Investigation of the development of atherosclerotic plaques in ApoE-/- mice using multi-modality imaging techniques in a longitudinal study

Abstract

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Objectives: The objective is to study longitudinally the development and characteristics of atherosclerotic plaques in ApoE-/- mice using multi-modality imaging techniques.

Methods: Seven groups of three ApoE-/- mice were fed with high fat diet that accelerates the growth of plaques starting at ~5-week of age and were imaged routinely at 2-3 weeks intervals using high-resolution Tc-99m Annexin-V pinhole (PH) SPECT (with ~1.25 mm resolution), contrast enhanced (CE) CT and US techniques till ~30-week. Autoradiography and histology data of the excised aorta were obtained after the last imaging point of each animal. The Annexin-V targets apoptosis involved in the development of plaques and the registered CE CT images identify the location of the plaques, initially in the aortic arch and later also in the descending aorta. US was used to demonstrate growth of plaque and narrowing of blood vessels over time. A high-resolution MRI technique (~250micron) was added to visualize the aortic vessel wall. Also, FDG PET imaging was attempted to image inflammation in the plaques.

Results: Most of the Tc-99m Annexin-V SPECT and CT images show increased apoptosis in plaques in the aorta over time. This was confirmed by autoradiography and histological data. In some cases, we found a decrease in the Annexin-V uptake concentration at later time points and calcium deposits in CT images. High-resolution MR images showed regional thickening of the vessel wall in ApeE-/- mice with demonstrated plaque growths with SPECT and US.

Conclusions: The multimodality imaging techniques provide a powerful tool to investigate the development and characterization of plaques in ApoE-/- mice over time.

Research Support: NIH EB1558