Title:
|
Magnetic resonance imaging of cellular and molecular events in inflammation
|
Imaging leucocyte trafficking is a major goal in inflammation research, since
one ofthe key features of the immune system is cell migration. Ultrasmall iron oxide
nanoparticles (USPIO) are iron-based T2-enhancing magnetic resonance (MR)
imaging contrast agents, which are a different class ofcontrast agent compared to the
more traditional, clinically-established Tl-enhancing agents such as GadoliniumDTPA.
The work presented in this project investigates different methods using both
these classes ofcontrast agent for imaging different aspects ofinflammation at
cellular and molecular levels.
The uptake and MR imaging ofUSPIO and Gadolinium-DTPA by leucocytes in-vitro
and in-vivo has been investigated. Activated endothelium is a proven surrogate for
inflammatory sites. E-selectin is an adhesion molecule which is luminally expressed
by activated endothelium early-on in the inflammatory process. This work has tested
the hypothesis that activated endothelium can be imaged using magnetic resonance.
USPIO have been conjugated with a monoclonal antibody targeting expressed Eselectin,
and tested in-vitro and in-vivo using a murine model ofoxazolone-induced
contact hypersensitivity inflammation in the ear. The majority ofMR studies in this
project were conducted at a high MR field strengths of9.4T.
The results indicate that MR imaging ofleucocyte migration and ofmolecular
markers of activated endothelium are feasible. However there are limitations on the
degree of success, which are presented and discussed. Targeted and cell specific
imaging ofinflammatory lesions has the potential to be important investigative tool.
|