Hyperpolarized Metabolite Generation With RF Pulses at Clinical MRI Scale
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Solution Overview
Problem
Existing PHIP-SAH polarization methods are unsuitable for preclinical or clinical HP MRI applications due to challenges in achieving sufficient volume and concentration of polarized samples, and radiation damping effects.
Innovation Solution
A system and method involving a chamber with RF coils, magnetic field source, gas-liquid exchange mechanism, and waveform generator to generate hyperpolarized precursors using parahydrogen-induced polarization, applying specific RF pulse sequences to increase nuclear spin polarization.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If existing PHIP-SAH polarization approaches are used, then low cost and high throughput are achieved, but sufficient volume and concentration of polarized samples cannot be obtained
Solution Approach 1:
The patent changes key parameters including using a high magnetic field strength (1.5-7 Tesla) compared to conventional low field systems, increasing sample volume to at least 1 mL, and optimizing precursor concentration to 10-1000 mM. These parameter changes enable simultaneous achievement of high polarization, sufficient volume, and high concentration, resolving the contradiction between quantity and reliability.
2Quantity of substance
If radiation damping effects are present, then polarization transfer is limited, but achieving sufficient polarization level becomes difficult
Solution Approach 1:
The patent applies preliminary anti-action by using high magnetic field strength (1.5-7 Tesla) to increase the Larmor frequency, which reduces the relative impact of radiation damping. The system also uses optimized RF pulse sequences and timing to counteract damping effects before they can significantly reduce polarization transfer efficiency.
3Volume of stationary object
If large volume samples are polarized, then sufficient material for MRI is obtained, but magnetic field inhomogeneity increases
Solution Approach 1:
The patent segments the polarization process into distinct stages: parahydrogen generation in a separate chamber, transport to the polarization chamber, and polarization transfer using optimized RF sequences. This segmentation allows each stage to be optimized independently, enabling large volume polarization while maintaining field homogeneity through controlled processing conditions.
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 method achieves nuclear spin polarization of at least 10% and produces polarized target molecules suitable for MRI applications, overcoming volume and concentration limitations.
Implementation Method 1
a magnetic field source configured to generate a magnetic field with the chamber having a field strength, at least within the sample region, of between 100 mT and 5000 mT
Implementation Method 2
a first pulse sequence configured to transfer polarization from protons associated with the parahydrogen to a nuclear spin of the precursor
Implementation Method 3
The mixing mechanism may comprise a gas-liquid exchange mechanism
Data Source
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AI summary
A method for preparing an NMR material, comprising generating parahydrogen in gas or liquid form at a first location; transporting the parahydrogen away from the first location; mixing a precursor compound including a metabolite component with a catalyst for hydrogenation; hydrogenating the precursor compound using the parahydrogen; transferring polarization in the precursor compound to a nuclear spin of the metabolite component; cleaving a side arm of the precursor compound in a chemical reaction, with the metabolite molecule being one of the products of the reaction; separating the metabolite molecule from the catalyst for hydrogenation and other products of the reaction; and generating metabolite molecules for use in an MRI scanner by extracting a sample of the metabolite molecule having at least 5% polarization.