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Detecting and assessing macrophages in vivo to evaluate atherosclerosis noninvasively using molecular MRI
Vardan Amirbekian1, Michael J Lipinski, Karen C Briley-Saebo
1Imaging Science Laboratories, Department of Radiology, the Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
Abstract:
We investigated the ability of targeted immunomicelles to detect and assess macrophages in atherosclerotic plaque using MRI in vivo. There is a large clinical need for a noninvasive tool to assess atherosclerosis from a molecular and cellular standpoint. Macrophages play a central role in atherosclerosis and are associated with plaques vulnerable to rupture. Therefore, macrophage scavenger receptor (MSR) was chosen as a target for molecular MRI. MSR-targeted immunomicelles, micelles, and gadolinium-diethyltriaminepentaacetic acid (DTPA) were tested in ApoE-/- and WT mice by using in vivo MRI. Confocal laser-scanning microscopy colocalization, macrophage immunostaining and MRI correlation, competitive inhibition, and various other analyses were performed. In vivo MRI revealed that at 24 h postinjection, immunomicelles provided a 79% increase in signal intensity of atherosclerotic aortas in ApoE-/- mice compared with only 34% using untargeted micelles and no enhancement using gadolinium-DTPA. Confocal laser-scanning microscopy revealed colocalization between fluorescent immunomicelles and macrophages in plaques. There was a strong correlation between macrophage content in atherosclerotic plaques and the matched in vivo MRI results as measured by the percent normalized enhancement ratio. Monoclonal antibodies to MSR were able to significantly hinder immunomicelles from providing contrast enhancement of atherosclerotic vessels in vivo. Immunomicelles provided excellent validated in vivo enhancement of atherosclerotic plaques. The enhancement seen is related to the macrophage content of the atherosclerotic vessel areas imaged. Immunomicelles may aid in the detection of high macrophage content associated with plaques vulnerable to rupture.
Insights
Targeted immunomicelles effectively detect macrophages in atherosclerotic plaques using MRI. This molecular imaging approach may help identify vulnerable plaques prone to rupture.
Area of Science:
- Biomedical imaging
- Molecular imaging
- Cardiovascular research
Background:
- Atherosclerosis assessment requires noninvasive molecular and cellular tools.
- Macrophages are key players in atherosclerosis and plaque vulnerability.
- Macrophage scavenger receptor (MSR) is a potential molecular target.
Purpose of the Study:
- To evaluate targeted immunomicelles for in vivo MRI detection of macrophages in atherosclerotic plaques.
- To assess the correlation between immunomicelle enhancement and macrophage content.
- To determine the potential of immunomicelles in identifying rupture-prone plaques.
Main Methods:
- In vivo MRI in ApoE-/- and WT mice using MSR-targeted immunomicelles, untargeted micelles, and gadolinium-DTPA.
- Confocal laser-scanning microscopy for colocalization studies.
- Macrophage immunostaining and competitive inhibition assays.
Main Results:
- Immunomicelles showed a 79% signal increase in atherosclerotic aortas, significantly higher than untargeted micelles (34%) or gadolinium-DTPA.
- Confocal microscopy confirmed immunomicelle colocalization with plaque macrophages.
- A strong correlation was observed between MRI enhancement and macrophage content.
Conclusions:
- MSR-targeted immunomicelles provide validated in vivo enhancement of atherosclerotic plaques.
- The observed enhancement is directly related to macrophage content.
- Immunomicelles show promise for detecting high macrophage content in vulnerable plaques.
