Magnetic microstructures for magnetic resonance imaging
Inventors
Zabow, Gary • Dodd, Stephen • Korelsky, Alan • Moreland, John M.
Assignees
National Institutes of Health NIH • United States Department of Commerce • Office of Technology Transfer
Publication Number
US-9084819-B2
Publication Date
2015-07-21
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 relates to magnetic resonance structures (MRS) that include either a cavity or reserved space providing contrast and the unique ability to produce a discrete and controllable characteristic frequency shift of NMR-susceptible nuclei, such as water protons. Each MRS design produces a frequency shift unique to that design, enabling identification and multiplexing capabilities in magnetic resonance imaging (MRI) that are not achievable with existing contrast agents. The MRS also includes nearly uniform solid T2* contrast agents with significantly higher magnetic moments compared to similarly sized existing MRI contrast agents.
The magnetic resonance contrast agents consist essentially of a plurality of disks of uniform size and magnetic moment made of a single magnetic material. The MRS with reserved spaces create an essentially uniform magnetic field inside the cavity or cavity volume, which is significantly different in magnitude from background fields. This uniform field induces shifted Larmor frequencies in the NMR-susceptible nuclei of fluid diffusing or flowing in and out of the reserved space, amplifying contrast signals and enabling lower detectable concentrations of contrast agents. The frequency shift produced by each MRS becomes a spectral signature that can be used to color-map and differentiate MRS in MRI data.
The problem being solved is the lack of multiplexing capabilities for MRI contrast agents and the limited ability to distinguish different cell types or track single cells. Existing contrast agents such as superparamagnetic iron oxide (SPIO) nanoparticles or microparticles produce only a continuous spatial decay of magnetic fields causing broad Larmor frequency ranges and monochrome contrast signals. This limits simultaneous detection of multiple agents and reduces signal specificity. In addition, existing strong T2* contrast agents can only be used in limited amounts due to cytotoxicity, hindering in vivo single-cell tracking.
Claims Coverage
The patent claims one independent claim that defines a magnetic resonance contrast agent composed of solid disk-shaped magnetic resonance structures with specific size, magnetic moment, and internal spacer properties.
Uniform solid disk-shaped magnetic resonance structures with internal spacer
The contrast agent comprises multiple solid disk-shaped magnetic resonance structures of uniform size and magnetic moment, each consisting of a pair of magnetic disks separated by an internal non-magnetic spacer. The structures have volumes in the range of 5×10−22 m3 to 5×10−15 m3 and are dispersed in a fluid medium.
The independent claim covers a magnetic resonance contrast agent featuring uniform solid disk-shaped MRS each composed of paired magnetic disks separated by an internal non-magnetic spacer, with defined size and magnetic moment ranges, designed for dispersion in a fluid medium.
Stated Advantages
The MRS provides discrete and controllable frequency-shifted spectral signatures that enable multiplexed MRI and spectral differentiation of contrast agents in imaging data.
The nearly uniform solid T2* contrast agents possess significantly higher magnetic moments than existing MRI contrast agents of similar size, enhancing visibility and contrast efficacy.
The uniformity in size and composition of the MRS permits use at lower detectable concentrations compared to existing agents, improving sensitivity and biocompatibility.
The diffusion or flow of fluid in and out of the reserved space substantially increases the volume of frequency-shifted nuclei, amplifying the contrast signal strength.
The MRS designs facilitate super-resolution tracking of individual particles within imaging voxels by analyzing contrast intensities.
Documented Applications
Magnetic resonance frequency shifts of water protons and other NMR-susceptible nuclei for magnetic resonance calibration, testing, and fabrication.
Magnetic resonance spatial calibration markers and locators affixed to substrates or moving surgical instruments for non-invasive tracking.
Specific detection, labeling, and tracking of biological cells via MRS microtags functionalized for cell-specific affinity.
Non-invasive monitoring and characterization of blood flow through stent devices equipped with MRS, including detection of flow speed, occlusions, and stent deformation.
Spin-tagging fluid flow and perfusion imaging by frequency-shifting fluid within reserved spaces of MRS situated in fluid vessels or microfluidic channels.
Magnetic resonance identity systems for marking and identifying objects using MRS microtags with unique frequency-shifts.
Sensors for magnetic fields, distance, pressure, vibration, and torque based on MRS frequency-shifting behavior responsive to physical forces.
Magnetic separation using the magnetic properties of MRS particles.
Micropumps or micromixers employing MRS particles rotated by external magnetic fields.
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