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Tritiated deoxyglucose autoradiography of symptomatic carotid artery plaque. The larger panel shows typical plaque architecture, whereas the inset shows that silver grains have accumulated at the lipid core/fibrous cap border region, predominately within macrophages . Magnification 10 and 20.
Source publication
This article is not available through ChesterRep. It can be accessed at http://circ.ahajournals.org/cgi/content/full/105/23/2708 This study demonstrates that atherosclerotic plaque inflammation can be imaged with 18FDG-PET, and that symptomatic, unstable plaques accumulate more 18FDG than asymptomatic lesions. This article was submitted to the RAE2...
Citations
... It is in routine clinical use for the staging of a range of cancers and the assessment of treatment responses. Notably, it is also the gold standard method for the identification and quantification of inflammatory activity, including in large arteries [13][14][15][16] . ...
Background
Anthracyclines, such as doxorubicin, are important anti-cancer therapies but are associated with arterial injury. Histopathological insights have been limited to small animal models and the role of inflammation in the arterial toxic effects of anthracycline is unclear in humans. Our aims were: 1) To evaluate aortic media fibrosis and injury in non-human primates treated with anthracyclines; 2) To assess the effect of anthracycline on aortic inflammation in patients treated for lymphoma.
Methods
1) African Green monkeys (AGM) received doxorubicin (30–60 mg/m ² /biweekly IV, cumulative dose: 240 mg/m ² ). Blinded histopathologic analyses of collagen deposition and cell vacuolization in the ascending aorta were performed 15 weeks after the last doxorubicin dose and compared to 5 age- and gender-matched healthy, untreated AGMs. 2) Analysis of the thoracic aorta of patients with diffuse large B-cell lymphoma (DLBCL), at baseline and after doxorubicin exposure, was performed using ¹⁸ F-fluorodeoxyglucose ( ¹⁸ F-FDG) positron emission tomography/computed tomography (PET/CT) in this observational study. The primary outcome was change in maximal tissue-to-background ratio (TBRmax) of the thoracic aorta from baseline to their end-of-treatment clinical PET/CT.
Results
In AGMs, doxorubicin exposure was associated with greater aortic fibrosis (collagen deposition: doxorubicin cohort 6.23±0.88% vs. controls 4.67±0.54%; p=0.01) and increased intracellular vacuolization (doxorubicin 66.3 ± 10.1 vs controls 11.5 ± 4.2 vacuoles/field, p<0.0001) than untreated controls.
In 101 patients with DLBCL, there was no change in aortic TBRmax after anthracycline exposure (pre-doxorubicin TBRmax 1.46±0.16 vs post-doxorubicin TBRmax 1.44±0.14, p=0.14). The absence of change in TBRmax was consistent across all univariate analyses.
Conclusions
In a large animal model, anthracycline exposure was associated with aortic fibrosis. In patients with lymphoma, anthracycline exposure was not associated with aortic inflammation.Further research is required to elucidate the mechanisms of anthracycline-related vascular harm.
... Furthermore, detection and quantification of the degree of inflammation has also been attracting attention with the usage of novel imaging techniques such as 18 F-FDG PET/ CT [38]. A higher FDG tracer uptake has been observed for actively metabolic plaques (unstable plaques), in accordance with the extent of the intra-plaque inflammatory processes. ...
Cardiovascular disease is a major cause of morbidity and mortality worldwide. In the last few years, the role of inflammation and inflammatory modulatory medications is investigated for the optimal treatment of coronary artery disease. It can be hypothesized that since inflammation is also involved in carotid artery stenosis development and progression, the same class of medication could be useful. Our objective with this review is to present the available evidence, published studies and promising ongoing trials on the role of anti-inflammatory medications – with a special emphasis on the most commonly used drug of this class: colchicine – in patients with carotid artery stenosis.
... To optimize the contrast between plaque and background [17][18][19], 3 h were allowed to elapse post-injection before the rats were re-anesthetized and positioned in a dedicated small animal PET/CT camera (D-PET, Inveon ® , Siemens Preclinical Solutions, Knoxville, Tennessee, U.S.A.). The rats were positioned with their thorax at the center of the field of view. ...
Background
The apolipoprotein E-deficient (apoE−/−) mouse is a well-established model for studying atherosclerosis. However, its small size limits its use in longitudinal positron emission tomography (PET) imaging studies. Recently, the apoE−/− rat has emerged as an alternative. With this study, we investigate the feasibility of using apoE−/− rats as an in vivo model for longitudinal atherosclerotic PET/CT imaging.
Results
ApoE−/− rats showed significantly higher [¹⁸F]FDG uptake than controls in the aortic arch (+ 18.5%, p < 0.001) and abdominal aorta (+ 31.0%, p < 0.001) at weeks 12, 26, and 51. ApoE−/− rats exhibited hypercholesterolemia, as evidenced by plasma cholesterol levels that were up to tenfold higher, and total hepatic cholesterol levels that were up to threefold higher than the control rats at the end of the study. Fast protein liquid chromatography cholesterol profiling indicated very high levels of pro-atherogenic apoB-containing very low-density lipoprotein and low-density lipoprotein fractions in the apoE−/− rats. Atherosclerotic lesions cover 19.9% of the surface of the aortic arch (p = 0.0013), and there was a significantly higher subendothelial accumulation of ED1-positive macrophages in the abdominal aorta of the apoE−/− rats compared to control rats (Ctrl) (p = 0.01). No differences in neutral sterols were observed but higher levels of bile acids were found in the apoE−/− rats.
Conclusion
These data demonstrate early signs of hypercholesterolemia, high levels of bile acids, the development of atherosclerotic lesions, and macrophage accumulation in apoE−/− rats. Therefore, this model shows promise for atherosclerosis imaging studies.
... At present, there are few easily accessible methods for the early detection of local plaque inflammation. The metabolic activity of inflammatory cells within carotid atherosclerotic plaque can be visualized and measured using 18 F-fluorodeoxyglucose positron emission tomography (6,7). However, this technique is not commonly used in clinical practice due to poor spatial resolution, radiation exposure, and cost. ...
Background
Carotid atherosclerotic plaque inflammation plays a critical role in guiding the prevention of secondary stroke. Increased perivascular adipose tissue attenuation observed on computed tomography angiography (CTA) may indicate local inflammation. Our objective was to investigate whether pericarotid adipose tissue (PCAT), as a local inflammation biomarker, could distinguish between different stages of carotid atherosclerotic disease plaques.
Methods
We prospectively enrolled 45 consecutive acute stroke patients with carotid artery stenosis from September 2019 to September 2021. We then matched them to non-stroke patients (n=67) and no carotid atherosclerotic disease controls (n=65) based on gender, age, and cardiovascular risk factors. We compared PCAT attenuation, carotid plaque features on CTA, clinical risk factors, and serum inflammatory factors across the different groups. To detect the association of PCAT attenuation with stage of carotid atherosclerotic disease, we used multivariable logistic regression analysis.
Results
Patients with acute stroke had a higher PCAT attenuation (−78.80±11.62 HU) than patients with non-stroke (−89.01±10.81 HU, P<0.001) and no carotid atherosclerotic disease controls (−95.24±10.81 HU, P<0.001). PCAT attenuation was significantly increased in non-stroke patients compared to non-stroke patients over no carotid atherosclerotic disease controls (P=0.004). The association between PCAT attenuation and the stage of carotid atherosclerotic disease was independent of age, gender, cardiovascular risk factors, and CTA plaque characteristics. No interaction was observed between clinical features and CTA plaque characteristics on PCAT attenuation.
Conclusions
PCAT attenuation, which is an imaging biomarker of local inflammation, independently distinguishes patients with different stages of carotid atherosclerotic disease. Quantitative evaluation of PCAT attenuation in carotid atherosclerotic disease is expected to guide targeted surgical treatment of carotid plaque.
... Among them, 18 F-fluorodeoxyglucose (FDG) positron emission tomography and computed tomography (PET/CT) is a widely validated noninvasive imaging method for detecting vulnerable plaque clinically and pre-clinically and uptakes of which are proportional to the areas of CD68 staining on histological section, which is a protein highly expressed by circulating macrophages [13][14][15]. Furthermore, FDG uptake of the arterial wall reflects the severity of inflammatory status in atherosclerosis [13,16], and a metaanalysis suggested that high FDG uptake can differentiate vulnerable or symptomatic plaques from stable or asymptomatic plaques [17]. ...
PurposeThis study aimed to compare the clinical significance of two parameters, division of standardized uptake value (SUV) of target arterial activity by background venous blood pool activity (SUVA/V) and subtraction of background venous blood pool activity from SUV of target arterial activity (SUVA-V) of carotid arteries with atherosclerotic plaques using 18F-fluorodeoxyglucose (FDG) positron emission tomography and computed tomography (PET/CT).Methods
Patients aged 50 years or more who were diagnosed with carotid artery stenosis of 50% or more with carotid Doppler ultrasonography and had torso 18F-FDG PET/CT were enrolled retrospectively and classified patients who developed cerebrovascular events (CVEs) within 5 years after 18F-FDG PET/CT scan as the active group and patients who did not experience the CVE within 5 years as an inactive group. We calculated SUVA/V and SUVA-V using measurements of SUVmax of carotid arteries and mean SUV of superior vena cava (SVC).ResultsSUVA-V, SUVA-V_high, and SUVA-V_low were significantly higher in the active group than in the inactive group, but neither SUVA/V, SUVA/V_high, nor SUVA/V_low showed significant differences between the active and inactive groups. The difference in rank between groups of SUVA/V_high and SUVA/V_low was greater than the difference in rank between groups of SUVA-V_high and SUVA-V_low. The CVE incidence differed between SUVA/V_high and SUVA/V_low of high carotid FDG uptake, but the CVE incidence did not differ between SUVA-V_high and SUVA-V_low of high carotid FDG uptake.ConclusionSUVA-V may be a more rational solution than SUVA/V for evaluating atherosclerotic plaque inflammation on 18F-FDG PET/CT.
... In 2002, Rudd et al reported that FDG-uptake was 27% higher in symptomatic carotid plaques when compared with the contralateral side in eight patients who subsequently underwent CEA. 14 Animal models subsequently illustrated the association between FDG-uptake and macrophage density in excised plaque. Using an animal model of atherosclerosis (Watanabe heritable hyperlipidemic [WHHL] rabbits), Ogawa et al showed that FDG accumulates in atherosclerotic plaque. ...
... Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 13 July 2023 doi:10.20944/preprints202307.0880.v114 ...
Atherosclerosis is a chronic systemic inflammatory condition of the vasculature and a leading cause of stroke. Luminal stenosis severity is an important factor in determining vascular risk. Conventional imaging modalities, such as angiography or duplex ultrasonography, are used to quantify stenosis severity and inform clinical care but provide limited information on plaque biology. Inflammatory processes are central to atherosclerotic plaque progression and destabilization. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is a validated technique for quantifying plaque inflammation. In this review, we discuss the evolution of FDG-PET as an imaging modality to quantify plaque vulnerability, challenges to standardization of image acquisition and analysis, its potential application to routine clinical care after stroke, and the possible role it will play in future drug discovery.
... 29 In patients with symptomatic carotid atherosclerosis undergoing FDG PET/CT, FDG uptake was 27% higher in symptomatic lesions than in contralateral non-culprit lesions. 30,31 FDG PET is an indicator of inflammation and plaque vulnerability. One study associating electronegative low-density lipoprotein (LDL) with plaque vulnerability utilized FDG uptake as a metric for inflammation in ischemic stroke patients. ...
Traditional atherosclerosis imaging modalities are limited to late stages of disease, prior to which patients are frequently asymptomatic. Positron emission tomography (PET) imaging allows for the visualization of metabolic processes underscoring disease progression via radioactive tracer, allowing earlier-stage disease to be identified. 2-deoxy-2-[fluorine-18]fluoro-D-glucose (18F-FDG) uptake largely reflects the metabolic activity of macrophages, but is unspecific and limited in its utility. By detecting areas of microcalcification, 18F-Sodium Fluoride (18F-NaF) uptake also provides insight into atherosclerosis pathogenesis. Gallium-68 DOTA-0-Tyr3-Octreotate (68Ga-DOTATATE) PET has also shown potential in identifying vulnerable atherosclerotic plaques with high somatostatin receptor expression. Finally, 11-carbon (11C)-choline and 18F-fluoromethylcholine (FMCH) tracers may identify high-risk atherosclerotic plaques by detecting increased choline metabolism. Together, these radiotracers quantify disease burden, assess treatment efficacy, and stratify risk for adverse cardiac events.
... As such, the authors concluded ACS survivors may have bilateral carotid inflammation; they hypothesized systemic immune activation leading to arterial dysfunction (via disseminated trans-coronary neutrophil activation with coronary plaque instability) and subsequent symptomatic atherosclerosis could be a linkage between ACS and ischemic stroke. Multiple similarly designed FDG-PET studies of patients with symptomatic internal carotid artery stenosis and atherosclerosis found serum LDL and total cholesterol were associated with carotid plaque inflammation and FDG uptake thereby corroborating a significant role of lipids in plaque development [23][24][25]. ...
Stroke is the leading cause of disability worldwide, the second most common cause of dementia and the third leading cause of death. Though the etiology of stroke has been explored extensively, there remains open questions in the scientific and clinical study of stroke. Traditional imaging techniques, such as magnetic resonance imaging and computed tomography, have been applied extensively and remain mainstays in clinical practice. Nevertheless , positron emission tomography has proven to be a powerful molecular imaging tool in exploring the scientific aspects of neurological disease, and stroke remains an area of great interest. This review article examines the role of positron emission tomography in the study of stroke including its contributions to elaborating related pathophysi-ology and delving into possible clinical applications.
... F-18-fluorodeoxyglucose positron emission tomography (FDG PET) provides an attractive and pragmatic means to measure and follow vascular inflammation in these patients, as it is the most widely validated and applied imaging probe in this regard. [10][11][12] Previous studies have shown that its uptake predicts MACE; [13][14][15] and it is also highly sensitive to short-term treatment effects. 16,17 Furthermore, PET myocardial perfusion imaging in conjunction with rubidium-82 ( 82 Rb) affords the ability to assess regional myocardial blood flow to the left ventricle in absolute terms (mLÁmin -1 Ág -1 ). ...
Aim
The aim of the study was to evaluate the changes in central vascular inflammation measured by FDG PET and myocardial blood flow reserve (MFR) determined by ⁸² Rb PET following therapy with biologic agents for 6 months in patients with psoriatic arthritis (PsA) and/or cutaneous psoriasis (PsO) (group 1) and compare with PsO subjects receiving non-biologic therapy (group 2) and controls (group 3).
Methods and Results
Target-to-background ratio (TBR) by FDG PET in the most diseased segment of the ascending aorta (TBR max ) was measured to assess vascular inflammation. ⁸² Rb PET studies were used to assess changes in left ventricular MFR. A total of 34 participants were enrolled in the study (11 in group 1, 13 in group 2, and 10 controls). A significant drop in the thoracic aorta uptake was observed in the biologic-treated group (ΔTBR max : − .46 ± .55) compared to the PsO group treated with non-biologic therapy (ΔTBR max : .23 ± .67). Those showing response to biologic agents maintained MFR compared to who showed no response.
Conclusion
In a cohort of psoriasis patients treated with biologics, FDG uptake in the thoracic aorta decreased over the study period. Patients who demonstrated a significant anti-inflammatory response on FDG PET imaging maintained their MFR compared to non-responders.
... Before endarterectomy, Tawakol et al. [164] used PET scanning on patients with severe carotid stenosis and discovered a strong relationship between the uptake of 18F-FDG in carotid plaques and the staining of macrophages on comparable pathologi-cal specimens. Rudd et al. [165] utilized autoradiography to show in a related investigation that 18F-FDG avid lesions in individuals with symptomatic carotid stenosis were associated with macrophage-rich plaque regions in endarterectomy specimens. Additionally, the researchers discovered that symptomatic carotid lesion uptake of 18F-FDG was 27% higher than ipsilateral asymptomatic lesions [165]. ...
... Rudd et al. [165] utilized autoradiography to show in a related investigation that 18F-FDG avid lesions in individuals with symptomatic carotid stenosis were associated with macrophage-rich plaque regions in endarterectomy specimens. Additionally, the researchers discovered that symptomatic carotid lesion uptake of 18F-FDG was 27% higher than ipsilateral asymptomatic lesions [165]. ...
Abnormal or excessive accumulation of adipose tissue leads to a condition called obesity. Long-term positive energy balance arises when energy intake surpasses energy expenditure, which increases the risk of metabolic and other chronic diseases, such as atherosclerosis. In industrialized countries, the prevalence of coronary heart disease is positively correlated with the human development index. Atherosclerotic cardiovascular disease (ACD) is among the primary causes of death on a global scale. There is evidence to support the notion that individuals from varied socioeconomic origins may experience varying mortality effects as a result of high blood pressure, high blood sugar, raised cholesterol levels, and high body mass index (BMI). However, it is believed that changes in the concentration of trace elements in the human body are the main contributors to the development of some diseases and the transition from a healthy to a diseased state. Metal trace elements, non-metal trace elements, and the sampling site will be examined to determine whether trace elements can aid in the diagnosis of atherosclerosis. This article will discuss whether trace elements, discussed under three sections of metal trace elements, non-metal trace elements, and the sampling site, can participate in the diagnosis of atherosclerosis.
