Characterization of a Next-Generation Iron Oxide Coupling Medium for Transcranial Magnetic Resonance-Guided Focused...

Alternative coupling baths for transcranial MR-guided focused ultrasound (tMRgFUS) procedures have been investigated for the purpose of improving image quality. This study characterizes the physical properties and assesses the cavitation properties of an improved coupling media consisting of poly(methacrylic acid)-coated iron oxide nanoparticles synthesized with optimized Fe³⁺ to Fe²⁺ molar ratios for improved magnetic properties and purified with tangential flow filtration for improved manufacturability.

A 380 mL volume of 73 mM Fe iron-based coupling medium (IBCM) was synthesized and diluted into 4 concentrations of interest (3.5, 7, 17.5 and 35 mM Fe) and characterized to determine their physical properties. Thereafter, cavitation thresholds (pressure at which probability of cavitation = 0.5) were determined under histotripsy parameters (<1% duty cycle, <20 μs duration, single-cycle pulses) with a 500 kHz transducer at peak negative pressures ranging from 0 to 35 MPa to determine the acoustic feasibility of the coupling media.

The IBCM produced in this study consisted of particles with a similar size distribution (31-37 nm intensity average hydrodynamic diameters) to prior IBCM formulations but exhibited better r₁ and r₂ relaxivity values (18.9 mM^-1 s^-1 and 63.6 mM^-1 s^-1 compared to 8.15 mM^-1 s^-1 and 58.4 mM^-1 s^-1). Cavitation threshold pressures of the IBCM did not significantly differ from the water controls, ranging from ∼26-29 MPa.

These findings support the feasibility of the IBCM as a replacement for the degassed water bath to improve imaging quality of tMRgFUS procedures without introducing negative acoustic effects.