Magnetic resonance properties of Gd(III)-bound lipid-coated microbubbles and their cavitation fragments
Jameel A Feshitan1, Michael A Boss, Mark A Borden
1Department of Mechanical Engineering, University of Colorado, Boulder, Colorado 80309, United States.
Abstract:
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 lipid headgroups, which revealed that the longitudinal molar relaxivity (r(1)) 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 article, we explore this mechanism by comparing the changes in r(1) and its transverse counterpart, r(2)*, after the 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 poly(ethylene glycol) (PEG) brush. Nuclear magnetic resonance (NMR) at 1.5 T was used to measure the contrast properties of the various microbubble constructs because this is the most common field strength used in clinical MRI. Results for the lipid-headgroup-labeled Gd(III) microbubbles revealed that r(1) increased after microbubble fragmentation, whereas r(2)* was unchanged. An analysis of PEG-labeled Gd(III) microbubbles revealed that both r(1) and r(2)* decreased after microbubble fragmentation. Further analysis revealed that the microbubble gas core enhanced the transverse MR signal (T(2)*) in a concentration-dependent manner but minimally affected the longitudinal (T(1)) signal. These results illustrate a new method for the use of NMR to measure the biomembrane packing structure and 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.
Insights
Gadolinium-labeled microbubbles show altered magnetic properties after fragmentation, depending on label location. This difference may enable MRI detection of microbubbles and their fragments for theranostics.
Area of Science:
- Biomaterials Science
- Medical Imaging
- Nanotechnology
Background:
- Gas-filled microbubbles are promising theranostic agents for MRI-guided focused ultrasound surgery (MRIgFUS).
- Previous studies at 9.4 T MRI showed increased longitudinal relaxivity (r(1)) of gadolinium (Gd(III))-labeled microbubbles after fragmentation, attributed to lipid monolayer-to-bilayer transition.
Purpose of the Study:
- To investigate the mechanism of relaxivity changes after microbubble fragmentation by comparing Gd(III) bound to lipid headgroups versus PEG brushes.
- To assess the impact of microbubble fragmentation on both longitudinal (r(1)) and transverse (r(2)*) relaxivity at a clinically relevant MRI field strength (1.5 T).
Main Methods:
- Synthesized Gd(III)-labeled microbubbles with labels at either the lipid headgroup or PEG brush regions.
- Measured longitudinal (r(1)) and transverse (r(2)*) molar relaxivities using Nuclear Magnetic Resonance (NMR) at 1.5 T before and after microbubble fragmentation.
- Analyzed the influence of the microbubble gas core on T(1) and T(2)* signals.
Main Results:
- Lipid-headgroup-labeled microbubbles showed increased r(1) and unchanged r(2)* post-fragmentation.
- PEG-labeled microbubbles exhibited decreased r(1) and r(2)* post-fragmentation.
- The microbubble gas core enhanced T(2)* signal concentration-dependently but minimally affected T(1).
Conclusions:
- Microbubble fragmentation alters MRI contrast properties differently based on Gd(III) labeling location.
- NMR can measure biomembrane packing structure and differentiate microbubble fragments.
- Two mechanisms, proton-exchange enhancement and gas/liquid interface magnetic inhomogeneity, can be exploited for MRI detection of microbubbles and their fragments.
