pH-Weighted CEST MRI Using Amine Proton Saturation

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Solution Overview

Problem

Current medical imaging techniques for detecting altered tissue pH, particularly in cancerous tissues, often require exogenous contrast agents and are invasive or have limitations in spatial resolution and scan time, making them inadequate for early identification of malignant transformation and tumor monitoring.

Innovation Solution

A pH-weighted chemical exchange saturation transfer (CEST) MRI technique that targets amine protons on amino acids, using a modified magnetization transfer RF saturation pulse with high-amplitude Gaussian pulses to generate contrast, allowing for non-invasive, high-resolution imaging without exogenous agents and reducing scan time.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If exogenous radiotracers or paramagnetic CEST contrast agents are used for pH-sensitive imaging, then pH sensitivity is improved, but invasiveness and regulatory approval status worsen

Engineering Contradiction:
ImprovepH sensitivityVSAvoidinvasiveness
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent utilizes endogenous amine protons from amino acids as the CEST source, eliminating the need for exogenous contrast agents. The body's own metabolites serve the imaging function, making the technique non-invasive while maintaining pH sensitivity through the chemical exchange properties of amine protons

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The patent uses amine protons as an intermediary substance that naturally exists in tissues and can be saturated through RF pulses. These amine protons act as a mediator between the imaging system and the pH environment, transferring pH information to the detectable CEST signal without requiring external agents

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If traditional CEST imaging sequences are used, then pH-weighted contrast is achieved, but scan time increases

Engineering Contradiction:
ImprovepH-weighted contrastVSAvoidscan time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent segments the CEST imaging process by focusing specifically on the amine proton resonance region (2.8-3.2 ppm) rather than acquiring the full spectral range. This selective segmentation of the frequency domain allows for faster acquisition while maintaining pH-weighted contrast through targeted saturation of amine protons

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent employs periodic RF saturation pulses at the amine proton frequency to maintain saturation during the imaging sequence. This periodic action ensures continuous pH-weighted contrast generation throughout the scan, enabling faster imaging compared to non-periodic or continuous saturation approaches

Inventive Principle:
Principle #19Periodic action

3Measurement precision

If high spatial resolution pH imaging is performed, then tumor microenvironment visualization is improved, but scan time and data complexity increase

Engineering Contradiction:
Improvespatial resolutionVSAvoidscan time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent applies local quality by targeting the specific amine proton frequency region (2.8-3.2 ppm) where pH-sensitive contrast is generated. This localized frequency targeting allows high spatial resolution imaging of pH changes in tumor microenvironments without requiring full spectral acquisition across all frequencies, thereby reducing scan time

Inventive Principle:
Principle #3Local quality

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 technique provides increased CEST contrast with decreasing pH, enabling improved visualization of tumor microenvironments and potential early detection of tumor invasion, proliferation, and angiogenesis, with faster scan times and higher spatial resolution compared to traditional methods.

Implementation Method 1

Chemical exchange saturation transfer (CEST) is a magnetic resonance imaging (MRI) technique that generates image contrast dependent on the chemical exchange between water protons and labile protons on various other molecules

Methodology Applied
Scientific EffectChemical exchange saturation transfer (CEST):

Implementation Method 2

The method uses a modified magnetization transfer (MT) radiofrequency (RF) saturation pulse for generation of image contrast

Methodology Applied
Scientific EffectMagnetization transfer: Magnetic Saturation

Data Source

PatentEP3304060B1PH-weighted MRI using fast amine chemical exchange saturation transfer (CEST) imaging
Publication Date: 2024.09.18 RGT UNIV OF CALIFORNIA
  • EP3304060B1 patent drawingFigure 1~2B
  • EP3304060B1 patent drawingFigure 3A~3C
  • EP3304060B1 patent drawingFigure 4A~4C

AI summary

A pH-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) method and system are provided that works by indirectly measuring the NMR signal from amine protons found on the backbones of amino acids and other metabolites, which resonate at a frequency of +2.8-3.2 ppm with respect to bulk water protons. The technique uses a modified magnetization transfer radiofrequency saturation pulse for the generation of image contrast. A train of three 100 ms Gaussian pulses at high amplitude (6 uT) or Sinc3 pulses are played at a particular frequency off-resonance from bulk water prior to a fast echo planar imaging (EPI) readout, with one full image acquired at each offset frequency. This non-invasive pH-weighted MRI technique does not require exogenous contrast agents and can be used in preclinical investigations and clinical monitoring in patients with malignant glioma, stroke, and other ailments.