Amide Proton CEST pH Measurement Method
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Solution Overview
Problem
Existing methods for measuring intracellular pH are limited by the need to estimate parameters like pKw and f amide, which is challenging in vivo, and assume amine and amide groups are from the same macromolecule, making clinical adoption difficult due to faster chemical exchange rates and direct water saturation effects.
Innovation Solution
A method using amide protons as endogenous contrast agents measures the chemical exchange saturation transfer effect ratio R under different saturation powers, establishing a function relation between pH and R, eliminating concentration dependencies and enabling accurate, non-invasive pH measurement by stabilizing imaging under clinical magnetic field strengths.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If amine groups are used for CEST imaging, then pH measurement can be performed, but the faster chemical exchange rate makes the CEST effect difficult to capture under clinical magnetic field strength
Solution Approach 1:
The patent changes the chemical parameter of the contrast agent from amine groups to amide groups, which have slower chemical exchange rates. This parameter change makes the CEST effect detectable under clinical magnetic field strengths while maintaining pH measurement capability, as amide protons exchange at rates suitable for clinical imaging conditions.
Solution Approach 2:
The patent uses endogenous amide protons as a naturally available contrast agent instead of requiring exogenous agents. These endogenous protons are always present in proteins and peptides, providing a convenient, cost-free contrast mechanism that works reliably under clinical conditions without requiring additional agent administration.
2Measurement precision
If exogenous contrast agents are used for CEST imaging, then pH measurement can be performed, but the method becomes less convenient for clinical adoption
Solution Approach 1:
The patent utilizes endogenous amide protons that are naturally present in body proteins and peptides as the contrast agent. This self-service approach eliminates the need for external agent administration, simplifying the clinical workflow and improving ease of operation while maintaining accurate pH measurement capability.
Solution Approach 2:
The patent leverages the universal presence of amide protons in proteins throughout the body as a universally applicable contrast mechanism. This multi-functional approach allows the same endogenous protons to serve both as structural components of proteins and as pH-sensitive contrast agents, simplifying clinical implementation.
3Measurement precision
If ratiometric imaging using amine and amide groups is performed, then pH measurement can be established, but the assumption that they are from the same macromolecule cannot be strictly proved
Solution Approach 1:
The patent extracts and isolates the amide proton signal as the sole contrast mechanism, eliminating the need for ratiometric comparison with amine groups. By focusing on a single well-defined proton type with known chemical properties, the method removes the unreliable assumption about macromolecular origin while maintaining pH measurement accuracy through the characteristic chemical shift and exchange rate of amide protons.
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 allows for more accurate and convenient pH measurement in organism tissues, facilitating clinical applications and improving the prediction of pathogenesis, development processes, and prognostic evaluations of diseases.
Implementation Method 1
Chemical exchange saturation transfer (CEST) imaging is a magnetic resonance molecular imaging technique, which is based on the chemical exchange effect between exchangeable protons in an endogenous or exogenous contrast agent and water molecules
Implementation Method 2
A reference document D1(US2015/0323632A1) provides systems and methods for indicating pH in a subject using a magnetic resonance imaging (MRI) system
Data Source
Figure 1~2
AI summary
Provided is a method for measuring pH. Using amide protons as an endogenous contrast agent, a chemical exchange saturation transfer effect ratio R of amide protons corresponding to a pH-known amide proton solution under different saturation powers is measured by the method, then a function relation between pH and R is established according to different pH-known amide proton solutions and the corresponding measured R thereto, and finally the desired pH is calculated according to experimentally measured Ri and the function relation. The method can eliminate the impact of concentration and does not require any estimation or measurement of the parameters such as the concentration of exchangeable protons, the longitudinal relaxation time of water, etc., and therefore can measure pH more accurately, conveniently and non-invasively. In addition, amide groups have a relatively low chemical exchange rate, and can be imaged stably under a clinical magnetic field strength, promising for clinical practices.