No abstract

Background-MRI of specific components in atherosclerotic plaque may provide information on plaque stability and its potential to rupture. We evaluated gadofluorine in atherosclerotic rabbits using a new MR sequence that allows plaque detection within 1 hour after injection and assessed enhancement in lipid-rich and non-lipid-rich plaques. Methods and Results-Twelve rabbits with aortic plaque and 6 controls underwent MRI before and up to 24 hours after gadofluorine injection (50 mol/kg). Two T1-weighted, segmented gradient-echo sequences (TFL) were compared to enhance vessel wall delineation after injection: (1) an inversion-recovery prepulse (IR-TFL) or (2) a combination of inversion-recovery and diffusion-based flow suppression prepulses (IR-DIFF-TFL). With the use of IR-TFL at 1 hour after injection, the vessel wall was not delineated because of poor flow suppression; at 24 hours after injection, the enhancement was 37% (PϽ0.01). IR-DIFF-TFL showed significant enhancement after versus before contrast (1 . There was no enhancement in the vessel wall after gadofluorine injection in the control group. A strong correlation was found (r 2 ϭ0.87; PϽ0.001) between the lipid-rich areas in histological sections and signal intensity in corresponding MR images. This suggests a high affinity of gadofluorine for lipid-rich plaques. Conclusions-Gadofluorine-enhanced MRI improves atherosclerotic plaque detection. The IR-DIFF-TFL method allows early detection of atherosclerotic plaque within 1 hour after gadofluorine injection.

As previously reported, Gadofluorine M-enhanced magnetic resonance imaging clearly demarcates atherosclerotic plaques from the normal vessel wall. To date, the underlying mechanism has remained unknown. Gadofluorine M is a gadolinium-containing macrocyclic contrast agent containing hydrophilic and hydrophobic moieties. To elucidate the mechanism of accumulation, fluorescently labeled and radioactively labeled derivates of Gadofluorine M were used to determine affinity and specificity of Gadofluorine M binding to blood serum and plaque components in vitro and for the distribution within the plaque of WHHL rabbits in vivo. Gadofluorine M binds to serum albumin, leading to a breakdown of micelles after intravenous injection. The affinity of Gadofluorine M to serum albumin is k(D) = 2 micromol/l. Gadofluorine then penetrates the atherosclerotic plaque while bound to albumin and then accumulates within the extracellular, fibrous parts of the plaque by binding to collagens, proteoglycans and tenascin, having the same affinity to these plaque constituents as to albumin. In contrast, weak binding was determined to LDL (k(D) = 2 mmol/l) and even no binding to hyaluronic acid. The driving force of binding and accumulation is the hydrophobic moiety of the molecules interacting with hydrophobic plaque materials. Thus, Gadofluorine M accumulates within the fibrous plaque or in the fibrous cap of a plaque containing high amounts of extracellular matrix components, but not in the lipid-rich areas. In combination with high-resolution MRI, Gadofluorine M might enable the detection of thin-cap fibroatheromas, also named the vulnerable plaque.

Gadomer-17 is a promising new MR contrast medium that has an intravascular distribution and a rapid renal elimination.