Non-invasive Nerve Fiber Density Imaging via Harmonic Generation
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Solution Overview
Problem
Current methods for observing intra-epidermal nerve fiber density in human skin are invasive, causing discomfort and potential injuries, and require complex chemical immunostaining techniques, limiting accuracy and efficiency.
Innovation Solution
A non-invasive harmonic generation microscopy apparatus captures intra-epidermal nerve fiber structural images using a nonlinear optical microscopy device, eliminating the need for invasive procedures and chemical staining, and enabling rapid and accurate density calculations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If punch biopsy method is used to observe intra-epidermal nerve fiber density, then nerve fiber images can be obtained, but the method causes discomfort and potential injuries to the patient
Solution Approach 1:
The patent replaces the mechanical punch biopsy system with a nonlinear optical microscopy system that uses laser light to image nerve fibers through the skin non-invasively. The harmonic generation microscopy device captures optical signals from nerve fibers without physical tissue removal, eliminating patient discomfort and injury risks while maintaining measurement capability
Solution Approach 2:
The patent introduces optical harmonic generation signals as an intermediary to visualize nerve fibers. Instead of directly exposing and removing tissue, the system uses laser-induced harmonic generation (second harmonic generation and third harmonic generation) to create optical contrast that reveals nerve fiber structures non-invasively, serving as a mediator between the imaging system and the nerve fibers
2Measurement precision
If chemical immunostaining technique is used to complete nerve fiber observation, then nerve fiber images can be obtained, but the medical procedure becomes complicated
Solution Approach 1:
The patent replaces the chemical immunostaining process with a physical optical imaging method. The nonlinear optical microscopy system uses laser excitation to generate harmonic signals that inherently provide nerve fiber contrast without requiring chemical stains, antibodies, or complex histological processing steps
Solution Approach 2:
The patent enables the nerve fibers to self-reveal their structure through intrinsic optical properties. The harmonic generation signals arise naturally from the nerve fiber structures themselves when illuminated by laser light, eliminating the need for external chemical staining agents to make the fibers visible
3Measurement precision
If chemical immunostaining technique is used for nerve fiber observation, then nerve fiber images can be obtained, but the accuracy is yet to be improved
Solution Approach 1:
The patent replaces chemical staining methods with optical harmonic generation imaging, which provides inherent contrast based on the physical structure of nerve fibers rather than chemical properties. This substitution improves reliability by eliminating variability introduced by staining protocols and providing more consistent, reproducible measurements
Solution Approach 2:
The patent transitions from two-dimensional planar imaging of stained tissue sections to three-dimensional optical sectioning capability. The nonlinear optical microscopy system can capture nerve fiber structures at different depths within the skin, providing spatial information in the vertical dimension that enhances measurement accuracy and diagnostic reliability
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
The apparatus allows for non-invasive, rapid, and accurate determination of intra-epidermal nerve fiber density, facilitating the evaluation of nerve fiber damage and diagnosis of neuropathies like peripheral neuropathy without causing harm to the patient.
Implementation Method 1
the continuous signals of the intra-epidermal nerve fiber structural image are third harmonic generation nonlinear optical signals generated after being excited by the laser light
Data Source
Figure 1~2
AI summary
The present invention relates to a method and apparatus for non-invasive image-observing the density of an intra-epidermal nerve fiber of human skin, in which the method includes: providing a nonlinear optical microscopy device for capturing an intra-epidermal nerve fiber structural image of an acquisition area of a to-be-tested human skin to observe continuous signals of intra-epidermal nerve fiber images, wherein the nonlinear optical microscopy device includes: a laser light source for emitting laser light with a pulsed laser, and an image processing member for processing image signals; focusing the laser light on the intra-epidermal nerve fiber to obtain nerve signals of the intra-epidermal nerve fiber that have a length of at least three points of the intra-epidermal nerve fiber, and constitute a plurality of nerve fibers; and calculating the total number of nerve fiber signals of the to-be-tested human skin, and dividing it by the total area of captured images to obtain the density of the to-be-tested human body; and evaluating and determining whether the human suffers from related neuropathy such as peripheral neuropathy.