MPO-Activated MRI for Unstable Atherosclerotic Plaque Detection
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for detecting unstable atherosclerotic plaques are inadequate, as they cannot reliably identify non-obstructive plaques that are prone to rupture, which contribute to a significant number of fatal heart attacks, and there is a need for non-invasive techniques that can visualize vulnerable plaque.
Innovation Solution
A non-invasive molecular MRI method using a gadolinium(III) chelate contrast agent activated by myeloperoxidase (MPO) in atherosclerotic plaques to enhance imaging, allowing for the determination of ΔCNR, fibrous cap thickness, and cap:lesion ratio, which indicate plaque instability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional imaging methods (angiography, optical coherence tomography, intravascular ultrasound) are used to assess coronary plaque, then structural information such as plaque burden and morphology can be obtained, but unstable plaques cannot be reliably detected
Solution Approach 1:
The patent introduces MPO-activated MRI contrast agents as an intermediary substance that specifically targets and accumulates in unstable atherosclerotic plaques. The contrast agent contains an MPO substrate moiety that is activated by myeloperoxidase enzyme present in unstable plaques, enabling selective detection of vulnerable plaques without requiring complex invasive procedures. This resolves the contradiction by providing high detection accuracy through a relatively simple MRI-based approach.
Solution Approach 2:
The patent replaces mechanical/invasive imaging systems (angiography catheters, optical coherence tomography probes, intravascular ultrasound transducers) with a non-invasive MRI-based molecular imaging system. By substituting the mechanical detection approach with a biochemical-magnetic resonance approach using MPO-activated contrast agents, the system achieves superior detection of unstable plaques while eliminating the complexity and invasiveness of conventional methods.
2Reliability
If invasive methods are used to detect plaque characteristics, then detailed plaque morphology can be visualized, but the detection process becomes invasive and less suitable for routine screening
Solution Approach 1:
The MPO-activated contrast agent performs self-service by automatically targeting and accumulating in unstable plaques through its biochemical interaction with MPO enzyme. The contrast agent's substrate moiety is selectively activated by MPO present in unstable plaques, causing the agent to accumulate specifically at the disease site without requiring external guidance or invasive delivery mechanisms. This enables reliable detection through a simple non-invasive MRI scan.
Solution Approach 2:
The patent uses the MPO-activated contrast agent as an intermediary that bridges the gap between non-invasive MRI imaging and specific plaque characterization. The contrast agent mediates the detection process by selectively accumulating in unstable plaques and providing enhanced MRI signal, thereby enabling reliable plaque detection through simple non-invasive imaging without requiring direct mechanical interaction with the vasculature.
3Loss of information
If non-specific contrast agents are used for plaque imaging, then general plaque burden can be visualized, but specific identification of unstable plaques is not achieved
Solution Approach 1:
The patent applies local quality by designing a contrast agent with specific biochemical properties that enable selective accumulation in unstable plaques. The MPO substrate moiety provides local specificity by being activated only by MPO enzyme present in unstable plaques, causing the contrast agent to concentrate specifically at vulnerable plaque sites rather than distributing uniformly throughout all plaques. This enables differentiation of plaque stability without requiring complex multi-component contrast systems.
Solution Approach 2:
The patent utilizes parameter changes in the contrast agent's biochemical state to achieve specificity. The MPO substrate moiety undergoes enzymatic transformation when activated by MPO enzyme in unstable plaques, changing its molecular properties and enabling accumulation at the target site. This biochemical parameter change provides specific identification of unstable plaques using a single contrast agent rather than requiring multiple agents with different properties.
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 the differentiation between stable and unstable plaques through enhanced imaging, providing thresholds for ΔCNR, cap thickness, and cap:lesion ratio, facilitating early detection and potential stabilization of unstable plaques.
Implementation Method 1
administering to the subject an MRI contrast agent capable of being activated by myeloperoxidase (MPO) in atherosclerotic plaque; allowing the contrast agent to be activated by MPO in atherosclerotic plaque, resulting in image enhancement
Data Source
AI summary
The technology relates to a method for detecting high-risk unstable atherosclerotic plaque in a subject, the method comprising: a) administering to the subject a magnetic resonance imaging (MRI) contrast agent capable of being activated by myeloperoxidase (MPO) in atherosclerotic plaque; b) allowing the contrast agent to be activated by myeloperoxidase in atherosclerotic plaque; c) obtaining an image of the atherosclerotic plaque from the subject using such molecular MRI, wherein enhanced imaging is indicative of unstable plaque. In some embodiments an MPO inhibitor is administered to a subject identified as having a high-risk unstable atherosclerotic plaque.