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Detection of Calcified Aortic Plaques in an Apolipoprotein E Animal Model Using a Human Computed Tomography System for Ultra–High-resolution Imaging

A Feasibility Study

Manta, Calin, PhD*; Meyer, Mathias, MD; Géraud, Cyrill, MD*; Roscher, Mareike, PhD; Goerdt, Sergij, MD*; Schoenberg, Stefan O., MD; Henzler, Thomas, MD; Ong, Melissa M., MD

doi: 10.1097/RTI.0000000000000375
Imaging in Cardiac Risk Prediction
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Purpose: The purpose of this study was to prospectively evaluate the feasibility of detecting calcified aortic plaques in apolipoprotein E knockout (ApoE-KO) mice using a state-of-the-art human computed tomography (CT) system.

Materials and Methods: Eleven ApoE-KO and 9 wild-type mice, all male, were examined in this study. After intraperitoneal injection of 6.6% ketamine all mice underwent 2 ultra–high-resolution CT protocols on a third-generation dual-source CT system at 120 kVp and 130 kVp tube voltage, both performed with a tube current time product of 1300 mAs. Images (0.4 mm) with an increment of 0.2 mm were reconstructed using an iterative reconstruction algorithm. Calcium detectability and scores (Agatston, volume, mass) were determined with a dedicated human calcium scoring software (CaScoring). After the CT examination, a calcium quantification assay of the aortae was performed to determine the aortic calcium content of each mouse. The CT scan time ranged between 40 and 48 seconds. All mice survived the procedure.

Results: Calcified plaques could be detected in 8 of 11 ApoE-KO mice. Quantification of calcium levels showed significant differences between those with morphologic calcium plaques detected in CT and those without (3.44±1.6 μg Ca2+/mg vs. 0.33±0.35 μg Ca2+/mg; P<0.05). The receiver-operating characteristics analysis revealed a total calcium cut-off value of 0.71 μg Ca2+/mg for the detection using calcium score algorithms (specificity: 100% and sensitivity: 90%).

Conclusion: Using a state-of-the-art human CT protocol and an in-human–established calcium scoring system allows for the detection and quantification of calcified aortic plaques in ApoE-KO mice. These results may facilitate preclinical imaging for translational and longitudinal atherosclerotic research studies.

*Department of Dermatology, Venereology and Allergology

Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Heidelberg University, Mannheim

Department of Radiopharmaceutical Chemistry, DKFZ, Heidelberg, Germany

C.M. and M.M. contributed equally.

The authors declare no conflicts of interest.

Reprints: Mathias Meyer, MD, Institute of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, Mannheim 68167, Germany (e-mail: mathias.meyer@medma.uni-heidelberg.de).

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