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Aims: Current risk scores do not accurately identify patients at highest risk of recurrent atherosclerotic cardiovascular disease (ASCVD) in need of more intensive therapeutic interventions. Advances in high-throughput plasma proteomics, analysed with machine learning techniques, may offer new opportunities to further improve risk stratification in these patients., Methods and Results: Targeted plasma proteomics was performed in two secondary prevention cohorts: the Second Manifestations of ARTerial disease (SMART) cohort (n = 870) and the Athero-Express cohort (n = 700). The primary outcome was recurrent ASCVD (acute myocardial infarction, ischaemic stroke, and cardiovascular death). Machine learning techniques with extreme gradient boosting were used to construct a protein model in the derivation cohort (SMART), which was validated in the Athero-Express cohort and compared with a clinical risk model. Pathway analysis was performed to identify specific pathways in high and low C-reactive protein (CRP) patient subsets. The protein model outperformed the clinical model in both the derivation cohort [area under the curve (AUC): 0.810 vs. 0.750; P < 0.001] and validation cohort (AUC: 0.801 vs. 0.765; P < 0.001), provided significant net reclassification improvement (0.173 in validation cohort) and was well calibrated. In contrast to a clear interleukin-6 signal in high CRP patients, neutrophil-signalling-related proteins were associated with recurrent ASCVD in low CRP patients., Conclusion: A proteome-based risk model is superior to a clinical risk model in predicting recurrent ASCVD events. Neutrophil-related pathways were found in low CRP patients, implying the presence of a residual inflammatory risk beyond traditional NLRP3 pathways. The observed net reclassification improvement illustrates the potential of proteomics when incorporated in a tailored therapeutic approach in secondary prevention patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.)

Background and Aims: Severe obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular disease. Experimental evidence suggests that this risk may be mediated by chronic sympathetic hyperactivation and systemic inflammation, but the precise mechanisms remain to be unraveled. Our aim was to evaluate whether severe OSA patients are characterized by increased sympathetic and hematopoietic activity, potentially driving atherosclerosis., Methods: Untreated patients with severe OSA (apnea-hypopnea index (AHI) > 30 per hour) were matched with mild OSA patients (AHI<15 & >5 per hour) according to age, sex, and body mass index. Study objectives were to assess baroreflex sensitivity (BRS) and heart-rate variability (HRV) using continuous finger blood pressure measurements, hematopoietic activity in the bone marrow and spleen, and arterial inflammation with 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT)., Results: A total of 34 subjects, 17 per group, were included in the analysis. Mean age was 60.7 ± 6.2 years, 24 (70.6%) were male. Mean AHI was 40.5 ± 12.6 per hour in the severe OSA group, and 10.5 ± 3.4 per hour in the mild OSA group. Participants with severe OSA were characterized by reduced BRS (5.7 [4.6-7.8] ms/mmHg in severe vs 8.2 [6.9-11.8] ms/mmHg in mild OSA, p = 0.033) and increased splenic activity (severe OSA 18 F-FDG uptake 3.56 ± 0.77 vs mild OSA 3.01 ± 0.68; p = 0.036). HRV, bone marrow activity and arterial inflammation were comparable between groups., Conclusions: Patients with severe OSA are characterized by decreased BRS and increased splenic activity. Randomized controlled trials are warranted to assess whether OSA treatment reduces sympathetic and splenic activity., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide. For many years guidelines have listed optimal preventive therapy. More recently, novel therapeutic options have broadened the options for state-of-the-art CV risk management (CVRM). In the majority of patients with CVD, risk lowering can be achieved by utilising standard preventive medication combined with lifestyle modifications. In a minority of patients, add-on therapies should be considered to further reduce the large residual CV risk. However, the choice of which drug combination to prescribe and in which patients has become increasingly complicated, and is dependent on both the absolute CV risk and the reason for the high risk. In this review, we discuss therapeutic decisions in CVRM, focusing on (1) the absolute CV risk of the patient and (2) the pros and cons of novel treatment options., (© 2021. The Author(s).)

Individuals with chronic kidney disease are at an increased risk for cardiovascular disease. This risk may partially be explained by a chronic inflammatory state in these patients, reflected by increased arterial wall and cellular inflammation. Statin treatment decreases cardiovascular risk and arterial inflammation in non-CKD subjects. In patients with declining kidney function, cardiovascular benefit resulting from statin therapy is attenuated, possibly due to persisting inflammation. In the current study, we assessed the effect of statin treatment on arterial wall and cellular inflammation. Fourteen patients with chronic kidney disease stage 3 or 4, defined by an estimated Glomerular Filtration Rate between 15 and 60 mL/min/1.73 m 2 , without cardiovascular disease were included in a single center, open label study to assess the effect of atorvastatin 40 mg once daily for 12 weeks (NTR6896). At baseline and at 12 weeks of treatment, we assessed arterial wall inflammation by 18 F-fluoro-deoxyglucose positron-emission tomography computed tomography ( 18 F-FDG PET/CT) and the phenotype of circulating monocytes were assessed. Treatment with atorvastatin resulted in a 46% reduction in LDL-cholesterol, but this was not accompanied by an attenuation in arterial wall inflammation in the aorta or carotid arteries, nor with changes in chemokine receptor expression of circulating monocytes. Statin treatment does not abolish arterial wall or cellular inflammation in subjects with mild to moderate chronic kidney disease. These results imply that CKD-associated inflammatory activity is mediated by factors beyond LDL-cholesterol and specific anti-inflammatory interventions might be necessary to further dampen the inflammatory driven CV risk in these subjects.

Aims: In the era of personalized medicine, it is of utmost importance to be able to identify subjects at the highest cardiovascular (CV) risk. To date, single biomarkers have failed to markedly improve the estimation of CV risk. Using novel technology, simultaneous assessment of large numbers of biomarkers may hold promise to improve prediction. In the present study, we compared a protein-based risk model with a model using traditional risk factors in predicting CV events in the primary prevention setting of the European Prospective Investigation (EPIC)-Norfolk study, followed by validation in the Progressione della Lesione Intimale Carotidea (PLIC) cohort., Methods and Results: Using the proximity extension assay, 368 proteins were measured in a nested case-control sample of 822 individuals from the EPIC-Norfolk prospective cohort study and 702 individuals from the PLIC cohort. Using tree-based ensemble and boosting methods, we constructed a protein-based prediction model, an optimized clinical risk model, and a model combining both. In the derivation cohort (EPIC-Norfolk), we defined a panel of 50 proteins, which outperformed the clinical risk model in the prediction of myocardial infarction [area under the curve (AUC) 0.754 vs. 0.730; P < 0.001] during a median follow-up of 20 years. The clinically more relevant prediction of events occurring within 3 years showed an AUC of 0.732 using the clinical risk model and an AUC of 0.803 for the protein model (P < 0.001). The predictive value of the protein panel was confirmed to be superior to the clinical risk model in the validation cohort (AUC 0.705 vs. 0.609; P < 0.001)., Conclusion: In a primary prevention setting, a proteome-based model outperforms a model comprising clinical risk factors in predicting the risk of CV events. Validation in a large prospective primary prevention cohort is required to address the value for future clinical implementation in CV prevention., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Atherosclerosis is a lipid-driven inflammatory disease, in which both lipids and inflammation can be considered treatment targets. The CANTOS-trial, using the IL-1β monoclonal antibody canakinumab, has proven the concept of targeting inflammation to reduce cardiovascular risk. In contrast, the anti-inflammatory drug methotrexate failed to show cardiovascular benefit. Colchicine is a drug used in gout patients, acting as a non-selective inflammasome inhibitor. The COLCOT-trial uncovered a significant reduction in ischemic cardiovascular events in subjects following an acute myocardial infarction, which was recently confirmed in the larger LoDoCo2-trial in stable coronary heart disease. Guideline committees will have to decide whether the trials have supplied sufficient evidence to implement the routine use of colchicine in the guidelines for cardiovascular risk management. These convincing endpoint trials have paved the way for tailored treatment regimens, comprising anti-inflammatory agents besides currently established treatment modalities in CVRM.

Background and Purpose: General population studies have shown that elevated Lp(a) (lipoprotein[a]) levels are an emerging risk factor for cardiovascular disease and subsequent cardiovascular events. The role of Lp(a) for the risk of secondary MACE in patients undergoing carotid endarterectomy (CEA) is unknown. Our objective is to assess the association of elevated Lp(a) levels with the risk of secondary MACE in patients undergoing CEA., Methods: Lp(a) concentrations were determined in preoperative blood samples of 944 consecutive patients with CEA included in the Athero-Express Biobank Study. During 3-year follow-up, major adverse cardiovascular events (MACE), consisting of myocardial infarction, stroke, and cardiovascular death, were documented., Results: After 3 years follow-up, Kaplan-Meier cumulative event rates for MACE were 15.4% in patients with high Lp(a) levels (>137 nmol/L; >80th cohort percentile) and 10.2% in patients with low Lp(a) levels (≤137 nmol/L; ≤80th cohort percentile; log-rank test: P =0.047). Cox regression analyses adjusted for conventional cardiovascular risk factors revealed a significant association between high Lp(a) levels and 3-year MACE with an adjusted hazard ratio of 1.69 (95% CI, 1.07-2.66). One-third of MACE occurred within 30 days after CEA, with an adjusted hazard ratio for the 30-day risk of MACE of 2.05 (95% CI, 1.01-4.17). Kaplan-Meier curves from time point 30 days to 3 years onward revealed no significant association between high Lp(a) levels and MACE. Lp(a) levels were not associated with histological carotid plaque characteristics., Conclusions: High Lp(a) levels (>137 nmol/L; >80th cohort percentile) are associated with an increased risk of 30-day MACE after CEA. This identifies elevated Lp(a) levels as a new potential risk factor for secondary cardiovascular events in patients after carotid surgery. Future studies are required to investigate whether Lp(a) levels might be useful in guiding treatment algorithms for carotid intervention.

Aims: Elevated lipoprotein(a) [Lp(a)] is strongly associated with an increased cardiovascular disease (CVD) risk. We previously reported that pro-inflammatory activation of circulating monocytes is a potential mechanism by which Lp(a) mediates CVD. Since potent Lp(a)-lowering therapies are emerging, it is of interest whether patients with elevated Lp(a) experience beneficial anti-inflammatory effects following large reductions in Lp(a)., Methods and Results: Using transcriptome analysis, we show that circulating monocytes of healthy individuals with elevated Lp(a), as well as CVD patients with increased Lp(a) levels, both have a pro-inflammatory gene expression profile. The effect of Lp(a)-lowering on gene expression and function of monocytes was addressed in two local sub-studies, including 14 CVD patients with elevated Lp(a) who received apolipoprotein(a) [apo(a)] antisense (AKCEA-APO(a)-LRx) (NCT03070782), as well as 18 patients with elevated Lp(a) who received proprotein convertase subtilisin/kexin type 9 antibody (PCSK9ab) treatment (NCT02729025). AKCEA-APO(a)-LRx lowered Lp(a) by 47% and reduced the pro-inflammatory gene expression in monocytes of CVD patients with elevated Lp(a), which coincided with a functional reduction in transendothelial migration capacity of monocytes ex vivo (-17%, P < 0.001). In contrast, PCSK9ab treatment lowered Lp(a) by 16% and did not alter transcriptome nor functional properties of monocytes, despite an additional reduction of 65% in low-density lipoprotein cholesterol (LDL-C)., Conclusion: Potent Lp(a)-lowering following AKCEA-APO(a)-LRx, but not modest Lp(a)-lowering combined with LDL-C reduction following PCSK9ab treatment, reduced the pro-inflammatory state of circulating monocytes in patients with elevated Lp(a). These ex vivo data support a beneficial effect of large Lp(a) reductions in patients with elevated Lp(a)., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Rationale: Patients with elevated levels of lipoprotein(a) [Lp(a)] are hallmarked by increased metabolic activity in the arterial wall on positron emission tomography/computed tomography, indicative of a proinflammatory state., Objective: We hypothesized that Lp(a) induces endothelial cell inflammation by rewiring endothelial metabolism., Methods and Results: We evaluated the impact of Lp(a) on the endothelium and describe that Lp(a), through its oxidized phospholipid content, activates arterial endothelial cells, facilitating increased transendothelial migration of monocytes. Transcriptome analysis of Lp(a)-stimulated human arterial endothelial cells revealed upregulation of inflammatory pathways comprising monocyte adhesion and migration, coinciding with increased 6-phophofructo-2-kinase/fructose-2,6-biphosphatase (PFKFB)-3-mediated glycolysis. ICAM (intercellular adhesion molecule)-1 and PFKFB3 were also found to be upregulated in carotid plaques of patients with elevated levels of Lp(a). Inhibition of PFKFB3 abolished the inflammatory signature with concomitant attenuation of transendothelial migration., Conclusions: Collectively, our findings show that Lp(a) activates the endothelium by enhancing PFKFB3-mediated glycolysis, leading to a proadhesive state, which can be reversed by inhibition of glycolysis. These findings pave the way for therapeutic agents targeting metabolism aimed at reducing inflammation in patients with cardiovascular disease.

Objective: Netrin-1 has been shown to play a role in the initiation of atherosclerosis in mice models. However, little is known about the role of Netrin-1 in humans. We set out to study whether Netrin-1 is associated with different stages of atherosclerosis. Approach and Results: Plasma Netrin-1 levels were measured in different patient cohorts: (1) 22 patients with high cardiovascular risk who underwent arterial wall inflammation assessment using positron-emission tomography / computed tomography, (2) 168 patients with a positive family history of premature atherosclerosis in whom coronary artery calcium scores were obtained, and (3) 104 patients with chest pain who underwent coronary computed tomography angiography imaging to evaluate plaque vulnerability and burden. Netrin-1 plasma levels were negatively correlated with arterial wall inflammation (β, -0.01 [95% CI, 0.02 to -0.01] R 2 , 0.61; P <0.0001), and concentrations of Netrin-1 were significantly lower when atherosclerosis was present compared with individuals without atherosclerosis (28.01 versus 10.51 ng/mL, P <0.001). There was no difference in Netrin-1 plasma concentrations between patients with stable versus unstable plaques (11.17 versus 11.74 ng/mL, P =0.511). However, Netrin-1 plasma levels were negatively correlated to total plaque volume (β, -0.09 [95% CI, -0.11 to -0.08] R 2 , 0.57, P <0.0001), calcified plaque volumes (β, -0.10 [95% CI, -0.12 to -0.08] R 2 , 0.53; P <0.0001), and noncalcified plaque volumes (β, -0.08 [95% CI, -0.10 to -0.06] R 2 , 0.41; P <0.0001). Treatment of inflammatory stimulated endothelial cells with plasma with high Netrin-1 level resulted in reduced endothelial inflammation and consequently, less monocyte adhesion., Conclusions: Netrin-1 plasma levels are lower in patients with subclinical atherosclerosis and in patients with arterial wall inflammation. Netrin-1 is not associated with plaque vulnerability; however, it is negatively correlated to plaque burden, suggesting that Netrin-1 is involved in some, but not all, stages of atherosclerosis.

A large number of cardiovascular events are not prevented by current therapeutic regimens. In search for additional, innovative strategies, immune cells have been recognized as key players contributing to atherosclerotic plaque progression and destabilization. Particularly the role of innate immune cells is of major interest, following the recent paradigm shift that innate immunity, long considered to be incapable of learning, does exhibit immunological memory mediated via epigenetic reprogramming. Compelling evidence shows that atherosclerotic risk factors promote immune cell migration by pre-activation of circulating innate immune cells. Innate immune cell activation via metabolic and epigenetic reprogramming perpetuates a systemic low-grade inflammatory state in cardiovascular disease (CVD) that is also common in other chronic inflammatory disorders. This opens a new therapeutic area in which metabolic or epigenetic modulation of innate immune cells may result in decreased systemic chronic inflammation, alleviating CVD, and its co-morbidities.

Aims: Lipoprotein(a) (Lp(a)) elevation is a causal risk factor for cardiovascular disease (CVD). It has however been suggested that elevated Lp(a) causes CVD mainly in individuals with high low-density lipoprotein cholesterol (LDL-C) levels. We hypothesized that the risk associated with high Lp(a) levels would largely be attenuated at low LDL-C levels., Methods and Results: In 16 654 individuals from the EPIC-Norfolk prospective population study, and in 9448 individuals from the Copenhagen City Heart Study (CCHS) parallel statistical analyses were performed. Individuals were categorized according to their Lp(a) and LDL-C levels. Cut-offs were set at the 80th cohort percentile for Lp(a). Low-density lipoprotein cholesterol cut-offs were set at 2.5, 3.5, 4.5, and 5.5 mmol/L. Low-density lipoprotein cholesterol levels in the primary analyses were corrected for Lp(a)-derived LDL-C (LDL-Ccorr). Multivariable-adjusted hazard ratios were calculated for each category. The category with LDL-Ccorr <2.5 mmol/L and Lp(a) <80th cohort percentile was used as reference category. In the EPIC-Norfolk and CCHS cohorts, individuals with an Lp(a) ≥80th percentile were at increased CVD risk compared with those with Lp(a) <80th percentile for any LDL-Ccorr levels ≥2.5 mmol/L. In contrast, for LDL-Ccorr <2.5 mmol/L, the risk associated with elevated Lp(a) attenuated. However, there was no interaction between LDL-Ccorr and Lp(a) levels on CVD risk in either cohort., Conclusion: Lipoprotein(a) and LDL-C are independently associated with CVD risk. At LDL-C levels below <2.5 mmol/L, the risk associated with elevated Lp(a) attenuates in a primary prevention setting.

Aims: Migration of monocytes into the arterial wall contributes to arterial inflammation and atherosclerosis progression. Since elevated low-density lipoprotein cholesterol (LDL-C) levels have been associated with activation of plasma monocytes, intensive LDL-C lowering may reverse these pro-inflammatory changes. Using proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs) which selectively reduce LDL-C, we studied the impact of LDL-C lowering on monocyte phenotype and function in patients with familial hypercholesterolaemia (FH) not using statins due to statin-associated muscle symptoms., Methods and Results: We assessed monocyte phenotype and function using flow cytometry and a trans-endothelial migration assay in FH patients (n = 22: LDL 6.8 ± 1.9 mmol/L) and healthy controls (n = 18, LDL 2.9 ± 0.8 mmol/L). Monocyte chemokine receptor (CCR) 2 expression was approximaterly three-fold higher in FH patients compared with controls. C-C chemokine receptor type 2 (CCR2) expression correlated significantly with plasma LDL-C levels (r = 0.709) and was positively associated with intracellular lipid accumulation. Monocytes from FH patients also displayed enhanced migratory capacity ex vivo. After 24 weeks of PCSK9 mAb treatment (n = 17), plasma LDL-C was reduced by 49%, which coincided with reduced intracellular lipid accumulation and reduced CCR2 expression. Functional relevance was substantiated by the reversal of enhanced migratory capacity of monocytes following PCSK9 mAb therapy., Conclusions: Monocytes of FH patients have a pro-inflammatory phenotype, which is dampened by LDL-C lowering by PCSK9 mAb therapy. LDL-C lowering was paralleled by reduced intracellular lipid accumulation, suggesting that LDL-C lowering itself is associated with anti-inflammatory effects on circulating monocytes., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

In the Netherlands dapsone is used for the treatment of dermatitis herpetiformis, leprosy and Pneumocystis jiroveci pneumonia and prophylaxis in case of cotrimoxazole allergy. An idiosyncratic drug reaction, known as the dapsone hypersensitivity syndrome (DHS), appears in about 0.5-3.6% of persons treated with dapsone. DHS can be associated with fever, rash and systemic involvement. We present a 35-year-old woman who developed severe DHS seven weeks after starting dapsone. Six weeks after being discharged in a good clinical condition she died from fulminant myocarditis, 11 weeks after the first DHS symptoms and the discontinuation of dapsone.

Purpose: To explore the use of breath-hold and navigator-gated noncontrast Steady State Free Precession (SSFP) MR angiography (MRA) protocols for the evaluation of renal artery stenosis (RAS)., Materials and Methods: Twenty patients referred to rule out RAS were imaged using two breath-hold and one navigator-gated SSFP MRA sequences. All patients underwent contrast-enhanced MRA (CE-MRA). Two radiologists evaluated all sequences both qualitatively (blur, artifacts, reader confidence) and quantitatively (maximum stenosis). Using CE-MRA as truth, a receiver operating characteristics (ROC) curve was generated and a statistical analysis of navigator-gated SSFP (Nav SSFP) was performed., Results: Seven patients had >50% renal artery stenosis by CE-MRA. Nav SSFP performed significantly better than either breath-hold SSFP technique in terms of blur, artifacts, and reader confidence. Using a 50% threshold for stenosis, sensitivity for detecting RAS was 100%, with a specificity of 85% and a negative predictive value of 100%. The average mean stenosis difference between Nav SSFP and CE-MRA was 9 +/- 9%., Conclusion: Nav SSFP outperformed breath-hold SSFP in measures of image quality and reader confidence. Sensitivity and negative predictive value for detecting RAS with Nav SSFP was perfect, with an acceptable specificity of 85%. This suggests further study is warranted to evaluate Nav SSFP as a noncontrast screening technique for renal artery stenosis., ((c) 2007 Wiley-Liss, Inc.)

Objective: The purpose of our study was to determine how well unenhanced navigator-gated steady-state free precession (Nav SSFP) MR angiography (MRA) performs as a screening test for the detection of renal artery stenosis., Subjects and Methods: Forty patients referred to rule out renal artery stenosis were imaged using an optimized Nav SSFP MRA sequence before conventional contrast-enhanced MRA (CE-MRA). Two radiologists evaluated Nav SSFP for maximum stenosis measurement, and comparison was made with CE-MRA results., Results: Fifteen of the 40 patients had greater than 50% renal artery stenosis as determined on CE-MRA. Sensitivity for detecting renal artery stenosis with Nav SSFP was 100%; specificity, 84%; negative predictive value, 100%; and positive predictive value, 79%. The average mean stenosis difference between Nav SSFP and CE-MRA was 10% +/- 9%., Conclusion: Sensitivity and negative predictive value for the detection of renal artery stenosis using Nav SSFP were perfect, with an acceptable specificity of 84%. This suggests Nav SSFP is a promising technique for simple unenhanced screening for the detection of renal artery stenosis.

Purpose: To evaluate the use of sensitivity encoding (SENSE) to reduce scan time and decrease detrimental artifacts arising from motion and bolus profile effects during contrast-enhanced MR angiography (CE-MRA) of the renal arteries (RAs)., Materials and Methods: A direct comparison of conventional and SENSE (acceleration factor 2) CE-MRA protocols was performed on 20 patients. Each patient underwent both scans. Both protocols achieved the same resolution, but the SENSE protocol was 50% faster and utilized a faster injection than the conventional scan. Three radiologists graded the images for image quality, artifact levels, and reader confidence., Results: While the signal-to-noise ratio (SNR) decreased (26+/-5 vs. 30+/-10; P=0.04) with the SENSE protocol, the image-quality scores for four identified segments of the RAs increased or were unchanged. The largest improvements in image quality occurred in the more distal segments of the RAs. Parenchymal ringing (P=0.005) and RA blurring (P=0.006) were significantly reduced, and there was a trend toward improvement of RA ringing despite the increased injection rate., Conclusion: The faster SENSE scan maintained nearly the same SNR (due to faster injection of Gd-chelate), reduced artifact levels, and improved image quality ratings for the distal renal vessels., (Copyright (c) 2006 Wiley-Liss, Inc.)

Purpose: To investigate if the use of parallel imaging is feasible and beneficial for peripheral contrast-enhanced magnetic resonance angiography (CE-MRA)., Materials and Methods: A total of 19 consecutive patients underwent peripheral CE-MRA using SENSE with two-fold reduction in the upper and lower leg stations. Conventional nonaccelerated imaging using constant level appearance (CLEAR) was used in the aortoiliac station. The findings were compared with those in a similar patient group that underwent peripheral CE-MR angiography using our standard imaging protocol without SENSE. Intraarterial digital subtraction angiography (IA-DSA) was used as the standard of reference. Lower extremity vessels were divided into anatomic segments (aortoiliac, upper legs, lower legs) for review. In each anatomic segment signal- and contrast-to-noise ratios (SNR, CNR), venous contamination, subjective image quality, as well as sensitivity and specificity, were determined for both patient groups., Results: SNR and CNR improved significantly for the aortoiliac and upper leg segments (all P-values < or = 0.001). Small reductions were seen in the frequency of disturbing venous enhancement (P = not significant). There were no significant differences with regards to subjective image quality or diagnostic accuracy (all P > 0.3). Overall sensitivity and specificity in the SENSE group were 81% and 95%, respectively. For the non-SENSE group, these values were 79% and 96%, respectively., Conclusion: Preliminary results show that three-station peripheral CE-MRA using a full length peripheral arterial coil in combination with SENSE in the upper and lower leg stations is feasible and useful for further optimization of peripheral MRA. Using SENSE allows for routine, high-quality depiction of the entire peripheral vascular tree including the pedal arch. Higher SENSE factors are needed for further optimization.

An 80-year-old female patient with arterial hypertension and slowly progressive deterioration of renal function was referred to our department for investigation of the renal arteries. Imaging of the renal arteries with ultrasound was inconclusive, due to obesity. Subsequently, imaging was performed with balanced turbo field echo which is a newly developed technique in our department. This new technique for the moment is still combined with contrast-enhanced magnetic resonance angiography. A therapeutic digital subtraction angiography was performed for stent placement.

The recently developed techniques of parallel imaging with phased array coils are rapidly becoming accepted for magnetic resonance angiography (MRA) applications. This article reviews the various current parallel imaging techniques and their application to MRA. The increased scan efficiency provided by parallel imaging allows increased temporal or spatial resolution, and reduction of artifacts in contrast-enhanced MRA (CE-MRA). Increased temporal resolution in CE-MRA can be used to reduce the need for bolus timing and to provide hemodynamic information helpful for diagnosis. In addition, increased spatial resolution (or volume coverage) can be acquired in a breathhold (eg, in renal CE-MRA), or in otherwise limited clinically acceptable scan durations. The increased scan efficiency provided by parallel imaging has been successfully applied to CE-MRA as well as other MRA techniques such as inflow and phase contrast imaging. The large signal-to-noise ratio available in many MRA techniques lends these acquisitions to increased scan efficiency through parallel imaging.

Purpose: To compare a multislab balanced turbo field-echo magnetic resonance (MR) angiographic technique, without the use of a contrast agent, with digital subtraction angiography (DSA) for imaging of the renal arteries., Materials and Methods: Twenty-five randomly selected patients (eight women and 17 men; age range, 27-88 years; mean age, 72 years) suspected of having renal artery stenosis underwent both DSA and balanced turbo field-echo MR angiography. A consensus result was obtained among three radiologists in evaluation of main renal arteries on balanced turbo field-echo images and DSA images. Sensitivity, specificity, and negative and positive predictive values of the balanced turbo field-echo technique were calculated, and receiver operating characteristic analysis was performed for depiction of hemodynamically significant stenosis. Cohen kappa analysis was used to assess agreement between the two imaging methods in grading of stenoses and depiction of significant stenosis. Accessory renal arteries also were evaluated., Results: Fifty main renal arteries and 11 accessory arteries were fully depicted with DSA. DSA depicted 11 stenotic lesions in the main renal arteries. In comparison, balanced turbo field-echo MR angiography enabled visualization of 46 of 50 main renal arteries to their first branching points and depicted 10 of 11 accessory arteries. Sensitivity, specificity, negative predictive value, and positive predictive value of this technique for depiction of significant stenosis were 100% (four of four), 98% (41 of 42), 100% (41 of 41), and 80% (four of five), respectively. The area under the receiver operating characteristic curve was 0.988. kappa was 0.782 for grading of stenoses and 0.877 for depiction of significant stenosis., Conclusion: Multislab balanced turbo field-echo imaging has potential as an MR angiography technique for depiction of normal and diseased renal arteries., (Copyright RSNA, 2004)

Sensitivity encoding (SENSE) uses multiple MRI receive coil elements to encode spatial information in addition to traditional gradient encoding. Requiring less gradient encodings translates into shorter scan times, which is extremely beneficial in many clinical applications. SENSE is available to routine diagnostic imaging for the past 2 years. This paper highlights the use of SENSE with scan time reduction factors up to 6 in contrast-enhanced MRA, routine abdominal imaging, mammography, cardiac and neuro imaging. It is shown that SENSE has opened new horizons in both routine and advanced MR imaging., (Copyright 2002 Elsevier Science Ireland Ltd.)

Purpose: To use the parallel imaging technique, sensitivity encoding (SENSE), to increase spatial resolution and decrease venous contamination in peripheral magnetic resonance angiography (MRA)., Materials and Methods: Moving table, single-bolus peripheral contrast-enhanced (CE) -MRA was performed on nine patients. Manual table movement combined with SENSE in the upper station allowed for more rapid overall scan coverage such that acquisition of the lower station began 34 seconds after aortic contrast arrival. True sub- millimeter isotropic resolution was achieved in the lower station., Results: Diagnostic MR angiograms of all three stations were obtained in all nine patients. Venous enhancement did not confound interpretation in any case. Sub-millimeter lower station resolution provided excellent vascular detail., Conclusion: Decreased delay time between upper and lower station acquisition in single bolus peripheral MR angiograms, now possible using parallel imaging techniques, combined with lower station sub-millimeter resolution may decrease venous contamination and increase overall interpretability, thus increasing clinical acceptance of peripheral MRA.

Over the past decade, magnetic resonance (MR) imaging has been developed toward a tool for guiding and evaluating diagnostic and therapeutic interventions. Within the field of vascular MR-guided interventions, MR has potential for providing on-line monitoring of the blood volume flow rate, which is relevant during procedures such as balloon angioplasty and stent placement. We recently reported a hardware and software environment for enabling flow quantification every 8 seconds using nontriggered phase-contrast imaging. In the present study, the objective was to increase temporal resolution further to one evaluation per 4 seconds. We achieve this by lowering spatial resolution to 3 pixels per lumen diameter. The accuracy of the measurements is preserved by applying model-based postprocessing for quantification of the volume flow rate. Phantom and volunteer studies are presented, demonstrating the accuracy of the model-driven approach for the applied short acquisitions. The capabilities of the presented approach are illustrated by the results of several hypercapnia experiments and carotid compression tests performed on healthy volunteers., (Copyright 2000 Wiley-Liss, Inc.)

Quantification of the degree of stenosis or vessel dimensions are important for diagnosis of vascular diseases and planning vascular interventions. Although diagnosis from three-dimensional (3-D) magnetic resonance angiograms (MRA's) is mainly performed on two-dimensional (2-D) maximum intensity projections, automated quantification of vascular segments directly from the 3-D dataset is desirable to provide accurate and objective measurements of the 3-D anatomy. A model-based method for quantitative 3-D MRA is proposed. Linear vessel segments are modeled with a central vessel axis curve coupled to a vessel wall surface. A novel image feature to guide the deformation of the central vessel axis is introduced. Subsequently, concepts of deformable models are combined with knowledge of the physics of the acquisition technique to accurately segment the vessel wall and compute the vessel diameter and other geometrical properties. The method is illustrated and validated on a carotid bifurcation phantom, with ground truth and medical experts as comparisons. Also, results on 3-D time-of-flight (TOF) MRA images of the carotids are shown. The approach is a promising technique to assess several geometrical vascular parameters directly on the source 3-D images, providing an objective mechanism for stenosis grading.

Magnetic resonance phase-contrast volume flow rate (VFR) measurement with limited resolution in small vessels is subject to two major sources of error: a) partial volume artifacts, causing systematic overestimation of the VFR, and b) errors related to the selection of vessel pixels [region of interest (ROI)], causing large inter-observer and intra-observer variability. Additionally, limited resolution results in Gibbs-ringing around vessels, which adversely affects VFR determination. In this paper, a semi-automatic model-based method is presented that effectively eliminates errors due to both partial volume effect and Gibbs-ringing and also minimizes errors from variability in the ROI selection. The model assumes a parabolic flow profile and cylindrical vessel geometry, incorporates inflow effects, and takes into account the point-spread function of the acquisition. The method automatically estimates maximum velocity, vessel radius, and VFR. The method is validated in phantoms under various conditions and evaluated in vivo. For small vessels with moderately pulsatile flow, it is demonstrated that accurate VFRs and diameter estimates are obtained, virtually independent of the ROI selection, even in vessels covered by just a few pixels. Compared with conventional VFR analysis, both accuracy and reproducibility improve significantly.

The use of complex subtraction in dynamic thick slab 2D MR digital subtraction angiography (MR-DSA) has been shown to eliminate partial volume effects, which are present if vessels cover a small fraction of the 2D slab. However, spin dephasing still results in a poor visualization of areas with complex flow. In this paper, it is shown that this can be overcome by using asymmetric echo (ASE) acquisition combined with complex subtraction. It is proven that an ASE acquisition does not destroy information necessary for complex subtraction if the subtraction is performed in k-space. As a consequence, the subtraction reconstruction is as reliable as the magnitude reconstruction of a single ASE data set. Experiments with ASE and complex subtraction show that flow voids near stenoses disappear, that the signal-to-noise ratio is improved and that temporal resolution is increased.

Our aim is to describe and demonstrate the steps we have found to be useful in the construction and evaluation of protocols for triggered and nontriggered measurement of blood flow by two-dimensional phase-contrast magnetic resonance angiography (MRA). To achieve this goal, we start with a survey of factors governing the accuracy (validity) and precision (repeatability) of MR flow measurements. This knowledge, combined with prior information regarding the diameter of the target vessel and the prevailing flow conditions, is then employed to define a protocol for measuring flow with negligible systematic error. In the absence of a gold standard for in vivo flow measurements, the protocol is subsequently validated for a range of flow conditions by representative phantom experiments. Precision is then calculated from the signal-to-noise ratio (SNR) of blood in the accompanying magnitude images or, less conveniently, estimated from the standard deviation of repeated measurements. The desired precision is finally achieved by adjusting the appropriate SNR parameters. All steps involved in protocol development are demonstrated for both flow-independent and flow-dependent acquisitions.

This work addresses the fundamental limits imposed by the MRI process on the accuracy with which vessel diameters and cross-sectional areas can be derived from time-of-flight (TOF) and phase-contrast (PC) MR source images. By means of simulations and in vitro experiments, it is demonstrated that, even in the absence of flow-related artifacts, severe inaccuracies in the determination of diameters or cross-sectional areas may occur solely because of the physical process of the MR image acquisition. Resolution and intraluminal saturation have strong effects on the vessel appearance and thus on the diameter estimation error. It is shown that low resolution leads to diameter overestimation or even underestimation and that intraluminal saturation causes severe underestimation, even for relatively low flip angles. Velocity and velocity encoding do not have a major influence on lumen appearance in PC images. Accurate diameter estimations can be attained only if lumen diameters constitute at least three pixels for both TOF and PC acquisitions, provided that intraluminal saturation is suppressed or avoided. Additionally, since the constitution of TOF and PC images is dissimilar, lumina should be analyzed differently to obtain accurate diameters and cross-sectional areas.

A problem of current MRA techniques is the inability to accurately depict the vascular anatomy, particularly in areas of disturbed flow. Various reasons, such as intravoxel phase dispersion, saturation, temporal variations, and maximum intensity projection (MIP) nonlinearity, cause a wrong delineation of vessel boundaries. A phase contrast (PC)-based postprocessing operation, the phase derivative (PhD), is introduced to detect phase fluctuations indicating flow. Two-dimensional and three-dimensional angiographic reconstruction algorithms are presented. Mathematical formulas are derived to predict the effect of sampling to flow profiles and the effect on the PhD of these profiles. Numerical, phantom, and preliminary in vivo experiments demonstrate that PhD images do not suffer from phase wraps and allow a velocity dynamic range extension only limited by a differential phase change. It is also shown that PhD MIPs produce higher signal-to-noise ratios than conventional PC angiograms and give a better impression of the anatomy of (stenotic) vessels and of their diameters for both laminar and disturbed flow.

In a 47-year-old healthy male volunteer, susceptibility-based magnetic resonance (MR) imaging was performed in the basilic vein in the right upper arm at 1.5 T. A conventional 3-F nonbraided polyethylene catheter with a 0.3-mm lumen diameter was locally impregnated with dysprosium oxide, and six ringed areas of increased susceptibility were created. passive tracking of the catheter was performed with near-real-time conventional two-dimensional gradient-echo angiography. The entire prepared part of the catheter was depicted without steering problems or complications. Passive tracking is expected to provide a valuable adjunct to active tracking for guiding endovascular interventions.

This paper reports the development of dedicated catheters and real-time MR scan techniques for guiding vascular interventional procedures. By way of phantom experiments, it is shown that proper modification of the magnetic properties of catheters allows their conspicuous and consistent visualization in subsecond 2D gradient echo images and phase contrast angiograms. Dynamic scan times as low as 0.5 s could be achieved by exploiting the keyhole technique and purposeful postprocessing. The temporal resolution and spatial resolution of the resultant scan protocol shows promise for adequate tracking of catheter manipulation.

The purpose of this study was to assess the accuracy and precision of time-averaged flow as measured by nontriggered 2D PC. Mono-, bi-, and triphasic flow patterns, modelling waveforms encountered in the human vascular system, were generated by a computer-controlled flow system. Time-averaged flow velocity was measured by conventional 2D cardiac-triggered cine PC and by nontriggered 2D PC for different settings of the excitation flip angle and the velocity sensitivity. Accuracy and precision were determined by repeating the measurements (N = 6) and comparing the results against precisely known calibration values. Measurements revealed waveform-specific deviations between triggered and nontriggered acquisitions that depended on the velocity sensitivity and, more strongly, on the flip angle of the nontriggered experiment. This confirmed the theoretically predicted predominance of amplitude over phase effects. Systematic errors could be reduced by decreasing the flip angle and the velocity sensitivity, although at the expense of signal-to-noise, so that additional signal averaging was required to maintain a specified precision. The attainable accuracy appeared to be acceptable only for waveforms with a relatively low pulsatility index. The study demonstrates the feasibility of accurate and precise nontriggered velocity measurements for weakly pulsatile flow and indicates a route towards improving the reliability for highly pulsatile flow.