Detection Of Intraplaque Hemorrhage Research Articles

Fast simultaneous noncontrast angiography and intraplaque hemorrhage (fSNAP) sequence for carotid artery imaging.

To propose a fast simultaneous noncontrast angiography and intraplaque hemorrhage (fSNAP) sequence for carotid artery imaging. The proposed fSNAP sequence uses a low-resolution reference acquisition for phase-sensitive reconstruction to speed up the scan, and an inversion recovery acquisition with arbitrary k-space filling order to generate similar contrast to conventional SNAP. Four healthy volunteers and eight patients were recruited to test the performance of fSNAP in vivo. The lumen area quantification, muscle-blood CNR, IPH-blood CNR, lumen SNR, and standard deviation and intraplaque hemorrhage (IPH) detection accuracy were compared between fSNAP and SNAP. By using a low-resolution reference acquisition with 1/4 matrix size of the full-resolution reference scan, the scan time of fSNAP was 37.5% less than that of SNAP. A high agreement of lumen area measurement (ICC = 0.97, 95% CI: 0.96-0.99) and IPH detection (Kappa = 1) were found between fSNAP and SNAP. Also, no significant difference was found for muscle-blood CNR (P = 0.25), IPH-blood CNR (P = 0.35), lumen SNR (P = 0.60), and standard deviation (P = 0.46) between the two techniques. The feasibility of fSNAP was validated. fSNAP can improve the imaging efficiency with similar performance to SNAP on carotid artery imaging. Magn Reson Med 77:753-758, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Abstract 25: Carotid Plaque Thickness, Stenosis, Ulceration, Age And Male Sex Optimally Predict Carotid Intraplaque Hemorrhage

Background and Purpose: MRI-detected intraplaque hemorrhage (IPH) is associated with acute and future stroke. IPH can be detected with a high sensitivity, specificity and accuracy using heavily T1-weighted sequences such as the magnetization-prepared rapid acquisition gradient echo (MPRAGE) sequence. This sequence is not always available in screening of potential carotid sources of stroke. The purpose of this study was to determine the discriminatory power of clinical and imaging markers in predicting carotid IPH. Methods: In this retrospective cross sectional study, patients undergoing stroke workup were imaged with magnetic resonance imaging (MRI) and IPH detection. A total of 726 carotid plaques were imaged. Carotid imaging characteristics were recorded, including percent diameter and mm stenosis, plaque thickness, ulceration, intraluminal thrombus and IPH. Clinical confounders were recorded and a multivariable logistic regression model was fitted. Backward-elimination was used to determine essential predictors of IPH with a threshold two-sided p<.10. Receiver operating characteristic (ROC) analysis was performed to determine discriminatory value. Results: Significant predictors of carotid IPH included plaque thickness (Odds ratio, OR=2.20, p<.001), mm stenosis (OR=0.46, p<.001), ulceration (OR=4.25, p=.020), age (OR=1.11, p=.001) and male sex (OR=3.23, p=.077). Percent diameter stenosis (OR=31.0, p=.001) could be used nearly interchangeably with mm stenosis. The final model discriminatory value was excellent (Area under the curve, AUC=0.932). This was significantly higher than models using only plaque thickness (AUC=0.881), only mm stenosis (AUC=0.830) or only ulceration (AUC=0.715) p<.001. Conclusions: Optimal discrimination of carotid IPH required information on plaque thickness, mm stenosis, ulceration, age and male sex. When these factors are recorded, IPH can be predicted with a high discriminatory power.

Detection of Intraplaque Hemorrhage in Mouse Atherosclerotic Lesions.

Intraplaque hemorrhage is defined as the presence of fresh or lysed erythrocytes, iron deposits in macrophages, and/or a fibrin clot in an atherosclerotic plaque. These features can be detected by hematoxylin and eosin, Martius scarlet Blue, and Perl's iron histological stainings. It is noteworthy that intraplaque hemorrhage is only present in murine atherosclerotic plaques after additional interventions or additional genetic traits affecting matrix degradation or thrombosis. In this chapter, we describe methods to detect intraplaque hemorrhage in mouse atherosclerotic lesions.

Intraluminal thrombus, intraplaque hemorrhage, plaque thickness, and current smoking optimally predict carotid stroke.

Intraplaque hemorrhage (IPH) is associated with acute and future stroke. IPH is also associated with lumen markers of stroke risk including stenosis, plaque thickness, and ulceration. Whether IPH adds further predictive value to these other variables is unknown. The purpose of this study was to determine whether IPH improves carotid-source stroke prediction. In this retrospective cross-sectional study, patients undergoing stroke workup were imaged with MRI and IPH detection. Seven hundred twenty-six carotid-brain image pairs were analyzed after excluding vessels with noncarotid plaque stroke sources (420) and occlusions (7) or near-occlusions (3). Carotid imaging characteristics were recorded, including percent diameter and mm stenosis, plaque thickness, ulceration, intraluminal thrombus, and IPH. Clinical confounders were recorded, and a multivariable logistic regression model was fitted. Backward elimination was used to determine essential carotid-source stroke predictors with a threshold 2-sided P<0.10. Receiver operating characteristic analysis was performed to determine discriminatory value. Significant predictors of carotid-source stroke included intraluminal thrombus (odds ratio=103.6; P<0.001), IPH (odds ratio=25.2; P<0.001), current smoking (odds ratio=2.78; P=0.004), and thickness (odds ratio=1.24; P=0.020). The final model discriminatory value was excellent (area under the curve=0.862). This was significantly higher than the final model without IPH (area under the curve=0.814), or models using only stenosis as a continuous variable (area under the curve=0.770) or cutoffs of 50% and 70% (area under the curve=0.669), P<0.001. After excluding patients with noncarotid plaque stroke sources, optimal discrimination of carotid-source stroke was obtained with intraluminal thrombus, IPH, plaque thickness, and smoking history but not ulceration and stenosis.

Imaging intracranial vessel wall pathology with magnetic resonance imaging: current prospects and future directions.

To date, the probable cause of ischemic stroke is often inferred from the size and location of the infarct, in combination with an evaluation of the heart and the presence of extracranial arterial occlusion or high-grade stenosis.1 Currently used conventional lumenography-based methods such as digital subtraction angiography, computed tomography angiography, and magnetic resonance (MR) angiography are used to determine the presence of such an acute occlusion or high-grade arterial stenosis. From extracranial studies, it is known that luminal narrowing may be absent in patients with severe atherosclerosis owing to arterial remodeling.2–4 Therefore, these methods do not provide information about the underlying pathological processes, which most often involve the vessel wall.5 Vessel wall changes such as vessel wall thickening, enhancement, or the presence of vulnerable atherosclerotic plaques without luminal stenosis are therefore often missed but might be of importance for a better understanding of ischemic stroke.6 Furthermore, intracranial atherosclerosis is an important cause of ischemic stroke7 and often involves the vessel wall. Patients with intracranial atherosclerosis have high recurrent stroke rates,8 and increasingly more attention is being directed to the assessment of the intracranial vessel wall, necessitating an imaging technique directly assessing the intracranial vessel wall. MR imaging (MRI) seems the most promising technique to reliably image intracranial vessel wall pathologies because of its superior soft tissue contrast. Recent advances in MRI9 have made it possible to obtain information about these abnormalities within the intracranial vessel wall, which provides an imaging tool to investigate the role of intracranial vessel wall abnormalities in the diagnosis of stroke. In this review, we discuss the current status of intracranial vessel wall MRI and its potential to identify different intracranial vessel wall pathologies. First, we present the state-of-the-art MRI methods to visualize the intracranial vessel wall …

Sustained Acceleration in Carotid Atherosclerotic Plaque Progression With Intraplaque Hemorrhage: A Long-Term Time Course Study

This study sought to determine the immediate and long-term effects of intraplaque hemorrhage (IPH) on plaque progression in the carotid artery. Previous studies have associated IPH in the carotid artery with more rapid plaque progression. However, the time course and long-term effect remain unknown. Carotid magnetic resonance imaging is a noninvasive imaging technique that has been validated with histology for the accurate in vivo detection of IPH and measurement of plaque burden. Asymptomatic subjects with 50% to 79% carotid stenosis underwent carotid magnetic resonance imaging at baseline and then serially every 18 months for a total of 54 months. Subjects with IPH present in at least 1 carotid artery at 54 months were selected. Subsequently, presence/absence of IPH and wall volume were determined independently in all time points for both sides. A piece-wise progression curve was fit by using a linear mixed model to compare progression rates described as annualized changes in wall volume between periods defined by their relationship to IPH development. From 14 subjects who exhibited IPH at 54 months, 12 arteries were found to have developed IPH during the study period. The progression rates were -20.5 ± 13.1, 20.5 ± 13.6, and 16.5 ± 10.8 mm(3)/year before, during, and after IPH development, respectively. The progression rate during IPH development tended to be higher than the period before (p = 0.080) but comparable to the period after (p = 0.845). The progression rate in the combined period during/after IPH development was 18.3 ± 6.5 mm(3)/year, which indicated significant progression (p = 0.008 compared with a slope of 0) and was higher than the period before IPH development (p = 0.018). No coincident ischemic events were noted for new IPH. The development of IPH posed an immediate and long-term promoting effect on plaque progression. IPH seems to alter the biology and natural history of carotid atherosclerosis. Early identification of patients with IPH may prove invaluable in optimizing management to minimize future sequelae.

Evaluation of multicontrast MRI including fat suppression and inversion recovery spin echo for identification of intra-plaque hemorrhage and lipid core in human carotid plaque using the mahalanobis distance measure

Intra-plaque hemorrhage (IPH) and lipid core, characteristics of rupture prone carotid plaques, are often visualized in vivo with MRI using T1 weighted gradient and spin echo, respectively. Increasing magnetic field strength may help to identify IPH and lipid core better. As a proof of concept, automatic segmentation of plaque components was performed with the Mahalanobis distance (MD) measure derived from image contrast from multicontrast MR images including inversion recovery spin echo and T1 weighted gradient echo with fat suppression. After MRI of nine formaldehyde-fixated autopsy specimens, the MDs and Euclidean Distances between plaque component intensities were calculated for each MR weighting. The distances from the carotid bifurcation and the size and shape of calcification spots were used as landmarks for coregistration of MRI and histology. MD between collagen/cell-rich area and IPH was largest with inversion recovery spin echo (4.2/9.3, respectively), between collagen/cell-rich area/foam cells and lipid core with T1 weighted gradient echo with fat suppression (26.9/38.2/4.6, respectively). The accuracy of detection of IPH, cell-rich area, and collagen increased when the MD classifier was used compared with the Euclidean Distance classifier. The enhanced conspicuity of lipid core and IPH in human carotid artery plaque, using ex vivo T1 weighted gradient echo with fat suppression and inversion recovery spin echo MRI and MD classifiers, demands further in vivo evaluation in patients.

Carotid Intraplaque Hemorrhage Imaging at 3.0-T MR Imaging: Comparison of the Diagnostic Performance of Three T1-weighted Sequences

To compare the diagnostic performances of three T1-weighted 3.0-T magnetic resonance (MR) sequences at carotid intraplaque hemorrhage (IPH) imaging, with histo logic analysis as the reference standard. Institutional review board approval and informed consent were obtained for this HIPAA-compliant study. Twenty patients scheduled for carotid endarterectomy underwent 3.0-T carotid MR imaging, including two-dimensional fast spin-echo, three-dimensional time-of-flight (TOF), and three-dimensional magnetization-prepared rapid acquisition gradient-echo (RAGE) sequences. Two reviewers blinded to the histologic findings assessed the presence, area, and signal intensity of IPH with each sequence. Detection statistics (sensitivity, specificity, and Cohen kappa values) and agreement between area measurements (Pearson correlation coefficient [r] values) were calculated for each sequence. When all 231 available MR sections were included for analysis, the magnetization-prepared RAGE (kappa = 0.53) and fast spin-echo (kappa = 0.42) sequences yielded moderate agreement between MR and histologic measurements, while the TOF sequence yielded fair agreement (k = 0.33). However, when 47 sections with either small IPHs or heavily calcified IPHs were excluded, sensitivity, specificity, and kappa values, respectively, were 80%, 97%, and 0.80 for magnetization-prepared RAGE imaging; 70%, 92%, and 0.63 for fast spin-echo imaging; and 56%, 96%, and 0.57 for TOF imaging. MR imaging-histologic analysis correlation for IPH area was highest with magnetization-prepared RAGE imaging (r = 0.813), followed by TOF (r = 0.745) and fast spin-echo (r = 0.497) imaging. The capability of these three sequences for IPH detection appeared to be in good agreement with the quantitative contrast of IPH versus background plaque tissue. The magnetization-prepared RAGE sequence, as compared with the fast spin-echo and TOF sequences, demonstrated higher diagnostic capability for the detection and quantification of IPH. Potential limitations of 3.0-T IPH MR imaging are related to hemorrhage size and coexisting calcification.

Development of Carotid Intraplaque Hemorrhage Demonstrated by Serial Magnetic Resonance Imaging

68-year-old man presented with a sudden onset of weakness and paresthesia of the left arm. He had a history of myocardial infarction 4 years earlier and a known renal artery stenosis. A nonenhanced computed tomographic scan of the brain showed no signs of hemorrhage or infarction. The patient underwent intravenous thrombolysis with alteplase (0.9 mg/kg body wt, 10% initial bolus dose over 1 minute, followed by infusion of the remaining 90% of the dose over 60 minutes). Soon after, the symptoms completely disappeared except for the persistence of a slight paresthesia of the left arm. Doppler ultrasonography revealed a hypoechoic plaque proximally in the right internal carotid artery causing a 50% to 69% stenosis. ECG showed sinus rhythm with complete right bundle-branch block without ST-segment or T-wave abnormalities. Transcranial Doppler imaging revealed no stenosis of the right middle cerebral artery. Serum lipid profile was within normal limits. In addition to the aspirin (100 mg once per day) and atorvastatin (40 mg once per day) he was already using, the patient was prescribed dipyridamole (200 mg twice per day) for secondary stroke prevention. Fifteen days after the initial onset of symptoms, the patient was enrolled in a clinical study investigating the natural history of carotid artery plaques. Magnetic resonance imaging scans of the brain and right carotid artery plaque were obtained, which revealed a recent discrete infarction of the right sensory region (Figure 1A and 1B) and a plaque with a large lipid-rich necrotic core with no or little hemorrhage (Figure 2A through 2D), respectively. Three months after the initial event, the patient once more presented with sudden onset of weakness and a numb feeling of the left arm. The patient again underwent intravenous thrombolysis with alteplase. However, the symptoms persisted. A nonenhanced computed tomographic scan, performed 24 hours after thrombolysis, revealed a hypodense area in the right motor region. Repeated Doppler ultrasonography showed no change in carotid plaque echogenicity and degree of luminal narrowing of the right internal carotid artery. Ten days after the onset of the second event, the patient underwent repeated magnetic resonance imaging scans of the brain and right internal carotid artery plaque. These scans confirmed recent infarction in the right motor region (Figure 1C and 1D) and revealed recent intraplaque hemorrhage (Figure 2E through 2H). Because of recurrent symptoms, the patient underwent carotid endarterectomy 20 days after the onset of the second event. Histological analysis of the excised plaque demonstrated large intraplaque hemorrhage (Figure 3A and 3B), confirming the magnetic resonance imaging findings. According to the American Heart Association, it was a type VI plaque (complex plaque with possible surface defect, hemorrhage, or thrombus). 1

Detection of intraplaque hemorrhage by magnetic resonance imaging in symptomatic patients with mild to moderate carotid stenosis predicts recurrent neurological events

Carotid endarterectomy is beneficial in severe (>70%) symptomatic carotid stenosis. The risk of stroke in moderate carotid stenosis (50%-69%) is modest, and so the role of carotid endarterectomy in this group is unclear. Intraplaque hemorrhage is associated with advanced atherosclerosis and can be detected in the carotid arteries by magnetic resonance imaging. This study evaluates whether magnetic resonance imaging detected intraplaque hemorrhage (MR IPH) can identify patients with symptomatic mild to moderate carotid stenosis who are at higher risk of ipsilateral transient ischemic attack (TIA) and stroke. Prospective longitudinal cohort study of symptomatic patients with mild to moderate (30%-69%) carotid stenosis followed up for 2 years after imaging for IPH using magnetic resonance imaging. Sixty four participants were followed up for a median of 28 months (interquartile range 26-30) after MRI of the carotid arteries. Thirty-nine (61%) ipsilateral arteries showed intraplaque hemorrhage. During follow-up, five ipsilateral strokes and a total of 14 ipsilateral ischemic events were observed. Thirteen of these ischemic events, of which five were strokes, occurred in those with ipsilateral carotid intraplaque hemorrhage (hazard ratio = 9.8, 95% confidence interval 1.3-75.1, P = .03). MR IPH is a good predictor of ipsilateral stroke and TIA in patients with symptomatic mild to moderate (30%-69%) carotid stenosis. This technique could help in the selection of patients for carotid endarterectomy.

Response to Letters by Hsieh and Chen, and by Tang et al

Response: We appreciate Hsieh and Chen’s interest in our study. We agree that understanding the pathomechansim of the development of intraplaque hemorrhage (IPH) is of key importance that may help to develop therapeutic strategies to arrest or reverse the processes of atherosclerosis. Although no direct causal relationship between IPH and embolic stroke has been established, a number of studies have highlighted IPH as a marker of plaque rupture.1–3 The noninvasive detection of MR IPH will prove very useful for future in vivo pathophysiological studies. We also thank Tang and colleagues for their interest in our work and the opportunity to clarify their misunderstanding. It was our study aim to evaluate the clinical relevance of a previously described and histologically validated MRI surrogate marker of the unstable plaque.4 From a clinical practice perspective it is desirable to identify patients at high or low …