Isotope-Labeled Compound MRS via Magnetization Transfer
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Solution Overview
Problem
Current MRS methods face challenges in selectively observing isotope-labeled probe agents in living bodies due to contamination signals from naturally abundant isotopes and low signal-to-noise ratios, especially when using carbon-13, which complicates the analysis of metabolic substances and their distribution.
Innovation Solution
A triple resonance method is employed, where an isotope-labeled compound with at least two nuclei having different nuclear magnetic resonance frequencies is used, allowing for magnetization transfer between these nuclei to selectively observe the probe agent's signal and provide spatial positional information, thereby reducing contamination signals and enhancing signal-to-noise ratios.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If 13CMRS is used to observe isotope-labeled compounds, then peak separation and chemical shift range are improved, but signal-to-noise ratio deteriorates due to low natural isotope abundance of carbon-13
Solution Approach 1:
The patent uses hydrogen-1 as an intermediary to transfer magnetization to carbon-13 nuclei. The hydrogen-1 nuclei are first excited by radiofrequency pulses, and then magnetization is transferred to the carbon-13 nuclei through scalar coupling, enabling detection of carbon-13 signals with enhanced intensity without requiring direct excitation of the low-abundance carbon-13 nuclei
Solution Approach 2:
The patent changes the detection parameter from direct carbon-13 excitation to hydrogen-1 excitation with subsequent magnetization transfer. By using the high-abundance hydrogen-1 nuclei as a proxy and transferring their magnetization to carbon-13, the method converts a low signal-to-noise ratio problem into a high signal-to-noise ratio solution by leveraging the abundant hydrogen-1 signal
2Reliability
If 1HMRS is used to observe hydrogen atoms, then signal-to-noise ratio is improved due to high natural isotope abundance, but peak separation deteriorates because multiple peaks overlap
Solution Approach 1:
The patent transitions from one-dimensional frequency spectrum (standard 1HMRS) to two-dimensional correlation spectrum by adding a second frequency dimension through heteronuclear magnetization transfer. This dimensional expansion allows separation of overlapping peaks through chemical shift correlation between hydrogen-1 and carbon-13, resolving the peak overlap problem while maintaining high signal-to-noise ratio
3Ease of operation
If conventional MRS methods are used in living bodies, then noninvasive detection is achieved, but contamination signals from natural isotopes interfere with probe agent observation
Solution Approach 1:
The patent applies local quality by creating a spatially selective detection mechanism through the combination of hydrogen-1 excitation and carbon-13 magnetization transfer. The method locally enhances the signal from isotope-labeled compounds by transferring magnetization only to carbon-13 nuclei bonded to the excited hydrogen-1 nuclei, thereby selectively observing the probe agent while suppressing background signals from natural isotopes in other locations
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 method enables highly selective observation of the probe agent's dynamic state in the living body with improved signal-to-noise ratios, allowing for precise analysis of metabolic substances and their distribution without significant contamination from natural isotopes.
Implementation Method 1
magnetization transfer from the first nucleus to a second nucleus, magnetization transfer from the second nucleus to a third nucleus, magnetization transfer from the third nucleus to the second nucleus, and magnetization transfer from the second nucleus to the first nucleus
Implementation Method 2
a nuclear magnetic resonance signal measuring method which aims a compound containing a nucleus capable of transmitting a nuclear magnetic resonance signal, as a measurement target
Data Source
AI summary
The present invention provides a method for measuring nuclear magnetic resonance that employs a compound in which a plurality of nuclei is labeled with isotopes as a probe agent, highly selectively and highly sensitively obtains a nuclear magnetic resonance signal of the above described probe agent, and can attach a spatial positional information to the above described nuclear magnetic resonance signal, and an apparatus therefore.