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 (n5127) 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 (n5118 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.