Cryogenic Pyruvic Acid Hyperpolarization Without Adulterants
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Solution Overview
Problem
Existing methods for generating hyperpolarized nuclear spins for NMR and MRI applications require adulterants that are often toxic and complicate drug approval, and these adulterants also increase the rate of hyperpolarization loss, making it difficult to achieve long storage and transport times for hyperpolarized materials.
Innovation Solution
A method of manipulating nuclear spin-relaxation times by cooling and maintaining pyruvic acid or similar samples in specific temperature ranges without adulterants, shifting the T1 versus temperature profile to enhance spin polarization retention, allowing for hyperpolarization without the need for toxic additives.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If adulterants are added to extend T1 relaxation time for hyperpolarization storage, then storage time is improved, but toxicity and device complexity increase
Solution Approach 1:
The patent removes adulterants from the hyperpolarization storage system entirely. Instead of using paramagnetic substances to extend T1, the invention uses pure frozen samples stored at cryogenic temperatures, eliminating the harmful adulterants while achieving the desired storage time extension through temperature control alone.
Solution Approach 2:
The patent changes the temperature parameter from moderate temperatures (where adulterants would be needed) to cryogenic temperatures (below freezing point). This parameter change fundamentally alters the relaxation behavior, extending T1 without requiring any adulterants, thus resolving the toxicity issue.
2Reliability
If adulterants are used to manipulate spin relaxation, then T1 control is improved, but manufacturing complexity and regulatory approval difficulty increase
Solution Approach 1:
The patent extracts and removes the adulterant component from the system, using only the pure pharmaceutical compound in frozen state. This simplifies manufacturing and eliminates regulatory hurdles associated with approving additional substances, while T1 control is achieved through temperature management.
Solution Approach 2:
The frozen sample itself provides the T1 extension effect without requiring external adulterants. The crystalline structure and molecular mobility restrictions in the frozen state inherently extend relaxation times, making the system self-sufficient and eliminating the need for additional approved substances.
3Ease of operation
If sample temperature is maintained above freezing point, then ease of handling is improved, but spin polarization retention deteriorates
Solution Approach 1:
The patent utilizes the phase transition from liquid to solid (freezing) to fundamentally change the sample's properties. In the frozen state, molecular motion is restricted, extending T1 and preserving spin polarization. The system is designed to operate in this frozen phase, with specialized handling procedures for cryogenic materials.
Solution Approach 2:
The patent changes the temperature parameter below the freezing point, which fundamentally alters the sample's physical state and relaxation behavior. This parameter change extends spin polarization lifetime by restricting molecular motion, accepting the trade-off of requiring cryogenic handling infrastructure.
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
This approach enables the retention of spin polarization in hyperpolarized samples, extending storage and transport times by minimizing exposure to unfavorable temperature conditions, thus enhancing the utility and safety of hyperpolarized materials for medical applications.
Implementation Method 1
In all steps leading to ULT-derived hyperpolarized products, the critical timescale is T1(B0,T). It defines the rate at which nuclear spins approach the Boltzmann condition for a given B0 and T
Implementation Method 2
A method of manipulating nuclear spin-relaxation times by cooling and maintaining pyruvic acid or similar samples in specific temperature ranges without adulterants
Data Source
AI summary
A method of providing a material sample in a state favorable to retaining spin polarization includes cooling a material sample from a temperature above a freezing point of the material sample down to a second temperature below the freezing point of the material sample; maintaining the sample at about the second temperature for a period of about several hours; and reducing temperature of the material sample to a third temperature lower than the second temperature to provide the material sample in a state favorable to retaining spin polarization, where the steps of cooling, maintaining and reducing are performed in the absence of an adulterant material. The method of providing a sample of pyruvic acid in a state favorable to retaining spin polarization may include cooling the sample of pyruvic acid in the absence of an adulterant material from a temperature above a freezing point of the sample of pyruvic acid down to less than about 200 Kelvin to provide the sample.