Dave, Jaydev K

Abstract Objective . The use of Feraheme (ferumoxytol) as a contrast agent in MR-guided focused ultrasound (MRgFUS) tumor ablations could enhance treatment safety and efficacy by improving vascular visualization through strong T1 and T2 shortening effects. However, Feraheme impact on MR thermometry and tissue heating is unclear. This study evaluates the feasibility of incorporating Feraheme into MRgFUS by assessing its impact on MR imaging contrast, MR thermometry, and thermal response in tissue-mimicking phantoms. Approach . Tissue-mimicking phantoms with 0 (baseline), 0.25, and 0.5 mM Feraheme concentrations were prepared using a validated recipe. Acoustic attenuation was measured with a commercial diagnostic ultrasound scanner. MR imaging at 1.5 T was performed to assess gradient-recalled-echo (GRE)-based thermometry signal-to-noise-ratio (SNR), relaxation rates, and relaxivities. MRgFUS system integrated with 1.5 T MRI was used to perform multiple sonications in the phantoms. Temperature elevations and focal heating areas were quantified from proton resonance frequency (PRF) shift thermometry. Experiments were repeated three times over the period of eight-weeks. Separately, temperature-dependent nuclear magnetic resonance (NMR) spectroscopy was performed at 3.0 T in saline-diluted Feraheme phantoms (0, 0.25, 0.5, and 1.0 mM) to assess the influence of Feraheme concentration on PRF coefficients used in MR thermometry. Main results . Phantoms showed nuclear relaxation times ( T 1: 1178.1 ± 77.8, T 2: 103.21 ± 2.45 ms) and attenuation coefficients (0.34–0.36 dB cm −1 MHz −1 ) within expected biological tissue ranges. Relaxivities demonstrated a strong linear dependence on Feraheme concentration ( r 1: 17.5 ± 0.2, r 2: 209.2 ± 2.6 s −1 mM −1 ). Relative to baseline (0 mM) phantom, the SNR of GRE-based thermometry increased by 12.6% at 0.25 mM and decreased by 27.1% at 0.5 mM. Sonications in Feraheme-containing phantoms resulted in statistically higher temperature elevations ( p < 0.001 ) although no statistically significant difference was observed between 0.25 and 0.5 mM. All NMR measurements demonstrated stable, linear PRF temperature dependence ( R 2 = 0.996–0.999), with PRF coefficients (between −0.0074 and −0.0082 ppm °C −1 ). The resulting thermometry bias was small and predictable (+0.67 and +1.73 per 20 °C at 3.0 T for 0.25 and 0.5 mM). Significance . These findings demonstrate that MR thermometry remains feasible at moderate Feraheme concentrations and support its potential use to enhance visualization of critical vasculature near targeted tissues during MRgFUS.

Subharmonic aided pressure estimation (SHAPE) is a technique that utilizes subharmonic signals from microbubble contrast agents for pressure estimation. Validation of the SHAPE technique relies on synchronous measurements of in vivo pressures using contrast microbubbles and a pressure catheter (reference standard). For the guidance and placement of pressure catheter in vivo, iodinated contrast is used with fluoroscopy. Therefore, during data acquisition for validation studies of the SHAPE technique, both contrast microbubbles and iodinated contrast are present simultaneously within the vasculature. This study aims to elucidate the effects of iodinated contrast (Visipaque, GE HealthCare) on subharmonic signal amplitude from contrast microbubbles (Definity, Lantheus Medical Imaging, Inc.). In an acrylic water tank, 0.06 mL of Definity and varied amounts of Visipaque (0.14, 0.43, 0.85, and 1.70 mL) were added to 425 mL of deionized water. Ultrasound scanning was performed with a SonixTablet scanner (BK Medical Systems) using optimized parameters for SHAPE with Definity ( f transmit/receive = 3.0/1.5 MHz; chirp down pulse). Subharmonic data was acquired and analyzed at 9 different incident acoustic outputs ( n = 3). Results showed an increase in subharmonic signal amplitude from Definity microbubbles in the presence of 0.14 mL Visipaque by 2.8 ± 1.3 dB ( p < .001), no change with 0.85 mL Visipaque (0.7 ± 1.2 dB; p = .09) and a decrease in subharmonic amplitude in the presence of 1.70 mL Visipaque by 1.9 ± 0.7 dB ( p < .001). While statistically significant effect on subharmonic signal amplitude of Definity microbubbles was noted due to the mixture, the magnitude of the effect was minimal (~2.8 dB) and unlikely to impact in vivo SHAPE measurements.