Magnetic microstructures for magnetic resonance imaging
Inventors
Zabow, Gary • Dodd, Stephen • Koretsky, Alan • Moreland, John
Assignees
Usa Represented By Secretary Of Commerce AS • US Department of Health and Human Services
Publication Number
US-11324840-B2
Publication Date
2022-05-10
Expiration Date
2029-04-20
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Abstract
The present invention relates to a magnetic resonance structure with a cavity or a reserved space that provides contrast and the additional ability to frequency-shift the spectral signature of the NMR-susceptible nuclei such as water protons by a discrete and controllable characteristic frequency shift that is unique to each MRS design. The invention also relates to nearly uniform solid magnetic resonance T2* contrast agents that have a significantly higher magnetic moment compared to similarly-sized existing MRI contrast agents.
Core Innovation
The invention describes a magnetic resonance structure (MRS) designed to provide enhanced contrast and discrete, controllable frequency shifts of the spectral signature of NMR-susceptible nuclei such as water protons. The MRS includes a cavity or reserved space that produces an essentially uniform magnetic field different from the background field, enabling the frequency-shifted spectral signature that is unique to each MRS design. This feature allows multiplexing capabilities in magnetic resonance imaging by color mapping individual MRS based on their frequency shifts.
The problem addressed arises from the limitations of existing magnetic resonance imaging contrast agents, such as superparamagnetic iron oxide (SPIO) nanoparticles and micrometer-sized particles of iron oxide (MPIOs), which provide only monochrome contrast and lack the ability to distinguish between different cell types at single-cell resolution. The continuous spatial decay of their external fields causes a broad range of Larmor frequencies leading to broadened spectral lines. Furthermore, existing T2* contrast agents are limited in amount due to cytotoxicity concerns, limiting their in vivo tracking capabilities at the single-cell level.
The invention also relates to nearly uniform solid magnetic resonance T2* contrast agents with significantly higher magnetic moments than similarly sized prior art agents, produced using top-down fabrication methods allowing uniformity in size and magnetic moment. These solid MRS contrast agents can achieve higher contrast at lower concentrations, enabling super-resolution tracking and improved quantitative imaging analysis. Both the reserved space MRS and solid particulate MRS address the need for improved contrast agents that offer enhanced sensitivity and multiplexing abilities.
Claims Coverage
The patent includes three independent claims focused on specific magnetic resonance contrast agents made of solid disks with defined uniformity in size, magnetic moment, and composition.
Solid disks of uniform size and magnetic moment with non-magnetic coatings
A magnetic resonance contrast agent comprising multiple solid disks each consisting of a single magnetic material and a coating made of non-magnetic material, wherein the disks have diameters of about 0.1 μm to about 10 μm and thicknesses of 0.5 μm to 2 μm.
Iron disks coated with titanium having specified dimensions
A magnetic resonance contrast agent comprising a plurality of solid disks consisting of iron and coated with titanium, where each disk has a diameter of about 0.1 μm to about 10 μm and a thickness of about 0.1 μm to about 10 μm.
Uniform iron disks coated with titanium of defined size and thickness
A magnetic resonance contrast agent comprising solid disks consisting of a single magnetic material which is iron, coated with a non-magnetic material which is titanium, where each disk has a diameter of about 1 μm to about 2 μm and a thickness of about 0.5 μm to about 2 μm.
The claims collectively define magnetic resonance contrast agents composed of uniform solid disks of magnetic materials, specifically iron, coated with non-magnetic materials such as gold or titanium, with precise control over disk dimensions and magnetic moments to achieve enhanced imaging characteristics.
Stated Advantages
Significantly higher magnetic moment compared to similarly-sized existing MRI contrast agents, enabling stronger contrast at lower concentrations.
Ability to frequency-shift the spectral signatures of NMR-susceptible nuclei discretely and controllably, allowing multiplexed imaging and identification of different MRS types in the same sample.
Production of nearly uniform particles in size and composition facilitating super-resolution tracking and quantitative analysis in magnetic resonance imaging.
Reduced required concentrations for detectability relative to existing contrast agents, enhancing safety and sensitivity.
Compatibility with top-down fabrication methods allowing reproducible manufacture of MRS with low variance in geometry and composition, enhancing spectral peak sharpness and imaging accuracy.
Documented Applications
Use as magnetic resonance imaging contrast agents providing both spatial contrast (T2*) and discrete frequency-shifted spectral contrast for multiplexing.
Microtags for marking and tracking biological cells, enabling specific detection and labeling with cell-specific coatings.
Non-invasive monitoring of blood flow characteristics and stent integrity by spin-tagging blood molecules flowing through MRS-integrated stents.
Perfusion imaging and flow visualization in microfluidic channels, industrial pipes, and biological vessels using spin-tagged fluid volume frequency-shifted by the MRS.
Magnetic resonance spatial calibration markers or locators attached to substrates or surgical instruments to aid in magnetic resonance device calibration and instrument tracking.
Magnetic field sensors employing arrays of MRS with varied frequency shifts to measure external magnetic field strengths visually.
Sensors for distance, pressure, vibration, torque, and orientation via changes in MRS geometry impacting frequency-shifting characteristics.
Magnetic separation using the magnetic properties of the microstructures.
Magnetically driven micropumps or mixers through externally applied rotating magnetic fields to rotate MRS particles.
Localized RF magnetic heating elements for targeted thermal ablation of cells, such as cancerous cells.
Applications employing MRS with coatings or fillers for activatable or environment-responsive sensors.
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