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Special Issue "Atherosclerosis and Vascular Imaging 2016"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 August 2016).

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editor

Guest Editor
Prof. Michael Henein

Department of Public Health and Clinical Medical and Heart Center, Umea University, Umea, Sweden
Website | E-Mail
Phone: +46 90 785 00 00
Fax: +46 90 13 76 33
Interests: non-invasive cardiology; echocardiography; coronary artery disease imaging; carotid atherosclerosis

Special Issue Information

Dear Colleagues,

Cardiovascular disease is the main cause of death in the West, and vascular disease is the most common cardiovascular clinical problem. The disease results in serious morbidity and mortality, and carries economic cost implications. While conventional risk factors are well established, and their biomarkers regularly monitored, patients may continue to suffer subclinical active disease, even in the absence of risk factors, until they present with sudden cardiac death or stroke. Early disease detection using direct imaging has shown to be more accurate in identifying vulnerable patients and unstable plaques than conventional risk factors. This IJMS Special Issue deals with the current opinion concerning the state-of-the-art imaging technologies available for clinical applications, and their unique value over the sole use of conventional risk factor analysis, in identifying vulnerable patients, recommending aggressive treatments, prognosticating, and in assessing related nutritional and environmental issues. This Special Issue is the continuation of our 2015 Special Issue “Atherosclerosis and Vascular Imaging” (https://www.mdpi.com/journal/ijms/special_issues/vascular_imaging).

Prof. Dr. Michael Henein
Guest Editor

Manuscript Submission Information

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Keywords

  • Intima Media Thickness (IMT) accuracy in identifying high risk individuals
  • IMT vs. conventional risk factors in improving risk stratification
  • carotid plaque characterization
  • coronary calcification for daily risk assessment
  • coronary calcification: a risk or benefit?
  • nutritional influences on cardiovascular calcification
  • environmental influences on cardiovascular calcification
  • MRA for plaque characterization
  • PET/CT use in assessing lipid cores and their clinical relevance
  • vascular imaging for direct treatment delivery
  • vascular calcification challenges in intervention

Related Special Issues

Published Papers (11 papers)

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Research

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Open AccessArticle
Validating Intravascular Imaging with Serial Optical Coherence Tomography and Confocal Fluorescence Microscopy
Int. J. Mol. Sci. 2016, 17(12), 2110; https://doi.org/10.3390/ijms17122110
Received: 31 August 2016 / Revised: 25 November 2016 / Accepted: 9 December 2016 / Published: 15 December 2016
Cited by 5 | PDF Full-text (7720 KB) | HTML Full-text | XML Full-text
Abstract
Atherosclerotic cardiovascular diseases are characterized by the formation of a plaque in the arterial wall. Intravascular ultrasound (IVUS) provides high-resolution images allowing delineation of atherosclerotic plaques. When combined with near infrared fluorescence (NIRF), the plaque can also be studied at a molecular level [...] Read more.
Atherosclerotic cardiovascular diseases are characterized by the formation of a plaque in the arterial wall. Intravascular ultrasound (IVUS) provides high-resolution images allowing delineation of atherosclerotic plaques. When combined with near infrared fluorescence (NIRF), the plaque can also be studied at a molecular level with a large variety of biomarkers. In this work, we present a system enabling automated volumetric histology imaging of excised aortas that can spatially correlate results with combined IVUS/NIRF imaging of lipid-rich atheroma in cholesterol-fed rabbits. Pullbacks in the rabbit aortas were performed with a dual modality IVUS/NIRF catheter developed by our group. Ex vivo three-dimensional (3D) histology was performed combining optical coherence tomography (OCT) and confocal fluorescence microscopy, providing high-resolution anatomical and molecular information, respectively, to validate in vivo findings. The microscope was combined with a serial slicer allowing for the imaging of the whole vessel automatically. Colocalization of in vivo and ex vivo results is demonstrated. Slices can then be recovered to be tested in conventional histology. Full article
(This article belongs to the Special Issue Atherosclerosis and Vascular Imaging 2016) Printed Edition available
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Open AccessArticle
Intracranial Thrombus Morphology and Composition Undergoes Time-Dependent Changes in Acute Ischemic Stroke: A CT Densitometry Study
Int. J. Mol. Sci. 2016, 17(11), 1959; https://doi.org/10.3390/ijms17111959
Received: 4 September 2016 / Revised: 13 November 2016 / Accepted: 18 November 2016 / Published: 23 November 2016
Cited by 3 | PDF Full-text (3758 KB) | HTML Full-text | XML Full-text
Abstract
The aim of our study was to assess whether cerebral artery clots undergo time-dependent morphological and compositional changes in acute ischemic stroke. We performed a retrospective chart review of patients admitted within 5 h from symptom onset to three European stroke centers and [...] Read more.
The aim of our study was to assess whether cerebral artery clots undergo time-dependent morphological and compositional changes in acute ischemic stroke. We performed a retrospective chart review of patients admitted within 5 h from symptom onset to three European stroke centers and evaluated non-contrast-enhanced CT (NECT) for hyperdense artery signs (HAS) in 2565 scans. The occlusion site, density of HAS expressed in Hounsfield units (HU), area of HAS, and relative density (rHU) (HU clot/HU non-affected artery) were studied and related to time from symptom onset, clinical severity, stroke etiology, and laboratory parameters. A HAS was present in the middle cerebral artery (MCA) in 185 (7.2%) and further explored. The mean time from symptom onset to CT was 100 min (range 17–300). We found a time-dependent loss of density in the occluded M1 segment within the first 5 h (N = 118, 95% CI [−15, −2], p = 0.01). Further, the thrombus area in the M2 segment decreased with time (cubic trend N = 67, 95% CI [−63, −8], p = 0.02). Overall, and especially in the M2 segment, a lower clot area was associated with higher fibrinogen (−21.7%, 95% CI [−34.8, −5.8], p = 0.009). In conclusion, our results disclosed time-dependent changes of intracranial thrombi with regard to occlusion site, density and area. Full article
(This article belongs to the Special Issue Atherosclerosis and Vascular Imaging 2016) Printed Edition available
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Open AccessArticle
Age-Related Renal Microvascular Changes: Evaluation by Three-Dimensional Digital Imaging of the Human Renal Microcirculation Using Virtual Microscopy
Int. J. Mol. Sci. 2016, 17(11), 1831; https://doi.org/10.3390/ijms17111831
Received: 31 August 2016 / Revised: 21 October 2016 / Accepted: 27 October 2016 / Published: 2 November 2016
Cited by 4 | PDF Full-text (3401 KB) | HTML Full-text | XML Full-text
Abstract
The renal microvasculature is targeted during aging, sometimes producing chronic kidney disease (CKD). Overdiagnosis of CKD in older persons is concerning. To prevent it, a new concept of “healthy aging” is arising from a healthy renal donor study. We investigated the renal microcirculatory [...] Read more.
The renal microvasculature is targeted during aging, sometimes producing chronic kidney disease (CKD). Overdiagnosis of CKD in older persons is concerning. To prevent it, a new concept of “healthy aging” is arising from a healthy renal donor study. We investigated the renal microcirculatory changes of three older persons and compared them with that of one patient with nephrosclerosis using a three-dimensional (3D) reconstruction technique that we previously developed. This method uses a virtual slide system and paraffin-embedded serial sections of surgical material that was double-immunostained by anti-CD34 and anti-α smooth muscle actin (SMA) antibodies for detecting endothelial cells and medial smooth muscle cells, respectively. In all cases, the 3D images proved that arteriosclerotic changes in large proximal interlobular arteries did not directly induce distal arterial change or glomerulosclerosis. The nephrosclerotic patient showed severe hyalinosis with luminal narrowing of small arteries directly inducing glomerulosclerosis. We also visualized an atubular glomerulus and intraglomerular dilatation of an afferent arteriole during healthy aging on the 3D image and showed that microcirculatory changes were responsible for them. Thus, we successfully visualized healthy aged kidneys on 3D images and confirmed the underlying pathology. This method has the ability to investigate renal microcirculatory damage during healthy aging. Full article
(This article belongs to the Special Issue Atherosclerosis and Vascular Imaging 2016) Printed Edition available
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Open AccessArticle
Preoperative 3D FSE T1-Weighted MR Plaque Imaging for Severely Stenotic Cervical ICA: Accuracy of Predicting Emboli during Carotid Endarterectomy
Int. J. Mol. Sci. 2016, 17(11), 1791; https://doi.org/10.3390/ijms17111791
Received: 27 July 2016 / Revised: 9 October 2016 / Accepted: 17 October 2016 / Published: 27 October 2016
Cited by 1 | PDF Full-text (2405 KB) | HTML Full-text | XML Full-text
Abstract
The aim of the present study was to determine whether preoperative three-dimensional (3D) fast spin-echo (FSE) T1-weighted magnetic resonance (MR) plaque imaging for severely stenotic cervical carotid arteries could accurately predict the development of artery-to-artery emboli during exposure of the carotid arteries in [...] Read more.
The aim of the present study was to determine whether preoperative three-dimensional (3D) fast spin-echo (FSE) T1-weighted magnetic resonance (MR) plaque imaging for severely stenotic cervical carotid arteries could accurately predict the development of artery-to-artery emboli during exposure of the carotid arteries in carotid endarterectomy (CEA). Seventy-five patients underwent preoperative MR plaque imaging and CEA under transcranial Doppler ultrasonography of the ipsilateral middle cerebral artery. On reformatted axial MR image slices showing the maximum plaque occupation rate (POR) and maximum plaque intensity for each patient, the contrast ratio (CR) was calculated by dividing the internal carotid artery plaque signal intensity by the sternocleidomastoid muscle signal intensity. For all patients, the area under the receiver operating characteristic curve (AUC)—used to discriminate between the presence and absence of microembolic signals—was significantly greater for the CR on the axial image with maximum plaque intensity (CRmax intensity) (0.941) than for that with the maximum POR (0.885) (p < 0.05). For 32 patients in whom both the maximum POR and the maximum plaque density were identified, the AUCs for the CR were 1.000. Preoperative 3D FSE T1-weighted MR plaque imaging accurately predicts the development of artery-to-artery emboli during exposure of the carotid arteries in CEA. Full article
(This article belongs to the Special Issue Atherosclerosis and Vascular Imaging 2016) Printed Edition available
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Open AccessArticle
Cerebral Hyperperfusion after Revascularization Inhibits Development of Cerebral Ischemic Lesions Due to Artery-to-Artery Emboli during Carotid Exposure in Endarterectomy for Patients with Preoperative Cerebral Hemodynamic Insufficiency: Revisiting the “Impaired Clearance of Emboli” Concept
Int. J. Mol. Sci. 2016, 17(8), 1261; https://doi.org/10.3390/ijms17081261
Received: 1 June 2016 / Revised: 25 July 2016 / Accepted: 25 July 2016 / Published: 3 August 2016
Cited by 5 | PDF Full-text (3908 KB) | HTML Full-text | XML Full-text
Abstract
The purpose of the present study was to determine whether cerebral hyperperfusion after revascularization inhibits development of cerebral ischemic lesions due to artery-to-artery emboli during exposure of the carotid arteries in carotid endarterectomy (CEA). In patients undergoing CEA for internal carotid artery stenosis [...] Read more.
The purpose of the present study was to determine whether cerebral hyperperfusion after revascularization inhibits development of cerebral ischemic lesions due to artery-to-artery emboli during exposure of the carotid arteries in carotid endarterectomy (CEA). In patients undergoing CEA for internal carotid artery stenosis (≥70%), cerebral blood flow (CBF) was measured using single-photon emission computed tomography (SPECT) before and immediately after CEA. Microembolic signals (MES) were identified using transcranial Doppler during carotid exposure. Diffusion-weighted magnetic resonance imaging (DWI) was performed within 24 h after surgery. Of 32 patients with a combination of reduced cerebrovascular reactivity to acetazolamide on preoperative brain perfusion SPECT and MES during carotid exposure, 14 (44%) showed cerebral hyperperfusion (defined as postoperative CBF increase ≥100% compared with preoperative values), and 16 (50%) developed DWI-characterized postoperative cerebral ischemic lesions. Postoperative cerebral hyperperfusion was significantly associated with the absence of DWI-characterized postoperative cerebral ischemic lesions (95% confidence interval, 0.001–0.179; p = 0.0009). These data suggest that cerebral hyperperfusion after revascularization inhibits development of cerebral ischemic lesions due to artery-to-artery emboli during carotid exposure in CEA, supporting the “impaired clearance of emboli” concept. Blood pressure elevation following carotid declamping would be effective when embolism not accompanied by cerebral hyperperfusion occurs during CEA. Full article
(This article belongs to the Special Issue Atherosclerosis and Vascular Imaging 2016) Printed Edition available
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Open AccessArticle
Mutant LRP6 Impairs Endothelial Cell Functions Associated with Familial Normolipidemic Coronary Artery Disease
Int. J. Mol. Sci. 2016, 17(7), 1173; https://doi.org/10.3390/ijms17071173
Received: 21 June 2016 / Revised: 13 July 2016 / Accepted: 14 July 2016 / Published: 22 July 2016
Cited by 4 | PDF Full-text (1839 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Mutations in the genes low-density lipoprotein (LDL) receptor-related protein-6 (LRP6) and myocyte enhancer factor 2A (MEF2A) were reported in families with coronary artery disease (CAD). We intend to determine the mutational spectrum of these genes among hyperlipidemic and normolipidemic [...] Read more.
Mutations in the genes low-density lipoprotein (LDL) receptor-related protein-6 (LRP6) and myocyte enhancer factor 2A (MEF2A) were reported in families with coronary artery disease (CAD). We intend to determine the mutational spectrum of these genes among hyperlipidemic and normolipidemic CAD families. Forty probands with early-onset CAD were recruited from 19 hyperlipidemic and 21 normolipidemic Chinese families. We sequenced all exons and intron-exon boundaries of LRP6 and MEF2A, and found a novel heterozygous variant in LRP6 from a proband with normolipidemic CAD. This variant led to a substitution of histidine to tyrosine (Y418H) in an evolutionarily conserved domain YWTD in exon 6 and was not found in 1025 unrelated healthy individuals. Co-segregated with CAD in the affected family, LRP6Y418H significantly debilitated the Wnt3a-associated signaling pathway, suppressed endothelial cell proliferation and migration, and decreased anti-apoptotic ability. However, it exhibited no influences on low-density lipoprotein cholesterol uptake. Thus, mutation Y418H in LRP6 likely contributes to normolipidemic familial CAD via impairing endothelial cell functions and weakening the Wnt3a signaling pathway. Full article
(This article belongs to the Special Issue Atherosclerosis and Vascular Imaging 2016) Printed Edition available
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Open AccessArticle
Asymmetric Dimethylarginine versus Proton Pump Inhibitors Usage in Patients with Stable Coronary Artery Disease: A Cross-Sectional Study
Int. J. Mol. Sci. 2016, 17(4), 454; https://doi.org/10.3390/ijms17040454
Received: 30 January 2016 / Revised: 7 March 2016 / Accepted: 22 March 2016 / Published: 15 April 2016
Cited by 4 | PDF Full-text (211 KB) | HTML Full-text | XML Full-text
Abstract
A recent experimental study suggested that proton pump inhibitors (PPI), widely used to prevent gastroduodenal complications of dual antiplatelet therapy, may increase the accumulation of the endogenous nitric oxide synthesis antagonist asymmetric dimethylarginine (ADMA), an adverse outcome predictor. Our aim was to assess [...] Read more.
A recent experimental study suggested that proton pump inhibitors (PPI), widely used to prevent gastroduodenal complications of dual antiplatelet therapy, may increase the accumulation of the endogenous nitric oxide synthesis antagonist asymmetric dimethylarginine (ADMA), an adverse outcome predictor. Our aim was to assess the effect of PPI usage on circulating ADMA in coronary artery disease (CAD). Plasma ADMA levels were compared according to PPI use for ≥1 month prior to admission in 128 previously described non-diabetic men with stable CAD who were free of heart failure or other coexistent diseases. Patients on PPI tended to be older and with insignificantly lower estimated glomerular filtration rate (GFR). PPI use was not associated with any effect on plasma ADMA (0.51 ± 0.11 (SD) vs. 0.50 ± 0.10 µmol/L for those with PPI (n = 53) and without PPI (n = 75), respectively; p = 0.7). Additionally, plasma ADMA did not differ between PPI users and non-users stratified by a history of current smoking, CAD severity or extent. The adjustment for patients’ age and GFR did not substantially change the results. Thus, PPI usage does not appear to affect circulating ADMA in non-diabetic men with stable CAD. Whether novel mechanisms of adverse PPI effects on the vasculature can be translated into clinical conditions, requires further studies. Full article
(This article belongs to the Special Issue Atherosclerosis and Vascular Imaging 2016) Printed Edition available
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Review

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Open AccessReview
Brain Vascular Imaging Techniques
Int. J. Mol. Sci. 2017, 18(1), 70; https://doi.org/10.3390/ijms18010070
Received: 24 October 2016 / Revised: 13 December 2016 / Accepted: 26 December 2016 / Published: 30 December 2016
Cited by 9 | PDF Full-text (304 KB) | HTML Full-text | XML Full-text
Abstract
Recent major improvements in a number of imaging techniques now allow for the study of the brain in ways that could not be considered previously. Researchers today have well-developed tools to specifically examine the dynamic nature of the blood vessels in the brain [...] Read more.
Recent major improvements in a number of imaging techniques now allow for the study of the brain in ways that could not be considered previously. Researchers today have well-developed tools to specifically examine the dynamic nature of the blood vessels in the brain during development and adulthood; as well as to observe the vascular responses in disease situations in vivo. This review offers a concise summary and brief historical reference of different imaging techniques and how these tools can be applied to study the brain vasculature and the blood-brain barrier integrity in both healthy and disease states. Moreover, it offers an overview on available transgenic animal models to study vascular biology and a description of useful online brain atlases. Full article
(This article belongs to the Special Issue Atherosclerosis and Vascular Imaging 2016) Printed Edition available
Open AccessReview
Molecular Imaging of Vulnerable Atherosclerotic Plaques in Animal Models
Int. J. Mol. Sci. 2016, 17(9), 1511; https://doi.org/10.3390/ijms17091511
Received: 26 July 2016 / Revised: 24 August 2016 / Accepted: 31 August 2016 / Published: 9 September 2016
Cited by 8 | PDF Full-text (7430 KB) | HTML Full-text | XML Full-text
Abstract
Atherosclerosis is characterized by intimal plaques of the arterial vessels that develop slowly and, in some cases, may undergo spontaneous rupture with subsequent heart attack or stroke. Currently, noninvasive diagnostic tools are inadequate to screen atherosclerotic lesions at high risk of acute complications. [...] Read more.
Atherosclerosis is characterized by intimal plaques of the arterial vessels that develop slowly and, in some cases, may undergo spontaneous rupture with subsequent heart attack or stroke. Currently, noninvasive diagnostic tools are inadequate to screen atherosclerotic lesions at high risk of acute complications. Therefore, the attention of the scientific community has been focused on the use of molecular imaging for identifying vulnerable plaques. Genetically engineered murine models such as ApoE−/− and ApoE−/−Fbn1C1039G+/− mice have been shown to be useful for testing new probes targeting biomarkers of relevant molecular processes for the characterization of vulnerable plaques, such as vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, intercellular adhesion molecule (ICAM)-1, P-selectin, and integrins, and for the potential development of translational tools to identify high-risk patients who could benefit from early therapeutic interventions. This review summarizes the main animal models of vulnerable plaques, with an emphasis on genetically altered mice, and the state-of-the-art preclinical molecular imaging strategies. Full article
(This article belongs to the Special Issue Atherosclerosis and Vascular Imaging 2016) Printed Edition available
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Open AccessReview
Diabetes and Hypertension Consistently Predict the Presence and Extent of Coronary Artery Calcification in Symptomatic Patients: A Systematic Review and Meta-Analysis
Int. J. Mol. Sci. 2016, 17(9), 1481; https://doi.org/10.3390/ijms17091481
Received: 4 June 2016 / Revised: 20 August 2016 / Accepted: 22 August 2016 / Published: 6 September 2016
Cited by 9 | PDF Full-text (397 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Background: The relationship of conventional cardiovascular risk factors (age, gender, ethnicity, diabetes, dyslipidaemia, hypertension, obesity, exercise, and the number of risk factors) to coronary artery calcification (CAC) presence and extent has never before been assessed in a systematic review and meta-analysis. Methods: We [...] Read more.
Background: The relationship of conventional cardiovascular risk factors (age, gender, ethnicity, diabetes, dyslipidaemia, hypertension, obesity, exercise, and the number of risk factors) to coronary artery calcification (CAC) presence and extent has never before been assessed in a systematic review and meta-analysis. Methods: We included only English language studies that assessed at least three conventional risk factors apart from age, gender, and ethnicity, but excluded studies in which all patients had another confirmed condition such as renal disease. Results: In total, 10 studies, comprising 15,769 patients, were investigated in the systematic review and seven studies, comprising 12,682 patients, were included in the meta-analysis, which demonstrated the importance of diabetes and hypertension as predictors of CAC presence and extent, with age also predicting CAC presence. Male gender, dyslipidaemia, family history of coronary artery disease, obesity, and smoking were overall not predictive of either CAC presence or extent, despite dyslipidaemia being a key risk factor for coronary artery disease (CAD). Conclusion: Diabetes and hypertension consistently predict the presence and extent of CAC in symptomatic patients. Full article
(This article belongs to the Special Issue Atherosclerosis and Vascular Imaging 2016) Printed Edition available
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Open AccessReview
The Clinical Value of High-Intensity Signals on the Coronary Atherosclerotic Plaques: Noncontrast T1-Weighted Magnetic Resonance Imaging
Int. J. Mol. Sci. 2016, 17(7), 1187; https://doi.org/10.3390/ijms17071187
Received: 7 June 2016 / Revised: 2 July 2016 / Accepted: 14 July 2016 / Published: 21 July 2016
Cited by 3 | PDF Full-text (991 KB) | HTML Full-text | XML Full-text
Abstract
Over the past several decades, significant progress has been made in the pathohistological assessment of vulnerable plaques and in invasive intravascular imaging techniques. However, the assessment of plaque morphology by invasive modalities is of limited value for the detection of subclinical coronary atherosclerosis [...] Read more.
Over the past several decades, significant progress has been made in the pathohistological assessment of vulnerable plaques and in invasive intravascular imaging techniques. However, the assessment of plaque morphology by invasive modalities is of limited value for the detection of subclinical coronary atherosclerosis and the subsequent prediction or prevention of acute cardiovascular events. Recently, magnetic resonance (MR) imaging technology has reached a sufficient level of spatial resolution, which allowed the plaque visualization of large and static arteries such as the carotids and aorta. However, coronary wall imaging by MR is still challenging due to the small size of coronary arteries, cardiac and respiratory motion, and the low contrast-to-noise ratio between the coronary artery wall and the surrounding structures. Following the introduction of carotid plaque imaging with noncontrast T1-weighted imaging (T1WI), some investigators have reported that coronary artery high-intensity signals on T1WI are associated with vulnerable plaque morphology and an increased risk of future cardiac events. Although there are several limitations and issues that need to be resolved, this novel MR technique for coronary plaque imaging could influence treatment strategies for atherothrombotic disease and may be useful for understanding the pathophysiological mechanisms of atherothrombotic plaque formation. Full article
(This article belongs to the Special Issue Atherosclerosis and Vascular Imaging 2016) Printed Edition available
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