Magnetic microstructures for magnetic resonance imaging
Inventors
Zabow, Gary • Dodd, Stephen • Koretsky, Alan • Moreland, John
Assignees
United States Department of Commerce • US Department of Health and Human Services
Publication Number
US-10220103-B2
Publication Date
2019-03-05
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 provides a magnetic resonance structure (MRS) with a cavity or reserved space that produces a substantially uniform magnetic field within this space, resulting in a discrete and controllable frequency shift of the spectral signature of NMR-susceptible nuclei, such as water protons. This frequency shift is unique to each MRS design and may be engineered by controlling geometry, enabling the identification and distinction of individual MRS types within magnetic resonance (MR) data through color mapping of spectral signatures, thus enhancing MR image information content.
The MRS includes a reserved space or cavity that allows diffusion and/or flow of NMR-susceptible nuclei in and out of the space, greatly expanding the volume of fluid frequency-shifted during repeated resonant electromagnetic pulses. This effect allows detection of lower densities of particles compared to prior art, thereby improving contrast sensitivity. In addition, the invention covers nearly uniform solid magnetic resonance T2* contrast agents with significantly higher magnetic moments than similarly-sized existing MRI contrast agents, fabricated by top-down methods from high-saturation magnetic density materials such as nickel or soft iron.
The problem addressed is the lack of multiplexing capabilities in magnetic resonance imaging contrast agents. Existing magnetic particles like superparamagnetic iron oxide (SPIO) nanoparticles produce only monochrome contrast due to continuous spatial decay of external fields, which limits information on distinct cell types. Moreover, existing T2* contrast agents have limitations on quantity due to cell viability concerns and insufficient magnetic moment to enable routine in vivo single-cell tracking. The invention solves these by providing MRS particles with controllable, discrete spectral frequency shifts and higher magnetic moments, uniform composition and size for precise imaging, and enhanced signal via fluid diffusion, enabling multiplexed, color-distinct contrast agents and improved sensitivity.
Claims Coverage
The patent claims cover two main inventive features related to magnetic resonance contrast agents and imaging methods.
Magnetic resonance contrast agent with dual-disc structure and non-magnetic spacer
A contrast agent comprising a plurality of contrast structures, each consisting of a pair of magnetic disks parallel and aligned along the same axis, separated by a non-magnetic spacer. The disks are made of one or more layers of ferromagnetic, paramagnetic, superparamagnetic materials, alloy, magnetic compound, or combinations thereof. The non-magnetic spacer is made of metal, photo-epoxy, hydrogel, polymer, ceramic, plastic, photoresist, or combinations thereof. The space between disks forms a spatially extended near-field region with a homogeneous magnetic field inducing a characteristic Larmor frequency causing the agent to emit a distinctive magnetic resonance signal.
Environmentally responsive geometry change in non-magnetic spacer
The non-magnetic spacer is configured to change geometry in response to environmental factors (e.g., pH, temperature, salinity), thereby altering the spacing between magnetic disks and changing the magnitude of the homogeneous magnetic field and consequently the frequency shift.
Magnetic resonance imaging method using the contrast agent
A method comprising providing the contrast agent dispersed in a medium (preferably liquid), illuminating it with an excitatory electromagnetic pulse, and detecting the emitted electromagnetic radiation from the agent with a detection system, enabling magnetic resonance imaging based on the agent's properties.
The claims define magnetic resonance contrast agents composed of dual-disk magnetic structures with a non-magnetic spacer forming a homogeneous magnetic field reserved space for frequency-shifted NMR signals, including environmental responsiveness of the spacer geometry, and methods of imaging using these agents dispersed in a medium.
Stated Advantages
Enables multiplexed magnetic resonance imaging with color-distinct spectral shifts unique to each MRS design, greatly enhancing informational content of MR images.
Significantly higher magnetic moment contrast agents compared to similarly-sized existing agents, improving sensitivity and enabling single particle detection.
Uniform size and composition ensure consistent and sharp frequency shifts, permitting precise super-resolution tracking within imaging voxels.
Fluid diffusion into the reserved space amplifies frequency-shifted signal volume, increasing contrast signal strength at lower particle concentrations.
The invention allows use of potentially less toxic magnetic materials with high saturation magnetic polarization, enhancing biocompatibility and imaging performance.
Documented Applications
Magnetic resonance frequency shifting for water protons and other NMR-susceptible nuclei in MR calibration, testing, and fabrication.
Magnetic resonance spatial calibration markers for higher calibration resolution in magnetic resonance systems.
Specific detection, labeling, and tracking of biological cells using conjugated or targeted MRS microtags.
Distance, pressure, vibration, and torque sensing by detecting geometry-dependent changes in frequency shifts of MRS.
Non-invasive monitoring of blood flow characteristics through stents incorporating MRS, including flow speed and occlusion detection.
Spin-tagging fluid flow and perfusion imaging at various size scales from microfluidics to large vessels.
Magnetic separation using the magnetic properties of microstructures.
Rotators for magnetic-field-driven micropumps, micromixers, and cell destruction applications.
Localized magnetic field gradient generation for alternative magnetic imaging and localized high magnetic force application.
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