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ECHOCARDIOGRAPHY

Detection of retained microbubbles in carotid arteries with real-time low mechanical index imaging in the setting of endothelial dysfunction

Jeane M. Tsutsui, MD^*, Feng Xie, MD^*, Martin Cano, BS, James Chomas, PhD, Patrick Phillips, PhD, Stanley J. Radio, MD, John Lof, MS^* and Thomas R. Porter, MD, FACC^*,*

^* Section of Cardiology, University of Nebraska Medical Center, Omaha, Nebraska, USA
Department of Pathology, University of Nebraska Medical Center, Omaha, Nebraska, USA
Siemens Medical Solutions, Mountain View, California, USA

Manuscript received March 30, 2004; revised manuscript received May 13, 2004, accepted May 18, 2004.

^* Reprint requests and correspondence: Dr. Thomas R. Porter, University of Nebraska Medical Center, 981165 Nebraska Medical Center, Omaha, Nebraska 68198-1165 (Email: trporter{at}unmc.edu).

OBJECTIVES: We sought to determine if intravenously injected microbubbles would be retained by the carotid arteries (CAs) in the setting of endothelial dysfunction (ED) using a linear transducer equipped with a low mechanical index pulse sequence scheme (PSS).

BACKGROUND: Microbubbles normally pass freely through large and small vessels but are retained in regions with ED. New high-frequency low mechanical index PSS can potentially be utilized to image these retained microbubbles.

METHODS: Intravenous albumin- and lipid-encapsulated microbubbles were administered in seven pigs while imaging the CAs before and after a 20% intralipid infusion to induce hypertriglyceridemia. The degree of microbubble retention was quantified by measuring endothelial acoustic intensity (AI) after clearance of free-flowing microbubbles. Microbubble adherence was also evaluated after selective balloon injury of the CAs. The CA diameter responses to acetylcholine were quantified.

RESULTS: After induction of hypertriglyceridemia, adherence of albumin-encapsulated microbubbles was visually evident in all CAs, and endothelial AI increased significantly (p < 0.001 compared with baseline). The CA responses to acetylcholine went from vasodilation at baseline to vasoconstriction during hypertriglyceridemia. Endothelial AI also increased in the balloon-stretched vessels (p < 0.01 compared with uninjured vessels) after albumin-encapsulated microbubble injection, with a ring of microbubbles selectively adhering to the injured segment. This retention was not observed with lipid-encapsulated microbubbles. Scanning electron microscopy confirmed that albumin-coated microbubbles adhered to endothelial cells.

CONCLUSIONS: Retention of intravenously injected albumin microbubbles occurs in the setting of both global and regional ED in large vessels and can be noninvasively imaged with high-frequency low mechanical index PSS.

Abbreviations and Acronyms   AI = acoustic intensity   CA = carotid artery   ED = endothelial dysfunction   PESDA = perfluorocarbon-exposed sonicated dextrose albumin   PSS = pulse sequence scheme   ROI = region of interest   SEM = scanning electron microscopy

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