Magnetic Resonance Spectroscopy Metabolite Quantification via Inversion Subtraction

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Solution Overview

Problem

Quantification of metabolites from proton magnetic resonance spectroscopy (MRS) of the human brain is confounded by overlap with varying compositions of lipids and macromolecules, leading to reduced reproducibility and operator bias, particularly in acute drug studies.

Innovation Solution

A magnetic resonance pulse sequence inversion technique that acquires water reference and water-suppressed metabolite spectra using frequency-selective inversion pulses, allowing for the subtraction of inverted from non-inverted spectra to isolate specific metabolite peaks with a flat baseline, facilitating easier quantification.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional MRS methods are used to measure metabolites, then the measurement process is simple, but the measurement precision is reduced due to overlapping signals from lipids and macromolecules

Engineering Contradiction:
Improvemetabolite quantification accuracyVSAvoidmeasurement process complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent segments the metabolite measurement process into two distinct components: inverted spectra and non-inverted spectra. By acquiring and subtracting these separate measurements, the method isolates specific metabolite peaks from overlapping lipid and macromolecule signals, thereby improving measurement precision without requiring complex hardware modifications

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces an intermediary processing step (spectral subtraction) that acts as a mediator between the raw MRS signals and the final metabolite quantification. The subtraction of inverted from non-inverted spectra serves as an intermediary operation that eliminates confounding signals from lipids and macromolecules, allowing accurate metabolite measurement

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If frequency-selective inversion pulses are used to isolate metabolite peaks, then the measurement precision improves, but the measurement time increases due to multiple acquisitions

Engineering Contradiction:
Improvemetabolite peak isolation accuracyVSAvoidacquisition time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent employs periodic action by acquiring spectra in alternating inverted and non-inverted states. This periodic acquisition strategy allows the system to collect both types of spectra efficiently, and their subtraction eliminates the need for prolonged continuous monitoring of confounding signals, thereby reducing overall acquisition time while maintaining high measurement precision

Inventive Principle:
Principle #19Periodic action

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 increases the consistency and reduces bias in metabolite measurement, improving the reproducibility of results and enabling more accurate diagnosis and drug effectiveness assessment in neurological disorders such as Alzheimer's and Parkinson's disease.

Implementation Method 1

receiving a first measurement for a metabolite group inverted spectra using magnetic resonance in a volume, receiving a second measurement for the metabolite group without inversion using magnetic resonance in the volume

Methodology Applied
Scientific EffectMagnetic resonance:

Implementation Method 2

CEST imaging uses an off-resonance saturation pulse at the resonance frequency of exchanging protons to null the signal from exchangeable protons in order to indirectly decrease bulk water signal through chemical exchange

Methodology Applied
Scientific EffectChemical exchange:

Data Source

PatentUS11337647B2Quantification of in vivo metabolite
Publication Date: 2022.05.24 THE TRUSTEES OF THE UNIV OF PENNSYLVANIA
  • US11337647B2 patent drawing
  • US11337647B2 patent drawing
  • US11337647B2 patent drawing

AI summary

A magnetic resonance pulse sequence technique may acquire a water reference spectrum and two water suppressed metabolite spectra and with frequency selective inversion pulse centered at either single frequency, at multiple frequencies, or in a single acquisition. Subtraction of the inverted from non-inverted water suppressed metabolite spectrum results in single or a combination of specific metabolite peak/peaks alone with a flat baseline for easier quantification.