Non-labeled Sugar MRI Contrast via CEST for Tissue Perfusion

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Solution Overview

Problem

Current methods for assessing tissue metabolism and perfusion, such as FDG-PET and DCE-MRI, rely on radioactive or potentially toxic agents, limiting their repeated use and safety, especially for cancer diagnosis and treatment monitoring, and lack sufficient contrast for vascular and chemical property analysis.

Innovation Solution

A method using non-labeled, biocompatible sugars like D-glucose administered to subjects for MR imaging or spectroscopy, where temporal variations in MR signals are detected to determine tissue-related parameters like metabolism and perfusion, utilizing chemical exchange saturation transfer (CEST) MRI sequences to generate contrast without radioactivity or toxicity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If FDG-PET is used to assess tissue metabolism, then glucose uptake measurement is improved, but radioactivity and short half-life limit repeated use

Engineering Contradiction:

Improveglucose uptake measurementVSAvoidrepeated use capability

Core Design Contradiction:

Measurement precisionVSReliability

Solution Approach 1:

The patent replaces expensive, radioactive, short-lived FDG with inexpensive, non-radioactive glucose that can be repeatedly administered. Normal glucose has no radioactive label but can be detected by MRI through metabolic byproducts, enabling multiple assessments without the constraints of radioactive half-life

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent uses MRI-detectable metabolic byproducts (lactate, alanine) as intermediaries to indirectly measure glucose uptake. Instead of directly detecting glucose or radioactive FDG, the method detects endogenous metabolites that result from glucose metabolism, providing a safe alternative that preserves measurement capability

Inventive Principle:

Principle #24Intermediary (Mediator)

2Measurement precision

If DCE-MRI with Gadolinium agents is used to assess tissue perfusion, then perfusion parameter measurement is improved, but safety issues arise in persons with kidney disease

Engineering Contradiction:

Improveperfusion parameter measurementVSAvoidnephrogenic systemic fibrosis risk

Core Design Contradiction:

Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent replaces potentially toxic Gadolinium contrast agents with endogenous metabolites (lactate, alanine) that are naturally produced by tissue metabolism. These metabolites require no exogenous administration and pose no kidney-related safety risks, enabling safe perfusion assessment in vulnerable populations

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent utilizes the body's own metabolic byproducts as contrast agents. Tissues naturally produce lactate and alanine during metabolism, and these endogenous substances serve as MRI-detectable markers for perfusion and metabolic assessment, eliminating the need for external contrast agents

Inventive Principle:

Principle #25Self-service

3Reliability

If non-labeled sugars are used for MR imaging, then safety and repeated use are improved, but signal contrast may be insufficient

Engineering Contradiction:

Improvesafety and repeated useVSAvoidsignal contrast

Core Design Contradiction:

ReliabilityVSMeasurement precision

Solution Approach 1:

The patent changes the detection parameter from direct glucose signal to metabolic byproduct signals (lactate, alanine). By detecting the chemical shift and signal characteristics of these metabolites rather than glucose itself, the method achieves sufficient contrast while using safe, non-labeled sugars

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent substitutes direct detection of administered sugar with detection of metabolic byproducts through chemical exchange saturation transfer (CEST) MRI. This indirect detection mechanism provides enhanced signal contrast by exploiting the magnetic resonance properties of metabolite protons rather than relying on direct sugar signal

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

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 safe, repeated assessment of tissue metabolism and perfusion without radioactive agents, providing sufficient contrast to probe metabolic and vascular properties, potentially reducing false-positive cancer detection rates and improving treatment monitoring, while being compatible with clinical MR scanners.

Implementation Method 1

utilizing chemical exchange saturation transfer (CEST) MRI sequences to generate contrast without radioactivity or toxicity

Methodology Applied

Scientific EffectChemical exchange saturation transfer (CEST):

Data Source

PatentUS10967076B2Use of non-labeled sugars and detection by MRI for assessing tissue perfusion and metabolism

Publication Date: 2021.04.06 JOHNS HOPKINS UNIVERSITY

AI summary

A method for magnetic resonance (MR) imaging or spectroscopy on a MR scanner to detect tissue physiological parameters in one or more tissue areas in a human or non-human subject includes administering to the subject a contrast enhancing physiologically tolerable amount of a sugar that is non-labeled, subjecting the subject to an MR procedure capable of generating MR signals encoding at least one tissue area in the subject in which the sugar either passes or is taken up, detecting a temporal variation in the MR signals in the at least one tissue area after the administering the sugar, determining at least one tissue-related parameter from the temporal variation, and ascertaining whether the at least one tissue-related parameter is abnormal.