Claudia Calcagno1, Olivier Lairez2, Julie Hawkins3, Steven W Kerr3, Melanie S Dugas3, Thomas Simpson4, Jelle Epskamp5, Philip M Robson1, Mootaz Eldib1, Ilda Bander1, Purushothaman K-Raman6, Sarayu Ramachandran1, Alison Pruzan1, Audrey Kaufman1, Venkatesh Mani1, Alexander Ehlgen7, Heiko G Niessen7, John Broadwater3, Zahi A Fayad8. 1. Translational 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. 2. Translational 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; Department of Cardiology and Cardiac Imaging Center, Rangueil University Hospital, Toulouse, France. 3. Department of CardioMetabolic Diseases Research, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut. 4. Department of Chemistry, West Chester University, West Chester, Pennsylvania. 5. Academisch Medisch Centrum, Amsterdam, the Netherlands. 6. Department of Cardiology, Icahn School of Medicine at Mount Sinai New York, New York. 7. Department of Translational Medicine & Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany. 8. Translational 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. Electronic address: zahi.fayad@mssm.edu.
Abstract
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.
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.
Authors: Zahi A Fayad; Filip K Swirski; Claudia Calcagno; Clinton S Robbins; Willem Mulder; Jason C Kovacic Journal: J Am Coll Cardiol Date: 2018-10-30 Impact factor: 24.094
Authors: Martin J Willemink; Bram F Coolen; Hadrien Dyvorne; Philip M Robson; Ilda Bander; Seigo Ishino; Alison Pruzan; Arthi Sridhar; Bei Zhang; Priti Balchandani; Venkatesh Mani; Gustav J Strijkers; Aart J Nederveen; Tim Leiner; Zahi A Fayad; Willem J M Mulder; Claudia Calcagno Journal: PLoS One Date: 2020-12-14 Impact factor: 3.240
Authors: Nicholas R Evans; Jason M Tarkin; Elizabeth Pv Le; Rouchelle S Sriranjan; Andrej Corovic; Elizabeth A Warburton; James Hf Rudd Journal: Br J Radiol Date: 2020-04-03 Impact factor: 3.039