Martine T.B. Truijman

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.

Combined 18F-FDG PET-CT and DCE-MRI to Assess Inflammation and Microvascularization in Atherosclerotic Plaques

Background and Purpose— Hallmarks of vulnerable atherosclerotic plaques are inflammation that can be assessed with 18fluorine-fluorodeoxyglucose positron emission tomography/computed tomography, and increased neovascularization that can be evaluated by dynamic contrast–enhanced-MRI. It remains unclear whether these parameters are correlated or represent independent imaging parameters. This study determines whether there is a correlation between inflammation and neovascularization in atherosclerotic carotid plaques. Methods— A total of 58 patients with transient ischemic attack or minor stroke in the carotid territory and ipsilateral carotid artery stenosis of 30% to 69% were included. All patients underwent positron emission tomography/computed tomography and dynamic contrast–enhanced-MRI of the carotid plaque. 18Fluorine-fluorodeoxyglucose standard uptake values with target/background ratio were determined. Neovascularization was quantified by the mean (leakage) volume transfer constant Ktrans. Spearman rank correlation coefficients between target/background ratio and Ktrans were calculated. Results— Images suitable for further analysis were obtained in 49 patients. A weak but significant positive correlation between target/background ratio and mean Ktrans (Spearman &rgr;=0.30 [P=0.035]) and 75th percentile Ktrans (Spearman &rgr;=0.29 [P=0.041]) was found. Conclusions— There is a weak but significant positive correlation between inflammation on positron emission tomography/computed tomography and neovascularization as assessed with dynamic contrast–enhanced-MRI. Future studies should investigate which imaging modality has the highest predictive value for recurrent stroke, as these are not interchangeable. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00451529.

Longitudinal MRI study on the natural history of carotid artery plaques in symptomatic patients.

Purpose To investigate the natural history of carotid atherosclerosis in patients who experienced a TIA or ischemic stroke. Patients and Methods Ninety-two TIA/stroke patients (57 men, mean age 67.7±9.8 years) with ipsilateral <70% carotid stenosis underwent multisequence MRI of the plaque ipsilateral to the symptomatic side at baseline and after one year. For each plaque, several parameters were assessed at both time points. Results Carotid lumen, wall and total vessel ( = carotid lumen and wall) volume did not significantly change. Forty-four patients had a plaque with a lipid-rich necrotic core (LRNC) at baseline, of which 34 also had a LRNC after one year. In three patients a LRNC appeared after one year. Thirty patients had a plaque with a thin and/or ruptured fibrous cap (FC) at both time points. In seven patients, FC status changed from thin and/or ruptured into thick and intact. In three patients, FC status changed from thick and intact into thin and/or ruptured. Twenty patients had intraplaque hemorrhage (IPH) at both time points. In four patients, IPH disappeared, whereas in three patients, new IPH appeared at follow-up. Conclusion In TIA/stroke patients, carotid plaque morphology does not significantly change over a one-year period. IPH and FC status change in a minority of patients.

Numerical simulations of carotid MRI quantify the accuracy in measuring atherosclerotic plaque components in vivo

Atherosclerotic carotid plaques can be quantified in vivo by MRI. However, the accuracy in segmentation and quantification of components such as the thin fibrous cap (FC) and lipid‐rich necrotic core (LRNC) remains unknown due to the lack of a submillimeter scale ground truth.

Multi-Center MRI Carotid Plaque Component Segmentation Using Feature Normalization and Transfer Learning

Automated segmentation of plaque components in carotid artery magnetic resonance imaging (MRI) is important to enable large studies on plaque vulnerability, and for incorporating plaque composition as an imaging biomarker in clinical practice. Especially supervised classification techniques, which learn from labeled examples, have shown good performance. However, a disadvantage of supervised methods is their reduced performance on data different from the training data, for example on images acquired with different scanners. Reducing the amount of manual annotations required for each new dataset will facilitate widespread implementation of supervised methods. In this paper we segment carotid plaque components of clinical interest (fibrous tissue, lipid tissue, calcification and intraplaque hemorrhage) in a multi-center MRI study. We perform voxelwise tissue classification by traditional same-center training, and compare results with two approaches that use little or no annotated same-center data. These approaches additionally use an annotated set of different-center data. We evaluate 1) a nonlinear feature normalization approach, and 2) two transfer-learning algorithms that use same and different-center data with different weights. Results showed that the best results were obtained for a combination of feature normalization and transfer learning. While for the other approaches significant differences in voxelwise or mean volume errors were found compared with the reference same-center training, the proposed approach did not yield significant differences from that reference. We conclude that both extensive feature normalization and transfer learning can be valuable for the development of supervised methods that perform well on different types of datasets.

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 χ2 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.

Seven-Tesla Magnetic Resonance Imaging of Atherosclerotic Plaque in the Significantly Stenosed Carotid Artery A Feasibility Study

ObjectivesThe objective of this study was to assess the feasibility of carotid vessel wall imaging at 7.0 for T magnetic resonance imaging (MRI) in a series of patients with a symptomatic greater than 70% stenosis of the internal carotid artery. Materials and MethodsFirst, a series of 6 healthy volunteers were scanned at 3.0 T and 7.0 T MRI to perform a signal-to-noise ratio comparison between these 2 field strengths. Second, in patients with a greater than 70% stenosed carotid artery, a 7.0 T MRI protocol, consisting of a dual-echo turbo spin echo sequence (echo times of 45 and 150 milliseconds) and a T1-weighted turbo spin echo sequence, was obtained. Lumen and vessel wall were delineated for interobserver and intraobserver reproducibility, and signal intensity distribution in the most severely stenosed part of the internal carotid artery was correlated with different plaque components on histopathologic findings. ResultsThe mean (SD) signal-to-noise ratio in the vessel wall was 42 (12) at 7.0 T and 24 (4) at 3.0 T. Nineteen patients were included, but technical issues yielded carotid MRI data of 14 patients available for the final analysis. Of these patients, 4 were diagnosed with stroke, 7 were diagnosed with a transient ischemic attack, and 3 were diagnosed with amaurosis fugax. Intraclass correlation coefficient of the agreements of lumen and vessel wall determination between 2 observers and between the repeated measures of 1 observer were above 0.80 in both 3.0 T and 7.0 T data sets of the healthy volunteers and also in the 7.0 T data set of the patients. Signal hyperintensity in the 7.0 T magnetic resonance images was inversely proportional to calcification. Other correlations between plaque components and signal intensity could not be confirmed. ConclusionsThis first series of patients with carotid atherosclerotic plaque who were scanned at 7.0 T MRI shows that 7.0 T MRI enables to adequately determine lumen and vessel wall areas. Signal hyperintensity in these 7.0 T magnetic resonance images was inversely proportional to calcification. However, at this stage, no other correlations between histologic findings and vessel wall contrast were found. Implementation of in vivo high-resolution 7.0 T MRI of plaque components for risk stratification remains challenging. Future development of hardware and software is still needed to attain a more robust setup and to enable complete plaque characterization, similar to what is currently possible with multiple MRI sequences at 1.5 T and 3.0 T MRI.

Visualization of Local Changes in Vessel Wall Morphology and Plaque Progression in Serial Carotid Artery Magnetic Resonance Imaging

Carotid atherosclerosis is an important cause of ischemic stroke. Assessment of plaque composition in addition to degree of luminal stenosis can be used to identify patients with increased risk of stroke and assess disease progression. Magnetic resonance imaging (MRI) is an excellent noninvasive imaging technique to assess vessel wall morphology and plaque composition, with good accuracy and reproducibility.1 Serial MRI of the carotid artery is used in several studies which focus on measuring the natural history of carotid artery plaques in symptomatic1 and asymptomatic2 patients and effects of lipid-lowering therapy using statins.3,4 The current standard to analyze serial MRI scans is to compare volume measurements based on manual segmentations of the vessel wall and plaque components. Before comparing the scans, the scans have to be aligned to each other on a slice level. Different approaches exist to align scans from different time points. One study aligns the scans by centering the image stack at each time point over the plaque,1 and another study uses the baseline scan as a reference at the follow-up session to ensure targeting the same arterial segment.4 Alternatively, postprocessing can be used to match the axial images from different time points according to their distance to the carotid bifurcation.2,3 Furthermore, comparison between time points is hindered by inconsistent repositioning of the artery from scan to scan in conjunction with thick image slices. Balu et al5 studied the influence of subject repositioning on measurement precision in serial MRI and identified orientation variability as the most important factor that affected reproducibility. Besides repositioning variability, the current comparison of time points is primarily based on volume measurements, which is a limited representation of the available image data, and no attention is given to local changes or visual …

Vessel Wall and Adventitial DCE-MRI Parameters Demonstrate Similar Correlations With Carotid Plaque Microvasculature on Histology

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.

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) Spearmans ρ > 0.93 (p < 0.001) and vp Spearmans 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.