Aldehyde-Binding Compounds for Non-Invasive CEST-MRI Detection

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Solution Overview

Problem

Current diagnostic technologies lack effective methods for detecting biologically relevant aldehydes, particularly in vivo, which are markers for conditions like concussions, neurodegenerative diseases, and cancer chemotherapy efficacy, due to limitations in existing imaging and detection techniques.

Innovation Solution

Development of aldehyde-binding compounds, such as those represented by Formula I, which can bind to aldehydes and be detected using MRI, CEST-MRI, PET, fluorescence, or electrochemical methods, allowing for the detection of freely diffusing small molecule aldehydes in biological samples or subjects.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional diagnostic methods (spectrophotometric methods, postmortem tissue sampling) are used to detect aldehydes, then detection capability is provided, but the methods are invasive and require postmortem sampling

Engineering Contradiction:
Improvedetection capabilityVSAvoidinvasiveness
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent introduces CEST-MRI as an intermediary detection method that enables non-invasive in vivo imaging. The technique uses magnetic resonance imaging with chemical exchange saturation transfer to detect aldehyde groups through their interaction with water protons, eliminating the need for invasive tissue sampling while maintaining detection reliability

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces mechanical/invasive sampling methods with a non-invasive imaging technique. Instead of physically extracting tissue for spectrophotometric analysis, the system uses magnetic field-based CEST-MRI to detect aldehydes through their chemical exchange properties, substituting mechanical intrusion with electromagnetic field interaction

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Ease of operation

If CEST-MRI is used to detect carbonyls under physiological conditions, then non-invasive detection is achieved, but detection of biologically significant functional groups remains challenging

Engineering Contradiction:
Improvenon-invasive detectionVSAvoiddetection sensitivity
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent optimizes CEST-MRI parameters including magnetic field strength, saturation pulse intensity, and exchange rate characteristics to enhance detection sensitivity. By adjusting these parameters, the system achieves reliable detection of biologically significant carbonyl groups under physiological conditions while maintaining non-invasive operation

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent enhances detection specificity by focusing on local chemical exchange properties of carbonyl groups. The CEST-MRI technique exploits the unique magnetic resonance characteristics of protons exchanging with water near carbonyl groups, allowing precise localization and detection of these functional groups amidst the complex biological environment

Inventive Principle:
Principle #3Local quality

3Reliability

If aldehyde-binding compounds are developed for detection, then specific binding capability is achieved, but the complexity of detection systems increases

Engineering Contradiction:
Improvebinding specificityVSAvoiddetection system complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent develops aldehyde-binding compounds that can be integrated into multiple detection modalities including CEST-MRI, fluorescence imaging, and PET. These compounds serve multiple functions: they bind specifically to aldehydes, provide contrast enhancement, and enable detection across different imaging platforms, reducing the need for separate specialized systems

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 non-invasive detection and monitoring of aldehydes indicative of concussions, neurodegenerative diseases, and cancer treatment efficacy, providing a tool for diagnosing and monitoring conditions associated with aldehyde production, such as brain injuries and neurodegenerative disorders.

Implementation Method 1

administering an aldehyde-binding compound of Formula I to the subject and detecting the product of the compound of Formula I and the freely diffusing small molecule aldehyde

Methodology Applied
Scientific EffectChemical reaction: Chemical Bonding

Implementation Method 2

Chemical Exchange Saturation Transfer magnetic resonance imaging (CEST-MRI) shows promise in detection of functional groups of physiological interest. CEST-MRI imaging can detect endogenous biomolecules that exchange protons with water

Methodology Applied
Scientific EffectChemical Exchange Saturation Transfer:

Implementation Method 3

detecting the product of the compound of Formula I and the freely diffusing small molecule aldehyde using magnetic resonance imaging (MRI), CEST-MRI or positron emission tomography (PET) imaging

Methodology Applied
Scientific EffectPositron emission: Radioactive Decay

Data Source

PatentUS20230358732A1Methods and compounds for detection and binding of aldehydes
Publication Date: 2023.11.09 UNIVERSITY OF OTTAWA
  • US20230358732A1 patent drawing
  • US20230358732A1 patent drawing
  • US20230358732A1 patent drawing

AI summary

Methods and kits for detecting a freely diffusing small molecule aldehyde in a subject or in a sample from a subject are described herein, comprising administering an aldehyde-binding compound of Formula I to the subject, or combining such a compound with the sample; and detecting the product of the compound of Formula I and the aldehyde. Detection of the product may involve imaging, such as MRI, CEST-MRI or positron emission tomography (PET) imaging; or may involve fluorescence or an electrochemical detection method. Relevant aldehydes detected according to the described method can be used to determine the presence or severity of a concussion in a subject.