Changes in intra- and extracranial carotid plaque calcification: a 2-year follow-up study.

Extra- and intracranial carotid plaque calcification might have plaque-stabilizing effects, yet information on changes in plaque calcification remains scarce. We evaluated changes in carotid plaque calcification over 2 years follow-up in patients with symptomatic carotid artery disease. This study is based on the PARISK-study, a multicenter cohort study, with TIA/minor stroke patients with ipsilateral mild-to-moderate carotid artery stenosis (< 70%). We included 79 patients (25% female, mean age 66 years) who underwent CTA imaging with 2 year interval. We assessed the volume of extra- and intracranial carotid artery calcification (ECAC and ICAC) and calculated the difference between baseline and follow-up ECAC and ICAC volume. We performed multivariable regression analyses to investigate the association between change of ECAC or ICAC with cardiovascular determinants. ECAC. We found increase (46.2%) and decrease (34%) in ECAC volume during 2 year follow-up, both significantly correlation with baseline ECAC volume (OR = 0.72, 95% CI 0.58-0.90 respectively OR = 2.24, 95% CI 1.60-3.13).We found significant correlation for change in ECAC volume with diabetes (ß = 0.46, 95% CI 0.03-0.89) and baseline ECAC volume (ß = 0.81, 95% CI 0.73-0.88). ICAC. We found increase (45.0%) and decrease (25.0%) in ICAC volume. The ICAC decrease was significantly correlated with baseline ICAC volume (OR = 2.17, 95% CI 1.48-3.16), age (OR = 2.00, 95% CI 1.19-3.38) and use of antihypertensive drugs (OR = 3.79, 95% CI 1.20-11.96]).The overall change of ICAC volume was also significantly correlated with diabetes (ß = 0.92, 95% CI 1.59-7.02), use of oral hypoglycemic drugs (ß = 0.86, 95% CI 0.12-1.59) and baseline ICAC volume (ß = 0.71, 95% CI 0.55-0.87). We provide novel insights into the dynamics of carotid plaque calcification in symptomatic stroke patients.

Cerebral volume is unaffected after pre-eclampsia.

OBJECTIVES: Pre-eclampsia has been associated with cardiovascular, cerebrovascular and/or psychological complaints. Signs of altered brain morphology and more white-matter hyperintensities (WMHs) during and shortly after pre-eclampsia have been observed in some, but not all, studies. We compared volumes of cerebral structures and the number of WMHs between formerly pre-eclamptic women and those with normotensive gestational history and assessed the effect of age on brain volumes. METHODS: Structural 7-Tesla magnetic resonance imaging of the brain was performed in 59 formerly pre-eclamptic women (aged 37 ± 6 years, 0.5-16 years postpartum) and 20 women with a history of normotensive pregnancy (aged 39 ± 5 years, 1-18 years postpartum). Fazekas scores were obtained to assess WMH load. Volumes of the whole brain, gray and white matter, brain lobes, and ventricular and pericortical cerebrospinal fluid (CSF) spaces were calculated after semiautomatic segmentation. Group differences were analyzed using ANCOVA and Bayes factors. Results were adjusted for age, educational attainment, presence of current hypertension and total intracranial volume. The effect of age on cerebral volumes was analyzed using linear regression analysis. RESULTS: No changes in global and local brain volumes were observed between formerly pre-eclamptic and control women. Also, no difference in WMH load was observed. Independent of pre-eclamptic history, gray-matter volume significantly decreased with age, while ventricular and pericortical CSF space volumes significantly increased with age. CONCLUSIONS: Volumetric changes of the cerebrum are age-related but are independent of pre-eclamptic history in the first two decades after childbirth. No evidence of greater WMH load after pre-eclampsia was found. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Proximal Region of Carotid Atherosclerotic Plaque Shows More Intraplaque Hemorrhage: The Plaque at Risk Study.

BACKGROUND AND PURPOSE: Intraplaque hemorrhage contributes to lipid core enlargement and plaque progression, leading to plaque destabilization and stroke. The mechanisms that contribute to the development of intraplaque hemorrhage are not completely understood. A higher incidence of intraplaque hemorrhage and thin/ruptured fibrous cap (upstream of the maximum stenosis in patients with severe [≥70%] carotid stenosis) has been reported. We aimed to noninvasively study the distribution of intraplaque hemorrhage and a thin/ruptured fibrous cap in patients with mild-to-moderate carotid stenosis. MATERIALS AND METHODS: Eighty-eight symptomatic patients with stroke (<70% carotid stenosis included in the Plaque at Risk study) demonstrated intraplaque hemorrhage on MR imaging in the carotid artery plaque ipsilateral to the side of TIA/stroke. The intraplaque hemorrhage area percentage was calculated. A thin/ruptured fibrous cap was scored by comparing pre- and postcontrast black-blood TSE images. Differences in mean intraplaque hemorrhage percentages between the proximal and distal regions were compared using a paired-samples t test. The McNemar test was used to reveal differences in proportions of a thin/ruptured fibrous cap. RESULTS: We found significantly larger areas of intraplaque hemorrhage in the proximal part of the plaque at 2, 4, and 6 mm from the maximal luminal narrowing, respectively: 14.4% versus 9.6% (P = .04), 14.7% versus 5.4% (P < .001), and 11.1% versus 2.2% (P = .001). Additionally, we found an increased proximal prevalence of a thin/ruptured fibrous cap on MR imaging at 2, 4, 6, and 8 mm from the MR imaging section with the maximal luminal narrowing, respectively: 33.7% versus 18.1%, P = .007; 36.1% versus 7.2%, P < .001; 33.7% versus 2.4%, P = .001; and 30.1% versus 3.6%, P = .022. CONCLUSIONS: We demonstrated that intraplaque hemorrhage and a thin/ruptured fibrous cap are more prevalent on the proximal side of the plaque compared with the distal side in patients with mild-to-moderate carotid stenosis.

Roadmap Consensus on Carotid Artery Plaque Imaging and Impact on Therapy Strategies and Guidelines: An International, Multispecialty, Expert Review and Position Statement.

Current guidelines for primary and secondary prevention of stroke in patients with carotid atherosclerosis are based on the quantification of the degree of stenosis and symptom status. Recent publications have demonstrated that plaque morphology and composition, independent of the degree of stenosis, are important in the risk stratification of carotid atherosclerotic disease. This finding raises the question as to whether current guidelines are adequate or if they should be updated with new evidence, including imaging for plaque phenotyping, risk stratification, and clinical decision-making in addition to the degree of stenosis. To further this discussion, this roadmap consensus article defines the limits of luminal imaging and highlights the current evidence supporting the role of plaque imaging. Furthermore, we identify gaps in current knowledge and suggest steps to generate high-quality evidence, to add relevant information to guidelines currently based on the quantification of stenosis.

Plaque Composition as a Predictor of Plaque Ulceration in Carotid Artery Atherosclerosis: The Plaque At RISK Study.

BACKGROUND AND PURPOSE: Plaque ulceration is a marker of previous plaque rupture. We studied the association between atherosclerotic plaque composition at baseline and plaque ulceration at baseline and follow-up. MATERIALS AND METHODS: We included symptomatic patients with a carotid stenosis of <70% who underwent MDCTA and MR imaging at baseline (n = 180). MDCTA was repeated at 2 years (n = 73). We assessed the presence of ulceration using MDCTA. Baseline MR imaging was used to assess the vessel wall volume and the presence and volume of plaque components (intraplaque hemorrhage, lipid-rich necrotic core, and calcifications) and the fibrous cap status. Associations at baseline were evaluated with binary logistic regression and reported with an OR and its 95% CI. Simple statistical testing was performed in the follow-up analysis. RESULTS: At baseline, the prevalence of plaque ulceration was 27% (49/180). Increased wall volume (OR = 12.1; 95% CI, 3.5-42.0), higher relative lipid-rich necrotic core (OR = 1.7; 95% CI, 1.3-2.2), higher relative intraplaque hemorrhage volume (OR = 1.7; 95% CI, 1.3-2.2), and a thin-or-ruptured fibrous cap (OR = 3.4; 95% CI, 1.7-6.7) were associated with the presence of ulcerations at baseline. In 8% (6/73) of the patients, a new ulcer developed. Plaques with a new ulceration at follow-up had at baseline a larger wall volume (1.04 cm3 [IQR, 0.97-1.16 cm3] versus 0.86 cm3 [IQR, 0.73-1.00 cm3]; P = .029), a larger relative lipid-rich necrotic core volume (23% [IQR, 13-31%] versus 2% [IQR, 0-14%]; P = .002), and a larger relative intraplaque hemorrhage volume (14% [IQR, 8-24%] versus 0% [IQR, 0-5%]; P < .001). CONCLUSIONS: Large atherosclerotic plaques and plaques with intraplaque hemorrhage and lipid-rich necrotic cores were associated with plaque ulcerations at baseline and follow-up.

Association between fibrinogen and fibrinogen γ' and atherosclerotic plaque morphology and composition in symptomatic carotid artery stenosis: Plaque-At-RISK study.

INTRODUCTION: Von Willebrand Factor (VWF), ADAMTS13, fibrinogen and fibrinogen γ' are associated with an increased risk of ischemic stroke. Carotid atherosclerosis is an important risk factor for ischemic stroke. Characteristics of the vulnerable plaque; intraplaque hemorrhage (IPH), plaque ulceration and lipid-rich necrotic core (LRNC) can be visualized with imaging techniques. Since atherosclerosis might attribute to the association between coagulation factors and ischemic stroke risk, the aim of this study is to investigate the association between coagulation factors and atherosclerotic plaque characteristics in more detail. MATERIALS AND METHODS: In 182 patients of the Plaque-At-RISK study (prospective multicenter cohort study) with a recent transient ischemic attack (TIA) or ischemic stroke and a symptomatic mild-to-moderate carotid artery stenosis, we measured VWF antigen (VWF:Ag), ADAMTS13 activity, fibrinogen (Clauss), and fibrinogen γ'. Presence of plaque ulceration, IPH volume and LRNC volume were determined by Multidetector-Row Computed Tomography (MDCTA, n = 160) and Magnetic Resonance Imaging (MRI, n = 172). Linear regression analysis was used to assess the association between imaging biomarkers and coagulation factors. RESULTS: VWF:Ag or ADAMTS13 levels were not significantly associated with plaque ulceration, IPH and LRNC. We found an inverse association between fibrinogen and fibrinogen γ' and IPH volume (B = -23.40 mm3/g/L, p = 0.01 and B = -161.73 mm3/g/L, p = 0.01) and between fibrinogen and fibrinogen γ' and LRNC volume (B = -38.89 mm3 g/L, p < 0.01 and B = -227.06 mm3 g/L, p = 0.01). Additional adjustments for C-reactive protein (CRP) did not change the results. CONCLUSIONS: Fibrinogen and fibrinogen γ' are inversely associated with IPH volume and LRNC volume, independent of inflammation. CLINICAL TRIAL REGISTRATION: clinicaltrials.govNCT01208025.

Carotid Artery Wall Imaging: Perspective and Guidelines from the ASNR Vessel Wall Imaging Study Group and Expert Consensus Recommendations of the American Society of Neuroradiology.

Identification of carotid artery atherosclerosis is conventionally based on measurements of luminal stenosis and surface irregularities using in vivo imaging techniques including sonography, CT and MR angiography, and digital subtraction angiography. However, histopathologic studies demonstrate considerable differences between plaques with identical degrees of stenosis and indicate that certain plaque features are associated with increased risk for ischemic events. The ability to look beyond the lumen using highly developed vessel wall imaging methods to identify plaque vulnerable to disruption has prompted an active debate as to whether a paradigm shift is needed to move away from relying on measurements of luminal stenosis for gauging the risk of ischemic injury. Further evaluation in randomized clinical trials will help to better define the exact role of plaque imaging in clinical decision-making. However, current carotid vessel wall imaging techniques can be informative. The goal of this article is to present the perspective of the ASNR Vessel Wall Imaging Study Group as it relates to the current status of arterial wall imaging in carotid artery disease.

Intraplaque Hemorrhage and the Plaque Surface in Carotid Atherosclerosis: The Plaque At RISK Study (PARISK).

BACKGROUND AND PURPOSE: An important characteristic of vulnerable plaque, intraplaque hemorrhage, may predict plaque rupture. Plaque rupture can be visible on noninvasive imaging as a disruption of the plaque surface. We investigated the association between intraplaque hemorrhage and disruption of the plaque surface. MATERIALS AND METHODS: We selected the first 100 patients of the Plaque At RISK study, an ongoing prospective noninvasive plaque imaging study in patients with mild-to-moderate atherosclerotic lesions in the carotid artery. In carotid artery plaques, disruption of the plaque surface (defined as ulcerated plaques and/or fissured fibrous cap) and intraplaque hemorrhage were assessed by using MDCTA and 3T MR imaging, respectively. We used a χ(2) test and multivariable logistic regression to assess the association between intraplaque hemorrhage and disrupted plaque surface. RESULTS: One hundred forty-nine carotid arteries in 78 patients could be used for the current analyses. Intraplaque hemorrhage and plaque ulcerations were more prevalent in symptomatic compared with contralateral vessels (hemorrhage, 38% versus 11%; P < .001; and ulcerations, 27% versus 7%; P = .001). Fissured fibrous cap was more prevalent in symptomatic compared with contralateral vessels (13% versus 4%; P = .06). After adjustment for age, sex, diabetes mellitus, and degree of stenosis, intraplaque hemorrhage was associated with disrupted plaque surface (OR, 3.13; 95% CI, 1.25-7.84) in all vessels. CONCLUSIONS: Intraplaque hemorrhage is associated with disruption of the plaque surface in patients with a carotid artery stenosis of <70%. Serial studies are needed to investigate whether intraplaque hemorrhage indeed increases the risk of plaque rupture and subsequent ischemic stroke during follow-up.

Phase-based vascular input function: Improved quantitative DCE-MRI of atherosclerotic plaques.

PURPOSE: Quantitative pharmacokinetic modeling of dynamic contrast-enhanced (DCE)-MRI can be used to assess atherosclerotic plaque microvasculature, which is an important marker of plaque vulnerability. Purpose of the present study was (1) to compare magnitude- versus phase-based vascular input functions (m-VIF vs ph-VIF) used in pharmacokinetic modeling and (2) to perform model calculations and flow phantom experiments to gain more insight into the differences between m-VIF and ph-VIF. METHODS: Population averaged m-VIF and ph-VIFs were acquired from 11 patients with carotid plaques and used for pharmacokinetic analysis in another 17 patients. Simulations, using the Bloch equations and the MRI scan geometry, and flow phantom experiments were performed to determine the effect of local blood velocity on the magnitude and phase signal enhancement. RESULTS: Simulations and flow phantom experiments revealed that flow within the lumen can lead to severe underestimation of m-VIF, while this is not the case for the ph-VIF. In line, the peak concentration of the m-VIF is significantly lower than ph-VIF (p < 0.001), in vivo. Quantitative model parameters for m- and ph-VIF differed in absolute values but were moderate to strongly correlated with each other [K(trans) Spearman's ρ > 0.93 (p < 0.001) and vp Spearman's ρ > 0.58 (p < 0.05)]. CONCLUSIONS: m-VIF is strongly influenced by local blood velocity, which leads to underestimation of the contrast medium concentration. Therefore, it is advised to use ph-VIF for DCE-MRI analysis of carotid plaques for accurate quantification.

Acute exercise does not decrease liver fat in men with overweight or NAFLD.

Elevated hepatic lipid content (IntraHepatic Lipid, IHL) increases the risk of metabolic complications. Although prolonged exercise training lowers IHL, it is unknown if acute exercise has the same effect. Furthermore, hepatic ATP content may be related to insulin resistance and IHL. We aimed to investigate if acute exercise leads to changes in IHL and whether this is accompanied by changes in hepatic ATP. Twenty-one men (age 54.8 ± 7.2 years, BMI 29.7 ± 2.2 kg/m(2)) performed a 2 h cycling protocol, once while staying fasted and once while ingesting glucose. IHL was determined at baseline, 30 min post-exercise and 4 h post-exercise. Additionally ATP/Total P ratio was measured at baseline and 4 h post-exercise. Compared with baseline values we did not observe any statistically significant changes in IHL within 30 min post-exercise in neither the fasted nor the glucose-supplemented condition. However, IHL was elevated 4 h post-exercise compared with baseline in the fasted condition (from 8.3 ± 1.8 to 8.7 ± 1.8%, p = 0.010), an effect that was blunted by glucose supplementation (from 8.3 ± 1.9 to 8.3 ± 1.9%, p = 0.789). Acute exercise does not decrease liver fat in overweight middle-aged men. Moreover, IHL increased 4 h post-exercise in the fasted condition, an increase that was absent in the glucose-supplemented condition. These data suggest that a single bout of exercise may not be able to lower IHL.

Abdominal aortic aneurysms with high thrombus signal intensity on magnetic resonance imaging are associated with high growth rate.

OBJECTIVES: A layer of intraluminal thrombus is commonly observed in abdominal aortic aneurysms (AAAs). The purpose of this study was to investigate whether AAAs with high thrombus signal intensity (SI) at T1-weighted (T1w) magnetic resonance imaging (MRI) exhibit a faster aneurysm growth rate. METHODS: This was a prospective follow-up study. Patients with a small AAA underwent MRI examinations at 6 month intervals. Aneurysm thrombus and psoas muscle SI at the point of maximal diameter on T1w images were measured and expressed as a ratio (thrombus SI/muscle SI). Based on these measurements, patients were categorized into three groups: AAA with relative thrombus SI above (group A) and below (group B) the mean relative thrombus SI of 1.20. Patients with AAA without thrombus constituted group C. Eight patients were scanned twice within 2 weeks to investigate scan-rescan reproducibility. Aneurysm growth rates were expressed as the change in maximal cross sectional area (cm(2)). RESULTS: A total of 35 patients (m/f: 26/9; age 72 ± 7 years; AAA maximal diameter 4.9 ± 0.5 cm) were included. Mean aneurysm growth rate for patients in group A (n = 11, 1.87 cm(2)/0.5 year) was two-fold higher than group B (n = 17, 0.78 cm(2)/0.5 year, p = .005) and eight-fold higher than group C (n = 7, 0.23 cm(2)/0.5 years, p = .004) at 6 months' follow-up. At 12 months' follow-up, the mean aneurysm growth rate remained significantly higher in group A (n = 7, 3.03 cm(2)/year) than groups B (n = 10, 1.63 cm(2)/year, p = .03) and C (n = 7, 0.73 cm(2)/year, p = .004). The reproducibility for thrombus SI measurements was found to be high with a coefficient of variation of 6.2%. Aneurysm maximal cross-sectional area at baseline was not significantly different for the three groups. CONCLUSIONS: Abdominal aortic aneurysms with high thrombus SI on T1w MR images are associated with higher aneurysm growth rates.

Plaque At RISK (PARISK): prospective multicenter study to improve diagnosis of high-risk carotid plaques.

BACKGROUND: Patients with symptomatic carotid artery stenosis are at high risk for recurrent stroke. To date, the decision to perform carotid endarterectomy in patients with a recent cerebrovascular event is mainly based on degree of stenosis of the ipsilateral carotid artery. However, additional atherosclerotic plaque characteristics might be better predictors of stroke, allowing for more precise selection of patients for carotid endarterectomy. AIMS AND HYPOTHESIS: We investigate the hypothesis that the assessment of carotid plaque characteristics with magnetic resonance imaging, multidetector-row computed tomography angiography, ultrasonography, and transcranial Doppler, either alone or in combination, may improve identification of a subgroup of patients with < 70% carotid artery stenosis with an increased risk of recurrent stroke. METHODS: The Plaque At RISK (PARISK) study is a prospective multicenter cohort study of patients with recent (<3 months) neurological symptoms due to ischemia in the territory of the carotid artery and < 70% ipsilateral carotid artery stenosis who are not scheduled for carotid endarterectomy or stenting. At baseline, 300 patients will undergo magnetic resonance imaging, multidetector-row computed tomography angiography, and ultrasonography examination of the carotid arteries. In addition, magnetic resonance imaging of the brain, ambulatory transcranial Doppler recording of the middle cerebral artery and blood withdrawal will be performed. After two-years, imaging will be repeated in 150 patients. All patients undergo a follow-up brain magnetic resonance imaging, and there will be regular clinical follow-up until the end of the study. STUDY OUTCOMES: The combined primary end-point contains ipsilateral recurrent ischemic stroke or transient ischemic attack or new ipsilateral ischemic brain lesions on follow-up brain magnetic resonance imaging.

Automated registration of multispectral MR vessel wall images of the carotid artery.

PURPOSE: Atherosclerosis is the primary cause of heart disease and stroke. The detailed assessment of atherosclerosis of the carotid artery requires high resolution imaging of the vessel wall using multiple MR sequences with different contrast weightings. These images allow manual or automated classification of plaque components inside the vessel wall. Automated classification requires all sequences to be in alignment, which is hampered by patient motion. In clinical practice, correction of this motion is performed manually. Previous studies applied automated image registration to correct for motion using only nondeformable transformation models and did not perform a detailed quantitative validation. The purpose of this study is to develop an automated accurate 3D registration method, and to extensively validate this method on a large set of patient data. In addition, the authors quantified patient motion during scanning to investigate the need for correction. METHODS: MR imaging studies (1.5T, dedicated carotid surface coil, Philips) from 55 TIA∕stroke patients with ipsilateral <70% carotid artery stenosis were randomly selected from a larger cohort. Five MR pulse sequences were acquired around the carotid bifurcation, each containing nine transverse slices: T1-weighted turbo field echo, time of flight, T2-weighted turbo spin-echo, and pre- and postcontrast T1-weighted turbo spin-echo images (T1W TSE). The images were manually segmented by delineating the lumen contour in each vessel wall sequence and were manually aligned by applying throughplane and inplane translations to the images. To find the optimal automatic image registration method, different masks, choice of the fixed image, different types of the mutual information image similarity metric, and transformation models including 3D deformable transformation models, were evaluated. Evaluation of the automatic registration results was performed by comparing the lumen segmentations of the fixed image and moving image after registration. RESULTS: The average required manual translation per image slice was 1.33 mm. Translations were larger as the patient was longer inside the scanner. Manual alignment took 187.5 s per patient resulting in a mean surface distance of 0.271 ± 0.127 mm. After minimal user interaction to generate the mask in the fixed image, the remaining sequences are automatically registered with a computation time of 52.0 s per patient. The optimal registration strategy used a circular mask with a diameter of 10 mm, a 3D B-spline transformation model with a control point spacing of 15 mm, mutual information as image similarity metric, and the precontrast T1W TSE as fixed image. A mean surface distance of 0.288 ± 0.128 mm was obtained with these settings, which is very close to the accuracy of the manual alignment procedure. The exact registration parameters and software were made publicly available. CONCLUSIONS: An automated registration method was developed and optimized, only needing two mouse clicks to mark the start and end point of the artery. Validation on a large group of patients showed that automated image registration has similar accuracy as the manual alignment procedure, substantially reducing the amount of user interactions needed, and is multiple times faster. In conclusion, the authors believe that the proposed automated method can replace the current manual procedure, thereby reducing the time to analyze the images.

High field carotid vessel wall imaging: a study on reproducibility.

PURPOSE: Currently, a multi-contrast protocol, including a combination of five MR-sequences is used as reference standard for morphologic imaging and quantitative measurements of the carotid artery vessel wall. The purpose of this study is to investigate the scan-rescan reproducibility together with intra- and inter-observer reproducibility of each of the five MR-sequences. METHODS: Twenty healthy volunteers (55% male, mean age=26 years) underwent repeated MR-examinations (3T-Philips-MRI) of the left carotid artery vessel wall with five sequences; T1-TFE, T2-TSE, PD-TSE, T1-TSE and 3D TOF. A standard phased-array coil with two flexible elements of 14cm×17cm was used to obtain nine transverse imaging sections of the left carotid artery with identical in-plane resolution (0.46mm×0.46mm). Reproducibility analysis was performed in 3 slices of the common carotid artery for all sequences. RESULTS: For, scan-rescan reproducibility, intra class correlation coefficients (ICC) were excellent for all sequences and ranged from 0.79 to 0.95. The intra-observer ICC ranged from 0.89 to 0.98 and the inter-observer ICC ranged from 0.84 to 0.96, for both lumen and vessel wall assessment. CONCLUSIONS: By high field MR imaging, vessel wall and lumen area of the carotid artery can be assessed with excellent scan-rescan, intra- and inter-observer reproducibility for all five sequences.

Efficacy of positive contrast imaging techniques for molecular MRI of tumor angiogenesis.

Superparamagnetic iron oxide particles (SPIOs) are promising contrast agents for molecular MRI. To improve the in vivo detection of iron-based contrast media, positive contrast imaging techniques have been developed. Here, the efficacy of two positive contrast techniques, white marker and susceptibility gradient mapping (SGM), were evaluated for molecular MRI of tumor angiogenesis and compared with conventional negative contrast gradient echo (GE) imaging. In vitro, cylindrical phantoms containing varying iron oxide concentrations were used to measure the response of positive contrast techniques. In vivo, tumor bearing mice were used as a model for tumor angiogenesis. Mice were injected with unlabeled SPIOs (n = 5) or SPIOs labeled with cyclic NGR peptide (cNGR) (n = 5), which homes specifically to angiogenic microvessels. Pre- and post-contrast GE and white marker images were acquired. Subsequently, SGM images and R(2)(*) maps were calculated. For image analysis, the contrast-to-noise ratio (CNR) and the percentage of enhanced voxels (EVs) in the tumor rim and core were calculated. In vitro, the linear increases in MRI signal response for increasing iron oxide concentration were much stronger for SGM than white marker. In vivo, the CNR of GE, white marker and SGM imaging was 5.7, 1.2 and 6.2, respectively, with equal acquisition times. Significant differences in the percentage of EVs between the tumor rim and core were found using R(2)(*) mapping, GE and SGM (p < 0.05). The two contrast agents had significantly different percentages of EVs by R(2)(*) mapping and SGM in the rim (p < 0.001). The in vivo efficacy of white marker and SGM was evaluated for molecular MRI relative to GE imaging and R(2)(*) mapping. Only SGM, and not white marker, can be used to transfer the negative contrast from targeted SPIOs in a positive contrast signal without loss of CNR.

Potential of integrated [18F] fluorodeoxyglucose positron-emission tomography/CT in identifying vulnerable carotid plaques.

BACKGROUND AND PURPOSE: There is a need for improved risk stratification of patients with TIA/stroke and carotid atherosclerosis. The purpose of this study was to prospectively investigate the potential of integrated (18)F-FDG PET/MDCT in identifying vulnerable carotid plaques. MATERIALS AND METHODS: Fifty patients with TIA/stroke with an ipsilateral carotid plaque causing <70% stenosis and a plaque on the contralateral asymptomatic side underwent integrated (18)F-FDG PET/MDCT within 36.1 ± 20.0 days (range, 9-95 days) of the last symptoms. Carotid plaque (18)F-FDG uptake was measured as both the mean and maximum blood-normalized SUV, known as the TBR. Using MDCT, we assessed volumes of vessel wall and individual plaque components. RESULTS: Mean TBR was only significantly larger in the ipsilateral plaques of patients who were imaged within 38 days (1.24 ± 0.04 [SE] versus 1.17 ± 0.05, P = .014). This also accounted for maximum TBR (1.53 ± 0.06 versus 1.42 ± 0.06, P = .015). MDCT-assessed vessel wall and LRNC volumes were larger in ipsilateral plaques of all patients (982.3 ± 121.3 versus 811.3 ± 106.6 mm(3), P = .016; 164.7 ± 26.1 versus 134.3 ± 35.2 mm(3), P = .026, respectively). CONCLUSIONS: In the present study, (18)F-FDG PET only detected significant differences between ipsilateral and contralateral asymptomatic plaques in patients with TIA/stroke who were imaged within 38 days, whereas MDCT detected larger vessel wall and LRNC volumes, regardless of time after symptoms. In view of the substantial overlap in measurements of both sides, it remains to be determined whether the differences we found will be clinically meaningful.

Exercise-induced modulation of cardiac lipid content in healthy lean young men.

Cardiac lipid accumulation is associated with decreased cardiac function and energy status (PCr/ATP). It has been suggested that elevated plasma fatty acid (FA) concentrations are responsible for the cardiac lipid accumulation. Therefore, the aim of the present study was to investigate if elevating plasma FA concentrations by exercise results in an increased cardiac lipid content, and if this influences cardiac function and energy status. Eleven male subjects (age 25.4 ± 1.1 years, BMI 23.6 ± 0.8 kg/m²) performed a 2-h cycling protocol, once while staying fasted and once while ingesting glucose, to create a state of high versus low plasma FA concentrations, respectively. Cardiac lipid content was measured by proton magnetic resonance spectroscopy (¹H-MRS) at baseline, directly after exercise and again 4 h post-exercise, together with systolic function (by multi-slice cine-MRI) and cardiac energy status (by ³¹P-MRS). Plasma FA concentrations were increased threefold during exercise and ninefold during recovery in the fasted state compared with the glucose-fed state (p < 0.01). Cardiac lipid content was elevated at the end of the fasted test day (from 0.26 ± 0.04 to 0.44 ± 0.04%, p = 0.003), while it did not change with glucose supplementation (from 0.32 ± 0.03 to 0.26 ± 0.05%, p = 0.272). Furthermore, PCr/ATP was decreased by 32% in the high plasma FA state compared with the low FA state (n = 6, p = 0.014). However, in the high FA state, the ejection fraction 4 h post-exercise was higher compared with the low FA state (63 ± 2 vs. 59 ± 2%, p = 0.018). Elevated plasma FA concentrations, induced by exercise in the fasted state, lead to increased cardiac lipid content, but do not acutely hamper systolic function. Although the lower cardiac energy status is in line with a lipotoxic action of cardiac lipid content, a causal relationship cannot be proven.

Leukocyte counts, myeloperoxidase, and pregnancy-associated plasma protein a as biomarkers for cardiovascular disease: towards a multi-biomarker approach.

We evaluated leukocyte counts and levels of CRP, fibrinogen, MPO, and PAPP-A in patients with stable and unstable angina pectoris, acute myocardial infarction, and healthy controls. All biomarkers were analyzed again after 6 months. Leukocyte counts and concentrations of fibrinogen, CRP, MPO, and PAPP-A were significantly increased in patients with acute myocardial infarction. Leukocyte counts and concentrations of MPO were significantly increased in patients with unstable angina pectoris compared with controls. After 6 months, leukocyte counts and MPO concentrations were still increased in patients with acute myocardial infarction when compared to controls. Discriminant analysis showed that leukocyte counts, MPO, and PAPP-A concentrations classified study group designation for acute coronary events correctly in 83% of the cases. In conclusion, combined assessment of leukocyte counts, MPO, and PAPP-A was able to correctly classify acute coronary events, suggesting that this could be a promising panel for a multibiomarker approach to assess cardiovascular risk.