HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Figures Only Full Text (PDF) All Versions of this Article: 2212001612v1 221/2/285    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yuan, C. Articles by Maravilla, K. R. Search for Related Content PubMed PubMed Citation Articles by Yuan, C. Articles by Maravilla, K. R.

Carotid Atherosclerotic Plaque: Noninvasive MR Characterization and Identification of Vulnerable Lesions¹

¹ From the Departments of Radiology (C.Y., L.M.M., K.R.M.) and Surgery (K.W.B.), University of Washington, Box 357115, Seattle, WA 98195. Received October 2, 2000; revision requested November 16; final revision received March 12, 2001; accepted March 29. Address correspondence to C.Y. (e-mail: cyuan@u.washington.edu).

	ABSTRACT

TOP ABSTRACT INTRODUCTION ATHEROSCLEROSIS AND THE CONCEPT... CAROTID US MR IMAGING CHARACTERIZATION OF... TECHNICAL ASPECTS OF CAROTID... REPRODUCIBILITY AND... TESTING PULSE SEQUENCES EX... PRACTICAL APPLICATIONS SUMMARY REFERENCES

 
Measurement of vessel stenosis by using ultrasonography or angiography remains the principal method for determining the severity of carotid atherosclerosis and the need for endarterectomy. The ipsilateral stroke rate, however—even in patients with severely stenotic vessels—is relatively low, which suggests that the amount of luminal narrowing may not represent the optimal means of assessing clinical risk. As a result, some patients may undergo unnecessary surgery. Improved imaging techniques are, therefore, needed to enable reliable identification of high-risk plaques that lead to cerebrovascular events. High-spatial-resolution magnetic resonance (MR) imaging has been described as one promising modality for this purpose, because the technique allows direct visualization of diseased vessel wall and can be used to characterize the morphology of individual atherosclerotic carotid plaques. The purpose of this report is to review the current state of carotid plaque MR imaging and the use of carotid MR to evaluate plaque morphology and composition.

Index terms: Carotid arteries, MR, 172.121411, 172.121412, 172.121417, 172.12143 • Carotid arteries, stenosis or obstruction, 172.721 • Carotid arteries, US, 172.12983 • Magnetic resonance (MR), utilization • Review

	INTRODUCTION

TOP ABSTRACT INTRODUCTION ATHEROSCLEROSIS AND THE CONCEPT... CAROTID US MR IMAGING CHARACTERIZATION OF... TECHNICAL ASPECTS OF CAROTID... REPRODUCIBILITY AND... TESTING PULSE SEQUENCES EX... PRACTICAL APPLICATIONS SUMMARY REFERENCES

 
Stroke is a serious public health problem, representing the leading cause of death (4.4 million deaths per year) and disability (affecting 5,000 per million persons) worldwide. In the United States, approximately 750,000 strokes occur each year, and although one-third of these patients die, one-half of the survivors are left with a disability. These numbers place U.S. estimates of the annual direct and indirect costs of the disease near $40 billion (1–3) and suggest the tremendous impact that improved methods for the diagnosis and treatment of stroke would have on the personal and public health burden caused by the disease.

Of the different causes of stroke, recent attention has been given to carotid atherosclerosis because the authors of randomized trials have reported the efficacy of carotid endarterectomy compared with medical treatment in patients with extracranial carotid artery stenosis. For example, in patients with a recent transient ischemic attack or nondisabling stroke, the North American Symptomatic Carotid Endarterectomy Trial and European Carotid Surgery Trial have provided evidence of the benefit of carotid endarterectomy in those symptomatic patients who were found to have a carotid artery stenosis that reduced the diameter of the diseased vessel by greater than 70% of the estimated normal luminal caliber (4,5). In asymptomatic patients, however, the results of similar large clinical trials are less clear. While several groups have reported no benefit from carotid endarterectomy (Mayo Asymptomatic Carotid Endarterectomy Trial, Canadian Stroke Consortium, Veterans Affairs Cooperative Study Group), the Asymptomatic Carotid Atherosclerosis Study reported that endarterectomy for asymptomatic stenoses greater than 60% reduced the 5-year ipsilateral stroke rate from 11.0% (medical group) to 5.1% (6,7).

In addition to these conflicting findings, several concerns have been raised since publication of the results from these large trials. The trials were conducted without the medical therapies that are currently available (7,8). Some question whether the surgical complication rates (3%–6%) achieved at these trial centers can be realized in general practice (6). Furthermore, the conclusions drawn from these trials are based on angiographic measures of atherosclerotic disease severity, which can be discrepant when determined with different techniques, do not correlate well with clinical symptoms, and are complicated by the presence of plaque ulceration and/or vessel wall remodeling (3,9,10).

Given that approximately 140,000 carotid endarterectomies are performed each year in the United States and that potentially 60% are performed in asymptomatic patients (6), these controversies highlight the need for better methods of assessing the severity of carotid atherosclerosis to improve both our understanding of the pathogenesis of the disease and our ability to select the optimal therapeutic intervention for the individual patient (7). Recently, there has been growing interest in endovascular revascularization techniques such as carotid angioplasty and stent placement. The efficacy of these invasive treatments for carotid stenoses, however, has not been proved, to our knowledge. Imaging techniques that characterize plaque morphology could be used to indicate those lesions that may be more amendable to endovascular intervention than to endarterectomy (7).

Early studies performed to elucidate the pathogenesis of acute ischemic syndromes related to coronary atherosclerosis surprisingly revealed that the degree of angiographic stenosis correlated poorly with the site of symptomatic occlusion (11,12). Subsequent histopathologic studies (13) have demonstrated that atherosclerotic disease progression is sporadic and related to plaque fissuring or rupture. Furthermore, the findings showed that the morphology of unstable plaques that were at risk for disruption typically contained a large acellular core that was separated from the lumen by a thin fibrous cap (13). Because plaques in the cervical carotid arteries are histologically similar to those in the coronary circulation, it is believed that similar events underlie the development of neurologic symptoms in patients with asymptomatic carotid arterial disease (14). Because carotid angiography does not demonstrate plaque morphology, with the exception of luminal ulceration (15), and the degree of stenosis is not associated with the presence of intraplaque hemorrhage or a necrotic core (16), noninvasive techniques that allow visualization of the carotid vessel wall are needed.

Currently, the predominant noninvasive imaging modalities being investigated for this purpose are ultrasonography (US) (17) and magnetic resonance (MR) imaging. Although carotid US is the most widely performed noninvasive test in the evaluation of a patient suspected of having carotid arterial disease, the modality is highly operator dependent and presently is not capable of consistent demonstration of plaque morphology (3,17,18). In contrast, a growing number of groups have demonstrated the abilities of high-spatial-resolution MR imaging for evaluation of atherosclerotic plaque composition both ex vivo and in vivo (19–28). The results from these groups demonstrate the potential that MR techniques have for development into a reliable means of characterizing plaque morphology. The primary purpose of this report is to describe the current state of carotid plaque characterization with MR imaging.

	ATHEROSCLEROSIS AND THE CONCEPT OF THE VULNERABLE PLAQUE

TOP ABSTRACT INTRODUCTION ATHEROSCLEROSIS AND THE CONCEPT... CAROTID US MR IMAGING CHARACTERIZATION OF... TECHNICAL ASPECTS OF CAROTID... REPRODUCIBILITY AND... TESTING PULSE SEQUENCES EX... PRACTICAL APPLICATIONS SUMMARY REFERENCES

 
Atherosclerosis, a disease of large and medium-sized arteries, is characterized by progressive intimal accumulation of lipid, protein, and cholesterol esters (29). Although considered to be a systemic disease, it has a propensity for segmental distribution and is found most commonly at major arterial bifurcations and at points of marked arterial angulation. Predominant sites of involvement include the coronary arteries, superficial femoral artery, infrarenal aorta, and carotid arteries at the area of the common carotid artery bifurcation (30).

Traditionally, the degree of luminal stenosis has been used as a measure of atherosclerotic disease severity. In 1988, however, Ambrose et al (11) and Little et al (12) demonstrated in angiographic studies that mild to moderate coronary artery stenosis may lead to acute myocardial infarction and suggested that luminal narrowing was not the sole predictor of clinical sequelae. Subsequent histopathologic study results then showed that plaque erosion and disruption were common morphologic features found in symptomatic lesions (31,32). For example, Falk (13) noted that more than 75% of major coronary thrombotic events were precipitated by atherosclerotic plaque rupture that exposed thrombogenic subendothelial plaque constituents to the bloodstream. These findings led to the hypothesis that the clinically recognized ischemic syndromes are the consequence of occlusive or embolic mural thrombi that develop after atherosclerotic plaque rupture.

Fuster et al (31), Bassiouny et al (14), Davies et al (33), and Falk (34) have since proposed that the atherosclerotic lesions that are at risk for rupture and the development of clinical symptoms can be identified in terms of their morphology. Although the morphology of these advanced plaques is complicated—such plaques are composed of varying amounts of collagen, smooth muscle cells, proteoglycans, extracellular lipids, cholesterol monohydrate crystals, thrombus, and calcifications—vulnerable lesions are typically described as containing a large necrotic core or intraplaque hemorrhage that is separated from the lumen by an unstable fibrous cap (14,33,34). Others, however, have described additional morphologic features that may be associated with plaque instability: (a) endothelial erosion of proteoglycan-rich areas (35), (b) a high concentration of cholesterol esters relative to the amount of insoluble cholesterol monohydrate crystals in the lipid core (36,37), and (c) inflammatory cell infiltration of the fibrous cap (38). The two predominant features of lesions that are at risk of rupturing, though, are the presence of a large soft core and the state of the fibrous cap, which could be intact, thin, disrupted, or infiltrated by inflammatory cells.

These histopathologic findings provide important biologic end points that could serve as measures of disease severity and clinical risk. The primary limitation of angiography is that the diseased vessel wall could compensate for a large carotid plaque by means of outward expansion of the adventitial boundary. Consequently, a large, complicated, and potentially unstable plaque may not compromise the lumen by an amount that would be considered a significant stenosis (39,40). This realization has created tremendous interest in the development of noninvasive methods that can help (a) quantify total plaque volume (disease burden) by using methods that do not depend on the size of the residual lumen and (b) reliably identify the morphologic features of the vulnerable plaque. Although still relatively new, success in this active area of research could have a tremendous impact on the diagnosis and management of cardiovascular disease (41,42).

	CAROTID US

TOP ABSTRACT INTRODUCTION ATHEROSCLEROSIS AND THE CONCEPT... CAROTID US MR IMAGING CHARACTERIZATION OF... TECHNICAL ASPECTS OF CAROTID... REPRODUCIBILITY AND... TESTING PULSE SEQUENCES EX... PRACTICAL APPLICATIONS SUMMARY REFERENCES

 
Doppler US has come into widespread use for classification of carotid stenoses since 1975, when a quantitative examination protocol was developed that is now nearly universal (43–45). With the parallel development of real-time two-dimensional B-mode US, beginning in around 1975, many investigators have attempted to develop US methods for measuring atherosclerotic plaque size, cap size, and wall thickness and for identifying plaque contents and ulceration.

Only one B-mode technique has gained widespread acceptance: measurement of the intima-media thickness in the common carotid artery (46). The intima-media thickness measurement technique has been used in a number of epidemiologic trials (47–50). By using ultrasound wavelengths of 200 µm (7.5 MHz), thicknesses from 200 to 2,000 µm can be measured. Although an increased common carotid intima-media thickness has been correlated with an increased risk of coronary artery disease, it has not been useful in evaluating carotid atherosclerosis.

Analysis of US images and echoes from carotid atherosclerotic stenoses have been used to differentiate "unstable plaque" from "stable plaque." Unstable plaque is defined as plaque that is associated with a patient’s past neurologic symptoms. The classification is intended for use as a predictor of future neurologic symptoms originating from the plaque. Plaque stability is thought to be related to plaque composition or to plaque motion during the cardiac cycle. Identified plaque constituents include calcium, hemorrhage, necrosis, lipid, and fibrous tissue. Discrimination between plaque materials has been based on the echogenicity of the plaque, as determined with mean pixel brightness on B-mode US images of the carotid artery (51); median pixel brightness (52); integrated backscatter of the radio-frequency echo; and the echo attenuation rate at different frequencies in endarterectomy samples (53–56) and pathologic samples (57) and on carotid artery images (58–61). Intravascular US images of pathologic samples have also been analyzed (62).

Calcium in plaques causes "bright" (hyperechoic) echoes at US with shadowing of echoes deep to the plaque, which could markedly limit the detection of plaque components (63). Fibrous plaques were associated with strong echoes, and hemorrhage was associated with weak echoes (64). Fibrous plaques exhibit higher echogenicity that is dependent on the incident angle of the ultrasound beam (65), implying an ordered structure in such tissues. Tissues with high elastin content produce strong echoes (66). It is generally agreed that unstable plaques are likely to have hypoechoic regions (67,68) or low ultrasound echogenicity (52,61,69).

Visual analysis of plaque appearance on B-mode US images has been the basis of most plaque characterization efforts; however, intra- and interobserver variability has been large in studies with this method (70–72), which makes the use of standardized methods between centers difficult (73). Variability between examinations can be reduced by quantitatively comparing plaque echogenicity on the image with that of nearby reference tissues such as blood and adventitia, which have known echogenicities—a technique only recently developed (74). Some authors are satisfied with their ability to reliably discriminate between plaque types (75–79). However, the overall result is that identification of unstable plaques with noninvasive B-mode US "has been largely unsuccessful" (80).

	MR IMAGING CHARACTERIZATION OF HUMAN CAROTID PLAQUE MORPHOLOGY

TOP ABSTRACT INTRODUCTION ATHEROSCLEROSIS AND THE CONCEPT... CAROTID US MR IMAGING CHARACTERIZATION OF... TECHNICAL ASPECTS OF CAROTID... REPRODUCIBILITY AND... TESTING PULSE SEQUENCES EX... PRACTICAL APPLICATIONS SUMMARY REFERENCES

 
The signal intensities on an MR image reflect the biochemical environment of protons in the tissue of interest. This allows tremendous flexibility in the design of imaging sequences and parameters, which can be adjusted to optimize the conspicuity of specific tissue types. With MR, it is possible to acquire a three-dimensional (3D) data set that provides reproducible quantitative tissue information from isotropic voxels. MR techniques are not dependent on the angle of the imaging plane and are less dependent on the skill of the operator than is US. For the purposes of vascular imaging, MR is unique in that the modality can provide excellent contrast between the vessel wall and adjacent lumen by using flow-sensitive pulse sequences. Thus, MR can be used to image the vessel lumen (flowing blood) and, at the same time, produce tissue information that describes the vessel wall. These features of MR imaging provide important advantages for the development of the modality as a means of noninvasive characterization of plaque morphology to help prospectively identify the unstable lesion and be used in serial studies investigating factors involved in the progression or regression of the disease.

As previously described, the typical morphology of the vulnerable plaque consists of a large necrotic core separated from the lumen by an unstable fibrous cap, which may be thin, ulcerated, fissured, or infiltrated by macrophages. Thus, the initial appeal of MR techniques for imaging atherosclerosis was its theoretical ability to demonstrate the lipids present in the soft core. Early work focused on the detection of lipid signals by using T1-weighted and chemical-selective techniques (21,81–83). The predominant lipids of atherosclerotic lesions are cholesterol and cholesteryl esters (84), rather than triglycerides. Because these lipids have a short T2, the initial attempts at plaque imaging produced limited success. Inclusion of sequences that were T2 weighted and T1 or intermediate weighted with a very short echo time improved the specificity of MR imaging techniques and allowed differentiation of necrotic cores from fibrous regions in ex vivo plaque specimens (19,24). As more experience was obtained, additional contrast weightings such as 3D time-of-flight (TOF) (85), magnetization transfer (86,87), and diffusion-sensitive (28,88) sequences were tested and have been found to facilitate atherosclerotic tissue characterization. Figure 1 illustrates the ability of T2-weighted imaging to noninvasively depict the presence of a lipid core and a thrombus that were confirmed histologically.

View larger version (86K): [in this window] [in a new window] [Download PPT slide]   Figure 1. In vivo transverse T2-weighted fast SE MR imaging of a left internal carotid artery. Plaque characterization was based on information obtained from T1-, intermediate-, and T2-weighted MR images. Left: T2-weighted MR image (repetition time, two R-R intervals; echo time, 55 msec; 3-mm section thickness; 450-µm in-plane resolution) shows low-signal-intensity lipid core (lc), high-signal-intensity fibrous cap (fc), and very high-signal-intensity thrombus (t). l = arterial lumen. Right: Corresponding histopathologic section. fc = fibrous cap, l = arterial lumen, lc = lipid core, t = thrombus. (Mason-eosin stain; original magnification, x10.) (Reprinted, with permission, from reference 26.)

View larger version (135K): [in this window] [in a new window] [Download PPT slide]   Figure 2. Human carotid endarterectomy cross section. A, Low-magnification photomicrograph of histopathologic section shows the lumen (L) and regions of calcification (C), fibrocellular tissue (F), and necrotic lipid-rich core (G). (Hematoxylin-eosin [H&E] stain; original magnification, x10.) B-L, MR images acquired with a 12.4-mm field of view, 256 x 256 matrix, 500-µm section thickness, and 48-µm in-plane resolution. TE = echo time (in milliseconds), TR = repetition time (in milliseconds). Images in B-D and F-H are were acquired with a SE sequence. Image in E is diffusion weighted (b = 1,766 sec/mm2). Image in I is the segmented image created from the MR criteria by using a semiautomated routine developed for this study. Images in J-L are parametric images of the calculated apparent diffusion coefficient (J), T2 (K), and T1 (L) maps for this cross section. In I, purple represents regions of calcification; green, fibrocellular tissue; yellow, lipid core; black, indeterminate; and white, saline. The area that is clearly lipid core in A shows variability on the MR images. This variability may reflect different levels of cellularity and collagen. E shows, at around 4 to 5 o’clock, a high-signal-intensity area that could be mistaken for thrombus. This area is not hyperintense in D. This highlights the difficulty of tissue identification even with the assistance of histologic examination. (Reprinted, with permission, from reference 28.)

View larger version (83K): [in this window] [in a new window] [Download PPT slide]   Figure 3. Plaque with fibrous cap rupture on gross section, histologic section, and MR images (see Table 2 for imaging parameters). A-C, Three contiguous transverse 3D TOF images of a diseased right common carotid artery. D, Gross section location corresponding to A-C. E, Low-power photomicrograph of a histologic section. (Masson trichrome stain; original magnification, x10.) F, Same MR image as in C. In D and E, there is an area of cap rupture (arrow 1) across from a region where the fibrous cap is thick (arrow 3). The site of cap rupture corresponds to a region where the hypointense band is absent, and a hyperintense region is seen adjacent to the lumen on MR images. The hyperintense region is a region in the plaque core on MR images that corresponds to regions of recent intraplaque hemorrhage on gross and histologic cross sections (arrow 2). The fibrous cap is composed of a dense layer of collagen that appears hypointense in A-C. (Reprinted, with permission, from reference 85.)

In Vivo Accuracy of MR for Identifying Soft Necrotic Cores
In addition to an unstable fibrous cap, a second important morphologic characteristic of the vulnerable plaque is the presence of a large soft core that is composed of an acellular lipid-rich region or hemorrhage (14). The growing experience with multi–contrast-weighted imaging techniques enabled the design of a recent study (91) to evaluate the in vivo accuracy of MR to demonstrate these soft cores in human carotid plaques. For this work, a multi–contrast-weighted MR protocol (3D TOF, DIR, intermediate-weighted, and T2-weighted sequences) was used to obtain carotid images preoperatively in 18 endarterectomy patients. On the basis of the plaque tissue contrast features described in Table 1, lipid-rich necrotic cores were identified as areas of high signal intensity on T1-weighted images, intermediate signal intensity on corresponding 3D TOF images, and variable signal intensity on intermediate- and T2-weighted images. Recent intraplaque hemorrhages were similarly identified in terms of their appearance on multi–contrast-weighted studies (high signal intensity on TOF, intermediate on T1-weighted, and variable on intermediate- and T2-weighted images). The results revealed that the MR findings agreed well with the histologic presence of a necrotic core or recent intraplaque hemorrhage, with a sensitivity of 85%, a specificity of 92%, and a calculated value of 0.69. Figure 4 illustrates the multicontrast appearance of a lipid-rich necrotic core.

View larger version (88K): [in this window] [in a new window] [Download PPT slide]   Figure 4. A-D, Transverse MR images obtained with TOF (A) and T1-weighted (B), intermediate-weighted (C), and T2-weighted (D) fast SE sequences (see Table 2 for parameters) at the same location in a right internal carotid artery demonstrate the contrast features of the large lipid-rich core depicted in the photomicrograph (E) of a histologic specimen. (Mallory trichrome stain; original magnification, x10.) The advanced plaques imaged had complex lipid-rich cores containing a variable amount of extracellular lipid, amorphous debris, cholesterol monohydrate crystals, calcifications, and hemorrhage. In B, the area of high signal intensity (arrow) and, in A, the area of low signal intensity correlate well in size and appearance with the large lipid-rich core that encircles the lumen at this level of the internal carotid artery. The hypointense appearance of the lipid-rich area in D is primarily due to its short T2. In C and D, a region of loose matrix surrounding the lumen is easily identified (arrowhead). Tissue information provided by C and D is similar. In E, the very narrowed lumen (*) can be seen.

	TECHNICAL ASPECTS OF CAROTID PLAQUE MR IMAGING

TOP ABSTRACT INTRODUCTION ATHEROSCLEROSIS AND THE CONCEPT... CAROTID US MR IMAGING CHARACTERIZATION OF... TECHNICAL ASPECTS OF CAROTID... REPRODUCIBILITY AND... TESTING PULSE SEQUENCES EX... PRACTICAL APPLICATIONS SUMMARY REFERENCES

 
The typical in-plane spatial resolution of 1 x 1 mm² obtained with a 1.5-T clinical MR unit for head or body imaging is too large to enable satisfactory detection of the small volumes of the major plaque components present in carotid lesions. For example, evaluation of histologically processed endarterectomy specimens revealed mean values for the volume of individual plaque components (lipid core, fibrous intimal tissue, and calcification) ranging from 0.3 mm³ and larger (92). Although submillimeter voxel sizes can be achieved with whole-body 1.5-T units, the use of a phased-array surface coil appears to be necessary to generate an acceptable signal-to-noise ratio (93) for the high-spatial-resolution images required for carotid plaque characterization. Since high-spatial-resolution imaging sequences may also result in relatively long acquisition times (several seconds to a few minutes), hardware and software techniques that reduce the effects of motion and flow artifacts become important. The following sections describe the hardware considerations and imaging sequences that we have found to be useful for performing diagnostic multi–contrast-weighted MR imaging of the carotid arteries.

Hardware Considerations
For carotid imaging with a 1.5-T whole-body imager, echo-planar capabilities are advantageous because the gradient amplifiers and higher slew rates supported by these systems allow shorter echo times and echo spacing (in fast SE sequences). As described earlier, these features reduce the overall acquisition times of the pulse sequences used and, as a result, minimize the effects of motion and flow artifacts.

The carotid arteries are superficial structures whose length is greater than their distance from the surface. This configuration is well suited for the use of phased-array surface coils, which are composed of several adjacent small surface coils that collect data simultaneously. For the purposes of carotid plaque imaging, a dedicated phased-array coil assembly (94) with overall dimensions of 6.4 x 10.8 cm was constructed. The assembly consists of two separate sets of coils to allow imaging of both carotid arteries during an examination. Each coil is made of a soft flexible material that can be comfortably fitted and secured about the patient’s neck (Fig 5). With this coil assembly, an effective longitudinal coverage of up to 5 cm can be achieved. Studies of the performance of these phased-array coils in healthy volunteers demonstrated a 37% improvement in the signal-to-noise ratio when compared with the performance of commercially available 3-inch-diameter (7.6-cm) surface coils. This greater signal-to-noise ratio enables acquisition of diagnostic images of the common, internal, and external carotid arteries with a best voxel size of 0.25 x 0.25 x 2.0 mm (0.25 cm³). In addition to the carotid phased-array assembly, a custom-designed head holder was constructed with vacuum-formed polyvinyl chloride plastic (Fig 5). The headholder provides support for the occiput and neck, which not only improves patient comfort but also facilitates repeatable positioning and reduces patient movement.

View larger version (124K): [in this window] [in a new window] [Download PPT slide]   Figure 5a. (a) Phased-array coil assembly and (b) head holder for carotid arteries MR imaging. Rulers indicate the relative size of the coils and the head-holder. The shape of the coil surface is designed to touch the patient’s skin.

View larger version (151K): [in this window] [in a new window] [Download PPT slide]   Figure 5b. (a) Phased-array coil assembly and (b) head holder for carotid arteries MR imaging. Rulers indicate the relative size of the coils and the head-holder. The shape of the coil surface is designed to touch the patient’s skin.

Black-blood techniques refer to MR techniques that suppress the signal from flowing blood (96). These sequences are ideal for plaque imaging, because the conspicuity of the vessel wall is increased when adjacent to a hypointense lumen and the echo and repetition times can be varied to optimize visualization of specific plaque components. The major disadvantages of black-blood techniques are relatively long acquisition times and the fact that these sequences are based on acquisition of two-dimensional data with a section thickness that varies between 2 and 5 mm.

Common flow-suppression techniques used with black-blood imaging are the use of (a) presaturation radio-frequency bands applied along the direction of arterial blood flow with an SE sequence or (b) a DIR sequence (97). When presaturation techniques are used, which are less effective than DIR with slowly flowing blood, the complex flow in the carotid bulb (98) often results in artifacts created by unsuppressed flow. Artifacts may be misinterpreted as representing signal from a diseased vessel wall and lead to an overestimation of the size of the atherosclerotic lesion (Fig 6) (99). On the other hand, DIR sequences tend to provide excellent flow suppression, as shown on T1-weighted images (Fig 7) (100). These images typically allow the most accurate quantitative measurements of disease burden and are used to identify soft cores in vivo (91).

View larger version (118K): [in this window] [in a new window] [Download PPT slide]   Figure 6. A-E, Effect of trigger delay on plaque-mimicking flow artifacts (arrows) in the internal carotid artery of a healthy individual. Transverse fast SE MR images were obtained at a location immediately distal from the flow divider. Bottom: Times are identified on the flow waveform measured in the common carotid artery of the same individual, as are the times of the electrocardiographic (ECG) and peripheral gating (PG) triggers. The designations a-e on the waveform correspond to the images in A-E. Q = flow rate. Note the virtual elimination of artifacts in B and C. The vessel at 1 o’clock from the internal carotid artery is a branch of the jugular vein.

View larger version (0K): [in this window] [in a new window] [Download PPT slide]   Figure 7. Permission to reprint this figure electronically was denied by the publisher. Please see print version.

View larger version (146K): [in this window] [in a new window] [Download PPT slide]   Figure 8. Fibrous caps from atherosclerotic common carotid artery in two patients. Transverse T1-weighted fast SE (A) and 3D GRE (B) MR images in one patient. The arrow in B points to a periluminal hypointense band, which indicates the presence of a uniformly thick fibrous cap. (The additional vessel at 1 o’clock in A is a branch of the jugular vein.) T1-weighted fast SE (C) and 3D fast GRE (D) images of the common carotid artery in another patient. The arrow in D points to the lumen boundary, which shows no distinct hypointense band, indicating the absence of a thick fibrous cap. Juxtaluminal calcifications (at 3 and 9-12 o’clock) are seen as dark areas with no visible fibrous caps. The imaging parameters were 9.6/2.2 (repetition time msec/echo time msec); field of view, 13 cm; section thickness, 2 mm with 1-mm section overlap; matrix, 256 x 256.

View larger version (86K): [in this window] [in a new window] [Download PPT slide]   Figure 9. MR images in a patient with moderate carotid stenosis. Left: Oblique fast SE image (600/10; field of view, 20 cm; section thickness, 2 mm; matrix, 256 x 256; with flow suppression) of the left carotid artery shows overall distribution of atherosclerotic plaque (arrow). A, B, Transverse cross-sectional shared-view acquisition with repeated echoes, or SHARE (intermediate- and T2-weighted), images obtained near the carotid bifurcation. C, 3D TOF image of the same location shows both the high-signal-intensity lumen and the plaque (arrow). D, T1-weighted fast SE DIR image of the same location (see Table 2 for imaging parameters of A-D). The lesion is eccentric and was caused a minor luminal stenosis. By comparing black-blood and bright-blood images, one can find at least two distinct tissue regions in the plaque: A region of recent intraplaque hemorrhage (arrows) that is hyperintense in C and D and hypointense in A and B and fibrous tissue (arrowheads) that is hypointense in C and hyperintense in A and B. The tissue contrast in A and B is similar.

Chemical-selective fat saturation is used for all sequences to reduce the signal from the subcutaneous tissues (22,105). Cardiac gating was found to reduce flow and motion artifacts and is incorporated with the long echo time and long repetition time sequences.

	REPRODUCIBILITY AND QUANTIFICATION OF DISEASE BURDEN

TOP ABSTRACT INTRODUCTION ATHEROSCLEROSIS AND THE CONCEPT... CAROTID US MR IMAGING CHARACTERIZATION OF... TECHNICAL ASPECTS OF CAROTID... REPRODUCIBILITY AND... TESTING PULSE SEQUENCES EX... PRACTICAL APPLICATIONS SUMMARY REFERENCES

 
To attain statistical significance, investigations to improve the delineation of clinical risk or assess the efficacy of new interventions typically involve large, multicenter, population-based studies or clinical trials (106,107). Thus, along with the growing evidence that MR imaging can help characterize plaque morphology, studies are also needed to assess the quantitative capabilities and reproducibility of MR techniques before they can be used in such investigations.

Plaque Area and Volume Measurements
Unlike luminal stenosis, plaque volume is considered to be a direct measure of the size and severity of atherosclerotic disease. Because MR imaging can help identify the adventitial boundary on transverse images of the vessel wall, it could provide a means of measuring the total volume of the diseased vessel wall and enable an accurate determination of plaque burden (100).

With the excellent contrast produced between diseased portions of the vessel, the lumen, and the adventitia, initial experiments to evaluate the quantitative capabilities of MR have been based on in vivo measures of plaque burden. In one such study (100), the cross-sectional areas of imaged carotid plaques measured preoperatively were compared with similar area measurements performed on excised endarterectomy specimens imaged ex vivo. A Bland-Altman analysis of the paired in vivo and ex vivo measurements of the same vessel segments demonstrated a strong correlation between the two values. These results provide evidence of the quantitative capabilities of MR imaging for the measurement of total plaque volume and disease burden.

Reproducibility
The ability to acquire serial images of the same segments of a carotid plaque and the reproducibility of quantitative measures of plaque burden obtained at different times were evaluated in two recent experiments (108,109).

By using the carotid bifurcation as an internal landmark, imaging sections of the same vessel segment can be reproducibly obtained at different examination times. A comparison of two images of a patient’s left common carotid artery obtained at different examinations performed on the same day demonstrates the reproducibility of this method of section prescription (Fig 10) (108). A second example (Fig 11) illustrates how these imaging techniques can be used to monitor the morphologic changes that occur in the carotid artery after endarterectomy is performed.

View larger version (51K): [in this window] [in a new window] [Download PPT slide]   Figure 10. A, B, Transverse intermediate-weighted fast SE MR images (see Table 2 for parameters) acquired at two sessions on the same day in a carotid endarterectomy patient before surgery. C, Histologic section demonstrates advanced lesions in the left carotid artery and shows that regions of hemorrhage and calcium, as well as the overall morphology, as depicted on two independent images were highly reproducible. (Hematoxylin-eosin stain; original magnification, x10.)

View larger version (104K): [in this window] [in a new window] [Download PPT slide]   Figure 11. Follow-up transverse T1-weighted fast SE black-blood MR studies in a patient who underwent carotid endarterectomy obtained preoperatively (A) and 1 month (B), 3 months (C), and 6 months (D) after surgery. Eight cross-sectional images show the carotid artery distal to the bifurcation. The long arrows indicate the distal direction from the bifurcation. (A-D) Note the appearance of the plaque (short arrow) in the internal carotid artery at different time points. Follow-up MR images (B-D) at locations that were comparable to those in A and also showed the open lumen after plaque removal. These sets of images clearly demonstrate the ability to use MR to monitor changes in atherosclerotic lesions over time.

	TESTING PULSE SEQUENCES EX VIVO

TOP ABSTRACT INTRODUCTION ATHEROSCLEROSIS AND THE CONCEPT... CAROTID US MR IMAGING CHARACTERIZATION OF... TECHNICAL ASPECTS OF CAROTID... REPRODUCIBILITY AND... TESTING PULSE SEQUENCES EX... PRACTICAL APPLICATIONS SUMMARY REFERENCES

 
One advantage of carotid imaging is the availability of endarterectomy specimens that can be studied ex vivo. A number of analytic methods that rely on ex vivo imaging have been designed to assist the comparison of in vivo MR images and histologic sections (110–113).

3D Imaging
Coombs et al (102) studied the potential benefits of the use of 3D data acquisition techniques to map detailed structures of plaques. This study was conducted with six carotid plaques excised en bloc from patients undergoing endarterectomy. Images with a spatial resolution of 200 x 200 x 200 µm were obtained by using a 3D fast imaging with steady-state precession, or FISP, sequence. As expected, the image contrast and spatial distribution of different tissues was better delineated on 3D FISP images than on two-dimensional images obtained with the same in-plane resolution but with a 2-mm section thickness (Fig 12). The results of this study illustrate the importance of high-spatial-resolution imaging techniques to visualize the fine structure of plaques, and the authors propose the use of isotropic imaging voxels to facilitate comparisons between the MR image features and the histologic sections of a specimen.

View larger version (51K): [in this window] [in a new window] [Download PPT slide]   Figure 12. Comparison of a transverse 0.2-mm-thick 3D GRE MR image (left), a transverse 2-mm-thick two-dimensional GRE image (middle), and a corresponding histologic section (right). (Hematoxylin-eosin stain; original magnification, x10.) The MR images were acquired with a fast inflow with steady-state precession sequence (30/12, 20° flip angle); in-plane resolution was 0.19 x 0.19 mm, and through-plane resolution was 2 mm for the two-dimensional image and 0.19 mm for the 3D image. Note that the 2-mm-thick image (middle) shows an apparently small lumen (due to partial volume thickening of the vessel wall on the right side of the image). Also, the location of calcification on the 3D study (left) correlates much better with that on the histologic section (right).

View larger version (115K): [in this window] [in a new window] [Download PPT slide]   Figure 13a. Distribution of magnetization transfer ratios for ex vivo carotid endarterectomy specimen. Four regions were identified at histologic examination as follows: 1, lumen (saline); 2, fibrin and/or cholesterol; 3, fibrous cap; and 4, necrotic core. (a) These regions were drawn on a 3D TOF MR image (26/3.5, 25° flip angle) of the specimen. (b) For each region, graph shows the distribution of magnetization transfer ratios.

View larger version (27K): [in this window] [in a new window] [Download PPT slide]   Figure 13b. Distribution of magnetization transfer ratios for ex vivo carotid endarterectomy specimen. Four regions were identified at histologic examination as follows: 1, lumen (saline); 2, fibrin and/or cholesterol; 3, fibrous cap; and 4, necrotic core. (a) These regions were drawn on a 3D TOF MR image (26/3.5, 25° flip angle) of the specimen. (b) For each region, graph shows the distribution of magnetization transfer ratios.

	PRACTICAL APPLICATIONS

TOP ABSTRACT INTRODUCTION ATHEROSCLEROSIS AND THE CONCEPT... CAROTID US MR IMAGING CHARACTERIZATION OF... TECHNICAL ASPECTS OF CAROTID... REPRODUCIBILITY AND... TESTING PULSE SEQUENCES EX... PRACTICAL APPLICATIONS SUMMARY REFERENCES

Also in the near future, these imaging techniques may be used in monitoring disease progression in patients at risk for heart attack or stroke. In its present state, carotid MR could be used by vascular surgeons to improve surgical planning, because the distribution and extent of involvement in both the common and internal carotid arteries is better delineated with MR imaging than with angiography. More important, these techniques are currently able to provide morphologic information that can suggest whether a lesion is unstable, regardless of the degree of stenosis.

Future applications of these imaging techniques could use the information from plaque tissue characterization and the measurement of plaque burden to assist clinicians in the selection of an optimal treatment method for each patient, based on the vulnerability of the atherosclerotic lesion. The authors of a recent report (117) have documented the direct association of the thickness of carotid intima and media and the incidence of myocardial infarction or stroke. It may be interesting to study the association of carotid atherosclerosis morphology directly and its association with myocardial infarction. With new techniques being developed and the advent of new MR imager hardware and software, it may be possible that the current imaging protocols can be converted into an efficient and economically feasible screening tool.

	SUMMARY

TOP ABSTRACT INTRODUCTION ATHEROSCLEROSIS AND THE CONCEPT... CAROTID US MR IMAGING CHARACTERIZATION OF... TECHNICAL ASPECTS OF CAROTID... REPRODUCIBILITY AND... TESTING PULSE SEQUENCES EX... PRACTICAL APPLICATIONS SUMMARY REFERENCES

 
Over the past decade, notable advances have been made in our understanding of vascular biology. We now accept the importance of plaque burden, morphology, and composition as appropriate objectives for noninvasive measurement and no longer rely solely on the degree of luminal narrowing to assess the severity of atherosclerotic disease. As discussed in this article, MR imaging holds much potential for developing into a modality that can be used to quantitatively characterize plaque morphology in vivo. Results of preliminary studies have demonstrated the ability of multi–contrast-weighted MR techniques to assist in prospective identification of the major components of human carotid plaques and characterization of the morphologic features associated with the vulnerable lesion (unstable fibrous cap, necrotic core, intimal calcification, and intraplaque hematoma). Although the sample sizes of these studies were limited, continued patient recruitment and a growing number of studies performed at different institutions will, we hope, establish the accuracy of these techniques. Nonetheless, the results and associated technical developments described open an exciting new era in vascular imaging and raise hopes that we may soon be able to (a) identify a vulnerable plaque noninvasively and prospectively, thereby allowing more timely intervention, and (b) quantitatively monitor changes in disease burden and biologic markers of instability to improve our understanding of the pathogenesis of the disease and better evaluate the efficacy of new therapies.

The high-spatial-resolution MR images presented in this article can be generated with a 1.5-T clinical imager and phased-array surface coil. Currently, pulse sequences consisting of both black- and bright-blood techniques are recommended to help characterize carotid plaque morphology in vivo; however, ongoing ex vivo experiments may demonstrate the utility of additional sequences such as 3D fast inflow with steady-state precession or magnetization transfer contrast. As the results from multiple institutions show, the techniques described can readily be transferred, with minimal changes, to whole-body imagers from the major manufacturers.

The state of carotid imaging and noninvasive plaque characterization is rapidly advancing as an increasing number of institutions begin experimental studies and develop imaging protocols. This growing interest will, we hope, produce the resources and patient sample sizes needed to realize the potential of MR for developing into a means of prospective identification of the vulnerable plaque.

	ACKNOWLEDGMENTS

 
The authors thank Drs A. Alexander, Z. A. Fayad, T. S. Hatsukami, W. S. Kerwin, D. L. Parker, D. Saloner, and D. A. Steinman for allowing us to use their images and for helpful discussions. The authors also thank M. S. Ferguson, BS, Z. E. Miller, BA, and D. X. Xu, PhD, for helping to prepare the manuscript.

	FOOTNOTES

 
Abbreviations: DIR = double inversion recovery, GRE = gradient recalled echo, SE = spin echo, 3D = three-dimensional, TOF = time of flight

	REFERENCES

TOP ABSTRACT INTRODUCTION ATHEROSCLEROSIS AND THE CONCEPT... CAROTID US MR IMAGING CHARACTERIZATION OF... TECHNICAL ASPECTS OF CAROTID... REPRODUCIBILITY AND... TESTING PULSE SEQUENCES EX... PRACTICAL APPLICATIONS SUMMARY REFERENCES

 

1. Gorelick PB, Sacco RL, Smith DB, et al. Prevention of a first stroke: a review of guidelines and a multidisciplinary consensus statement from the National Stroke Association. JAMA 1999; 281:1112- 1120.
2. Hankey GJ. Stroke: how large a public health problem, and how can the neurologist help?. Arch Neurol 1999; 56:748-754.
3. Dogan A, Dempsey RJ. Diagnostic modalities for carotid artery disease. Neurosurg Clin N Am 2000; 11:205-220.
4. North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade stenosis. N Engl J Med 1991; 325:445-453.
5. Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST). Lancet 1998; 351:1379-1387.
6. Chaturvedi S. Public health impact of carotid endarterectomy. Neuroepidemiology 1999; 18:15-21.
7. Connors JJ, Seidenwurm D, Wojak JC, et al. Treatment of atherosclerotic disease at the cervical carotid bifurcation: current status and review of the literature. AJNR Am J Neuroradiol 2000; 21:444-450.
8. Brott T, Bogousslavsky J. Treatment of acute ischemic stroke. N Engl J Med 2000; 343:710-721.
9. Topol EJ, Nissen SE. Our preoccupation with coronary luminology: the dissociation between clinical and angiographic findings in ischemic heart disease. Circulation 1995; 92:2333-2342.
10. Wasserman BA, Haacke EM, Li D. Carotid plaque formation and its evaluation with angiography, ultrasound, and MR angiography. J Magn Reson Imaging 1994; 4:515-527.
11. Ambrose JA, Tannenbaum MA, Alexopoulos D, et al. Angiographic progression of coronary artery disease and the development of myocardial infarction. J Am Coll Cardiol 1988; 12:56-62.
12. Little WC, Constantinescu M, Applegate RJ, et al. Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease?. Circulation 1988; 78(5 pt 1):1157-1166.
13. Falk E. Why do plaques rupture?. Circulation 1992; 86(suppl 6):III30-III42.
14. Bassiouny HS, Sakaguchi Y, Mikucki SA, et al. Juxtalumenal location of plaque necrosis and neoformation in symptomatic carotid stenosis. J Vasc Surg 1997; 26:585-594.
15. Edwards JH, Kricheff II, Riles T, Imparato A. Angiographically undetected ulceration of the carotid bifurcation as a cause of embolic stroke. Radiology 1979; 132:369-373.
16. Mann JM, Davies MJ. Vulnerable plaque: relation of characteristics to degree of stenosis in human coronary arteries. Circulation 1996; 94:928-931.
17. Gronholdt MM. Ultrasound and lipoproteins as predictors of lipid-rich, rupture-prone plaques in the carotid artery. Arterioscler Thromb Vasc Biol 1999; 19:2-13.
18. Kimura BJ, Bhargava V, DeMaria AN. Value and limitations of intravascular ultrasound imaging in characterizing coronary atherosclerotic plaque. Am Heart J 1995; 130:386-396.
19. Gold GE, Pauly JM, Glover GH, Moretto JC, Macovski A, Herfkens RJ. Characterization of atherosclerosis with a 1.5-T imaging system. J Magn Reson Imaging 1993; 3:399-407.
20. Martin AJ, Gotlieb AI, Henkelman RM. High-resolution MR imaging of human arteries. J Magn Reson Imaging 1995; 5:93-100.
21. Mohiaddin RH, Longmore DB. MRI studies of atherosclerotic vascular disease: structural evaluation and physiological measurements. Br Med Bull 1989; 45:968-990.
22. Merickel MB, Carman CS, Brookeman JR, Mugler JP, Brown MF, Ayers CR. Identification and 3-D quantification of atherosclerosis using magnetic resonance imaging. Comput Biol Med 1988; 18:89-102.
23. Pearlman JD, Southern JF, Ackerman JL. Nuclear magnetic resonance microscopy of atheroma in human coronary arteries. Angiology 1991; 42:726-733.
24. Toussaint JF, Southern JF, Fuster V, Kantor HL. T2-weighted contrast for NMR characterization of human atherosclerosis. Arterioscler Thromb Vasc Biol 1995; 15:1533-1542.
25. Toussaint JF, LaMuraglia GM, Southern JF, Fuster V, Kantor HL. Magnetic resonance images lipid, fibrous, calcified, hemorrhagic, and thrombotic components of human atherosclerosis in vivo. Circulation 1996; 94:932-938.
26. Fayad ZA, Fuster V. Characterization of atherosclerotic plaques by magnetic resonance imaging. Ann N Y Acad Sci 2000; 902:173-186.
27. Yuan C, Murakami JW, Hayes CE, et al. Phased-array magnetic resonance imaging of the carotid artery bifurcation: preliminary results in healthy volunteers and a patient with atherosclerotic disease. J Magn Reson Imaging 1995; 5:561-565.
28. Shinnar M, Fallon JT, Wehrli S, et al. The diagnostic accuracy of ex vivo MRI for human atherosclerotic plaque characterization. Arterioscler Thromb Vasc Biol 1999; 19:2756-2761.
29. Davies MJ, Woolf N. Atherosclerosis: what is it and why does it occur?. Br Heart J 1993; 69(suppl 1):S3-S11.
30. Rubin JR, Goldstone J. Peripheral vascular disease: treatment and referral of the elderly—part I. Geriatrics 1985; 40:34-39.
31. Fuster V, Stein B, Ambrose JA, Badimon L, Badimon JJ, Chesebro JH. Atherosclerotic plaque rupture and thrombosis: evolving concepts. Circulation 1990; 82(suppl 3):II47-II59.
32. Libby P. The interface of atherosclerosis and thrombosis: basic mechanisms. Vasc Med 1998; 3:225-229.
33. Davies MJ, Thomas AC. Plaque fissuring: the cause of acute myocardial infarction, sudden ischaemic death, and crescendo angina. Br Heart J 1985; 53:363-373.
34. Falk E. Stable versus unstable atherosclerosis: clinical aspects. Am Heart J 1999; 138(5 pt 2):S421-S425.
35. Farb A, Burke AP, Tang AL, et al. Coronary plaque erosion without rupture into a lipid core. Circulation 1996; 93:1354-1363.
36. Arroyo LH, Lee RT. Mechanisms of plaque rupture: mechanical and biologic interactions. Cardiovasc Res 1999; 41:369-375.
37. Shah PK. Plaque disruption and thrombosis: potential role of inflammation and infection. Cardiol Clin 1999; 17:271-281.
38. Glagov S, Bassiouny HS, Giddens DP, Zarins CK. Pathobiology of plaque modeling and complication. Surg Clin North Am 1995; 75:545-556.
39. Glagov S, Weisenberg E, Zarins CK, Stankunavicius R, Kolettis GJ. Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med 1987; 316:1371-1375.
40. Budinger T, Berson A, McVeigh E, et al. Magnetic resonance imaging of the cardiovascular system. J Cardiovasc Magn Res 1999; 1:53-58.
41. Falk E, Fernandez-Ortiz A. Role of thrombosis in atherosclerosis and its complications. Am J Cardiol 1995; 75:3B-11B.
42. Kullo IJ, Edwards WD, Schwartz RS. Vulnerable plaque: pathobiology and clinical implications. Ann Intern Med 1998; 129:1050-1060.
43. Roederer GO, Langlois YE, Jaeger KA, et al. A simple spectral parameter for accurate classification of severe carotid disease. Bruit 1984; 8:174-178.
44. Kohler T, Langlois Y, Roederer GO, et al. Sources of variability in carotid duplex examination: a prospective study. Ultrasound Med Biol 1985; 11:571-576.
45. Langlois YE, Roederer GO, Strandness DE, Jr. Vascular ultrasound: ultrasonic evaluation of the carotid bifurcation. Echocardiography 1987; 4:141-159.
46. Pignoli P. Ultrasound B-mode imaging for arterial wall thickness measurement. Atherosclerosis Rev 1984; 12:177-184.
47. Riley WA, Barnes RW, Evans GW, Burke GL. Ultrasonic measurement of the elastic modulus of the common carotid artery: the Atherosclerosis Risk in Communities (ARIC) Study. Stroke 1992; 23:952-956.
48. Howard G, Sharrett AR, Heiss G, et al. Carotid artery intimal-medial thickness distribution in general populations as evaluated by B-mode ultrasound: ARIC Investigators. Stroke 1993; 24:1297-1304.
49. Burke GL, Evans GW, Riley WA, et al. Arterial wall thickness is associated with prevalent cardiovascular disease in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study. Stroke 1995; 26:386-391.
50. Chambless LE, Folsom AR, Clegg LX, et al. Carotid wall thickness is predictive of incident clinical stroke: the Atherosclerosis Risk in Communities (ARIC) study. Am J Epidemiol 2000; 151:478-487.
51. Aly S, Bishop CC. An objective characterization of atherosclerotic lesion: an alternative method to identify unstable plaque. Stroke 2000; 31:1921-1924.
52. Biasi GM, Mingazzini PM, Baronio L, et al. Carotid plaque characterization using digital image processing and its potential in future studies of carotid endarterectomy and angioplasty. J Endovasc Surg 1998; 5:240-246.
53. Noritomi T, Sigel B, Swami V, et al. Carotid plaque typing by multiple-parameter ultrasonic tissue characterization. Ultrasound Med Biol 1997; 23:643-650.
54. Bridal SL, Beyssen B, Fornes P, Julia P, Berger G. Multiparametric attenuation and backscatter images for characterization of carotid plaque. Ultrason Imaging 2000; 22:20-34.
55. Lee DJ, Sigel B, Swami VK, et al. Determination of carotid plaque risk by ultrasonic tissue characterization. Ultrasound Med Biol 1998; 24:1291-1299.
56. Raynaud JS, Bridal SL, Toussaint JF, et al. Characterization of atherosclerotic plaque components by high resolution quantitative MR and US imaging. J Magn Reson Imaging 1998; 8:622-629.
57. Bridal SL, Fornes P, Bruneval P, Berger G. Correlation of ultrasonic attenuation (30 to 50 MHz and constituents of atherosclerotic plaque. Ultrasound Med Biol 1997; 23:691-703.
58. Takiuchi S, Rakugi H, Masuyama T, et al. Clinical implications of ultrasonic tissue characterization for atherosclerotic carotid intima-media. Nippon Ronen Igakkai Zasshi 2000; 37:137-142[Japanese].
59. Noritomi T, Sigel B, Gahtan V, et al. In vivo detection of carotid plaque thrombus by ultrasonic tissue characterization. J Ultrasound Med 1997; 16:107-111.
60. Chan KL. Quantitative characterization of carotid atheromatous plaques using ultrasonic rf A-scan data. Ultrasonics 1995; 33:163-164.
61. Urbani MP, Picano E, Parenti G, et al. In vivo radio frequency-based ultrasonic tissue characterization of the atherosclerotic plaque. Stroke 1993; 24:1507-1512.
62. Prati F, Arbustini E, Labellarte A, et al. Intravascular ultrasound insights into plaque composition. Z Kardiol 2000; 89(suppl 2):117-123.
63. Wolverson MK, Bashiti HM, Peterson GJ. Ultrasonic tissue characterization of atheromatous plaques using a high resolution real time scanner. Ultrasound Med Biol 1983; 9:599-609.
64. Widder B, Paulat K, Hackspacher J, et al. Morphological characterization of carotid artery stenoses by ultrasound duplex scanning. Ultrasound Med Biol 1990; 16:349-354.
65. Hiro T, Leung CY, Karimi H, Farvid AR, Tobis JM. Angle dependence of intravascular ultrasound imaging and its feasibility in tissue characterization of human atherosclerotic tissue. Am Heart J 1999; 137:476-481.
66. Gussenhoven EJ, Essed CE, Lancee CT, et al. Arterial wall characteristics determined by intravascular ultrasound imaging: an in vitro study. J Am Coll Cardiol 1989; 14:947-952.
67. Pourcelot L, Tranquart F, De Bray JM, Philippot M, Bonithon MC, Salez F. Ultrasound characterization and quantification of carotid atherosclerosis lesions. Minerva Cardioangiol 1999; 47:15-24.
68. Iannuzzi A, Wilcosky T, Mercuri M, Rubba P, Bryan FA, Bond MG. Ultrasonographic correlates of carotid atherosclerosis in transient ischemic attack and stroke. Stroke 1995; 26:614-619.
69. Geroulakos G, Domjan J, Nicolaides A, et al. Ultrasonic carotid artery plaque structure and the risk of cerebral infarction on computed tomography. J Vasc Surg 1994; 20:263-266.
70. Arnold JA, Modaresi KB, Thomas N, Taylor PR, Padayachee TS. Carotid plaque characterization by duplex scanning: observer error may undermine current clinical trials. Stroke 1999; 30:61-65.
71. de Bray JM, Baud JM, Delanoy P, et al. Reproducibility in ultrasonic characterization of carotid plaques. Cerebrovasc Dis 1998; 8:273-277.
72. Montauban van Swijndregt AD, Elbers HR, Moll FL, de Letter J, Ackerstaff RG. Ultrasonographic characterization of carotid plaques. Ultrasound Med Biol 1998; 24:489-493.
73. Ricotta JJ. Plaque characterization by B-mode scan. Surg Clin North Am 1990; 70:191-199.
74. Sabetai MM, Tegos TJ, Nicolaides AN, Dhanjil S, Pare GJ, Stevens JM. Reproducibility of computer-quantified carotid plaque echogenicity: can we overcome the subjectivity?. Stroke 2000; 31:2189-2196.
75. Bluth EI. Evaluation and characterization of carotid plaque. Semin Ultrasound CT MR 1997; 18:57-65.
76. Bluth EI. Extracranial carotid arteries: intraplaque hemorrhage and surface ulceration. Minerva Cardioangiol 1998; 46:81-85.
77. European Carotid Plaque Study Group. Carotid artery plaque composition: relationship to clinical presentation and ultrasound B-mode imaging. Eur J Vasc Endovasc Surg 1995; 10:23-30.
78. Geroulakos G, Ramaswami G, Nicolaides A. Characterization of symptomatic and asymptomatic carotid plaques using high-resolution real-time ultrasonography. Br J Surg 1993; 80:1274-1277.
79. AbuRahma AF, Kyer PD, III, Robinson PA, Hannay RS. The correlation of ultrasonic carotid plaque morphology and carotid plaque hemorrhage: clinical implications. Surgery 1998; 124:721-728.
80. Estes JM, Quist WC, Lo Gerfo FW, Costello P. Noninvasive characterization of plaque morphology using helical computed tomography. J Cardiovasc Surg (Torino) 1998; 39:527-534.
81. Kaufman L, Crooks LE, Sheldon PE, Rowan W, Miller T. Evaluation of NMR imaging for detection and quantification of obstructions in vessels. Invest Radiol 1982; 17:554-560.
82. Herfkens RJ, Higgins CB, Hricak . Nuclear magnetic resonance imaging of atherosclerotic disease. Radiology 1983; 148:161-166.
83. Vinitski S, Consigny PM, Shapiro MJ, Janes N, Smullens SN, Rifkin MD. Magnetic resonance chemical shift imaging and spectroscopy of atherosclerotic plaque. Invest Radiol 1991; 26:703-714.
84. Small DM, Shipley GG. Physical-chemical basis of lipid deposition in atherosclerosis. Science 1974; 185:222-229.
85. Hatsukami TS, Ross R, Polissar NL, Yuan C. Visualization of fibrous cap thickness and rupture in human atherosclerotic carotid plaque in vivo with high-resolution magnetic resonance imaging. Circulation 2000; 102:959-964.
86. Pachot-Clouard M, Vaufrey F, Darrasse L, Toussainti JF. Magnetization transfer characteristics in atherosclerotic plaque components assessed by adapted binomial preparation pulses. MAGMA 1998; 7:9-15.
87. Kerwin W, Ferguson MS, Small R, Hatsukami TS, Yuan C. Magnetization transfer as a contrast enhancing mechanism in magnetic resonance images of human atherosclerotic plaques (abstr). Atherosclerosis 2000; 151:25.
88. Toussaint JF, Southern JF, Fuster V, Kantor HL. Water diffusion properties of human atherosclerosis and thrombosis measured by pulse field gradient nuclear magnetic resonance. Arterioscler Thromb Vasc Biol 1997; 17:542-546.
89. Ingersleben GV, Schmiedl UP, Hatsukami TS, et al. Characterization of atherosclerotic plaques at the carotid bifurcation: correlation of high-resolution MR with histology. RadioGraphics 1997; 17:1417-1423.
90. Parker DL, Yuan C, Blatter DD. MR angiography by multiple thin slab 3D acquisition. Magn Reson Med 1991; 17:434-451.
91. Mitsumori LM, Yuan C, Ferguson MS, Hatsukami TS. In vivo identification of lipid cores in advanced carotid atherosclerotic plaques by high resolution MR imaging (abstr). Circulation 2000; 102(suppl):II252.
92. Hatsukami TS, Ferguson MS, Beach KW, et al. Carotid plaque morphology and clinical events. Stroke 1997; 28:95-100.
93. Erlichman M. Surface/specialty coil devices and gating techniques in magnetic resonance imaging. Health Technol Assess Rep 1990; 3:1-23.
94. Hayes CE, Mathis CM, Yuan C. Surface coil phased arrays for high-resolution imaging of the carotid arteries. J Magn Reson Imaging 1996; 6:109-112.
95. Fayad ZA, Fallon JT, Shinnar M, et al. Noninvasive in vivo high-resolution magnetic resonance imaging of atherosclerotic lesions in genetically engineered mice. Circulation 1998; 98:1541-1547.
96. Finn JP, Edelman RR. Black-blood and segmented k-space magnetic resonance angiography. Magn Reson Imaging Clin N Am 1993; 1:349-357.
97. Edelman RR, Chien D, Kim D, et al. Fast selective black blood MR imaging. Radiology 1991; 181:655-660.
98. Milner JS, Moore JA, Rutt BK, Steinman DA. Hemodynamics of human carotid artery bifurcations: computational studies with models reconstructed from magnetic resonance imaging of normal subjects. J Vasc Surg 1998; 28:143-156.
99. Steinman DA, Rutt BK. On the nature and reduction of plaque-mimicking flow artifacts in black blood MRI of the carotid bifurcation. Magn Reson Med 1998; 39:635-641.
100. Yuan C, Beach KW, Smith LH, Jr, Hatsukami TS. Measurement of atherosclerotic carotid plaque size in vivo using high resolution magnetic resonance imaging. Circulation 1998; 98:2666-2671.
101. Aoki S, Aoki K, Ohsawa S, Nakajima H, Kumagai H, Araki T. Dynamic MR imaging of the carotid wall. J Magn Reson Imaging 1999; 9:420-427.
102. Coombs BD, Ursell PC, Reilly LM, Rarp JH, Saloner D. Carotid bifurcation plaque structure: high resolution MRI with histologic correlation (abstr) In: Proceedings of the Sixth Meeting of the International Society for Magnetic Resonance in Medicine. Berkeley, Calif: International Society for Magnetic Resonance in Medicine, 1998; 591.
103. Du YP, Parker DL, Davis WL, Cao G. Reduction of partial-volume artifacts with zero-filled interpolation in three-dimensional MR angiography. J Magn Reson Imaging 1994; 4:733-741.
104. Johnson BA, Fram EK, Drayer BP, Dean BL, Keller PJ, Jacobowitz R. Evaluation of shared-view acquisition using repeated echoes (SHARE): a dual-echo fast spin-echo MR technique. AJNR Am J Neuroradiol 1994; 15:667-673.
105. Yuan C, Petty C, O’Brien KD, Hatsukami TS, Eary JF, Brown BG. In vitro and in situ magnetic resonance imaging signal features of atherosclerotic plaque-associated lipids. Arterioscler Thromb Vasc Biol 1997; 17:1496-1503.
106. Kuller LH. AHA Symposium/Epidemiology Meeting: atherosclerosis—discussion: why measure atherosclerosis?. Circulation 1993; 87(suppl 3):II34-II37.
107. Probstfield JL, Byington RP, Egan DA, et al. Methodological issues facing studies of atherosclerotic change. Circulation 1993; 87(suppl 3):II74-II81.
108. Yuan C, Schmiedl UP, Maravilla KR, et al. MR imaging of human carotid plaques: assessment of reproducibility and reader variability (abstr). Radiology 1996; 201(P):134-135.
109. Kang XJ, Polissar NL, Han C, Lin E, Yuan C. Analysis of the measurement precision of arterial lumen and wall areas using high resolution magnetic resonance imaging. Magn Reson Med 2000; 44:968-972.
110. Beach KW, Hatsukami T, Detmer PR, et al. Carotid artery intraplaque hemorrhage and stenotic velocity. Stroke 1993; 24:314-319.
111. Eubank WB, Yuan C, Fisher ER, Luna JA, et al. Endarterectomy specimen shrinkage: comparison of T2-weighted MR imaging of specimen ex vivo to histological processes. J Vasc Interv Radiol 1998; 4:161-170.
112. Thackray BD, Burns DH, Ferguson MS, et al. A new method for studying plaque morphology. Am J Card Imaging 1995; 9:149-156.
113. Rhim EY, Yuan C, Kaneko E, Reichenbach DD, Nelson JA. MR imaging of normal and atherosclerotic arteries: analysis of contrast features. J Vasc Invest 1997; 3:42-51.
114. Balaban RS, Ceckler TL. Magnetization transfer contrast in magnetic resonance imaging. Magn Reson Q 1992; 8:116-137.
115. Corti R, Badimon JJ, Worthley SG, Helft G, Fayad ZA, Fuster V. Statin therapy reduces burden in human atherosclerotic lesions: longitudinal study using noninvasive MRI (abstr). Circulation 2000; 102:II459.
116. Libby P, Aikawa M, Schonbeck U. Cholesterol and atherosclerosis. Biochim Biophys Acta 2000; 1529:299-309.
117. O’Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK, Jr. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. N Engl J Med 1999; 340:14-22.

This article has been cited by other articles:

				R. H. Swartz, S. S. Bhuta, R. I. Farb, R. Agid, R. A. Willinsky, K. G. terBrugge, J. Butany, B. A. Wasserman, D. M. Johnstone, F. L. Silver, et al. Intracranial arterial wall imaging using high-resolution 3-tesla contrast-enhanced MRI Neurology, February 17, 2009; 72(7): 627 - 634. [Abstract] [Full Text] [PDF]

				U. Ravnskov and K. S. McCully Vulnerable Plaque Formation from Obstruction of Vasa Vasorum by Homocysteinylated and Oxidized Lipoprotein Aggregates Complexed with Microbial Remnants and LDL Autoantibodies Ann. Clin. Lab. Sci., January 1, 2009; 39(1): 3 - 16. [Abstract] [Full Text] [PDF]

				J M U-King-Im, T Y Tang, A Patterson, M J Graves, S Howarth, Z-Y Li, R Trivedi, D Bowden, P J Kirkpatrick, M E Gaunt, et al. Characterisation of carotid atheroma in symptomatic and asymptomatic patients using high resolution MRI J. Neurol. Neurosurg. Psychiatry, August 1, 2008; 79(8): 905 - 912. [Abstract] [Full Text] [PDF]

				K. Yoshida, O. Narumi, M. Chin, K. Inoue, T. Tabuchi, K. Oda, M. Nagayama, N. Egawa, M. Hojo, Y. Goto, et al. Characterization of Carotid Atherosclerosis and Detection of Soft Plaque with Use of Black-Blood MR Imaging AJNR Am. J. Neuroradiol., May 1, 2008; 29(5): 868 - 874. [Abstract] [Full Text] [PDF]

				T. Saam, H. R. Underhill, B. Chu, N. Takaya, J. Cai, N. L. Polissar, C. Yuan, and T. S. Hatsukami Prevalence of American Heart Association type VI carotid atherosclerotic lesions identified by magnetic resonance imaging for different levels of stenosis as measured by duplex ultrasound. J. Am. Coll. Cardiol., March 11, 2008; 51(10): 1014 - 1021. [Abstract] [Full Text] [PDF]

				S. V. Raman, M. W. Winner III, T. Tran, M. Velayutham, O. P. Simonetti, P. B. Baker, J. Olesik, B. McCarthy, A. K. Ferketich, and J. L. Zweier In vivo atherosclerotic plaque characterization using magnetic susceptibility distinguishes symptom-producing plaques. J. Am. Coll. Cardiol. Img., January 1, 2008; 1(1): 49 - 57. [Abstract] [Full Text] [PDF]

				T. Saam, T. S. Hatsukami, N. Takaya, B. Chu, H. Underhill, W. S. Kerwin, J. Cai, M. S. Ferguson, and C. Yuan The Vulnerable, or High-Risk, Atherosclerotic Plaque: Noninvasive MR Imaging for Characterization and Assessment Radiology, July 1, 2007; 244(1): 64 - 77. [Abstract] [Full Text] [PDF]

				T. Saam, J. Cai, L. Ma, Y.-Q. Cai, M. S. Ferguson, N. L. Polissar, T. S. Hatsukami, and C. Yuan Comparison of Symptomatic and Asymptomatic Atherosclerotic Carotid Plaque Features with in Vivo MR Imaging. Radiology, August 1, 2006; 240(2): 464 - 472. [Abstract] [Full Text] [PDF]

				D. S. Berman, R. Hachamovitch, L. J. Shaw, J. D. Friedman, S. W. Hayes, L. E.J. Thomson, D. S. Fieno, G. Germano, N. D. Wong, X. Kang, et al. Roles of Nuclear Cardiology, Cardiac Computed Tomography, and Cardiac Magnetic Resonance: Noninvasive Risk Stratification and a Conceptual Framework for the Selection of Noninvasive Imaging Tests in Patients with Known or Suspected Coronary Artery Disease J. Nucl. Med., July 1, 2006; 47(7): 1107 - 1118. [Abstract] [Full Text] [PDF]

				R. L. Wilensky, H. K. Song, and V. A. Ferrari Role of magnetic resonance and intravascular magnetic resonance in the detection of vulnerable plaques. J. Am. Coll. Cardiol., April 18, 2006; 47(8 Suppl): C48 - C56. [Abstract] [Full Text] [PDF]

				G. Schueller, E. Kaindl, W. K. Matzek, F. Semturs, C. Schueller-Weidekamm, and T. H. Helbich Image Quality of a Wet Laser Printer Versus a Paper Printer for Full-Field Digital Mammograms Am. J. Roentgenol., January 1, 2006; 186(1): 38 - 43. [Abstract] [Full Text] [PDF]

				J. R. Davies, J. H.F. Rudd, T. D. Fryer, M. J. Graves, J. C. Clark, P. J. Kirkpatrick, J. H. Gillard, E. A. Warburton, and P. L. Weissberg Identification of Culprit Lesions After Transient Ischemic Attack by Combined 18F Fluorodeoxyglucose Positron-Emission Tomography and High-Resolution Magnetic Resonance Imaging Stroke, December 1, 2005; 36(12): 2642 - 2647. [Abstract] [Full Text] [PDF]

				E. Larose, Y. Yeghiazarians, P. Libby, E.K. Yucel, M. Aikawa, D. F. Kacher, E. Aikawa, S. Kinlay, F. J. Schoen, A. P. Selwyn, et al. Characterization of Human Atherosclerotic Plaques by Intravascular Magnetic Resonance Imaging Circulation, October 11, 2005; 112(15): 2324 - 2331. [Abstract] [Full Text] [PDF]

				M. Y. Desai, A. Rodriguez, B. A. Wasserman, G. Gerstenblith, S. Agarwal, M. Kennedy, D. A Bluemke, and J. A.C. Lima Association of Cholesterol Subfractions and Carotid Lipid Core Measured by MRI Arterioscler. Thromb. Vasc. Biol., June 1, 2005; 25(6): e110 - e111. [Full Text] [PDF]

				V. C. Cappendijk, K. B. J. M. Cleutjens, A. G. H. Kessels, S. Heeneman, G. W. H. Schurink, R. J. T. J. Welten, W. H. Mess, M. J. A. P. Daemen, J. M. A. van Engelshoven, and M. E. Kooi Assessment of Human Atherosclerotic Carotid Plaque Components with Multisequence MR Imaging: Initial Experience Radiology, February 1, 2005; 234(2): 487 - 492. [Abstract] [Full Text] [PDF]

				T. Saam, M.S. Ferguson, V.L. Yarnykh, N. Takaya, D. Xu, N.L. Polissar, T.S. Hatsukami, and C. Yuan Quantitative Evaluation of Carotid Plaque Composition by In Vivo MRI Arterioscler. Thromb. Vasc. Biol., January 1, 2005; 25(1): 234 - 239. [Abstract] [Full Text] [PDF]

				R. A. Trivedi, J. M. U-King-Im, M. J. Graves, P. J. Kirkpatrick, and J. H. Gillard Noninvasive imaging of carotid plaque inflammation Neurology, July 13, 2004; 63(1): 187 - 188. [Full Text] [PDF]

				V. Mani, V. V. Itskovich, M. Szimtenings, J. G. S. Aguinaldo, D. D. Samber, G. Mizsei, and Z. A. Fayad Rapid Extended Coverage Simultaneous Multisection Black-Blood Vessel Wall MR Imaging Radiology, July 1, 2004; 232(1): 281 - 288. [Abstract] [Full Text] [PDF]

				M. Sirol, V. V. Itskovich, V. Mani, J. G. S. Aguinaldo, J. T. Fallon, B. Misselwitz, H.-J. Weinmann, V. Fuster, J.-F. Toussaint, and Z. A. Fayad Lipid-Rich Atherosclerotic Plaques Detected by Gadofluorine-Enhanced In Vivo Magnetic Resonance Imaging Circulation, June 15, 2004; 109(23): 2890 - 2896. [Abstract] [Full Text] [PDF]

				M. Tatsumi, C. Cohade, Y. Nakamoto, and R. L. Wahl Fluorodeoxyglucose Uptake in the Aortic Wall at PET/CT: Possible Finding for Active Atherosclerosis Radiology, December 1, 2003; 229(3): 831 - 837. [Abstract] [Full Text] [PDF]

				S. Zhang, J. Cai, Y. Luo, C. Han, N. L. Polissar, T. S. Hatsukami, and C. Yuan Measurement of Carotid Wall Volume and Maximum Area with Contrast-enhanced 3D MR Imaging: Initial Observations Radiology, July 1, 2003; 228(1): 200 - 205. [Abstract] [Full Text] [PDF]

				R. F. Redberg, R. A. Vogel, M. H. Criqui, D. M. Herrington, J. A. C. Lima, and M. J. Roman Task force #3--what is the spectrum of current and emerging techniques for the noninvasive measurement of atherosclerosis? J. Am. Coll. Cardiol., June 4, 2003; 41(11): 1886 - 1898. [Full Text] [PDF]

				M.E. Kooi, V.C. Cappendijk, K.B.J.M. Cleutjens, A.G.H. Kessels, P.J.E.H.M. Kitslaar, M. Borgers, P.M. Frederik, M.J.A.P. Daemen, and J.M.A. van Engelshoven Accumulation of Ultrasmall Superparamagnetic Particles of Iron Oxide in Human Atherosclerotic Plaques Can Be Detected by In Vivo Magnetic Resonance Imaging Circulation, May 20, 2003; 107(19): 2453 - 2458. [Abstract] [Full Text] [PDF]

				Z. A. Fayad, V. Fuster, K. Nikolaou, and C. Becker Computed Tomography and Magnetic Resonance Imaging for Noninvasive Coronary Angiography and Plaque Imaging: Current and Potential Future Concepts Circulation, October 8, 2002; 106(15): 2026 - 2034. [Full Text] [PDF]

				R. P. Choudhury, V. Fuster, J. J. Badimon, E. A. Fisher, and Z. A. Fayad MRI and Characterization of Atherosclerotic Plaque: Emerging Applications and Molecular Imaging Arterioscler. Thromb. Vasc. Biol., July 1, 2002; 22(7): 1065 - 1074. [Abstract] [Full Text] [PDF]

				C. Yuan, S.-x. Zhang, N. L. Polissar, D. Echelard, G. Ortiz, J. W. Davis, E. Ellington, M. S. Ferguson, and T. S. Hatsukami Identification of Fibrous Cap Rupture With Magnetic Resonance Imaging Is Highly Associated With Recent Transient Ischemic Attack or Stroke Circulation, January 15, 2002; 105(2): 181 - 185. [Abstract] [Full Text] [PDF]

This Article Abstract Figures Only Full Text (PDF) All Versions of this Article: 2212001612v1 221/2/285    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yuan, C. Articles by Maravilla, K. R. Search for Related Content PubMed PubMed Citation Articles by Yuan, C. Articles by Maravilla, K. R.