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

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Fluid-filled vascular network phantom for image-based particle steering.Sequence of 16 waypoints for 2 mm diameter sphere are labeled. Image coordinate frame indices correspond to the target waypoint, i.e., frame k is defined at waypoint (k − 1) with its x-axis pointing in the scan direction toward waypoint k. Particle path between waypoints for an MRI imaging frequency of 117 Hz is shown and video of particle motion is provided in the Supplementary Movie.
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f5: Fluid-filled vascular network phantom for image-based particle steering.Sequence of 16 waypoints for 2 mm diameter sphere are labeled. Image coordinate frame indices correspond to the target waypoint, i.e., frame k is defined at waypoint (k − 1) with its x-axis pointing in the scan direction toward waypoint k. Particle path between waypoints for an MRI imaging frequency of 117 Hz is shown and video of particle motion is provided in the Supplementary Movie.

Mentions: To illustrate the use of simultaneous imaging and propulsion for active steering, experiments were conducted using the fluid-filled vascular network phantom of Fig. 5. A sequence of 16 waypoints was defined as shown and the MRI scanner was programmed to apply pulse sequences that would propel a 2 mm diameter chrome steel sphere through the sequence of waypoints as fast as possible (see methods). It was determined experimentally that 117 Hz was the highest imaging frequency that could reliably generate sufficient force to propel the particle through a combination of rolling and sliding along the bottom of the fluid-filled channel. The Supplementary Movie depicts the particle motion.


Simultaneous steering and imaging of magnetic particles using MRI toward delivery of therapeutics
Fluid-filled vascular network phantom for image-based particle steering.Sequence of 16 waypoints for 2 mm diameter sphere are labeled. Image coordinate frame indices correspond to the target waypoint, i.e., frame k is defined at waypoint (k − 1) with its x-axis pointing in the scan direction toward waypoint k. Particle path between waypoints for an MRI imaging frequency of 117 Hz is shown and video of particle motion is provided in the Supplementary Movie.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5036040&req=5

f5: Fluid-filled vascular network phantom for image-based particle steering.Sequence of 16 waypoints for 2 mm diameter sphere are labeled. Image coordinate frame indices correspond to the target waypoint, i.e., frame k is defined at waypoint (k − 1) with its x-axis pointing in the scan direction toward waypoint k. Particle path between waypoints for an MRI imaging frequency of 117 Hz is shown and video of particle motion is provided in the Supplementary Movie.
Mentions: To illustrate the use of simultaneous imaging and propulsion for active steering, experiments were conducted using the fluid-filled vascular network phantom of Fig. 5. A sequence of 16 waypoints was defined as shown and the MRI scanner was programmed to apply pulse sequences that would propel a 2 mm diameter chrome steel sphere through the sequence of waypoints as fast as possible (see methods). It was determined experimentally that 117 Hz was the highest imaging frequency that could reliably generate sufficient force to propel the particle through a combination of rolling and sliding along the bottom of the fluid-filled channel. The Supplementary Movie depicts the particle motion.

View Article: PubMed Central - PubMed

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.

No MeSH data available.