Imaging of neuroinflammation and anti-inflammatory treatment with molecular MRI
Introduction:
Stroke is one of the leading causes of death and disability. The only current acute treatment,
thrombolysis with rTPA, is limited to a time window of 3 hours after stroke onset due to the increased
risk of hemorrhage. A potential target for late stroke treatment is neuroinflammation. Leukocytes are
the cellular mediators of neuroinflammation. They infiltrate the injured brain tissue over a prolonged
time after stroke and contribute to worsening of stroke outcome. Cell adhesion molecules (CAMs) are
upregulated in the first days after stroke and are responsible for adhesion and migration of the
leukocytes. The spatiotemporal profile of CAMs is still largely unresolved, even though they are crucial
for efficient anti-inflammatory therapies. Our overall goal is to elucidate the spatiotemporal profile of
CAM after experimental stroke with novel in vivo molecular imaging methods. More knowledge of the
spatiotemporal profile of CAMs may lead the way to successful application and monitoring of promising
anti-inflammatory treatment strategies after stroke.
Student Project:
To elucidate the spatiotemporal profile of CAMs in vivo, we plan to develop contrast agent that targets a
specific CAM. The coupling of a CAM-targeted moiety to a lipid-based contrast agent will be optimized in
this project and the contrast agent will be tested in vitro before application in a mouse stroke model.
Multiple imaging techniques (MRI, confocal microscopy) in combination with chemical synthesis and cell
assays will be used to develop a targeted contrast agent for imaging of neuroinflammation after stroke.
Details:
Estimated time for the project is 6-9 months with the earliest starting September 2009. The project is a
collaboration between the Image Sciences Institute (UMC Utrecht) and the Molecular Cell Biology and
Immunology (VU Medical Center, Amsterdam). Experiments will be conducted at both locations.
Contact:
Lisette Deddens
lisette@invivonmr.uu.nl