Delayed plaque enhancement by CT angiography.

High-risk coronary atherosclerotic plaques that are believed to lead to acute coronary events usually demonstrate 2 distinct features on computed tomography (CT) angiography: low ( 30 HU) attenuation presumably representing the necrotic core and positive remodeling (plaque area/reference area, 1.1) of the affected vascular segments (1). Plaques that lack these 2 features are less commonly associated with subsequent adverse coronary events. In addition to low attenuation and remodeling, the identification of other characteristics of high-risk plaque, such as inflammation and neovascularization, are not amenable to standard CT angiography (2). By a molecular targeting strategy, intravenous administration of a CT angiographic contrast agent comprising iodinated nanoparticles dispersed with surfactant has been employed to image macrophages and inflammation in atherosclerotic plaques (3). On the other hand, coronary plaque neovascularization has been reported with contrast-enhanced ultrasound and cardiac magnetic resonance (4,5) but not by CT. Because microvessels are below the threshold of spatial resolution of CT, we hypothesized that serial CT acquisitions at a short imaging interval following contrast injection should allow analysis of plaque enhancement as a marker of neovascularization. We investigated 13 patients with stable angina (63.5 10.3 years, all men, body mass index 24.4 2.1 kg/m). The study was approved by the ethics and human research subjects review committee; delayed enhancement protocols, incremental radiation dose, and the research components of the study were discussed with patients and they voluntarily consented to participate in the study. All patients were in sinus rhythm and atenolol (25 mg) was administered orally or propranolol (2 to 10 mg) intravenously before the CT procedure to achieve a heart rate 60 beats/min (mean 51.1 4.9 beats/min; range: 43 to 60 beats/min). Coronary CT angiography was performed using a 320-row area detector CT (Toshiba, Ohtawara, Japan) with prospectively ECG-gated axial single-beat acquisition at 75% of R-R, 320 0.5 mm collimation, 175 ms temporal resolution, and 120 kV tube voltage. Mean tube current per acquisition was 119 21.0 mA and mean radiation exposure was 7.9 1.6 mSv for both acquisitions combined. The injection rate of contrast agent was determined as the patient’s weight 0.06 ml/s and scanning started when arrival of the contrast medium in the left ventricle was visually confirmed. Without a second contrast injection, and using identical parameters, data acquisition was repeated after an interval of 3 min. Contrast-enhanced coronary CT angiography in the 13 patients demonstrated 8 coronary segments showing 2 features of high-risk plaques (i.e., positive remodeling and low attenuation plaques). In 13 segments, although a plaque was identified, the lesions did not show both characteristic features of high-risk plaques. In all plaques, CT attenuation was obtained through the minimum CT value from 5 circular regions (area 1 mm) of interest. By using landarks, such as calcifications and/or side branches, attenution measurements were repeated at exactly the same ocation in the datasets obtained 3 min after contrast njection. Contrast washout between the initial and delayed T datasets was determined as a percent value both for all laques (early plaque attenuation delayed plaque attenation)/(early plaque attenuation) and for the ascending ortic lumen (early aortic attenuation delayed aortic attenuation)/(early aortic attenuation). Table 1 demontrates the observed values. There was no significant differnce in the CT attenuation of the aortic lumen in 8 patients ith and 11 patients without high-risk coronary plaque, ndicating similar kinetics of contrast enhancement in the 2 roups. However, the washout of contrast from high-risk laques after 3 min ( 8.0 6.1%) was significantly lower han the washout from plaques without high-risk morpholgy (4.1 8.0%, p 0.005) (Figs. 1A and 1B). A possible explanation for this observation may be intraplaque neovascularization with different contrast enhancement patterns in stable and high-risk coronary atherosclerotic lesions. Further investigation of this phenomenon is warranted.