Contrast-enhanced imaging of SPIO-labeled platelets using magnetomotive ultrasound

Abstract

The ability to image platelets in vivo can provide insight into blood clotting processes and coagulopathies, and aid in identifying sites of vascular endothelial damage related to trauma or cardiovascular disease. Toward this end, we have developed a magnetomotive ultrasound (MMUS) system that provides contrast-enhanced imaging of superparamagnetic iron oxide (SPIO) labeled platelets via magnetically-induced vibration. Platelets are a promising platform for functional imaging contrast because they readily take up SPIOs and are easily harvested from blood. Here we report a novel MMUS system that accommodates an arbitrarily thick sample while maintaining portability. We employed a frequency- and phase-locked motion detection algorithm based on bandpass filtering of the differential RF phase, which allows for the detection of sub-resolution vibration amplitudes on the order of several nanometers. We then demonstrated MMUS in homogenous tissue phantoms at SPIO concentrations as low as 0.09 mg/ml Fe (p < 0.0001, n = 6, t-test). Finally, we showed that our system is capable of 3-dimensional imaging of a 185 μL simulated clot containing SPIO-platelets. This highlights the potential utility for non-invasive imaging of platelet-rich clots, which would constitute a fundamental advance in technology for the study of hemostasis and detection of clinically relevant thrombi.

Multimodal detection of iron oxide nanoparticles in rat lymph nodes using magnetomotive ultrasound imaging and magnetic resonance imaging

“…The design with a magnetic field generator on the opposite side of the ultrasound transducer will naturally pose a challenge for a clinical translation. current efforts focus on a solution in which the magnetic field can be applied from the same side as the ultrasound probe, similar to the design that recently was suggested by Pope et al [23]. It is also crucial to show the validity of the technique in live animals, which includes the choice of a suitable magnetic field frequency that does not interfere with any physiological activity, such as heart rhythm.…”

Blind source separation - based motion detector for sub-micrometer, periodic displacement in ultrasonic imaging

“…Six inclusion phantoms mimicking the mechano-acoustic properties of human tissue were prepared using the procedures described in [1]. They were prepared by melting agar, in hot colloidal mixture of 0.4 mg Fe/ml SPIO (inclusion) with graphite nano powder, and congealing into cylindrical molds.…”

“…Two sets of data were collected by turning on and off the magnetic field. Further detail regarding the MMUS imaging set-up can be found in [1]. Acquired RF data were transferred to a computational work station for constructing MMUS images using FPL and BSS with kernel sizes of 0.014 and 0.043 mm (Figure 1) [1].…”

“…Further detail regarding the MMUS imaging set-up can be found in [1]. Acquired RF data were transferred to a computational work station for constructing MMUS images using FPL and BSS with kernel sizes of 0.014 and 0.043 mm (Figure 1) [1]. The performance between BSS and FPL was compared using SNR, which was calculated by taking ratio of median pixel intensity inside vs outside of the inclusion (Figure 3 (b–c)).…”

“…In magnetomotive ultrasound (MMUS) [1], an oscillating external magnetic field displaces tissue loaded with superparamagnetic iron oxide (SPIO) particles, whereas in Shearwave Dispersion Ultrasound Vibrometry (SDUV) [2], [3] and Harmonic Motion Imaging (HMI)[4], [5], periodic motion is induced using ARF to measure the viscoelastic properties of tissue. Frequency- and phase-locked (FPL) [1], Kalman filtering [7], and normalized cross-correlation (NCC) [6] methods have been used to detect motion in MMUS, SDUV, and HMI, respectively. In MMUS, parametric images of the detected motion magnitude at the oscillation frequency and phase are rendered.…”