![Quantification of Atherosclerotic Plaque Activity and Vascular Inflammation using [18-F] Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography FDG-PET/CT](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F3777.jpg&w=3840&q=50)
Combined PET/DCE-MRI in a Rabbit Model of Atherosclerosis: Integrated Quantification of Plaque Inflammation,
Claudia Calcagno1, Olivier Lairez2, Julie Hawkins3
1Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, New York.
Objectives:
The authors sought to develop combined positron emission tomography (PET) dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) to quantify plaque inflammation, permeability, and burden to evaluate the efficacy of a leukotriene A4 hydrolase (LTA4H) inhibitor in a rabbit model of atherosclerosis.
Background:
Multimodality PET/MRI allows combining the quantification of atherosclerotic plaque inflammation, neovascularization, permeability, and burden by combined 18F-fluorodeoxyglucose (18F-FDG) PET, DCE-MRI, and morphological MRI. The authors describe a novel, integrated PET-DCE/MRI protocol to noninvasively quantify these parameters in aortic plaques of a rabbit model of atherosclerosis. As proof-of-concept, the authors apply this protocol to assess the efficacy of the novel LTA4H inhibitor BI691751.
Methods:
New Zealand White male rabbits (N = 49) were imaged with integrated PET-DCE/MRI after atherosclerosis induction and 1 and 3 months after randomization into 3 groups: 1) placebo; 2) high-dose BI691751; and 3) low-dose BI691751. All animals were euthanized at the end of the study.
Results:
Among the several metrics that were quantified, only maximum standardized uptake value and target-to-background ratio by 18F-FDG PET showed a modest, but significant, reduction in plaque inflammation in rabbits treated with low-dose BI691751 (p = 0.03), whereas no difference was detected in the high-fat diet and in the high-dose BI691751 groups. No differences in vessel wall area by MRI and area under the curve by DCE-MRI were detected in any of the groups. No differences in neovessel and macrophage density were found at the end of study among groups.
Conclusions:
The authors present a comprehensive, integrated 18F-FDG PET and DCE-MRI imaging protocol to noninvasively quantify plaque inflammation, neovasculature, permeability, and burden in a rabbit model of atherosclerosis on a simultaneous PET/MRI scanner. A modest reduction was found in plaque inflammation by 18F-FDG PET in the group treated with a low dose of the LTA4H inhibitor BI691751.
Insights
This study developed a combined positron emission tomography (PET) and dynamic contrast-enhanced (DCE) MRI protocol to assess atherosclerosis. The novel imaging method showed a modest reduction in plaque inflammation with a low dose of a leukotriene A4 hydrolase (LTA4H) inhibitor.
Area of Science:
- Cardiovascular Imaging
- Pharmacology
- Biomedical Engineering
Background:
- Multimodality PET/MRI offers comprehensive quantification of atherosclerotic plaque characteristics.
- Integrated PET-DCE/MRI protocols enable noninvasive assessment of plaque inflammation, neovascularization, permeability, and burden.
- Assessing novel therapeutic agents like leukotriene A4 hydrolase (LTA4H) inhibitors in atherosclerosis models is crucial.
Purpose of the Study:
- To develop and validate an integrated positron emission tomography (PET)/dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) protocol.
- To quantify plaque inflammation, permeability, and burden in a rabbit model of atherosclerosis.
- To evaluate the efficacy of a novel LTA4H inhibitor (BI691751) using the developed imaging protocol.
Main Methods:
- New Zealand White rabbits (N=49) with induced atherosclerosis underwent integrated PET-DCE/MRI.
- Animals were randomized into placebo, high-dose BI691751, and low-dose BI691751 groups.
- Quantitative metrics including maximum standardized uptake value (SUVmax), target-to-background ratio (TBR), vessel wall area, and DCE-MRI parameters were analyzed.
Main Results:
- 18F-FDG PET metrics (SUVmax and TBR) showed a modest, significant reduction in plaque inflammation in the low-dose BI691751 group (p=0.03).
- No significant differences in plaque inflammation were observed in the high-fat diet or high-dose BI691751 groups.
- MRI-derived vessel wall area and DCE-MRI parameters did not differ among groups; neovessel and macrophage density were also similar.
Conclusions:
- A comprehensive, integrated 18F-FDG PET and DCE-MRI protocol was successfully developed for noninvasive quantification of atherosclerotic plaque parameters.
- The LTA4H inhibitor BI691751 demonstrated a modest, dose-dependent reduction in plaque inflammation at a low dose.
- This integrated imaging approach holds promise for evaluating therapeutic interventions in atherosclerosis.
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