Phase-locked magnetomotive ultrasound imaging of superparamagnetic iron-oxide nanoparticles

It has recently been shown that superparamagnetic iron oxide nanoparticles (SPIO-NP) can be used as ultrasound contrast agents, by moving the particles using a time-varying external magnetic field and thereby moving nanoparticle laden tissue. However, the difficulty to distinguish magneto-motive motion from indirect motion induced outside areas containing nanoparticles, or other motion artifacts, which restrict the use in vivo, is not well reported. Using a high-frequency linear array system we found that displacements outside nanoparticle-laden areas could be in the same range as the displacement in areas containing nanoparticles. We also found in our setup that the movement in areas between the nanoparticles areas were approximately radians out of phase relative the nanoparticles areas. To suppress undesirable signals we developed an algorithm based on frequency-tracking and phase-locking, where the energy of the processed signal is color-coded and overlaid on the B-mode image. The signal-to-clutter ratio showed a 14.5 dB improvement between the image color-coded with the total power and the image coded with regard to phase and frequency. The capability to distinguish areas containing SPIO-NP from those that do not is a crucial step for detection of nanoparticles in vivo.