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Purpose: Intraplaque haemorrhage (IPH) is a well-known risk factor for faster plaque progression (volume increase); however, its etiology is unclear. We aimed at determining what other local plaque- and systemic factors contribute to plaque progression and to the development and progression of IPH., Methods: We examined 98 asymptomatic participants with carotid plaque using serial multi-contrast magnetic resonance imaging. We measured the percent of wall volume (%WV=100 x [wall volume] / [total vessel volume]) and measured IPH and calcification volumes. We used generalized estimating equations-based regression to analyze predictors of %WV change and new IPH while accounting for covariates (sex, age and statin use), and multiple non-independent observations per participant., Results: Total follow-up was 1.8 ± 0.8 years on average. The presence of IPH (β: 0.6 %/y, p = 0.033) and calcification (β: 1.2 %/y, p = 0.028) were each associated with faster plaque progression. New IPH, detected on a subsequent scan in 4 % of arteries that did not initially have IPH, was associated with larger calcification (odds ratio [OR]: 2.6 per 1-SD increase, p = 0.038) and higher pulse pressure (OR: 2.3 per 1-SD increase, p = 0.016). Larger calcification was associated with greater increases in pulse pressure (β: 1.4 mm Hg/y per 1-SD increase, p = 0.040)., Conclusions: IPH and calcification are each independently associated with faster plaque progression. The association of carotid calcification to increased pulse pressure and new IPH development suggests a possible mechanism by which calcification drives IPH development and plaque progression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Presence of intraplaque hemorrhage (IPH) is a known risk factor for stroke and plaque progression. Accurate and reproducible measurement of IPH volume are required for further risk stratification., Purpose: To develop a semiautomatic method to measure carotid IPH volume., Study Type: Retrospective., Population: Patients scheduled for carotid endarterectomy and patients with 16-79% asymptomatic carotid stenosis by ultrasound., Field Strength: 3T., Sequence: Simultaneous noncontrast angiography and intraplaque hemorrhage (SNAP) MRI., Assessment: A semiautomated volumetric measurement of IPH using signal intensity thresholding of 3D SNAP volume was implemented. Fourteen carotid endarterectomy patients were enrolled to determine the signal intensity threshold of IPH using histology. Thirty-three patients with 16-79% asymptomatic stenosis were scanned twice within 1 month to evaluate reproducibility. The normalized SNAP intensity with the highest Youden index for predicting IPH on histology was used for thresholding. Scan-rescan reproducibility of IPH measurement was assessed using the intraclass correlation coefficient (ICC) and coefficient of variation (CV)., Statistical Tests: Receiver operating characteristic curve, area under the curve, Cohen's kappa, intraclass correlation coefficient, coefficient of variance (CV), and paired t-test., Results: IPH detection by the algorithm had substantial agreement with manual review (kappa: 0.92; 95% confidence interval [CI]: 0.83, 1.00) and moderate agreement with histology (kappa: 0.55; 95% CI: 0.34, 0.68). IPH volume measurements by the algorithm were strongly correlated with histology (Spearman's rho = 0.76, P = 0.002). IPH measurements were also reproducible, with ICCs of 0.86 (95% CI: 0.57, 0.96), 0.77 (95% CI: 0.32, 0.94), and 0.99 (95% CI: 0.93, 1.00) for maximum/mean normalized intensity and IPH volume, respectively. The corresponding CVs were 10.6%, 5.2%, and 11.8%., Data Conclusion: IPH volume measurements on SNAP MRI are highly reproducible using semiautomatic measurement. Level of Evidence 2 Technical Efficacy Stage 2 J. Magn. Reson. Imaging 2019;50:1055-1062., (© 2019 International Society for Magnetic Resonance in Medicine.)

Purpose: To evaluate in a proof-of-concept study the feasibility of Simultaneous Noncontrast Angiography and intraPlaque hemorrhage (SNAP) imaging as a clinical magnetic resonance angiography (MRA) technique for measuring carotid stenosis. There is a growing interest in detecting intraplaque hemorrhage (IPH) during the clinical management of carotid disease, yet luminal stenosis has remained indispensable during clinical decision-making. SNAP imaging has been proposed as a novel IPH imaging technique that provides carotid MRA with no added scan time. Flowing blood shows negative signal on SNAP because of phase-sensitive inversion recovery., Materials and Methods: In all, 58 asymptomatic subjects with 16-79% stenosis on ultrasound were scanned at 3T by SNAP with 0.8 mm isotropic resolution and 16 cm longitudinal coverage. Two readers measured luminal stenosis of bilateral carotid arteries (n = 116) on minimum intensity projections of SNAP using the NASCET criteria. In the subset (48 arteries) with contrast-enhanced (CE) MRA available for comparison, luminal stenosis was also measured on maximum intensity projections of CE-MRA., Results: Intraclass correlation coefficients (ICCs) with 95% confidence intervals were 0.94 (0.90-0.96) and 0.93 (0.88-0.96) for intra- and interreader agreement on stenosis measurements, respectively. Corresponding kappas for grading stenosis (0-29%, 30-69%, 70-99%, and 100%) were 0.79 (0.67-0.89) and 0.80 (0.68-0.90). Agreement between SNAP and CE-MRA was high (ICC: 0.95 [0.90-0.98]; kappa: 0.82 [0.71-0.93])., Conclusion: As a dedicated IPH-imaging sequence, SNAP also provided carotid stenosis measurement that showed high intra- and interreader consistency and excellent agreement with CE-MRA. Further comparisons with digital subtraction angiography and other noninvasive techniques are warranted., Level of Evidence: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1045-1052., (© 2017 International Society for Magnetic Resonance in Medicine.)

Background and Aims: Prospective studies have shown a strong association between carotid intraplaque hemorrhage (IPH), detected by magnetic resonance imaging (MRI), and cerebrovascular ischemic events. However, IPH is also observed in a substantial number of asymptomatic patients. We hypothesized that there are differences in the characteristics of IPH+ plaques associated with recent symptoms, compared to IPH+ plaques not associated with recent symptoms., Methods: Patients with recent (≤2 weeks) anterior circulation ischemic events were scanned using a standardized multisequence protocol. Those showing IPH bilaterally were included and analyzed for differences in T1/T2 signals, plaque morphology, and coexisting plaque characteristics between the ipsilateral symptomatic and contralateral asymptomatic sides., Results: Thirty-one subjects (67 ± 9 years, 97% males) with bilateral IPH were studied. Despite comparable luminal stenosis (53 ± 42% vs. 53 ± 39%, p = 0.99), T1 signal of IPH measured as signal-intensity-ratio compared to muscle was stronger (SIR IPH-to-muscle : 5.8 ± 2.4 vs. 4.7 ± 1.8, p = 0.004) and tended to be more extensively distributed (IPH volume: 150 ± 199 vs. 88 ± 106 mm 3 , p = 0.071) on the symptomatic side. IPH+ plaques on the symptomatic side were longer (24 ± 6 vs. 21 ± 7 mm, p = 0.026) and associated with larger necrotic core volume (406 ± 354 vs. 291 ± 293 mm 3 , p = 0.039) than those on the asymptomatic side., Conclusions: In recently symptomatic patients with bilateral carotid IPH, the symptomatic side showed stronger T1 signals, larger necrotic cores, and longer plaque length than the asymptomatic side. Serial studies on the temporal relationship between these imaging features and clinical events will eventually establish their diagnostic and prognostic value beyond the mere presence of IPH., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background and Aims: Plaque fissuring, a phenomenon morphologically distinct from the classical rupture of a thinned fibrous cap, has not been well characterized in carotid atherosclerosis. The aim of this study was to establish the prevalence of plaque fissures in advanced carotid plaques with an otherwise intact luminal surface, and to determine whether they might be a source of intraplaque hemorrhage (IPH)., Methods: We evaluated 244 surgically intact, 'en bloc' embedded, serially sectioned carotid endarterectomy specimens and included only those plaques with a grossly intact luminal surface., Results: Among the 67 plaques with grossly intact luminal surface, cap fissure was present in 39 (58%) plaques. A total of 60 individual fissures were present, and longitudinally mean fissure length was 1.3 mm. Most fissures were found distal to the bifurcation (63%), proximal to the stenosis (88%), and in the posterior (opposite the flow divider) or lateral quadrants (80%). 36% of the fissures remained in the superficial third of the plaque. 52% extended from the lumen surface to the middle third of the plaque and 12% reached the outer third of the plaque on cross section. Fissures often occurred between two tissue planes and were connected to IPH (fresh: 63%; any type: 92%) and calcifications (43%). No correlation was found with patient characteristics such as symptom status, carotid stenosis, hypertension, diabetes, smoking and medications (statins or antiplatelet agents)., Conclusions: Plaque fissures are common in advanced carotid plaques with an otherwise grossly intact luminal surface and are associated with fresh intraplaque hemorrhage. As they occur on the interface between plaque components with different mechanical properties, further biomechanical studies are needed to unravel the underlying failure mechanisms., (Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Background: Intraplaque hemorrhage (IPH) is associated with atherosclerosis progression and subsequent cardiovascular events. We sought to develop a semi-automatic method with an optimized threshold for carotid IPH detection and quantification on MP-RAGE images using matched histology as the gold standard., Methods: Fourteen patients scheduled for carotid endarterectomy underwent 3D MP-RAGE cardiovascular magnetic resonance (CMR) preoperatively. Presence and area of IPH were recorded using histology. Presence and area of IPH were also recorded on CMR based on intensity thresholding using three references for intensity normalization: the sternocleidomastoid muscle (SCM), the adjacent muscle and the automatically generated local median value. The optimized intensity thresholds were obtained by maximizing the Youden's index for IPH detection. Using leave-one-out cross validation, the sensitivity and specificity for IPH detection based on our proposed semi-automatic method and the agreement with histology on IPH area quantification were evaluated., Results: The optimized intensity thresholds for IPH detection were 1.0 times the SCM intensity, 1.6 times the adjacent muscle intensity and 2.2 times the median intensity. Using the semi-automatic method with the optimized intensity threshold, the following IPH detection and quantification performance was obtained: sensitivities up to 59, 68 and 80 %; specificities up to 85, 74 and 79 %; Pearson's correlation coefficients (IPH area measurement) up to 0.76, 0.93 and 0.90, respectively, using SCM, the adjacent muscle and the local median value for intensity normalization, after heavily calcified and small IPH were excluded., Conclusions: A semi-automatic method with good performance on IPH detection and quantification can be obtained in MP-RAGE CMR, using an optimized intensity threshold comparing to the adjacent muscle. The automatically generated reference of local median value provides comparable performance and may be particularly useful for developing automatic classifiers. Use of the SCM intensity as reference is not recommended without coil sensitivity correction when surface coils are used.

Objective: Effective prevention and management strategies of intraplaque hemorrhage (IPH) remain elusive because of our limited knowledge regarding its contributing factors. This hypothesis-generating study aimed to investigate associations between cardiovascular risk factors and IPH for improved understanding of the pathogenesis of IPH., Approach and Results: Asymptomatic subjects with 16% to 79% stenosis on ultrasound underwent carotid magnetic resonance imaging using a large-coverage, 3-dimensional magnetic resonance imaging protocol. Individual plaques (maximum thickness >1.5 mm) in bilateral carotid arteries were identified, and presence of IPH was determined. From 80 subjects, 176 de novo plaques were measured, of which 38 (21.6%) contained IPH. Blood pressure (BP), primarily low diastolic BP, was associated with IPH in multivariate analysis adjusted for age, sex, and plaque size (odds ratio with 95% confidence interval per 10-mm Hg increase: 0.51 [0.30-0.88]), which was little changed after adjusting for antihypertensive use and systemic atherosclerosis. Antiplatelet use was associated with IPH in age and sex-adjusted models (P=0.018), for which a trend remained after considering plaque size and past medical history (odds ratio for aspirin alone versus none: 3.1 [0.66-14.8]; odds ratio for clopidogrel or dual therapy versus none: 5.3 [0.80-35.0]; P=0.083)., Conclusions: Low diastolic BP was independently associated with IPH, which was not attributed to treatment difference or BP changes from systemic atherosclerosis. Hemodynamic changes from lowering diastolic BP may be the pathophysiological link. Prospective serial studies are needed to assess whether BP and antiplatelet use are associated with the development of new or repeated IPH., (© 2016 American Heart Association, Inc.)

Objectives: Simultaneous Non-contrast Angiography and intraPlaque hemorrhage (SNAP) technique was recently proposed for joint MRA and intraplaque hemorrhage (IPH) imaging. The purpose of this study is to validate SNAP's MRA performance in patients with suspected intracranial artery disease., Methods: SNAP and time-of-flight (TOF) techniques with matched field of view and resolution were applied on 15 patients with suspected intracranial artery disease. Both techniques were evaluated based on their detection of luminal stenosis of bilateral middle cerebral arteries (MCA) and the delineation of smallest visible branches (SVB) of the MCA. Statistical analysis was conducted on the artery level., Results: The SNAP MRA was found to provide similar stenosis detection performance when compared with TOF (Cohen's κ 0.79; 95% Confidence Interval: 0.56-0.99). For the SVB comparison, SNAP was found to provide significantly better small artery delineation than TOF (p = 0.017). Inter-reader reproducibility for both measurements on SNAP was over 0.7. SNAP also detected IPH lesions on 13% of the patients., Conclusions: The SNAP technique's MRA performance was optimized and compared against TOF for intracranial artery atherosclerosis imaging and was found to provide comparable stenosis detection accuracy. Along with its IPH detection capability, SNAP holds the potential to become a first-line screening tool for high risk intracranial atherosclerosis disease evaluation.

Purpose: Although transcatheter embolization is a well established technique to treat adults in the trauma setting, evidence is lacking in the pediatric population. This study assesses the safety and efficacy of arterial embolization for blunt abdominal and pelvic trauma in the pediatric population., Materials and Methods: A retrospective review of abdominal and pelvic angiograms in 97 pediatric patients with blunt trauma was conducted over an 11-year period. Abdominal angiography and embolization was performed for ongoing hepatic, renal, splenic, or nonvisceral retroperitoneal injury. Pelvic angiography was performed in the setting of pelvic fracture with ongoing pelvic hemorrhage. Complications and clinical success rates of these procedures were assessed., Results: Of the 97 pediatric patients who underwent angiography for acute abdominal or pelvic trauma, 54 (56%) required embolization involving 62 separate sites. Injury severity score greater than 15 was present in 94% of patients. Targets of embolization included the pelvis (n = 39), liver (n = 8), kidney (n = 7), spleen (n = 6), and retroperitoneum (n = 2). Effective hemorrhage control was achieved in 47 patients (87%). Overall mortality rate was 22% (12 of 54), with most deaths related to traumatic brain injury. Five complications occurred in four patients (7%), including three major complications (hepatic abscess, bile leak, and urinary incontinence)., Conclusions: Angiography and embolization is relatively safe and potentially effective in the setting of abdominal and pelvic trauma in the pediatric population. Angiography with embolization should be considered in the treatment algorithm for this patient population., (© 2014 The Society of Interventional Radiology Published by SIR All rights reserved.)

A simultaneous noncontrast angiography and intraplaque hemorrhage (SNAP) MR imaging technique is proposed to detect both luminal stenosis and hemorrhage in atherosclerosis patients in a single scan. Thirteen patients with diagnosed carotid atherosclerotic plaque were admitted after informed consent. All scans were performed on a 3T MR imaging system with SNAP, 2D time-of-flight and magnetization-prepared 3D rapid acquisition gradient echo sequences. The SNAP sequence utilized a phase sensitive acquisition, and was designed to provide positive signals corresponding to intraplaque hemorrhage and negative signals corresponding to lumen. SNAP images were compared to time-of-flight images to evaluate lumen size measurements using linear mixed models and the intraclass correlation coefficient. Intraplaque hemorrhage identification accuracy was evaluated by comparing to magnetization-prepared 3D rapid acquisition gradient echo images using Cohen's Kappa. Diagnostic quality SNAP images were generated from all subjects. Quantitatively, the lumen size measurements by SNAP were strongly correlated (intraclass correlation coefficient = 0.96, P < 0.001) with those measured by time-of-flight. For intraplaque hemorrhage detection, strong agreement (κ = 0.82, P < 0.001) was also identified between SNAP and magnetization-prepared 3D rapid acquisition gradient echo images. In conclusion, a SNAP imaging technique was proposed and shows great promise for imaging both lumen size and carotid intraplaque hemorrhage with a single scan., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: Carotid intraplaque hemorrhage (IPH) and lipid rich necrotic core (LRNC) have been associated with accelerated plaque growth, luminal narrowing, future surface disruption and development of symptomatic events. The aim of this study was to evaluate the quantitative relationships between high intensity signals (HIS) in the plaque on TOF-MRA and IPH or LRNC volumes as measured by multicontrast weighted CMR., Methods: Seventy six patients with a suspected carotid artery stenosis or carotid plaque by ultrasonography underwent multicontrast carotid CMR. HIS presence and volume were measured from TOF-MRA MIP images while IPH and LRNC volumes were separately measured from multicontrast CMR., Results: For detecting IPH, HIS on MIP images overall had high specificity (100.0%, 95% CI: 93.0 - 100.0%) but relatively low sensitivity (32%, 95% CI: 20.8 - 47.9%). However, the sensitivity had a significant increasing relationship with underlying IPH volume (p = 0.033) and degree of stenosis (p = 0.022). Mean IPH volume was 2.7 times larger in those with presence of HIS than in those without (142.8 ± 97.7 mm(3) vs. 53.4 ± 56.3 mm(3), p = 0.014). Similarly, mean LRNC volume was 3.4 times larger in those with HIS present (379.8 ± 203.4 mm(3) vs. 111.3 ± 122.7 mm(3), p = 0.001). There was a strong correlation between the volume of the HIS region and the IPH volume measured from multicontrast CMR (r = 0.96, p < 0.001)., Conclusion: MIP images are easily reformatted from three minute, routine, clinical TOF sequences. High intensity signals in carotid plaque on TOF-MRA MIP images are associated with increased intraplaque hemorrhage and lipid-rich necrotic core volumes. The technique is most sensitive in patients with moderate to severe stenosis.

Objectives: This study sought to determine the immediate and long-term effects of intraplaque hemorrhage (IPH) on plaque progression in the carotid artery., Background: 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., Methods: 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., Results: 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., Conclusions: 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., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Intraplaque hemorrhage (IPH) is associated with plaque progression and ischemic events, and plaque lipid content (% lipid core) predicts the residual atherosclerotic cardiovascular disease risk. This study examined the impact of IPH on lipid content change in the setting of intensive lipid-lowering therapy. Methods: In total, 214 AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low High-Density Lipoprotein/High Triglycerides: Impact on Global Health Outcomes) participants with clinically established ASCVD and low high-density lipoprotein cholesterol received cartoid MRI at baseline and 2 years to assess changes in carotid morphology and composition. Patients were randomized to extended-release niacin or placebo, and all received simvastatin with optional ezetimibe as necessary to lower low-density lipoprotein cholesterol to 40 to 80 mg/dL. Changes in lipid content and carotid morphology were tested using the Wilcoxon signed-rank test. Differences between subjects with and without IPH and between subjects assigned extended-release niacin or placebo were tested using the Wilcoxon rank-sum test. Linear regression was used to test the association of IPH and lipid content changes after adjusting for clinical risk factors. Results: Among 156 patients (61±9 years; 81% men) with complete MRI, prior statin use: <1 year, 26%; 1 to 5 years, 37%; >5 years, 37%. Triglycerides and ApoB decreased significantly, whereas high-density lipoprotein cholesterol and ApoA1 increased significantly over time. Plaque lipid content was significantly reduced (−0.5±2.4 %/year, P = 0.017) without a significant difference between the 2 treatment groups. However, the lipid content increased in plaques with IPH but regressed in plaques without IPH (1.2±2.5 %/year versus −1.0±2.2, P = 0.006). Additionally, IPH was associated with a decrease in lumen area (−0.4±0.9 mm2/year versus 0.3±1.4, P = 0.033). IPH remained significantly associated with increase in lipid content in multivariable analysis (54.4%, 95% CI: 26.8, 88.0, P < 0.001). Conclusions: Carotid plaques under continued intensive lipid-lowering therapy moved toward stabilization. However, plaques with IPH showed greater increases in lipid content and greater decreases in lumen area than plaques without IPH. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01178320. [ABSTRACT FROM AUTHOR]

Background: Carotid intraplaque hemorrhage (IPH) and lipid rich necrotic core (LRNC) have been associated with accelerated plaque growth, luminal narrowing, future surface disruption and development of symptomatic events. The aim of this study was to evaluate the quantitative relationships between high intensity signals (HIS) in the plaque on TOF-MRA and IPH or LRNC volumes as measured by multicontrast weighted CMR. Methods: Seventy six patients with a suspected carotid artery stenosis or carotid plaque by ultrasonography underwent multicontrast carotid CMR. HIS presence and volume were measured from TOF-MRA MIP images while IPH and LRNC volumes were separately measured from multicontrast CMR. Results: For detecting IPH, HIS on MIP images overall had high specificity (100.0%, 95% CI: 93.0 - 100.0%) but relatively low sensitivity (32%, 95% CI: 20.8 - 47.9%). However, the sensitivity had a significant increasing relationship with underlying IPH volume (p = 0.033) and degree of stenosis (p = 0.022). Mean IPH volume was 2.7 times larger in those with presence of HIS than in those without (142.8 ± 97.7 mm3 vs. 53.4 ± 56.3 mm3, p = 0.014). Similarly, mean LRNC volume was 3.4 times larger in those with HIS present (379.8 ± 203.4 mm3 vs. 111.3 ± 122.7 mm3, p = 0.001). There was a strong correlation between the volume of the HIS region and the IPH volume measured from multicontrast CMR (r = 0.96, p < 0.001). Conclusion: MIP images are easily reformatted from three minute, routine, clinical TOF sequences. High intensity signals in carotid plaque on TOF-MRA MIP images are associated with increased intraplaque hemorrhage and lipid-rich necrotic core volumes. The technique is most sensitive in patients with moderate to severe stenosis. [ABSTRACT FROM AUTHOR]