Vascular inflammation evaluated by [18F]-fluorodeoxyglucose positron emission tomography is associated with the metabolic syndrome.

OBJECTIVES: We investigated factors for carotid artery inflammation by [(18)F]-fluorodeoxyglucose (FDG) positron emission tomography (PET). BACKGROUND: Inflammation is present in some atherosclerotic plaques. The FDG-PET is capable of identifying and quantifying vascular inflammation within atherosclerotic plaques. METHODS: The FDG-PET imaging was performed in 216 consecutive patients (63 +/- 9 years, men:women 147:69) for cancer screening. Vascular inflammation in carotid atherosclerosis was quantified by measuring the standardized uptake value (SUV) of FDG into the artery. RESULTS: Multiple stepwise regression analysis revealed significant relationships between SUV and waist circumference (p < 0.001), hypertensive medication (p < 0.001), carotid intima-media thickness (p < 0.001), high-density lipoprotein cholesterol (p < 0.01, inversely), homeostasis model assessment of insulin resistance (p < 0.05), or high sensitivity C-reactive protein (p < 0.05). Age- and gender-adjusted SUV of FDG was significantly higher (p < 0.0001) in proportion to the accumulation of the number of the components of the metabolic syndrome. Thus, the metabolic syndrome was associated with increased FDG uptake in carotid atherosclerosis. CONCLUSIONS: Our present study may suggest that the metabolic syndrome is associated with inflammation in carotid atherosclerosis. (Detection of Plaque Inflammation by Positron Emission Tomography (PET); http://www.clinicaltrials.gov/ct/show/NCT00114504; NCT00114504).     

The prevalence of inflammation in carotid atherosclerosis: analysis with fluorodeoxyglucose-positron emission tomography.

AIMS: There is increasing evidence that (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) imaging can be useful for non-invasive measurement of atherosclerotic plaque inflammation in humans. However, it is unknown how often atherosclerosis has inflammation in humans. Thus, we examined the prevalence of inflammation in documented carotid atherosclerosis using FDG-PET imaging. METHODS AND RESULTS: FDG-PET imaging was performed in 100 consecutive patients who underwent carotid artery ultrasonography (CA-US) for screening of carotid atherosclerosis. Carotid atherosclerosis was considered when patients had the plaque score >or=5 and/or the focal thickening of the maximum intima-media complex >or=2 mm (localized plaque) by CA-US. The inflammation of carotid atherosclerosis was quantified by measuring the standardized uptake value (SUV) of FDG of the carotid artery. Inflammation was defined as present if the SUV score was >or=1.60 (>or=1 x standard deviation above the average). FDG-PET imaging revealed inflammation in 12 of 41 (29%) patients having carotid atherosclerosis, whereas in 6 of 59 (10%) patients not having carotid atherosclerosis (P < 0.01). In patients with documented atherosclerosis by CA-US, body mass index, waist circumference, and the number of localized plaques were greater in a subset with inflammation than in a subset without. CONCLUSION: Inflammation was visualized by FDG-PET imaging in approximately 30% of patients with documented carotid atherosclerosis.     

Assessment of atherosclerotic plaque activity in patients with sleep apnea using hybrid positron emission tomography/magnetic resonance imaging (PET/MRI): a feasibility study

Purpose

Evidence suggests that the inflammatory state of an atherosclerotic plaque is important in predicting future risk of plaque rupture. This study aims to investigate the feasibility of measuring plaque inflammation in patients with obstructive sleep apnea (OSA) utilizing advanced vascular imaging — hybrid positron-emission tomography/magnetic resonance imaging (PET/MRI) with fluorodeoxyglucose (FDG) tracer—before and after continuous positive airway pressure (CPAP).

Methods

Patients with newly diagnosed moderate to severe OSA underwent baseline PET/MRI for assessment of vascular inflammation of the carotid arteries and thoracic aorta prior to initiation of CPAP. Those adherent to CPAP returned for repeat imaging after 3–6 months of CPAP use. Atherosclerotic plaque activity, as measured by arterial wall FDG uptake, was calculated using target-to-background ratios (TBR) before and after CPAP.

Results

Five patients were recruited as part of a focused project. Mean age was 52 years (80% male), and mean apnea-hypopnea index (AHI) was 33. Three patients were objectively adherent with CPAP. In the pre-CPAP phase, all patients had focal FDG uptake in the carotid arteries and aorta. After CPAP, there was an average reduction in TBR of 5.5% (TBR_mean) and 6.2% (TBR_max) in carotid and aortic plaque inflammation, similar in magnitude to the reduction observed with statin therapy alone in non-OSA patients (previously reported by others).

Conclusions

We demonstrate the feasibility of using hybrid PET/MRI to assess atherosclerotic plaque inflammation in patients with OSA before and after CPAP. Use of the vascular PET/MRI platform in patients with OSA may provide better insight into the role of OSA and its treatment in reducing atherosclerotic inflammation.

     

联合应用无创影像学技术预警颈动脉不稳定斑块的相关研究

目的应用高分辨率动态对比增强磁共振成像(DCE-MRI),正电子发射断层显像(PET)技术检测患者颈动脉粥样硬化斑块,比较不同斑块成分之间的炎性程度,为早期预警颈动脉粥样硬化提供临床依据。方法选取颈动脉超声下斑块厚度>2mm的患者41例,分别行DCE-MRI和PET检查。以DCE-MRI图像分析结果,依照粥样硬化斑块表面纤维帽(无纤维帽、厚纤维帽、薄纤维帽、纤维帽破裂)或斑块内血管成分(钙化、胶原、脂质、出血),分析不同斑块性质影像学区别。以DCE-MRI为向导标记PET斑块位置,计算局部放射性活度标准化靶-本底比值(TBR),将DCE-MRI及PET对比研究,比较不同成分斑块间炎性反应程度,以鉴别不稳定斑块。结果不同斑块表面纤维帽中:纤维帽破裂TBRmax值最高,无纤维帽TBRmax值最低,两者比较差异有统计学意义(P<0.01);不同斑块成分中TBRmax值由大到小排列为:斑块出血、富含脂质坏死核、斑块胶原、斑块钙化,除斑块胶原与斑块钙化比较无显著差异外,其他斑块血管成分间差异均有统计学意义(P<0.01)。结论 DCE-MRI和PET无创检查技术联合应用,可以用于颈动脉粥样硬化的早期诊断与评估。     

Novel non-invasive approach for visualizing inflamed atherosclerotic plaques using fluorodeoxyglucose-positron emission tomography

There is an increasing body of evidence that a dynamic inflammatory process plays a role in the initiation, progression and destabilization of atherosclerotic plaques. The biological composition and inflammatory state of an atherosclerotic plaque, rather than the degree of stenosis or its size, are the major determinants of life-threatening events, such as ischemic cerebrovascular accident and acute coronary syndrome. To date, there is no non-invasive method clinically available for visualizing inflammation of individual plaques. Recently, we and others have shown that 18(F)-fluorodeoxyglucose (FDG) uptake, namely inflammation, can be evaluated quantitatively in the aortic, carotid, iliac and femoral plaques by using FDG positron emission tomography (PET) co-registered with computed tomography (FDG-PET/CT). Therefore, FDG-PET/CT, a combined functional and structural wholebody imaging modalities, holds great promise for non-invasive evaluation of inflammation – namely, activity – of atherosclerotic plaques of large arteries.     

Simvastatin attenuates plaque inflammation: evaluation by fluorodeoxyglucose positron emission tomography.

OBJECTIVES: We investigated whether simvastatin attenuates plaque inflammation by using 18F-fluorodeoxyglucose positron emission tomography (18FDG-PET) co-registered with computerized tomography. BACKGROUND: Inflammation plays a key role in progression and destabilization of atherosclerotic plaque. 18F-fluorodeoxyglucose PET is a promising tool for visualizing inflammation of atherosclerotic plaque. Antiinflammatory action is one of the pleiotropic effects of statins. METHODS: Forty-three consecutive subjects, who underwent 18FDG-PET for cancer screening and had 18FDG uptakes in the thoracic aorta and/or the carotid arteries, were randomized to either statin group receiving simvastatin (n = 21) or diet group receiving dietary management only (n = 22). The maximum standardized uptake values (SUVs) were measured in individual plaques, and were averaged for analysis of the subjectwise results. The responses were assessed after 3-month treatments. RESULTS: Positron emission tomography revealed 117 and 123 18FDG-positive plaques in the statin and diet groups, respectively. Simvastatin, but not diet alone, attenuated plaque (18)FDG uptakes and decreased the SUVs (p < 0.01). Simvastatin reduced low-density lipoprotein cholesterol (LDL-C) by 30% (p < 0.01) and increased high-density lipoprotein cholesterol (HDL-C) by 15% (p < 0.01), whereas LDL-C and HDL-C levels were not changed in the diet group. In the statin group, the decrease in the SUV was well correlated with the HDL-C elevation (p < 0.01) but not with the LDL-C reduction. CONCLUSIONS: 18F-fluorodeoxyglucose PET visualized plaque inflammation and simvastatin attenuated it. The LDL-C-independent effects of simvastatin may participate in the beneficial effect. 18F-fluorodeoxyglucose PET has a potential for visually monitoring plaque inflammation and the therapeutic effectiveness of statins.     

(18)Fluorodeoxyglucose positron emission tomography imaging of atherosclerotic plaque inflammation is highly reproducible: implications for atherosclerosis therapy trials.

OBJECTIVES: This study tested the near-term reproducibility of (18)fluorodeoxyglucose positron emission tomography (FDG-PET) imaging of atherosclerosis. BACKGROUND: It is known that FDG-PET can measure inflammation within the aorta, carotid, and vertebral arteries with histologic validation in humans and animal models of disease. By tracking changes in inflammation over time, PET could be used as a surrogate marker of antiatheroma drug efficacy. However, the short-term variability and reproducibility of the technique are unknown. METHODS: We imaged the carotid arteries and aorta in 11 subjects with FDG-PET/computed tomography twice, 14 days apart. We assessed interobserver and intraobserver agreement and interscan variability. RESULTS: Interscan plaque FDG variability over 2 weeks was very low; intraclass correlation coefficients (ICC) ranged between 0.79 and 0.92. Interobserver agreement was high across all territories imaged except aortic arch (ICC values from 0.90 to 0.97, arch 0.71). Intraobserver agreement was high, with ICC values between 0.93 and 0.98. CONCLUSIONS: Spontaneous change in plaque FDG uptake is low over 2 weeks, with favorable inter- and intraobserver agreement. Power calculations suggest that drug studies using FDG-PET imaging would require few subjects compared with other imaging modalities. This study strengthens the case for FDG-PET as a noninvasive plaque imaging technique.     

Imaging of vulnerable atherosclerotic plaques with FDG-microPET: no FDG accumulation

BACKGROUND: Non-invasive methods of evaluating atherosclerosis in humans and experimental animals are needed. Studies indicate that FDG-PET has a potential to detect vulnerable, inflamed atherosclerotic lesions. METHODS: Nine atherosclerotic apoE-deficient mice were PET scanned. Four to determine optimal timing for imaging, and five post mortem after 1h redistribution of FDG and again after sequential removal of the interscapular brown fat and the atherosclerotic aortic arch. Uptake in various tissues in fasting (n=13) and non-fasting (n=7) apoE-deficient mice, including atherosclerotic and non-atherosclerotic aorta, was measured. Finally, accelerated atherosclerosis was induced by carotid ligation (n=12), and FDG-uptake was measured. RESULTS: FDG accumulation initially thought to correspond to the atherosclerotic aortic arch was recorded. Removal of interscapular brown fat, but not atherosclerotic aortic arch, removed the signal. The aortic arch accumulated less FDG than the non-atherosclerotic thoracic aorta both in fasting (ratio 0.5, p=0.008) and non-fasting (ratio 0.33, p=0.02) conditions. Carotid atherosclerosis likewise failed to increase FDG-uptake compared to the non-ligated artery (ratio 1.03). CONCLUSION: Spontaneously developed advanced atherosclerotic lesions in aorta were, paradoxically, associated with reduced FDG uptake, and accelerated carotid atherosclerosis also failed to increase FDG-uptake. The results seriously question the potential of FDG-PET for imagining of advanced, vulnerable atherosclerotic lesions.     

Identification of Inflamed Aortic Plaque in Conventional Fluorodeoxyglucose–Positron Emission Tomography Myocardial Viability Studies

Background

It has been shown that ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is useful in identifying inflamed plaque in major arteries. This study evaluated the feasibility of inflamed plaque detection with routinely acquired cardiac FDG-PET viability studies in patients with severe coronary artery disease and left ventricular dysfunction.

Methods

Clinically indicated myocardial viability scans using FDG and PET combined with computed tomography from 103 patients were retrospectively analyzed for FDG uptake in the proximal, ascending, and descending thoracic aorta. Aortic uptake was graded on the basis of peak and mean target-to-background ratio (TBR): grade 0, < 1; grade 1, 1.01-1.49; grade 2, 1.5-1.99; and grade 3, > 2.

Results

Of the 103 patients, 71 (68.9%) had a history of myocardial infarction, 88 (85.4%) were on statins, and 70 (68%) were on angiotensin-converting enzyme (ACE) inhibitors. Increased FDG uptake (mean TBR grade 1-3) was seen in 79 of 103 patients (77%), and grade 3 aortic uptake based on peak TBR was found in 12 of 103 patients (12%).

Conclusions

Detection of inflamed atherosclerotic plaque in the aorta with conventional FDG viability scans is feasible. The rate of very positive uptake in this population of ischemic heart disease patients is low, possibly reflecting aggressive secondary risk factor modification including statin and ACE inhibitor use.     

Imaging of Coronary Inflammation with FDG-PET: Feasibility and Clinical Hurdles

Conventional algorithms and noninvasive imaging tests for the identification of stable, hemodynamically significant coronary artery disease offer little insight into the detection of potentially vulnerable and inflamed coronary plaques, those most likely to rupture and cause acute coronary syndromes. Positron emission tomography (PET) with fluorodeoxyglucose (FDG) serves as a potential novel modality for the identification of plaque inflammation, as initial studies in animal and human studies have demonstrated that FDG uptake correlates with macrophage accumulation and inflammation. Therapy with anti-inflammatory agents has also been demonstrated in the arterial vasculature to reduce plaque FDG uptake. Although imaging of coronary inflammation with FDG-PET holds tremendous promise, several hurdles remain to be surmounted prior to widespread clinical application.     

FDG PET/CT for evaluating systemic arterial inflammation induced by anthracycline-based chemotherapy of Hodgkin lymphoma: A retrospective cohort study

To evaluate arterial fluorodeoxyglucose (FDG) uptake as a marker of arterial inflammation in multiple vascular beds in patients treated with anthracycline-based chemotherapy for Hodgkin lymphoma (HL).We used maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR) to quantify arterial FDG uptake in the carotid artery, ascending aorta, abdominal aorta, and femoral artery obtained on positron emission tomography/computed tomography (PET/CT) imaging performed at baseline before chemotherapy and after completion of chemotherapy in patients with HL treated with an anthracycline-containing regimen. We compared the SUVmax and TBR obtained at baseline with that obtained post-chemotherapy for each arterial bed to evaluate the effect of anthracycline-based chemotherapy. We evaluated the effect of cardiovascular risk factors such as human immunodeficiency virus (HIV) infection, smoking, hypertension, and diabetes on the changes in SUVmax and TBR seen in the different arterial beds after anthracycline-based chemotherapy.Fifty-two patients were included with a mean age of 34.56 ± 10.19 years. There were 33 males, and 18 patients were HIV-infected. The mean interval between completion of chemotherapy and follow-up flourine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scan was 65 weeks. We found no significant difference in arterial FDG uptake measured by SUVmax and TBR in all arterial beds between the pre- and post-chemotherapy FDG PET/CT. There was no significant impact of HIV infection, smoking, and hypertension on the changes in arterial FDG uptake following treatment with anthracycline-based chemotherapy.In patients with HL who were treated with anthracycline-based chemotherapy, we found no significant increase in arterial inflammation measured by FDG PET/CT after an average follow-up period of about 65 weeks since completion of chemotherapy.     

Changing patterns of abnormal vascular wall F-18 fluorodeoxyglucose uptake on follow-up PET/CT studies.

BACKGROUND: Fluorine 18 fluorodeoxyglucose (FDG) uptake may be increased in atherosclerotic plaques in asymptomatic patients. Repeat positron emission tomography (PET)/computed tomography (CT) studies were assessed for changes in patterns of FDG uptake and CT calcifications. METHODS AND RESULTS: Fifty consecutive cancer patients (mean age, 68 +/- 8 years) had repeat PET/CT studies 8 to 26 months apart. PET, CT, and PET/CT images were retrospectively evaluated for vascular wall abnormalities and for interval changes in the thoracic and abdominal aortas, as well as in carotid and iliac arteries, classified as PET+/CT+, PET+/CT-, and PET-/CT+. There were 485 abnormal sites in the first study and 495 in the second. CT calcifications were found in 46 patients (92%) in the first study and in 47 (94%) in the second. Vascular wall FDG uptake was found in both studies in 37 patients (74%). The pattern changed in 57 of 119 PET+ sites (48%) in the second study compared with 15 of 366 PET- sites (4%) (P < .0001). In the second study new PET+ sites were observed in 36 of 111 sites (32%) versus new PET-/CT+ sites in 19 of 384 sites (5%) (P < .0001). CONCLUSIONS: Changes in vascular FDG activity and CT calcifications can be assessed by repeat PET/CT. FDG-avid foci may represent a dynamic process, transient inflammation, whereas CT calcifications may indicate stable atherosclerosis. These preliminary results support the need for further research.     

Molecular imaging of coronary inflammation

Coronary inflammation is related to atherosclerotic disease and, less frequently, systemic vasculitis. Regardless of the etiology, coronary inflammation is associated with adverse cardiac events. Molecular imaging with ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET/CT) allows in vivo assessment of coronary inflammation and evaluation of response to therapy. The aim of this review is to give an update on the recent development of FDG-PET/CT, discuss the potential roles of coronary inflammation imaging, review the limitations of FDG-PET/CT imaging, and give an overview of the new tracers available for PET/CT plaque imaging.     

Increased peripheral benzodiazepine receptors in arterial plaque of patients with atherosclerosis: an autoradiographic study with [(3)H]PK 11195

Inflammation in atherosclerotic plaques makes them unstable and can cause thrombosis. Therefore, it is important to detect macrophage activity for clinical management of atherosclerosis. Peripheral benzodiazepine receptor (PBR) is expressed in various tissue and organs including macrophages. In this study, we tested whether inflammation characterized by macrophage infiltration can be detected by PBR binding. Six patients diagnosed as carotid atherosclerosis underwent endarterectomy. Using the fresh frozen sections, presence of PBRs and macrophages was examined by in vitro autoradiography using [(3)H]PK 11195 and immunohistochemical staining of CD68, respectively. All sections showed specific binding of [(3)H]PK 11195, and the staining with CD68 indicating macrophage infiltration. Density and distribution of PBR detected by [(3)H]PK 11195 autoradiography were consistent with those of the immunohistochemical staining. In conclusion, this study demonstrated that macrophage and inflammatory activity in atherosclerotic plaque can be imaged specifically by the binding of PBR indicating future application of PET imaging for PBR.     

Positive correlation between malondialdehyde-modified low-density lipoprotein cholesterol and vascular inflammation evaluated by F-FDG PET/CT

Objective: The purpose of this study was to investigate the relationship between serum levels of malondialdehyde-modified low-density lipoprotein cholesterol (MDA-LDL) and vascular inflammation evaluated by fluorine-18 fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT). Methods/results: The study involved 106 consecutive patients (75 males and 31 female, mean age 62.5 ± 7.7 years) who visited our hospital for cardiovascular risk screening and underwent carotid ultrasonography, ¹⁸F-FDG PET/CT, complete history, physical examinations, and determination of blood chemistry including high-sensitivity C-reactive protein (hsCRP), asymmetric dimethylarginine (ADMA), and MDA-LDL. Vascular inflammation, was measured as blood-normalized standardized ¹⁸F-FDG uptake value, known as the target-to-background ratio (TBR) of carotid arteries. Univariate and multiple stepwise regression analyses were performed for determining independent correlates of carotid TBR values. Median MDA-LDL, mean carotid TBR values and carotid intima-media thickness (IMT) were 127.5 (IQR 92.0–147.8) U/l, 1.55 ± 0.22, and 0.72 ± 0.15 mm, respectively. Univariate analysis revealed that carotid TBR values positively correlated with MDA-LDL (p = 0.043) and carotid IMT (p = 0.049). Multiple stepwise regression analysis demonstrated that MDA-LDL (p = 0.043) and carotid IMT (p = 0.038) were independently associated with carotid TBR values. Conclusion: The present study reveals that serum levels of MDA-LDL are independently associated with vascular inflammation evaluated by ¹⁸F-FDG PET/CT. Circulating MDA-LDL may be a more useful clinical biomarker for vascular inflammation within the atherosclerotic plaques than hsCRP or ADMA.     

Assessment of calcification and inflammation with positron emission tomography in aortic stenosis and atherosclerosis

BackgroundCalcification and inflammation are key pathological processes in aortic stenosis and atherosclerosis. Using combined positron emission tomography and computed tomography (PET/CT), we sought to investigate their contribution to disease progression in aortic stenosis and to help identify vulnerable atherosclerotic plaque.MethodsIn the first part of the study patients with calcific aortic valve disease stenosis were prospectively compared with age-matched and sex-matched controls with normal valves. Aortic valve severity was determined at baseline and 1 year by echocardiography and CT calcium scoring. Calcification and inflammation in the valve were assessed by sodium 18-fluoride (NaF) and 18-fluorodeoxyglucose (FDG) uptake with PET. In the second part of the study NaF and FDG activity was assessed in the coronary arteries both in patients with stable coronary disease and in patients after myocardial infarction.Findings101 patients with aortic stenosis were compared with 20 controls. Tracer activity (target to background ratio [TBR]) was higher in patients with aortic stenosis than in controls (mean NaF 2·87 [SD 0·82] vs 1·55 [0·17], FDG 1·58 [0·21] vs 1·30 [0·13]; both p<0·01). NaF uptake displayed a progressive rise with valve severity (r²=0·540) with a more modest increase observed for FDG (r²=0·218). Baseline NaF correlated closely with alkaline phosphatase staining on immunohistochemistry (r²=0·79) and was a better predictor of disease progression at 1 year (r²=0·44, n=20) than was FDG (r²=0·02) or baseline calcium score (r²=0·36, current best predictor). Increased NaF activity was observed in 45 (42%) of 106 patients with stable coronary atherosclerosis and was localised to individual coronary plaques. These patients had higher rates of previous major adverse cardiovascular events (p=0·016) and higher Framingham risk scores (p=0·011) than did patients without increased uptake. In patients after myocardial infarction (n=15) intense NaF activity was observed at the site of the culprit lesion, with increased uptake compared with the maximum uptake elsewhere in the coronary arteries (TBR median 1·56 [IQR 1·49–1·82] vs 1·23 [1·15–1·48], p=0·02).InterpretationIn the valve, NaF holds promise in predicting aortic stenosis progression. In the coronary arteries it identifies culprit plaque post myocardial infarction and stable patients at elevated cardiac risk.FundingBritish Heart Foundation.     

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.     

Association between sRAGE, esRAGE levels and vascular inflammation: analysis with (18)F-fluorodeoxyglucose positron emission tomography

BackgroundThe receptor for advanced glycation end-products (RAGE) and its diverse ligands play a pivotal role in the development of cardiovascular disease. Soluble forms of RAGE (sRAGE), including the splice variant endogenous secretory RAGE (esRAGE), may neutralize AGE-RAGE mediated vascular damage by acting as a decoy. ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a novel imaging technique for detecting vascular inflammation.MethodsWe examined vascular inflammation measured using FDG-PET in 41 type 2 diabetes patients and 41 healthy control subjects in the right carotid artery. Vascular ¹⁸F-FDG uptake was measured as the blood-normalized standardized uptake value (SUV), known as the target-to-background ratio (TBR). In addition, their relationship with carotid intima-media thickness (CIMT), estimated GFR (eGFR), and other cardiovascular risk factors was evaluated.ResultsBoth mean and maximum TBR values were significantly higher in patients with type 2 diabetes compared to healthy subjects. After adjusting for age and gender, sRAGE levels were significantly correlated with both mean and maximum TBR values, but not with CIMT values. Multiple linear regression analysis showed that maximum TBR values were independently associated with sRAGE levels in addition to HbA1c and eGFR.ConclusionsCirculating sRAGE showed significant association with TBR values measured using FDG-PET, which reflect vascular inflammation.     

Subclinical atherosclerosis in psoriatic arthritis: a case-control study

OBJECTIVE: To investigate the prevalence of subclinical atherosclerosis among patients with psoriatic arthritis (PsA). METHODS: Forty patients with PsA were enrolled. Controls were matched by age, sex, and atherosclerotic risk factors. All patients and controls underwent duplex scan of the carotid arteries. Carotid intima-media thickness (IMT) was evaluated and the presence of atherosclerotic plaques was recorded. The plaques were graded and carotid plaque index was calculated. RESULTS: Patients with PsA had a higher IMT (mean +/- standard deviation, 1.04 +/- 0.35 mm vs 0.88 +/- 0.29 mm in controls; p = 0.03), and had a higher carotid plaque index than did matched controls (2.3 +/- 2.6, compared to 1.12 +/- 2.09; p = 0.03). Multivariate analysis demonstrated that PsA status as well as age and triglyceride levels were associated with the presence of carotid plaque. Other traditional risk factors were more prevalent among patients with PsA; however, they were not statistically significant. CONCLUSION: Our study demonstrates that patients with PsA may have an increased prevalence of subclinical atherosclerosis. These findings may not be solely attributable to traditional risk factors alone. Special attention and strict control of atherosclerotic risk factors in patients with PsA is warranted.     

Non-FDG imaging of atherosclerosis: will imaging of MMPs assess plaque vulnerability?

Acute ruptures of atherosclerotic plaques with subsequent occlusion account for the vast majority of clinical events such as myocardial infarction or stroke. New imaging approaches focusing on the visualization of inflammation in the vessel wall could emerge as tools for individualized risk assessment and prevention of events. To this end, PET employing (18)F-fluorodeoxyglucose (FDG) has recently been introduced for the first clinical trials. Although this approach nicely visualizes plaques inflammation questions remain with respect to if and how this inflammatory signal can be employed for predicting individual plaque rupture. Molecular imaging of proteases such as matrix-metalloproteinases (MMPs) involved in several steps in plaque progression driving plaques into vulnerable, rupture-prone states seems a promising alternative approach. This review introduces and discusses the vulnerable plaque concept, animal models with human-like plaque ruptures and the potential of a FDG versus a non-FDG MMP-targeted strategy to image rupture-prone plaques.