| Title: |
Molecular MRI of fresh thrombi using a bimodal α2-antiplasmin-based contrast agent |
| Authors: |
Miserus, RJHM Robbert-Jan; Herias, MV; Prinzen, L; Lobbes, MBI; Suylen, R-J Van; Dirksen, A Anouk; Hackeng, TM Tilman; Heemskerk, JWM Johan; Engelshoven, JMA van; Daemen, MJAP Mat; Zandvoort, M Marc van; Heeneman, S; Kooi, ME Marianne Eline |
| Source: |
ISSN:1936-878X. |
| Publication Year: |
2009 |
| Collection: |
Eindhoven University of Technology (TU/e): Research Portal |
| Description: |
Objectives: We aimed to investigate whether early thrombus formation can be visualized with in vivo magnetic resonance imaging (MRI) by the use of a novel bimodal a2-antiplasmin-based contrast agent (CA). Background: Thrombus formation plays a central role in several vascular diseases. During the early phases of thrombus formation, activated factor XIII (FXIIIa) covalently cross-links a2-antiplasmin to fibrin, indicating the potential of a2-antiplasmin-based CAs in the detection of early thrombus formation. Methods: A bimodal CA was synthesized by coupling gadolinium-diethylene triamine pentaacetic acid and rhodamine to an a2-antiplasmin-based peptide. For the control CA, a glutamine residue essential for cross-linking was replaced by alanine. In vitro-generated thrombi were exposed to both CAs and imaged by MRI and 2-photon laser-scanning microscopy. Immunohistochemistry was performed on human pulmonary thromboemboli sections to determine the presence of a2-antiplasmin and FXIII in different thrombus remodeling phases. In vivo feasibility of the CA in detecting early thrombus formation specifically was investigated with MRI. Results: In vitro-generated thrombi exposed to the a2-antiplasmin-based CA showed hyperintense magnetic resonance signal intensities at the thrombus edge. No hyperintense signal was observed when we used the a2-antiplasmin-based CA in the presence of FXIII inhibitor dansylcadaverine nor when we used the control CA. Two-photon laser-scanning microscopy demonstrated that the a2-antiplasmin-based CA bound to fibrin. Immunohistochemistry demonstrated substantial a2-antiplasmin staining in fresh compared with lytic and organized thrombi. The administration of CA in vivo within seconds after inducing thrombus formation increased contrast-to-noise ratios (CNRs 2.28 ± 0.39, n=6) at the site of thrombus formation compared with the control CA (CNRs -0.14 ± 0.55, p = 0.003, n = 6) and a2-antiplasmin-based CA administration 24 to 48 h after thrombus formation (CNRs 0.11 ± 0.23, p = 0.006, n = 6). ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
http://repository.tue.nl/713325 |
| Availability: |
http://repository.tue.nl/713325 |
| Rights: |
Copyright (c) Miserus, RJHM Robbert-Jan ; Copyright (c) Herias, MV ; Copyright (c) Prinzen, L ; Copyright (c) Lobbes, MBI ; Copyright (c) Suylen, R-J Van ; Copyright (c) Dirksen, A Anouk ; Copyright (c) Hackeng, TM Tilman ; Copyright (c) Heemskerk, JWM Johan ; Copyright (c) Engelshoven, JMA van ; Copyright (c) Daemen, MJAP Mat ; Copyright (c) Zandvoort, M Marc van ; Copyright (c) Heeneman, S ; Copyright (c) Kooi, ME Marianne Eline |
| Accession Number: |
edsbas.1F66B24E |
| Database: |
BASE |