Detection of Arterial Vascular Disorders and Macrophage Accumulation Using Diffusion Reflection Measurements with Gold Nanorods

Dorit Leshem-Lev 1 Rinat Ankri 2 Dror Fixler 2 Rachela Popovtzer 2 Menachem Motiei 2 Edit Hochhauser 1 Ran Kornowski 1 Eli Lev 1
1Cardiology, Rabin Medical Center-FMRC
2Faculty of Engineering, Bar Ilan University

Atherosclerosis and its consequences are thought to be a major cause of premature morbidity and death. Formation of macrophage foam cells in the intima and inflammation are hallmarks of atherosclerosis and contribute to the initiation, progression, and rupture of lipid-rich vascular lesions.

Despite the rapid progression in imaging techniques to detect atherosclerosis, the identification of inflamed “active” lesions within the coronary circulation, prone to rupture remains elusive. Accordingly, the aim of our study was to develop a new non-invasive method to detect in the atherosclerosis inflamed plaques, based on macrophages accumulation.

Recently, gold nanoparticles (GNP) combined with the diffusion reflection (DR) method have demonstrated great potential for detection, and therapy as drug carriers in various disease states. , We hypothesized that the GNP/DR technique may be used for the detection of unstable inflamed atherosclerotic plaques.

In this study we report the use of gold nanorods (GNRs) as absorption contrast agents in the diffusion reflection (DR) method for the in vivo detection of atherosclerotic injury, based on macrophage accumulation.

We demonstrated that macrophages, which are a major component of unstable “vulnerable” atherosclerotic plaques, are able to uptake GNP in culture conditions in vitro, resulting in a change in the optical properties of tissue-like phantoms and a unique DR measurement. We have also shown in vivo; using a rat model of balloon injured carotid artery, that the DR- GNP combined method enables the detection of macrophages accumulation following vascular injury. Furthermore the difference between the injured arteries compared with healthy arteries was shown clearly by both DR profiles and high resolution CT.

Based on these findings, we believe that the combined DR-GNP method provide a potential novel detection tool for identification of atherosclerosis at its early stages, especially the detection of unstable atherosclerotic plaques.









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