Article
Histopathological correlation and feasibility of atherosclerotic carotid lesion classification usingT2* weighted imaging at 9.4T MRI
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Published: | March 23, 2011 |
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Outline
Abstract
Introduction: Patients suffering from stroke often show severe carotid artery atherosclerosis. To prevent this outcome, early detection and clear determination of lesion compounds in-vivo would be helpful for early treatment.
Material and methods: Carotid artery lesions of 27 patients with ≥70% internal carotid artery stenosis who underwent surgery were firstly analyzed using a 3D multi-contrast MRI protocol at 9.4 Tesla consisting of T1, T2, and T2* weighted sequences (spatial resolution ~100μm3). Thereafter, histology as the gold standard procedure was used for comparison. After formalin fixation the lesions were examined histologically using hematoxylin-Eosin and Elastic-van-Gieson stainings. They were classified according to the modified AHA criteria scheme and corresponding MRI slices were assessed.
Results: Accuracy of plaque classification based on MR images using modified AHA criteria was 87.5% (86% to 89%).
Conclusion: Compared to standard multi-contrast techniques, incorporation of T2* weighted imaging into multi-contrast MRI has proven to be valuable for identification of intraplaque hemorrhage and intraluminal thrombi. Further combinations e.g. with proton density may enhance accuracy regarding lesion composition and may help to identify patients eligible for preemptive treatment before symptom onset.
Introduction
Stenotic atherosclerosis in the internal carotid artery (ICA) is a major source of embolic stroke [1]. Non-invasive assessment per magnetic resonance imaging (MRI) [2] especially of so-called vulnerable plaques [3] should help to determine plaques that are susceptible to complications [4] and future cerebrovascular events [5]. Standard MR plaque imaging protocols identifies relevant plaque components with sensitivities and specificities of ~80–90% [6], [7], [8], [9], [10]. Since blood degradation products such as ferritin and hemosiderin significantly increase MRI susceptibility and T2* relaxation times and T2* sequences are routinely used for the detection of cerebral microbleeding or intracranial hemorrhage [11]. Ex-vivo MRI at high fields is ideally suited to evaluate the impact of new MRI sequences [12], [13]. The aim of this study was to test the feasibility of a new protocol including T2* measurement and to compare its accuracy with the histology of the plaques with respect to the modified American Heart Association (AHA) lesion type classification [14], [15].
Methods
27 patients (age = 68.4 ±9.0 years, 6 female) with internal carotid artery (ICA) stenosis ≥70% as determined by Doppler ultrasound (83.3 ±7.1%, range 70–95%) according to the European Carotid Surgery Trial (ECST) criteria [16] were prospectively included. In all patients, carotid eversion endarterectomy was performed and the tissue was immediately fixed in 4% formalin after resection to allow for later use in the MRI-examination. MRI imaging was performed on a 9.4T MRI system (Bruker BioSpin 94/20, Ettlingen, Germany, maximum gradient amplitude = 675 mT/m) using a transmit/receive 1H quadrature birdcage resonator (inner diameter: 35 mm).
The MRI protocol included 3D pulse sequences as follows:
T1 weighted (T1w) gradient echo (GRE) imaging, T2 weighted (T2w) fast spin echo (RARE), T2* weighted (T2*w) gradient echo GRE imaging. Total scan duration for the completion of the multi-contrast protocol was approximately 9 hours. Intensities of different plaque components (hypointense, isointense, hypereintens appearance) in relation to the formalin buffer a pilot study was performed earlier on a different set of plaques.
After MR imaging, formalin fixed plaques were decalcified with EDTA solution to allow for clear cutting of sections for further histological examinations. Sections were orientated from the distal to the proximal part of the plaque to enable a reliable matching with MR images. Tissue was processed for paraffin embedding and hematoxylin-eosin (HE) and Elastica-van-Gieson (EvG) stains were applied. Plaque classification [14], [15], [17] was done according to the modified AHA classification. In total, 115 MR image slices were available for comparison with histology.
Results
As to be expected the atherosclerotic lesions showed advanced lesions with 50% belonging to the class VI (complicated lesion) according to the AHA classification (Table 1 [Tab. 1]). Despite the decalcification process prior to embedding for histological analysis, sites of calcifications were detecable and corresponded to MRI detected areas. The lesion classification by MRI was accurate in 93.4% when compared to the histological view.
Calcifications and areas of neovascularization were hypodense in T1 and T2* with slightly sharper demarcation in T2*. Thrombi were slightly hyperdense in T1 and hypodense in T2* Fresh hemorrhages showed a hyperdense behaviour in T1 but as hypodense area in T2*.
Discussion
The results of this study show that the addition of T2* weight MR imaging enhanced the detection of intraplaque hemorrhage and thrombus formation of atherosclerotic lesions. Since those are important in plaque destabilization which may lead to plaque rupture and subsequent complete obliteration and blood flow cessation the better detection may help to find vulnerable plaques and earlier treatment of the patients. The correlation between MRI and histology was high thus showing that non-invasive imaging is reliable for classification of high grade atherosclerotic lesion components. Nevertheless, the study also showed that still there have to be further investigations as to how facilitate the clear detection of calcified areas versus hemorrhage/neovascularisation and specification of older hemorrhagic fields. Furthermore, shorter MRI protocols need to be tested for the applications in a patient in-vivo setting.
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