BackgroundAngiopoietin-like protein 4 (ANGPTL4) inhibits lipoprotein lipase and associates with dyslipidemia. The expression of ANGPTL4 is regulated by free fatty acids (FFA) that activate lipid-sensing peroxisome proliferator-activated receptors (PPARs), but FFA can also activate pattern recognition receptors including Toll-like receptor 4 (TLR4) in macrophages.ObjectiveTo assess whether systemic low-grade inflammation is a determinant for plasma ANGPTL4 levels in patients with the metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM).DesignWe studied 335 male participants: healthy controls (Controls), patients with the MetS without inflammation (MetS−I) and with low-grade inflammation (MetS+I), and patients with T2DM. All patients without diabetes included in the present study were initially matched for waist circumference. In plasma, ANGPTL4, C reactive protein (CRP) and metabolic parameters were determined. Underlying mechanisms were examined using human macrophages in vitro.ResultsAs compared with Controls, plasma ANGPTL4 levels were increased in patients with MetS−I, MetS+I, and T2DM. Furthermore, ANGPTL4 was increased in T2DM compared with MetS−I. In fact, plasma CRP correlated positively with plasma ANGPTL4. In vitro studies showed that TLR 3/4 activation largely increased the expression and release of ANGPTL4 by macrophages.ConclusionsPlasma ANGPTL4 levels in humans are predicted by CRP, a marker of inflammation, and ANGPTL4 expression by macrophages is increased by inflammatory stimuli.

Purpose: To develop and validate an automated segmentation technique for the detection of the lumen and outer wall boundaries in MR vessel wall studies of the common carotid artery. Materials and Methods:A new segmentation method was developed using a three-dimensional (3D) deformable vessel model requiring only one single user interaction by combining 3D MR angiography (MRA) and 2D vessel wall images. This vessel model is a 3D cylindrical Non-Uniform Rational B-Spline (NURBS) surface which can be deformed to fit the underlying image data. Image data of 45 subjects was used to validate the method by comparing manual and automatic segmentations. Vessel wall thickness and volume measurements obtained by both methods were compared.Results: Substantial agreement was observed between manual and automatic segmentation; over 85% of the vessel wall contours were segmented successfully. The interclass correlation was 0.690 for the vessel wall thickness and 0.793 for the vessel wall volume. Compared with manual image analysis, the automated method demonstrated improved interobserver agreement and inter-scan reproducibility. Additionally, the proposed automated image analysis approach was substantially faster. ATHEROSCLEROSIS IS A progressive disease which, at an early stage, is characterized by vessel wall thickening causing outward remodeling, then narrowing of the lumen, and at a later stage by the formation of plaque lesions inside the vessel wall (1). In patients with unstable plaques, the thin fibrous cap can rupture causing the plaque contents to enter the vessel lumen causing a stroke. Therefore, accurate assessment of the vessel wall dimensions and composition of the vessel wall is essential for identifying patients at risk. The 3.0 Tesla (T) MRI offers high-resolution noninvasive imaging of the vessel wall of the carotid artery. For quantitative assessment of the vessel wall morphology and plaque composition, contours describing the boundaries of the vessel wall are needed (2). Vessel wall thickness measurements have been shown to correlate well with ultrasound (US) intima media thickness measurements (IMT) (3-5). IMT has emerged as a marker for cardiovascular disease and has been used as an endpoint in clinical trials assessing the effect of pharmacological treatment of systemic atherosclerosis (6,7). In turn, MRI is also used in clinical trials (8,9), but compared with US, it offers the advantage that it can provide a 3D image of the vascular structure instead of a 2D image that is dependent on the angle of insonation (5). Other advantages of MRI over US are lower measurement variability (5), enabling smaller sample sizes and potentially shorter study duration in clinical trials. ConclusionCurrently, quantitative assessment of the vessel wall dimensions is based on manual tracing of the lumen and outer wall boundaries, which is timeconsuming and subject to inter-and intra-observer variation. Consequently, computerized segmentation

Purpose:To examine the reproducibility of carotid artery dimension measurements using 3T MRI. Materials and Methods:Ten healthy volunteers underwent three scans on two occasions for assessment of total vessel wall area (TVWA), total luminal area (TLA), and minimum (MinT) and maximum (MaxT) vessel wall thickness. A double inversion-recovery (IR) fast gradient-echo (FGRE) sequence was used on a commercial 3T system. During the first visit the subjects were scanned twice. The third scan was performed at least four days later. One observer traced all scans, and a second observer retraced the first scan series. Conclusion:With the use of a commercial 3T MR system, TVWA, TLA, and wall thickness measurements of the carotid artery can be assessed with good reproducibility.

In non-diabetic subjects with the metabolic syndrome and a lung function that is within the normal range, visceral fat is negatively correlated with FEV1 and FVC.

OBJECTIVE -To evaluate the influence of lipid and glucose metabolism in the metabolic syndrome on aortic pulse wave velocity (PWV) and left ventricular (LV) diastolic function using magnetic resonance imaging (MRI).RESEARCH DESIGN AND METHODS -Aortic PWV and LV diastolic function were assessed using MRI in 16 subjects with the metabolic syndrome and 16 subjects without the metabolic syndrome matched for age, waist circumference, and blood pressure. The groups were compared using the unpaired t test or Mann-Whitney U test, and linear regression analysis was applied.RESULTS -Aortic PWV was increased and LV diastolic function was decreased in subjects with compared with those without the metabolic syndrome. HDL cholesterol was independently associated with aortic PWV (R ϭ Ϫ0.470, P Ͻ 0.01) and LV diastolic function (R ϭ Ϫ0.421, P ϭ 0.02).CONCLUSIONS -Increased aortic PWV and decreased LV diastolic function is observed in subjects with the metabolic syndrome, regardless of blood pressure. Moreover, HDL cholesterol is independently associated with aortic PWV and LV diastolic function.

4 J. Magn. Reson. Imaging 2017;45:215-228.

BackgroundRecently published randomised clinical trials indicate that prolonged electrocardiom (ECG) monitoring might enhance the detection of paroxysmal atrial fibrillation (AF) in cryptogenic stroke or transient ischaemic attack (TIA) patients. A device that might be suitable for prolonged ECG monitoring is a smartphone-compatible ECG device (Kardia Mobile, Alivecor, San Francisco, CA, USA) that allows the patient to record a single-lead ECG without the presence of trained health care staff. The MOBILE-AF trial will investigate the effectiveness of the ECG device for AF detection in patients with cryptogenic stroke or TIA. In this paper, the rationale and design of the MOBILE-AF trial is presented.MethodsFor this international, multicentre trial, 200 patients with cryptogenic stroke or TIA will be randomised. One hundred patients will receive the ECG device and will be asked to record their ECG twice daily during a period of 1 year. One hundred patients will receive a 7-day Holter monitor.DiscussionThe primary outcome of this study is the percentage of patients in which AF is detected in the first year after the index ischaemic stroke or TIA. Secondary outcomes include markers for AF prediction, orally administered anticoagulation therapy changes, as well as the incidence of recurrent stroke and major bleeds. First results can be expected in mid-2019.Trial registrationClinicalTrials.gov, ID: NCT02507986. Registered on 15 July 2015.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-017-2131-0) contains supplementary material, which is available to authorized users.

OBJECTIVE -To determine whether, in accordance with observations in mouse models, high concentrations of the lipoprotein lipase inhibitors apolipoprotein (Apo) CI and ApoCIII are associated with increased triglyceride concentrations and decreased fat mass in men with the metabolic syndrome.RESEARCH DESIGN AND METHODS -Plasma ApoCI, ApoCIII, and triglyceride concentrations were measured in the postabsorptive state in 98 men with the metabolic syndrome. Subcutaneous and visceral fat areas were measured by 3T-magnetic resonance imaging.RESULTS -Triglyceride concentrations were 49% higher, and the average visceral fat area was 26% lower (both P Ͻ 0.001), in subjects with high ApoCI and ApoCIII compared with low ApoCI and ApoCIII. Subjects with either high ApoCI or ApoCIII had 16% (P Ͻ 0.05) and 18% (P Ͻ 0.01) decreased visceral fat area, respectively.CONCLUSIONS -High concentrations of ApoCI and ApoCIII are associated with increased triglycerides and decreased visceral fat mass in men with the metabolic syndrome. These findings translate mouse studies into human pathophysiology. Diabetes Care 32:184-186, 2009A polipoprotein (Apo) CI and Apo-CIII are present on HDL and triglyceride (TG)-rich lipoproteins (1) and mainly affect plasma lipid metabolism by inhibition of lipoprotein lipase (LPL) (2). This enzyme hydrolyzes TG in VLDL and chylomicrons, releasing fatty acids for storage by adipocytes or for energy metabolism in muscles (2,3). Overexpression of human ApoCI in mice increases VLDL-associated TG plasma levels in combination with decreased body fat (4). The effect of ApoCIII overexpression is unknown, but ApoCIII deficiency in mice led to lower VLDLassociated TG levels and increased dietinduced obesity (5). Because it has recently been shown that LPL activity is higher in visceral adipose tissue (VAT) compared with subcutaneous adipose tissue (SAT) (6), LPL inhibitors such as ApoCI and ApoCIII may differentially affect VAT compared with SAT. The objective of this study was to determine whether, like in mouse models, high ApoCI and ApoCIII concentrations are associated with increased TG concentrations and decreased fat mass (VAT vs. SAT) in men with the metabolic syndrome.RESEARCH DESIGN AND METHODS -We studied 98 male subjects aged 50 -70 years with the metabolic syndrome (defined using International Diabetes Federation criteria [7]). Exclusion criteria were the presence of type 2 diabetes, overt cardiovascular disease, use of statins or fibrates, and a BMI Ͼ40 kg/m 2 . The study protocol was approved by the local ethics committee. Blood samples were collected after a 12-h overnight fast. Plasma concentrations of ApoCI and ApoCIII were determined using sandwich enzyme-linked immunosorbent assays specific for human ApoCI and ApoCIII (8).Magnetic resonance imaging (MRI), measuring SAT and VAT area at the level of the intervertebral disk level between the fourth and fifth lumbar vertebra, was performed on a 3T scanner (Philips; Achieva, Best, the Netherlands) as described previously (9).To address the question whet...