Sudden fibrous cap disruption of 'high-risk' atherosclerotic plaques can trigger the formation of an occlusive thrombus in coronary arteries, causing acute coronary syndromes. High-risk atherosclerotic plaques are characterized by their specific cellular and biological content (in particular, a high density of macrophages), rather than by their impact on the vessel lumen. Early identification of high-risk plaques may be useful for preventing ischemic events. One major hurdle in detecting high-risk atherosclerotic plaques in coronary arteries is the lack of an imaging modality that allows for the identification of atherosclerotic plaque composition with high spatial and temporal resolutions. Here we show that macrophages in atherosclerotic plaques of rabbits can be detected with a clinical X-ray computed tomography (CT) scanner after the intravenous injection of a contrast agent formed of iodinated nanoparticles dispersed with surfactant. This contrast agent may become an important adjunct to the clinical evaluation of coronary arteries with CT.

We investigated the ability of targeted immunomicelles to detect and assess macrophages in atherosclerotic plaque using MRI in vivo. There is a large clinical need for a noninvasive tool to assess atherosclerosis from a molecular and cellular standpoint. Macrophages play a central role in atherosclerosis and are associated with plaques vulnerable to rupture. Therefore, macrophage scavenger receptor (MSR) was chosen as a target for molecular MRI. MSR-targeted immunomicelles, micelles, and gadolinium-diethyltriaminepentaacetic acid (DTPA) were tested in ApoE؊/؊ and WT mice by using in vivo MRI. Confocal laser-scanning microscopy colocalization, macrophage immunostaining and MRI correlation, competitive inhibition, and various other analyses were performed. In vivo MRI revealed that at 24 h postinjection, immunomicelles provided a 79% increase in signal intensity of atherosclerotic aortas in ApoE؊/؊ mice compared with only 34% using untargeted micelles and no enhancement using gadolinium-DTPA. Confocal laser-scanning microscopy revealed colocalization between fluorescent immunomicelles and macrophages in plaques. There was a strong correlation between macrophage content in atherosclerotic plaques and the matched in vivo MRI results as measured by the percent normalized enhancement ratio. Monoclonal antibodies to MSR were able to significantly hinder immunomicelles from providing contrast enhancement of atherosclerotic vessels in vivo. Immunomicelles provided excellent validated in vivo enhancement of atherosclerotic plaques. The enhancement seen is related to the macrophage content of the atherosclerotic vessel areas imaged. Immunomicelles may aid in the detection of high macrophage content associated with plaques vulnerable to rupture. macrophage scavenger receptor ͉ molecular imaging ͉ vulnerable plaque ͉ immunomicelles ͉ gadolinium

Cardiovascular diseases are the leading cause of death not only in Europe but also in the rest of the World. Preventive measures, however, often fail and cardiovascular disease may manifest as an acute coronary syndrome, stroke or even sudden death after years of silent progression. Thus, there is a considerable need for innovative diagnostic and therapeutic approaches to improve the quality of care and limit the burden of cardiovascular diseases. During the past 10 years, several retrospective and prospective clinical studies have been published using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to quantify inflammation in atherosclerotic plaques. However, the current variety of imaging protocols used for vascular (arterial) imaging with FDG PET considerably limits the ability to compare results between studies and to build large multicentre imaging registries. Based on the existing literature and the experience of the Members of the European Association of Nuclear Medicine (EANM) Cardiovascular Committee, the objective of this position paper was to propose optimized and standardized protocols for imaging and interpretation of PET scans in atherosclerosis. These recommendations do not, however, replace the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual study protocols used and the individual patient, in consultation with the patient and, where appropriate and necessary, the patient’s guardian or carer. These recommendations suffer from the absence of conclusive evidence on many of the recommendations. Therefore, they are not intended and should not be used as "strict guidelines" but should, as already mentioned, provide a basis for standardized clinical atherosclerosis PET imaging protocols, which are subject to further and continuing evaluation and improvement. However, this EANM position paper might indeed be a first step towards "official" guidelines on atherosclerosis imaging with PET.

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Objective-The association of inflammatory cells and neovessels in atherosclerosis is considered a histological hallmark of high-risk active lesions. Therefore, the development and validation of noninvasive imaging techniques that allow for the detection of inflammation and neoangiogenesis in atherosclerosis would be of major clinical interest. Our aim was to test 2 techniques, black blood dynamic contrast enhanced MRI (DCE-MRI) and 18-fluorine-fluorodeoxyglucose (18F-FDG) PET, to quantify inflammation expressed as plaque neovessels content in a rabbit model of atherosclerosis. Methods and Results-Atherosclerotic plaques were induced in the aorta of 10 rabbits by a combination of 2 endothelial abrasions and 4 months hyperlipidemic diet. Six rabbits underwent MRI during the injection of Gd-DTPA, whereas 4 rabbits were imaged after injection of 18F-FDG with PET. We found a positive correlation between neovessels count in atherosclerotic plaques and (1) Gd-DTPA uptake parameters evaluated by Pϭ0.016) and (2) 18F-FDG uptake evaluated by PET (rϭ0.5, Pϭ0.103 after clustered robust, Huber-White, standard errors analysis). Key Words: atherosclerosis Ⅲ inflammation Ⅲ neovessels Ⅲ MRI Ⅲ PET N eovascularization is one of the hallmarks of high-risk/ vulnerable atherosclerotic lesions. It is characterized by the formation of new capillaries in the atherosclerotic plaque, and it is usually considered a response to the hypoxic conditions within the vessel wall during plaque growth. 1 However, more recent reports have identified hypoxia independent pathways of angiogenesis mediated primarily by inflammation 2,3 : these studies have highlighted the link between the presence of neovessels, the extravasation and activation of inflammatory cells, and lipid deposition in the vessel wall. Neovessels seem to play a key role in the progression of atherosclerotic plaques and plaque rupture. 1 From those reports it appears that the presence and extent of neovessels and inflammation in atherosclerotic plaques can be considered a marker of risk associated with the lesion. Therefore it would be of clinical relevance to develop techniques capable of quantifying the degree of plaque inflammation in a noninvasive and reliable manner. DCE-MRI is an imaging technique extensively used to study the vascularity of tumors. 4 This technique takes advantage of the administration of clinically-available contrast agents (ie, Gadolinium (Gd)-chelates) to quantify the extent of tumor blood supply and its associated physiological characteristics, such as permeability surface area product, extraction fraction, and blood flow. Recent studies on human carotid atherosclerotic plaques have shown that several gadolinium uptake parameters, evaluated by kinetic modeling 5 of DCE-MRI bright blood acquisitions, correlate with the extent of plaque vascularity and macrophage burden (confirmed by staining of histological specimens). 6,7 However, the use of the bright blood DCE technique makes it intrinsically difficult to reliably delineate the vessel lumen from the w...

Echocardiography plays a key role in the diagnosis of infective endocarditis (IE) but can be inconclusive in patients in whom prosthetic valve endocarditis (PVE) is suspected. The incremental diagnostic value of 18 F-FDG PET and radiolabeled leukocyte scintigraphy in IE patients has already been reported. The aim of this study was to compare the respective performance of 18 F-FDG PET and leukocyte scintigraphy for the diagnosis of PVE in 39 patients. Methods: 18 F-FDG PET and leukocyte scintigraphy were performed on 39 consecutive patients admitted because of clinically suspected PVE and inconclusive echocardiography results. The results of 18 F-FDG PET and leukocyte scintigraphy were analyzed separately and retrospectively by experienced physicians masked to the results of the other imaging technique and to patient outcome. The final Duke-Li IE classification was made after a 3-mo follow-up. Results: Of the 39 patients, 14 were classified as having definite IE, 4 as having possible IE, and 21 as not having IE. The average interval between 18 F-FDG PET and leukocyte scintigraphy was 7 ± 7 d. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 93%, 71%, 68%, 94%, and 80%, respectively, for 18 F-FDG PET and 64%, 100%, 100%, 81%, and 86%, respectively, for leukocyte scintigraphy. Discrepancies between the results of 18 F-FDG PET and leukocyte scintigraphy occurred in 12 patients (31%). In patients with definite IE, 5 had true-positive 18 F-FDG PET results but false-negative leukocyte scintigraphy results. Of these 5 patients, 3 had nonpyogenic microorganism IE (Coxiella or Candida). Of patients for whom endocarditis had been excluded, 6 had true-negative leukocyte scintigraphy results but false-positive 18 F-FDG PET results. These 6 patients had been imaged in the first 2 mo after the last cardiac surgery. The last patient with a discrepancy between 18 F-FDG PET and leukocyte scintigraphy was classified as having possible endocarditis and had positive 18 F-FDG PET results and negative leukocyte scintigraphy results. Conclusion: 18 F-FDG PET offers high sensitivity for the detection of active infection in patients with suspected PVE and inconclusive echocardiography results. Leukocyte scintigraphy offers a higher specificity, however, than 18 F-FDG PET for diagnosis of IE and should be considered in cases of inconclusive 18 F-FDG PET findings or in the first 2 mo after cardiac surgery.

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Use of combined early- and late-perfusion MR imaging sequences helps to distinguish AMI from myocarditis.