Hyperacute direct thrombus imaging using computed tomography and gold nanoparticles.

Abstract

OBJECTIVE:

Advancing the understanding and management of thromboembolic stroke requires simple and robust new methods that would be useful for the in vivo assessment of thrombus burden/distribution and for characterizing its evolution in a prompt and quantitative manner.

METHODS:

Animals (n=127) with experimental models of thrombosis were imaged with microcomputed tomography 5 minutes (and/or ~3 weeks) after intravenous injection of glycol chitosan (GC) gold nanoparticles (AuNPs).

RESULTS:

Nanoparticles accumulated in the thrombus, allowing computed tomography visualization of both the presence and extent of primary and recurrent thrombi in mouse carotid arteries without a single failure of detection. Nanoparticle thrombus imaging was also effective in monitoring the therapeutic efficacy of thrombolysis (n=118 tissue plasminogen activator [tPA] therapies). Thrombus evolution (either spontaneous or post-tPA) could be mapped at high resolution in both space and time. Due to a long circulating half-life, GC-AuNPs remain available for entrapment into fibrin matrix for an extended period of time (up to 3 weeks), allowing repetition or ongoing monitoring of thrombogenesis and thrombolysis.

INTERPRETATION:

This is the first report on a hyperacute direct thrombus imaging technique using thrombus-seeking AuNPs and computed tomography. When translated into stroke practice, the thrombus imaging may allow us to advance to personalized thrombolytic therapy by demonstrating thrombus burden, distribution, and character in a prompt and quantitative manner. Further study into this area is indicated.

• Authors: Dong-Eog Kim, Jeong-Yeon Kim, In-Cheol Sun, Dawid Schellingerhout, Su-Kyoung Lee, Cheol-Hee Ahn, Ick Chan Kwon, Kwangmeyung Kim
• Journal: Annals of neurology (Ann Neurol) Vol. 73 Issue 5 Pg. 617-25 (May 2013) ISSN: 1531-8249 [Electronic] United States
• PMID: 23495101 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 American Neurological Association.

Chemical References

• Anticholesteremic Agents
• Gold
• Chitosan
• Tissue Plasminogen Activator

Topics

• Animals
• Animals, Newborn
• Anticholesteremic Agents (therapeutic use)
• Brain Mapping
• Chitosan (therapeutic use)
• Disease Models, Animal
• Gold (therapeutic use)
• Magnetic Resonance Imaging
• Mice
• Mice, Inbred C57BL
• Nanoparticles
• Thrombosis (diagnostic imaging, drug therapy)
• Time Factors
• Tissue Plasminogen Activator (therapeutic use)
• Tomography, X-Ray Computed