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(Circulation. 2002;105:181.)
© 2002 American Heart Association, Inc.
Clinical Investigation and Reports |
From the Departments of Radiology (C.Y., S.Z., D.E., G.O., J.W.D., M.S.F) and Medicine (E.E.), University of Washington, Seattle; Mountain-Whisper-Light Statistical Consulting (N.L.P.), Seattle; and Surgery and Perioperative Care, VA Puget Sound Health Care System (T.S.H.), Seattle, Wash.
Correspondence to Chun Yuan, PhD, University of Washington, Department of Radiology, Box 357115, 1959 NE Pacific Ave, Seattle, WA 98195. E-mail cyuan{at}u.washington.edu
| Abstract |
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Methods and Results Fifty-three consecutive patients (mean age, 71 years; 49 male) scheduled for carotid endarterectomy were recruited after obtaining informed consent. Twenty-eight subjects had a recent history of TIA or stroke on the side appropriate to the index carotid lesion, and 25 were asymptomatic. Preoperative carotid MRI was performed in a 1.5-T GE Signa scanner that generated T1-, PD-, and T2-weighted and three-dimensional time-of-flight images. Using previously reported MRI criteria, the fibrous cap was categorized as intact-thick, intact-thin, or ruptured for each carotid plaque by blinded review. There was a strong and statistically significant trend showing a higher percentage of symptomatic patients for ruptured caps (70%) compared with thick caps (9%) (P=0.001 Mann-Whitney test for cap status versus symptoms). Compared with patients with thick fibrous caps, patients with ruptured caps were 23 times more likely to have had a recent TIA or stroke (95% CI=3, 210).
Conclusions MRI identification of a ruptured fibrous cap is highly associated with a recent history of TIA or stroke. Ongoing prospective studies will determine the predictive value fibrous cap characteristics, as visualized by MRI, for risk of subsequent ischemic events.
Key Words: magnetic resonance imaging atherosclerosis carotid arteries stroke
| Introduction |
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Of the clinical imaging modalities presently used to study atherosclerosis, MRI is unique because it is noninvasive, capable of identifying plaque tissue components with submillimeter resolution, able to provide quantitative measures of disease severity, and suitable for serial investigations.714 Recent studies demonstrated that high-resolution MRI is capable of distinguishing intact, thick fibrous caps from thin or ruptured caps in human carotid atherosclerosis in vivo. Thick fibrous caps appear as a juxtaluminal band of low signal in time-of-flight (TOF) MR images. In plaques with thin fibrous caps, this dark juxtaluminal band is absent. In plaques with fibrous cap rupture, the dark band is absent and there is a region of hyperintense signal adjacent to the lumen.15
Using a multiple contrast-weighted, high-resolution MR carotid artery imaging protocol,16 we evaluated the relationship between carotid plaque fibrous cap characteristics and their association with the patients neurological symptoms. The aim of this study was to test the hypothesis that if a patient has a carotid plaque with a thin or ruptured fibrous cap, as identified by MRI, then the patient is more likely to have had a recent transient ischemic attack (TIA) or stroke, appropriate to the side of the index carotid lesion.
| Methods |
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MRI Protocol
The MRI scans were performed within 1 week before the surgical procedure and neurological examination. Patients were placed in a head holder, which improves comfort and reduces motion artifacts, and were imaged using specially designed phased-array surface coils17 in a 1.5-T GE Signa scanner (Horizon EchoSpeed, version 5.8, GE Medical Systems).
A standardized protocol was used to obtain 4 different contrast-weighted image sets (three-dimensional [3D] TOF axial source images and T1-, proton density [PD]-, and T2-weighted images) of the carotid arteries for each patient.16 The imaging plane was transverse, and the slice readout was in the right to left direction. Fat suppression was used to reduce the signal from the subcutaneous tissues, and a zero-filled Fourier transform was used to reduce the apparent pixel size, thereby minimizing partial volume artifacts. Although the imaging protocol varied depending on patient body habitus, a typical set of parameters for the 3 sequences used to generate the images was as follows: (1) double inversion recovery T1-weighted 2D fast spin-echo (repetition time [TR], 800 ms; echo time [TE], 9.3 ms; field of view [FOV], 13 cm; thickness, 2 mm; 256x256 matrix; number of excitations [NEX], 2); (2) cardiac-gated, shared echo and fast spin-echo for PD- and T2-weighted images (TR, 3 R-R intervals; first echo TE, 20 ms; second echo TE, 40 ms; FOV, 13 cm; thickness, 2 mm; 256x256 matrix; NEX, 2); and (3) 3D TOF (TR, 23 ms; TE, 3.8 ms; flip angle, 25 degrees; FOV, 13 cm; thickness, 2 mm; 256x256 matrix; NEX, 2). Including set-up time and localizer sequences, the length of each examination averaged 40 minutes. Best voxel size achieved was 0.25x0.25x2.0 mm3. The slice levels prescribed were centered around the carotid bifurcation on the operative side in each patient.
Review of MRI
For each artery, images of the 4 contrast weightings from 12 locations (centered at the bifurcation) were matched and filmed (2.4-cm total longitudinal extent of coverage). The appearance of the fibrous cap was categorized as intact and thick (rating I), intact and thin (rating II), or ruptured (rating III) on the basis of the following definitions: intact and thick cap: a uniform, continuous dark band adjacent to the lumen on the TOF image and a smooth lumen surface on TOF and T1-, PD-, and T2-weighted images; intact, thin cap: no visible dark band adjacent to the lumen on the TOF image and a smooth lumen surface on TOF and T1-, PD-, and T2-weighted images; and ruptured cap: disrupted or no visible dark band adjacent to the lumen on TOF images, irregular lumen boundary on TOF and T1-, PD-, and T2-weighted images, and a hyperintense, bright signal adjacent to the lumen (Figures 1 through 3). The fibrous cap state was categorized by a reader who was blinded to the clinical status of the patient. The presence of calcification near the lumen surface, which may also appear as a hypointense region on the TOF images, was distinguished from a thick cap on the basis of its appearance on the T1-, PD-, or T2-weighted images. Calcification appeared as a dark region on TOF and T1-, PD-, and T2-weighted images, whereas a thick fibrous cap appeared as a dark band only on the TOF images. All MRI cross-sections for the index carotid artery were reviewed, and a single rating was assigned for the index artery (highest rating).
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Statistical Analysis
Logistic regression analysis was performed to determine odds ratios for the risk of symptoms by categories of cap status, and the nonparametric (Mann-Whitney test) was performed to compare cap status (ordered as thick, thin, and ruptured) versus presence or absence of symptoms. Students t tests and Fishers exact test were performed to compare the descriptive characteristics of the symptomatic and asymptomatic groups. All analyses were carried out using SPSS for Windows (version 7.5.1).
| Results |
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| Discussion |
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=0.83, weighted
=0.87, 89% agreement, Spearmans correlation coefficient=0.88).15 In a follow-up study, we compared multispectral MR images to 91 matched histological sections. The sensitivity and specificity (95% CI) of MRI for distinguishing thin and ruptured cap from thick fibrous caps was 81±6% and 90±2%, respectively.18 On the basis of histological examination of excised coronary and carotid artery specimens, studies published by Davies and Thomas,19 Falk,20 Fuster et al,21 Virmani et al,4 and others have established that an important morphological component of the vulnerable atherosclerotic plaque is the presence of a fibrous cap that is thinned or ruptured. Falk20 noted that >75% of major coronary thrombotic events were precipitated by atherosclerotic plaque rupture. In a study involving 44 carotid endarterectomy specimens (25 asymptomatic and 19 symptomatic), Carr et al5 noted fibrous cap rupture in 74% of symptomatic plaques, compared with 32% of asymptomatic lesions, and fibrous cap thinning in 95% of symptomatic lesions compared with 48% of asymptomatic plaques.
In concurrence with this histological evidence, this study found a strong and highly significant association between the in vivo state of the fibrous cap and patient symptoms using a noninvasive high-resolution MRI technique. Seventy percent of patients with ruptured fibrous caps and 50% with thin fibrous caps had a history of recent TIA or stroke, compared with only 9% of those with thick fibrous caps on MRI. Remarkably, there was an estimated 23-fold increase in the likelihood of having recent ischemic neurologic symptoms if MRI identified a ruptured fibrous cap, compared with a thick cap. The rate of TIA or stroke is much more similar between the thin and ruptured cap groups than between either of these groups and those with a thick fibrous cap. This similarity of the thin and ruptured cap groups suggests that these two categories combined constitute the high-risk cohort of patients, as determined by MRI.
The use of gradient echo-based 3D TOF sequence is critically important to differentiate the fibrous cap from the underlying intimal tissue. Presumably, the visibility of the fibrous cap on the TOF images is attributable to the T2* effects caused by the layered organization of the matrix proteins that are present in the cap22,23 and the short effective echo time of gradient echo data acquisition.24,25 The macromolecular structure of the collagen in the cap could create a barrier to molecular motion, thereby creating a T2* mechanism as water molecules traverse across layers.22,23,26,27 The T2* sensitivity of the GRE-weighted 3D TOF sequence would then allow detection of disruptions or absence of the collagen layers in the fibrous cap that would be caused by plaque rupture or the presence of proteoglycan-rich regions.28 Because T1 relaxation is less dependent on the static component of dipole-dipole coupling, this effect is not evident in T1-weighted images.29
Because the conspicuity of the fibrous cap is dependent on the contrast present at the fibrous cap (lumen interface and between the cap and the underlying intima), the state of the cap was difficult to determine when there were areas of low signal adjacent to the lumen surface. In the present study, the instances where the hypointense juxtaluminal band on the 3D TOF images was obscured were typically related to flow artifacts or juxtaluminal calcifications. In several image locations that contained intraluminal flow disturbances, the double-inversion recovery sequence, which was designed to reduce turbulence-induced dephasing,30 was found to improve visualization of the luminal surface. When large intimal calcifications were present, the SE sequences were less sensitive than the TOF to the calcium-related susceptibility artifacts.31 At these locations, the PD-weighted images were able to depict the presence of fibrous tissue immediately adjacent to intimal calcifications.
In conclusion, this study provides strong evidence of the association between the state of the fibrous cap, as detected by MRI, and recent ischemic neurological events. The ability to noninvasively detect atherosclerotic plaques that are at risk of rupturing before the development of ischemic complications in vivo has tremendous clinical importance. Ongoing prospective studies are presently underway that will determine the predictive value of fibrous cap characteristics on MRI for risk of subsequent ischemic events.
| Acknowledgments |
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Received September 24, 2001; accepted November 5, 2001.
| References |
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