Revealing tumor microstructure with oscillating diffusion encoding MRI in pre-surgical and post-treatment glioma patients.

PURPOSE: We hypothesized that the time-dependent diffusivity at short diffusion times, as measured by oscillating gradient spin echo (OGSE) diffusion MRI, can characterize tissue microstructures in glioma patients. THEORY AND METHODS: Five adult patients with known diffuse glioma, including two pre-surgical and three with new enhancing lesions after treatment for high-grade glioma, were scanned in an ultra-high-performance gradient 3.0T MRI system. OGSE diffusion MRI at 30-100 Hz and pulsed gradient spin echo diffusion imaging (approximated as 0 Hz) were obtained. The ADC and trace-diffusion-weighted image at each acquired frequency were calculated, that is, ADC (f) and TraceDWI (f). RESULTS: In pre-surgical patients, biopsy-confirmed solid enhancing tumor in a high-grade glioblastoma showed higher ADC ( f ) ADC ( 0 Hz ) $$ \frac{\mathrm{ADC}\ (f)}{\mathrm{ADC}\ \left(0\ \mathrm{Hz}\right)} $$ and lower TraceDWI ( f ) TraceDWI ( 0 Hz ) $$ \frac{\mathrm{TraceDWI}\ (f)}{\mathrm{TraceDWI}\ \left(0\ \mathrm{Hz}\right)} $$ , compared to that at same OGSE frequency in a low-grade astrocytoma. In post-treatment patients, the enhancing lesions of two patients who were diagnosed with tumor progression contained more voxels with high ADC ( f ) ADC ( 0 Hz ) $$ \frac{\mathrm{ADC}\ (f)}{\mathrm{ADC}\ \left(0\ \mathrm{Hz}\right)} $$ and low TraceDWI ( f ) TraceDWI ( 0 Hz ) $$ \frac{\mathrm{TraceDWI}\left(\mathrm{f}\right)}{\mathrm{TraceDWI}\left(0\ \mathrm{Hz}\right)} $$ , compared to the enhancing lesions of a patient who was diagnosed with treatment effect. Non-enhancing T2 signal abnormality lesions in both the pre-surgical high-grade glioblastoma and post-treatment tumor progressions showed regions with high ADC ( f ) ADC ( 0 Hz ) $$ \frac{\mathrm{ADC}\ (f)}{\mathrm{ADC}\ \left(0\ \mathrm{Hz}\right)} $$ and low TraceDWI ( f ) TraceDWI ( 0 Hz ) $$ \frac{\mathrm{TraceDWI}\ \left(\mathrm{f}\right)}{\mathrm{TraceDWI}\ \left(0\ \mathrm{Hz}\right)} $$ , consistent with infiltrative tumor. The solid tumor of the glioblastoma, the enhancing lesions of post-treatment tumor progressions, and the suspected infiltrative tumors showed high diffusion time-dependency from 30 to 100 Hz, consistent with high intra-tumoral volume fraction (cellular density). CONCLUSION: Different characteristics of OGSE-based time-dependent diffusivity can reveal heterogenous tissue microstructures that indicate cellular density in glioma patients.

Multinational Survey of Current Practice from Imaging to Treatment of Atherosclerotic Carotid Stenosis.

BACKGROUND: In the last 20-30 years, there have been many advances in imaging and therapeutic strategies for symptomatic and asymptomatic individuals with carotid artery stenosis. Our aim was to examine contemporary multinational practice standards. METHODS: Departmental Review Board approval for this study was obtained, and 3 authors prepared the 44 multiple choice survey questions. Endorsement was obtained by the European Society of Neuroradiology, American Society of Functional Neuroradiology, and African Academy of Neurology. A link to the online questionnaire was sent to their respective members and members of the Faculty Advocating Collaborative and Thoughtful Carotid Artery Treatments (FACTCATS). The questionnaire was open from May 16 to July 16, 2019. RESULTS: The responses from 223 respondents from 46 countries were included in the analyses including 65.9% from academic university hospitals. Neuroradiologists/radiologists comprised 68.2% of respondents, followed by neurologists (15%) and vascular surgeons (12.9%). In symptomatic patients, half (50.4%) the respondents answered that the first exam they used to evaluate carotid bifurcation was ultrasound, followed by computed tomography angiography (CTA, 41.6%) and then magnetic resonance imaging (MRI 8%). In asymptomatic patients, the first exam used to evaluate carotid bifurcation was ultrasound in 88.8% of respondents, CTA in 7%, and MRA in 4.2%. The percent stenosis upon which carotid endarterectomy or stenting was recommended was reduced in the presence of imaging evidence of "vulnerable plaque features" by 66.7% respondents for symptomatic patients and 34.2% for asymptomatic patients with a smaller subset of respondents even offering procedural intervention to patients with <50% symptomatic or asymptomatic stenosis. CONCLUSIONS: We found heterogeneity in current practices of carotid stenosis imaging and management in this worldwide survey with many respondents including vulnerable plaque imaging into their decision analysis despite the lack of proven benefit from clinical trials. This study highlights the need for new clinical trials using vulnerable plaque imaging to select high-risk patients despite maximal medical therapy who may benefit from procedural intervention.

MR Angiography Series: Neurovascular MR Angiography.

Neurovascular MR angiography (MRA) is an evolving imaging technique and is crucial for the workup of numerous neurologic disorders. While CT angiography (CTA) provides a more rapid imaging assessment, in select patients it can impart a small risk of contrast material-induced nephrotoxicity or radiation-associated cancers. In addition, MRA offers some advantages over CTA for neurovascular evaluation, including higher temporal resolution and the capability for vessel wall imaging. This module is the third in a series created on behalf of the Society for Magnetic Resonance Angiography (SMRA), a group of researchers and clinicians who are passionate about the benefits of MRA but understand its challenges. The full digital presentation is available online. Work of the U.S. Government published under an exclusive license with the RSNA.

MR Angiography Series: Fundamentals of Contrast-enhanced MR Angiography.

The Society for Magnetic Resonance Angiography (SMRA) is a group of researchers and clinicians who are passionate about the benefits of MR angiography (MRA) but understand its challenges. Their mission is to study MRA, continually improve and innovate for the benefit of patients, and most important, educate the medical community so they can take full advantage of the benefits of MRA and overcome its challenges. In support of that mission, the authors have created a series of self-learning modules on behalf of the SMRA to demystify MRA protocols and help the reader perform patient-friendly high-quality MRA on a routine basis in clinical practice. The full digital presentation is available online. ©RSNA, 2021.

Oscillating diffusion-encoding with a high gradient-amplitude and high slew-rate head-only gradient for human brain imaging.

PURPOSE: We investigate the importance of high gradient-amplitude and high slew-rate on oscillating gradient spin echo (OGSE) diffusion imaging for human brain imaging and evaluate human brain imaging with OGSE on the MAGNUS head-gradient insert (200 mT/m amplitude and 500 T/m/s slew rate). METHODS: Simulations with cosine-modulated and trapezoidal-cosine OGSE at various gradient amplitudes and slew rates were performed. Six healthy subjects were imaged with the MAGNUS gradient at 3T with OGSE at frequencies up to 100 Hz and b = 450 s/mm2 . Comparisons were made against standard pulsed gradient spin echo (PGSE) diffusion in vivo and in an isotropic diffusion phantom. RESULTS: Simulations show that to achieve high frequency and b-value simultaneously for OGSE, high gradient amplitude, high slew rates, and high peripheral nerve stimulation limits are required. A strong linear trend for increased diffusivity (mean: 8-19%, radial: 9-27%, parallel: 8-15%) was observed in normal white matter with OGSE (20 Hz to 100 Hz) as compared to PGSE. Linear fitting to frequency provided excellent correlation, and using a short-range disorder model provided radial long-term diffusivities of D∞,MD = 911 ± 72 µm2 /s, D∞,PD = 1519 ± 164 µm2 /s, and D∞,RD = 640 ± 111 µm2 /s and correlation lengths of lc,MD = 0.802 ± 0.156 µm, lc,PD = 0.837 ± 0.172 µm, and lc,RD = 0.780 ± 0.174 µm. Diffusivity changes with OGSE frequency were negligible in the phantom, as expected. CONCLUSION: The high gradient amplitude, high slew rate, and high peripheral nerve stimulation thresholds of the MAGNUS head-gradient enables OGSE acquisition for in vivo human brain imaging.

Highly efficient head-only magnetic field insert gradient coil for achieving simultaneous high gradient amplitude and slew rate at 3.0T (MAGNUS) for brain microstructure imaging.

PURPOSE: To develop a highly efficient magnetic field gradient coil for head imaging that achieves 200 mT/m and 500 T/m/s on each axis using a standard 1 MVA gradient driver in clinical whole-body 3.0T MR magnet. METHODS: A 42-cm inner diameter head-gradient used the available 89- to 91-cm warm bore space in a whole-body 3.0T magnet by increasing the radial separation between the primary and the shield coil windings to 18.6 cm. This required the removal of the standard whole-body gradient and radiofrequency coils. To achieve a coil efficiency ~4× that of whole-body gradients, a double-layer primary coil design with asymmetric x-y axes, and symmetric z-axis was used. The use of all-hollow conductor with direct fluid cooling of the gradient coil enabled ≥50 kW of total heat dissipation. RESULTS: This design achieved a coil efficiency of 0.32 mT/m/A, allowing 200 mT/m and 500 T/m/s for a 620 A/1500 V driver. The gradient coil yielded substantially reduced echo spacing, and minimum repetition time and echo time. In high b = 10,000 s/mm2 diffusion, echo time (TE) < 50 ms was achieved (>50% reduction compared with whole-body gradients). The gradient coil passed the American College of Radiology tests for gradient linearity and distortion, and met acoustic requirements for nonsignificant risk operation. CONCLUSIONS: Ultra-high gradient coil performance was achieved for head imaging without substantial increases in gradient driver power in a whole-body 3.0T magnet after removing the standard gradient coil. As such, any clinical whole-body 3.0T MR system could be upgraded with 3-4× improvement in gradient performance for brain imaging.

Indications for the Performance of Intracranial Endovascular Neurointerventional Procedures: A Scientific Statement From the American Heart Association.

Intracranial endovascular interventions provide effective and minimally invasive treatment of a broad spectrum of diseases. This area of expertise has continued to gain both wider application and greater depth as new and better techniques are developed and as landmark clinical studies are performed to guide their use. Some of the greatest advances since the last American Heart Association scientific statement on this topic have been made in the treatment of ischemic stroke from large intracranial vessel occlusion, with more effective devices and large randomized clinical trials showing striking therapeutic benefit. The treatment of cerebral aneurysms has also seen substantial evolution, increasing the number of aneurysms that can be treated successfully with minimally invasive therapy. Endovascular therapies for such other diseases as arteriovenous malformations, dural arteriovenous fistulas, idiopathic intracranial hypertension, venous thrombosis, and neoplasms continue to improve. The purpose of the present document is to review current information on the efficacy and safety of procedures used for intracranial endovascular interventional treatment of cerebrovascular diseases and to summarize key aspects of best practice.

Diagnostic accuracy of a clinical carotid plaque MR protocol using a neurovascular coil compared to a surface coil protocol.

BACKGROUND: Carotid plaque imaging with MRI is becoming more commonplace, but practical challenges exist in performing plaque imaging with surface coils. PURPOSE: To compare the diagnostic performance of a carotid plaque MRI protocol using a standard neurovascular coil (Neurovascular Coil Protocol) to a higher-resolution carotid plaque MRI using carotid surface coils (Surface Coil Protocol) in characterizing carotid plaque. STUDY TYPE: Prospective study comparing two MR techniques in plaque characterization. POPULATION: Thirty-eight consecutive carotid artery disease patients. FIELD STRENGTH/SEQUENCE: Patients underwent 3T MRI using 1) a Neurovascular Coil Protocol including the following sequences: 3D-FSE T1 pre/postcontrast and precontrast 3D IR-FSPGR, and 2) a Surface Coil Protocol using standard multicontrast MRI sequences. ASSESSMENT: Plaque characteristics analyzed by two independent neuroradiologists included intraplaque hemorrhage (IPH), lipid-rich necrotic-core (LRNC), and thin/ruptured fibrous cap (TRFC). STATISTICAL TESTS: Diagnostic performance of the Neurovascular Coil Protocol was compared to the Surface Coil Protocol reference standard using receiver-operating curves. RESULTS: For IPH, sensitivity, specificity, and area under the curve (AUC) of the Neurovascular Coil Protocol were 91.1% (95% confidence interval [CI] = 78.8-97.5%), 87.0% (95% CI = 66.4-97.2%), and 0.92, respectively. For LRNC without IPH sensitivity, specificity, and AUC were 73.3% (95% CI = 44.9-92.2%), 85.7% (95% CI = 67.3-96.0%), and 0.84, respectively. For TRFC, sensitivity, specificity, and AUC were 35.3% (95% CI = 14.2-61.7%), 97.6% (95% CI = 87.4-99.9%), and 0.66 respectively. Interobserver agreement for IPH, LRNC, and TRFC using the Neurovascular Coil Protocol were k = 0.87 (95% CI = 0.75-0.99), k = 0.54 (95% CI = 0.29-0.80), and k = 0.41 (95% CI = 0.08-0.74), respectively. DATA CONCLUSION: Our Neurovascular Coil Protocol has high sensitivity, specificity, and accuracy in identifying IPH and LRNC but is limited in assessment of TRFC. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1264-1272.

Semi-automatic carotid intraplaque hemorrhage detection and quantification on Magnetization-Prepared Rapid Acquisition Gradient-Echo (MP-RAGE) with optimized threshold selection.

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.

Ultrasound Characteristics of Symptomatic Carotid Plaques: A Systematic Review and Meta-Analysis.

BACKGROUND: Ultrasound is the most commonly used imaging modality for assessing carotid artery stenosis. A number of studies have demonstrated that surface irregularities, heterogeneous echotexture and hypoechoic plaques are risk factors for acute ischemic stroke. We performed a systematic review and meta-analysis of the literature to better define the risk of stroke based on the sonographic characteristics of carotid plaques. MATERIALS AND METHODS: We performed a comprehensive search for studies reporting imaging findings of symptomatic and asymptomatic carotid plaques on ultrasound using MEDLINE and EMBASE. We included both case-control and cohort studies examining the relationship between complex plaque and acute ischemic stroke or transient ischemic attack. Complex plaque was defined as plaque that had any of the following characteristics: heterogeneous echogenicity, echolucency, neovascularization, surface irregularity, ulceration, and intraplaque motion. Meta-analyses using the random-effects model were performed for complex plaque and each of the individual complex plaque characteristics. p < 0.05 was considered statistically significant. We explored the impact of publication bias by constructing funnel plots and testing their symmetry. We conducted the meta-analysis using Comprehensive Meta-analysis version 2.2, Englewood, N.J., USA. RESULTS: A total of 1,013 articles were screened and 23 studies with 6,706 carotid plaques were included. Ultrasound plaque characteristics with a higher prevalence in individuals with symptomatic compared to asymptomatic carotid artery stenosis included plaque neovascularity (OR = 19.68, 95% CI = 3.14-123.16), complex plaque (OR = 5.12, 95% CI = 3.42-7.67), plaque ulceration (OR = 3.58, 95% CI = 1.66-7.71), plaque echolucency (OR = 3.99, 95% CI = 3.06-5.19) and intraplaque motion (OR = 1.57, 95% CI = 1.02-2.41). Variables not associated with symptom status included heterogenous echotexture (OR = 2.68, 95% CI = 0.56-12.80) and surface irregularity without ulceration (OR = 2.38, 95% CI = 0.70-8.11). No evidence of publication bias was observed based on Eggers test (p value of 0.05 for complex plaque and 0.53 for plaque echolucency). The remaining plaque features had insufficient data to assess for publication bias. CONCLUSIONS: Our meta-analysis and systematic review of the literature demonstrated that plaques with complex features, particularly those with echolucency, neovascularization, ulceration and intraplaque motion are associated with ischemic symptoms. Assessment of carotid plaque on ultrasound may provide stroke risk information beyond measurement of luminal stenosis. Thus, sonographic evaluation of carotid artery stenosis should focus on the detection of these plaque characteristics in addition to quantifying the degree of stenosis.

Imaging of high-risk carotid artery plaques: current status and future directions.

In this paper, the authors review the definition of high-risk plaque as developed by experienced researchers in atherosclerosis, including pathologists, clinicians, molecular biologists, and imaging scientists. Current concepts of vulnerable plaque are based on histological studies of coronary and carotid artery plaque as well as natural history studies and include the presence of a lipid-rich necrotic core with an overlying thin fibrous cap, plaque inflammation, fissured plaque, and intraplaque hemorrhage. The extension of these histologically identified high-risk carotid plaque features to human in vivo MRI is reviewed as well. The authors also assess the ability of in vivo MRI to depict these vulnerable carotid plaque features. Next, the ability of these MRI-demonstrated high-risk carotid plaque features to predict the risk of ipsilateral carotid thromboembolic events is reviewed and compared with the risk assessment provided by simple carotid artery stenosis measurements. Lastly, future directions of high-risk carotid plaque MRI are discussed, including the potential for increased clinical availability and more automated analysis of carotid plaque MRI. The ultimate goal of high-risk plaque imaging is to design and run future multicenter trials using carotid plaque MRI to guide individual patient selection and decisions about optimal atherosclerotic treatment strategies.

Carotid Plaque-RADS: A Novel Stroke Risk Classification System.

BACKGROUND: Carotid artery atherosclerosis is highly prevalent in the general population and is a well-established risk factor for acute ischemic stroke. Although the morphological characteristics of vulnerable plaques are well recognized, there is a lack of consensus in reporting and interpreting carotid plaque features. OBJECTIVES: The aim of this paper is to establish a consistent and comprehensive approach for imaging and reporting carotid plaque by introducing the Plaque-RADS (Reporting and Data System) score. METHODS: A panel of experts recognized the necessity to develop a classification system for carotid plaque and its defining characteristics. Using a multimodality analysis approach, the Plaque-RADS categories were established through consensus, drawing on existing published reports. RESULTS: The authors present a universal classification that is applicable to both researchers and clinicians. The Plaque-RADS score offers a morphological assessment in addition to the prevailing quantitative parameter of "stenosis." The Plaque-RADS score spans from grade 1 (indicating complete absence of plaque) to grade 4 (representing complicated plaque). Accompanying visual examples are included to facilitate a clear understanding of the Plaque-RADS categories. CONCLUSIONS: Plaque-RADS is a standardized and reliable system of reporting carotid plaque composition and morphology via different imaging modalities, such as ultrasound, computed tomography, and magnetic resonance imaging. This scoring system has the potential to help in the precise identification of patients who may benefit from exclusive medical intervention and those who require alternative treatments, thereby enhancing patient care. A standardized lexicon and structured reporting promise to enhance communication between radiologists, referring clinicians, and scientists.

Prognostic Value of Intraplaque Neovascularization Detected by Carotid Contrast-Enhanced Ultrasound in Patients Undergoing Stress Echocardiography.

BACKGROUND: Stress echocardiography (SE) is used for diagnosis and risk stratification of patients with known or suspected coronary artery disease (CAD). Contrast-enhanced ultrasound (CEUS) detects carotid intraplaque neovascularization (IPN). The aim of this study was to test the hypothesis that combining SE with carotid CEUS in patients with known or suspected CAD might provide incremental prognostic value beyond clinical risk factors and either test alone for the occurrence of cardiovascular events. METHODS: One hundred eighty-five patients (mean age, 69 ± 8 years; 79% men) with known or suspected CAD referred for SE and found to have carotid plaque on screening were recruited for carotid CEUS imaging. IPN was graded by presence and location within plaque. Patients were followed for cardiovascular events (CVEs) including cardiac death, myocardial infarction, unstable angina, and transient ischemic attack or stroke. A subset of patients (n = 27) underwent carotid magnetic resonance imaging within 1 month of CEUS; carotid plaque was assessed for lipid-rich necrotic core, loose matrix, and presence of intraplaque hemorrhage. RESULTS: Sixty-nine patients had abnormal findings on SE. IPN was identified in 112 patients; 52 patients had IPN localized to plaque shoulder (IPNS). Plaques with IPNS had larger lipid-rich necrotic cores and were more likely to have intraplaque hemorrhage. During follow-up (median, 31 months), 26 CVEs occurred. Multivariate Cox proportional-hazard analysis showed IPN and IPNS to be predictors of CVEs (hazard ratios, 3.34 [95% CI, 1.25-8.93; P = .02] and 4.88 [95% CI, 1.77-13.49; P = .002], respectively). The presence of IPNS increased the likelihood of CVEs beyond SE and history of CAD (χ2 = 9.0, P = .02). CONCLUSIONS: Carotid IPN detected by CEUS and localized to plaque shoulder was an independent predictor of CVEs in patients referred for SE.

Sex differences in patients with asymptomatic carotid atherosclerotic plaque: in vivo 3.0-T magnetic resonance study.

BACKGROUND AND PURPOSE: Stroke prevention with carotid endarterectomy in asymptomatic men with carotid stenosis is greater than in women. Men have a higher incidence of stroke <75 years of age. Sex differences in plaque characteristics may help explain this, because several plaque features, including a thin/ruptured fibrous cap, larger lipid-rich/necrotic core, and hemorrhage, are associated with increased risk of stroke. We hypothesize that MRI carotid plaque features will demonstrate sex differences indicative of higher-risk plaque in men. METHODS: One hundred thirty-one patients (men, 67; women, 64) with >or=50% asymptomatic carotid stenosis on duplex ultrasound were included. Two blinded reviewers interpreted multicontrast MRI. Presence of a thin/ruptured fibrous cap, plaque components (lipid-rich/necrotic core, hemorrhage, and calcification), and percent component volume were documented. The associations between sex and individual plaque characteristics were examined using logistic and linear regression models (2-part models) controlling for demographic characteristics and MR angiographic findings. RESULTS: Presence of a thin/ruptured fibrous cap (48% versus 17%, adjusted OR=4.41, P<0.01) and lipid-rich/necrotic core (73% versus 50%, adjusted OR=3.66, P=0.01) were more common in men. There was a trend for more highly prevalent hemorrhage (33% versus, 17%, adjusted OR=2.15, P=0.07) in men. Calcification was not significantly associated with sex. Men demonstrated larger volumes of percent lipid-rich/necrotic core (median, 7.7% versus 3.2%, P=0.01), and percent hemorrhage (median, 6.1% versus 1.5%, P<0.01). CONCLUSIONS: In patients with asymptomatic >or=50% carotid stenosis by duplex ultrasound, men had higher-risk plaque features compared with women after controlling for potential confounders. These findings may help explain sex differences in stroke incidence and prevention.

Carotid intraplaque hemorrhage imaging at 3.0-T MR imaging: comparison of the diagnostic performance of three T1-weighted sequences.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

An optimized 3D spoiled gradient recalled echo pulse sequence for hemorrhage assessment using inversion recovery and multiple echoes (3D SHINE) for carotid plaque imaging.

Intraplaque hemorrhage into the carotid atherosclerotic plaque has been shown to create instability and progression. We have developed an optimized 3D Spoiled Gradient recalled echo pulse sequence for Hemorrhage assessment using INversion recovery and multiple Echoes (3D SHINE) for carotid plaque imaging. The sequence was developed by incorporating multiecho acquisition to its clinically validated optimized single-echo counterpart 3D inversion recovery prepared fast spoiled gradient recalled sequence. With similar scan time (4 min), 3D spoiled gradient recalled echo pulse sequence for hemorrhage assessment using inversion recovery and multiple echoes maintained comparable high-resolution volumetric coverage, black-blood effect, contrast, signal-to-noise and contrast-to-noise ratios, and similar sensitivity and specificity in detecting whether intraplaque hemorrhage was present on an artery. The multiple echoes acquired with 3D SHINE allowed the estimation of intraplaque hemorrhage T*(2) and then the subsequent characterization of intraplaque hemorrhage (T*(2) for type I < 14 msec, and for type II > 14 msec). The type I intraplaque hemorrhage size estimated by 3D SHINE was significantly and positively correlated with the size estimated manually by an expert reviewer using the histology-validated multicontrast MRI technique (r = 0.836 ± 0.080, p < 0.001). With only one fast sequence, 3D SHINE can detect and characterize intraplaque hemorrhage that has previously required a multicontrast approach using a combination of black-blood T(1)-weighted, black-blood T(2)-weighted, and time-of-flight imaging techniques.

MR imaging of vulnerable carotid plaque.

Current risk stratification for stroke is still based upon percentage of carotid stenosis, despite this measure providing minimal patient-specific information on the actual risk of stroke for both symptomatic individuals without significant carotid artery stenosis as well as asymptomatic carotid stenosis patients. A continuously growing body of literature suggests that the identification and quantification of certain carotid plaque characteristics, including lipid-rich necrotic core (LRNC), thin/ruptured fibrous cap (FC), and intraplaque hemorrhage (IPH), provide a superior means of predicting future stroke. These characteristics are identifiable via magnetic resonance imaging (MRI), with most features detectable using commercially available coils and sequences utilized in routine clinical practice in as little as 4 minutes. The presence of LRNC, a thin/ruptured FC, and IPH is associated with increased risk of future stroke or TIA. Plaques with greater than 40% LRNC with a thin overlying FC are prone to rupture. LRNC is T2 hypointense and lacks enhancement on contrast enhanced T1 weighted images. Increasing LRNC size is associated with the development of new ulceration, FC rupture, increasing plaque burden, as well as fatal and nonfatal myocardial infarction, ischemic stroke, hospitalization for acute coronary syndrome (ACS), and symptom-driven revascularization, allowing for MR biomarkers of carotid plaque vulnerability to be utilized for systemic athero-thrombotic risk and not just stroke/TIA. LRNC typically shrinks with appropriate statin therapy, with PCSK9 inhibitors possibly playing a role in patients with inadequate response. Carotid plaques with IPH represent a more advanced stage of atherosclerotic disease. IPH is detectable with field strengths of both 3.0 T and 1.5 T and will demonstrate high signal on all T1 weighted imaging sequences. The presence of IPH increases the risk of future stroke in both symptomatic and asymptomatic patients, with multivariate analysis identifying IPH as a predictor of stroke, independent of percent stenosis, with no statistical difference in men vs. women, demonstrating that simple carotid stenosis measurements and traditional risk factor analysis may be inadequate in identifying patients at the highest risk for adverse cerebrovascular events. In the evaluation for recurrent stroke in recently symptomatic patients with >50% carotid stenosis, the estimated annual stroke risk is 23.2% in IPH+ patients and only 0.6% in IPH- patients, calling into question the current risk-benefit assessment for CEA. Additionally, a recent meta-analysis suggests that IPH+ plaque in patients with symptomatic <50% stenosis may be the etiology of embolic strokes previously labeled as "embolic stroke of undetermined source" (ESUS). There are no prospective drug trials testing the ability of any lipid-lowering therapies to decrease IPH and/or total plaque volume (TPV). Given the continuously increasing evidence of IPH as a significant predictor of carotid plaque progression and future adverse vascular events, trials aimed at targeted therapy for IPH represents a significant need.

Computational Modeling of Carotid Bruits.

The sound generated by diseased carotid arteries was investigated through computational means using three-dimensional, idealized, stenosed carotid bifurcation models. Stenosis levels of 50% and 70% with axi-symmetric and asymmetric stenosis shapes were considered. The hemodynamic flow field was obtained by solving the incompressible, Navier-Stokes equations. The resulting pressure fluctuations at the vessel walls were then used as input for a linearized wave equation for the propagation of vibrations through the modeled surrounding tissue. As observed in prior studies, the sound spectra obtained at the tissue surface indicate a 'break frequency', i.e. a frequency beyond which there is a drop-off in sound spectra intensity. This frequency was found to scale with stenosis diameter and average velocity at the stenosis throat, provided the stenosis shape remained the same. This has important implications on past attempts to estimate stenosis diameter from the break frequency.

Author Correction: Combined spatiotemporal and frequency-dependent shear wave elastography enables detection of vulnerable carotid plaques as validated by MRI.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Combined spatiotemporal and frequency-dependent shear wave elastography enables detection of vulnerable carotid plaques as validated by MRI.

Fatal cerebrovascular events are often caused by rupture of atherosclerotic plaques. However, rupture-prone plaques are often distinguished by their internal composition rather than degree of luminal narrowing, and conventional imaging techniques might thus fail to detect such culprit lesions. In this feasibility study, we investigate the potential of ultrasound shear wave elastography (SWE) to detect vulnerable carotid plaques, evaluating group velocity and frequency-dependent phase velocities as novel biomarkers for plaque vulnerability. In total, 27 carotid plaques from 20 patients were scanned by ultrasound SWE and magnetic resonance imaging (MRI). SWE output was quantified as group velocity and frequency-dependent phase velocities, respectively, with results correlated to intraplaque constituents identified by MRI. Overall, vulnerable lesions graded as American Heart Association (AHA) type VI showed significantly higher group and phase velocity compared to any other AHA type. A selection of correlations with intraplaque components could also be identified with group and phase velocity (lipid-rich necrotic core content, fibrous cap structure, intraplaque hemorrhage), complementing the clinical lesion classification. In conclusion, we demonstrate the ability to detect vulnerable carotid plaques using combined SWE, with group velocity and frequency-dependent phase velocity providing potentially complementary information on plaque characteristics. With such, the method represents a promising non-invasive approach for refined atherosclerotic risk prediction.