To study the interscan reproducibility of manual versus automated segmentation of carotid artery plaque components, and the agreement between both methods, in high and lower quality MRI scans.
24 ...patients with 30-70% carotid artery stenosis were planned for 3T carotid MRI, followed by a rescan within 1 month. A multicontrast protocol (T1w,T2w, PDw and TOF sequences) was used. After co-registration and delineation of the lumen and outer wall, segmentation of plaque components (lipid-rich necrotic cores (LRNC) and calcifications) was performed both manually and automated. Scan quality was assessed using a visual quality scale.
Agreement for the detection of LRNC (Cohen's kappa (k) is 0.04) and calcification (k = 0.41) between both manual and automated segmentation methods was poor. In the high-quality scans (visual quality score ≥ 3), the agreement between manual and automated segmentation increased to k = 0.55 and k = 0.58 for, respectively, the detection of LRNC and calcification larger than 1 mm2. Both manual and automated analysis showed good interscan reproducibility for the quantification of LRNC (intraclass correlation coefficient (ICC) of 0.94 and 0.80 respectively) and calcified plaque area (ICC of 0.95 and 0.77, respectively).
Agreement between manual and automated segmentation of LRNC and calcifications was poor, despite a good interscan reproducibility of both methods. The agreement between both methods increased to moderate in high quality scans. These findings indicate that image quality is a critical determinant of the performance of both manual and automated segmentation of carotid artery plaque components.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Background Patients with familial hypercholesterolemia (FH) are characterized by elevated atherogenic lipoprotein particles, predominantly low-density lipoprotein cholesterol (LDL-C), which ...is associated with accelerated atherogenesis and increased cardiovascular risk. Objectives This study used18 F-fluorodeoxyglucose positron emission tomography (18 FDG-PET) to investigate whether arterial inflammation is higher in patients with FH and, moreover, whether lipoprotein apheresis attenuates arterial wall inflammation in FH patients. Methods In total, 38 subjects were recruited: 24 FH patients and 14 normolipidemic controls. All subjects underwent FDG-PET imaging at baseline. Twelve FH patients who met the criteria for lipoprotein apheresis underwent apheresis procedures followed by a second FDG-PET imaging 3 days (range 1 to 4 days) after apheresis. Subsequently, the target-to-background ratio (TBR) of FDG uptake within the arterial wall was assessed. Results In FH patients, the mean arterial TBR was higher compared with healthy controls (2.12 ± 0.27 vs. 1.92 ± 0.19; p = 0.03). A significant correlation was observed between baseline arterial TBR and LDL-C (R = 0.37; p = 0.03) that remained significant after adjusting for statin use (β = 0.001; p = 0.02) and atherosclerosis risk factors (β = 0.001; p = 0.03). LDL-C levels were significantly reduced after lipoprotein apheresis (284 ± 118 mg/dl vs. 127 ± 50 mg/dl; p < 0.001). There was a significant reduction of arterial inflammation after lipoprotein apheresis (TBR: 2.05 ± 0.31 vs. 1.91 ± 0.33; p < 0.02). Conclusions The arterial wall of FH patients is characterized by increased inflammation, which is markedly reduced after lipoprotein apheresis. This lends support to a causal role of apoprotein B–containing lipoproteins in arterial wall inflammation and supports the concept that lipoprotein-lowering therapies may impart anti-inflammatory effects by reducing atherogenic lipoproteins.
OBJECTIVE—Circulating levels of C-reactive protein (CRP) are associated with an increased risk of coronary artery disease (CAD), stroke, and peripheral artery disease (PAD). Observational and ...experimental evidence suggest that CRP might differentially predict fatal and nonfatal cardiovascular events. Here, we sought to determine the predictive value of CRP for fatal and nonfatal CAD, stroke, or PAD.
APPROACH AND RESULTS—CRP levels were measured in 18 450 apparently healthy participants in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohort. Cox proportional hazards models were used to quantify the association between CRP levels and fatal and nonfatal CAD events, strokes, and PAD events. Bootstrapping was applied to test for significant differences between the risk of fatal and nonfatal events. During 208 485 person-years at risk, 2915 CAD events, 361 strokes, and 657 PAD events occurred. CRP was associated with fatal and nonfatal CAD events and nonfatal PAD events. When adding CRP to predictive risk models for fatal and nonfatal events corrected for known cardiovascular risk factors, the net reclassification index was 2.1% for fatal and 1.9% for nonfatal events. Multivariate adjusted hazard ratios for fatal CAD events (hazard ratio, 1.36; 95% confidence interval, 1.27–1.46) differed significantly (mean difference, 13%; 95% confidence interval, 5.1%–21.9%; P<0.001) from the multivariate adjusted hazard ratio for nonfatal CAD events (hazard ratio, 1.21; 95% confidence interval, 1.15–1.26).
CONCLUSIONS—In the EPIC-Norfolk cohort, CRP was associated with fatal and nonfatal CAD events, as well as nonfatal PAD events. Adding CRP to risk stratification models resulted in a small improvement in classification for both fatal and nonfatal events. Importantly, CRP was significantly more strongly associated with fatal CAD events than with nonfatal CAD events.
Abstract 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 63 h (LN-PLP 1.5 mg/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.
Background
Conflicting data exist about the cardiovascular risk of metabolically healthy obese persons. The prognostic value of C‐reactive protein (CRP) in this intriguing group is unknown. We ...assessed the association between CRP levels and the risk of coronary heart disease (CHD) in metabolically healthy persons with abdominal obesity.
Methods and Results
In the European Prospective Investigation of Cancer–Norfolk prospective cohort, CRP levels and information on metabolic syndrome criteria were available for 7279 participants, of whom 825 (11%) developed CHD during a follow‐up period of 10.9±1.8 years. There was a trend toward a higher multivariable‐adjusted hazard ratio for CHD in metabolically healthy obese participants with CRP levels >2 mg/L compared with <2 mg/L (hazard ratio 1.59, 95% CI 0.97–2.62, P=0.066). Metabolically unhealthy obese participants had significantly higher CHD risk compared with metabolically healthy obese participants with CRP levels <2 mg/L (hazard ratio 1.88, 95% CI 1.20–2.94, P=0.006). Most important, we found that the risk of CHD among metabolically healthy obese persons with CRP levels <2 mg/L was comparable to that of metabolically healthy nonobese persons (hazard ratio 0.91, 95% CI 0.60–1.39, P=0.674).
Conclusions
Among metabolically healthy obese persons, low CRP levels were associated with a CHD risk comparable to that of metabolically healthy nonobese persons. CRP appears to be an easy and widely available method for identifying a low‐risk subpopulation among metabolically healthy obese persons.
Objective
To evaluate the agreement and scan–rescan repeatability of automated and manual plaque segmentation for the quantification of in vivo carotid artery plaque components from multi-contrast ...MRI.
Materials and methods
Twenty-three patients with 30–70 % stenosis underwent two 3T MR carotid vessel wall exams within a 1 month interval. T1w, T2w, PDw and TOF images were acquired around the region of maximum vessel narrowing. Manual delineation of the vessel wall and plaque components (lipid, calcification, loose matrix) by an experienced observer provided the reference standard for training and evaluation of an automated plaque classifier. Areas of different plaque components and fibrous tissue were quantified and compared between segmentation methods and scan sessions.
Results
In total, 304 slices from 23 patients were included in the segmentation experiment, in which 144 aligned slice pairs were available for repeatability analysis. The correlation between manual and automated segmented areas was 0.35 for lipid, 0.66 for calcification, 0.50 for loose matrix and 0.82 for fibrous tissue. For the comparison between scan sessions, the coefficient of repeatability of area measurement obtained by automated segmentation was lower than by manual delineation for lipid (9.9 vs. 17.1 mm
2
), loose matrix (13.8 vs. 21.2 mm
2
) and fibrous tissue (24.6 vs. 35.0 mm
2
), and was similar for calcification (20.0 vs. 17.6 mm
2
).
Conclusion
Application of an automated classifier for segmentation of carotid vessel wall plaque components from in vivo MRI results in improved scan–rescan repeatability compared to manual analysis.
Different in-plane resolutions have been used for carotid 3T MRI. We compared the reproducibility, as well as the within- and between reader variability of high and routinely used spatial resolution ...in scans of patients with atherosclerotic carotid artery disease. Since no consensus exists about the optimal segmentation method, we analysed all imaging data using two different segmentation methods.
In 31 patient with carotid atherosclerosis a high (0.25 × 0.25 mm2; HR) and routinely used (0.50 × 0.50 mm2; LR) spatial resolution carotid MRI scan were performed within one month. A fully blinded closed and a simultaneously open segmentation were used to quantify the lipid rich necrotic core (LRNC), calcified and loose matrix (LM) plaque area and the fibrous cap (FC) thickness.
No significant differences were observed between scan-rescan reproducibility for HR versus LR measurements, nor did we find any significant difference between the within-reader and between-reader reproducibility. The same applies for differences between the open and closed reads. All intraclass correlation coefficients between scans and rescans for the LRNC, calcified and LM plaque area, as well as the FC thickness measurements with the open segmentation method were excellent (all above 0.75).
Increasing the spatial resolution at the expense of the contrast-to-noise ratio does not improve carotid plaque component scan-rescan reproducibility in patients with atherosclerotic carotid disease, nor does using a different segmentation method.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Low HDL-C is a potent risk factor for cardiovascular disease (CVD). Yet, mutations in ABCA1, a major determinant of circulating HDL-C levels, were previously not associated with CVD risk in cohort ...studies. To study the consequences of low plasma levels of high-density lipoprotein cholesterol (HDL-C) due to ATP-binding cassette transporter A1 (ABCA1) dysfunction for atherosclerotic vascular disease in the carotid arteries.
We performed 3.0 Tesla magnetic resonance imaging (MRI) measurements of the carotid arteries in 36 carriers of high impact functional ABCA1 mutations and 36 normolipidemic controls. Carriers presented with 42% lower HDL-C levels (P < 0.001), a larger mean wall area (18.6 ± 6.0 vs. 15.8 ± 4.3 mm(2); P = 0.02), a larger mean wall thickness (0.82 ± 0.21 vs. 0.70 ± 0.14 mm; P = 0.005), and a higher normalized wall index (0.37 ± 0.06 vs. 0.33 ± 0.04; P = 0.005) compared with controls, retaining significance after adjustment for smoking, alcohol consumption, systolic blood pressure, diabetes, body mass index, history of CVD, LDL-C, and statin use (P = 0.002).
Carriers of loss of function ABCA1 mutations display a larger atherosclerotic burden compared with age and sex-matched controls, implying a higher risk for CVD. Further studies are needed to elucidate the full function of ABCA1 in the protection against atherosclerosis. These data support the development of strategies to up-regulate ABCA1 in patients with established CVD.
Inflammation has been widely acknowledged to contribute throughout all stages of atherogenesis. However, these recent advances in our understanding have not been translated into clinical practice in ...which the mainstay of treatment is still lipid-targeted therapy. This review provides an overview of promising anti-inflammatory therapies in atherosclerosis, and discusses potential drawbacks and clinical benefits.
Immunosuppressive drugs are likely to beneficially affect atherogenesis. Several novel anti-inflammatory targets have been scrutinized, of which some have reached clinical development stage, such as cytokine targets interleukin-1 and interleukin-6, CCR2 antagonist, selective phospholipase, and leukotriene inhibitors. Novel imaging modalities such as MRI and PET-computed tomography provide valuable surrogate inflammatory endpoints for risk stratification and testing anti-inflammatory agents in cardiovascular randomized trials.
Anti-inflammatory therapies hold great promise in cardiovascular prevention regimens; however, atherosclerosis is a chronic disease, and systemic long-term use of anti-inflammatory agents carries the risk of complications arising from immunosuppression. In order to successfully add immunosuppressive drugs to our routine armament, we need to identify high-risk patients who benefit from anti-inflammatory treatment, increase our insight into the inflammatory pathogenesis of atherogenesis, and find safe and effective compounds capable of directly suppressing plaque inflammation.
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