Magnetic microstructures for magnetic resonance imaging
Inventors
Zabow, Gary • Dodd, Stephen • Koretsky, Alan • Moreland, John M
Assignees
United States Department of Commerce • US Department of Health and Human Services
Publication Number
US-10215825-B2
Publication Date
2019-02-26
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. The invention also relates to a magnetic resonance sensor that alters it shape in response to a condition of an environment such that the condition may be detected.
Core Innovation
The invention relates to magnetic resonance structures (MRS) designed to provide contrast and the capability to frequency-shift the spectral signature of NMR-susceptible nuclei such as water protons by a discrete, controllable, and unique frequency shift for each MRS design. The MRS can be constructed with a cavity or reserved space generating an essentially uniform magnetic field within, distinct from the background field, allowing detection and multiplexed imaging through color mapping of shifted spectral signatures.
The MRS may also be solid magnetic resonance T2* contrast agents having a significantly higher magnetic moment than similarly sized existing MRI contrast agents. Using top-down fabrication methods, these MRS exhibit uniform size and composition, allowing for super-resolution tracking and detection at minimal concentrations. The invention includes magnetic resonance sensors that change shape in response to environmental conditions, altering the spacing between magnetic elements, thereby producing detectable changes in resonance frequency used to measure physiological or environmental factors.
The problem being addressed stems from existing MRI contrast agents, such as superparamagnetic iron oxide nanoparticles (SPIOs) or micrometer-sized particles (MPIOs), which produce spatially decaying magnetic fields leading to a broad range of Larmor frequencies. This results in monochrome contrast that cannot distinguish between different particle types for cell tracking, limiting multiplexing capabilities. Moreover, existing T2* contrast agents compromise cell viability when used in large quantities, hindering in vivo single-cell tracking. There is a need for improved contrast agents capable of multiplexing and higher magnetic moments while maintaining uniformity and functionality for biological, diagnostic, and sensing applications.
Claims Coverage
The patent contains one independent claim focusing on a magnetic resonance structure responding to environmental conditions via adjustable disk spacing.
Magnetic resonance structure with adjustable disk spacing responsive to environmental conditions
The invention comprises a magnetic resonance structure including a pair of magnetic material disks aligned parallel and held apart by a flexible, non-magnetic spacer. The disks are made from magnetic materials selected from ferromagnetic, paramagnetic, superparamagnetic materials, magnetic alloys, or compounds. The spacer is configured to adjust the distance between the disks in response to environmental conditions when located therein, and is made from photo-epoxy, hydrogel, or polymers.
Sensing environmental conditions through NMR frequency shift changes
The spacer material is designed to expand or contract according to specific environmental conditions such as pH level, temperature, or presence of biomolecules (glucose, metabolites, antigens, proteins, enzymes). This change in disk spacing produces a measurable shift in nuclear magnetic resonance (NMR) frequency when subjected to excitatory electromagnetic pulses, enabling detection of the environmental condition.
State change based sensor actuation
The spacer material can change state by dissolving, melting, or collapsing in response to an environmental condition, thereby altering the physical alignment of disk pairs (losing coaxial orientation), effectively switching the sensor's resonant frequency response on or off.
Method for detecting environmental conditions using MRS sensor structures
A method applies the magnetic resonance structures into a substance, exposes them to electromagnetic pulses, obtains NMR data, and uses known NMR shifts induced by disk spacing to determine the presence of environmental conditions within the substance.
The claims delineate a magnetic resonance sensor structure featuring adjustable disk spacing mediated by flexible spacer materials responsive to environmental changes, enabling detection of such conditions through shifts in resonant NMR frequencies. This includes mechanisms of reversible expansion/contraction and irreversible spacer state changes, and a method to exploit these properties for condition sensing.
Stated Advantages
The invention provides significantly higher magnetic moments compared to existing MRI contrast agents, enabling enhanced contrast and detection at lower concentrations.
Highly uniform size and composition of the MRS allow for consistent and discrete frequency shifts, facilitating multiplexed magnetic resonance imaging and super-resolution tracking.
The reserved cavity or space design enables uniform magnetic fields that yield sharp, controllable frequency shifts of NMR-susceptible nuclei, improving signal-to-noise ratio and informational content of MR images through color mapping.
The sensor design with flexible, responsive spacers allows dynamic, reversible, or irreversible detection of environmental or physiological conditions non-invasively via NMR frequency shifts.
Documented Applications
Magnetic resonance contrast agents for MRI applications including multiplexed imaging and super-resolution single-particle tracking.
Microtags to label biological cells or objects for specific detection, labeling, and tracking.
Non-invasive monitoring of blood flow and stent condition by incorporating MRS into stent devices.
Spin-tagging of fluid flow in microfluidics, blood vessels, and industrial pipes to measure flow speed, mass flow, and flow profiles.
Magnetic resonance spatial calibration markers and locators for MRI.
Magnetic field sensors for in-situ magnetic field measurement using arrays of MRS particles.
Distance, pressure, vibration, and torque sensors based on geometry-dependent NMR frequency shifts.
Environmental sensors using MRS responsive to physiological variables like pH, temperature, glucose, metabolites, and specific proteins or enzymes.
Magnetic separation, fluid micropumps, micromixers, and targeted destruction of biological cells via magnetically driven rotation or heating.
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