Optical Sectioning for Real-Time Tissue Imaging
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Solution Overview
Problem
Current surgical pathology imaging methods are time-consuming and inefficient, particularly for large tissue specimens, due to the need for physical sectioning and lengthy processing times, which can delay surgical procedures and require multiple surgeries for complete tissue removal.
Innovation Solution
A system combining a primary imaging system for optically sectioned microscopy with fluorescent contrast agents and an auxiliary imaging system for low-magnification guidance, enabling real-time evaluation of large tissue areas and identification of surgical markings without physical sectioning, using multiphoton, confocal, or structured illumination microscopy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If physical sectioning and staining is performed to achieve high diagnostic sensitivity, then measurement precision is improved, but loss of time increases significantly
Solution Approach 1:
The patent replaces the mechanical sectioning process with optical sectioning using multiphoton excitation microscopy. The mechanical microtome sectioning that traditionally requires embedding tissue in paraffin and cutting thin slices is substituted by optical methods that can section and image tissue in its native state, eliminating the need for physical sectioning while maintaining diagnostic capability
Solution Approach 2:
The patent changes the physical state and optical parameters of tissue imaging by using multiphoton excitation at specific wavelengths to achieve optical sectioning. By adjusting excitation wavelength and using fluorescent contrast agents, the system can selectively image different depths and structures within intact tissue, replacing the need for physical sectioning and chemical staining
2Loss of time
If optical depth sectioning is used to reduce processing time, then loss of time is reduced, but measurement precision deteriorates due to inability to resolve nuclei
Solution Approach 1:
The patent replaces conventional reflectance confocal microscopy with multiphoton excitation microscopy. The multiphoton technique uses nonlinear optical absorption to achieve optical sectioning with superior depth resolution and the ability to resolve cellular nuclei, which was the critical limitation of previous optical sectioning methods
Solution Approach 2:
The patent employs a composite approach combining multiphoton excitation with fluorescent contrast agents that have specificity for cell nuclei. This combination enables both optical sectioning to reduce processing time and nuclear resolution to maintain diagnostic precision, overcoming the limitations of using either method alone
3Measurement precision
If conventional transillumination microscopy is used to achieve diagnostic quality images, then measurement precision is improved, but device complexity increases due to need for physical sectioning equipment
Solution Approach 1:
The patent replaces the complex mechanical sectioning equipment (microtome, embedding apparatus, slide mounting equipment) with an optical sectioning system based on multiphoton microscopy. The inverted microscope configuration with optical sectioning capability eliminates the need for mechanical sectioning while producing diagnostic-quality images through optical methods
Solution Approach 2:
The patent creates an optical copy or representation of the tissue structure through multiphoton excitation and fluorescent imaging. Instead of physically cutting and mounting tissue sections on slides, the system generates optical images that replicate the diagnostic information needed for pathology evaluation, eliminating the need for physical sectioning equipment
4Measurement precision
If large tissue specimens are evaluated to ensure complete resection, then measurement precision is improved, but loss of time increases due to extensive processing required
Solution Approach 1:
The patent replaces the time-consuming process of sectioning, mounting, and staining large tissue specimens with direct optical sectioning and imaging. The multiphoton microscopy system can rapidly evaluate large tissue areas in their native state without mechanical processing, maintaining the ability to assess resection adequacy while dramatically reducing evaluation time
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 rapid, real-time assessment of large tissue specimens for pathology, reducing the need for multiple surgeries by providing high-resolution images of focal pathologies and guiding the evaluation of surgical margins, thus improving surgical efficiency and patient outcomes.
Implementation Method 1
a primary imaging system that uses an illumination source and which is an inverted microscope that produces a sequence of images through one or more spectrally separated channels of a tissue specimen that has been labeled with a fluorescent contrast agent with specificity for cell nuclei or components of cell nuclei
Implementation Method 2
resolves nuclei labeled by the fluorescent contrast agent and which performs optical depth sectioning
Implementation Method 3
an auxiliary imaging system that is configured to acquire an auxiliary image over a greater area than the primary imaging system
Data Source
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AI summary
An apparatus and method for real-time optical imaging of a tissue specimen. The apparatus comprises a primary- imaging system configured to use an illumination source to acquire images of a tissue specimen through one or more spectrally separated channels, and configured to perform optical depth sectioning; an auxiliary imaging system, configured to acquire an auxiliary image of the tissue specimen; a specimen holder having a transparent window therewithin, window, the specimen holder comprising one or more position sensors, wherein the specimen holder is configured to be translatable in the specimen plane; a user input device configured to accept user input, wherein the specimen holder is configured to translate in response to the user input in real-time; a processing unit configured to execute a sequence of instructions on the sequence of images acquired by the primary imaging system, the auxiliary image, and at least one specimen holder position to generate a composite representation of the tissue specimen that includes a representation of ceil nuclei in the specimen; and a display device configured to display the composite representation of the tissue specimen in real-time.