Hyperspectral Microscope Off-Axis Illumination Real-Time Tissue Imaging

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Solution Overview

Problem

Current medical diagnostics for tissue evaluation are limited by time-consuming processes and lack of real-time capabilities, making it difficult for surgeons to receive clinically relevant information during surgery, especially for identifying suspect lesions.

Innovation Solution

A high-resolution optical imaging method utilizing off-axis illumination and long working distance objectives for hyperspectral/multimodal imaging, which enhances image contrast and visibility of tissue structures, allowing for real-time monitoring of microstructures and cells with high signal sensitivity and spatial resolution down to 0.5 μm.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional histological evaluation (fixation, sectioning, staining) is used, then high contrast tissue images are obtained, but the process is time-consuming and cannot provide real-time information

Engineering Contradiction:
Improvetissue evaluation accuracyVSAvoidprocessing time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent replaces mechanical histological processing (fixation, sectioning, staining) with optical spectroscopic techniques (autofluorescence and light scattering) that can be performed on intact tissue in real-time, eliminating the need for physical sample preparation while providing comparable diagnostic information

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The system utilizes endogenous tissue properties (autofluorescence from natural fluorophores and intrinsic light scattering) to generate contrast without requiring external stains or dyes, allowing real-time imaging of intact tissue with minimal intervention

Inventive Principle:
Principle #25Self-service

2Productivity

If frozen section analysis is used, then real-time information is provided, but it can be used only for readily identifiable lesions

Engineering Contradiction:
Improvereal-time information deliveryVSAvoidlesion detection capability
Core Design Contradiction:
ProductivityVSAdaptability or versatility

Solution Approach 1:

The system changes the detection parameters by using multiple excitation wavelengths and analyzing both autofluorescence emission and light scattering properties, enabling detection of subtle biochemical and structural changes that indicate early or subtle lesions beyond what frozen section morphology can identify

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The optical spectroscopic system provides multiple diagnostic functions simultaneously (autofluorescence imaging, light scattering imaging, spectral analysis) that can detect various types of lesions including early cancer, precancerous changes, and subtle tissue abnormalities, making it more versatile than frozen section analysis

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

3Measurement precision

If confocal microscopy is used for microscopic tissue imaging, then spatial resolution is improved, but light collection efficiency is reduced due to photo-bleaching and limited excitation energy

Engineering Contradiction:
Improvespatial resolutionVSAvoidlight collection efficiency
Core Design Contradiction:
Measurement precisionVSUse of energy by moving object

Solution Approach 1:

The system uses ultrashort pulsed laser excitation with durations in the picosecond to nanosecond range, delivering high peak power in brief intervals that minimize cumulative photo-bleaching while maintaining sufficient excitation energy for high-resolution imaging and spectral detection

Inventive Principle:
Principle #19Periodic action

Solution Approach 2:

The system changes the temporal parameters of laser excitation from continuous wave to ultrashort pulses, and optimizes pulse duration and repetition rate to maximize signal collection efficiency while minimizing photo-bleaching damage to tissue fluorophores

Inventive Principle:
Principle #35Parameter changes

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 fast and sensitive imaging of tissues, suitable for in vivo applications, facilitating real-time surgical guidance, tumor margin delineation, and disease diagnosis, while providing simpler and cost-effective instrumentation for clinical use.

Implementation Method 1

a micro-scale instrument that utilizes autofluorescence emission and/or polarized elastic light scattering for real-time monitoring of microstructures and cells in tissues

Methodology Applied
Scientific EffectAutofluorescence emission: Fluorescence

Implementation Method 2

a micro-scale instrument that utilizes autofluorescence emission and/or polarized elastic light scattering for real-time monitoring of microstructures and cells in tissues

Methodology Applied
Scientific EffectPolarized elastic light scattering: Scattering

Data Source

PatentUS7945077B2Hyperspectral microscope for in vivo imaging of microstructures and cells in tissues
Publication Date: 2011.05.17 LAWRENCE LIVERMORE NAT SECURITY LLC
  • US7945077B2 patent drawing
  • US7945077B2 patent drawing
  • US7945077B2 patent drawing

AI summary

An optical hyperspectral/multimodal imaging method and apparatus is utilized to provide high signal sensitivity for implementation of various optical imaging approaches. Such a system utilizes long working distance microscope objectives so as to enable off-axis illumination of predetermined tissue thereby allowing for excitation at any optical wavelength, simplifies design, reduces required optical elements, significantly reduces spectral noise from the optical elements and allows for fast image acquisition enabling high quality imaging in-vivo. Such a technology provides a means of detecting disease at the single cell level such as cancer, precancer, ischemic, traumatic or other type of injury, infection, or other diseases or conditions causing alterations in cells and tissue micro structures.