Original Paper

Cerebrovasc Dis 2013;35:370377 DOI: 10.1159/000348846

Received: December 17, 2012 Accepted: February 4, 2013 Published online: April 30, 2013

Validity of Dual MRI and 18F-FDG PET Imaging in Predicting Vulnerable and Inflamed Carotid Plaque
Hisayasu Saito a Satoshi Kuroda a Kenji Hirata b Keiichi Magota b Tohru Shiga b Nagara Tamaki b Daisuke Yoshida c Satoshi Terae c Naoki Nakayama a Kiyohiro Houkin a
Departments of a Neurosurgery, b Nuclear Medicine, and c Radiology, Hokkaido University Graduate School of Medicine, Sapporo, Japan

Key Words Carotid stenosis FDG-PET Ischemic stroke MRI Vulnerable plaque

Abstract Background: Vulnerable and inflamed plaques in the carotid artery are at high risk of ischemic stroke, suggesting the importance of diagnostic modalities to detect them in patients with carotid stenosis with high sensitivity and specificity. Although many investigators have reported that magnetic resonance imaging (MRI) is a useful tool to predict the vulnerable components of carotid plaque, its validity is not established. On the other hand, 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) may be an alternative modality to directly identify the inflamed plaque in carotid artery stenosis. Therefore, this study aimed at evaluating the validity of MRI and FDG-PET to predict vulnerable and inflamed carotid plaque. Methods: This prospective study totally included 25 patients who underwent carotid endarterectomy (CEA) for carotid artery stenosis at our institute between January 2009 and January 2012. Prior to CEA, FDG-PET, black-blood T1-weighted imaging (BB-T1WI), and 3-dimensional time-of-flight (TOF) imaging were performed. The specimens were stained with hematoxylin-eosin to assess the different plaque components (lipid, hemorrhage,

calcification, and fibrous tissue). In addition, they were stained with primary antibodies against CD68 (activated macrophages) and matrix metalloproteinase (MMP)-9. Results: High FDG uptake was detected in 13 (52.0%) of 25 patients. All of them had lipid-rich plaque. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) to identify the lipid-rich plaques were all 100% for FDG-PET. More importantly, all of the FDG-positive plaques had strong immunoreactivity against both CD68 and MMP-9. There was a significant correlation between the findings on FDG-PET and those on immunohistochemistry against CD68 and MMP-9 (p = 0.006 and 0.004, respectively). On the other hand, 16 (64.0%) of 25 patients had high signal intensity plaque on BB-T1WI. In 7 of these 16 patients, the lesions also showed high signal intensity on TOF imaging. All of them had a large intraplaque hemorrhage. The sensitivity, specificity, PPV, and NPV to identify a large intraplaque hemorrhage were 70, 100, 100, and 83%, respectively, for MRI. Conclusions: These findings suggest that FDG-PET and MRI are complementary to predict high-risk carotid plaque, such as lipid-rich or hemorrhagic plaque. FDG-PET can accurately predict the lipid-rich and inflamed plaque. MRI is valuable to identify unstable plaque with a large intraplaque hemorrhage. The combination of these two modalities may play an important role in predicting carotid plaque at high risk of ischemic stroke. Copyright 2013 S. Karger AG, Basel

2013 S. Karger AG, Basel 10159770/13/03540370$38.00/0 E-Mail karger@karger.com www.karger.com/ced

Satoshi Kuroda, MD, PhD Department of Neurosurgery Graduate School of Medicine and Pharmaceutical Science for Education University of Toyama, 2630 Sugitani, Toyama 930-0194 (Japan) E-Mail skuroda@med.u-toyama.ac.jp

Introduction

Carotid atherosclerosis is an important cause of ischemic stroke. The effectiveness of carotid endarterectomy (CEA) in patients with more than a certain degree of stenosis has been proven to prevent ischemic stroke in several multicenter randomized clinical trials (RCTs). In these RCTs, the degree of stenosis has been employed as a surrogate marker to determine the candidate for CEA [14]. However, recent studies have strongly suggested that the component of carotid plaque may also play an important role in the occurrence of ischemic stroke, even when the degree of stenosis is mild or moderate [58]. Thus, inflamed and/or lipid-rich carotid plaques may readily cause artery-to-artery thromboembolism through plaque rupture [5, 6, 9]. Intraplaque hemorrhage strongly suggests the existence of aggressive angiogenesis in the carotid plaque and may also trigger ischemic stroke through similar mechanisms [8, 1012]. These findings suggest the importance of noninvasive diagnostic modalities with a high accuracy to detect intraplaque hemorrhages in patients with carotid artery stenosis. Although many investigators have reported that magnetic resonance imaging (MRI) is a useful tool to predict the components of carotid plaque, its validity is not established [1018]. On the other hand, 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) may be an alternative modality to directly identify the inflamed plaque in carotid artery stenosis [9, 1925]. Therefore, this study was aimed at evaluating the validity of dual imaging with MRI and FDG-PET to predict the vulnerable components of carotid plaques.

Magnetic Resonance Imaging MRI examinations were performed using a 1.5-Tesla scanner (MR Systems Achieva; Philips). Patients underwent black-blood MRI and magnetic resonance (MR) angiography. Black-blood MRI used a fat-suppressed T1-weighted fast spin-echo sequence with a double inversion recovery technique with repetition time (TR)/echo time (TE)/flip angle (FA) = 8001,200 ms/10 ms/90. Other parameters included a 256 256 matrix, 4-mm slice thickness, and 180-mm field of view (FOV). The fat signal was suppressed by chemical shift-selective fat suppression of spectral presaturation with inversion recovery. MR angiography of the carotid arteries was performed with a 3-dimensional time-of-flight (TOF) sequence (TR/TE/FA = 22ms/6.9 ms/17) in the transaxial direction. Other parameters included a 256 195 matrix, 2-mm slice thickness, and 250-mm FOV. The signal intensity of carotid plaque on black-blood T1weighted imaging (BB-T1WI) was evaluated using the proximal submandibular gland as a reference. Signal intensity of carotid plaques was visually classified into high, iso-, and low signal intensity. Likewise, the signal intensity of plaque on TOF imaging was visually classified into high and iso-signal intensity. All MR images were analyzed by a neuroradiologist and a neurosurgeon (D.Y.andH.S.) who were blinded to radiological, histopathological, and clinical characteristics. F-Fluorodeoxyglucose Positron Emission Tomography After overnight fasting, serum glucose level was measured to confirm normoglycemia in each patient. Sixty minutes after intravenous injection of 18F-FDG (400 MBq), PET images were acquired with either an integrated PET-computed tomography (CT) scanner (Biograph 64; Asahi-Siemens Medical Technologies Ltd., Tokyo, Japan) or stand-alone PET scanner (ECAT HR+ scanner; Asahi-Siemens Medical Technologies Ltd.). For the PET-CT scanner, noncontrast-enhanced CT scanning was performed for the head and neck region, followed by 10-min emission scanning. The images were reconstructed using 3-dimensional ordered subsets expectation maximization corrected with point spread function (TrueX algorithm) with a Hann filter of 4 mm full width at half maximum (FWHM) [26]. Photon attenuation was corrected based on CT images. The reconstructed matrix was 168 168 with a voxel size of 2.0 2.0 3.0 mm. The stand-alone PET scanner was operated in a 3-dimensional acquisition mode. The transmission data set was acquired for 3min using a 68Ge/68Ga retractable line source. A static emission data set was then acquired for 10 min. The images were reconstructed using a direct inversion Fourier transformation method with a Hann filter of 4 mm FWHM [27]. The reconstruction matrix was 256 256 with a voxel size of 1.3 1.3 2.4 mm. Stenotic lesions of the internal carotid artery were identified on CT angiography or MR angiography. A spherical region of interest with a diameter of 1 cm was then positioned on the corresponding area by an experienced nuclear physician (K.H.). Standardized uptake value (SUV) was calculated by the following formula: SUV = (tissue activity [Bq/ml])(body weight [g])/(injected radioisotope activity [Bq]) The maximum value of SUV (SUVmax) in each region of interest was measured and then compared with pathological findings. A 3-dimentional PET-CT viewer (Vox-Base II; J-Mac Sys18

Methods
Patients This prospective study totally included 25 patients who underwent CEA for carotid artery stenosis at our institute between January 2009 and January 2012. There were 22 men and 3 women. Their mean age was 68 years, ranging from 49 to 82 years. The lesions that caused ipsilateral ischemic events, including ischemic stroke, transient ischemic attack, and retinal ischemia, within the previous 6 months were defined as symptomatic. As a result, 10lesions were symptomatic and the remaining 15 were asymptomatic. The patients clinical data are shown in table1. The severity of carotid artery stenosis was defined using the North American Symptomatic Carotid Endarterectomy Trial Collaborators (NASCET) criteria on digital subtraction angiography or 3-dimensional computed tomography angiography (3D-CTA) [4]. The inclusion criteria for CEA comprised >70% carotid stenosis for both symptomatic and asymptomatic cases. Prior to CEA, FDG-PET and MRI were performed in all 25 patients.

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Table 1. Details of 25 patients included in this study

Case No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

Age years 78 74 49 75 76 65 82 67 69 73 62 58 64 69 72 75 58 81 59 76 61 64 54 76 65

Sex male male male male male female male male female male male male male male female male male male male male male male male male male

Symptom symptomatic symptomatic symptomatic symptomatic symptomatic asymptomatic symptomatic asymptomatic asymptomatic asymptomatic symptomatic asymptomatic asymptomatic asymptomatic asymptomatic asymptomatic asymptomatic symptomatic symptomatic asymptomatic asymptomatic asymptomatic asymptomatic asymptomatic symptomatic

FDG-PET positive positive positive positive positive positive positive positive positive positive positive positive positive negative negative negative negative negative negative negative negative negative negative negative negative

BB-T1WI H H H H H H H H H H I I I H H H H H I H I I I L L

TOF H H I I I I I I I I I I I H H H H H I I I I I I I

Plaque components LC+IPH LC+IPH LC+IPH LC+IPH LC LC LC LC LC LC LC LC LC IPH IPH IPH IPH IPH IPH FT FT FT FT FT Calc

CD68 II II III II III II III II II II III II III II II II I I II N/A I II II I I

MMP-9 III II II II III II III III III II III II III II II II II I II N/A I II I I II

H = High intensity; I = iso-intensity; L = low intensity; N/A = not available.

tem, Inc., Sapporo, Japan) and a software package implementing a mutual information-based image co-registration algorithm (Neurostat; University of Washington, Seattle, Wash., USA) [28, 29], both of which worked on Windows XP, were used for image analysis. The SUVmax of 2.0 was defined as positive according to Wu et al. [25]. Histological Evaluations The specimens were fixed in buffered formalin (4%) immediately after removal and were embedded in paraffin. Then, 4-m-thick cross sections were prepared for subsequent staining. They were stained with standard hematoxylin and eosin (H&E). In addition, the sections were stained with primary antibody against CD68 (mouse monoclonal anti-human CD68 antibody, 1:100 dilution; Dako Cytomation, Glostrup, Denmark) to identify the activated macrophages. They were also stained with primary antibody against matrix metalloproteinase (MMP)-9 (rabbit polyclonal anti-human MMP-9 antibody, 1: 50 dilution; Cell Signaling Technology, Boston, Mass., USA). The immunoreactivity was visualized using a streptavidin-biotin-peroxidase system kit (Histofine SAB-PO kit; Nichirei, Tokyo, Japan). The histologic slices were examined microscopically by 2 experienced readers (S.K. and H.S.) who were blinded to the MRI and 18F-FDG-PET results.

The plaque components of lipid, hemorrhage, calcification, and fibrous tissue were separately calculated as the percentages of the total plaque area on the H&E-stained section at the most stenotic site to match the FDG-PET and MRI slices. In this study, the principal components were classified into a large lipid core with no or minimal intraplaque hemorrhage (LC), a lipid core mixed with intraplaque hemorrhage (LC+IPH), a large intraplaque hemorrhage with minimal lipid component (IPH), calcification (Calc), and fibrous tissue (FT) according to the following criteria: LC, lipid >25% and hemorrhage 25%; IPH, hemorrhage >25% and lipid 25%; LC+IPH, lipid >25% and hemorrhage >25%; Calc, calcification >25%; FT, fibrous tissue>50% without LC, IPH, and LC+IPH. CD68 and MMP-9 staining was evaluated by using a score of: I = absent or minor staining; II = mild and local staining, and III = marked and diffuse staining in the entire section. Statistical Analysis The correlation between the findings on FDG-PET and those on MRI or histology were assessed using the 2 test. The level of statistical significance was p < 0.05. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) to identify the vulnerable plaque with LC or IPH were measured for FDG-PET and MRI.

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Table 2. Diagnostic power of each modality to identify lipid-rich plaques of the carotid arteries

Imaging modality FDG-PET positive BB-T1WI high signal BB-T1WI high signal and TOF iso-signal

Sensitivity, % 100 (13/13) 77 (10/13) 62 (8/13)

Specificity, % 100 (12/12) 50 (6/12) 92 (11/12)

PPV, % 100 (13/13) 63 (10/16) 89 (8/9)

NPV, % 100 (12/12) 67 (6/9) 69 (11/16)

Results

Table 3. Relationships between FDG-PET findings and immuno-

reactivity against CD68 and MMP-9

FDG-PET and MRI On FDG-PET, 13 patients (52.0%) had FDG-positive plaque and 12 had FDG-negative plaque. On the other hand, 16 patients (64.0%) had high signal intensity plaque on BB-T1WI. In 7 of these 16 patients, the lesions also showed high signal intensity on TOF imaging. Of 13 FDG-positive plaques, 10 (76.9%) showed high signal intensity on BB-T1WI. Of 12 FDG-negative plaques, however, 6 (50%) demonstrated high signal intensity on BB-T1WI. As a result, no significant correlation was found between the findings on FDG-PET and those on BB-T1WI (p = 0.211). Plaque Histology Histological examinations (H&E staining) disclosed LC in 9 plaques, LC+IPH in 4, IPH in 6, Calc in 1, and FT in 5. Relationship between FDG-PET and Histology Histological examinations showed that all of 13 FDGpositive plaques mainly had a lipid-rich component, including LC in 9 plaques and LC+IPH in 4. On the other hand, none of the other 12 FDG-negative plaques were rich in lipid component. Thus, histological diagnosis included IPH in 6 plaques, Calc in 1, and FT in 5. None of them had a large lipid core. The sensitivity and specificity to identify the lipid-rich plaques (LC and LC+IPH) were 100% for FDG-PET. Likewise, PPV and NPV were also 100% for FDG-PET (table2). More importantly, all of the FDG-positive plaques had strong immunoreactivity against both CD68 and MMP-9. As shown in table3, there was a significant correlation between the findings on FDG-PET and those on immunohistochemistry against CD68 and MMP-9 (p = 0.006 and 0.004, respectively). Relationship between MRI and Histology Of these 16 plaques with high signal intensity on BBT1WI, 9 (50%) had iso-signal intensity on TOF imaging. Histologically, 8 of these 9 plaques were classified into LC
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I CD68 FDG-PET positive FDG-PET negative MMP-9 FDG-PET positive FDG-PET negative 0 5 0 4

II 8 6 6 7

III 5 0 7 0

or LC+IPH. The sensitivity, specificity, PPV, and NPV to identify the lipid-rich plaques was 62, 92, 89, and 69% for BB-T1WI and TOF imaging, respectively. Combination with TOF imaging improved the power to identify the lipid-rich plaques, but the values were still lower than those for FDG-PET (table2). On the other hand, 7 of 16 plaques with high signal intensity on BB-T1WI also had high signal intensity on TOF imaging. All of these 7 plaques with high signal intensity on both BB-T1WI and TOF imaging had a significant intraplaque hemorrhage classified into IPH in 5plaques and LC+IPH in 2. As a result, the sensitivity, specificity, PPV, and NPV to identify a large intraplaque hemorrhage (IPH and LC+IPH) was 70, 100, 100, and 83%, respectively, for MRI (table4). Representative Cases Case 5 This 76-year-old male developed right hemiparesis and was admitted to our institute. Radiological examinations revealed 90% stenosis of the left internal carotid artery. Carotid plaque showed high signal intensity on BB-T1WI (fig.1a, arrow) and iso-signal intensity on TOF imaging (fig.1b, arrow). FDG uptake was high and its SUVmax was 2.13 (fig.1c, arrow). The carotid plaque was very soft (fig. 1d). Histological examinations revealed that the plaque was lipid rich (fig.1e) and was strongly positive for CD68 (fig.1f) and MMP-9 (fig.1g).
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Color version available online

Fig. 1. An example of the carotid plaque

with LC (case 5). MRI showed the carotid plaque with high intensity relative to the mandibular gland (asterisk) on BB-T1WI (a, arrow) and iso-intensity on TOF imaging (b, arrow). There was high FDG uptake in the carotid plaque (c, arrow). The intraoperative picture (d) and photomicrograph of H&E stained specimen (e) showed a soft plaque with large lipid core. This plaque had strong immunoreactivity against CD68 (f) and MMP9 (g).

Color version available online

Fig. 2. An example of carotid plaque with IPH (case 18). MRI showed the carotid plaque with high intensity on BB-T1WI (a, arrow) and TOF imaging (b, arrow). There was low FDG uptake in the carotid plaque (c, arrow). The intraoperative picture (d) and photomicrograph of H&E stained specimen (e) showed a plaque with large hematoma. This plaque had weak immunoreactivity against CD68 (f) and MMP9 (g).

Table 4. Diagnostic power of each modality to identify plaques with large intraplaque hemorrhages of the carotid arteries

Imaging modality FDG-PET positive BB-T1WI high signal BB-T1WI high signal and TOF high signal

Sensitivity, % 40 (4/10) 90 (9/10) 70 (7/10)

Specificity, % 40 (6/15) 53 (8/15) 100 (15/15)

PPV, % 31 (4/13) 56 (9/16) 100 (7/7)

NPV, % 50 (6/12) 89 (8/9) 83 (15/18)

Case 18 This 81-year-old male had repeated transient right hemiparesis and motor aphasia, and was admitted to our institute. Radiological examinations revealed 95% stenosis of the left internal carotid artery. Carotid plaque showed high signal intensity on both BB-T1WI (fig.2a, arrow) and TOF imaging (fig. 2b, arrow). FDG uptake was low and its SUVmax was 1.59 (fig.2c, arrow). Intraoperative observations demonstrated that the carotid plaque had a large intraplaque hemorrhage (fig.2d). Histological examinations revealed that the hematoma largely occupied the plaque (fig.2e) and that the plaque was negative for CD68 (fig.2f) and MMP-9 (fig.2g).
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Discussion

This study clearly demonstrates that high FDG uptake can highly predict lipid-rich plaque of the carotid artery. Its diagnostic power is significantly higher than MRI, including BB-T1WI and TOF imaging. All of the FDG-positive plaques were positive for both CD68 and MMP-9. Therefore, FDG-PET may be a powerful modality to predict lipid-rich and inflamed carotid plaques. This is the first report to demonstrate the validity of FDG-PET in the detection of inflammation in severe (>70%) carotid artery stenosis in Asian populations. On the other hand, carotid plaques with high signal intensity
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on both BB-T1WI and TOF imaging are highly likely to have a large intraplaque hematoma. These findings strongly suggest that FDG-PET and MRI are complementary in predicting vulnerable carotid plaque at a high risk of subsequent ischemic stroke. As mentioned above, anatomical information, such as the degree of stenosis, has previously been accepted as the most important index to determine the candidates for CEA. For this purpose, cerebral angiography, ultrasound, and 3D-CTA have been employed. However, recent studies have clarified that the morphology [30] and/or components of carotid plaque are alternative factors to determine the outcome in patients with carotid artery stenosis [10, 11, 31, 32]. Recently, there has been an increasing body of evidence that a dynamic inflamed process plays a role in the initiation, progression, and destabilization of atherosclerotic plaque [20]. Especially the macrophages are known to play a major role in plaque pathogenesis. They ingest the lipids and transform into foam cells, secreting various kinds of inflammatory cytokines and proteinases such as MMPs. The highly inflamed vulnerable plaque is typified by an abundance of inflammatory cells and proteins. FDG is a glucose analogue that is taken up by glucose-using cells and accumulates in proportion to their metabolic activity [20, 22, 23]. In atherosclerosis, FDG-PET has been reported to be a valuable tool to identify the inflamed and unstable plaques in the aorta, coronary and carotid arteries [9, 1925]. Rudd et al. [21] first reported that the macrophage-rich plaque was visible on FDG-PET in all 8 patients with symptomatic carotid artery stenosis. Reiter et al. [9] also reported that FDG uptake was high in 10 (83%) of 12 patients with carotid lesions that were compatible with their recent transient ischemic attack. Wu et al. [25] performed FDG-PET in 25 patients with significant carotid stenosis and reported a significant correlation between FDG uptake and the serum level of MMP-1. Taken together, previous studies have suggested that FDG-PET may be useful to noninvasively identify macrophage-rich (i.e. inflamed) carotid plaques at high risk of cerebrovascular events. On the other hand, MRI may be the most accurate tool to clarify the plaque morphology with high spatial resolution among the current clinically available imaging modalities [16, 17]. Especially black-blood MRI has been used for an in vivo noninvasive diagnostic method of atherosclerosis in human carotid arteries [18]. Many investigators have reported that the hemorrhagic component had high signal intensity on TOF and T1WI [1013, 16,
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17]. MRI is useful to detect intraplaque hemorrhage, which is one component of vulnerable plaque. The present data correlate very well with previous findings. On the contrary, many studies have focused on MRI to characterize lipid cores by using various imaging sequences and contrasts [18, 3335]. However, standardized sequence parameters and evaluation criteria to identify lipid on MRI have not yet been established. In fact, its diagnostic ability to predict lipid-rich plaques was lower than that of FDG-PET (table2). One of the most exciting findings of this study is the ability of the combination of FDG-PET and MRI to predict vulnerable carotid plaques, including those with a lipid-rich component and with a large intraplaque hemorrhage. When these modalities are combined, vulnerable or high-risk plaques can be identified very accurately (table2, 4). To the best of our knowledge, this is the first report that proves the usefulness of multidisciplinary modalities to identify vulnerable plaques in carotid arteries with a high certainty. For clinicians such as neurologists and neurosurgeons, the information on plaque composition is important to decide on therapeutic strategies in each patient with carotid artery stenosis. Thus, the thin or ruptured fibrous cap, the large underlying necrotic lipid core, or the presence of intraplaque hemorrhage or thrombus have recently been revealed to increase the risk of subsequent ischemic events [36, 37]. Very recently, Kobayashi et al. [38] also reported 2 patients who had unilateral internal carotid artery stenosis (<50% with echolucent plaque and ulceration) and suffered recurrent ischemic stroke despite treatment with antiplatelet and anticoagulation drugs. They found fresh thrombi in the ulcer within atheromatous plaque. Furthermore, several multicenter RCTs have been conducted to compare the therapeutic significance of CEA and carotid artery stenting in patients with carotid artery stenosis [3944]. Only the degree of stenosis has still been employed as the most important inclusion criterion in these studies. However, it is well known that carotid artery stenting may often cause postprocedural lesions on diffusion-weighted MRI and/or ischemic stroke in patients with lipid-rich carotid plaque [45]. Therefore, the presented dual imaging approach may help the clinician to make a decision on therapeutic strategies and options with low morbidity and mortality. From the viewpoint of cost effectiveness balance, however, it would be difficult to routinely perform dual PET/MRI examination for all patients with internal carotid artery stenosis. Therefore, the present findings should be extrapolated into routine clinical practice.
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Our study has several limitations. First, the small study size limits our interpretation and discussion. Second, the pulse triggering technique in black-blood MRI makes it difficult to shorten the TR enough for T1WI. Therefore, T1WI in this study might produce a contrast like proton density imaging, which is not good at identifying lipid components. Third, this study assessed compositional plaque features only by noncontrast MRI. Several studies have shown that dynamic contrast-enhanced MRI and ultra-small superparamagnetic particles of iron oxide-enhanced MRI are also useful techniques to evaluate inflammation in carotid plaques [14, 15, 19]. In future studies, it would be better to examine whether findings of these techniques correlate with FDG-PET.

Conclusions

This study strongly suggests that FDG-PET and MRI are complementary in predicting high-risk carotid plaques with inflamed or hemorrhagic components. The former technique would be valuable to identify lipidrich, inflamed plaques, and the latter would be useful to identify vulnerable plaques with a large hematoma. Therefore, the combination of these two modalities may noninvasively provide useful information on the plaque composition in the carotid arteries, contributing to improving the long-term outcome in patients with carotid artery stenosis.

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Imaging of Vulnerable Carotid Plaque

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