- Meeting abstract
- Open Access
2115 A novel targeted iron oxide nanocolloid agent for rapid detection of fibrin clots via T1 and T2 weighted MRI
© Caruthers et al; licensee BioMed Central Ltd. 2008
- Published: 22 October 2008
- Iron Oxide
- Blood Pool Clearance
- Susceptibility Heterogeneity
- Emulsion Nanoparticles
- Endothelial Cell Surface Marker
Targeted iron oxide nanoparticles are easily detected with MR by their exaggerated signal dropout. Recent advanced techniques are emerging to visualize iron oxide particles as "hot spots" rather than signal dearth. For background blood pool clearance, a typical delay of 24 hr is required between contrast treatment and imaging. Although targeted USPIO or MION agents bind endothelial cell surface markers, they also further extravasate into plaque, binding macrophages or other intraplaque constituents during the 24-hour wait. This confounds the morphological source of the MR signal. Moreover, in coronary MR imaging_where high temporal and spatial resolution are required and inherent anatomic magnetic susceptibility heterogeneity masks that of the iron oxide agents_dark spot T2-weighted gradient echo imaging of targeted iron oxides is challenging and has not yet been demonstrated. The objective of this research was to develop an intravascular, fibrin-specific iron oxide agent useful for early, rapid detection and quantification of ruptured plaque in coronary arteries with MRI.
Superparamagnetic nanocolloid particles were developed with the core having multiple magnetite nanoparticles suspended in vegetable oil and encased in a lipid membrane. The MR T1 and T2 properties of the nanocolloid were determined using serial dilutions of the agent from 100% to 1% and MR acquisitions including Look-Locker (inversion recovery) and multi-echo gradient-echo techniques. To assess signal on both T1- and T2-weighted images, functionalized particles were targeted to clot surfaces with biotin and an antibody targeted to fibrin-rich thrombi (n = 7) suspended in saline in vitro; one clot served as an untreated control reference. Imaging of the clots was performed at 1.5 T using a high-resolution (0.3 × 0.3 × 1.2 mm3) 3D T1-weighted turbo spin-echo sequence for ROI analysis and lower-resolution (1 × 1 × 5 mm3) gradient-echo imaging, both T1-and T2*-weighted, for visual inspection.
These larger, fibrin-specific superparamagnetic nanocolloids may provide highly sensitive, bright-contrast detection of microthrombi exposed in ruptured plaque. The combination of high MR sensitivity and the imaging speed advantages of short T1-weighted pulse sequences may overcome the cardiac motion barrier to MR coronary molecular imaging.
This article is published under license to BioMed Central Ltd.