Kai-Uwe Jarr1, Jianqin Ye1, Yoko Kojima1, Vivek Nanda1,2, Alyssa M Flores1, Pavlos Tsantilas1,3, Ying Wang1, Niloufar Hosseini-Nassab4, Anne V Eberhard1, Mozhgan Lotfi1, Max Käller1, Bryan R Smith5,6, Lars Maegdefessel3,7, Nicholas J Leeper1,8,9. 1. Division of Vascular Surgery, Department of Surgery (K.-U.J., J.Y., Y.K., V.N., A.M.F., P.T., Y.W., A.V.E., M.L., M.K., N.J.L.), Stanford University School of Medicine, CA. 2. Department of Pathology, The University of Alabama at Birmingham (V.N.). 3. Department for Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University Munich, Germany (P.T., L.M.). 4. Department of Radiology (N.H.-N.), Stanford University School of Medicine, CA. 5. Department of Biomedical Engineering, Michigan State University, East Lansing (B.R.S.). 6. Institute for Quantitative Health Science and Engineering, East Lansing, MI (B.R.S.). 7. German Center for Cardiovascular Research (DZHK partner site Munich), Germany (L.M.). 8. Division of Cardiovascular Medicine, Department of Medicine (N.J.L.), Stanford University School of Medicine, CA. 9. Stanford Cardiovascular Institute, Stanford University, CA (N.J.L.).
Abstract
OBJECTIVE: This study sought to determine whether 18F-fluorodeoxyglucose-positron emission tomography/computed tomography could be applied to a murine model of advanced atherosclerotic plaque vulnerability to detect response to therapeutic intervention and changes in lesion stability. Approach and Results: To analyze plaques susceptible to rupture, we fed ApoE-/- mice a high-fat diet and induced vulnerable lesions by cast placement over the carotid artery. After 9 weeks of treatment with orthogonal therapeutic agents (including lipid-lowering and proefferocytic therapies), we assessed vascular inflammation and several features of plaque vulnerability by 18F-fluorodeoxyglucose-positron emission tomography/computed tomography and histopathology, respectively. We observed that 18F-fluorodeoxyglucose-positron emission tomography/computed tomography had the capacity to resolve histopathologically proven changes in plaque stability after treatment. Moreover, mean target-to-background ratios correlated with multiple characteristics of lesion instability, including the corrected vulnerability index. CONCLUSIONS: These results suggest that the application of noninvasive 18F-fluorodeoxyglucose-positron emission tomography/computed tomography to a murine model can allow for the identification of vulnerable atherosclerotic plaques and their response to therapeutic intervention. This approach may prove useful as a drug discovery and prioritization method.
OBJECTIVE: This study sought to determine whether 18F-fluorodeoxyglucose-positron emission tomography/computed tomography could be applied to a murine model of advanced atherosclerotic plaque vulnerability to detect response to therapeutic intervention and changes in lesion stability. Approach and Results: To analyze plaques susceptible to rupture, we fed ApoE-/- mice a high-fat diet and induced vulnerable lesions by cast placement over the carotid artery. After 9 weeks of treatment with orthogonal therapeutic agents (including lipid-lowering and proefferocytic therapies), we assessed vascular inflammation and several features of plaque vulnerability by 18F-fluorodeoxyglucose-positron emission tomography/computed tomography and histopathology, respectively. We observed that 18F-fluorodeoxyglucose-positron emission tomography/computed tomography had the capacity to resolve histopathologically proven changes in plaque stability after treatment. Moreover, mean target-to-background ratios correlated with multiple characteristics of lesion instability, including the corrected vulnerability index. CONCLUSIONS: These results suggest that the application of noninvasive 18F-fluorodeoxyglucose-positron emission tomography/computed tomography to a murine model can allow for the identification of vulnerable atherosclerotic plaques and their response to therapeutic intervention. This approach may prove useful as a drug discovery and prioritization method.
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