Contrast Agent Velocity Estimation via Spatiotemporal Dispersion Analysis

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Solution Overview

Problem

Current methods for estimating contrast agent velocity in vascular networks are limited by the ambiguity between dispersion and convective processes in measured indicator dilution curves, only allowing for the estimation of combined parameters rather than independent values, which hinders the accurate assessment of angiogenesis.

Innovation Solution

A method that utilizes spatiotemporal dependency to estimate contrast agent velocity by fusing spatial and temporal information, incorporating causality and time-delay measures, and employing convection-diffusion models, Wiener-Hopf equations, and compartment models to separately determine velocity and dispersion values, along with machine learning algorithms to generate 2D or 3D images indicating angiogenic regions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional indicator dilution curve analysis is used to estimate contrast agent transport, then the measurement process is simple, but only combined parameters (ratio of convection to dispersion) can be estimated, not independent velocity and dispersion values

Engineering Contradiction:
Improvevelocity estimation accuracyVSAvoidmeasurement system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent transitions from analyzing single-point indicator dilution curves to utilizing spatiotemporal concentration distributions across multiple spatial locations and time points. By adding the spatial dimension to the traditional temporal analysis, the system can independently estimate both velocity and dispersion parameters through the relationship between spatial concentration gradients and temporal evolution, resolving the parameter ambiguity inherent in single-point measurements.

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

Solution Approach 2:

The patent introduces a convection-diffusion model as an intermediary framework that connects measurable spatiotemporal concentration data with the underlying physical parameters (velocity and dispersion). This model acts as a mediator that translates complex spatiotemporal observations into independent estimates of velocity and dispersion coefficients, enabling accurate parameter extraction without directly measuring each parameter separately.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If transrectal systematic needle biopsies are used for prostate cancer diagnosis, then tumor detection is possible, but nearly a quarter of clinically significant cancers are missed and exact tumor locations are not provided

Engineering Contradiction:
Improvetumor localization accuracyVSAvoidinfection risk
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary action by performing non-invasive DCE-US imaging and spatiotemporal analysis before any invasive biopsy procedure. The method pre-identifies regions with abnormal angiogenic activity and generates probable tumor location maps, allowing clinicians to target biopsies more accurately and avoid unnecessary invasive procedures in benign areas, thereby reducing infection risk while improving detection accuracy.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent replaces the mechanical invasive biopsy system with a non-invasive imaging-based detection system. By using DCE-US imaging combined with spatiotemporal convection-diffusion analysis, the system substitutes physical needle insertion with optical/acoustic field-based measurement, eliminating infection risks associated with transrectal biopsies while providing superior tumor localization through angiogenic activity mapping.

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

3Measurement precision

If Doppler of contrast-enhanced imaging is used to assess flow and perfusion, then angiogenic activity can be detected, but the measurement is complicated by low blood flow values in micro vessels requiring high sensitivity

Engineering Contradiction:
Improvemicro vessel flow detection sensitivityVSAvoidimaging system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent applies hydraulic principles by analyzing contrast agent transport through the microvascular network using convection-diffusion equations that model fluid dynamics in porous media. Instead of relying on Doppler velocity measurements that struggle with low flow speeds, the method tracks the temporal evolution of contrast concentration, effectively using the contrast agent as a hydraulic tracer to infer flow characteristics from concentration-time curves, achieving high sensitivity in low-flow microvascular environments.

Inventive Principle:
Principle #29Pneumatics and hydraulics

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 the independent estimation of contrast agent velocity and dispersion, providing improved indications of angiogenesis and allowing for more accurate localization of angiogenic regions, as demonstrated by enhanced ROC curve areas and diagnostic performance in prostate cancer imaging.

Implementation Method 1

The dispersion kinetics of the agent reflects the microvascular architecture, being mainly determined by multipath trajectories. The results show the potential of the method. However, only the ratio between convection (squared velocity) and dispersion can be estimated

Methodology Applied
Scientific EffectConvection: Convection

Implementation Method 2

a new method has been introduced by contrast-enhanced MRI and ultrasound that permits the local estimation of a parameter related to the dispersion kinetics of a contrast agent flowing through a microvascular network

Methodology Applied
Scientific EffectDispersion: Dispersion (of waves)

Implementation Method 3

Diffusion tensor MRI (DT-MRI) was the first non-invasive in-vivo imaging modality that enables the generation of fiber trajectories in soft fibrous tissues, such as nerves and muscles. It is based on the anisotropic nature of water diffusion in well-ordered structures

Methodology Applied
Scientific EffectDiffusion: Diffusion

Data Source

PatentEP3347874B1Imaging of dispersion and velocity of contrast agents
Publication Date: 2021.05.12 ANGIOGENESIS ANALYTICS BV
  • EP3347874B1 patent drawingFigure 1A
  • EP3347874B1 patent drawingFigure 1B
  • EP3347874B1 patent drawingFigure 2(a)~2(e)

AI summary

The invention relates to a method of estimating a velocity of a contrast agent. The method comprises receiving a plurality of video frames that were produced using a dynamic contrast enhanced imaging process, each video frame comprising a plurality of pixels/voxels. Information from the video frames is used to estimate velocity vectors indicating the velocity and direction of the agent with the vascular networks. The estimated velocity can be used to diagnose cancer, such as prostate cancer. Instead of velocity vectors, agent trajectories can be determined also used for the same purpose.