Parahydrogen Hyperpolarization of Imaging Agents at Clinical Concentration
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Solution Overview
Problem
Existing methods for hyperpolarizing biorelevant imaging agents are unable to produce clinically relevant volumes, concentrations, and purities of these agents, limiting their application in preclinical or clinical MRI.
Innovation Solution
A method involving parahydrogen induced polarization (PHIP) and signal amplification by reversible exchange (SABRE) is used to generate hyperpolarized target compounds, followed by precipitation and redissolution to achieve desired concentrations and purities, utilizing a magnetic shield for large-volume, homogenous magnetic field modulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If dynamic nuclear polarization (DNP) is used to enhance signal, then sensitivity is improved, but the process is time-consuming and not suitable for clinical use
Solution Approach 1:
The patent replaces the mechanical/chemical DNP process with a quantum mechanical effect (parahydrogen-induced polarization or PHIP). By using parahydrogen and catalytic hydrogenation, the system achieves hyperpolarization through quantum spin effects rather than traditional DNP mechanisms, enabling faster polarization transfer and clinical applicability
2Measurement precision
If parahydrogen is used for hyperpolarization, then signal enhancement is achieved, but the system complexity increases
Solution Approach 1:
The patent employs a universal catalyst system that can process multiple substrates through hydrogenation. The same parahydrogen generation and catalysis platform works across different chemical reactions and target molecules, reducing the need for specialized equipment for each application and simplifying overall system complexity
Solution Approach 2:
The patent uses a catalyst as an intermediary to mediate between parahydrogen and target substrates. This catalyst facilitates the hydrogenation reaction and enables polarization transfer without requiring direct complex interactions between parahydrogen and various target molecules, thereby simplifying the system architecture
3Measurement precision
If hyperpolarized compounds are generated for clinical MRI, then diagnostic capability is improved, but current methods are not scalable to clinical production
Solution Approach 1:
The patent performs hyperpolarization immediately before the MRI scan rather than requiring advance preparation and storage. By generating the hyperpolarized state right before use through in-line hydrogenation, the system maintains high signal intensity without degradation and enables scalable clinical production workflows
Solution Approach 2:
The patent changes the physical-chemical parameters of the system by using ambient temperature and pressure conditions for hydrogenation reactions, replacing the need for cryogenic temperatures required by DNP. This parameter change enables standard clinical equipment to be used and facilitates scalable production
Data Source
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AI summary
Systems and methods are disclosed for generation of hyperpolarized target compounds. Generation of a hyperpolarized target compound can include application of a sequence of microwave pulses to a solution containing the target compound or a precursor of the target compound; or modulation of a magnetic field applied to the solution. When the precursor is hyperpolarized, the precursor can be cleaved to generate the hyperpolarized target compound. The hyperpolarized target compound can then be induced to precipitate out of the solution. The precipitate can be redissolved in a specified volume of solvent to form a solution having a desired concentration of the hyperpolarized target compound.