Phase Transfer Process for Hyperpolarized MRI Solutions
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for preparing hyperpolarized molecules for in vivo MRI diagnostic imaging face challenges such as the use of toxic hydrogenation catalysts, organic solvents, and the need for complex dissolution procedures, which hinder the production of aqueous solutions suitable for in vivo applications.
Innovation Solution
A one-step phase transfer process is developed to isolate hyperpolarized molecules from crude organic solutions, eliminating organic solvents and catalyst impurities, using para-hydrogenation with catalysts like Rh(I) complexes in organic solvents, followed by rapid dilution into an aqueous phase to obtain impurity-free aqueous solutions for MRI imaging.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If para-hydrogenation is performed using traditional hydrogenation catalysts, then hyperpolarized molecules are produced, but toxic catalyst impurities contaminate the aqueous solution
Solution Approach 1:
The patent extracts and removes the harmful catalyst from the reaction mixture by performing the hydrogenation reaction in an organic solvent system, then separating the aqueous phase containing thehyperpolarized molecule from the organic phase containing the catalyst. This phase separation effectively extracts the toxic catalyst impurity from the final product solution.
Solution Approach 2:
The patent introduces an organic solvent as an intermediary medium to facilitate the hydrogenation reaction. The organic solvent serves as a mediator that allows the catalyst to function effectively while enabling subsequent separation from the aqueous phase, thus protecting the final product from catalyst contamination.
2Reliability
If hyperpolarized molecules are prepared using conventional methods, then polarization is achieved, but complex dissolution and purification procedures are required
Solution Approach 1:
The patent combines the hyperpolarization process with the dissolution step by performing the para-hydrogenation reaction directly in a solvent system that facilitates subsequent aqueous phase separation. This merging of steps eliminates the need for separate dissolution and purification procedures, simplifying the overall process while maintaining hyperpolarization effectiveness.
Solution Approach 2:
The patent segments the reaction mixture into two distinct phases: an organic phase containing the catalyst and unreacted materials, and an aqueous phase containing thehyperpolarized molecule. This segmentation allows for easy separation and eliminates the need for complex purification procedures, as the desired product is already isolated in the aqueous phase.
3Productivity
If organic solvents are used for hydrogenation reaction, then reaction efficiency is improved, but organic solvent residues remain in the final solution
Solution Approach 1:
The patent extracts the organic solvent from the final product solution by utilizing phase separation. The hydrogenation reaction is performed in an organic solvent to maintain high reaction efficiency, but the subsequent separation of aqueous and organic phases removes the organic solvent residues, leaving only the aqueous phase containing thehyperpolarized molecule.
Solution Approach 2:
The patent exploits phase transition between organic and aqueous phases to separate the reaction mixture. By performing the hydrogenation in an organic solvent and then introducing an aqueous phase, the system transitions to a two-phase system where the organic solvent and aqueous solution separate, allowing removal of organic solvent residues while retaining thehyperpolarized molecule in the aqueous phase.
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 process enables the efficient production of hyperpolarized molecules in an aqueous solution, ready for use in MRI diagnostics without further purification, overcoming the limitations of existing methods by ensuring the molecules are free from organic solvents and catalyst impurities, and maintaining polarization for sufficient imaging time.
Implementation Method 1
The alternative use ofhyperpolarized molecules obtained by addition of para-hydrogen on unsaturated substrates by means of a procedure known as Para Hydrogen Induced Polarization (PHIP)
Implementation Method 2
The population difference between nuclear spin levels can also be increased through exploiting the 'Overhauser' effect between the nucleus of interest and the unpaired electrons of coupled paramagnetic species, according to a technique known as Dynamic Nuclear Polarization or DNP
Implementation Method 3
A one-step phase transfer process is developed to isolatehyperpolarized molecules from crude organic solutions, eliminating organic solvents and catalyst impurities
Implementation Method 4
Magnetic Resonance Imaging is a well established powerful tool for medical and biological investigations both in vitro and in vivo. The main drawback of this technique is due to the intrinsic low sensitivity of the NMR spectroscopy on which MRI is based
Data Source
Figure 1
Figure 2a~3b
Figure 4
AI summary
The invention relates to a one-step process for the preparation of aqueous solutions of hyperpolarized molecules in which, in a single step, the said hyperpolarized molecules are separated from the crude solution by means of a fast phase-transfer extraction and isolated in an impurity-free aqueous solution, ready for use in the MRI diagnostic imaging of organs, region or tissues of the human or animal body.