Atherosclerotic carotid plaque characteristics vary with time from ischemic event: A multicenter, prospective magnetic resonance vessel wall imaging registry study.

Recent studies report that the rate of recurrent stroke is highest in the stages immediately following cerebral infarction and decreases over time in patients with atherosclerotic carotid stenosis. The purpose of this study was to identify temporal differences in early stage carotid plaque components from acute cerebrovascular ischemic events using carotid MRI. Carotid plaque images were obtained on 3 T MRI from 128 patients enrolled in MR-CAS. Among the 128 subjects, 53 were symptomatic and 75 asymptomatic. The symptomatic patients were classified into three groups based on interval from onset of symptoms to the date of the carotid MRI (Group <14 days; 15-30 days; and > 30 days). The volume of each plaque component was identified and quantified from MR images. The presence of juxtaluminal loose matrix/inflammation (LM/I) was identified as a possible indicator of inflammation on the luminal side. Plaque components were compared between groups using the Wilcoxon rank-sum or the Chi-square test. Patient characteristics and carotid plaque morphology were similar among all four groups. The median volume of LM/I in Group >30 days was significantly lower than in other groups (0 mm3 vs 12.3 mm3 and 18.1 mm3; p = 0.003). In addition, the prevalence of juxtaluminal LM/I decreased over time (ptrend = 0.002). There were no statistically significant differences in other plaque components between the symptomatic groups. The volume of LM/I was significantly smaller in Group >30 days and prevalence of juxtaluminal LM/I in the atherosclerotic carotid plaque was high in the early stages after events. This suggests that carotid plaques undergo rapid evolution after an acute cerebrovascular ischemic event.

Evaluation of 3D multi-contrast carotid vessel wall MRI: a comparative study.

BACKGROUND: Conventional reference multi-contrast black-blood (BB) MRI can be used for measuring luminal stenosis severity and plaque components, and its performance has been validated by intra- and inter-reader reproducibility test and histology. Recently, a set of 3D multi-contrast BB sequences have been developed, but its accuracy and reliability have not been well investigated. In this study, we evaluated the performance of 3D multi-contrast MRI (3D-MERGE, T2-VISTA, and SNAP) by comparing it with reference multi-contrast vessel wall MRI and assessing the inter-reader reproducibility. METHODS: In total, 27 patients were recruited in this study. Twenty-six participants underwent reference and 3D multi-contrast imaging in a 3.0T MR scanner. One participant underwent carotid endarterectomy (CEA) after 3D MR imaging. Two trained reviewers interpreted reference and 3D datasets. Lumen area (LA), wall area (WA), normalized wall index (NWI), maximum wall thickness (MaxWT), and mean wall thickness (MWT) were measured, and the presence of lipid-rich necrotic core (LRNC), intra-plaque hemorrhage (IPH) and calcification (CA) were identified. Inter-reader reproducibility of 3D interpretation was assessed. RESULTS: 3D imaging provided comparable measurements with reference imaging in LA (43.81±25.74 vs. 43.35±24.66 mm2) and MaxWT (1.65±1.33 vs. 1.62±1.10 mm), with a lower NWI (0.40±0.15 vs. 0.43±0.11), WA (29.40±21.92 vs. 30.64±16.17 mm2) and MWT (1.09±0.69 vs. 1.14±0.47), and showed good agreement for identification of LRNC (κ=0.66, 95% CI: 0.30-1.00) and CA (κ=0.69, 95% CI: 0.42-0.97), and excellent agreement for IPH (κ=1.00, 95% CI: 1.00-1.00). Inter-reader agreement of 3D analysis was good (LRNC, κ=0.87, 95% CI: 0.61-1.00; CA, κ=0.66, 95% CI: 0.36-0.96; IPH, κ=1.00, 95% CI: 1.00-1.00). CONCLUSIONS: 3D multi-contrast vessel wall imaging provides comparable performance in morphological measurements and identification of carotid plaque components as reference multi-contrast MRI, with good inter-reader reproducibility.

Semiautomatic carotid intraplaque hemorrhage volume measurement using 3D carotid MRI.

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.

Carotid plaque fissure: An underestimated source of intraplaque hemorrhage.

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.

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.

High resolution FDG-microPET of carotid atherosclerosis: plaque components underlying enhanced FDG uptake.

This study sought to discover which atherosclerotic plaque components co-localize with enhanced [(18)F]-fluorodeoxyglucose (FDG) uptake in carotid positron emission tomography (PET) images. Although in vivo PET currently lacks the resolution, high-resolution ex vivo FDG-microPET with histology validation of excised carotid plaque might accomplish this goal. Thirteen patients were injected with FDG before carotid endarterectomy. After excision, the plaque specimens were scanned by microPET and magnetic resonance imaging, and then serially sectioned for histological analysis. Two analyses were performed using generalized linear mixed models: (1) a PET-driven analysis which sampled high and low FDG uptake areas from PET images to identify their components in matched histology specimens; and (2) a histology-driven analysis where specific plaque components were selected and matched to corresponding PET images. In the PET-driven analysis, regions of high FDG uptake were more likely to contain inflammatory cells (p < 0.001) and neovasculature (p = 0.008) than regions of low FDG uptake. In the histology-driven analysis, regions with inflammatory cells (p = 0.001) and regions with loose extracellular matrix (p = 0.001) were associated with enhanced FDG uptake. Furthermore, areas of complex inflammatory cell infiltrate (co-localized macrophages, lymphocytes and foam cells) had the highest FDG uptake among inflammatory subgroups (p < 0.001). In conclusion, in carotid plaque, regions of inflammatory cell infiltrate, particularly complex one, co-localized with enhanced FDG uptake in high-resolution FDG-microPET images. Loose extracellular matrix and areas containing neovasculature also produced FDG signal. This study points to the potential ability of FDG-PET to detect the cellular components of the vulnerable plaque.

Simultaneous noncontrast angiography and intraplaque hemorrhage (SNAP) imaging for carotid atherosclerotic disease evaluation.

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.

Quantitative evaluation of high intensity signal on MIP images of carotid atherosclerotic plaques from routine TOF-MRA reveals elevated volumes of intraplaque hemorrhage and lipid rich necrotic core.

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.

Improved carotid intraplaque hemorrhage imaging using a slab-selective phase-sensitive inversion-recovery (SPI) sequence.

Intraplaque hemorrhage in atherosclerotic plaques has been associated with accelerated plaque growth as well as exacerbation of clinical symptoms. The identification of intraplaque hemorrhage using magnetic resonance imaging primarily relies on the detection of methemoglobin on T(1) weighted images. Current techniques are limited by insufficient intraplaque hemorrhage-wall contrast and poor blood suppression. In this study, a slab-selective phase-sensitive inversion-recovery (SPI) technique is proposed by combining a phase-sensitive reconstruction with a T(1) weighted sequence specifically designed to achieve improved intraplaque hemorrhage imaging. The SPI sequence was optimized and then used on ex vivo plaque specimens for histology based validation and intraplaque hemorrhage-wall contrast-to-noise ratio comparison with magnetization-prepared 3D rapid acquisition gradient echo MP-RAGE. SPI and MP-RAGE were also tested on a group of atherosclerosis patients to compare in vivo intraplaque hemorrhage-wall contrast-to-noise ratio and blood suppression effectiveness. On ex vivo specimens SPI had better intraplaque hemorrhage identification accuracy and a significantly higher intraplaque hemorrhage-wall contrast-to-noise ratio (P = 0.01) than MP-RAGE. Similar results were found in the in vivo test: Slab-selective phase-sensitive inversion-recovery provided a significantly improved intraplaque hemorrhage-wall contrast-to-noise ratio (P < 0.01) and blood suppression efficiency (P < 0.01). In conclusion, SPI is a novel technique optimized for intraplaque hemorrhage detection and validated against histology. It has demonstrated its capability for improved in vivo intraplaque hemorrhage identification and blood suppression in atherosclerosis patients.

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.

Cardiovascular magnetic resonance in carotid atherosclerotic disease.

Atherosclerosis is a chronic, progressive, inflammatory disease affecting many vascular beds. Disease progression leads to acute cardiovascular events such as myocardial infarction, stroke and death. The diseased carotid alone is responsible for one third of the 700,000 new or recurrent strokes occurring yearly in the United States. Imaging plays an important role in the management of atherosclerosis, and cardiovascular magnetic resonance (CMR) of the carotid vessel wall is one promising modality in the evaluation of patients with carotid atherosclerotic disease. Advances in carotid vessel wall CMR allow comprehensive assessment of morphology inside the wall, contributing substantial disease-specific information beyond luminal stenosis. Although carotid vessel wall CMR has not been widely used to screen for carotid atherosclerotic disease, many trials support its potential for this indication. This review summarizes the current state of knowledge regarding carotid vessel wall CMR and its potential clinical application for management of carotid atherosclerotic disease.

The added value of longitudinal black-blood cardiovascular magnetic resonance angiography in the cross sectional identification of carotid atherosclerotic ulceration.

BACKGROUND: Carotid atherosclerotic ulceration is a significant source of stroke. This study evaluates the efficacy of adding longitudinal black-blood (BB) cardiovascular magnetic resonance (CMR) angiography to cross-sectional CMR images in the identification of carotid atherosclerotic ulceration. METHODS: Thirty-two subjects (30 males and two females with ages between 48 and 83 years) scheduled for carotid endarterectomy were imaged on a 1.5T GE Signa scanner using multisequence [3D time-of-flight, T1, proton density, T2, contrast enhanced T1], cross-sectional CMR images and longitudinal BB CMR angiography (0.625 x 0.625 mm/pixel). Two rounds of review (round 1: cross-sectional CMR images alone and round 2: cross-sectional CMR images plus longitudinal BB CMR angiography) were conducted for the presence and volume measurements of ulceration. Ulceration was defined as a distinct depression into the plaque containing blood flow signal on cross-sectional CMR and longitudinal BB CMR angiography. RESULTS: Of the 32 plaques examined by histology, 17 contained 21 ulcers. Using the longitudinal BB CMR angiography sequence in addition to the cross-sectional CMR images in round 2, the sensitivity improved to 80% for ulcers of at least 6 mm3 in volume by histology and 52.4% for all ulcers, compared to 30% and 23.8% in round 1, respectively. There was a slight decline in specificity from 88.2% to 82.3%, though both the positive and negative predictive values increased modestly from 71.4% to 78.6% and from 48.4% to 58.3%, respectively. CONCLUSION: The addition of longitudinal BB CMR angiography to multisequence cross-sectional CMR images increases accuracy in the identification of carotid atherosclerotic ulceration.

Magnetic [corrected] resonance imaging [corrected] features of the disruption-prone and the disrupted carotid plaque.

Stroke is a leading cause of long-term disability and is the third most common cause of death in the U.S. and western countries. Twenty percent of strokes are thought to arise from the carotid artery. Histopathological studies have suggested that plaque disruption is a key factor in the etiology of carotid-related ischemic events. Features associated with plaque disruption include intraplaque hemorrhage, large necrotic cores with thin overlying fibrous caps, plaque neovasculature, and inflammatory cell infiltrate. In vivo high-spatial-resolution, multicontrast-weighted cardiac magnetic resonance (CMR) has been extensively evaluated using histology as the gold standard, and has documented reliability in the identification of these key carotid plaque features. This pictorial essay illustrates the capability of CMR for identifying features of disruption-prone and disrupted atherosclerotic carotid plaques.

An optimized 3D inversion recovery prepared fast spoiled gradient recalled sequence for carotid plaque hemorrhage imaging at 3.0 T.

An optimized 3D inversion recovery prepared fast spoiled gradient recalled sequence (IR FSPGR) on a 3-T scanner for carotid plaque imaging is described. It offers clear blood and fat signal suppression at the carotid artery bifurcation and highlights the regions of carotid plaque affected by hemorrhage at 3 T with high contrast and contrast-to-noise ratio compared with other sequences. It can potentially be used to replace the more traditional noncontrast T(1)-weighted 2D black-blood imaging for hemorrhage detection and offers additional benefits of high-resolution 3D volumetric visualization.

Plaque rupture in the carotid artery is localized at the high shear stress region: a case report.

BACKGROUND AND PURPOSE: Cerebrovascular events are related to atherosclerotic disease in the carotid arteries and are frequently caused by rupture of a vulnerable plaque. These ruptures are often observed at the upstream region of the plaque, where the wall shear stress (WSS) is considered to be highest. High WSS is known for its influence on many processes affecting tissue regression. Until now, there have been no serial studies showing the relationship between plaque rupture and WSS. Summary of Case- We investigated a serial MRI data set of a 67-year-old woman with a plaque in the carotid artery at baseline and an ulcer at 10-month follow up. The lumen, plaque components (lipid/necrotic core, intraplaque hemorrhage), and ulcer were segmented and the lumen contours at baseline were used for WSS calculation. Correlation of the change in plaque composition with the WSS at baseline showed that the ulcer was generated exclusively at the high WSS location. CONCLUSIONS: In this serial MRI study, we found plaque ulceration at the high WSS location of a protruding plaque in the carotid artery. Our data suggest that high WSS influences plaque vulnerability and therefore may become a potential parameter for predicting future events.

The vulnerable, or high-risk, atherosclerotic plaque: noninvasive MR imaging for characterization and assessment.

"Vulnerable" plaques are atherosclerotic plaques that have a high likelihood to cause thrombotic complications, such as myocardial infarction or stroke. Plaques that tend to progress rapidly are also considered to be vulnerable. Besides luminal stenosis, plaque composition and morphology are key determinants of the likelihood that a plaque will cause cardiovascular events. Noninvasive magnetic resonance (MR) imaging has great potential to enable characterization of atherosclerotic plaque composition and morphology and thus to help assess plaque vulnerability. A classification for clinical, as well as pathologic, evaluation of vulnerable plaques was recently put forward in which five major and five minor criteria to define vulnerable plaques were proposed. The purpose of this review is to summarize the status of MR imaging with regard to depiction of the criteria that define vulnerable plaques by using existing MR techniques. The use of MR imaging in animal models and in human disease in various vascular beds, particularly the carotid arteries, is presented.

MRI of atherosclerosis in clinical trials.

Magnetic resonance imaging (MRI) of the arterial wall has emerged as a viable technology for characterizing atherosclerotic lesions in vivo, especially within carotid arteries and other large vessels. This capability has facilitated the use of carotid MRI in clinical trials to evaluate therapeutic effects on atherosclerotic lesions themselves. MRI is specifically able to characterize three important aspects of the lesion: size, composition and biological activity. Lesion size, expressed as a total wall volume, may be more sensitive than maximal vessel narrowing (stenosis) as a measure of therapeutic effects, as it reflects changes along the entire length of the lesion and accounts for vessel remodeling. Lesion composition (e.g. lipid, fibrous and calcified content) may reflect therapeutic effects that do not alter lesion size or stenosis, but cause a transition from a vulnerable plaque composition to a more stable one. Biological activity, most notably inflammation, is an emerging target for imaging that is thought to destabilize plaque and which may be a systemic marker of vulnerability. The ability of MRI to characterize each of these features in carotid atherosclerotic lesions gives it the potential, under certain circumstances, to replace traditional trials involving large numbers of subjects and hard end-points--heart attacks and strokes--with smaller, shorter trials involving imaging end-points. In this review, the state of the art in MRI of atherosclerosis is presented in terms of hardware, image acquisition protocols and post-processing. Also, the results of validation studies for measuring lesion size, composition and inflammation will be summarized. Finally, the status of several clinical trials involving MRI of atherosclerosis will be reviewed.

Inflammation in carotid atherosclerotic plaque: a dynamic contrast-enhanced MR imaging study.

PURPOSE: To prospectively evaluate if there is an association between plaque enhancement at magnetic resonance (MR) imaging and proinflammatory cardiovascular risk factors and plaque content. MATERIALS AND METHODS: This study was performed with informed consent, HIPAA compliance, and institutional review board approval. Contrast agent dynamics within carotid plaques were measured in 30 patients (29 men, one woman; mean age, 67.7 years +/- 10.7 [standard deviation]) who were scheduled to undergo carotid endarterectomy. Measurements were based on kinetic modeling of images obtained at 15-second intervals during which a gadolinium-based contrast agent was injected. The time-varying signal intensities within the plaques were used to estimate the fractional plasma volume (vp) and transfer constant (Ktrans) of contrast material into the extracellular space. Pearson correlation coefficients were computed between blinded MR measurements and histologic measurements of plaque composition, including macrophages, neovasculature, necrotic core, calcification, loose matrix, and dense fibrous tissue. Correlation coefficients or mean differences were computed regarding clinical markers of cardiovascular risk. RESULTS: Analyzable MR images and histologic results were obtained in 27 patients. Measurements of Ktrans correlated with macrophage (r = 0.75, P < .001), neovasculature (r = 0.71, P < .001), and loose matrix (r = 0.50, P = .01) content. Measurements of v(p) correlated with macrophage (r = 0.54, P = .004), neovasculature (r = 0.68, P < .001), and loose matrix (r = 0.42, P = .03) content. For clinical parameters, significant associations were correlated with Ktrans only, with decreased high-density lipoprotein levels (r = -0.66, P < .001) and elevated Ktrans measurements in smokers compared with nonsmokers (mean, 0.134 min(-1) vs 0.074 min(-1), respectively; P = .01). CONCLUSION: The correlations between Ktrans and histologic markers of inflammation suggest that Ktrans is a quantitative and noninvasive marker of plaque inflammation, which is further supported by the correlation of Ktrans with proinflammatory cardiovascular risk factors, decreased high-density lipoprotein levels, and smoking.

Comparison of symptomatic and asymptomatic atherosclerotic carotid plaque features with in vivo MR imaging.

PURPOSE: To retrospectively determine if in vivo magnetic resonance (MR) imaging can simultaneously depict differences between symptomatic and asymptomatic carotid atherosclerotic plaque. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained for this HIPAA-compliant study. Twenty-three patients (21 men, two women; mean age, 66.1 years +/- 11.0 [standard deviation]) with unilateral symptomatic carotid disease underwent 1.5-T time-of-flight MR angiography and 1.5-T T1-, intermediate-, and T2-weighted MR imaging. Both carotid arteries were reviewed. One observer recorded quantitative and morphologic information, which included measurement of the area of the lumen, artery wall, and main plaque components; fibrous cap status (thick, thin, or ruptured); American Heart Association (AHA) lesion type (types I-VIII); and location (juxtaluminal vs intraplaque) and type of hemorrhage. Plaques associated with neurologic symptoms and asymptomatic plaques were compared with Wilcoxon signed rank and McNemar tests. RESULTS: Compared with asymptomatic plaques, symptomatic plaques had a higher incidence of fibrous cap rupture (P = .007), juxtaluminal hemorrhage or thrombus (P = .039), type I hemorrhage (P = .021), and complicated AHA type VI lesions (P = .004) and a lower incidence of uncomplicated AHA type IV and V lesions (P = .005). Symptomatic plaques also had larger hemorrhage (P = .003) and loose matrix (P = .014) areas and a smaller lumen area (P = .008). No significant differences between symptomatic and asymptomatic plaques were found for quantitative measurements of the lipid-rich necrotic core, calcification, and the vessel wall or for the occurrence of intraplaque hemorrhage or type II hemorrhage. CONCLUSION: This study revealed significant differences between symptomatic and asymptomatic plaques in the same patient.

Intra- and interreader reproducibility of magnetic resonance imaging for quantifying the lipid-rich necrotic core is improved with gadolinium contrast enhancement.

PURPOSE: To test the hypothesis that intra- and interreader reproducibility for measuring the lipid-rich necrotic core (LR-NC) size is significantly improved with gadolinium (Gd) contrast-enhanced magnetic resonance imaging (CEMRI) compared to non-CEMRI. MATERIALS AND METHODS: Thirty-seven individuals with >50% carotid artery stenosis underwent carotid MRI at 1.5T (pre- and postcontrast T1-weighted (T1W), T2-weighted (T2W), proton density-weighted (PDW), and three-dimensional time-of-flight (TOF) sequences). Two independent readers measured the mean area of the LR-NC from the precontrast images only, followed by a second measurement using the additional postcontrast images. One reader repeated the measurements after an interval of five months. Intra- and interreader reproducibility was analyzed by means of the intraclass correlation coefficient (ICC), coefficient of variation (CV), and standard deviation (SD). RESULTS: The CV decreased from 33.7% to 8.8% for intrareader measurements of the LR-NC, and from 33.5% to 17.6% for interreader measurements. The SD was significantly smaller with CEMRI than with non-CEMRI (P = 0.003 and P = 0.006, respectively). The ICC increased from 0.94 to 0.99 and from 0.85 to 0.93 for the intra- and interreader measurements, respectively. CONCLUSION: Reader reproducibility for in vivo MRI quantification of LR-NC size is significantly improved by the addition of Gd contrast in individuals with >50% carotid stenosis.