Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
von Elverfeldt, D; Meissner, M; Peter, K; Paul, D; Meixner, F; Neudorfer, I; Merkle, A; Harloff, A; Zirlik, A; Schöllhorn, J; Markl, M; Hennig, J; Bode, C; von zur Muhlen, C.
An approach towards molecular imaging of activated platelets allows imaging of symptomatic human carotid plaques in a new model of a tissue flow chamber.
CONTRAST MEDIA MOL I. 2012; 7(2): 204-213.
Doi: 10.1002/cmmi.482
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- Co-Autor*innen der Med Uni Graz
- Zirlik Andreas
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- Abstract:
- The development of magnetic resonance imaging (MRI) contrast agents targeting epitopes in atherosclerosis is of general interest. In particular, early detection of activated platelets as key players in plaque rupture could provide improved triage of patients. However, so far the efficiency of contrast agents targeting human pathologies can only be examined in animal experiments, which do not necessarily reflect human in vivo conditions. We therefore describe application of a contrast agent targeting activated human platelets in an MRI tissue flow chamber, allowing detection and characterization of contrast agent binding. Microparticles of iron oxide (MPIO) were conjugated to an antibody targeting ligand-induced binding sites (LIBS) on the activated platelet glycoprotein IIb/IIIa-receptor or to control antibody, resulting in LIBS-MPIO or control-MPIO contrast agent. Human endarterectomy specimens from patients with acute stroke or transient ischemic attack were imaged ex vivo before and after contrast agent perfusion using a 9.4 T MRI system. Specimens were measured under static (n = 18) or flow conditions (n = 18) in a specially designed flow chamber setup, simulating physiological conditions in a stenosed vessel. A significant MPIO-induced negative contrast was achieved in MRI by LIBS-MPIO in specimens under static and flow conditions (LIBS-MPIO vs control-MPIO: p < 0.01), and the location of LIBS-MPIO binding corresponded well between histology and MRI (p < 0.05). The number of MPIOs per platelet area on endarterectomy specimens in histology was significantly higher with LIBS-MPIO (p < 0.001). Furthermore, the intensity of contrast agent binding and signal change showed the potential to reflect the severity of clinical symptoms. LIBS-MPIO allows the detection of activated platelets on the surface of symptomatic atherosclerotic human plaques using molecular MRI. Furthermore, the MRI tissue flow chamber setup described could help to evaluate binding properties of contrast agents, and might therefore be an interesting tool for contrast agent development from animal experiments towards clinical application. Copyright © 2012 John Wiley & Sons, Ltd.
- Find related publications in this database (using NLM MeSH Indexing)
- Aged -
- Binding Sites -
- Carotid Stenosis - physiopathology
- Carotid Stenosis - surgery
- Contrast Media -
- Endarterectomy, Carotid -
- Female -
- Ferric Compounds - chemistry
- Humans -
- Ligands -
- Magnetic Resonance Imaging -
- Male -
- Models, Biological -
- Molecular Imaging - methods
- Platelet Activation - physiology
- Rheology - instrumentation
- Rheology - methods
- Find related publications in this database (Keywords)
- magnetic resonance imaging
- platelets
- atherosclerosis
- carotid endarterectomy