Semi-Automatic Graphical Tool for Measuring Coronary Artery Spatially Weighted Calcium Score from Gated Cardiac Computed Tomography Images.

The current standard for measuring coronary artery calcification to determine the extent of atherosclerosis is by calculating the Agatston score from computed tomography (CT). However, the Agatston score disregards pixel values less than 130 Hounsfield Units (HU) and calcium regions less than 1 mm2. Due to this thresholding, the score is not sensitive to small, weakly attenuating regions of calcium deposition and may not detect nascent micro-calcification. A recently proposed metric called the spatially weighted calcium score (SWCS) also utilizes CT but does not include a threshold for HU and does not require elevated signals in contiguous pixels. Thus, the SWCS is sensitive to weakly attenuating, smaller calcium deposits and may improve the measurement of coronary heart disease risk. Currently, the SWCS is underutilized owing to the added computational complexity. To promote translation of the SWCS into clinical research and reliable, repeatable computation of the score, the aim of this study was to develop a semi-automatic graphical tool that calculates both the SWCS and the Agatston score. The program requires gated cardiac CT scans with a calcium hydroxyapatite phantom in the field of view. The phantom allows for deriving a weighting function, from which each pixel's weight is adjusted, allowing for the mitigation of signal variations and variability between scans. With all three anatomical views visible simultaneously, the user traces the course of the four main coronary arteries by placing points or regions of interest. Features such as scroll-to-zoom, double-click to delete, and brightness/contrast adjustment, along with written guidance at every step, make the program user-friendly and easy to use. Once tracing the arteries is complete, the program generates reports, which include the scores and snapshots of any visible calcium. The SWCS may reveal the presence of subclinical disease, which may be used for early intervention and lifestyle changes.

Pharyngeal Inflammation on Positron Emission Tomography/Magnetic Resonance Imaging Before and After Obstructive Sleep Apnea Treatment.

Rationale: There is upper airway inflammation in patients with obstructive sleep apnea (OSA), which reduces with continuous positive airway pressure (CPAP) therapy. Objectives: Validate the use of positron emission tomography (PET)/magnetic resonance imaging (MRI) to quantify metabolic activity within the pharyngeal mucosa of patients with OSA against nasal lavage proteomics and assess the impact of CPAP therapy. Methods: Adults with OSA underwent [18F]-Fluoro-2-deoxy-D-glucose PET/MRI of the neck before and 3 months after initiating CPAP. Nasal lavage samples were collected. Inflammatory protein expression from samples was analyzed using the Olink platform. Upper airway imaging segmentation was performed. Target-to-background ratio (TBRmax) was calculated from target pharyngeal maximum standard uptake values (SUV) and personalized background mean SUV. Most-diseased segment TBRmax was identified per participant at locations with the highest PET avidity. Correlation analysis was performed between baseline TBRmax and nasal lavage proteomics. TBRmax was compared before and after CPAP using linear mixed-effect models. Results: Among 38 participants, the baseline mean age was 46.3 years (standard deviation [SD], 12.5), 21% were female, the mean body mass index was 30.9 kg/m2 (SD, 4.6), and the mean respiratory disturbance index measured by peripheral arterial tonometry was 31 events/h (SD, 16.4). There was a significant positive correlation between pharyngeal mucosa most-diseased segment TBRmax and nasal lavage proteomic inflammation (r = 0.41 [P < 0.001, false discovery rate = 0.002]). Primary analysis revealed a reduction in the most-diseased segment TBRmax after a median of 2.91 months of CPAP therapy (-0.86 [standard error (SE) ± 0.30; P = 0.007]). Stratified analysis by smoking status revealed a significantly decreased most-diseased segment TBRmax after CPAP therapy among never-smokers but not among ever-smokers (-1.01 [SE ± 0.39; P = 0.015] vs. -0.64 [SE ± 0.49; P = 0.201]). Conclusions: CPAP therapy reduces metabolic activity measured by PET/MRI within the upper airway of adults with OSA. Furthermore, PET/MRI measures of upper airway metabolic activity correlate with a noninvasive marker of inflammation (i.e., nasal lavage inflammatory protein expression).

Reducing cardiovascular risk with immunomodulators: a randomised active comparator trial among patients with rheumatoid arthritis.

OBJECTIVE: Recent large-scale randomised trials demonstrate that immunomodulators reduce cardiovascular (CV) events among the general population. However, it is uncertain whether these effects apply to rheumatoid arthritis (RA) and if certain treatment strategies in RA reduce CV risk to a greater extent. METHODS: Patients with active RA despite use of methotrexate were randomly assigned to addition of a tumour necrosis factor (TNF) inhibitor (TNFi) or addition of sulfasalazine and hydroxychloroquine (triple therapy) for 24 weeks. Baseline and follow-up 18F-fluorodeoxyglucose-positron emission tomography/CT scans were assessed for change in arterial inflammation, an index of CV risk, measured as an arterial target-to-background ratio (TBR) in the carotid arteries and aorta. RESULTS: 115 patients completed the protocol. The two treatment groups were well balanced with a median age of 58 years, 71% women, 57% seropositive and a baseline disease activity score in 28 joints of 4.8 (IQR 4.0, 5.6). Baseline TBR was similar across the two groups. Significant TBR reductions were observed in both groups-ΔTNFi: -0.24 (SD=0.51), Δtriple therapy: -0.19 (SD=0.51)-without difference between groups (difference in Δs: -0.02, 95% CI -0.19 to 0.15, p=0.79). While disease activity was significantly reduced across both treatment groups, there was no association with change in TBR (ß=0.04, 95% CI -0.03 to 0.10). CONCLUSION: We found that addition of either a TNFi or triple therapy resulted in clinically important improvements in vascular inflammation. However, the addition of a TNFi did not reduce arterial inflammation more than triple therapy. TRIAL REGISTRATION NUMBER: NCT02374021.

Scan-rescan measurement repeatability of 18F-FDG PET/MR imaging of vascular inflammation.

Non-invasive positron emission tomography (PET) of vascular inflammation and atherosclerotic plaque by identifying increased uptake of 18F-fluordeoxyglucose (18F-FDG) is a powerful tool for monitoring disease activity, progression, and its response to therapy. 18F-FDG PET/computed tomography (PET/CT) of the aorta and carotid arteries has become widely used to assess changes in inflammation in clinical trials. However, the recent advent of hybrid PET/magnetic resonance (PET/MR) scanners has advantages for vascular imaging due to the reduction in radiation exposure and improved soft tissue contrast of MR compared to CT. Important for research and clinical use is an understanding of the scan-rescan repeatability of the PET measurement. While this has been studied for PET/CT, no data is currently available for vascular PET/MR imaging. In this study, we determined the scan-rescan measurement repeatability of 18F-FDG PET/MR in the aorta and carotid arteries was less than 5%, comparable to similar findings for 18F-FDG PET/CT.

Testing the Effects of Disease-Modifying Antirheumatic Drugs on Vascular Inflammation in Rheumatoid Arthritis: Rationale and Design of the TARGET Trial.

Individuals with rheumatoid arthritis (RA) are at increased risk for atherosclerotic cardiovascular disease (ASCVD) events relative to the general population, potentially mediated by atherosclerotic plaques that are more inflamed and rupture prone. We sought to address whether RA immunomodulators reduce vascular inflammation, thereby reducing ASCVD risk, and whether such reduction depends on the type of immunomodulator. The TARGET (Treatments Against RA and Effect on 18-Fluorodeoxyglucose [18 F-FDG] Positron Emission Tomography [PET]/Computed Tomography [CT]) trial (NCT02374021) will enroll 150 patients with RA with active disease and an inadequate response to methotrexate. Participants will be randomized to add either a tumor necrosis factor (TNF) inhibitor (etanercept or adalimumab) or sulfasalazine and hydroxychloroquine to their background methotrexate. Participants will undergo full-body 18 F-FDG-labelled PET scanning at baseline and after 6 months. Efficacy and safety evaluations will occur every 6 weeks, with therapy modified in a treat-to-target approach. The primary outcome is the comparison of change in arterial inflammation in the wall of the aorta and carotid arteries between the randomized treatment groups, specifically, the change in the mean of the maximum target-to-background ratio of arterial 18 F-FDG uptake in the most diseased segment of either the aorta and carotid arteries. A secondary analysis will compare the effects of achieving low disease activity or remission with those of moderate to high disease activity on vascular inflammation. The TARGET trial will test, for the first time, whether RA treatments reduce arterial inflammation and whether such reduction differs according to treatment strategy with either TNF inhibitors or a combination of nonbiologic disease-modifying antirheumatic drugs.

Atherosclerosis inflammation and burden in young adult smokers and vapers measured by PET/MR.

BACKGROUND AND AIMS: Electronic cigarette (EC) use is popular among youth, touted as a safer alternative to smoking and promoted as a tool to aid in smoking cessation. EC cardiovascular safety however is not well established. The aim of this study was to examine cardiovascular consequences of EC use by evaluating their effect on the entire atherosclerotic cascade in young adults using noninvasive combined positron emission tomography (PET)/magnetic resonance imaging (MR) and comparing EC use with age matched smokers of traditional cigarettes and nonsmoking controls. METHODS: Carotid PET/MR was applied to look at vascular inflammation (18-fluorodeoxyglucose (FDG)-PET) and plaque burden (multi-contrast MR of vessel wall) from 60 18-30 year-old subjects (20 electronic cigarette users, 20 traditional smokers and 20 nonsmokers). RESULTS: Groups were reasonably well balanced in terms of age, gender, demographics, cardiovascular risk and most biomarkers. There were no differences in vascular inflammation as measured by 18-FDG-PET target to background ratios (TBR) between EC users, traditional cigarette smokers and nonsmokers. However, measures of carotid plaque burden - wall area, normalized wall index, and wall thickness - measured from MR were significantly higher in both traditional smokers and EC users than in nonsmokers. CONCLUSIONS: Young adult EC users, smokers and nonsmokers in our study did not exhibit vascular inflammation as defined by 18-F-FDG-PET TBR max, but smokers and EC users had significantly more carotid plaque burden compared to matched nonsmokers. Results could indicate that vaping does not cause an increase in vascular inflammation as measured by FDG-PET.

Review of radiographic findings in COVID-19.

The purpose of this study is to review the published literature for the range of radiographic findings present in patients suffering from coronavirus disease 2019 infection. This novel corona virus is currently the cause of a worldwide pandemic. Pulmonary symptoms and signs dominate the clinical picture and radiologists are called upon to evaluate chest radiographs (CXR) and computed tomography (CT) images to assess for infiltrates and to define their extent, distribution and progression. Multiple studies attempt to characterize the disease course by looking at the timing of imaging relative to the onset of symptoms. In general, plain CXR show bilateral disease with a tendency toward the lung periphery and have an appearance most consistent with viral pneumonia. Chest CT images are most notable for showing bilateral and peripheral ground glass and consolidated opacities and are marked by an absence of concomitant pulmonary nodules, cavitation, adenopathy and pleural effusions. Published literature mentioning organ systems aside from pulmonary manifestations are relatively less common, yet present and are addressed in this review. Similarly, publications focusing on imaging modalities aside from CXR and chest CT are sparse in this evolving crisis and are likewise addressed in this review. The role of imaging is examined as it is currently being debated in the medical community, which is not at all surprising considering the highly infectious nature of Severe Acute Respiratory Syndrome coronavirus 2.

Immune Checkpoint Inhibitor Therapy Aggravates T Cell-Driven Plaque Inflammation in Atherosclerosis.

BACKGROUND: Immunotherapy has revolutionized cancer treatment. However, immune checkpoint inhibitors (ICIs) that target PD-1 (programmed cell death protein-1) and/or CTLA-4 (cytotoxic T lymphocyte-associated antigen-4) are commonly associated with acute immune-related adverse events. Accumulating evidence also suggests that ICIs aggravate existing inflammatory diseases. OBJECTIVES: As inflammation drives atherosclerotic cardiovascular disease, we studied the propensity of short-term ICI therapy to aggravate atherosclerosis. METHODS: We used 18F-FDG (2-deoxy-2-[fluorine-18]fluoro-D-glucose) positron emission tomography-computed tomography to detect macrophage-driven vascular and systemic inflammation in pembrolizumab and nivolumab/ipilimumab-treated melanoma patients. In parallel, atherosclerotic Ldlr -/- mice were treated with CTLA-4 and PD-1 inhibition to study the proinflammatory consequences of immune checkpoint inhibition. RESULTS: ICI treatment did not affect 18F-FDG uptake in the large arteries, spleen, and bone marrow of melanoma patients, nor myeloid cell activation in blood and lymphoid organs in hyperlipidemic mice. In contrast, we found marked changes in the adaptive immune response (i.e., increased CD4+ effector T cell and CD8+ cytotoxic T cell numbers in lymphoid organs and the arterial wall of our hyperlipidemic mice). Although plaque size was unaffected, plaques had progressed toward a lymphoid-based inflammatory phenotype, characterized by a 2.7-fold increase of CD8+ T cells and a 3.9-fold increase in necrotic core size. Increased endothelial activation was observed with a 2.2-fold and 1.6-fold increase in vascular cell adhesion molecule-1 and intercellular adhesion molecule-1, respectively. CONCLUSIONS: This study demonstrates that combination therapy with anti-CTLA-4 and anti-PD-1 antibodies does not affect myeloid-driven vascular and systemic inflammation in melanoma patients and hyperlipidemic mice. However, short-term ICI therapy in mice induces T cell-mediated plaque inflammation and drives plaque progression.

Sex Differences in the Association Between Smoking and Sleep-Disordered Breathing in the Hispanic Community Health Study/Study of Latinos.

BACKGROUND: Results of previous studies examining associations between cigarette smoking and sleep-disordered breathing (SDB) are inconsistent. We therefore investigated this association in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). METHODS: A total of 13,863 US Hispanic/Latino subjects, 18 to 76 years old, provided smoking histories and underwent home SDB testing. Logistic regression analyses were conducted to assess the independent association of smoking and SDB with covariate adjustment. Sex- and age-stratified analyses were performed. RESULTS: The weighted prevalence of moderate to severe SDB was 9.7% (95% CI, 9.0-10.5). No independent and statistically significant association was observed between ever smoking (defined as minimum lifetime cigarette use of 100) and moderate to severe SDB (defined as an apnea-hypopnea index ≥ 15 events per hour) (OR, 1.02; 95% CI, 0.85-1.22; P = .85). Sex and age were effect modifiers of the aforementioned association. Stratification according to age and sex revealed that younger (aged 35-54 years) female smokers had 83% higher odds of SDB compared with younger female never smokers (OR, 1.83; 95% CI, 1.19-2.81; P = .01). A significant dose-response relation was noted between smoking intensity and SDB in younger female smokers (P < .01). Lastly, use of ≥ 10 cigarettes per day was associated with a nearly threefold increase in SDB odds in younger female ever smokers. These associations were not observed in younger male subjects. CONCLUSIONS: In the HCHS/SOL, no independent and statistically significant association was found between smoking and SDB. Sex and age stratification revealed a novel statistically significant association between smoking and SDB in younger (35-54 years old) female smokers. Our findings highlight the importance of investigating sex- and age-specific associations of SDB risk factors.

Rationale and Design of Family-Based Approach in a Minority Community Integrating Systems-Biology for Promotion of Health (FAMILIA).

BACKGROUND: The 2020 American Heart Association Impact Goal aims to improve cardiovascular health of all Americans by 20% while reducing deaths from cardiovascular disease and stroke by 20%. A large step toward this goal would be to better understand and take advantage of the significant intersection between behavior and biology across the entire life-span. In the proposed FAMILIA studies, we aim to directly address this major knowledge and clinical health gap by implementing an integrated family-centric health promotion intervention and focusing on the intersection of environment and behavior, while understanding the genetic and biologic basis of cardiovascular disease. METHODS: We plan to recruit 600 preschool children and their 600 parents or caregivers from 12-15 Head Start schools in Harlem, NY, and perform a 2:1 (2 intervention/1 control) cluster randomization of the schools. The preschool children will receive our intensive 37-hour educational program as the intervention for 4 months. For the adults, those in the "intervention" group will be randomly assigned to 1 of 2 intervention programs: an "individual-focused" or "peer-to-peer based." The primary outcome in children will be a composite score of knowledge (K), attitudes (A), habits (H), related to body mass index Z score (B), exercise (E), and alimentation (A) (KAH-BEA), using questionnaires and anthropometric measurements. For adults, the primary outcome will be a composite score for behaviors/outcomes related to blood pressure, exercise, weight, alimentation (diet) and tobacco (smoking; Fuster-BEWAT score). Saliva will be collected from the children for SNP genotyping, and blood will be collected from adults for RNA sequencing to identify network models and predictors of primary prevention outcomes. CONCLUSION: The FAMILIA studies seek to demonstrate that targeting a younger age group (3-5 years) and using a family-based approach may be a critical strategy in promoting cardiovascular health across the life-span.

Vascular disease in cocaine addiction.

Cocaine, a powerful vasoconstrictor, induces immune responses including cytokine elevations. Chronic cocaine use is associated with functional brain impairments potentially mediated by vascular pathology. Although the Crack-Cocaine epidemic has declined, its vascular consequences are increasingly becoming evident among individuals with cocaine use disorder of that period, now aging. Paradoxically, during the period when prevention efforts could make a difference, this population receives psychosocial treatment at best. We review major postmortem and in vitro studies documenting cocaine-induced vascular toxicity. PubMed and Academic Search Complete were used with relevant terms. Findings consist of the major mechanisms of cocaine-induced vasoconstriction, endothelial dysfunction, and accelerated atherosclerosis, emphasizing acute, chronic, and secondary effects of cocaine. The etiology underlying cocaine's acute and chronic vascular effects is multifactorial, spanning hypertension, impaired homeostasis and platelet function, thrombosis, thromboembolism, and alterations in blood flow. Early detection of vascular disease in cocaine addiction by multimodality imaging is discussed. Treatment may be similar to indications in patients with traditional risk-factors, with few exceptions such as enhanced supportive care and use of benzodiazepines and phentolamine for sedation, and avoiding ß-blockers. Given the vascular toxicity cocaine induces, further compounded by smoking and alcohol comorbidity, and interacting with aging of the crack generation, there is a public health imperative to identify pre-symptomatic markers of vascular impairments in cocaine addiction and employ preventive treatment to reduce silent disease progression.

Relation between resting amygdalar activity and cardiovascular events: a longitudinal and cohort study.

BACKGROUND: Emotional stress is associated with increased risk of cardiovascular disease. We imaged the amygdala, a brain region involved in stress, to determine whether its resting metabolic activity predicts risk of subsequent cardiovascular events. METHODS: Individuals aged 30 years or older without known cardiovascular disease or active cancer disorders, who underwent 18F-fluorodexoyglucose PET/CT at Massachusetts General Hospital (Boston, MA, USA) between Jan 1, 2005, and Dec 31, 2008, were studied longitudinally. Amygdalar activity, bone-marrow activity, and arterial inflammation were assessed with validated methods. In a separate cross-sectional study we analysed the relation between perceived stress, amygdalar activity, arterial inflammation, and C-reactive protein. Image analyses and cardiovascular disease event adjudication were done by mutually blinded researchers. Relations between amygdalar activity and cardiovascular disease events were assessed with Cox models, log-rank tests, and mediation (path) analyses. FINDINGS: 293 patients (median age 55 years [IQR 45·0-65·5]) were included in the longitudinal study, 22 of whom had a cardiovascular disease event during median follow-up of 3·7 years (IQR 2·7-4·8). Amygdalar activity was associated with increased bone-marrow activity (r=0·47; p<0·0001), arterial inflammation (r=0·49; p<0·0001), and risk of cardiovascular disease events (standardised hazard ratio 1·59, 95% CI 1·27-1·98; p<0·0001), a finding that remained significant after multivariate adjustments. The association between amygdalar activity and cardiovascular disease events seemed to be mediated by increased bone-marrow activity and arterial inflammation in series. In the separate cross-sectional study of patients who underwent psychometric analysis (n=13), amygdalar activity was significantly associated with arterial inflammation (r=0·70; p=0·0083). Perceived stress was associated with amygdalar activity (r=0·56; p=0·0485), arterial inflammation (r=0·59; p=0·0345), and C-reactive protein (r=0·83; p=0·0210). INTERPRETATION: In this first study to link regional brain activity to subsequent cardiovascular disease, amygdalar activity independently and robustly predicted cardiovascular disease events. Amygdalar activity is involved partly via a path that includes increased bone-marrow activity and arterial inflammation. These findings provide novel insights into the mechanism through which emotional stressors can lead to cardiovascular disease in human beings. FUNDING: None.

Imaging Macrophage and Hematopoietic Progenitor Proliferation in Atherosclerosis.

RATIONALE: Local plaque macrophage proliferation and monocyte production in hematopoietic organs promote progression of atherosclerosis. Therefore, noninvasive imaging of proliferation could serve as a biomarker and monitor therapeutic intervention. OBJECTIVE: To explore (18)F-FLT positron emission tomography-computed tomography imaging of cell proliferation in atherosclerosis. METHODS AND RESULTS: (18)F-FLT positron emission tomography-computed tomography was performed in mice, rabbits, and humans with atherosclerosis. In apolipoprotein E knock out mice, increased (18)F-FLT signal was observed in atherosclerotic lesions, spleen, and bone marrow (standardized uptake values wild-type versus apolipoprotein E knock out mice, 0.05 ± 0.01 versus 0.17 ± 0.01, P<0.05 in aorta; 0.13 ± 0.01 versus 0.28 ± 0.02, P<0.05 in bone marrow; 0.06 ± 0.01 versus 0.22 ± 0.01, P<0.05 in spleen), corroborated by ex vivo scintillation counting and autoradiography. Flow cytometry confirmed significantly higher proliferation of macrophages in aortic lesions and hematopoietic stem and progenitor cells in the spleen and bone marrow in these mice. In addition, (18)F-FLT plaque signal correlated with the duration of high cholesterol diet (r(2)=0.33, P<0.05). Aortic (18)F-FLT uptake was reduced when cell proliferation was suppressed with fluorouracil in apolipoprotein E knock out mice (P<0.05). In rabbits, inflamed atherosclerotic vasculature with the highest (18)F-fluorodeoxyglucose uptake enriched (18)F-FLT. In patients with atherosclerosis, (18)F-FLT signal significantly increased in the inflamed carotid artery and in the aorta. CONCLUSIONS: (18)F-FLT positron emission tomography imaging may serve as an imaging biomarker for cell proliferation in plaque and hematopoietic activity in individuals with atherosclerosis.

Prednisolone-containing liposomes accumulate in human atherosclerotic macrophages upon intravenous administration.

Drug delivery to atherosclerotic plaques via liposomal nanoparticles may improve therapeutic agents' risk-benefit ratios. Our paper details the first clinical studies of a liposomal nanoparticle encapsulating prednisolone (LN-PLP) in atherosclerosis. First, PLP's liposomal encapsulation improved its pharmacokinetic profile in humans (n=13) as attested by an increased plasma half-life of 63h (LN-PLP 1.5mg/kg). Second, intravenously infused LN-PLP appeared in 75% of the macrophages isolated from iliofemoral plaques of patients (n=14) referred for vascular surgery in a randomized, placebo-controlled trial. LN-PLP treatment did however not reduce arterial wall permeability or inflammation in patients with atherosclerotic disease (n=30), as assessed by multimodal imaging in a subsequent randomized, placebo-controlled study. In conclusion, we successfully delivered a long-circulating nanoparticle to atherosclerotic plaque macrophages in patients, whereas prednisolone accumulation in atherosclerotic lesions had no anti-inflammatory effect. Nonetheless, the present study provides guidance for development and imaging-assisted evaluation of future nanomedicine in atherosclerosis. FROM THE CLINICAL EDITOR: In this study, the authors undertook the first clinical trial using long-circulating liposomal nanoparticle encapsulating prednisolone in patients with atherosclerosis, based on previous animal studies. Despite little evidence of anti-inflammatory effect, the results have provided a starting point for future development of nanomedicine in cardiovascular diseases.

Dietary oil composition differentially modulates intestinal endotoxin transport and postprandial endotoxemia.

BACKGROUND: Intestinal derived endotoxin and the subsequent endotoxemia can be considered major predisposing factors for diseases such as atherosclerosis, sepsis, obesity and diabetes. Dietary fat has been shown to increase postprandial endotoxemia. Therefore, the aim of this study was to assess the effects of different dietary oils on intestinal endotoxin transport and postprandial endotoxemia using swine as a model. We hypothesized that oils rich in saturated fatty acids (SFA) would augment, while oils rich in n-3 polyunsaturated fatty acids (PUFA) would attenuate intestinal endotoxin transport and circulating concentrations. METHODS: Postprandial endotoxemia was measured in twenty four pigs following a porridge meal made with either water (Control), fish oil (FO), vegetable oil (VO) or coconut oil (CO). Blood was collected at 0, 1, 2, 3 and 5 hours postprandial and measured for endotoxin. Furthermore, ex vivo ileum endotoxin transport was assessed using modified Ussing chambers and intestines were treated with either no oil or 12.5% (v/v) VO, FO, cod liver oil (CLO), CO or olive oil (OO). Ex vivo mucosal to serosal endotoxin transport permeability (Papp) was then measured by the addition of fluorescent labeled-lipopolysaccharide. RESULTS: Postprandial serum endotoxin concentrations were increased after a meal rich in saturated fatty acids and decreased with higher n-3 PUFA intake. Compared to the no oil control, fish oil and CLO which are rich in n-3 fatty acids reduced ex vivo endotoxin Papp by 50% (P < 0.05). Contrarily, saturated fatty acids increased the Papp by 60% (P = 0.008). Olive and vegetable oils did not alter intestinal endotoxin Papp. CONCLUSION: Overall, these results indicate that saturated and n-3 PUFA differentially regulate intestinal epithelial endotoxin transport. This may be associated with fatty acid regulation of intestinal membrane lipid raft mediated permeability.

Relationship between particulate matter exposure and atherogenic profile in "Ground Zero" workers as shown by dynamic contrast enhanced MR imaging.

In this pilot study, we hypothesize that dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) has the potential to evaluate differences in atherosclerosis profiles in patients subjected to high (initial dust cloud) and low (after 13 September 2001) particulate matter (PM) exposure. Exposure to PM may be associated with adverse health effects leading to increased morbidity. Law enforcement workers were exposed to high levels of particulate pollution after working at "Ground Zero" and may exhibit accelerated atherosclerosis. 31 subjects (28 male) with high (n = 19) or low (n = 12) exposure to PM underwent DCE-MRI. Demographics (age, gender, family history, hypertension, diabetes, BMI, and smoking status), biomarkers (lipid profiles, hs-CRP, BP) and ankle-brachial index (ABI) measures (left and right) were obtained from all subjects. Differences between the high and low exposures were compared using independent samples t test. Using linear forward stepwise regression with information criteria model, independent predictors of increased area under curve (AUC) from DCE-MRI were determined using all variables as input. Confidence interval of 95 % was used and variables with p > 0.1 were eliminated. p < 0.05 was considered significant. Subjects with high exposure (HE) had significantly higher DCE-MRI AUC uptake (increased neovascularization) compared to subjects with lower exposure (LE). (AUC: 2.65 ± 0.63 HE vs. 1.88 ± 0.69 LE, p = 0.016). Except for right leg ABI, none of the other parameters were significantly different between the two groups. Regression model indicated that only HE to PM, CRP > 3.0 and total cholesterol were independently associated with increased neovascularization (in decreasing order of importance, all p < 0.026). HE to PM may increase plaque neovascularization, and thereby potentially indicate worsening atherogenic profile of "Ground Zero" workers.

Impact of noninsulin-dependent type 2 diabetes on carotid wall 18F-fluorodeoxyglucose positron emission tomography uptake.

OBJECTIVES: In this study, the impact of noninsulin-dependent type 2 diabetes mellitus on carotid wall (18)F-fluorodeoxyglucose (FDG) uptake in patients with documented or suspected cardiovascular disease was evaluated. BACKGROUND: Inflammation is a pivotal process in the progression of atherosclerosis, which can be noninvasively imaged by FDG positron emission tomography (FDG-PET). METHODS: Carotid artery wall FDG uptake was quantified in 134 patients (age 60.2 ± 9.7 years; diabetic subjects, n = 43). The pre-scan glucose (gluc) level corrected mean of the maximum standardized uptake value (SUV) values ((mean)SUV(gluc)), mean of the maximum target-to-background ratio ((mean)TBR(gluc)), and single hottest segment (SHS(gluc)) of FDG uptake in the artery wall were calculated. Associations between FDG uptake, the presence of risk factors for atherosclerosis, and diabetes were then assessed by multiple regression analysis with backward elimination. RESULTS: The study demonstrated a significant association between diabetes and FDG uptake in the arterial wall (diabetes (mean)SUV(gluc) ß = 0.324, (mean)TBR(gluc) ß = 0.317, and SHS(gluc) ß = 0.298; for all, p < 0.0001). In addition, in diabetic patients, both body mass index ≥ 30 kg/m(2) ((mean)SUV(gluc) ß = 0.4, (mean)TBR(gluc) ß = 0.357, and SHS(gluc) ß = 0.388; for all, p < 0.015) and smoking ((mean)TBR(gluc), ß = 0.312; SHS(gluc), ß = 0.324; for all, p < 0.04) were significantly associated with FDG uptake. CONCLUSIONS: Type 2 diabetes was significantly associated with carotid wall FDG uptake in patients with known or suspected cardiovascular disease. In diabetic patients, obesity and smoking add to the risk of increased FDG uptake values.

Feasibility of [18F]-2-Fluoro-A85380-PET imaging of human vascular nicotinic acetylcholine receptors in vivo.

OBJECTIVES: The aim of this feasibility study was to evaluate [(18)F]-2-Fluoro-A85380 for in vivo imaging of arterial nicotinic acetylcholine receptors (nAChRs) in humans. Furthermore, potentially different vascular uptake patterns of this new tracer were evaluated in healthy volunteers and in patients with neurodegenerative disorders. BACKGROUND: [(18)F]-2-Fluoro-A85380 was developed for in vivo positron emission tomography (PET) imaging of nAChR subunits in the human brain. These nAChRs are also found in arteries and seem to mediate the deleterious effects of nicotine as a part of tobacco smoke in the vasculature. It has been previously shown that uptake patterns of the radiotracer in the brain differs in patients with neurodegenerative disorders compared with healthy controls. METHODS: [(18)F]-2-Fluoro-A85380 uptake was quantified in the ascending and descending aorta, the aortic arch, and the carotids in 5 healthy volunteers and in 6 patients with either Parkinson's disease or multiple system atrophy, respectively, as the maximum target-to-background ratio. The maximal standardized uptake value values, the single hottest segment, and the percent active segments of the [(18)F]-2-Fluoro-A85380 uptake in the arteries were also assessed. RESULTS: [(18)F]-2-Fluoro-A85380 uptake was clearly visualized and maximum target-to-background ratio uptake values corrected for the background activity of the tracer showed specific tracer uptake in the arterial walls. Significantly higher uptake values were found in the descending aorta. Comparison between volunteers and patients revealed significant differences, with lower [(18)F]-2-Fluoro-A85380 uptake in the patient group when comparing single arterial territories but not when all arterial territories were pooled together. CONCLUSIONS: [(18)F]-2-Fluoro-A85380 can provide specific information on the nAChR distribution in human arteries. Vascular nAChR density seems to be lower in patients with Parkinson's disease or multiple system atrophy. Once confirmed in larger study populations and in the experimental setting, this approach might provide insights into the pathogenic role of nAChRs in the human vasculature.

Noninvasive cardiovascular imaging in rheumatoid arthritis: current modalities and the emerging role of magnetic resonance and positron emission tomography imaging.

OBJECTIVES: Rheumatoid arthritis (RA) is associated with premature atherosclerosis and increased prevalence of cardiovascular disease. The objective of this review is to summarize current and emerging imaging modalities for the evaluation of subclinical atherosclerosis in RA, with an emphasis on potential application of novel modalities, high-resolution magnetic resonance imaging and positron emission tomography, as screening tools for early cardiovascular disease risk stratification. METHODS: A PubMed literature search was undertaken using the search terms "rheumatoid arthritis" AND "cardiovascular disease" OR "atherosclerosis" OR "plaque" and including all relevant terms for imaging modalities. RESULTS: Two noninvasive imaging modalities have been widely adopted for direct visualization of arterial wall: carotid ultrasonography and cardiac computed tomography. Published studies in the RA population using these 2 modalities are reviewed. Novel cardiovascular imaging modalities are described, with an emphasis on high-resolution magnetic resonance imaging and positron emission tomography. Emerging research tools in vascular imaging, including dynamic and cardiac stress perfusion contrast-enhanced magnetic resonance imaging, are presented. The incremental imaging capabilities to characterize plaque composition and vessel wall inflammation as well myocardial abnormalities and published studies are systematically reviewed. CONCLUSIONS: An increasing number of cardiovascular imaging modalities with improved characterization of features associated with plaque vulnerability have been developed. Given the heightened cardiovascular risk profile of the RA population, these novel imaging modalities offer promise for risk stratification and drug safety evaluation.

Prevalence and risk factors of carotid vessel wall inflammation in coronary artery disease patients: FDG-PET and CT imaging study.

OBJECTIVES: We investigated the prevalence and clinical risk factors of carotid vessel wall inflammation by means of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in a population consisting of coronary artery disease (CAD) patients. BACKGROUND: The atherosclerotic disease process is characterized by infiltration and retention of oxidized lipids in the artery wall, triggering a disproportionate inflammatory response. Efforts have been made to use noninvasive imaging to quantify this inflammatory response in the vessel wall. Recently, carotid FDG-PET has been shown to reflect the metabolic rate of glucose, a process known to be enhanced in inflamed tissue. METHODS: Carotid inflammation was quantified in 82 CAD patients (age 62 ± 10 years) as the maximum target-to-background ratio ((wholevessel)TBR(max)). Furthermore, we assessed the maximal standardized uptake value values ((wholevessel)SUV(max)), the single hottest segment (SHS), and the percent active segments (PAS) of the FDG uptake in the artery wall, measured by FDG-PET. RESULTS: Whole-vessel TBR(max) >1.8 was present in 67%, >2.0 in 39%, >2.2 in 23%, and >2.4 in 12% of the population. Multiple linear regression analysis with backward elimination revealed that body mass index (BMI) ≥30 kg/m2 (p < 0.0001), age >65 years (p = 0.01), smoking (p = 0.02), and hypertension (p = 0.01) were associated with (wholevessel)TBR(max). The number of components of the metabolic syndrome was also associated with (wholevessel)TBR(max) (p = 0.02). In similar analyses, (wholevessel)SUV(max) was associated with BMI ≥30 kg/m2 (p < 0.0001), age >65 years (p = 0.004), male gender (p = 0.02), and hypertension (p = 0.04); SHS with BMI ≥30 kg/m2 (p < 0.0001), age >65 years (p = 0.02), smoking (p = 0.04), and hypertension (p = 0.05); PAS with BMI ≥30 kg/m2 (p = 0.001), smoking (p = 0.03), and hypertension (p = 0.01). CONCLUSIONS: Carotid inflammation as revealed by FDG-PET is highly prevalent in the CAD population and is associated with obesity, age over 65 years, history of hypertension, smoking, and male gender. Artery wall FDG uptake increased when components of the metabolic syndrome clustered.