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Magnetic Resonance Properties of Gd(III)-Bound Lipid-Coated Microbubbles and their Cavitation Fragments



Jameel Feshitan, Michael A. Boss, Mark Borden


Gas-filled microbubbles are potentially useful theranostic agents for magnetic resonance imaging guided focused ultrasound surgery (MRIgFUS). Previously, MRI at 9.4 T was used to measure the contrast properties of lipid-coated microbubbles with Gadolinium (Gd(III)) bound to the lipid headgroups, which revealed that the longitudinal molar relaxivity (r1) increased after microbubble fragmentation. This behavior was attributed to an increase in water proton exchange with the Gd(III)-bound lipid fragments caused by an increase in the lipid headgroup area that accompanied the lipid shell monolayer-to-bilayer transition. In this report, we sought to explore this mechanism by comparing the changes in r1 and r2* after fragmentation of microbubbles consisting of Gd(III) bound to two different locations on the lipid monolayer shell: the phosphatidylethanolamine (PE) lipid headgroup region or the distal region of the polyethylene-glycol (PEG) brush. Nuclear magnetic resonance (NMR) at 1.5 T was used to measure the contrast properties of the various constructs. Results for the lipid headgroup-labeled Gd(III)-microbubbles revealed that r1 increased after microbubble fragmentation, while r2* was unchanged. Analysis of PEG-labeled Gd(III)-microbubbles revealed that both r1 and r2* decreased after microbubble fragmentation. Further analysis revealed that the microbubble gas core enhanced the transverse MR signal (T2*) in a concentration-dependent manner, but minimally affected the longitudinal (T1) signal. These results illustrate a new method of using NMR to measure biomembrane packing structure, and they suggest that two mechanisms, proton exchange enhancement by lipid membrane relaxation and magnetic field inhomogeneity imposed by the gas/liquid interface, may be used to detect and differentiate Gd(III)-labeled microbubbles and their cavitation fragments with MRI.


Phospholipid, PEG, Proton Exchange, Susceptibility, Theranostic, Contrast Agent, medical imaging


Feshitan, J. , Boss, M. and Borden, M. (2012), Magnetic Resonance Properties of Gd(III)-Bound Lipid-Coated Microbubbles and their Cavitation Fragments, Langmuir, [online], (Accessed June 17, 2024)


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Created October 29, 2012, Updated October 12, 2021