Intralipid Contrast Agent for Capillary Blood Flow Imaging

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Solution Overview

Problem

Current methods for imaging blood flow in capillaries, such as Optical Doppler Tomography (ODT), face challenges in detecting minute microcirculation and quantitatively imaging capillary blood flow due to low sensitivity and difficulty in distinguishing between different types of microvasculature, especially in highly scattering media like the brain.

Innovation Solution

Intralipid is injected into the bloodstream to enhance imaging by generating a Doppler frequency shift with a laser beam, allowing for the creation of three-dimensional tomographic images and calculating blood flow velocity, thereby improving the sensitivity and accuracy of capillary flow detection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional ODT methods are used to image capillary blood flow, then the imaging can be performed without contrast agents, but the sensitivity is insufficient to detect minute microcirculation and distinguish different types of microvasculature

Engineering Contradiction:
Improvedetection sensitivity of capillary blood flowVSAvoidimaging system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

Intralipid is introduced as an intermediary contrast agent that mediates between the imaging system and the blood flow being imaged. The lipid microparticles in Intralipid serve as additional scattering centers that enhance the Doppler signal from capillary blood flow, enabling detection of minute microcirculation that would otherwise be below the detection threshold of conventional ODT methods

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention changes the optical scattering parameters of the blood by introducing Intralipid, which contains lipid microparticles with specific size distributions (0.03-20 μm). This parameter change enhances the Doppler frequency shift signals from capillary flows, improving the measurement precision of blood flow velocity and flow direction detection in previously undetectable microvasculature

Inventive Principle:
Principle #35Parameter changes

2Reliability

If red blood cells are used as the sole scattering particles for Doppler detection, then the method remains noninvasive, but the latency between red blood cells passing through the detection volume limits continuous flow detection

Engineering Contradiction:
Improvecontinuity of Doppler signalVSAvoidlatency between red blood cell passages
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

Intralipid provides continuous Doppler signals by introducing a high concentration of lipid microparticles that continuously scatter laser light as they flow through the detection volume. This eliminates the gaps in the Doppler signal that occur when using only red blood cells, as the lipid microparticles are present in much higher concentrations and provide uninterrupted scattering events, enabling continuous monitoring of blood flow velocity and direction

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

The lipid microparticles in Intralipid act as artificial scattering particles that copy the Doppler scattering function of red blood cells. These microparticles mimic the light-scattering behavior of RBCs but are present in sufficient concentrations to provide continuous signals, effectively creating a surrogate scattering medium that maintains the noninvasive nature of the imaging while solving the latency problem

Inventive Principle:
Principle #26Copying

3Measurement precision

If high spatial resolution is achieved in ODT for imaging tissue structure, then the ability to image both structure and flow is improved, but the detection of minute microcirculation remains challenging in highly scattering media

Engineering Contradiction:
Improvespatial resolution of tissue structureVSAvoiddetection of minute microcirculation in scattering media
Core Design Contradiction:
Measurement precisionVSDifficulty of detecting and measuring

Solution Approach 1:

The invention enhances the optical contrast in highly scattering media by introducing Intralipid, which modifies the scattering properties of the blood. The lipid microparticles create additional scattering centers that increase the Doppler signal strength from capillary flows, effectively changing the optical interaction characteristics to improve detection of minute microcirculation while maintaining the high spatial resolution structural imaging capability of ODT

Inventive Principle:
Principle #32Color 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

The method significantly enhances the detection and quantification of capillary flow, maintaining sensitivity and accuracy for physiological and pharmacological studies, and effectively differentiates between tumor and non-tumor microvasculature, with intralipid providing continuous Doppler signals that overcome the limitations of red blood cell latency.

Implementation Method 1

applying a laser beam to the specific site so as to generate a Doppler frequency shift of the laser caused by the intralipid flowing through the blood vessels at the specific site

Methodology Applied
Scientific EffectDoppler frequency shift: Doppler Effect

Implementation Method 2

ODT is an optical technique for imaging both the tissue structure and the flow velocity of moving particles in highly scattering media

Methodology Applied
Scientific EffectLight scattering: Scattering

Data Source

PatentUS10531803B2Intralipid as a contrast agent to enhance subsurface blood flow imaging
Publication Date: 2020.01.14 THE RES FOUNDATION FOR THE STATE UNIV OF NEW YORK
  • US10531803B2 patent drawing
  • US10531803B2 patent drawing
  • US10531803B2 patent drawing

AI summary

The present invention provides a method of imaging blood vessels or blood flow in blood vessels in an animal comprising:(i) injecting a lipid solution into the bloodstream of the animal;(ii) imaging the blood vessels by an imaging method; and(iii) calculating the blood flow velocity in the blood vessels.