Early in vivo discrimination of vulnerable atherosclerotic plaques that disrupt: A serial MRI study
Tuan A Pham1, Ning Hua2, Alkystis Phinikaridou3
1Department of Biomedical Engineering, Boston University, Boston, MA, USA.
Background And Aims:
MRI has been validated as a suitable imaging modality for in vivo, non-invasive detection of atherosclerosis and has provided quantitative predictors of high-risk plaque. Here, we apply serial MRI to monitor the natural progression of plaques over a 3-month period in a rabbit model of atherothrombosis to determine differences over time between plaques that ultimately disrupt to form a luminal mural thrombus and plaques that remain stable.
Methods:
Atherosclerotic plaques were induced in 12 male New Zealand White (NZW) rabbits by aortic endothelial injury and a 1% cholesterol diet. The rabbits were imaged 5 times: at baseline, 1, 2, and 3 months, and 48hr after pharmacological triggering for plaque disruption.
Results:
Starting at 2 months, plaques that disrupted after triggering exhibited a higher remodeling ratio (RR, 1.05 ± 0.11 vs 0.97 ± 0.10, p = 0.0002) and a larger vessel wall area (VWA, 6.99 ± 1.54 mm(2) vs 6.30 ± 1.37 mm(2), p = 0.0072) than the stable non-disrupted plaques. The same trends were observed at 3 months: plaques that disrupted had a higher RR (1.04 ± 0.02 vs 0.99 ± 0.01, p = 0.0209), VWA (8.19 ± 2.69 mm(2) vs 6.81 ± 1.60 mm(2), p = 0.0001), and increased gadolinium uptake (75.51 ± 13.77% for disrupted vs 31.02 ± 6.45% for non-disrupted, p = 0.0022).
Conclusions:
MR images of plaques that disrupted revealed larger VWAs, RRs, and increased gadolinium uptake at 2 months and continued progression of these vulnerable features between 2 and 3 months. Non-disrupted plaques had an independent history without these hallmarks of vulnerability. Our results show that MRI can provide early detection of plaques at a higher-risk for luminal thrombosis.
Insights
Serial MRI can detect vulnerable atherosclerotic plaques at high risk for luminal thrombosis. This study monitored plaque progression in rabbits, identifying key MRI markers that predict future disruption and thrombus formation.
Area of Science:
- Cardiovascular Imaging
- Atherosclerosis Research
- Preclinical Models
Background:
- Magnetic Resonance Imaging (MRI) is a validated non-invasive tool for detecting atherosclerosis.
- MRI provides quantitative predictors of high-risk plaques.
- Atherothrombosis research requires methods to monitor plaque progression and identify vulnerable lesions.
Purpose of the Study:
- To apply serial MRI to monitor the natural progression of atherosclerotic plaques over 3 months in a rabbit model.
- To determine differences between plaques that ultimately disrupt and those that remain stable.
- To identify MRI-based predictors of plaque vulnerability and thrombotic events.
Main Methods:
- Atherosclerotic plaques were induced in 12 rabbits via aortic endothelial injury and a cholesterol-rich diet.
- Rabbits underwent serial MRI scans at baseline, 1, 2, and 3 months, and 48 hours post-pharmacological triggering for disruption.
- Key imaging parameters included remodeling ratio (RR) and vessel wall area (VWA).
Main Results:
- Plaques that disrupted after triggering showed significantly higher RR and VWA at 2 months compared to stable plaques.
- These trends persisted at 3 months, with disrupted plaques also exhibiting increased gadolinium uptake.
- Non-disrupted plaques lacked these hallmarks of vulnerability throughout the study period.
Conclusions:
- Serial MRI can identify vulnerable plaques characterized by larger VWAs, RRs, and increased gadolinium uptake.
- These vulnerable features progress between 2 and 3 months in plaques destined to disrupt.
- MRI offers early detection of plaques with a higher risk for luminal thrombosis, aiding in risk stratification.
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