Solid-State MRI Oxygen Sensor for Tumor Hypoxia Mapping
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Solution Overview
Problem
Current methods for measuring tumor oxygenation levels are limited by the lack of accurate, spatially resolved, and clinically compatible techniques, which hinders the adjustment of radiation doses in radiotherapy, particularly in hypoxic tumors, leading to reduced therapeutic efficacy and increased resistance to treatment.
Innovation Solution
The development of MRI-based methods and devices using solid-state contrast agents for oxygen sensing, which allow for the insertion of oxygen sensors into tumors to measure MR relaxation times, enabling precise quantification of oxygen levels and adjustment of high-dose rate brachytherapy doses based on tumor oxygenation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If the Eppendorf Oxygen Electrode (EOE) is used for oxygen measurement, then absolute oxygen measurements can be achieved, but the probe needs to be re-inserted for each measurement and is incompatible with MRI
Solution Approach 1:
The patent replaces the electrochemical EOE probe with an MRI-based detection system using solid-state contrast agents. The contrast agents (paramagnetic or diamagnetic materials) provide oxygen sensitivity through magnetic properties rather than electrochemical reactions, enabling non-invasive, repeated measurements without re-insertion and full MRI compatibility.
Solution Approach 2:
The patent introduces solid-state contrast agents as intermediaries between oxygen and the MRI detection system. These agents (such as oxygen-permeable membranes containing paramagnetic materials) translate oxygen concentration into measurable MRI signal changes, bridging the gap between biological oxygen and magnetic resonance detection.
2Reliability
If HIF-1α marker is used for hypoxia detection, then cellular response to hypoxia can be tracked, but the marker may be upregulated due to non-hypoxia triggers and is not always correlated with tumor oxygenation
Solution Approach 1:
The patent replaces biological marker detection (HIF-1α immunoassay) with direct physical measurement of oxygen using MRI and solid-state contrast agents. This substitutes indirect biochemical inference with direct physical measurement of oxygen concentration, eliminating the correlation issues inherent in marker-based methods.
Solution Approach 2:
The solid-state contrast agents directly sense oxygen through their inherent magnetic properties without requiring external biochemical markers or complex biological pathways. The oxygen-permeable membranes allow direct oxygen diffusion to the contrast agents, enabling self-contained, direct oxygen measurement.
3Measurement precision
If PET-based oxygen measurement with 18F-fluoromisonidazole is used, then oxygen-sensitive tracer imaging can be performed, but spatial resolution is limited and co-registration with anatomical features is difficult
Solution Approach 1:
The patent merges oxygen sensing functionality with MRI imaging, which provides both high spatial resolution and excellent anatomical detail in a single modality. The solid-state contrast agents are imaged using standard MRI sequences, combining functional oxygen mapping with high-resolution anatomical imaging without requiring separate PET and MRI systems or complex co-registration.
Solution Approach 2:
The patent replaces PET tracer-based oxygen measurement with MRI-based detection using solid-state contrast agents. This substitution leverages MRI's superior spatial resolution and anatomical imaging capabilities while maintaining oxygen sensitivity through the magnetic properties of the contrast agents.
4Measurement precision
If TOLD MRI is used for oxygen measurement, then tissue oxygen level can be assessed, but performance characteristics deteriorate with physiologic motion and tissue-air interfaces
Solution Approach 1:
The patent uses solid-state contrast agents enclosed in oxygen-permeable membranes as intermediaries that are less sensitive to motion and interface artifacts than direct tissue imaging methods. These agents provide stable, localized oxygen sensing that is more robust to physiologic motion and tissue-air interfaces compared to conventional TOLD MRI.
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 provides accurate, spatially resolved oxygen measurements, allowing for tailored radiation delivery to hypoxic tumor regions, enhancing treatment efficacy and reducing resistance, thereby improving clinical outcomes in cancer therapy.
Implementation Method 1
using magnetic resonance (MR) to assess an MR property of the at least one oxygen sensor unit... The MR property may be the MR relaxation time (T1) of protons in the at least one oxygen sensor unit
Data Source
AI summary
An oxygen sensor is provided for measuring a dissolved oxygen concentration when deployed or implanted at a tissue site. The oxygen sensor includes a solid-state contrast agent for oxygen. The oxygen sensor is configured to indicate the dissolved oxygen concentration of a tissue when subjected to a magnetic resonance based method. The oxygen sensor may be used to map tumor oxygenation levels and for adaptive planning in brachytherapy.