Optical Probe for Sarcomere Imaging via Inversion and SHG
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Solution Overview
Problem
Conventional biomedical imaging techniques for thick tissues are invasive and provide low-quality images due to the need for foreign matter pre-treatment and sensitivity to physiological motions, limiting their applicability for high-resolution imaging of skeletal and cardiac muscle tissues.
Innovation Solution
A minimally invasive optical probe system that uses intrinsic biocellular sources to generate high-resolution images by stimulating tissues with light pulses and collecting signals such as fluorescence and second harmonic generation (SHG), avoiding the need for foreign matter and mitigating motion artifacts through fast line scan rates.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If transmission-mode SHG imaging is used for high-resolution imaging of thick tissue, then image resolution is improved, but invasiveness increases due to requiring a sensing device on the opposite side of the tissue
Solution Approach 1:
The patent inverts the conventional transmission-mode imaging approach by using reverse-direction detection. Instead of placing the sensing device on the opposite side of the tissue to detect forward-directed SHG signals, the patent detects back-directed SHG signals on the same side where the light source is located. This inversion eliminates the need for invasive placement of sensing devices within the tissue while maintaining imaging capability.
2Object-affected harmful factors
If reverse-direction systems are used to reduce invasiveness, then invasiveness is reduced, but image quality deteriorates due to insufficient signal strength
Solution Approach 1:
The patent changes key parameters of the imaging system to optimize signal detection. This includes using specific wavelength ranges (e.g., 800-1000 nm) that maximize SHG signal generation and detection efficiency. The patent also adjusts detection sensitivity parameters and signal processing parameters to extract adequate image quality from the back-directed SHG signals without requiring invasive tissue treatment.
3Length of stationary object
If conventional imaging is used for thick tissue, then imaging depth is improved, but motion artifacts increase due to sensitivity to physiological motions
Solution Approach 1:
The patent implements continuous or high-frequency sequential imaging to capture multiple frames of the tissue. By acquiring images continuously at high frame rates, the system captures tissue structure during brief intervals between physiological motions (such as cardiac cycles or respiratory phases). This continuous action allows for motion artifact reduction through post-processing techniques that align and average images taken during consistent physiological phases.
4Power
If foreign matter pre-treatment is applied to enhance signals, then signal strength is improved, but invasiveness increases due to introduction of foreign substances
Solution Approach 1:
The patent exploits the tissue's own intrinsic properties to generate the imaging signal. Specifically, it utilizes the endogenous second harmonic generation capability of collagen and other structural proteins naturally present in the tissue. By tuning the excitation light wavelength to match the nonlinear optical properties of these endogenous structures, the system generates sufficient signal strength without requiring any foreign dyes, contrast agents, or genetic modifications.
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 high-resolution imaging of thick tissues with subcellular detail, reducing invasiveness and motion artifacts, allowing for accurate characterization of sarcomere lengths and tissue functionality without pre-treatment or significant physiological compensation.
Implementation Method 1
stimulating structures intrinsic to the thick tissue. The probe is also used to collect the resulting signal for characterization of the tissue structure... uses a microendoscopic probe inserted, like a needle, as part of a minimally-invasive imaging procedure for stimulating structures intrinsic to the thick tissue... collect the resulting signal... using predominantly intrinsic biocellular sources... stimulate the generation of signals, such as fluorescence and/or SHG
Implementation Method 2
collecting signals such as fluorescence and second harmonic generation (SHG)... stimulate the generation of signals, such as fluorescence and/or SHG
Data Source
AI summary
Biological tissue such as skeletal and cardiac muscle can be imaged by using an objective-based probe in the tissue and scanning at a sufficiently fast rate to mitigate motion artifacts due to physiological motion. According to one example embodiment, such a probe is part of a system that is capable of reverse-direction high-resolution imaging without needing to stain or otherwise introduce a foreign element used to generate or otherwise increase the sensed light. The probe can include a light generator for generating light pulses that are directed towards structures located within the thick tissue. The system can additionally include aspects that lessen adverse image-quality degradation. Further, the system can additionally be constructed as a hand-held device.