Microbubble Contrast Agents for Angle-Independent Photoacoustic Imaging

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Solution Overview

Problem

Conventional photoacoustic imaging techniques face challenges in visualizing tissue structures due to angle dependence and bandwidth mismatch, where only boundaries facing the ultrasound transducer are clearly visible, and a significant portion of the photoacoustic signal energy falls outside the receive frequency range of regular medical ultrasound transducers.

Innovation Solution

The use of free-floating microbubbles positioned in close proximity to photoacoustic contrast agents, which re-radiate acoustic energy omnidirectionally, allowing for more comprehensive visualization of tissue structures and overcoming angle dependence, while nanoparticles intercept and amplify acoustic energy to relay it within the receive frequency range of ultrasound transducers.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional photoacoustic imaging is used to detect tissue structures, then the imaging technique can identify tissue boundaries, but only boundaries facing the ultrasound transducer are clearly visible due to angle dependence

Engineering Contradiction:
Improvevisibility of tissue boundariesVSAvoidorientation independence
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent introduces air-filled cavities as intermediary structures within the tissue. These cavities act as acoustic lenses that focus and redirect acoustic waves, enabling the ultrasound transducer to detect tissue boundaries regardless of their orientation. The cavities mediate between the acoustic waves and the tissue structures, solving the angle dependence problem.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention creates three-dimensional networks of interconnected air-filled cavities that extend throughout the tissue. This 3D structure allows acoustic waves to be focused and redirected from multiple directions, enabling detection of boundaries in all orientations rather than just those facing the transducer directly.

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

2Power

If photoacoustic contrast agents are used to generate acoustic signals, then acoustic waves are produced via optical absorption, but a significant portion of the signal energy falls outside the receive frequency range of regular medical ultrasound transducers

Engineering Contradiction:
Improveacoustic signal energyVSAvoidenergy outside receive frequency range
Core Design Contradiction:
PowerVSLoss of energy

Solution Approach 1:

The patent modifies the physical parameters of the tissue by introducing air-filled cavities with specific size distributions (ranging from micrometers to millimeters). These parameter changes create acoustic lenses that focus and redirect broadband acoustic energy into the receive frequency range of medical ultrasound transducers, reducing energy loss.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention creates localized regions with different acoustic properties by introducing air-filled cavities at specific locations within the tissue. These localized modifications enable frequency conversion and energy redirection without affecting the entire tissue volume, allowing targeted enhancement of signal energy within the useful frequency range.

Inventive Principle:
Principle #3Local quality

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 enhances the detection of tissue structures by increasing the visibility of structures regardless of their orientation relative to the transducer and amplifies the usable acoustic energy, enabling more accurate and detailed imaging.

Implementation Method 1

photoacoustics relies on detection of the acoustic waves generated via optical absorption and the consequent heating/expansion process

Methodology Applied
Scientific EffectPhotoacoustic effect: Photoacoustic Effect

Implementation Method 2

The light gets absorbed by blood/tissue chromophores, or non-targeted and targeted exogenous contrast agents such as optical dyes or nanoparticles configured for this purpose. The absorption, and consequent expansion, produces the acoustic wave

Methodology Applied
Scientific EffectThermal expansion: Thermal Expansion

Implementation Method 3

the bubbles re-radiate the energy principally within the receive frequency range of a regular medical ultrasound transducer

Methodology Applied
Scientific EffectAcoustic resonance: Resonance

Implementation Method 4

The energy re-radiated has been amplified, and has spread out in all directions, including in the direction of an ultrasound transducer

Methodology Applied
Scientific EffectAcoustic scattering: Scattering

Implementation Method 5

an intensity modulated light source, or short pulse source (i.e., laser), is used as the excitation source. The light is typically shined at the tissue surface

Methodology Applied
Scientific EffectPiezoelectric effect: Piezoelectric Effect

Data Source

PatentEP2654551B1Photo-acoustic signal enhancement with microbubble-based contrast agents
Publication Date: 2020.05.27 KONINKLIJKE PHILIPS NV
  • EP2654551B1 patent drawingFigure 1
  • EP2654551B1 patent drawingFigure 2

AI summary

Bubbles (118-122) are utilized in some embodiments as part of a photoacoustic contrast agent (162) and, in some embodiments, to localize one or more locations (126- 38) of a source of acoustic energy. The bubbles, such as microbubbles, can be used in proximity of nanoparticles of a first photoacoustic contrast agent, thereby affording a second photoacoustic contrast agent. The bubbles can intercept and re-radiate acoustic energy emitted by light-based activation of the first photoacoustic contrast agent in the immediate vicinity of the bubbles. As a further option, if the nanoparticles permeate further to tissue structures but remain in close enough proximity, their positions can be triangulated by the nearby bubbles, based on direction (144-148) and time delays (150- 160) of ultrasound received by a transducerarray.