Carotid Intraplaque Hemorrhage Research Articles

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

BackgroundThe 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. MethodsTIA 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 MRI after 2 years (n=69). Trained observers delineated IPH, a hyperintense region compared to surrounding muscle tissue on hyper T1-weighted MR 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. ResultsDuring 5.1 (interquartile range (IQR): 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 (HR: 0.89 [95% CI: 0.67-1.10] and HR: 0.91 [0.69-1.19] per 100µl increase, respectively) nor with the imaging-based endpoint (OR: 1.04 [0.75-1.45] and OR: 1.21 [0.87-1.68] per 100µl increase, respectively). ConclusionsIPH SIR and IPH volume were not associated with future ipsilateral ischemic cerebrovascular events. Therefore, quantitative assessment of IPH does not seem to provide additional value beyond the presence of IPH for stroke risk assessment.Trial registrationThe PARISK study was registered on ClinicalTrials.gov with ID NCT01208025 on 21 September 2010 (https://clinicaltrials.gov/study/NCT01208025).

Abstract 19141: Carotid Artery Plaque Rim Sign on Computed Tomography Angiography is Associated With Intraplaque Hemorrhage and Inflammatory Microenvironment

Introduction: The carotid artery rim sign on CTA is characterized by soft-plaque components surrounded by a rind of thin, adventitial calcification and its role in plaque instability is not established yet. Intraplaque hemorrhage (IPH) and the inflammatory microenvironment in carotid atheroma are considered features of atherosclerotic plaque vulnerability leading to cerebrovascular events. Hypothesis: The association between rim sign on CTA and carotid IPH and inflammation remains scantly investigated. In this study, we aimed to determine whether rim sign is associated with IPH on MRA and with the extent of IPH and inflammation on histology. We hypothesized that rim sign may be a radiological predictor of carotid IPH and inflammation. Methods: We retrospectively enrolled 100 consecutive patients who underwent carotid endarterectomy (CEA) and neck CTA before CEA. On CTA, the ipsilateral rim sign was defined as the presence of adventitial calcifications with internal soft-tissue plaque of ≥2 mm in maximum thickness. Of the included patients, 25 had MRA with 3D magnetization-prepared rapid acquisition with gradient echo (MPRAGE) sequence. Carotid plaque specimens were collected and stained with H&E to quantify IPH (%). Histologically, we defined IPH as an area of carotid plaque with blood elements, and inflammatory microenvironment as the presence of lymphocytes and plasma cells (chronic inflammation) and foam cells. Results: The rim sign on CTA was present in 56 (56%) of patients. IPH on MRA was present in 11 (44%) patients. The rim sign was significantly associated with the presence of IPH on MRA [9 (81.8%) vs 2 (14.3%); p=0.003]. On histology, the rim sign was associated with a higher extent of IPH [5.0 % (IQR 2.0-25.0) vs 5.0% (IQR 0.0-10.0); p=0.017], with chronic inflammation [44 (78.6%) vs 12 (21.4%); p=0.003], and foam cells [51 (91.1%) vs 5 (8.9%); p<0.001]. Conclusions: These findings suggest that rim sign on CTA may be proposed as a potential imaging marker of IPH as well as a histologic predictor of IPH extent and carotid plaque inflammatory microenvironment.

Application of mask images of contrast-enhanced MR angiography to detect carotid intraplaque hemorrhage in patients with moderate to severe symptomatic and asymptomatic carotid stenosis

PurposeCarotid intraplaque hemorrhage (IPH) on MRI predicts stroke. Magnetization-prepared rapid acquisition gradient (MP-RAGE) is widely used to detect IPH. CE-MRA is used routinely to assess stenosis. Initial studies indicated that IPH can be identified on mask images of CE-MRA, while Time-of-Flight (TOF) images were reported to have high specificity but lower sensitivity. We investigated the diagnostic accuracy of detecting IPH on mask images of CE-MRA and TOF. MethodsThirty-six patients with ≥ 50% stenosis enrolled in the ongoing 2nd European Carotid Surgery Trial underwent carotid MRI. A 5-point quality score was used. Inter-observer agreement between two independent readers was determined. The sensitivity and specificity of IPH detection on mask MRA and TOF were calculated with MP-RAGE as a reference standard. ResultsOf the 36 patients included in the current analysis, 66/72 carotid arteries could be scored. The inter-observer agreements for identifying IPH on MP-RAGE, mask, and TOF were outstanding (κ: 0.93, 0.96, and 0.85). The image quality of mask (1.42 ± 0.66) and TOF (2.42 ± 0.66) was significantly lower than MP-RAGE (3.47 ± 0.61). When T1w images were used to delineate the outer carotid wall, very high specificities (>95%) of IPH detection on mask and TOF images were found, while the sensitivity was high for mask images (>81%) and poor for TOF (50–60%). Without these images, the specificity was still high (>97%), while the sensitivity reduced to 62–71%. ConclusionDespite the lower image quality, routinely acquired mask images from CE-MRA, but not TOF, can be used as an alternative to MP-RAGE images to visualize IPH.

Radiomics assessment of carotid intraplaque hemorrhage: detecting the vulnerable patients

BackgroundIntraplaque hemorrhage (IPH), one of the key features of vulnerable plaques, has been shown to be associated with increased risk of stroke. The aim is to develop and validate a CT-based radiomics nomogram incorporating clinical factors and radiomics signature for the detection of IPH in carotid arteries.MethodsThis retrospective study analyzed the patients with carotid plaques on CTA from January 2013 to January 2021 at two different institutions. Radiomics features were extracted from CTA images. Demographics and CT characteristics were evaluated to build a clinical factor model. A radiomics signature was constructed by the least absolute shrinkage and selection operator method. A radiomics nomogram combining the radiomics signature and independent clinical factors was constructed. The area under curves of three models were calculated by receiver operating characteristic analysis.ResultsA total of 46 patients (mean age, 60.7 years ± 10.4 [standard deviation]; 36 men) with 106 carotid plaques were in the training set, and 18 patients (mean age, 61.4 years ± 10.1; 13 men) with 38 carotid plaques were in the external test sets. Stenosis was the independent clinical factor. Eight features were used to build the radiomics signature. The area under the curve (AUC) of the radiomics nomogram was significantly higher than that of the clinical factor model in both the training (p = 0.032) and external test (p = 0.039) sets.ConclusionsA CT-based radiomics nomogram showed satisfactory performance in distinguishing carotid plaques with and without intraplaque hemorrhage.

MRI Detection of Carotid Intraplaque Hemorrhage and Postintervention Cognition.

Cognitive improvement has been reported after carotid revascularization and attributed to treating stenosis and correcting hypoperfusion. This study investigated the effect of carotid intraplaque hemorrhage on postintervention cognition. In this institutional review board-approved single-center study, consecutive patients scheduled for carotid surgery were recruited for preoperative carotid MR imaging (MPRAGE) and pre- and postintervention cognitive testing using the Repeatable Battery for the Assessment of Neuropsychological Status. Pre- and postintervention scores were compared using t tests and multivariable linear regression. Twenty-three participants were included, with endarterectomy performed in 20 (87%) and angioplasty/stent placement, in 3 (13%). Overall, statistically significant improvements occurred in the pre- versus postintervention mean Total Scale score (92.1 [SD, 15.5] versus 96.1 [SD, 15.8], P = .04), immediate memory index (89.4 [SD, 18.2] versus 97.7 [SD, 14.9], P < .001), and verbal index (96.1 [SD, 14.1] versus 103.0 [SD, 12.0], P = .002). Intraplaque hemorrhage (+) participants (n = 11) had no significant improvement in any category, and the attention index significantly decreased (99.4 [SD, 18.0] versus 93.5 [SD, 19.4], P = .045). Intraplaque hemorrhage (-) participants (n = 12) significantly improved in the Total Scale score (86.4 [SD, 11.8] versus 95.5 [SD, 12.4], P = .004), immediate memory index (82.3 [SD, 14.6] versus 96.2 [SD, 14.1], P = .002), delayed memory index (94.3 [SD, 14.9] versus 102.4 [SD, 8.0], P = .03), and verbal index (94.3 [SD, 13.2] versus 101.5 [SD, 107.4], P = .009). Postintervention minus preintervention scores for intraplaque hemorrhage (+) versus (-) groups showed statistically significant differences in the Total Scale score (-0.4 [SD, 6.8] versus 8.0 [SD, 8.5], P = .02), attention index (-5.9 [SD, 8.5] versus 4.3 [SD, 11.9], P = .03), and immediate memory index (4.2 [SD, 6.7] versus 12.2 [SD, 10.2], P = .04). Cognitive improvement was observed after carotid intervention, and this was attributable to intraplaque hemorrhage (-) plaque. MR imaging detection of intraplaque hemorrhage status may be an important determinant of cognitive change after intervention.

Prevalence of Symptomatic Nonstenotic Carotid Disease Using Simultaneous Non-Contrast Angiography and Intraplaque Hemorrhage Imaging for MR Screen Protocol.

Background: To determine the prevalence of symptomatic nonstenotic carotid disease (SyNC) using simultaneous non-contrast angiography and intraplaque hemorrhage (SNAP) imaging for patients with acute stroke as an MR screen protocol and to assess imaging findings of carotid plaques. Patients and Methods: From May 2020 to October 2021, 2459 patients with suspected acute neurological symptoms were evaluated with brain diffusion-weighted imaging (DWI) and carotid SNAP imaging. We analyzed the degree of stenosis and intraplaque hemorrhage (IPH) using SNAP imaging. Prevalence of SyNC and risk factors for stroke in patients with SyNC were determined. We performed subgroup multivariate analysis between SyNC and other etiologies of stroke (non-SyNC). Results: Of 4608 carotid arteries in 2304 patients enrolled in this study, 454 (9.9%) plaques (both lesions in 128 patients) were found on SNAP imaging. Of these plaques, 353 (77.8%) showed stenosis of <50%. Of plaques with <50% stenosis, 47 (13.3%) patients had a territorial acute focal infarction. Seventeen (36.2%) were classified with embolic stroke of undetermined source (ESUS) and SyNC. High maximal wall thickness and carotid IPH were identified as influencing factors for SyNC. Conclusion: For patients with <50% stenosis and territorial infarction, SyNC is a relatively important source of stroke. Especially, high maximal wall thickness and carotid IPH are important risk factors for SyNC.

Slice-based and time-specific hemodynamic measurements discriminate carotid artery vulnerable atherosclerotic plaques

Background and objectiveHemodynamic patterns play key roles in progression of carotid vulnerable plaques. However, most of previous studies utilized maximum or averaged value of hemodynamic measurements which is not an ideal representative of hemodynamic patterns. This study aimed to investigate the association of slice-based and time-specific hemodynamic measurements with carotid vulnerable plaque using magnetic resonance (MR) vessel wall imaging and histology. MethodsThirty-two patients (mean age: 63.9±8.1 years; 25 males) with carotid atherosclerotic stenosis (≥50% stenosis) referred to carotid endarterectomy were recruited and underwent MR vessel wall imaging. Carotid plaque burden was evaluated on MR images and vulnerable plaque features including calcification, lipid-rich necrotic core, and intra-plaque hemorrhage (IPH) were identified by histology. The slice-based and time-specific hemodynamic measurements were extracted from computational fluid dynamics simulation of 3D carotid arterial model. Correlation coefficients between hemodynamic measurements and carotid plaque features were calculated and the logistic regressions with generalized estimating equation (GEE) were conducted. The value in discriminating carotid vulnerable plaque features was determined by receiver-operating-characteristic analysis. ResultsOf 102 MR-histology matched slices from 32 patients, time-averaged wall shear stress (TAWSS) (r=0.263, p=0.008), oscillatory shear index (OSI) (r=-0.374, p<0.001), and peakWSS (r=0.232, p=0.019) were significantly associated with carotid IPH. The logistic regression with GEE revealed that peakWSS (OR, 1.206; 95% CI, 1.026-1.418; p, 0.023) and TAWSS (OR, 0.364, 95% CI, 0.138-0.959; p, 0.041) were significantly associated with presence of IPH after adjusting for age and BMI. In discriminating carotid IPH, the AUC of TAWSS, OSI, combined TAWSS with maximum wall thickness (MWT) and combined OSI with MWT was 0.656, 0.722, 0.761, and 0.764, respectively. ConclusionsSlice-based and time-specific hemodynamic characteristics could effectively discriminate carotid IPH. Combination of hemodynamic measurements with carotid plaque burden might be a stronger indicator for carotid vulnerable plaque features than each measurement alone.

Associations Between Carotid Plaque Characteristics and Perioperative Cerebral Blood Flow Determined by Arterial Spin Labeling Imaging in Patients With Moderate-to-Severe Stenosis Undergoing Carotid Endarterectomy.

PurposeTo examine the associations between carotid plaque characteristics and perioperative cerebral blood flow (CBF) by arterial spin labeling (ASL) imaging.Materials and MethodsPatients with unilateral moderate-to-severe carotid stenosis referred for carotid endarterectomy (CEA) were recruited and underwent carotid vessel wall and brain ASL magnetic resonance imaging. The following imaging features were measured: relative CBF (rCBF = CBFindex−hemisphere/CBFcontralateral−hemisphere) in the middle cerebral artery territory; plaque burden and the presence of lipid-rich necrotic core; intraplaque hemorrhage (IPH); calcification; ulcer and fibrous-cap rupture; and the volume and maximum plaque components' area percentages. The associations between plaque characteristics and perioperative CBF were analyzed.ResultsSixty-one patients (mean age, 66.6 ± 7.8 years; 55 males) were included. Univariate linear regression showed that rCBFpre−CEA was associated with stenosis [β, −0.462; 95% confidence interval (CI), from −0.797 to −0.126; p = 0.008], calcification (β, 0.103; 95% CI, 0.005–0.201; p = 0.040), maximum IPH area percentage (β, −0.127; 95% CI, from −0.223 to −0.030; p = 0.012), and ulcer (β, 0.069; 95% CI, 0.025–0.113; p = 0.005); rCBFpost−CEA was associated with the IPH volume (β, −0.060; 95% CI, from −0.107 to −0.014; p = 0.013). After adjusting for the confounding factors, the associations of calcification with rCBFpre−CEA (β, 0.099; 95% CI, from 0.004 to −0.194; p = 0.042) and IPH volume with rCBFpost−CEA (β, −0.060; 95% CI, from −0.109 to −0.011; p = 0.020) remained statistically significant, while those of rCBFpre−CEA with maximum IPH area percentage (β, −0.089; 95% CI, from −0.188 to 0.011; p = 0.080) and ulcer (β, 0.050; 95% CI, from −0.012 to 0.112; p = 0.100) did not remain statistically significant.ConclusionThe compositional characteristics of carotid atherosclerotic plaques, particularly IPH, were associated with perioperative CBF in patients with unilateral moderate-to-severe carotid stenosis undergoing CEA. Our findings indicated that the patients with larger carotid IPH could expect smaller improvement in CBF following CEA.

Differential Gene Expression and Immune Cell Infiltration in Carotid Intraplaque Hemorrhage Identified Using Integrated Bioinformatics Analysis.

BackgroundIntraplaque hemorrhage (IPH) is an important feature of unstable plaques and an independent risk factor for cardiovascular events. However, the molecular mechanisms contributing to IPH are incompletely characterized. We aimed to identify novel biomarkers and interventional targets for IPH and to characterize the role of immune cells in IPH pathogenesis.MethodsThe microarray dataset GSE163154 which contain IPH and non-IPH plaque samples was obtained from the Gene Expression Omnibus (GEO). R software was adopted for identifying differentially expressed genes (DEGs) and conducting functional investigation. The hub genes were carried by protein-protein interaction (PPI) network and were validated by the GSE120521 dataset. CIBERSORT deconvolution was used to determine differential immune cell infiltration and the relationship of immune cells and hub genes. We confirmed expression of proteins encoded by the hub genes by immunohistochemistry and western blotting in 8 human carotid endarterectomy samples with IPH and 8 samples without IPH (non-IPH).ResultsWe detected a total of 438 differentially expressed genes (DEGs), of which 248 were upregulated and 190 were downregulated. DEGs were mainly involved in inflammatory related pathways, including neutrophil activation, neutrophil degranulation, neutrophil-mediated immunity, leukocyte chemotaxis, and lysosomes. The hub genes found through the method of degree in the PPI network showed that ITGB2 and ITGAM might play an important role in IPH. Receiver operating characteristic (ROC) results also showed a good performance of these two genes in the test and validation dataset. We found that the proportions of infiltrating immune cells in IPH and non-IPH samples differed, especially in terms of M0 and M2 macrophages. Immunohistochemistry and western blotting analysis showed that expression levels of ITGB2 and ITGAM increased significantly in carotid atherosclerotic plaques with IPH.ConclusionITGB2 and ITGAM are key hub genes of IPH and may play an important role in the biological process of IPH. Our findings advance our understanding of the underlying mechanisms of IPH pathogenesis and provide valuable information and directions for future research into novel targets for IPH diagnosis and immunotherapy.

Change of Heart: The Underexplored Role of Plaque Hemorrhage in the Evaluation of Stroke of Undetermined Etiology.

In the evaluation of embolic strokes of undetermined source, great emphasis is often placed on cardiovascular disease, namely on atrial fibrillation. Other pathophysiologic mechanisms, however, may also be involved. Carotid artery intraplaque hemorrhage (IPH)—the presence of blood components within an atheromatous plaque—has become increasingly recognized as a possible etiologic mechanism in some cryptogenic strokes. IPH is a marker of plaque instability and is associated with ipsilateral neurologic ischemic events, even in nonstenotic carotid plaques. As recognition of carotid IPH as an etiology of embolic strokes has grown, so too has the complexity with which such patients are evaluated and treated, particularly because overlaps exist in the risk factors for atrial fibrillation and IPH. In this article, we review what is currently known about carotid IPH and how this clinical entity should be approached in the context of the evaluation of embolic strokes of undetermined source.

Cerebral Small Vessel Disease Burden Related to Carotid Intraplaque Hemorrhage Serves as an Imaging Marker for Clinical Symptoms in Carotid Stenosis.

Objectives: In patients with carotid stenosis, to investigate the relationship between carotid intraplaque hemorrhage (IPH) and total burden of cerebral small vessel disease (CSVD) and preliminarily explore whether the total CSVD burden as an imaging marker can distinguish the severity of clinical symptoms.Methods: A total of 108 patients (the mean age was 66 ± 7 years, and 85.2% were male) with unilateral carotid stenosis ≥50% underwent brain MRI and high-resolution MRI for carotid plaque characterization. The total burden of CSVD was calculated by accumulating one point according to the presence or severity of each of the four MRI markers: white matter hyperintensities, lacunes, perivascular spaces, and cerebral microbleeds. Recent clinical symptoms including transient ischemic attack, amaurosis fugax, and ischemic stroke were recorded. The association between intraplaque hemorrhage (IPH) and total CSVD burden was examined adjusted for other risk factors. The symmetry of CSVD burdens between the ipsilateral and contralateral hemispheres of IPH was tested. Imaging features (CSVD score, IPH, degree of stenosis, and completeness of the circle of Willis) were correlated with clinical symptoms by Kruskal–Wallis H test, Chi-square test, and Fisher's exact test.Results: Multivariable logistic regression analysis showed that IPH (OR = 2.98, 95% CI [1.39, 6.40], p = 0.005) was independently associated with a higher CSVD score. The presence of unilateral IPH was associated with the inter-hemispheric CSVD score difference (p = 0.004). Patients with stroke had a higher ipsilateral CSVD score than asymptomatic patients (p = 0.004) and those with transient ischemic attack/amaurosis fugax (p = 0.008). The statistical difference was marginally significant between symptoms and IPH (p = 0.057). No statistical difference was found between the symptoms and degree of stenosis and the completeness of the circle of Willis (p > 0.05).Conclusions: Carotid IPH is associated with an elevated total burden of CSVD in patients with carotid stenosis. Compared with the degree of stenosis, primary collaterals, and IPH, the total CSVD score might be a more effective imaging marker linked with clinical symptoms.

Association Between Carotid Artery Perivascular Fat Density and Intraplaque Hemorrhage.

Objectives: Perivascular adipose tissue plays a key role in atherosclerosis, but its effects on the composition of carotid atherosclerotic plaques are unknown. This study aimed to investigate the association between inflammatory carotid artery and intraplaque hemorrhage (IPH) in the carotid artery.Methods: This is a single-center retrospective study. Carotid inflammation was assessed by perivascular fat density (PFD) in 72 participants (mean age, 65.1 years; 56 men) who underwent both computed tomography angiography (CTA) and magnetic resonance imaging (MRI) within 2 weeks. The presence of IPH was assessed with MRI. Carotid stenosis, maximum plaque thickness, calcification, and ulceration were evaluated through CTA. The association between PFD and the occurrence of IPH was studied using generalized estimating equations analysis.Results: Of 156 plaques, 72 plaques (46.2%) had IPH. Plaques with IPH showed higher PFD than those without [−41.4 ± 3.9 vs. −55.8 ± 6.5 Hounsfield unit (HU); p < 0.001]. After age, calcification, degree of stenosis, maximum plaque thickness, and ulceration were adjusted for, PFD (OR, 1.96; 95% CI, 1.41–2.73; p < 0.001) was found to be strongly associated with the presence of IPH.Conclusions: A higher PFD is associated with the presence of IPH in the carotid artery. These findings may provide a novel marker to identify carotid IPH and risk stratification.

Evaluation of Plaque Vulnerability via Combination of Hemodynamic Analysis and Simultaneous Non-Contrast Angiography and Intraplaque Hemorrhage (SNAP) Sequence for Carotid Intraplaque Hemorrhage.

The purpose of this study was to assess the vulnerability of plaque using a combination of simultaneous non-contrast angiography, intraplaque hemorrhage (SNAP) sequence, and local hemodynamic analysis in an intraplaque hemorrhage (IPH), and to evaluate the association between morphological and hemodynamic factors and IPH by comparing the IPH (presence of IPH) and non-IPH (plaque with absence of IPH) groups. In total, 27 IPH patients and 27 non-IPH patients were involved in this study, and baseline characteristics were collected. For morphological factors, diameters, and areas of the internal carotid artery (ICA), external carotid artery, and common carotid artery were measured, and bifurcation angle (α) and ICA angle (β) were also measured for comparison between the IPH group and non-IPH group. For hemodynamic factors, time-averaged wall shear stress (WSS), minimum WSS, maximum WSS, and oscillatory shear index were calculated using computational fluid dynamics (CFD) simulations. For the qualitative analysis, cross-sectional images with analyzed WSS and SNAP sequences were combined to precisely assess local hemodynamics. Bifurcation angle (α) was significantly different between the IPH and non-IPH groups (39.47 degrees vs. 47.60 degrees, p = 0.041). Significantly higher time-averaged WSS, minimum WSS, and maximum WSS were observed in the IPH group compared to the non-IPH group. In the IPH group, when using the combined analysis with SNAP sequences and WSS, the WSS of the region with IPH was significantly higher than the region without IPH (2.32 vs. 1.21 Pa, p = 0.005). A smaller bifurcation angle (α) and higher time-averaged WSS, minimum WSS, and maximum WSS were associated with IPH. The combined analysis of SNAP sequences and WSS might help to evaluate the risk of carotid IPH.

Differentiation of symptomatic and asymptomatic carotid intraplaque hemorrhage using 3D high-resolution diffusion-weighted stack of stars imaging.

Ischemic events related to carotid disease are far more strongly associated with plaque instability than stenosis. 3D high-resolution diffusion-weighted (DW) imaging can provide quantitative diffusion measurements on carotid atherosclerosis and may improve detection of vulnerable intraplaque hemorrhage (IPH). The 3D DW-stack of stars (SOS) sequence was implemented with 3D SOS acquisition combined with DW preparation. After simulation of signals created from 3D DW-SOS, phantom studies were performed. Three healthy subjects and 20 patients with carotid disease were recruited. Apparent diffusion coefficient (ADC) values were statistically analyzed on three subgroups by using a two-group comparison Wilcoxon-Mann-Whitney U test with p values less than 0.05: symptomatic versus asymptomatic; IPH-positive versus IPH-negative; and IPH-positive symptomatic versus asymptomatic plaques to determine the relationship with plaque vulnerability. ADC values calculated by 3D DW-SOS provided values similar to those calculated from other techniques. Mean ADC of symptomatic plaque was significantly lower than asymptomatic plaque (0.68 ±0.18 vs. 0.98 ±0.16 x 10-3 mm2 /s, p<0.001). ADC was also significantly lower in IPH-positive versus IPH-negative plaque (0.68 ±0.13 vs. 1.04 ±0.11 x 10-3 mm2 /s, p<0.001). Additionally, ADC was significantly lower in symptomatic versus asymptomatic IPH-positive plaque (0.57 ±0.09 vs. 0.75 ±0.11 x 10-3 mm2 /s, p<0.001). Our results provide strong evidence that ADC measurements from 3D DW-SOS correlate with the symptomatic status of extracranial internal carotid artery plaque. Further, ADC improved discrimination of symptomatic plaque in IPH. These data suggest that diffusion characteristics may improve detection of destabilized plaque leading to elevated stroke risk.

Normalized intraplaque hemorrhage signal on MP-RAGE as a marker for acute ischemic neurological events.

This study sought to validate whether the signal intensity ratio (SIR) of carotid intraplaque hemorrhage (IPH) was associated with acute ischemic neurologic events. A retrospective review was completed of consecutive patients that underwent neck magnetic resonance angiography using magnetization prepared-rapid gradient echo (MP-RAGE) and T1-CUBE sequences between 2017 and 2020. Patients with magnetic resonance evidence of IPH were included. SIRs were measured by comparing the maximum IPH signal with the mean intramuscular signal from the adjacent sternocleidomastoid. Patients were stratified into ischemic or non-ischemic groups based on the presence of acute ipsilateral ischemic events (stroke, retinal artery occlusion). Logistic regression analysis was performed to determine if increasing IPH SIR was associated with an increased risk of ipsilateral ischemic events. Of 85 included patients (85 arteries), 66 were male (77.6%). Mean age was 71.0 (SD ± 11.1). There were 70 arteries with IPH that were ipsilateral to an ischemic event, and 15 that belonged to patients without an ischemic event. No association was found between increasing IPH SIR seen on MP-RAGE (odds ratio (OR): 0.82; 95% confidence interval (CI): 0.58-1.4; P = 0.43) or T1-CUBE sequences (OR: 0.85; 95% CI: 0.53-1.5; P = 0.56). There was no association between the SIR of IPH and acute ischemia on either MP-RAGE or T1-CUBE sequences. Further investigation is required prior to widespread acceptance of SIR as a predictive imaging marker of symptomatic carotid plaque.

One-step evaluation of intraplaque hemorrhage in the carotid artery and vertebrobasilar artery using simultaneous non-contrast angiography and intraplaque hemorrhage

PurposeTo investigate the one-step detection of intraplaque hemorrhage (IPH) in the carotid artery (CA) and vertebrobasilar artery (VBA) using simultaneous non-contrast angiography and intraplaque hemorrhage (SNAP). MethodsFrom January 2019 to March 2020, 1820 consecutive patients who visited our emergency room for evaluation of neurologic symptoms underwent brain MR imaging, including the SNAP sequence. SNAP imaging examined the coronal section from the CA to the VBA. IPH was defined as plaque in the CA and VBA with 200 % higher signal intensity on SNAP than in adjacent muscle in at least two consecutive slices. ResultsOf these patients, 360 (19.8 %) had carotid plaque (both sides = 141, 39.2 %; single side = 219, 61.8 %). Of patients with carotid plaque, 185 (51.4 %) had IPH. Of 141 patients with plaques on both sides, 35 (24.8 %) had bilateral IPH. In total, 73 (4.0 %) patients had VBA IPH (30 with carotid plaque, 43 without carotid plaque). In addition, 18 (1.0 %) patients had carotid IPH and VBA IPH. Maximal wall thickness was significantly higher in the carotid IPH groups (4.5 ± 0.1 vs. 4.1 ± 0.1, p = 0.009). Prevalence of high grade stenosis (>70 %) was significantly higher in the carotid IPH group (17.5 % vs. 6.2 %, p < 0.001). ConclusionsSNAP imaging can be evaluated with a one-step examination of CA and VBA IPH.

Carotid Intraplaque Hemorrhage and Stenosis: At What Stage of Plaque Progression Does Intraplaque Hemorrhage Occur, and When is It Most Likely to Be Associated with Symptoms?

The relationship between carotid intraplaque hemorrhage and luminal stenosis severity is not well-established. We sought to determine whether intraplaque hemorrhage is related to carotid stenosis and at what degree of stenosis intraplaque hemorrhage most likely contributes to ischemic symptoms. Consecutive patients who underwent MR carotid plaque imaging with MPRAGE sequences to identify intraplaque hemorrhage were retrospectively reviewed. Degrees of stenoses were categorized as minimal (<30%), moderate (30%-69%), and severe (>70%). Arteries were categorized into 2 groups: symptomatic (ipsilateral to a cerebral ischemic event) and asymptomatic (from a patient without an ischemic event). Multiple regression analyses were used to determine independent associations between the degree of stenosis and intraplaque hemorrhage and the presence of intraplaque hemorrhage with symptoms among categories of stenosis. We included 449 patients with 449 carotid arteries: Two hundred twenty-five (50.1%) were symptomatic, and 224 (49.9%) were asymptomatic. An increasing degree of stenosis was independently associated with the presence of intraplaque hemorrhage (OR = 1.02; 95% confidence interval, 1.01-1.03). Intraplaque hemorrhage was independently associated with ischemic events in arteries with <30% stenosis (OR = 5.68; 95% CI, 1.49-21.69). No such association was observed in arteries with >30% stenosis. Of symptomatic arteries with minimal stenosis, 8.7% had intraplaque hemorrhage versus 1.7% of asymptomatic arteries (P = .02). No differences in intraplaque hemorrhage prevalence were found between symptomatic and asymptomatic groups with moderate (P = .18) and severe stenoses (P = .99). The presence of intraplaque hemorrhage on high-resolution plaque imaging is likely most useful in identifying symptomatic plaques in cases of minimal stenosis.

The Frequency of Carotid Intraplaque Hemorrhage on Vessel Wall Imaging in Patients With Retinal Artery Occlusion: A Cross-Sectional Prevalence Study.

Intraplaque hemorrhage (IPH) in a carotid artery plaque viewed on vessel wall imaging has been shown to be associated with ischemic stroke. Whether such an association between carotid IPH and retinal artery occlusion (RAO) exists remains unknown. This was a cross-sectional prevalence study. Medical and imaging records of all patients who underwent neck MRA with plaque imaging sequences at our institution from 2015 to 2020 were retrospectively reviewed. Fourteen patients with confirmed RAO and plaque imaging performed within 6 weeks of presentation were included. A group of 211 patients without a prior ischemic event (RAO, stroke, etc.) with plaque imaging were used as controls. A single artery from control patients was randomly selected. The prevalence of IPH and degree of ipsilateral carotid stenosis were compared between RAO and control patients. Multiple regression analysis was performed to determine independent associations between variables and RAO. Five patients (35.7%) with RAO had imaging evidence of ipsilateral IPH in contrast to 7 of 211 (3.3%) patients in the control group (odds ratio [OR]: 16.2, 95% confidence interval [95% CI]: 4.3-61.1, P = 0.0002). Of the 5 patients with RAO and ipsilateral IPH, only one (20.0%) was found to ipsilateral carotid stenosis greater than 70%. Carotid IPH was the only variable that was independently associated with RAO (OR: 12.6, 95% CI = 2.2-73.6, P = 0.005). Carotid IPH is independently associated with RAO. The use of plaque imaging in the evaluation of patients with acute RAO is therefore supported.

Variations in the Presence of Carotid Intraplaque Hemorrhage Across Age Categories: What Age Groups Are Most Likely to Benefit From Plaque Imaging?

Although carotid artery intraplaque hemorrhage (IPH) is a known risk-factor for cerebral ischemic events in patients of advanced age, its prevalence in younger cohorts is less certain. The purpose of this study was to assess the prevalence of carotid artery IPH across the age spectrum. A retrospective review was completed of all adult patients from our institution who underwent neck MRA with high-resolution carotid plaque imaging between 2017 and 2020. The mean ages of patients with and without IPH were calculated. The prevalence of IPH was compared between patients that were categorized into age groups. Patients with and without a cerebral ischemic event (e.g., stroke, retinal ischemia) were included. Unilateral anterior circulation ischemic events in patients without atrial fibrillation were presumed to be likely related to ipsilateral carotid artery disease. Multiple regression analysis was performed to determine independent associations with IPH. 634 patients were included (1,268 carotid arteries). Increasing age (OR: 1.04; 95% CI: 1.02–1.06; P = 0.001) was independently associated with IPH. 211 patients had unilateral anterior circulation ischemic events. The mean age of patients with carotid IPH was 71.4 years (SD = 9.9), compared to 62.8 years (SD = 15.8) of those without (P ≤ 0.0001). The prevalence of IPH increased with age in all patients (P = 0.0002). Among patients with ipsilateral anterior circulation ischemic events, each age category above 50 years had a significantly higher prevalence of IPH when compared to patients 18–50 years (P ≤ 0.05 for all comparisons). The prevalence of carotid IPH increases with age and is rare in patients under 50 years. The approximate threshold age for IPH development is likely around 50 years.

Histological validation of simultaneous non-contrast angiography and intraplaque hemorrhage imaging (SNAP) for characterizing carotid intraplaque hemorrhage.

This study sought to validate the performance of simultaneous non-contrast angiography and intraplaque hemorrhage (SNAP) imaging in characterizing carotid IPH by histology. Thirty-five patients with carotid atherosclerotic disease (symptomatic 50-70% stenosis or > 70% stenosis) scheduled for carotid endarterectomy underwent 3.0-T carotid MR imaging by acquiring SNAP and magnetization-prepared rapid acquisition gradient-echo (MP-RAGE) sequences. Presence and area of IPH were separately evaluated on SNAP and MP-RAGE images. Presence and area of IPH were also assessed on histology. Agreement between SNAP/MP-RAGE and histology was determined in identify and quantify IPH using Cohen kappa, Spearman correlation, and Bland-Altman analyses. Of all 35 patients (mean age: 63.1 ± 8.8 years; 27 males), 128 slices with successful registration were eligible for analysis. The accuracy, sensitivity, specificity, and positive and negative predictive values were 86.7%, 85%, 89.6%, 93.2%, and 78.2% for SNAP, and76.6%, 75%, 79.2%, 85.7%, and 65.5% for MP-RAGE in identification of IPH, respectively. In identification of IPH, the kappa value between SNAP and histology and between MP-RAGE and histology was 0.725 and 0.520, respectively. The correlation between SNAP and histology (r = 0.805, p < 0.001) was stronger than that between MP-RAGE and histology (r = 0.637, p < 0.001) in measuring IPH area. Bland-Altman analysis showed that, in measuring IPH area, the bias of SNAP (1.4 mm2, 95% CI: - 0.016 to 2.883) was smaller than that of MP-RAGE (1.7 mm2, 95% CI: - 0.039 to 3.430) compared with histology. This validation study by histology demonstrates that SNAP sequence better identifies and quantifies carotid intraplaque hemorrhage compared with traditional MP-RAGE sequence. • SNAP imaging showed better agreement with histology compared with MP-RAGE imaging, especially for the IPHs with small size. • SNAP sequence is a more effective tool to identify and quantify carotid IPH than traditional sequence of MP-RAGE that can help clinicians to optimizing the treatment strategy. • The plaque components of rich lipid pools or loose matrix and chronic/old IPH (cholesterol crystals) can lead to false positive and false negative results in SNAP and MP-RAGE imaging for identifying IPH.