Hyperpolarization Particles With Crystalline Matrices for Extended T1

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Solution Overview

Problem

Existing hyperpolarization probes for MRI have short T1 relaxation times, making them impractical for clinical use due to rapid loss of polarization, and current methods to extend T1, such as isotopic substitution and RF irradiation, are either ineffective or impractical for clinical applications.

Innovation Solution

Particles comprising a crystalline matrix with a dopant, where the matrix is isotopically enriched and doped with biological compounds, combined with homonuclear decoupling to extend T1 times, allowing for stable hyperpolarization of probes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of energy

If hyperpolarization probes are used for MRI, then signal enhancement is achieved, but T1 relaxation time is too short causing rapid polarization loss

Engineering Contradiction:

Improvepolarization retentionVSAvoidT1 relaxation time

Core Design Contradiction:

Loss of energyVSDuration of action of moving object

Solution Approach 1:

The patent introduces a nanoparticle carrier as an intermediary system that hosts the hyperpolarized probe molecule. The nanoparticle's crystalline lattice structure acts as a protective environment that extends the T1 relaxation time of the embedded hyperpolarized nucleus, thereby slowing polarization loss while maintaining signal enhancement capability

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention creates a composite material system consisting of a nanoparticle core (with specific crystalline structure and composition) combined with a hyperpolarized probe molecule. This composite structure leverages the long T1 properties of the nanoparticle material to extend the polarization lifetime of the probe, resolving the contradiction between signal enhancement and polarization retention

Inventive Principle:

Principle #40Composite materials

2Duration of action of moving object

If isotopic substitution is used to extend T1 time, then polarization retention improves, but manufacturing complexity and cost increase

Engineering Contradiction:

ImproveT1 relaxation timeVSAvoidprobe production

Core Design Contradiction:

Duration of action of moving objectVSEase of manufacture

Solution Approach 1:

The patent employs nanoparticles made from abundant, non-enriched materials (such as calcium phosphate or silica) that do not require expensive isotopic enrichment. These nanoparticles serve as disposable carriers that can be synthesized through straightforward wet-chemical methods, avoiding the complex and costly isotopic substitution process while still achieving extended T1 times through their crystalline structure

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

3Duration of action of moving object

If RF irradiation is applied to extend T1 time, then polarization retention improves, but device complexity and operational difficulty increase

Engineering Contradiction:

ImproveT1 relaxation timeVSAvoidhyperpolarization system

Core Design Contradiction:

Duration of action of moving objectVSDevice complexity

Solution Approach 1:

The invention extracts the T1 extension function from the probe molecule itself and transfers it to the nanoparticle carrier material. This eliminates the need for complex RF irradiation systems or continuous electromagnetic field application, as the extended T1 is an intrinsic property of the nanoparticle-hosted probe system, thereby reducing device complexity and operational difficulty

Inventive Principle:

Principle #2Taking out (Extraction)

4Measurement precision

If hyperpolarized probes are administered for clinical MRI, then imaging sensitivity improves, but polarization is lost during circulation through the body

Engineering Contradiction:

Improveimaging sensitivityVSAvoidpolarization lifetime in circulation

Core Design Contradiction:

Measurement precisionVSDuration of action of moving object

Solution Approach 1:

The patent performs preliminary hyperpolarization of the probe molecule while it is embedded within the nanoparticle carrier in a controlled environment. The nanoparticle's protective crystalline structure is already in place before administration, pre-establishing the extended T1 relaxation environment that will preserve polarization during circulation and imaging, rather than attempting to maintain polarization without such protection

Inventive Principle:

Principle #10Preliminary action

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

The described particles provide hyperpolarized probes with extended T1 times, enabling practical clinical use by maintaining polarization during the journey through the body and facilitating imaging.

Implementation Method 1

The T1 time constant is highly compound specific, and since it arises from the most immediate environment of the nuclei in the compound it is exceedingly hard to manipulate and control.

Methodology Applied

Scientific EffectSpin-lattice relaxation:

Implementation Method 2

combined with homonuclear decoupling to extend T1 times, allowing for stable hyperpolarization of probes

Methodology Applied

Scientific EffectHomonuclear decoupling:

Implementation Method 3

dynamic nuclear polarization (DNP), which is perhaps the most robust and widely used technique. In DNP, one brings unpaired electrons to within interaction range from the target nuclei. The spins are now subject to interaction both with the external field and with each other. Under this modified interaction, appropriate microwave (MW) irradiation, for example at a frequency corresponding to the difference or sum of the electron and nucleus Larmor frequencies, can induce what is known as zero quantum (ZQ) or double quantum (DQ) transitions, respectively. By saturating these transitions, one may impose the electron population difference on the nuclei population giving rise to 3 orders of magnitude increase in polarization.

Methodology Applied

Scientific EffectDynamic nuclear polarization:

Implementation Method 4

appropriate microwave (MW) irradiation, for example at a frequency corresponding to the difference or sum of the electron and nucleus Larmor frequencies, can induce what is known as zero quantum (ZQ) or double quantum (DQ) transitions, respectively

Methodology Applied

Scientific EffectZero quantum transition:

Implementation Method 5

Methodology Applied

Scientific EffectDouble quantum transition:

Implementation Method 6

Particles comprising a crystalline matrix with a dopant, where the matrix is isotopically enriched and doped with biological compounds, combined with homonuclear decoupling to extend T1 times

Methodology Applied

Scientific EffectCrystalline structure effect: Crystallisation

Data Source

PatentUS12409239B2Particles for use in hyperpolarization

Publication Date: 2025.09.09 BEACON MRI LTD

AI summary

Described herein are particles comprising a crystalline matrix and a dopant, wherein one of the atoms of the matrix is 19F and 31P, or 13C, 15N, 29Si, 16O, 17O, 23Na, 39K, 25Mg, 40Ca, 43Ca or deuterium; and the dopant is a compound involved in a biological process in a mammalian organism; and wherein the dopant is present in an amount of between 0.01% and 20% of the plurality of particles, and wherein when the matrix comprises an atom selected from the group of 13C, 15N, 29Si, 16Q, 17O, 23Na, 39K, 25Mg, 40Ca, 43Ca and deuterium, and the dopant is isotopically enriched.