Ex vivo differential phase contrast and magnetic resonance imaging for characterization of human carotid atherosclerotic plaques
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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.
KeywordsX-rays Synchrotron Differential phase contrast Magnetic resonance imaging Carotid plaque Atherosclerosis
Differential phase contrast
Magnetic resonance imaging
Magnetization transfer contrast
Lumen of the blood vessel
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.
Compliance with Ethical Standards
Conflict of interest
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.).
- 1.World Health Organization, Mackay J, Mensah GA, Mendis S, Greenlund K (2004) The atlas of heart disease and stroke. World Health Organization, GenevaGoogle Scholar
- 2.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
- 12.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 CrossRefPubMedGoogle Scholar
- 13.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 15:1512–1531CrossRefPubMedGoogle Scholar
- 16.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 CrossRefPubMedGoogle Scholar
- 20.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 CrossRefPubMedGoogle Scholar
- 21.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 150:321–329CrossRefPubMedGoogle Scholar
- 26.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 CrossRefPubMedGoogle Scholar
- 27.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 CrossRefPubMedGoogle Scholar
- 28.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 PubMedCentralCrossRefPubMedGoogle Scholar
- 29.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 CrossRefPubMedGoogle Scholar