Tomographic Fluorescence Imaging for Tumor Depth Resolution

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current surgical methods struggle to accurately visualize and remove invasive tumor portions, especially those with irregular boundaries or located deep within organs, due to limited visibility and the difficulty in distinguishing between normal and abnormal tissues during surgery.

Innovation Solution

A tomographic fluorescent imaging device and method that uses a scanned laser and image processing to model light paths through tissue, determining the depth of fluorophores and displaying tomographic images to help surgeons locate and remove tumors by administering a prodrug that metabolizes into fluorescent molecules, preferentially accumulating in tumor tissues.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional surgical visualization methods are used, then the surgical procedure is simple and quick to perform, but the ability to visualize and distinguish tumor tissue from normal tissue is insufficient

Engineering Contradiction:
Improvetissue differentiation accuracyVSAvoidimaging system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The prodrug is administered to the patient before surgery, allowing tumor cells to accumulate the fluorescent compound in advance. This preliminary action ensures that when the laser excitation occurs during surgery, the tumor tissue is already marked with sufficient fluorescence intensity for clear visualization, resolving the contradiction between detection accuracy and system complexity.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

A fluorescent prodrug serves as an intermediary substance that is selectively taken up by tumor cells. When excited by laser light, this intermediary emits fluorescence that clearly distinguishes tumor tissue from normal tissue. This intermediary approach enables high-precision visualization without requiring complex imaging equipment, as the contrast is provided by the fluorescent marker itself.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If frozen section examination is performed to verify complete tumor removal, then tumor detection accuracy is improved, but surgical time and anesthesia duration are significantly extended

Engineering Contradiction:
Improvetumor detection accuracyVSAvoidsurgical time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The fluorescent prodrug enables the tumor tissue to self-mark and self-visualize during surgery. The tumor cells that have taken up the prodrug emit fluorescence when illuminated by the laser, allowing the surgeon to directly observe tumor boundaries and completeness of resection in real-time without requiring external pathological examination. This self-visualizing capability eliminates the time-consuming frozen section process while maintaining high detection accuracy.

Inventive Principle:
Principle #25Self-service

3Reliability

If extensive tissue removal is performed to ensure complete tumor excision, then tumor removal completeness is improved, but damage to surrounding healthy tissue increases

Engineering Contradiction:
Improvetumor removal completenessVSAvoidhealthy tissue damage
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The fluorescent prodrug exhibits local quality by being selectively accumulated in tumor cells through their altered metabolism, while normal cells show minimal uptake. This creates a localized fluorescence signal precisely at the tumor site and its invasive margins, allowing the surgeon to precisely delineate and remove only the abnormal tissue without unnecessarily damaging surrounding healthy structures.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The invention replaces the mechanical approach of extensive tissue removal with a optical-based visualization system. Instead of relying on physical margins and gross morphological assessment, the surgeon uses fluorescence imaging to precisely identify tumor boundaries. This substitution of mechanical resection margins with optical guidance enables complete tumor removal while preserving healthy tissue that would otherwise be removed as a safety margin.

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

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

Enhances the ability to visualize and remove tumors with high accuracy, reducing the need for extensive tissue removal and minimizing damage to surrounding healthy tissue, while improving surgical outcomes and patient survival rates.

Implementation Method 1

A tomographic fluorescent imaging device and method that uses a scanned laser and image processing to model light paths through tissue

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 2

determining the depth of fluorophores and displaying tomographic images

Methodology Applied
Scientific EffectLight scattering: Scattering

Implementation Method 3

model light paths through tissue

Methodology Applied
Scientific EffectLight absorption: Absorption (EM radiation)

Data Source

PatentUS8948851B2Method and apparatus for depth-resolved fluorescence, chromophore, and oximetry imaging for lesion identification during surgery
Publication Date: 2015.02.03 TRUSTEES OF DARTMOUTH COLLEGE THE
  • US8948851B2 patent drawing
  • US8948851B2 patent drawing
  • US8948851B2 patent drawing

AI summary

A tomographic fluorescent imaging device for imaging fluorophores in biological tissues has a scanned laser for scanning the tissue and a camera for receiving light from the biological tissue at an angle to the beam at a second wavelength ten or more nanometers greater in wavelength than the wavelength of the laser. Use of both intrinsic and extrinsic fluorophores is described. Images are obtained at each of several positions of the beam. An image processing system receives the series of images, models a path of the beam through the tissue, and determines depth of fluorophore in tissue from intersections of the modeled path of the beam and the path of the received light. The laser is of 600 nm or longer wavelength, to provide penetration of tissue. The imaging device is used during surgery to visualize lesions of various types to ensure complete removal of malignant tumors. An alternative embodiment uses differences in intensity of fluorescent radiation from tissue as observed at different wavelengths to determine depth of fluorophore in tissue. An embodiment operates at multiple wavelengths to construct tomographic images of chromophores, such as hemoglobin, and is capable of dynamic imaging.