Abstract
Purpose
The aim of this study was to investigate in 18 patients with ischaemic stroke classified as cryptogenic and presenting non-stenotic carotid atherosclerotic plaques the morphological and biological aspects of these plaques with magnetic resonance imaging (MRI) and 18F-fluoro-deoxyglucose positron emission tomography (18F-FDG PET) imaging.
Methods
Carotid arteries were imaged 150 min after injection of 18F-FDG with a combined PET/MRI system. American Heart Association (AHA) lesion type and plaque composition were determined on consecutive MRI axial sections (n = 460) in both carotid arteries. 18F-FDG uptake in carotid arteries was quantified using tissue to background ratio (TBR) on corresponding PET sections.
Results
The prevalence of complicated atherosclerotic plaques (AHA lesion type VI) detected with high-resolution MRI was significantly higher in the carotid artery ipsilateral to the ischaemic stroke as compared to the contralateral side (39 vs 0 %; p = 0.001). For all other AHA lesion types, no significant differences were found between ipsilateral and contralateral sides. In addition, atherosclerotic plaques classified as high-risk lesions with MRI (AHA lesion type VI) were associated with higher 18F-FDG uptake in comparison with other AHA lesions (TBR = 3.43 ± 1.13 vs 2.41 ± 0.84, respectively; p < 0.001). Furthermore, patients presenting at least one complicated lesion (AHA lesion type VI) with MRI showed significantly higher 18F-FDG uptake in both carotid arteries (ipsilateral and contralateral to the stroke) in comparison with carotid arteries of patients showing no complicated lesion with MRI (mean TBR = 3.18 ± 1.26 and 2.80 ± 0.94 vs 2.19 ± 0.57, respectively; p < 0.05) in favour of a diffuse inflammatory process along both carotid arteries associated with complicated plaques.
Conclusion
Morphological and biological features of high-risk plaques can be detected with 18F-FDG PET/MRI in non-stenotic atherosclerotic plaques ipsilateral to the stroke, suggesting a causal role for these plaques in stroke. Combined 18F-FDG PET/MRI systems might help in the evaluation of patients with ischaemic stroke classified as cryptogenic.
Similar content being viewed by others
References
Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, et al. Heart disease and stroke statistics--2014 update: a report from the American Heart Association. Circulation 2014;129:e28–e292.
Krishnamurthi RV, Feigin VL, Forouzanfar MH, Mensah GA, Connor M, Bennett DA, et al. Global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990-2010: findings from the Global Burden of Disease Study 2010. Lancet Glob Health 2013;1:e259–81.
Bonita R. Epidemiology of stroke. Lancet 1992;339:342–4.
Risk of stroke in the distribution of an asymptomatic carotid artery. The European Carotid Surgery Trialists Collaborative Group. Lancet 1995;345:209–12.
Redgrave JN, Lovett JK, Gallagher PJ, Rothwell PM. Histological assessment of 526 symptomatic carotid plaques in relation to the nature and timing of ischemic symptoms: the Oxford plaque study. Circulation 2006;113:2320–8.
Adams RJ, Albers G, Alberts MJ, Benavente O, Furie K, Goldstein LB, et al. Update to the AHA/ASA recommendations for the prevention of stroke in patients with stroke and transient ischemic attack. Stroke 2008;39:1647–52.
Naghavi M, Libby P, Falk E, Casscells SW, Litovsky S, Rumberger J, et al. From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part II. Circulation 2003;108:1772–8.
Rudd JH, Hyafil F, Fayad ZA. Inflammation imaging in atherosclerosis. Arterioscler Thromb Vasc Biol 2009;29:1009–16.
Yuan C, Mitsumori LM, Beach KW, Maravilla KR. Carotid atherosclerotic plaque: noninvasive MR characterization and identification of vulnerable lesions. Radiology 2001;221:285–99.
Yuan C, Mitsumori LM, Ferguson MS, Polissar NL, Echelard D, Ortiz G, et al. In vivo accuracy of multispectral magnetic resonance imaging for identifying lipid-rich necrotic cores and intraplaque hemorrhage in advanced human carotid plaques. Circulation 2001;104:2051–6.
Tawakol A, Migrino RQ, Bashian GG, Bedri S, Vermylen D, Cury RC, et al. In vivo 18F-fluorodeoxyglucose positron emission tomography imaging provides a noninvasive measure of carotid plaque inflammation in patients. J Am Coll Cardiol 2006;48:1818–24.
Rudd JH, Warburton EA, Fryer TD, Jones HA, Clark JC, Antoun N, et al. Imaging atherosclerotic plaque inflammation with [18F]-fluorodeoxyglucose positron emission tomography. Circulation 2002;105:2708–11.
Judenhofer MS, Wehrl HF, Newport DF, Catana C, Siegel SB, Becker M, et al. Simultaneous PET-MRI: a new approach for functional and morphological imaging. Nat Med 2008;14:459–65.
Rischpler C, Nekolla SG, Beer AJ. PET/MR imaging of atherosclerosis: initial experience and outlook. Am J Nucl Med Mol Imaging 2013;3:393–6.
Amarenco P. Underlying pathology of stroke of unknown cause (cryptogenic stroke). Cerebrovasc Dis 2009;27 Suppl 1:97–103.
Freilinger TM, Schindler A, Schmidt C, Grimm J, Cyran C, Schwarz F, et al. Prevalence of nonstenosing, complicated atherosclerotic plaques in cryptogenic stroke. JACC Cardiovasc Imaging 2012;5:397–405.
Bayer-Karpinska A, Schwarz F, Wollenweber FA, Poppert H, Boeckh-Behrens T, Becker A, et al. The carotid plaque imaging in acute stroke (CAPIAS) study: protocol and initial baseline data. BMC Neurol 2013;13:201.
Martinez-Möller A, Souvatzoglou M, Delso G, Bundschuh RA, Chefd’hotel C, Ziegler SI, et al. Tissue classification as a potential approach for attenuation correction in whole-body PET/MRI: evaluation with PET/CT data. J Nucl Med 2009;50:520–6.
Delso G, Fürst S, Jakoby B, Ladebeck R, Ganter C, Nekolla SG, et al. Performance measurements of the Siemens mMR integrated whole-body PET/MR scanner. J Nucl Med 2011;52:1914–22.
Schwaiger M, Ziegler SI, Nekolla SG. PET/CT challenge for the non-invasive diagnosis of coronary artery disease. Eur J Radiol 2010;73:494–503.
Saam T, Raya JG, Cyran CC, Bochmann K, Meimarakis G, Dietrich O, et al. High resolution carotid black-blood 3T MR with parallel imaging and dedicated 4-channel surface coils. J Cardiovasc Magn Reson 2009;11:41.
Hutton BF, Braun M, Thurfjell L, Lau DY. Image registration: an essential tool for nuclear medicine. Eur J Nucl Med Mol Imaging 2002;29:559–77.
Rosset A, Spadola L, Ratib O. OsiriX: an open-source software for navigating in multidimensional DICOM images. J Digit Imaging 2004;17:205–16.
Rudd JH, Myers KS, Bansilal S, Machac J, Pinto CA, Tong C, et al. Atherosclerosis inflammation imaging with 18F-FDG PET: carotid, iliac, and femoral uptake reproducibility, quantification methods, and recommendations. J Nucl Med 2008;49:871–8.
Cai JM, Hatsukami TS, Ferguson MS, Small R, Polissar NL, Yuan C. Classification of human carotid atherosclerotic lesions with in vivo multicontrast magnetic resonance imaging. Circulation 2002;106:1368–73.
Kerwin W, Xu D, Liu F, Saam T, Underhill H, Takaya N, et al. Magnetic resonance imaging of carotid atherosclerosis: plaque analysis. Top Magn Reson Imaging 2007;18:371–8.
Saam T, Ferguson MS, Yarnykh VL, Takaya N, Xu D, Polissar NL, et al. Quantitative evaluation of carotid plaque composition by in vivo MRI. Arterioscler Thromb Vasc Biol 2005;25:234–9.
Kampschulte A, Ferguson MS, Kerwin WS, Polissar NL, Chu B, Saam T, et al. Differentiation of intraplaque versus juxtaluminal hemorrhage/thrombus in advanced human carotid atherosclerotic lesions by in vivo magnetic resonance imaging. Circulation 2004;110:3239–44.
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;102:959–64.
Meyer BC, Hemmen TM, Jackson CM, Lyden PD. Modified National Institutes of Health Stroke Scale for use in stroke clinical trials: prospective reliability and validity. Stroke 2002;33:1261–6.
Silvera SS, Aidi HE, Rudd JH, Mani V, Yang L, Farkouh M, et al. Multimodality imaging of atherosclerotic plaque activity and composition using FDG-PET/CT and MRI in carotid and femoral arteries. Atherosclerosis 2009;207:139–43.
Saito H, Kuroda S, Hirata K, Magota K, Shiga T, Tamaki N, et al. Validity of dual MRI and F-FDG PET imaging in predicting vulnerable and inflamed carotid plaque. Cerebrovasc Dis 2013;35:370–7.
Figueroa AL, Subramanian SS, Cury RC, Truong QA, Gardecki JA, Tearney GJ, et al. Distribution of inflammation within carotid atherosclerotic plaques with high-risk morphological features: a comparison between positron emission tomography activity, plaque morphology, and histopathology. Circ Cardiovasc Imaging 2012;5:69–77.
Tang TY, Howarth SP, Miller SR, Graves MJ, UKing-Im JM, Li ZY, et al. Comparison of the inflammatory burden of truly asymptomatic carotid atheroma with atherosclerotic plaques in patients with asymptomatic carotid stenosis undergoing coronary artery bypass grafting: an ultrasmall superparamagnetic iron oxide enhanced magnetic resonance study. Eur J Vasc Endovasc Surg 2008;35:392–8
Kwee RM, Truijman MT, Mess WH, Teule GJ, ter Berg JW, Franke CL, et al. Potential of integrated [18F] fluorodeoxyglucose positron-emission tomography/CT in identifying vulnerable carotid plaques. AJNR Am J Neuroradiol 2011;32:950–4.
Kwee RM, Teule GJ, van Oostenbrugge RJ, Mess WH, Prins MH, van der Geest RJ, et al. Multimodality imaging of carotid artery plaques: 18F-fluoro-2-deoxyglucose positron emission tomography, computed tomography, and magnetic resonance imaging. Stroke 2009;40:3718–24.
Rominger A, Saam T, Wolpers S, Cyran CC, Schmidt M, Foerster S, et al. 18F-FDG PET/CT identifies patients at risk for future vascular events in an otherwise asymptomatic cohort with neoplastic disease. J Nucl Med 2009;50:1611–20.
Marnane M, Prendeville S, McDonnell C, Noone I, Barry M, Crowe M, et al. Plaque inflammation and unstable morphology are associated with early stroke recurrence in symptomatic carotid stenosis. Stroke 2014;45:801–6.
Marnane M, Merwick A, Sheehan OC, Hannon N, Foran P, Grant T, et al. Carotid plaque inflammation on 18F-fluorodeoxyglucose positron emission tomography predicts early stroke recurrence. Ann Neurol 2012;71:709–18.
Huet P, Burg S, Le Guludec D, Hyafil F, Buvat I. Variability and uncertainty of 18F-FDG PET imaging protocols for assessing inflammation in atherosclerosis: suggestions for improvement. J Nucl Med 2015;56:552–9.
Eldib M, Bini J, Robson PM, Calcagno C, Faul DD, Tsoumpas C, et al. Markerless attenuation correction for carotid MRI surface receiver coils in combined PET/MR imaging. Phys Med Biol 2015;60:4705–17.
Bini J, Eldib M, Robson PM, Calcagno C, Fayad ZA. Simultaneous carotid PET/MR: feasibility and improvement of magnetic resonance-based attenuation correction. Int J Cardiovasc Imaging 2015
Acknowledgments
We thank Sylvia Schachoff, Anna Winter, and Claudia Meisinger for their valuable help in acquiring PET/MR images in the patients of this study and Isabelle Dregelly for setting up MRI sequences.
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The local Ethics Committee approved the study and all participants provided written informed consent.
Clinical Trial Registration: Unique Identifier NCT01284933; URL: https://clinicaltrials.gov
Funding sources
This work was supported by the Advanced Research Grant “Multimodal Molecular Imaging” (MUMI; Grant number: 294582; European Research Council Executive Agency) and by the Deutsche Forschungsgemeinschaft (DFG; Grossgeräteinitiative).
Conflicts of interest
Markus Schwaiger has a research cooperation contract with Siemens Healthcare AG. The other authors have no potential conflicts of interest relevant to this article.
Author information
Authors and Affiliations
Corresponding author
Additional information
Fabien Hyafil and Andreas Schindler contributed equally to this work.
Rights and permissions
About this article
Cite this article
Hyafil, F., Schindler, A., Sepp, D. et al. High-risk plaque features can be detected in non-stenotic carotid plaques of patients with ischaemic stroke classified as cryptogenic using combined 18F-FDG PET/MR imaging. Eur J Nucl Med Mol Imaging 43, 270–279 (2016). https://doi.org/10.1007/s00259-015-3201-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00259-015-3201-8