An approach towards molecular imaging of activated platelets allows imaging of symptomatic human carotid plaques in a new model of a tissue flow chamber

Dominik von Elverfeldt, Mirko Meißner, Karlheinz Peter, Dominik Paul, Fabian Meixner, Irene Neudorfer, Annette Merkle, Andreas Harloff, Andreas Zirlik, Joachim Schöllhorn, Michael Markl, Jürgen Hennig, Christoph Bode, C. von zur Muhlen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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 9.4T 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.

Original languageEnglish (US)
Pages (from-to)204-213
Number of pages10
JournalContrast Media and Molecular Imaging
Volume7
Issue number2
DOIs
StatePublished - Mar 2012

Keywords

  • Atherosclerosis
  • Carotid endarterectomy
  • Magnetic resonance imaging
  • Platelets

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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