Positron Emission Tomography and Magnetic Resonance Imaging of Cellular Inflammation in Patients with Abdominal Aortic Aneurysms.

OBJECTIVES: Inflammation is critical in the pathogenesis of abdominal aortic aneurysm (AAA) disease. Combined (18)F-fludeoxyglucose ((18)F-FDG) positron emission tomography with computed tomography (PET-CT) and ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) are non-invasive methods of assessing tissue inflammation. The aim of this study was to compare these techniques in patients with AAA. MATERIALS AND METHODS: Fifteen patients with asymptomatic AAA with diameter 46 ± 7 mm underwent PET-CT with (18)F-FDG, and T2*-weighted MRI before and 24 hours after administration of USPIO. The PET-CT and MRI data were then co-registered. Standardised uptake values (SUVs) were calculated to measure (18)F-FDG activity, and USPIO uptake was determined using the change in R2*. Comparisons between the techniques were made using a quadrant analysis and a voxel-by-voxel evaluation. RESULTS: When all areas of the aneurysm were evaluated, there was a modest correlation between the SUV on PET-CT and the change in R2* on USPIO-enhanced MRI (n = 70,345 voxels; r = .30; p < .0001). Although regions of increased (18)F-FDG and USPIO uptake co-localised on occasion, this was infrequent (kappa statistic 0.074; 95% CI 0.026-0.122). (18)F-FDG activity was commonly focused in the shoulder region whereas USPIO uptake was more apparent in the main body of the aneurysm. Maximum SUV was lower in patients with mural USPIO uptake. CONCLUSIONS: Both (18)F-FDG PET-CT and USPIO-MRI uptake identify vascular inflammation associated with AAA. Although they demonstrate a modest correlation, there are distinct differences in the pattern and distribution of uptake, suggesting a differential detection of macrophage glycolytic and phagocytic activity respectively.

Aortic stenosis, atherosclerosis, and skeletal bone: is there a common link with calcification and inflammation?

AIMS: The pathophysiology of aortic stenosis shares many similarities with atherosclerosis and skeletal bone formation. Using non-invasive imaging, we compared aortic valve calcification and inflammation activity with that measured in atherosclerosis and bone. METHODS AND RESULTS: Positron emission and computed tomography was performed using 18F-sodium fluoride (18F-NaF, calcification) and 18F-fluorodeoxyglucose (18F-FDG, inflammation) in 101 patients with calcific aortic valve disease (81 aortic stenosis and 20 aortic sclerosis). Calcium scores and positron emission tomography tracer activity (tissue-to-background ratio; TBR) were measured in the aortic valve, coronary arteries, thoracic aorta, and bone. Over 90% of the cohort had coexistent calcific atheroma, yet correlations between calcium scores were weak or absent (valve vs. aorta r(2) = 0.015, P = 0.222; valve vs. coronaries r(2) = 0.039, P = 0.049) as were associations between calcium scores and bone mineral density (BMD vs. valve r(2) = 0.000, P = 0.766; vs. aorta r(2) = 0.052, P = 0.025; vs. coronaries r(2) = 0.016, P = 0.210). 18F-NaF activity in the valve was 28% higher than in the aorta (TBR: 2.66 ± 0.84 vs. 2.11 ± 0.31, respectively, P < 0.001) and correlated more strongly with the severity of aortic stenosis (r(2) = 0.419, P < 0.001) than 18F-NaF activity outwith the valve (valve vs. aorta r(2) = 0.167, P < 0.001; valve vs. coronary arteries r(2) = 0.174, P < 0.001; valve vs. bone r(2) = 0.001, P = 0.806). In contrast, 18F-FDG activity was lower in the aortic valve than the aortic atheroma (TBR: 1.56 ± 0.21 vs. 1.81 ± 0.24, respectively, P < 0.001) and more closely associated with uptake outwith the valve (valve vs. aorta r(2) = 0.327, P < 0.001). CONCLUSION: In patients with aortic stenosis, disease activity appears to be determined by local calcific processes within the valve that are distinct from atherosclerosis and skeletal bone metabolism.

Vascular imaging with positron emission tomography.

Atherosclerosis is an inflammatory disease that causes most myocardial infarctions, strokes and acute coronary syndromes. Despite the identification of multiple risk factors and widespread use of drug therapies, it still remains a global health concern with associated costs. Although angiography is established as the gold standard means of detecting coronary artery stenosis, it does not image the vessel wall itself, reporting only on its consequences such as luminal narrowing and obstruction. MRI and computed tomography provide more information about the plaque structure, but recently positron emission tomography (PET) imaging using [(18) F]-fluorodeoxyglucose (FDG) has been advocated as a means of measuring arterial inflammation. This results from the ability of FDG-PET to highlight areas of high glucose metabolism, a feature of macrophages within atherosclerosis, particularly in high-risk plaques. It is suggested that the degree of FDG accumulation in the vessel wall reflects underlying inflammation levels and that tracking any changes in FDG uptake over time or with drug therapy might be a way of getting an early efficacy readout for novel anti-atherosclerotic drugs. Early reports also demonstrate that FDG uptake is correlated with the number of cardiovascular risk factors and possibly even the risk of future cardiovascular events. This review will outline the evidence base, shortcomings and emerging applications for FDG-PET in vascular imaging. Alternative PET tracers and other candidate imaging modalities for measuring vascular inflammation will also be discussed.

Complications of myocardial infarction on multidetector-row computed tomography of chest.

Myocardial infarction (MI) secondary to coronary artery disease remains the leading cause of death in the western world. The advent of early reperfusion therapy has substantially decreased in-hospital mortality and has improved the outcome in survivors of the acute phase of MI. Complications of MI include ischaemic, mechanical, arrhythmic, embolic and inflammatory disturbances. Although some of these complications may be infrequent, their importance is underscored because of the potential ability to correct them with early diagnosis and appropriate treatment. The majority of these complications will be detected on clinical examination and confirmed by echocardiography. Some patients may undergo non-electrocardiogram (ECG)-gated thoracic multidetector-row computed tomography (MDCT) due to non-specific presentation. In this group, it is imperative for the radiologist to be aware of and be confident in diagnosing the complications secondary to MI. This review illustrates the spectrum and imaging features of acute and chronic complications of MI that can be visualized on both ECG-gated cardiac and non-ECG-gated thoracic MDCT.

Imaging atherosclerotic plaque inflammation with [18F]-fluorodeoxyglucose positron emission tomography.

BACKGROUND: Atherosclerotic plaque rupture is usually a consequence of inflammatory cell activity within the plaque. Current imaging techniques provide anatomic data but no indication of plaque inflammation. The glucose analogue [18F]-fluorodeoxyglucose (18FDG) can be used to image inflammatory cell activity non-invasively by PET. In this study we tested whether 18FDG-PET imaging can identify inflammation within carotid artery atherosclerotic plaques. METHODS AND RESULTS: Eight patients with symptomatic carotid atherosclerosis were imaged using 18FDG-PET and co-registered CT. Symptomatic carotid plaques were visible in 18FDG-PET images acquired 3 hours post-18FDG injection. The estimated net 18FDG accumulation rate (plaque/integral plasma) in symptomatic lesions was 27% higher than in contralateral asymptomatic lesions. There was no measurable 18FDG uptake into normal carotid arteries. Autoradiography of excised plaques confirmed accumulation of deoxyglucose in macrophage-rich areas of the plaque. CONCLUSIONS: This study demonstrates that atherosclerotic plaque inflammation can be imaged with 18FDG-PET, and that symptomatic, unstable plaques accumulate more 18FDG than asymptomatic lesions.

Evaluation of translocator protein quantification as a tool for characterising macrophage burden in human carotid atherosclerosis.

Macrophage presence within atherosclerotic plaque is a feature of instability and a risk factor for plaque rupture and clinical events. Activated macrophages express high levels of the translocator protein/peripheral benzodiazepine receptor (TSPO/PBR). In this study, we investigated the potential for quantifying plaque inflammation by targeting this receptor. TSPO expression and distribution in the plaque were quantified using radioligand binding assays and autoradiography. We show that cultured human macrophages expressed 20 times more TSPO than cultured human vascular smooth muscle cells (VSMCs), the other abundant cell type in plaque. The TSPO ligands [3H](R)-1-(2-chlorophenyl)-N-methyl-(1-methylpropyl)-3-isoquinoline carboxamide ([3H](R)-PK11195) and [3H]N-(2,5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide ([3H]-DAA1106) bound to the same sites in human carotid atherosclerotic plaques in vitro, and demonstrated significant correlation with macrophage-rich regions. In conclusion, our data indicate that radioisotope-labelled DAA1106 has the potential to quantify the macrophage content of atherosclerotic plaque.