
Interventional radiology
On-demand degradable microspheres

ASJC Scopus subject areas

Biophysics
Bioengineering
Ceramics and Composites
Biomaterials
Mechanics of Materials

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10.1016/j.biomaterials.2020.120408

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title = "On-demand degradable embolic microspheres for immediate restoration of blood flow during image-guided embolization procedures",

abstract = "Degradable embolic agents that provide transient arterial occlusion during embolization procedures have been of interest for many years. Ideally, embolic agents are visible with standard imaging modalities and offer on-demand degradability, permitting physicians to achieve desired arterial occlusion tailored to patient and procedure indication. Subsequent arterial recanalization potentially enhances the overall safety and efficacy of embolization procedures. Here, we report on-demand degradable and MRI-visible microspheres for embolotherapy. Embolic microspheres composed of calcium alginate and USPIO nanoclusters were synthesized with an air spray atomization and coagulation reservoir equipped with a vacuum suction. An optimized distance between spray nozzle and reservoir allowed uniform size and narrow size distribution of microspheres. The fabricated alginate embolic microspheres crosslinked with Ca2+ demonstrated highly responsive on-demand degradation properties in vitro and in vivo. Finally, the feasibility of using the microspheres for clinical embolization and recanalization procedures was evaluated with interventional radiologists in rabbits. Digital subtraction angiography (DSA) guided embolization of hepatic arteries with these embolic microspheres was successfully performed and the occlusion of artery was confirmed with DSA images and contrast enhanced MRI. T2 MRI visibility of the microspheres allowed to monitor the distribution of intra-arterial (IA) infused embolic microspheres. Subsequent on-demand image-guided recanalization procedures were also successfully performed with rapid degradation of microspheres upon intra-arterial infusion of an ion chelating agent. These instant degradable embolic microspheres will permit effective on-demand embolization/recanalization procedures offering great promise to overcome limitations of currently available permanent and biodegradable embolic agents.",

keywords = "Embolic agents, Embolization, Embolotherapy, Interventional radiology, On-demand degradable microspheres",

author = "Hyunjun Choi and Bongseo Choi and Bo Yu and Weiguo Li and Matsumoto, {Monica M.} and Harris, {Kathleen R.} and Lewandowski, {Robert J.} and Larson, {Andrew C.} and Mouli, {Samdeep K.} and Kim, {Dong Hyun}",

note = "Publisher Copyright: {\textcopyright} 2020 Elsevier Ltd",

year = "2021",

month = jan,

doi = "10.1016/j.biomaterials.2020.120408",

language = "English (US)",

volume = "265",

journal = "Biomaterials",

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T1 - On-demand degradable embolic microspheres for immediate restoration of blood flow during image-guided embolization procedures

AU - Choi, Hyunjun

AU - Choi, Bongseo

AU - Yu, Bo

AU - Li, Weiguo

AU - Matsumoto, Monica M.

AU - Harris, Kathleen R.

AU - Lewandowski, Robert J.

AU - Larson, Andrew C.

AU - Mouli, Samdeep K.

AU - Kim, Dong Hyun

PY - 2021/1

Y1 - 2021/1

N2 - Degradable embolic agents that provide transient arterial occlusion during embolization procedures have been of interest for many years. Ideally, embolic agents are visible with standard imaging modalities and offer on-demand degradability, permitting physicians to achieve desired arterial occlusion tailored to patient and procedure indication. Subsequent arterial recanalization potentially enhances the overall safety and efficacy of embolization procedures. Here, we report on-demand degradable and MRI-visible microspheres for embolotherapy. Embolic microspheres composed of calcium alginate and USPIO nanoclusters were synthesized with an air spray atomization and coagulation reservoir equipped with a vacuum suction. An optimized distance between spray nozzle and reservoir allowed uniform size and narrow size distribution of microspheres. The fabricated alginate embolic microspheres crosslinked with Ca2+ demonstrated highly responsive on-demand degradation properties in vitro and in vivo. Finally, the feasibility of using the microspheres for clinical embolization and recanalization procedures was evaluated with interventional radiologists in rabbits. Digital subtraction angiography (DSA) guided embolization of hepatic arteries with these embolic microspheres was successfully performed and the occlusion of artery was confirmed with DSA images and contrast enhanced MRI. T2 MRI visibility of the microspheres allowed to monitor the distribution of intra-arterial (IA) infused embolic microspheres. Subsequent on-demand image-guided recanalization procedures were also successfully performed with rapid degradation of microspheres upon intra-arterial infusion of an ion chelating agent. These instant degradable embolic microspheres will permit effective on-demand embolization/recanalization procedures offering great promise to overcome limitations of currently available permanent and biodegradable embolic agents.

AB - Degradable embolic agents that provide transient arterial occlusion during embolization procedures have been of interest for many years. Ideally, embolic agents are visible with standard imaging modalities and offer on-demand degradability, permitting physicians to achieve desired arterial occlusion tailored to patient and procedure indication. Subsequent arterial recanalization potentially enhances the overall safety and efficacy of embolization procedures. Here, we report on-demand degradable and MRI-visible microspheres for embolotherapy. Embolic microspheres composed of calcium alginate and USPIO nanoclusters were synthesized with an air spray atomization and coagulation reservoir equipped with a vacuum suction. An optimized distance between spray nozzle and reservoir allowed uniform size and narrow size distribution of microspheres. The fabricated alginate embolic microspheres crosslinked with Ca2+ demonstrated highly responsive on-demand degradation properties in vitro and in vivo. Finally, the feasibility of using the microspheres for clinical embolization and recanalization procedures was evaluated with interventional radiologists in rabbits. Digital subtraction angiography (DSA) guided embolization of hepatic arteries with these embolic microspheres was successfully performed and the occlusion of artery was confirmed with DSA images and contrast enhanced MRI. T2 MRI visibility of the microspheres allowed to monitor the distribution of intra-arterial (IA) infused embolic microspheres. Subsequent on-demand image-guided recanalization procedures were also successfully performed with rapid degradation of microspheres upon intra-arterial infusion of an ion chelating agent. These instant degradable embolic microspheres will permit effective on-demand embolization/recanalization procedures offering great promise to overcome limitations of currently available permanent and biodegradable embolic agents.

KW - Embolic agents

KW - Embolization

KW - Embolotherapy

KW - Interventional radiology

KW - On-demand degradable microspheres

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VL - 265

JO - Biomaterials

JF - Biomaterials

M1 - 120408

ER -

On-demand degradable embolic microspheres for immediate restoration of blood flow during image-guided embolization procedures

Abstract

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Keywords

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