PDE-Constrained Bioluminescence Tomography for Small Animal Imaging

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Solution Overview

Problem

Current bioluminescence tomography methods face challenges in accurately reconstructing the three-dimensional distribution of light sources within tissue structures, particularly in small animal imaging, due to high absorption coefficients and dominant boundary effects, leading to less accurate results when using the diffusion approximation in media with small geometries.

Innovation Solution

A PDE-constrained multispectral bioluminescence tomography algorithm that simultaneously solves the forward and inverse problems using a multispectral PDE-constrained optimization approach, reducing computational time and improving accuracy by treating forward and inverse variables independently, and employing regularization terms to mitigate noise sensitivity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Device complexity

If the diffusion approximation is used to solve the radiative transfer equation in small animal imaging, then the computational complexity is reduced and analytical solutions become available, but the reconstruction accuracy deteriorates due to high absorption coefficients and dominant boundary effects in small geometries

Engineering Contradiction:
Improvecomputational complexityVSAvoidreconstruction accuracy
Core Design Contradiction:
Device complexityVSMeasurement precision

Solution Approach 1:

The patent changes the mathematical parameters and formulation of the radiative transfer equation by using a pseudo-inverse solution approach with modified boundary conditions. This transforms the problem from one requiring diffusion approximation to one that can be solved directly using linear algebra techniques, thereby maintaining reconstruction accuracy in small geometries while managing computational complexity through efficient matrix operations.

Inventive Principle:
Principle #35Parameter changes

2Ease of manufacture

If conventional bioluminescence tomography methods are used in media with small geometries and high absorption coefficients, then the method is simpler to implement, but the reconstruction accuracy deteriorates due to less accurate diffusion approximation

Engineering Contradiction:
Improvemethod implementation simplicityVSAvoidreconstruction accuracy
Core Design Contradiction:
Ease of manufactureVSMeasurement precision

Solution Approach 1:

The patent substitutes the diffusion approximation mathematical model with a direct pseudo-inverse solution approach. This replacement eliminates the need for iterative numerical methods while providing accurate reconstruction results in small geometries, thus maintaining implementation simplicity while significantly improving reconstruction accuracy in challenging imaging conditions.

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

3Productivity

If the number of measurements is much smaller than the number of unknown sources, then the measurement system is simpler and faster, but the solution becomes sensitive to random noise

Engineering Contradiction:
Improveimaging speedVSAvoidnoise sensitivity
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent introduces regularization terms as intermediary elements in the objective function to stabilize the inverse solution. These regularization terms act as mediators that prevent overfitting to noisy measurements while preserving the ability to reconstruct source distributions accurately, thus reducing noise sensitivity without sacrificing imaging speed or requiring additional measurements.

Inventive Principle:
Principle #24Intermediary (Mediator)

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

This approach results in a significant speedup of the reconstruction process, achieving a 20-fold acceleration, enabling real-time image construction and reducing the computational requirements, thus allowing for lower-cost devices and improved diagnostic capabilities in imaging tissues for pathology and drug tracking.

Implementation Method 1

Bioluminescence may be generated by cells that have been transfected with a luminescent label such as luciferase. It may also be used to label molecules of interest.

Methodology Applied
Scientific EffectBioluminescence: Bioluminescence

Implementation Method 2

Light from radiant energy sources is strongly scattered in most tissue structures of interest. In addition, tissue structures often contain absorbers.

Methodology Applied
Scientific EffectScattering: Scattering

Implementation Method 3

Light from radiant energy sources is strongly scattered in most tissue structures of interest. In addition, tissue structures often contain absorbers.

Methodology Applied
Scientific EffectAbsorption: Absorption (EM radiation)

Implementation Method 4

A PDE-constrained multispectral bioluminescence tomography algorithm provides fast image reconstruction while maintaining accuracy. The high speed may be obtained by solving forward and inverse problems simultaneously using a multispectral PDE-constrained optimization approach.

Methodology Applied
Scientific EffectPartial differential equation constraint optimization:

Data Source

PatentUS10200655B2Tomographic imaging methods, devices, and systems
Publication Date: 2019.02.05 THE TRUSTEES OF COLUMBIA UNIV IN THE CITY OF NEW YORK
  • US10200655B2 patent drawing
  • US10200655B2 patent drawing
  • US10200655B2 patent drawing

AI summary

A multispectral bioluminescence optical tomography algorithm makes use of a partial differential equation (PDE) constrained approach. A sequential quadratic programming (SQP) method is demonstrated that allows for solving both forward and inverse problems at once by updating the forward and inverse variables simultaneously at each step of the optimization iterations. Light propagation in biological tissue is modeled by using the equation of radiative transfer (ERT) and performance of the ERT-based PDE-constrained approach is modeled through numerical and experimental studies.