Magnetic microstructures for magnetic resonance imaging
Inventors
Zabow, Gary • Dodd, Stephen • Koretsky, Alan • Moreland, John
Assignees
United States, As Represented By Sectretary Of Commerce • US Department of Health and Human Services
Publication Number
US-10350312-B2
Publication Date
2019-07-16
Expiration Date
2029-04-20
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Abstract
The present invention relates to magnetic contrast structures for magnetic resonance imaging, and methods of their use. The contrast structures include magnetic materials arranged as a pair of disk-shaped magnetic components with a space between a circular surface of each disk shape, or a tubular magnetic structure, a substantially cylindrical magnetic structure, a substantially spherical shell-formed magnetic structure, or a substantially ellipsoidal shell-formed structure, each defining a hollow region therein. The space and/or hollow region in the contrast structure creates a spatially extended region contained within a near-field region of the contrast structure over which an applied magnetic field results in a homogeneous field, such that nuclear magnetic moments of a second material when arranged within the spatially extended region precess at a characteristic Larmor frequency, whereby the contrast structure is adapted to emit a characteristic magnetic resonance signal of the magnetic material.
Core Innovation
The invention relates to magnetic contrast structures for magnetic resonance imaging (MRI) and methods of their use, including magnetic materials arranged as a pair of disk-shaped magnetic components with a space between their circular surfaces, or in tubular, cylindrical, spherical shell-formed, or ellipsoidal shell-formed configurations defining hollow regions therein. These contrast structures create a spatially extended region within a near-field region where an applied magnetic field results in a homogeneous field. This enables nuclear magnetic moments of a second material arranged within this spatially extended region to precess at a characteristic Larmor frequency identifiable with the contrast structure, emitting characteristic magnetic resonance signals of the magnetic material.
MRI lacks the sensitivity and multiplexing capabilities of optical imaging techniques, which utilize colored fluorophores and other multiplexed labels, limiting its ability to distinguish between different types of cells at the single-cell level. Current MRI cell-tracking methods employ superparamagnetic iron oxide nanoparticles or micrometer-sized iron oxide particles; however, these produce continuous spatial decay external fields that broaden water resonance lines and obscure distinctions between different magnetic particle types. There is a need for improved MRI contrast agents that can transform monochrome or binary agents into spectrally distinct tags by frequency shifting water signals discretely and controllably.
The invention addresses this problem by designing microfabricated magnetic resonance contrast agents that generate local regions of substantially uniform magnetic fields causing nuclear spins within those regions to produce frequency-shifted signals. The geometries, compositions, and arrangements of magnetic portions are engineered to produce discrete, homogeneous local fields, enabling multiplexed spectral tagging. Such agents, including double-disc microstructures and hollow cylindrical shells, enhance MRI sensitivity by exploiting diffusion and enable individually detectable, spectrally distinct micro-tags with signal frequencies determined by structure shape and composition rather than chemical or nuclear shifts.
Claims Coverage
The patent includes one independent claim focused on a method of magnetic resonance imaging using magnetic contrast structures with defined geometries producing characteristic frequency shifts.
Magnetic contrast structures constituted by continuous spherical or ellipsoidal shells with access hole
The method uses magnetic contrast structures formed as continuous shells of magnetic material in substantially spherical or ellipsoidal shapes, each having one access hole and defining a hollow region.
Creation of homogeneous local magnetic fields within hollow regions for characteristic Larmor frequency shifts
The hollow region creates a spatially extended region within the near-field region over which the contrast structure alone or with an applied magnetic field produces a substantially homogeneous magnetic field, causing nuclear magnetic moments of a second material inside to precess at a characteristic identifiable Larmor frequency.
Use of the frequency-shifted signals for magnetic resonance imaging with fluid-permeable regions
Magnetic resonance signals are induced and detected via excitation and detection systems. The contrast structures permit fluid to flow or diffuse through at least a portion of the local magnetic field region, enabling frequency-shifted nuclear magnetic resonance signals usable for MRI or NMR.
The independent claim covers a method employing unique magnetic resonance contrast structures formed as spherical or ellipsoidal shells with hollow access regions that create homogeneous local magnetic fields. These structures enable characteristic frequency-shifted magnetic resonance signals detectable during imaging, with provisions for fluid flow or diffusion through the hollow region, thereby providing a novel approach to MRI contrast enhancement and signal multiplexing.
Stated Advantages
Increased MRI sensitivity by orders of magnitude compared to traditional agents.
Ability to produce individually detectable, spectrally distinct micro-tags enabling multiplexed spectral imaging.
Frequency shifts are tunable by structural parameters rather than chemical composition, enabling broad and customizable spectral ranges.
Open designs allow fluid diffusion enhancing signal-to-noise ratio through magnetization transfer techniques.
Reduced required agent concentrations well below existing contrast agents, improving safety and imaging speed.
Automatic magnetic self-alignment of microstructures ensures correct orientation in magnetic fields.
Potential for dynamic or physiological sensing via changes in spacer materials or structure dimensions, enabling smart contrast agents.
Documented Applications
Magnetic resonance imaging contrast agents dispersed in liquids or gels for enhanced cellular and molecular imaging.
MRI identity systems with excitation and detection components to identify and differentiate magnetic microstructures.
Spin-tagging of fluid flow, including blood flow through stents or tubular vessels, to measure flow speed and direction.
Micro-RFID tags for labeling biological cells or objects, providing spectral signatures analogous to colored fluorophores and quantum dots.
Magnetic field sensors and spatial calibration markers for MRI systems.
Sensors for physical parameters such as distance, pressure, vibration, torque, or fluid flow via changes in resonant frequencies.
Magnetic separation processes using magnetic microstructures analogous to magnetic beads.
Localized RF magnetic heating for targeted thermal ablation of cells.
Flow cytometry and microfluidics monitoring applications where objects in fluid streams are spectrally tagged without requiring optical access.
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