Lactic Acid Glassification Agent for MR Probe Hyperpolarization

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Solution Overview

Problem

Existing magnetic resonance (MR) probe compositions and methods face challenges such as adverse effects from water addition, toxicity, metabolic perturbations, and impurities, particularly with glassification agents like pyruvic acid and glycerol, which affect hyperpolarization and EPA removal.

Innovation Solution

The use of lactic acid as a glassification agent in MR probe compositions, which facilitates hyperpolarization without crystallization, reduces toxicity, and aids in the removal of electron paramagnetic agents, forming a stable amorphous solid that can be dissolved into a hyperpolarized liquid probe solution.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If water is added to the MR probe composition, then the glassification agent concentration is adjusted, but crystallization occurs and hyperpolarization is adversely affected

Engineering Contradiction:

Improveglassification agent concentrationVSAvoidhyperpolarization effectiveness

Core Design Contradiction:

Quantity of substanceVSReliability

Solution Approach 1:

The patent changes the chemical composition parameter by substituting lactic acid for traditional glassification agents like glycerol or pyruvic acid. This parameter change allows the system to achieve the desired glassification effect without the crystallization problems that occur when water is added to conventional formulations, thereby maintaining hyperpolarization effectiveness.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

Lactic acid serves as a biodegradable, metabolically compatible glassification agent that is naturally present in the body. This allows the use of a safer, more transient substance that performs its glassification function during the hyperpolarization process and then naturally metabolizes, avoiding the persistence and toxicity issues of conventional agents.

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

2Reliability

If traditional glassification agents like pyruvic acid or glycerol are used, then hyperpolarization can be achieved, but toxicity and metabolic perturbations occur

Engineering Contradiction:

Improvehyperpolarization achievementVSAvoidtoxicity and metabolic perturbations

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

Lactic acid is a naturally occurring metabolite that is rapidly metabolized by the body through the Cori cycle and other metabolic pathways. This biodegradable approach replaces persistent, toxic conventional glassification agents with a transient, metabolically compatible substance that safely performs its function and then naturally disappears from the system.

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent changes the chemical identity parameter of the glassification agent from toxic substances (pyruvic acid, glycerol) to a biocompatible substance (lactic acid). This parameter change fundamentally alters the toxicity profile while maintaining the glassification functionality needed for hyperpolarization.

Inventive Principle:

Principle #35Parameter changes

3Ease of manufacture

If conventional glassification agents are used, then the MR probe can be prepared, but impurities and adverse effects from water addition are introduced

Engineering Contradiction:

ImproveMR probe preparationVSAvoidimpurity contributions

Core Design Contradiction:

Ease of manufactureVSLoss of substance

Solution Approach 1:

Lactic acid's biodegradable nature means it and its metabolic byproducts are naturally processed and eliminated by the body's metabolic systems. This eliminates the impurity accumulation problem associated with conventional agents, as lactic acid metabolites are part of normal physiological cycles rather than foreign substances that accumulate as impurities.

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

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

Lactic acid enables effective hyperpolarization of MR probes with improved polarization levels, reduced metabolic perturbations, and lower impurity contributions, allowing for safer and more accurate MR imaging and spectroscopy without adverse effects from water addition or toxicity.

Implementation Method 1

The glassification agent includes lactic acid... obtaining a hyperpolarized amorphous solid MR probe material... lactic acid enables effective hyperpolarization of MR probes... forming a stable amorphous solid that can be dissolved

Methodology Applied

Scientific EffectGlassification: Vitrification

Implementation Method 2

liquefying the hyperpolarized amorphous solid MR probe material by dissolving the hyperpolarized amorphous solid MR probe material to obtain a hyperpolarized liquid MR probe solution

Methodology Applied

Scientific EffectDissolution: Solvation

Data Source

PatentUS20230400538A1Use of lactic acid in hyperpolarization for magnetic resonance applications

Publication Date: 2023.12.14 GE PRECISION HEALTHCARE LLC

AI summary

A composition is provided. The composition includes a magnetic resonance (MR) probe and a glassification agent. The glassification agent includes lactic acid.