In Vivo Molecular K-Edge Imaging of Atherosclerotic Plaque Using Photon-counting CT.

Background Macrophage burden is a major factor in the risk of atherosclerotic plaque rupture, and its evaluation remains challenging with molecular noninvasive imaging approaches. Photon-counting CT (PCCT) with k-edge imaging aims to allow for the specific detection of macrophages using gold nanoparticles. Purpose To perform k-edge imaging in combination with gold nanoparticles to detect and quantify the macrophage burden within the atherosclerotic aortas of rabbits. Materials and Methods Atherosclerotic and control New Zealand white rabbits were imaged before and at several time points up to 2 days after intravenous injection of gold nanoparticles (3.5 mL/kg, 65 mg gold per milliliter). Aortic CT angiography was performed at the end of the follow-up using an intravenous injection of an iodinated contrast material. Gold k-edge and conventional CT images were reconstructed for qualitative and quantitative assessment of the macrophage burden. PCCT imaging results were compared with findings at histologic examination, quantitative histomorphometry, transmission electron microscopy, and quantitative inductively coupled plasma optical emission spectrometry. Pearson correlations between the macrophage area measured in immunostained sections and the concentration of gold and attenuation measured in the corresponding PCCT sections were calculated. Results Seven rabbits with atherosclerosis and four control rabbits without atherosclerosis were analyzed. In atherosclerotic rabbits, calcifications were observed along the aortic wall before injection. At 2 days after injection of gold nanoparticles, only gold k-edge images allowed for the distinction of plaque enhancement within calcifications and for lumen enhancement during angiography. A good correlation was observed between the gold concentration measured within the wall and the macrophage area in 35 plaques (five per rabbit) (r = 0.82; 95% CI: 0.67, 0.91; P < .001), which was higher than that observed on conventional CT images (r = 0.41; 95% CI: 0.09, 0.65; P = .01). Transmission electron microscopy and inductively coupled plasma optical emission spectrometry analyses confirmed the gold k-edge imaging findings. Conclusion Photon-counting CT with gold nanoparticles allowed for the noninvasive evaluation of both molecular and anatomic information in vivo in rabbits with atherosclerotic plaques. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Leiner in this issue.

High-resolution magnetic resonance imaging of carotid atherosclerosis identifies vulnerable carotid plaques.

OBJECTIVE: Carotid magnetic resonance imaging (MRI) may be a useful tool in characterizing carotid plaque vulnerability, but large studies are still lacking. The purpose of this study was to assess carotid MRI features of vulnerable plaque in a large study and the changes in carotid plaque morphology with respect to time since the neurological event. METHODS: We included 161 patients with carotid plaque more than 3 mm thick. All patients underwent carotid MRI to obtain 3-T high-resolution magnetic resonance sequences. Large lipid core, intraplaque hemorrhage (IPH), fibrous cap rupture (FCR), and gadolinium enhancement (GE) were assessed and classified as present or absent. Prevalences of these features were then compared between symptomatic and asymptomatic patients and time since stroke. RESULTS: Seven patients were excluded because of poor image quality. Of the remaining 154 patients, 52 were symptomatic and 102 were asymptomatic. The prevalences of IPH (39 vs 16%; P = .002), FCR (30 vs 9%; P = .001), and GE (75 vs 55%; P = .015) were significantly higher in symptomatic than asymptomatic patients. After multivariate analysis, the prevalences of IPH (odds ratio, 2.6; P = .023) and FCR (odds ratio, 2.8; P = .038) were still significantly higher. The prevalence of IPH was significantly higher in symptomatic patients with plaque regardless of the time since the neurological event. For FCR, the difference between symptomatic and asymptomatic patients was significant only during the first 15 days after the neurological event. CONCLUSIONS: Carotid MRI can identify plaque features that are associated with symptomatic presentation and may be indicative of plaque vulnerability. These features may ultimately be used in the management of extracranial carotid stenosis.

Rapid-clearance iron nanoparticles for inflammation imaging of atherosclerotic plaque: initial experience in animal model.

PURPOSE: To evaluate the use of a recently developed fast-clearing ultrasmall superparamagnetic iron oxide (USPIO) for detection of vascular inflammation in atherosclerotic plaque. MATERIALS AND METHODS: The study protocol was approved by the animal experimentation ethics committee. A recently introduced USPIO, P904, and a reference-standard USPIO, ferumoxtran-10, were tested in a rabbit model of induced aortic atherosclerosis. In vivo magnetic resonance (MR) angiography and T2*-weighted plaque MR imaging were performed at baseline and after administration of P904 and ferumoxtran-10 (administered dose for both, 1000 micromol of iron per kilogram of body weight) in 26 hyperlipidemic New Zealand white rabbits. The variation in vessel wall area over time was evaluated with nonparametric testing. Ex vivo MR imaging findings were compared with iron content at linear regression analysis. RESULTS: With in vivo MR imaging, plaque analysis was possible as early as 24 hours after P904 injection. The authors observed a 27.75% increase in vessel wall area due to susceptibility artifacts on day 2 (P = .04) and a 38.81% increase on day 3 (P = .04) after P904 administration compared with a 44.5% increase in vessel wall area on day 7 (P = .04) and a 34.8% increase on day 10 (P = .22) after ferumoxtran-10 administration. These susceptibility artifacts were correlated with intraplaque iron uptake in the corresponding histologic slices. The number of pixels with signal loss on the ex vivo MR images was linearly correlated with the logarithm of the iron concentration (P = .0001; R(2) = 0.93). CONCLUSION: Plaque inflammation in rabbits can be detected earlier with P904 than with ferumoxtran-10 owing to the faster blood pharmacokinetics and the early uptake of P904 in the reticuloendothelial system. SUPPLEMENTAL MATERIAL: http://radiology.rsnajnls.org/cgi/content/full/252/2/401/DC1.

Concordance rate differences of 3 noninvasive imaging techniques to measure carotid stenosis in clinical routine practice: results of the CARMEDAS multicenter study.

BACKGROUND AND PURPOSE: To replace digital subtraction angiography (DSA) in carotid stenosis evaluation, noninvasive imaging techniques have to reach a high concordance rate. Our purpose is to compare the concordance rates of contrast-enhanced MR angiography (CEMRA) and CT angiography (CTA) with Doppler ultrasound (DUS) in clinical routine practice. METHODS: We evaluated prospectively with DUS, CEMRA, and CTA 150 patients suspected of carotid stenosis. The overall concordance rates of the 3 techniques were calculated for symptomatic stenosis > or =50% and > or =70%, for asymptomatic stenosis > or =60%, and for occlusion. For the carotid arteries treated by surgery (n=97), the results of each method and combined techniques were recorded, and misclassification rates were evaluated from surgical reports. RESULTS: The overall concordance rates of DUS-CEMRA, DUS-CTA, and CEMRA-CTA were not statistically different. However, the concordance rate of DUS-CEMRA (92.53%) was significantly higher than that for DUS-CTA (79.10%) in the surgical asymptomatic stenosis group (P=0.0258). CTA considered alone would misclassify the stenosis in a significant number of cases (11 of 64) in the surgical asymptomatic group compared with CEMRA (3 of 67) and DUS (1 of 66) (P=0.0186 versus MRA, P=0.0020 versus DUS). CONCLUSIONS: With the techniques as utilized in our study, the overall concordance rates of combined noninvasive methods are similar for measuring carotid stenosis in clinical routine practice, but in asymptomatic carotid stenosis, the decision making for surgery is significantly altered if DUS and CTA are considered in place of DUS and CEMRA.