Quantification of left ventricular myocardial strain: Comparison between MRI tagging, MRI feature tracking, and ultrasound speckle tracking.

Ultrasound speckle tracking is frequently used to quantify myocardial strain, and magnetic resonance imaging (MRI) feature tracking is rapidly gaining interest. Our aim is to validate cardiac MRI feature tracking by comparing it with the gold standard method (i.e., MRI tagging) in healthy subjects and patients. Furthermore, we aim to perform an indirect validation by comparing ultrasound speckle tracking with MRI feature tracking. Forty-two subjects (17 formerly preeclamptic women, three healthy women, and 22 left bundle branch block patients of both sexes) received 3-T cardiac MRI and echocardiography. Cine and tagged MRI, and B-mode ultrasound images, were acquired. Intrapatient global and segmental left ventricular circumferential (MRI tagging vs. MRI feature tracking) and longitudinal (MRI feature tracking vs. ultrasound speckle tracking) peak strain and time to peak strain were compared between the three techniques. Intraclass correlation coefficient (ICC) (< 0.50 = poor, 0.50-0.75 = moderate, > 0.75-0.90 = good, > 0.90 = excellent) and Bland-Altman analysis were used to assess correlation and bias; p less than 0.05 indicates a significant ICC or bias. Global peak strain parameters showed moderate-to-good correlations between methods (ICC = 0.71-0.83, p < 0.01) with no significant biases. Global time to peak strain parameters showed moderate-to-good correlations (ICC = 0.56-0.82, p < 0.01) with no significant biases. Segmental peak strains showed significant biases in all parameters and moderate-to-good correlation (ICC = 0.62-0.77, p < 0.01), except for lateral longitudinal peak strain (ICC = 0.23, p = 0.22). Segmental time to peak strain parameters showed moderate-to-good correlation (ICC = 0.58-0.74, p < 0.01) with no significant biases. MRI feature tracking is a valid method to examine myocardial strain, but there is bias in absolute segmental strain values between imaging techniques. MRI feature tracking shows adequate comparability with ultrasound speckle tracking.

Signal intensity and volume of carotid intraplaque hemorrhage on magnetic resonance imaging and the risk of ipsilateral cerebrovascular events: The Plaque At RISK (PARISK) study.

BACKGROUND: The Plaque At RISK (PARISK) study demonstrated that patients with a carotid plaque with intraplaque hemorrhage (IPH) have an increased risk of recurrent ipsilateral ischemic cerebrovascular events. It was previously reported that symptomatic carotid plaques with IPH showed higher IPH signal intensity ratios (SIR) and larger IPH volumes than asymptomatic plaques. We explored whether IPH SIR and IPH volume are associated with future ipsilateral ischemic cerebrovascular events beyond the presence of IPH. METHODS: Transient ischemic attack and ischemic stroke patients with mild-to-moderate carotid stenosis and an ipsilateral IPH-positive carotid plaque (n = 89) from the PARISK study were included. The clinical endpoint was a new ipsilateral ischemic cerebrovascular event during 5 years of follow-up, while the imaging-based endpoint was a new ipsilateral brain infarct on brain magnetic resonance imaging (MRI) after 2 years (n = 69). Trained observers delineated IPH, a hyperintense region compared to surrounding muscle tissue on hyper T1-weighted magnetic resonance images. The IPH SIR was the maximal signal intensity in the IPH region divided by the mean signal intensity of adjacent muscle tissue. The associations between IPH SIR or volume and the clinical and imaging-based endpoint were investigated using Cox proportional hazard models and logistic regression, respectively. RESULTS: During 5.1 (interquartile range: 3.1-5.6) years of follow-up, 21 ipsilateral cerebrovascular ischemic events were identified. Twelve new ipsilateral brain infarcts were identified on the 2-year neuro MRI. There was no association for IPH SIR or IPH volume with the clinical endpoint (hazard ratio (HR): 0.89 [95% confidence interval: 0.67-1.10] and HR: 0.91 [0.69-1.19] per 100-µL increase, respectively) nor with the imaging-based endpoint (odds ratio (OR): 1.04 [0.75-1.45] and OR: 1.21 [0.87-1.68] per 100-µL increase, respectively). CONCLUSION: IPH SIR and IPH volume were not associated with future ipsilateral ischemic cerebrovascular events. Therefore, quantitative assessment of IPH of SIR and volume does not seem to provide additional value beyond the presence of IPH for stroke risk assessment. TRIAL REGISTRATION: The PARISK study was registered on ClinicalTrials.gov with ID NCT01208025 on September 21, 2010 (https://clinicaltrials.gov/study/NCT01208025).

Serum sex hormone-binding globulin is a mediator of the association between intrahepatic lipid content and type 2 diabetes: the Maastricht Study.

AIMS/HYPOTHESIS: Serum sex hormone-binding globulin (SHBG) has been proposed to act as a hepatokine that contributes to the extrahepatic complications observed in non-alcoholic fatty liver disease (NAFLD). However, it remains uncertain whether serum SHBG mediates the association between intrahepatic lipids (IHL) and type 2 diabetes. Therefore, we studied whether, and to what extent, serum SHBG mediates the association between IHL content and type 2 diabetes. METHODS: We used cross-sectional data from the Maastricht Study (n=1554), a population-based cohort study with oversampling of individuals with type 2 diabetes. Type 2 diabetes status was assessed by oral glucose tolerance test, and IHL content was measured using 3T Dixon MRI. Mediation analyses were performed to assess the role of serum SHBG in mediating the association between IHL content and type 2 diabetes. RESULTS: IHL content was significantly associated with type 2 diabetes in women and men (OR 1.08 [95% CI 1.04, 1.14] and OR 1.12 [95% CI 1.08, 1.17], respectively). Serum SHBG significantly mediated the association between IHL content and type 2 diabetes. The contribution of serum SHBG was higher in women (OR 1.04 [95% CI 1.02, 1.07]; proportion mediated 50.9% [95% CI 26.7, 81.3]) than in men (OR 1.02 [95% CI 1.01, 1.03]; proportion mediated 17.2% [95% CI 9.6, 27.6]). Repeat analyses with proxies of type 2 diabetes and adjustment for covariates did not substantially affect the results. CONCLUSIONS/INTERPRETATION: In this large-scale population-based cohort study, serum SHBG was found to be a mediator of the association between IHL content and type 2 diabetes. These findings extend our understanding of the potential mechanisms by which NAFLD is a risk factor for type 2 diabetes, and further elaborate on the role of SHBG as a hepatokine.

Sex differences in body composition in people with prediabetes and type 2 diabetes as compared with people with normal glucose metabolism: the Maastricht Study.

AIMS/HYPOTHESIS: Obesity is a major risk factor for type 2 diabetes. However, body composition differs between women and men. In this study we investigate the association between diabetes status and body composition and whether this association is moderated by sex. METHODS: In a population-based cohort study (n=7639; age 40-75 years, 50% women, 25% type 2 diabetes), we estimated the sex-specific associations, and differences therein, of prediabetes (i.e. impaired fasting glucose and/or impaired glucose tolerance) and type 2 diabetes (reference: normal glucose metabolism [NGM]) with dual-energy x-ray absorptiometry (DEXA)- and MRI-derived measures of body composition and with hip circumference. Sex differences were analysed using adjusted regression models with interaction terms of sex-by-diabetes status. RESULTS: Compared with their NGM counterparts, both women and men with prediabetes and type 2 diabetes had more fat and lean mass and a greater hip circumference. The differences in subcutaneous adipose tissue, hip circumference and total and peripheral lean mass between type 2 diabetes and NGM were greater in women than men (women minus men [W-M] mean difference [95% CI]: 15.0 cm2 [1.5, 28.5], 3.2 cm [2.2, 4.1], 690 g [8, 1372] and 443 g [142, 744], respectively). The difference in visceral adipose tissue between type 2 diabetes and NGM was greater in men than women (W-M mean difference [95% CI]: -14.8 cm2 [-26.4, -3.1]). There was no sex difference in the percentage of liver fat between type 2 diabetes and NGM. The differences in measures of body composition between prediabetes and NGM were generally in the same direction, but were not significantly different between women and men. CONCLUSIONS/INTERPRETATION: This study indicates that there are sex differences in body composition associated with type 2 diabetes. The pathophysiological significance of these sex-associated differences requires further study.

Attenuated cognitive functioning decades after preeclampsia.

BACKGROUND: Preeclampsia, a hypertensive pregnancy disorder, is a leading cause of maternal and fetal morbidity and mortality, with remote cardio- and cerebrovascular implications. After preeclampsia, women may report serious disabling cognitive complaints, especially involving executive function, but the extent and time course of these complaints are unknown. OBJECTIVE: This study aimed to determine the impact of preeclampsia on perceived maternal cognitive functioning decades after pregnancy. STUDY DESIGN: This study is part of a cross-sectional case-control study named Queen of Hearts (ClinicalTrials.gov Identifier: NCT02347540), a collaboration study of 5 tertiary referral centers within the Netherlands investigating long-term effects of preeclampsia. Eligible participants were female patients aged ≥18 years after preeclampsia and after normotensive pregnancy between 6 months and 30 years after their first (complicated) pregnancy. Preeclampsia was defined as new-onset hypertension after 20 weeks of gestation along with proteinuria, fetal growth restriction, or other maternal organ dysfunction. Women with a history of hypertension, autoimmune disease, or kidney disease before their first pregnancy were excluded. Attenuation of higher-order cognitive functions, that is, executive function, was measured with the Behavior Rating Inventory of Executive Function for Adults. Crude and covariate-adjusted absolute and relative risks of clinical attenuation over time after (complicated) pregnancy were determined with moderated logistic and log-binomial regression. RESULTS: This study included 1036 women with a history of preeclampsia and 527 women with normotensive pregnancies. Regarding overall executive function, 23.2% (95% confidence interval, 19.0-28.1) of women experienced clinically relevant attenuation after preeclampsia, as opposed to 2.2% (95% confidence interval, 0.8-6.0) of controls immediately after childbirth (adjusted relative risk, 9.20 [95% confidence interval, 3.33-25.38]). Group differences diminished yet remained statistically significant (P < .05) at least 19 years postpartum. Regardless of history of preeclampsia, women with lower educational attainment, mood or anxiety disorders, or obesity were especially at risk. Neither severity of preeclampsia, multiple gestation, method of delivery, preterm birth, nor perinatal death was related to overall executive function. CONCLUSION: After preeclampsia, women were 9 times more likely to experience clinical attenuation of higher-order cognitive functions as opposed to after normotensive pregnancy. Despite overall steady improvement, elevated risks persisted over decades after childbirth.

The association between antiplatelet therapy and changes in intraplaque hemorrhage in patients with mild to moderate symptomatic carotid stenosis: a longitudinal MRI study.

INTRODUCTION: Carotid atherosclerotic intraplaque hemorrhage (IPH) predicts stroke. Patients with a history of stroke are treated with antiplatelet agents to prevent secondary cardiovascular events. A positive association between previous antiplatelet use and IPH was reported in a cross-sectional analysis. We investigated changes in IPH over two years in patients who recently started versus those with continued antiplatelet use. METHODS: In the Plaque at Risk (PARISK) study, symptomatic patients with <70% ipsilateral carotid stenosis underwent carotid plaque MRI at baseline and after two years to determine IPH presence and volume. Participants were categorized into new users (starting antiplatelet therapy following the index event) and continued users (previous use of antiplatelet therapy before the index event). The association between previous antiplatelet therapy and the presence of IPH at baseline MRI was investigated using multivariable logistic regression analysis. IPH volume change over a period of two years, defined as the difference in volume between follow-up and baseline, was investigated in each group with a Wilcoxon signed-rank test. The IPH volume change was categorized as progression, regression, or no change. Using multivariable logistic regression, we investigated the association between new antiplatelet use and 1) newly developed ipsilateral or contralateral IPH and 2) IPH volume progression. RESULTS: A total of 108 patients underwent carotid MRI at baseline and follow-up. At baseline, previous antiplatelet therapy was associated with any IPH (OR=5.6, 95% CI: 1.3-23.1; p=0.02). Ipsilateral IPH volume did not change significantly during the two years in patients who continued receiving antiplatelet agents (86.4 mm3 [18.2-235.9] vs. 59.3 mm3 [11.4-260.3]; p=0.6) nor in the new antiplatelet users (n=31) (61.5 mm3 [0.0-166.9] vs. 27.7 mm3 [9.5-106.4]; p=0.4). Similar results of a nonsignificant change in contralateral IPH volume during those two years were observed in both groups (p>0.05). No significant associations were found between new antiplatelet use and newly developed IPH at two years (odds ratio (OR)=1.0, 95% CI:0.1-7.4) or the progression of IPH (ipsilateral: OR=2.4, 95% CI:0.3-19.1; contralateral: OR=0.3, 95% CI:0.01-8.5). CONCLUSION: Although the baseline association between IPH and previous antiplatelet therapy was confirmed in this larger cohort, the new onset of antiplatelet therapy after TIA/stroke was not associated with newly developed IPH or progression of IPH volume over the subsequent two years.

Associations between plasma sulfur amino acids and specific fat depots in two independent cohorts: CODAM and The Maastricht Study.

PURPOSE: Sulfur amino acids (SAAs) have been associated with obesity and obesity-related metabolic diseases. We investigated whether plasma SAAs (methionine, total cysteine (tCys), total homocysteine, cystathionine and total glutathione) are related to specific fat depots. METHODS: We examined cross-sectional subsets from the CODAM cohort (n = 470, 61.3% men, median [IQR]: 67 [61, 71] years) and The Maastricht Study (DMS; n = 371, 53.4% men, 63 [55, 68] years), enriched with (pre)diabetic individuals. SAAs were measured in fasting EDTA plasma with LC-MS/MS. Outcomes comprised BMI, skinfolds, waist circumference (WC), dual-energy X-ray absorptiometry (DXA, DMS), body composition, abdominal subcutaneous and visceral adipose tissues (CODAM: ultrasound, DMS: MRI) and liver fat (estimated, in CODAM, or MRI-derived, in DMS, liver fat percentage and fatty liver disease). Associations were examined with linear or logistic regressions adjusted for relevant confounders with z-standardized primary exposures and outcomes. RESULTS: Methionine was associated with all measures of liver fat, e.g., fatty liver disease [CODAM: OR = 1.49 (95% CI 1.19, 1.88); DMS: OR = 1.51 (1.09, 2.14)], but not with other fat depots. tCys was associated with overall obesity, e.g., BMI [CODAM: ß = 0.19 (0.09, 0.28); DMS: ß = 0.24 (0.14, 0.34)]; peripheral adiposity, e.g., biceps and triceps skinfolds [CODAM: ß = 0.15 (0.08, 0.23); DMS: ß = 0.20 (0.12, 0.29)]; and central adiposity, e.g., WC [CODAM: ß = 0.16 (0.08, 0.25); DMS: ß = 0.17 (0.08, 0.27)]. Associations of tCys with VAT and liver fat were inconsistent. Other SAAs were not associated with body fat. CONCLUSION: Plasma concentrations of methionine and tCys showed distinct associations with different fat depots, with similar strengths in the two cohorts.

Sex Differences in Plaque Composition and Morphology Among Symptomatic Patients With Mild-to-Moderate Carotid Artery Stenosis.

BACKGROUND AND PURPOSE: Incidence of ischemic stroke differs between men and women, with substantially higher rates in men. The underlying mechanism of this difference remains poorly understood but may be because of differences in carotid atherosclerosis. Using an in-depth imaging-based approach, we investigated differences between carotid plaque composition and morphology in male and female patients with stroke, taking into account differences in total plaque burden. Additionally, we investigated all possible within-artery combinations of plaque characteristics to explore differences between various plaque phenotypes. METHODS: We included 156 men and 68 women from the PARISK (Plaque At Risk) study, a prospective cohort study of patients with recent ischemic cerebrovascular symptoms and <70% ipsilateral carotid stenosis. Plaque characteristics (intraplaque hemorrhage [IPH], lipid-rich necrotic core [LRNC], calcifications, thin-or-ruptured fibrous cap, ulcerations, total plaque volume) were assessed with magnetic resonance imaging and multidetector-row computed tomography angiography. We used multivariable logistic and linear regression analyses to assess sex differences in plaque characteristics. RESULTS: We found significant difference in total plaque volume between men and women (ß=22.9 mm3 [95% CI, 15.4-30.5]; mean volume in men 1399±425 mm3, in women 1011±242 mm3). Additionally, men were more likely to have IPH (odds ratio [OR]=2.8 [95% CI, 1.3-6.3]; IPH proportion in men 49%, in women 16%) and LRNC (OR=2.4 [95% CI, 1.2-4.7]; LRNC proportion in men 73%, in women 41%) even after adjustment for total plaque volume. We found no sex-specific differences in plaque volume-corrected volumes of IPH, LRNC, and calcifications. In terms of coexistence of plaque characteristics, we found that men had more often a plaque with coexistence of calcifications, LRNC, and IPH (OR=2.7 [95% CI, 1.2-7.0]), with coexistence of thin-or-ruptured fibrous cap/ulcerations, LRNC, and IPH (OR=2.4 [95% CI, 1.1-5.9]), and with coexistence of all plaque characteristics (OR=3.0 [95% CI, 1.2-8.6]). CONCLUSIONS: In symptomatic patients with mild-to-moderate carotid stenosis, men are more likely to have a high-risk carotid plaque with IPH and LRNC than women, regardless of total plaque burden. Men also have more often a plaque with multiple vulnerable plaque components, which could comprise an even higher stroke risk. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01208025.

Optimal Management of Asymptomatic Carotid Stenosis in 2021: The Jury is Still Out. An International, Multispecialty, Expert Review and Position Statement.

OBJECTIVES: The recommendations of international guidelines for the management of asymptomatic carotid stenosis (ACS) often vary considerably and extend from a conservative approach with risk factor modification and best medical treatment (BMT) alone, to a more aggressive approach with a carotid intervention plus BMT. The aim of the current multispecialty position statement is to reconcile the conflicting views on the topic. MATERIALS AND METHODS: A literature review was performed with a focus on data from recent studies. RESULTS: Several clinical and imaging high-risk features have been identified that are associated with an increased long-term ipsilateral ischemic stroke risk in patients with ACS. Such high-risk clinical/imaging features include intraplaque hemorrhage, impaired cerebrovascular reserve, carotid plaque echolucency/ulceration/ neovascularization, a lipid-rich necrotic core, a thin or ruptured fibrous cap, silent brain infarction, a contralateral transient ischemic attack/stroke episode, male patients < 75 years and microembolic signals on transcranial Doppler. There is growing evidence that 80-99% ACS indicate a higher stroke risk than 50-79% stenoses. CONCLUSIONS: Although aggressive risk factor control and BMT should be implemented in all ACS patients, several high-risk features that may increase the risk of a future cerebrovascular event are now documented. Consequently, some guidelines recommend a prophylactic carotid intervention in high-risk patients to prevent future cerebrovascular events. Until the results of the much-anticipated randomized controlled trials emerge, the jury is still out regarding the optimal management of ACS patients.

Association between Intraplaque Hemorrhage and Vascular Remodeling in Carotid Arteries: The Plaque at RISK (PARISK) Study.

INTRODUCTION: Vascular remodeling is a compensatory enlargement of the vessel wall in response to atherosclerotic plaque growth. We aimed to investigate the association between intraplaque hemorrhage (IPH), vascular remodeling, and luminal dimensions in recently symptomatic patients with mild to moderate carotid artery stenosis in which the differences in plaque size were taken into account. MATERIALS AND METHODS: We assessed vessel dimensions on MRI of the symptomatic carotid artery in 164 patients from the Plaque At RISK study. This study included patients with recent ischemic neurological event and ipsilateral carotid artery stenosis <70%. The cross section with the largest wall area (WA) in the internal carotid artery (ICA) was selected for analysis. On this cross section, the following parameters were determined: WA, total vessel area (TVA), and lumen area (LA). Vascular remodeling was quantified as the remodeling ratio (RR) and was calculated as TVA at this position divided by the TVA in an unaffected distal portion of the ipsilateral ICA. Adjustment for WA was performed to correct for plaque size. RESULTS: Plaques with IPH had a larger WA (0.56 vs. 0.46 cm2; p < 0.001), a smaller LA (0.17 vs. 0.22 cm2; p = 0.03), and a higher RR (2.0 vs. 1.9; p = 0.03) than plaques without IPH. After adjustment for WA, plaques containing IPH had a smaller LA (B = -0.052, p = 0.01) than plaques without IPH, but the RR was not different. CONCLUSION: After correcting for plaque size, plaques containing IPH had a smaller LA than plaques without IPH. However, RR was not different.

Dark-blood late gadolinium enhancement cardiovascular magnetic resonance for improved detection of subendocardial scar: a review of current techniques.

For almost 20 years, late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) has been the reference standard for the non-invasive assessment of myocardial viability. Since the blood pool often appears equally bright as the enhanced scar regions, detection of subendocardial scar patterns can be challenging. Various novel LGE methods have been proposed that null or suppress the blood signal by employing additional magnetization preparation mechanisms. This review aims to provide a comprehensive overview of these dark-blood LGE methods, discussing the magnetization preparation schemes and findings in phantom, preclinical, and clinical studies. Finally, conclusions on the current evidence and limitations are drawn and new avenues for future research are discussed. Dark-blood LGE methods are a promising new tool for non-invasive assessment of myocardial viability. For a mainstream adoption of dark-blood LGE, however, clinical availability and ease of use are crucial.

Microvasculature and intraplaque hemorrhage in atherosclerotic carotid lesions: a cardiovascular magnetic resonance imaging study.

BACKGROUND: The presence of intraplaque haemorrhage (IPH) has been related to plaque rupture, is associated with plaque progression, and predicts cerebrovascular events. However, the mechanisms leading to IPH are not fully understood. The dominant view is that IPH is caused by leakage of erythrocytes from immature microvessels. The aim of the present study was to investigate whether there is an association between atherosclerotic plaque microvasculature and presence of IPH in a relatively large prospective cohort study of patients with symptomatic carotid plaque. METHODS: One hundred and thirty-two symptomatic patients with ≥2 mm carotid plaque underwent cardiovascular magnetic resonance (CMR) of the symptomatic carotid plaque for detection of IPH and dynamic contrast-enhanced (DCE)-CMR for assessment of plaque microvasculature. Ktrans, an indicator of microvascular flow, density and leakiness, was estimated using pharmacokinetic modelling in the vessel wall and adventitia. Statistical analysis was performed using an independent samples T-test and binary logistic regression, correcting for clinical risk factors. RESULTS: A decreased vessel wall Ktrans was found for IPH positive patients (0.051 ± 0.011 min- 1 versus 0.058 ± 0.017 min- 1, p = 0.001). No significant difference in adventitial Ktrans was found in patients with and without IPH (0.057 ± 0.012 min- 1 and 0.057 ± 0.018 min- 1, respectively). Histological analysis in a subgroup of patients that underwent carotid endarterectomy demonstrated no significant difference in relative microvessel density between plaques without IPH (n = 8) and plaques with IPH (n = 15) (0.000333 ± 0.0000707 vs. and 0.000289 ± 0.0000439, p = 0.585). CONCLUSIONS: A reduced vessel wall Ktrans is found in the presence of IPH. Thus, we did not find a positive association between plaque microvasculature and IPH several weeks after a cerebrovascular event. Not only leaky plaque microvessels, but additional factors may contribute to IPH development. TRIAL REGISTRATION: NCT01208025 . Registration date September 23, 2010. Retrospectively registered (first inclusion September 21, 2010). NCT01709045 , date of registration October 17, 2012. Retrospectively registered (first inclusion August 23, 2011).

Metformin and sulodexide restore cardiac microvascular perfusion capacity in diet-induced obese rats.

BACKGROUND: Disturbances in coronary microcirculatory function, such as the endothelial glycocalyx, are early hallmarks in the development of obesity and insulin resistance. Accordingly, in the present study myocardial microcirculatory perfusion during rest and stress was assessed following metformin or sulodexide therapy in a rat model of diet-induced obesity. Additionally, the effect of degradation of the glycocalyx on myocardial perfusion was assessed in chow-fed rats. METHODS: Rats were fed a high fat diet (HFD) for 8 weeks and were divided into a group without therapy, and groups that received the anti-diabetic drug metformin or the glycocalyx-stabilizing drug sulodexide in their drinking water during the last 4 weeks of the feeding period. Myocardial microvascular perfusion was determined using first-pass perfusion MRI before and after adenosine infusion. The effect of HFD on microcirculatory properties was also assessed by sidestream darkfield (SDF) imaging of the gastrocnemius muscle. In an acute experimental setting, hyaluronidase was administered to chow-fed control rats to determine the effect of enzymatical degradation of the glycocalyx on myocardial perfusion. RESULTS: HFD-rats developed central obesity and insulin sensitivity was reduced as evidenced by the marked reduction in insulin-induced phosphorylation of Akt in both cardiac and gastrocnemius muscle. We confirmed our earlier findings that the robust increase in myocardial perfusion in chow-fed rats after an adenosine challenge (+56%, p = 0.002) is blunted in HFD rats (+8%, p = 0.68). In contrast, 4-weeks treatment with metformin or sulodexide partly restored the increase in myocardial perfusion during adenosine infusion in HFD rats (+81%, p = 0.002 and +37%, p = 0.02, respectively). Treating chow-fed rats acutely with hyaluronidase, to enzymatically degrade the glyocalyx, completely blunted the increase in myocardial perfusion during stress. CONCLUSIONS: In early stages of HFD-induced insulin resistance myocardial perfusion becomes compromised, a process that can be countered by treatment with both metformin and sulodexide. The adverse effect of acute glycocalyx degradation and protective effect of long-term sulodexide administration on myocardial perfusion provides indirect evidence, suggesting a role for the glycocalyx in preserving coronary microvascular function in pre-diabetic animals.

Vessel wall and adventitial DCE-MRI parameters demonstrate similar correlations with carotid plaque microvasculature on histology.

PURPOSE: To assess parameter agreement of volume transfer coefficient (Ktrans ) between two vascular regions and to study the correlation with microvessel density on histology. The dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameter Ktrans is frequently used to study atherosclerotic plaque microvasculature. Ktrans has been reported using different descriptive statistics (mean, median, 75th percentile) either for the whole vessel wall or the adventitia in previous studies. MATERIALS AND METHODS: DCE-MRI parameter agreement was analyzed in 110 symptomatic patients with ≥2 mm carotid plaque that underwent a 3T carotid DCE-MRI examination. Ktrans was estimated in the entire vessel wall and adventitia. Twenty-three patients underwent carotid endarterectomy and were used for comparison with histological quantification of microvessel density of the plaque using CD31 immunohistochemistry. DCE-MRI parameters in the vessel wall regions were compared using Pearson's correlation coefficient, Bland-Altman analysis, and a two-sided paired samples t-test. Correlation of the DCE-MRI parameters with histology was studied using the Pearson's correlation coefficient. RESULTS: Median adventitial Ktrans was 5% higher (P = 0.003) than entire vessel wall Ktrans , with no differences for other descriptive statistics. Vessel wall and adventitial Ktrans showed similar moderately strong correlations with plaque microvessel density on histology (Pearson's ρ: 0.59-0.65 [P < 0.003] and 0.52-0.64 [P < 0.011], respectively). CONCLUSION: The similar moderately strong correlations for vessel wall and adventitial Ktrans with microvessel density on histology suggested that both regions reflected plaque microvessel density. Care should to be taken when comparing absolute values between studies. Future studies incorporating thresholds for risk stratification need to agree upon standardization of DCE-MRI parameters. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1053-1059.

Gadobutrol versus gadofosveset-trisodium in MR venography of the lower extremities.

OBJECTIVES: MR venography (MRV) protocols have used bloodpool contrast agents and long scan sequences to identify patients suitable for treatment and preoperatively. However, variable availability of bloodpool contrast agents, high costs and a need to shorten acquisition times for routine MR protocols hamper everyday practice. MATERIALS: 20 patients (11 men; mean age 54 ± 11.8 years; body mass index 23.6 ± 2.5) were enrolled in this prospective study. An intra-individual comparison of image quality, interpretation and findings for two different contrast agents (regular gadolinium contrast agent gadobutrol vs. bloodpool contrast agent gadofosveset-trisodium) and two different scan protocols (long acquisition time protocol using a high-resolution fast field echo (FFE) sequence vs. short acquisition time protocol using an ultra-fast gradient echo (GE) sequence) were performed. RESULTS: Image quality (average of 4.94 vs. 4.92 on a five-point scale), interpretation and contrast-to-noise ratio (44 vs. 45) were equal for both contrast agents. Image findings showed no statistical significant differences between the MR protocols or contrast agents (overall p = 0.328). CONCLUSIONS: For high-resolution MRV, it is possible to replace gadofosveset-trisodium with gadobutrol. Furthermore, an ultra-fast GE sequence for MRV might considerably shorten acquisition time, without loss of image quality or diagnostic yield. KEY POINTS: • High-quality MRV can be performed with a regular gadolinium-based contrast agent. • Ultra-fast GRE vs. HR-FFE MRV: equally suitable for evaluation of venous obstruction. • Regular gadolinium-based contrast agent can supersede a bloodpool contrast agent for MRV. • Equal confidence for gadobutrol vs gadofosveset-trisodium in MRV. • MRV accessible for routine daily practice.

Ischemic Stroke Patients Demonstrate Increased Carotid Plaque Microvasculature Compared to (Ocular) Transient Ischemic Attack Patients.

BACKGROUND: Patients with a recent ischemic stroke have a higher risk of recurrent stroke compared to (ocular) transient ischemic attack (TIA) patients. Plaque microvasculature is considered as a feature of plaque vulnerability and can be quantified with carotid dynamic contrast-enhanced MRI (DCE-MRI). The purpose of this cross-sectional study was to explore the association between plaque microvasculature and the type of recent cerebrovascular events in symptomatic patients with mild-to-moderate carotid stenosis. METHODS: A total of 87 symptomatic patients with a recent stroke (n = 35) or (ocular) TIA (n = 52) underwent carotid DCE-MRI examination. Plaque microvasculature was studied in the vessel wall and adventitia using DCE-MRI and the pharmacokinetic modeling parameter Ktrans. Statistical analysis was performed with logistic regression, correcting for associated clinical risk factors. RESULTS: The 75th percentile adventitial (OR 1.97, 95% CI 1.18-3.29) Ktrans was significantly associated with a recent ischemic stroke compared to (ocular) TIA in multivariate analysis, while clinical risk factors were not significantly associated with the type of event. CONCLUSIONS: This study indicates a positive association of leaky plaque microvasculature with a recent ischemic stroke compared to (ocular) TIA. Prospective longitudinal studies are needed to investigate whether Ktrans or other plaque characteristics may serve as an imaging marker for predicting (the type of) future cerebrovascular events.

Dynamic Contrast-Enhanced MRI to Study Atherosclerotic Plaque Microvasculature.

Rupture of a vulnerable atherosclerotic plaque of the carotid artery is an important underlying cause of clinical ischemic events, such as stroke. Abundant microvasculature has been identified as an important aspect contributing to plaque vulnerability. Plaque microvasculature can be studied non-invasively with dynamic contrast-enhanced (DCE-)MRI in animals and patients. In recent years, several DCE-MRI studies have been published evaluating the association between microvasculature and other key features of plaque vulnerability (e.g., inflammation and intraplaque hemorrhage), as well as the effects of novel therapeutic interventions. The present paper reviews this literature, focusing on DCE-MRI methods of acquisition and analysis of atherosclerotic plaques, the current state and future potential of DCE-MRI in the evaluation of plaque microvasculature in clinical and preclinical settings.

Use of Antiplatelet Agents Is Associated With Intraplaque Hemorrhage on Carotid Magnetic Resonance Imaging: The Plaque at Risk Study.

BACKGROUND AND PURPOSE: Intraplaque hemorrhage (IPH), visualized by magnetic resonance imaging, has shown to be associated with the risk of stroke in patients with carotid artery stenosis. The mechanisms of IPH development are poorly understood. In this study, we investigated the association between clinical patient characteristics and carotid IPH on high-resolution magnetic resonance imaging. METHODS: Patients participate in the Plaque at Risk (PARISK) study. This prospective, multicenter cohort study included patients with recent amaurosis fugax, hemispheric transient ischemic attack, or nondisabling stroke in the internal carotid artery territory and an ipsilateral carotid stenosis of <70%, who were not scheduled for carotid revascularization procedure. One hundred patients, recruited between 2010 and 2012, underwent a 3-T high-resolution carotid magnetic resonance imaging. We documented clinical patient characteristics and performed multivariable logistic regression analysis to investigate their association with IPH. RESULTS: IPH was observed in 45 patients (45%) in 1 or both carotid arteries. Male sex and the use of antiplatelet agents before the index event were associated with IPH in univariable analysis. In a multivariable analysis, only previous use of antiplatelet agents was significantly associated with IPH (odds ratio, 2.71; 95% confidence interval, 1.12-6.61). Risk factors of atherosclerotic arterial disease, including a history of symptomatic arterial diseases, were not associated with IPH. CONCLUSIONS: In this cohort of 100 patients with recently symptomatic carotid stenosis, the previous use of antiplatelet agents is associated with carotid IPH on magnetic resonance imaging. Antiplatelet therapy may increase the risk of IPH, but our findings need to be confirmed in larger patient cohorts. The implications for risk stratification remain to be determined.