Liver Function Assessment via 13C-Substrate Breath Analysis

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Solution Overview

Problem

Current methods for assessing liver function are not individually specific, only provide statistical statements about patient populations, and are not sufficient for direct clinical decision-making, lacking sensitivity to evaluate complex biological processes and changes in liver function.

Innovation Solution

A method involving the administration of a 13C-labeled substrate, such as 13C-methacetin, to measure the 13CO2 content in exhaled air, with data fitted to a first-order differential equation to determine the maximum metabolism dynamics and time constant, allowing for a detailed analysis of liver function.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional laboratory parameters are used to evaluate liver function, then the testing process is simple, but the sensitivity is insufficient to reliably evaluate complex biological processes and changes in liver function

Engineering Contradiction:
Improvesensitivity of liver function evaluationVSAvoidcomplexity of testing process
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention changes the measurement parameter from conventional laboratory parameters to the concentration of 13CO2 in exhaled air, which provides higher sensitivity for evaluating liver function while maintaining a relatively simple testing process through breath analysis

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If statistical statements about patient populations are used, then general trends can be identified, but individual-specific liver function assessment is not possible

Engineering Contradiction:
Improveindividual specificity of liver function assessmentVSAvoidamount of data required for assessment
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The invention extracts the individual-specific metabolic response from the population by measuring the personalized kinetics of 13CO2 elimination, allowing individual liver function assessment without requiring large datasets for each patient

Inventive Principle:
Principle #2Taking out (Extraction)

3Speed

If oral administration of 13C-labeled substrate is used, then the substrate can be administered easily, but the initiation of metabolism is delayed and resolution is insufficient for real-time dynamics

Engineering Contradiction:
Improvespeed of metabolism initiationVSAvoidease of substrate administration
Core Design Contradiction:
SpeedVSEase of operation

Solution Approach 1:

The invention uses intravenous administration (hydraulic route) instead of oral administration to achieve rapid substrate delivery to the liver, enabling real-time measurement of metabolism dynamics without compromising administrative feasibility

Inventive Principle:
Principle #29Pneumatics and hydraulics

4Measurement precision

If respiratory gas samples are collected and stored with partial removal, then the measurement process can be simplified, but procedural errors may occur and measurement precision is reduced

Engineering Contradiction:
Improveprecision of metabolization measurementVSAvoidcomplexity of gas sampling system
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention measures 13CO2 in exhaled air directly in real-time without requiring intermediate storage or partial removal of gas samples, allowing the system to self-monitor continuously and eliminating procedural errors associated with sample handling

Inventive Principle:
Principle #25Self-service

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

Enables a precise, high-resolution evaluation of liver function by providing initial data for diagnosis, enabling individualized assessments of liver performance and metabolic capacity, improving clinical decision-making.

Implementation Method 1

The liver is an organ that is vital for the functioning of a living being, especially humans, since many substances, such as medicines, are broken down enzymatically in the liver

Methodology Applied
Scientific EffectMetabolism: Fermentation

Implementation Method 2

determining the content of a 13CO2 formed from a 13C-labeled substrate to be metabolized in the liver cell tissue

Methodology Applied
Scientific EffectRadioactive tracing: Radioactive Tracing

Data Source

PatentEP2365777B1Determining the liver function by quantitatively measuring the metabolism of substrates
Publication Date: 2013.08.07 HUMEDICS
  • EP2365777B1 patent drawingFigure 1
  • EP2365777B1 patent drawingFigure 2
  • EP2365777B1 patent drawingFigure 3

AI summary

A method for determining the liver performance of a living organism, in particular a human, comprising administering at least one 13C labelled substrate, which is converted by the liver by releasing at least one 13C labelled metabolization product, and determining the amount of the at least one 13C labelled metabolization product in the exhalation air over a definite time interval by the means of at least one measuring device with at least one evaluation unit is disclosed. Using this method, it is possible to describe the measured initial increase of the amount of the at least one 13C labelled metabolization product in the exhalation air using a differential equation of first order and to determine a value Amax (DOBmax) and a time constant tau of the increase of the amount of 13C labelled metabolization product from the solution of the differential equation of first order.