Performance evaluation of a dedicated preclinical PET/CT system for the assessment of mineralization process in a mouse model of atherosclerosis

International audiencePurpose: The purpose of this study was to assess the impact of positron emission tomography/X-ray computed tomography (PET/CT) acquisition and reconstruction parameters on the assessment of mineralization process in a mouse model of atherosclerosis.Procedures: All experiments were performed on a dedicated preclinical PET/CT system. CT was evaluated using five acquisition configurations using both a tungsten wire phantom for in-plane resolution assessment and a bar pattern phantom for cross-plane resolution. Furthermore, the radiation dose of these acquisition configurations was calculated. The PET system was assessed using longitudinal line sources to determine the optimal reconstruction parameters by measuring central resolution and its coefficient of variation. An in vivo PET study was performed using uremic ApoE($^{-/-}$), non-uremic ApoE($^{-/-}$), and control mice to evaluate optimal PET reconstruction parameters for the detection of sodium [$^{18}$F]fluoride (Na[$^{18}$F]F) aortic uptake and for quantitative measurement of Na[$^{18}$F]F bone influx (Ki) with a Patlak analysis.Results: For CT, the use of 1x1 and 2x2 binning detector mode increased both in-plane and cross-plane resolution. However, resolution improvement (163 to 62m for in-plane resolution) was associated with an important radiation dose increase (1.67 to 32.78Gy). With PET, 3D-ordered subset expectation maximization (3D-OSEM) algorithm increased the central resolution compared to filtered back projection (1.420.35mm vs. 1.91 +/- 0.08, p<0.001). The use of 3D-OSEM with eight iterations and a zoom factor 2 yielded optimal PET resolution for preclinical study (FWHM=0.98mm). These PET reconstruction parameters allowed the detection of Na[$^{18}$F]F aortic uptake in 3/14 ApoE(-/-) mice and demonstrated a decreased Ki in uremic ApoE(-/-) compared to non-uremic ApoE(-/-) and control mice (p<0.006).Conclusions: Optimizing reconstruction parameters significantly impacted on the assessment of mineralization process in a preclinical model of accelerated atherosclerosis using Na[$^{18}$F]F PET. In addition, improving the CT resolution was associated with a dramatic radiation dose increase

Molecular imaging of endothelial activation and mineralization in a mouse model of accelerated atherosclerosis

International audiencePurpose Preclinical imaging of endothelial activation and mineralization using both positron emission tomography (PET) and magnetic resonance (MR) remains scarce. Procedures A group of uremic ApoE(-/-) (Ur), non-uremic ApoE(-/-) (NUr), and control C57Bl/6 J mice (Ctl) were investigated. Mineralization process was assessed using sodium fluoride ([18F]NaF) PET, and MR imaging combined with intravenous injection of MPIO-alpha VCAM-1 was used to evaluate endothelial activation. Micro- and macrocalcifications were evaluated by flame atomic absorption spectroscopy and von Kossa staining, respectively. Results Ur mice showed an active and sustained mineralization process compared to Ctl mice (p = 0.002) using [18F]NaF PET imaging. Calcium plasma level was increased in Ur (2.54 +/- 0.09 mM, n = 17) compared to NUr and Ctl mice (2.24 +/- 0.01, n = 22, and 2.14 +/- 0.02, n = 27, respectively; p < 0.0001). Likewise, vascular calcium content was increased in Ur (0.51 +/- 0.06 mu g Ca2+ per milligram of dry weight aorta, n = 11) compared to NUr (0.27 +/- 0.05, n = 9, p = 0.013) and Ctl (0.28 +/- 0.05, n = 11, p = 0.014). Ur mice also had a higher inflammatory state using MPIO-alpha VCAM-1 MR (p global = 0.01, post hoc analysis Ur vs. Ctl p = 0.003) associated with increased VCAM-1 expression (p global = 0.02). Aortic remodeling at the level of the brachiocephalic trunk, brachiocephalic trunk itself, and aortic arch in Ur mice was also demonstrated using MR. Conclusions Preclinical molecular imaging allowed in vivo characterization of the early phase of atherosclerosis. [18F]NaF PET showed early and sustained vascular mineralization in uremic ApoE(-/-) mice. MPIO-alpha VCAM-1 MR imaging demonstrated aortic endothelial activation, predominantly in segments with vascular remodeling