Non-linear Luminescent Markers for Tomography Autofluorescence
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Solution Overview
Problem
Current fluorescence molecular imaging and tomography systems face challenges with low resolution and contrast due to sensitivity to endogenous tissue autofluorescence, especially in scattering media, which limits the signal-to-background sensitivity and makes diagnostic tasks difficult.
Innovation Solution
The use of non-linear luminescent markers, such as upconverting nanocrystals, which convert incoming near-infrared light to shorter wavelengths, allowing for improved contrast and resolution by reducing autofluorescence interference and enhancing the signal-to-background ratio through a non-linear dependence on excitation light intensity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If Stokes-shifted fluorophores are used for fluorescence imaging in scattering media, then the imaging can be performed with conventional light sources, but the signal-to-background sensitivity is limited due to autofluorescence interference
Solution Approach 1:
Instead of using conventional Stokes-shifted fluorophores that emit longer wavelengths than excitation, this patent employs anti-Stokes shifted fluorophores that emit shorter wavelengths than excitation. This inversion of the typical fluorescence wavelength relationship allows excitation in the near-infrared region (where tissue autofluorescence is minimal) and emission in the visible range, effectively reversing the traditional approach to avoid autofluorescence interference.
Solution Approach 2:
The patent changes the fundamental optical parameter of the fluorophore by utilizing anti-Stokes shifted fluorophores with emission wavelengths shorter than excitation wavelengths, rather than conventional Stokes-shifted fluorophores. This parameter change enables excitation at near-infrared wavelengths (800-1000 nm) where biological tissue has minimal autofluorescence, thereby improving signal-to-background ratio.
2Measurement precision
If conventional fluorescence imaging systems are used, then the system setup is relatively simple, but the image resolution and contrast are low making diagnostic tasks difficult
Solution Approach 1:
The patent inverts the conventional fluorescence approach by using anti-Stokes shifted fluorophores that require higher energy excitation (near-infrared) and emit lower energy light (visible). This inversion enables deeper tissue penetration during excitation while maintaining high contrast imaging in the visible spectrum, improving resolution and contrast for diagnostic applications.
Solution Approach 2:
By changing the fluorophore properties to anti-Stokes shifted characteristics, the system achieves improved image resolution and contrast. The near-infrared excitation penetrates deeper into tissue with less scattering, while the visible emission provides high-contrast images, effectively resolving the limitation of conventional systems without requiring fundamentally new imaging hardware.
3Measurement precision
If Stokes-shifted fluorophores are used, then the fluorescence emission is at longer wavelengths, but the autofluorescence conceals the fluorescence signal effectively
Solution Approach 1:
The patent applies the inversion principle by using anti-Stokes shifted fluorophores that emit at shorter wavelengths than excitation. This allows the fluorescence signal to be detected in the visible range while exciting in the near-infrared range, where tissue autofluorescence is minimal. The inversion effectively separates the signal wavelength from the dominant autofluorescence background.
Solution Approach 2:
The patent changes the emission wavelength parameter to be shorter than the excitation wavelength (anti-Stokes shift), rather than longer as in conventional fluorophores. This parameter change positions the fluorescence emission in a spectral region with minimal tissue autofluorescence background, enabling effective signal detection.
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 significantly improves the contrast and resolution of fluorescence imaging and tomography, enabling more accurate diagnostic information with reduced autofluorescence interference, as demonstrated by experimental and simulation results.
Implementation Method 1
non-linear luminescent markers, such as upconverting nanocrystals, which convert incoming near-infrared light to shorter wavelengths
Implementation Method 2
Photoluminescence is a process in which a substance absorbs photons and then re-radiates photons
Data Source
Figure 1~1A
Figure 1B~7(c)
Figure 2a~2c
AI summary
A method and system for luminescence molecular imaging or tomography of a region of interest in a scattering medium is disclosed. The system comprises a non-linear luminescent marker material arranged in the scattering medium. Contrast and resolution of the imaging or tomography is thus improved. The non-linear marker is for instance configured to upconvert incoming light of an illumination wavelength. The non-linear power dependence of the marker enables further improvement of the imaging by using images taken with two or more excitation beams simultaneously.