In vivo detection of vulnerable atherosclerotic plaque by MRI in a rabbit model
Alkystis Phinikaridou1, Frederick L Ruberg, Kevin J Hallock
1Department of Physiology and Biophysics, Boston University School of Medicine, Boston, MA 02118, USA.
Background:
The ability to identify atherosclerotic plaques with a high risk for sudden disruption before stroke or myocardial infarction would be of great utility. We used a rabbit model of controlled atherothrombosis to test whether in vivo MRI can noninvasively distinguish between plaques that disrupt after pharmacological triggering (vulnerable) and those that do not (stable).
Methods And Results:
Atherosclerosis was induced in male New Zealand White (n=17) rabbits by cholesterol diet and endothelial denudation of the abdominal aorta. After baseline (pretrigger) MRI with and without gadolinium contrast, the rabbits underwent 2 pharmacological triggerings to induce atherothrombosis, followed by another MRI 48 hours later (post-triggering). Atherosclerosis was identified by the pretriggered images in all rabbits, and thrombosis was identified in 9 of 17 animals (53%) by post-trigger MRI. After the animals were euthanized, 95 plaques were analyzed; 28 (29.5%) had thrombi (vulnerable) and 67 did not (stable) (70.5%). Pretriggered MRI revealed comparable stenosis in stable and vulnerable plaques, but vulnerable plaques had a larger plaque area (4.8+/-1.6 versus 3.0+/-1.0 mm(2); P=0.01), vessel area (9.2+/-3.0 versus. 15.8+/-4.9 mm(2); P=0.01), and higher remodeling ratio (1.16+/-0.2 versus 0.93+/-0.2; P=0.01) compared with stable plaques. Furthermore, vulnerable plaques more frequently exhibited (1) positive remodeling (67.8% versus 22.3%; P=0.01), in which the plaque is hidden within the vessel wall instead of occluding the lumen; and (2) enhanced gadolinium uptake (78.6% versus 20.9%; P=0.01) associated with histological findings of neovascularization, inflammation, and tissue necrosis.
Conclusions:
We demonstrate that in vivo MRI at 3.0 T detects features of vulnerable plaques in an animal model of controlled atherothrombosis. These findings suggest that MRI may be used as a noninvasive modality for localization of plaques that are prone to disruption.
Insights
In vivo magnetic resonance imaging (MRI) can identify vulnerable atherosclerotic plaques prone to rupture. This noninvasive technique aids in localizing plaques that may cause stroke or heart attack.
Area of Science:
- Cardiovascular Imaging
- Atherosclerosis Research
- Medical Diagnostics
Background:
- Identifying high-risk atherosclerotic plaques before rupture is crucial for preventing stroke and myocardial infarction.
- Atherosclerosis can lead to plaque instability and rupture, causing thrombotic events.
- Noninvasive imaging methods are needed to differentiate vulnerable from stable plaques.
Purpose of the Study:
- To evaluate the utility of in vivo magnetic resonance imaging (MRI) in distinguishing vulnerable atherosclerotic plaques from stable ones.
- To assess if MRI can noninvasively detect features associated with plaque vulnerability in an animal model.
- To determine the potential of MRI for identifying plaques prone to rupture.
Main Methods:
- Atherosclerosis was induced in rabbits using a cholesterol diet and endothelial denudation.
- In vivo MRI was performed before and after pharmacological triggering to induce atherothrombosis.
- Plaques were analyzed post-mortem to correlate MRI findings with histological characteristics.
Main Results:
- MRI successfully identified atherosclerosis and detected thrombosis in 53% of rabbits post-triggering.
- Vulnerable plaques, identified by thrombi, showed larger plaque and vessel areas and higher remodeling ratios compared to stable plaques.
- Vulnerable plaques exhibited positive remodeling and enhanced gadolinium uptake, linked to neovascularization, inflammation, and necrosis.
Conclusions:
- In vivo MRI at 3.0 T can detect features indicative of vulnerable atherosclerotic plaques in an animal model.
- These findings suggest MRI's potential as a noninvasive tool for localizing plaques at high risk of disruption.
- MRI may aid in early detection and risk stratification of patients with atherosclerosis.


