Poster R4 - Synthesis and purification of superparamagnetic iron oxide nanoparticles for use in MRI-guided focused ultrasound

Introduction: Magnetic resonance imaging (MRI)-guided focused ultrasound is a cutting-edge medical technology that combines magnetic resonance imaging with focused ultrasound (FUS) waves to treat various medical conditions like essential tremor and Parkinson's disease. An acoustic coupling bath, usually composed of degassed water, ensures efficient transmission of ultrasound waves between the transducer and the skin or tissue being imaged and treated. However, the MRI signal from the water in the bath overlaps significantly with the signal from water in the body’s tissues which generates imaging artifacts, resulting in significant degradation of the MR image resolution. To deal with this problem, superparamagnetic iron oxide nanoparticles (SPIONs) are dispersed in the aqueous acoustic coupling bath, speeding up the relaxation rate of protons in the water bath compared to that of the protons of water in tissue. Prior work has shown that this results in a significant improvement of the MR image resolution while minimizing cavitation in the acoustic coupling bath. This present work concerns the synthesis, purification, and characterization of the SPIONs that our group is investigating to determine the efficacy of employing an iron-based coupling medium (IBCM) in FUS procedures to improve MRI resolution while ensuring minimal interference with image quality.

Materials and

Methods: Flash nanoprecipitation (FNP) method was employed, which can produce well-defined, colloidally stable nanoparticles. FNP utilizes impinging jets to mix an iron salt stream with ammonium hydroxide in a highly turbulent flow, resulting in effective blending times on the order of ~ 50 milliseconds or less. This results in relatively rapid nucleation of particles, followed by aggregation until particle growth is arrested by a polymer coating. Superparamagnetic magnetite nanoparticles surrounded by poly(methyl acrylic acid) (PMAA) were synthesized by the FNP method. Tangential flow filtration (TFF) is a filtration technique used in various industries, including biotechnology and pharmaceuticals, to separate particles from a fluid based on their size. This setup allows smaller particles to pass through the membrane while larger particles, such as impurities, are retained. TFF is particularly useful for concentrating, purifying, or clarifying solutions without causing excessive shear or damage to sensitive components. The TFF method was used in this study to rapidly purify nanoparticles from unreacted iron salts and larger particles. The particle size distribution was characterized by dynamic light scattering (DLS).

Results, Conclusions, and Discussions: The uniformity in size distribution, which came from DLS measurement, demonstrates the effectiveness of using FNP to obtain very fast mixing times, compared to other, slower mixing methods, resulting in more homogeneous reactions that form smaller particles with uniform size distributions. Prior work from our team shows that this results in an acoustic coupling bath containing SPIONs with a higher T2 relaxation rate than that of deionized water. In a typical experiment, over 99% of the iron oxide nanoparticles are present in the peak in the DLS results corresponding to a hydrodynamic diameter of 93 nm. Utilizing SPIONs dispersed in an aqueous acoustic coupling bath, MRI resolution was enhanced by accelerating the relaxation rate of protons in the coupling fluid. In conclusion, the integration of an iron-based coupling medium holds promise for enhancing MRI resolution in FUS surgeries. DLS elucidated the effectiveness of combining FNP with the TFF filtration method in synthesizing and purifying SPIONs, which is crucial for optimizing FUS procedures. FNP was considered an effective way to synthesize iron oxide nanoparticles compared to conventional synthesizing methods. It is concluded that the filtration time can be shortened by TFF filtration method compared to dialysis techniques yet having high filtration efficiency. Ongoing work is investigating the effect of varying reaction parameters to tailor the SPION size in order to improve MR imaging when combined with FUS.

Acknowledgements (Optional): The authors would like to extend their sincere appreciation to the National Institutes of Health for their financial support.