Magnetic Microstructures for MRI Single-Cell Contrast Shifting

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Solution Overview

Problem

Current magnetic resonance imaging (MRI) contrast agents lack the ability to distinguish between different cell types at the single-cell level, limiting their application in cellular biology and early disease detection due to the continuous decay of external magnetic fields which broadens the water hydrogen proton line, obscuring spectral distinctions.

Innovation Solution

A magnetic resonance contrast agent comprising a plurality of solid individual disks with uniform size and magnetic moment, optionally coated with a biologically inert coating, allowing for precise control of size and magnetic properties to produce discrete frequency shifts for multiplexed imaging.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If small magnetic particles are used to reduce artifacts and improve resolution, then image quality is improved, but the particles become susceptible to superparamagnetic effects and require complex functional coatings

Engineering Contradiction:
Improveimage qualityVSAvoidparticle structure complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The magnetic particle is divided into two distinct functional domains: a non-magnetic core and a magnetic shell. This segmentation allows the core to provide structural stability and surface area while the shell provides the necessary magnetic properties, resolving the contradiction by eliminating the need for complex functional coatings on superparamagnetic particles.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention uses a composite structure combining non-magnetic material (core) and magnetic material (shell). This composite approach allows optimization of each component's properties independently, achieving stable magnetic behavior with enhanced image quality without requiring additional complex coatings.

Inventive Principle:
Principle #40Composite materials

2Measurement precision

If magnetic particles are used for MRI contrast, then image quality is improved, but iron oxide particles undergo oxidative degradation and aggregate

Engineering Contradiction:
Improveimage qualityVSAvoidparticle stability
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The problematic magnetic core material is extracted and replaced with a stable non-magnetic core, eliminating the oxidative degradation issue. The magnetic functionality is then provided by a protective shell that prevents aggregation and maintains stability in physiological conditions.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

A protective shell is applied beforehand to the magnetic core to prevent oxidative degradation and aggregation. This protective layer acts as a cushion against environmental factors that would otherwise degrade the particle stability.

Inventive Principle:
Principle #11Beforehand cushioning (Prior cushioning)

3Quantity of substance

If iron oxide particles are used, then magnetic contrast is provided, but the particles aggregate and require extensive surface modification

Engineering Contradiction:
Improvemagnetic contrastVSAvoidsurface modification complexity
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

Instead of modifying the surface of magnetic particles to prevent aggregation, the invention inverts the approach by placing the magnetic material on the outside of a stable core. This creates a structure where the magnetic shell is inherently protected and stabilized by the core, eliminating the need for extensive surface modifications.

Inventive Principle:
Principle #13The other way round (Inversion)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

Enables enhanced multiplexing capabilities and improved contrast, allowing for the identification of individual cells and specific cell types within MRI images, reducing the required concentration of contrast agents and increasing the visibility of single cells in vivo.

Implementation Method 1

the magnetic shell has a magnetic anisotropy that promotes alignment of the magnetization along the radial direction

Methodology Applied
Scientific EffectMagnetic anisotropy: Magnetic Hysteresis

Implementation Method 2

Magnetic resonance imaging (MRI) is a widely used medical imaging modality

Methodology Applied
Scientific EffectMagnetic resonance: Magnetic Field

Data Source

PatentEP2413796B1Magnetic microstructures for magnetic resonance imaging
Publication Date: 2024.02.28 THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY DEPARTMENT OF HEALTH & HUMAN SERVICES
  • EP2413796B1 patent drawingFigure 1
  • EP2413796B1 patent drawingFigure 2
  • EP2413796B1 patent drawingFigure 3

AI summary

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.