Inner Ear Cell Imaging via Two-Photon Fluorescence
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Solution Overview
Problem
Current imaging techniques are inadequate for visualizing inner ear cells due to the challenging access provided by the hard bone surrounding them, limiting diagnosis and treatment options for sensorineural hearing loss.
Innovation Solution
The method involves directing illumination radiation through a layer of bone or cartilage to induce nonlinear responses such as two-photon fluorescence and harmonic generation in inner ear cells, allowing for high-resolution imaging without the need for staining, using systems that include radiation sources, spatial light modulators, and endoscopes to adjust radiation distribution and detect emitted signals.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional imaging techniques (CT scanning, MRI) are used to image inner ear cells, then the imaging can be performed non-invasively, but the resolution is insufficient to establish diagnosis
Solution Approach 1:
The patent changes the parameter of light wavelength to infrared range (e.g., 800-1000 nm) to enable deeper penetration through bone tissue while maintaining high resolution imaging capability through two-photon excitation microscopy
Solution Approach 2:
The patent replaces mechanical biopsy procedures with optical imaging methods that use infrared light to penetrate bone and image cells non-invasively, eliminating the need for surgical intervention
2Measurement precision
If staining is applied to inner ear cells to enhance imaging contrast, then the imaging quality improves, but cell death occurs
Solution Approach 1:
The patent exploits the natural autofluorescence properties of cellular components (NADH, FAD, collagen) to generate imaging contrast without external staining agents, allowing cells to serve themselves for contrast generation
Solution Approach 2:
The patent uses two-photon excitation with infrared light to stimulate autofluorescence from endogenous chromophores, changing the excitation mechanism to avoid toxic staining while maintaining contrast
3Ease of operation
If the bone layer surrounding inner ear cells is removed to access cells for imaging, then direct cell access is achieved, but hearing function is destroyed
Solution Approach 1:
The patent uses infrared light as an intermediary that can penetrate through the bone layer to reach inner ear cells without physical contact or removal of bone, enabling imaging through the natural barrier
Solution Approach 2:
The patent replaces mechanical access methods (drilling, removing bone) with optical penetration using infrared light, substituting physical intervention with electromagnetic wave transmission
4Length of stationary object
If standard imaging wavelengths are used to image through bone, then the imaging setup is simple, but the penetration depth is insufficient
Solution Approach 1:
The patent changes the wavelength parameter to infrared range (800-1000 nm) where bone tissue has higher transmission properties, enabling deeper penetration while using standard two-photon microscopy equipment
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 enables non-invasive, high-resolution imaging and identification of inner ear cells, including damaged ones, by analyzing emission spectra, facilitating better diagnosis and potential treatments for hearing-related issues.
Implementation Method 1
The wavelength of the radiation, and in some embodiments, the temporal and/or spatial distributions of the radiation, are selected to induce nonlinear responses in the cells that are illuminated. Examples of nonlinear responses that can be generated using the methods and systems disclosed herein include two-photon fluorescence (TPF) emission
Implementation Method 2
Examples of nonlinear responses that can be generated using the methods and systems disclosed herein include two-photon fluorescence (TPF) emission and harmonic generation (HG), e.g., second harmonic generation (SHG)
Implementation Method 3
In some implementations of these methods, the system is configured to focus on autofluorescence due to flavin adenine dinucleotide (FAD)
Data Source
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AI summary
Systems and methods for imaging ear tissue include: directing illumination radiation to pass through an intact biological structure and be incident on ear tissue that does not include an exogenous fluorophore, at a plurality of locations, the illumination radiation including a plurality of light pulses each having a temporal duration of 500 femtoseconds or less; for each one of the plurality of locations, using a detector to detect radiation emitted from the location that passes through the intact biological structure; and forming an image of the tissue based on the detected radiation at each of the plurality of locations, where the emitted radiation corresponds to endogenous two-photon fluorescence of the tissue.