Simultaneous steering and imaging of magnetic particles using MRI toward delivery of therapeutics

Abstract

Magnetic resonance navigation (MRN) offers the potential for real-time steering of drug particles and cells to targets throughout the body. In this technique, the magnetic gradients of an MRI scanner perform image-based steering of magnetically-labelled therapeutics through the vasculature and into tumours. A major challenge of current techniques for MRN is that they alternate between pulse sequences for particle imaging and propulsion. Since no propulsion occurs while imaging the particles, this results in a significant reduction in imaging frequency and propulsive force. We report a new approach in which an imaging sequence is designed to simultaneously image and propel particles. This sequence provides a tradeoff between maximum propulsive force and imaging frequency. In our reported example, the sequence can image at 27 Hz while still generating 95% of the force produced by a purely propulsive pulse sequence. We implemented our pulse sequence on a standard clinical scanner using millimetre-scale particles and demonstrated high-speed (74 mm/s) navigation of a multi-branched vascular network phantom. Our study suggests that the magnetic gradient magnitudes previously demonstrated to be sufficient for pure propulsion of micron-scale therapeutics in magnetic resonance targeting (MRT) could also be sufficient for real-time steering of these particles.

Selective embolization with magnetized microbeads using magnetic resonance navigation in a controlled‐flow liver model

“…According to the manufacturer, reducing the activation time will allow reaching a 40‐mT/m magnitude while remaining below the recommended temperature threshold. To synchronize the gradient activation, real‐time information on aggregate position must be acquired, which can be done using a catheter equipped with distal bead capture and release system followed by predictive modeling or by aggregate tracking using MRI …”

“…Navigation across two vascular bifurcations was also possible with a 1‐mm macrobead using an insert gradient coil and gradient magnitudes ranging between 24 and 64 mT/m . Recently, synchronization of steering and imaging sequences has been demonstrated for in vitro navigation of a 1‐mm macrobead using imaging gradient coils in a clinical MRI scanner . 50‐μm MDEBs were successfully navigated in vitro in a single‐bifurcation system and in vivo in the left and right branches of the hepatic artery in a rabbit model with a magnetic gradient coil insert and a gradient magnitude of 280 mT/m with an acceptable degree of selectivity (70–80%) .…”

“…50‐μm MDEBs were successfully navigated in vitro in a single‐bifurcation system and in vivo in the left and right branches of the hepatic artery in a rabbit model with a magnetic gradient coil insert and a gradient magnitude of 280 mT/m with an acceptable degree of selectivity (70–80%) . One technical limitation of those studies was the use of large beads, which possess higher magnetization but are not optimal for hepatic embolization. Currently available DEB size ranges between 70 and 300 μm which can be chosen depending on the target tumor vascularity .…”

“…Another limitation was the use of magnetic gradient coil inserts which are more powerful than built‐in imaging gradient coils but are not usable clinically due to their limited bore size. Prior studies also lack anatomical and physiological realism; they were either performed in nonbifurcating arteries, in vitro in small animal models or in nontubular channels with slow flow, which maximize steering efficiency due to the weakness of the magnetic force but that are not representative of physiologic rheological conditions . For a realistic MRN proof of concept, we first need to evaluate how to control the flow in large animal model.…”

Biohybrid and Bioinspired Magnetic Microswimmers

“…Magnetically controlled biohybrids or magnetically powered bioinspired microswimmers can be externally controlled, obviate fuel requirements, and hold the potential for online biomedical imaging . The latter feature is crucial for application scenarios where microswimmers shall be controlled inside the human body since control implies the existence of a feedback signal .…”