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

TY - JOUR

T1 - Detection of Calcified Aortic Plaques in an Apolipoprotein E Animal Model Using a Human Computed Tomography System for Ultra-High-resolution Imaging

T2 - A Feasibility Study

AU - Manta, Calin

AU - Meyer, Mathias

AU - Géraud, Cyrill

AU - Roscher, Mareike

AU - Goerdt, Sergij

AU - Schoenberg, Stefan O

AU - Henzler, Thomas

AU - Ong, Melissa M

PY - 2019/1

Y1 - 2019/1

N2 - 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 Ca/mg vs. 0.33±0.35 μg Ca/mg; P<0.05). The receiver-operating characteristics analysis revealed a total calcium cut-off value of 0.71 μg Ca/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.

AB - 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 Ca/mg vs. 0.33±0.35 μg Ca/mg; P<0.05). The receiver-operating characteristics analysis revealed a total calcium cut-off value of 0.71 μg Ca/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.

KW - Animals

KW - Apolipoproteins E/deficiency

KW - Computed Tomography Angiography/methods

KW - Coronary Angiography/methods

KW - Coronary Artery Disease/diagnostic imaging

KW - Disease Models, Animal

KW - Feasibility Studies

KW - Male

KW - Mice, Inbred C57BL

KW - Plaque, Atherosclerotic/diagnostic imaging

KW - Prospective Studies

U2 - 10.1097/RTI.0000000000000375

DO - 10.1097/RTI.0000000000000375

M3 - SCORING: Journal article

C2 - 30480591

VL - 34

SP - 41

EP - 47

JO - J THORAC IMAG

JF - J THORAC IMAG

SN - 0883-5993

IS - 1

ER -