Abstract
Non-invasive detection of specific atherosclerotic plaque components related to vulnerability is of high clinical relevance to prevent cerebrovascular events. The feasibility of magnetic resonance imaging (MRI) for characterization of plaque components was already demonstrated. We aimed to evaluate the potential of ex vivo differential phase contrast X-ray tomography (DPC) to accurately characterize human carotid plaque components in comparison to high field multicontrast MRI and histopathology. Two human plaque segments, obtained from carotid endarterectomy, classified according to criteria of the American Heart Association as stable and unstable plaque, were examined by ex vivo DPC tomography and multicontrast MRI (T1-, T2-, and proton density-weighted imaging, magnetization transfer contrast, diffusion-weighted imaging). To identify specific plaque components, the plaques were subsequently sectioned and stained for fibrous and cellular components, smooth muscle cells, hemosiderin, and fibrin. Histological data were then matched with DPC and MR images to define signal criteria for atherosclerotic plaque components. Characteristic structures, such as the lipid and necrotic core covered by a fibrous cap, calcification and hemosiderin deposits were delineated by histology and found with excellent sensitivity, resolution and accuracy in both imaging modalities. DPC tomography was superior to MRI regarding resolution and soft tissue contrast. Ex vivo DPC tomography allowed accurate identification of structures and components of atherosclerotic plaques at different lesion stages, in good correlation with histopathological findings.
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Abbreviations
- DPC:
-
Differential phase contrast
- MRI:
-
Magnetic resonance imaging
- PD:
-
Proton density
- MTC:
-
Magnetization transfer contrast
- DW:
-
Diffusion-weighted
- L:
-
Lumen of the blood vessel
- M:
-
Media
- Int:
-
Intima
- IT:
-
Intimal thickening
- FC:
-
Fibrous cap
- LC:
-
Lipid core
- NC:
-
Necrotic core
- U:
-
Ulceration site
References
World Health Organization, Mackay J, Mensah GA, Mendis S, Greenlund K (2004) The atlas of heart disease and stroke. World Health Organization, Geneva
Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Judd SE, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Mackey RH, Magid DJ, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER, III, Moy CS, Mussolino ME, Neumar RW, Nichol G, Pandey DK, Paynter NP, Reeves MJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Wong ND, Woo D, Turner MB, American Heart Association Statistics C, Stroke Statistics S (2014) Heart disease and stroke statistics–2014 update: a report from the American Heart Association. Circulation 129:e28–e292. doi:10.1161/01.cir.0000441139.02102.80
Finn AV, Nakano M, Narula J, Kolodgie FD, Virmani R (2010) Concept of vulnerable/unstable plaque. Arterioscler Thromb Vasc Biol 30:1282–1292. doi:10.1161/ATVBAHA.108.179739
Pinzer BR, Cacquevel M, Modregger P, McDonald SA, Bensadoun JC, Thuering T, Aebischer P, Stampanoni M (2012) Imaging brain amyloid deposition using grating-based differential phase contrast tomography. Neuroimage 61:1336–1346. doi:10.1016/j.neuroimage.2012.03.029
Stampanoni M, Groso A, Isenegger A, Mikuljan G, Chen Q, Bertrand A, Henein S, Betemps R, Frommherz U, Bohler P, Meister D, Lange M, Abela R (2006) Trends in synchrotron-based tomographic imaging: the SLS experience. Dev X-Ray Tomogr 5:6318. doi:10.1117/12.679497
Weitkamp T, Diaz A, David C, Pfeiffer F, Stampanoni M, Cloetens P, Ziegler E (2005) X-ray phase imaging with a grating interferometer. Opt Express 13:6296–6304
Toussaint JF, LaMuraglia GM, Southern JF, Fuster V, Kantor HL (1996) Magnetic resonance images lipid, fibrous, calcified, hemorrhagic, and thrombotic components of human atherosclerosis in vivo. Circulation 94:932–938
Shinnar M, Fallon JT, Wehrli S, Levin M, Dalmacy D, Fayad ZA, Badimon JJ, Harrington M, Harrington E, Fuster V (1999) The diagnostic accuracy of ex vivo MRI for human atherosclerotic plaque characterization. Arterioscler Thromb Vasc Biol 19:2756–2761
Cai JM, Hatsukami TS, Ferguson MS, Small R, Polissar NL, Yuan C (2002) Classification of human carotid atherosclerotic lesions with in vivo multicontrast magnetic resonance imaging. Circulation 106:1368–1373
Qiao Y, Ronen I, Viereck J, Ruberg FL, Hamilton JA (2007) Identification of atherosclerotic lipid deposits by diffusion-weighted imaging. Arterioscler Thromb Vasc Biol 27:1440–1446. doi:10.1161/ATVBAHA.107.141028
Qiao Y, Hallock KJ, Hamilton JA (2011) Magnetization transfer magnetic resonance of human atherosclerotic plaques ex vivo detects areas of high protein density. J Cardiovasc Magn Reson 13:73. doi:10.1186/1532-429X-13-73
Müller A, Mu L, Meletta R, Beck K, Rancic Z, Drandarov K, Kaufmann PA, Ametamey SM, Schibli R, Borel N, Krämer SD (2014) Towards non-invasive imaging of vulnerable atherosclerotic plaques by targeting co-stimulatory molecules. Int J Cardiol 174:503–515. doi:10.1016/j.ijcard.2014.04.071
Stary HC, Chandler AB, Dinsmore RE, Fuster V, Glagov S, Insull W Jr, Rosenfeld ME, Schwartz CJ, Wagner WD, Wissler RW (1995) A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Arterioscler Thromb Vasc Biol 15:1512–1531
Saam T, Ferguson MS, Yarnykh VL, Takaya N, Xu D, Polissar NL, Hatsukami TS, Yuan C (2005) Quantitative evaluation of carotid plaque composition by in vivo MRI. Arterioscler Thromb Vasc Biol 25:234–239. doi:10.1161/01.ATV.0000149867.61851.31
Lacolley P, Regnault V, Nicoletti A, Li Z, Michel JB (2012) The vascular smooth muscle cell in arterial pathology: a cell that can take on multiple roles. Cardiovasc Res 95:194–204. doi:10.1093/cvr/cvs135
Riviere C, Boudghene FP, Gazeau F, Roger J, Pons JN, Laissy JP, Allaire E, Michel JB, Letourneur D, Deux JF (2005) Iron oxide nanoparticle-labeled rat smooth muscle cells: cardiac MR imaging for cell graft monitoring and quantitation. Radiology 235:959–967. doi:10.1148/radiol.2353032057
Tavora F, Cresswell N, Li L, Ripple M, Burke A (2010) Immunolocalisation of fibrin in coronary atherosclerosis: implications for necrotic core development. Pathology 42:15–22. doi:10.3109/00313020903434348
Coombs BD, Rapp JH, Ursell PC, Reilly LM, Saloner D (2001) Structure of plaque at carotid bifurcation: high-resolution MRI with histological correlation. Stroke 32:2516–2521
Li T, Li X, Zhao X, Zhou W, Cai Z, Yang L, Guo A, Zhao S (2012) Classification of human coronary atherosclerotic plaques using ex vivo high-resolution multicontrast-weighted MRI compared with histopathology. AJR Am J Roentgenol 198:1069–1075. doi:10.2214/AJR.11.6496
Nikolaou K, Becker CR, Muders M, Babaryka G, Scheidler J, Flohr T, Loehrs U, Reiser MF, Fayad ZA (2004) Multidetector-row computed tomography and magnetic resonance imaging of atherosclerotic lesions in human ex vivo coronary arteries. Atherosclerosis 174:243–252. doi:10.1016/j.atherosclerosis.2004.01.041
Worthley SG, Helft G, Fuster V, Fayad ZA, Fallon JT, Osende JI, Roque M, Shinnar M, Zaman AG, Rodriguez OJ, Verhallen P, Badimon JJ (2000) High resolution ex vivo magnetic resonance imaging of in situ coronary and aortic atherosclerotic plaque in a porcine model. Atherosclerosis 150:321–329
Gury-Paquet L, Millon A, Salami F, Cernicanu A, Scoazec JY, Douek P, Boussel L (2012) Carotid plaque high-resolution MRI at 3 T: evaluation of a new imaging score for symptomatic plaque assessment. Magn Reson Imaging 30:1424–1431. doi:10.1016/j.mri.2012.04.024
Worthley SG, Helft G, Fuster V, Fayad ZA, Rodriguez OJ, Zaman AG, Fallon JT, Badimon JJ (2000) Noninvasive in vivo magnetic resonance imaging of experimental coronary artery lesions in a porcine model. Circulation 101:2956–2961
Yuan C, Kerwin WS, Ferguson MS, Polissar N, Zhang S, Cai J, Hatsukami TS (2002) Contrast-enhanced high resolution MRI for atherosclerotic carotid artery tissue characterization. J Magn Reson Imaging 15:62–67
Appel AA, Chou CY, Larson JC, Zhong Z, Schoen FJ, Johnston CM, Brey EM, Anastasio MA (2013) An initial evaluation of analyser-based phase-contrast X-ray imaging of carotid plaque microstructure. Br J Radiol 86:20120318. doi:10.1259/bjr.20120318
Hetterich H, Fill S, Herzen J, Willner M, Zanette I, Weitkamp T, Rack A, Schuller U, Sadeghi M, Brandl R, Adam-Neumair S, Reiser M, Pfeiffer F, Bamberg F, Saam T (2013) Grating-based X-ray phase-contrast tomography of atherosclerotic plaque at high photon energies. Z Med Phys 23:194–203. doi:10.1016/j.zemedi.2012.12.001
Hetterich H, Willner M, Fill S, Herzen J, Bamberg F, Hipp A, Schuller U, Adam-Neumair S, Wirth S, Reiser M, Pfeiffer F, Saam T (2014) Phase-contrast CT: qualitative and quantitative evaluation of atherosclerotic carotid artery plaque. Radiology 271:870–878. doi:10.1148/radiol.14131554
Saam T, Herzen J, Hetterich H, Fill S, Willner M, Stockmar M, Achterhold K, Zanette I, Weitkamp T, Schuller U, Auweter S, Adam-Neumair S, Nikolaou K, Reiser MF, Pfeiffer F, Bamberg F (2013) Translation of atherosclerotic plaque phase-contrast CT imaging from synchrotron radiation to a conventional lab-based X-ray source. PLoS One 8:e73513. doi:10.1371/journal.pone.0073513
Fujimoto S, Kondo T, Kodama T, Fujisawa Y, Groarke J, Kumamaru KK, Takamura K, Matsunaga E, Miyauchi K, Daida H, Rybicki FJ (2014) A novel method for non-invasive plaque morphology analysis by coronary computed tomography angiography. Int J Cardiovasc Imaging 30:1373–1382. doi:10.1007/s10554-014-0461-5
Donnelly EH, Nemhauser JB, Smith JM, Kazzi ZN, Farfan EB, Chang AS, Naeem SF (2010) Acute radiation syndrome: assessment and management. South Med J 103:541–546. doi:10.1097/SMJ.0b013e3181ddd571
Corti R, Fuster V (2011) Imaging of atherosclerosis: magnetic resonance imaging. Eur Heart J 32:1709-19b. doi:10.1093/eurheartj/ehr068
Acknowledgments
The authors are grateful to Dr. Bernd R. Pinzer and Sabina Wunderlin for technical support. The Scientific Center for Optical and Electron Microscopy (ScopeM) of the ETH Zurich is acknowledged for support. We thank the surgeon Zoran Rancic (Z.R.) from the Clinic for Cardiovascular Surgery, University Hospital Zurich, for the initial macroscopic classification of the plaques. The team of Prof. Philipp A. Kaufmann from the Department of Nuclear Medicine, Cardiac Imaging, University Hospital Zurich, is acknowledged for coordinating the plaque collection.
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This work was financially supported by the Clinical Research Priority Program (CRPP) of the University of Zurich on Molecular Imaging (MINZ) and the Swiss National Science Foundation (Grant PZ00P3_136822 to J.K.).
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Meletta, R., Borel, N., Stolzmann, P. et al. Ex vivo differential phase contrast and magnetic resonance imaging for characterization of human carotid atherosclerotic plaques. Int J Cardiovasc Imaging 31, 1425–1434 (2015). https://doi.org/10.1007/s10554-015-0706-y
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DOI: https://doi.org/10.1007/s10554-015-0706-y