Liposome‐enhanced MRI of neointimal lesions in the ApoE‐KO mouse

Abstract

Conventional high-resolution MRI is capable of detecting lipidrich atherosclerotic plaques in both human atherosclerosis and animal models of atherosclerosis. In this study we induced neointimal lesions in ApoE-KO mice by placing a constrictive collar around the right carotid artery. The model was imaged with conventional multispectral MRI, and the thickened wall could not be distinguished from surrounding tissue. We then tested paramagnetic liposomes (mean size ‫؍‬ 90 nm) for their ability to improve MRI visualization of induced thickening, using Gd-DTPA as a control. T 1 -weighted (T 1 -w), black-blood MRI of the neck area of the mice was performed before and 15 min, 45 min, and 24 hr after intravenous injection of either paramagnetic liposomes or Gd-DTPA. The collared vessel wall of mice that were injected with liposomes showed a pronounced signal enhancement of ϳ100% immediately after injection, which was sustained largely until 24 hr postinjection. In contrast, the vessel wall of all controls (left carotid artery and animals injected with Gd-DTPA) did not show significant contrast enhancement at those time points. This study demonstrates that intimal thickening in ApoE-KO mice can be effectively detected by contrast-enhanced (CE)-MRI upon injection of paramagnetic liposomes.

Development of111In-Labeled Liposomes for Vulnerable Atherosclerotic Plaque Imaging

“…Liposomes can act as a platform for various other imaging modalities, such as MR imaging and optical imaging. Recently, several liposome-based atherosclerosis imaging probes for various imaging modalities have been reported (33)(34)(35). Because liposomes are biocompatible and have long histories as drug carriers for human use (36), such imaging probes, including the liposome system we have described, should be good candidates for clinical use in the future.…”

MRI-determined carotid artery flow velocities and wall shear stress in a mouse model of vulnerable and stable atherosclerotic plaque

“…MRI has been used to study plaque burden in the abdominal aorta of mice [12][13][14][15], and recently, several studies have focused on pre-clinical evaluation of novel targeted contrast agents to identify molecular fingerprints of plaque vulnerability [7,[16][17][18][19][20]. The apoE−/− mouse with tapered cast represents an extremely attractive model of atherosclerosis as it allows for studying plaques with both stable and vulnerable characteristics within one animal and within a single vascular segment.…”

Gadolinium-containing phosphatidylserine liposomes for molecular imaging of atherosclerosis

“…The carrier moieties by virtue of preferential uptake by, or delivery to, specifi c pathways or receptors of relevance to the macrophage allow for "highpayload" delivery of the contrast agent and facilitate imaging with adequate signal to background noise ratios. Examples of such approaches include HDL (4) and LDL (5) lipoproteins incorporating Gd, polyethyleneglycol (PEG) grafted immunomicels ( 6,7 ), and liposome vesi cles ( 8 ) conjugated to antibodies targeting the macrophage scavenger receptor. In general, these approaches have been shown to provide enhanced detection of macrophage-rich areas, allowing monitoring of macrophagerich areas.…”