Multimodality Microscopic Imaging System for Biological Structures

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Solution Overview

Problem

Current optical imaging techniques face challenges in providing comprehensive, high-resolution, and high-speed multimodality imaging of biological specimens, particularly in vivo, due to limitations in resolution, speed, and the ability to capture dynamic morphological and functional data without altering the specimen.

Innovation Solution

A multimodality microscopic imaging system that combines optical coherence tomography (OCT) with other modalities like spectral-domain OCT, optical coherence microscopy, and spectrally encoded confocal microscopy, using broad bandwidth or wavelength-tuning sources, allows for simultaneous or serial data acquisition without moving the specimen, enabling high-speed, high-resolution, and four-dimensional imaging with isotropic cellular resolution.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If multiple separate imaging modalities are used to achieve comprehensive biological structure analysis, then measurement precision and resolution are improved, but device complexity and imaging speed deteriorate due to sequential imaging requirements

Engineering Contradiction:
Improvemicrostructure characterization resolutionVSAvoidimaging speed
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent combines multiple imaging modalities (OCT, confocal microscopy, two-photon microscopy) into a single integrated system that can acquire images simultaneously or in rapid succession. The system uses a unified optical platform with multiple light sources and detection paths that share common optical components, enabling comprehensive microstructure characterization without the time delays inherent in sequential imaging with separate devices.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The imaging system is designed with multi-functionality to perform various imaging modalities through a single apparatus. By incorporating multiple light sources (broadband source for OCT, laser for confocal, pulsed laser for two-photon) and configurable optical paths within one system, the device can switch between or combine different imaging techniques without requiring separate specialized equipment, thereby improving both comprehensive analysis capability and imaging efficiency.

Inventive Principle:
Principle #6Universality (Multi-functionality)

2Measurement precision

If exogenous contrast agents are used to enhance imaging contrast, then measurement precision is improved, but harmful factors increase due to specimen alteration and preparation complexity

Engineering Contradiction:
Improvecontrast resolutionVSAvoidspecimen alteration
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The system utilizes endogenous contrast mechanisms where the biological specimen's own structural and optical properties provide the contrast needed for imaging. By leveraging natural differences in light scattering, absorption, and fluorescence emission from cellular components, the system achieves high-contrast images without introducing external contrast agents, thereby avoiding specimen alteration and the associated harmful effects.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The system achieves contrast enhancement by varying imaging parameters such as wavelength, numerical aperture, and detection sensitivity rather than by introducing exogenous agents. The multi-modal approach allows optimization of contrast for different tissue types and structures by adjusting optical parameters within each modality, maintaining specimen integrity while achieving superior contrast resolution.

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If high numerical aperture objective lenses are used to achieve subcellular resolution, then measurement precision is improved, but penetration depth deteriorates due to increased light scattering

Engineering Contradiction:
Improvesubcellular resolutionVSAvoidpenetration depth
Core Design Contradiction:
Measurement precisionVSLength of stationary object

Solution Approach 1:

The system divides the imaging task into multiple modalities, each optimized for different depth and resolution requirements. OCT provides deeper penetration with moderate resolution for overall structural assessment, while confocal and two-photon microscopy provide higher resolution at shallower depths. This segmentation allows the system to achieve both deep penetration and subcellular resolution by selecting or combining appropriate modalities for different imaging depths.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The system transitions from a single imaging plane to multi-depth imaging capabilities by combining techniques that operate at different depth ranges. OCT enables imaging at greater depths with lower resolution, while confocal and two-photon microscopy provide high-resolution images at shallower depths. This dimensional approach to depth resolution allows comprehensive characterization from surface to deep tissue structures.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

4Productivity

If rapid scanning is used to achieve high imaging speed, then productivity is improved, but measurement precision deteriorates due to motion artifacts from specimen movement

Engineering Contradiction:
Improveimaging speedVSAvoidimage accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The system employs continuous wave or rapidly repeated pulsed light sources that maintain constant illumination during the imaging process, enabling continuous data acquisition without interruption. This continuous action allows for rapid scanning while maintaining image quality by minimizing the time window for motion artifacts to develop, and the integrated system can perform real-time image reconstruction and correction.

Inventive Principle:
Principle #20Continuity of useful action

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 system provides a comprehensive view of biological specimens with high-speed, high-resolution, and four-dimensional imaging capabilities, enabling detailed morphological and functional analysis of biological structures, such as the embryonic heart, with improved penetration depth and resolution, facilitating the detection of subtle abnormalities.

Implementation Method 1

A first data set is obtained from a biological specimen using optical coherence tomography information associated with a signal provided by a source arrangement in which a wavelength of light varies over time

Methodology Applied
Scientific EffectLight: Light

Implementation Method 2

The exemplary TDOCT techniques can use low-coherence interferometry to obtain cross-sectional images with ~10 μm resolution and at depths of up to 2 mm

Methodology Applied
Scientific EffectInterference: Interference

Data Source

PatentEP2279691B1Arrangements And Methods For Providing Multimodality Microscopic Imaging Of One Or More Biological Structures
Publication Date: 2023.07.19 THE GENERAL HOSPITAL CORP
  • EP2279691B1 patent drawingFigure 1
  • EP2279691B1 patent drawingFigure 2
  • EP2279691B1 patent drawingFigure 3

AI summary

Method and apparatus according to an exemplary embodiment of the present invention can be provided. For example, first data associated with a first signal received from at least one region of at least one sample can be provided based on a first modality, and second data associated with a second signal received from the at least one sample can be provided based on a second modality which is different from the first modality. Third data associated with a reference can be received. Further data can be generated based on the first, second and third data. In addition, third data associated with a second signal received from the at least one sample can be obtained. Each of the third data can be based on a further modality which is different from the first modality and the second modality, and the further data can be further determined based on the third data. Further, the first modality can be a spectral-encoded modality, and the second modality can be a non-spectral-encoding modality.