CH. 17 Harmonics and Contrast Agents

Harmonic Imaging

Uses higher harmonic echoes of the transmitted (fundamental) frequency for imaging

What are Harmonics used to improve?

• Signal-to-noise-ratio

– Contrast resolution

– Artifacts

Fundamental Frequency

Frequency created by the transducer & transmitted into body

Harmonic Frequency/ 2nd Harmonic frequency is twice the

Fundamental Frequency

Harmonics arise from

nonlinear sound wave behavior

Fundamental Image

Reflections at the same frequency as transmitted sound

– Linear Behavior

Harmonic Image

Reflections at twice the transmitted (fundamental) frequency

– Nonlinear Behavior

Linear Behavior

Sound wave & soft tissue response are proportional & predictable

■ Wave maintains its original shape & frequency as it moves through tissue

■ Produces consistent, predictable waveforms

– Results in lower image quality

Nonlinear Behavior

Sound wave & tissue response are disproportional & unpredictable

■ Occurs when waves distort due to pressure variations in tissue

■ Distortion creates new frequencies (harmonics)

– Multiples of original frequency

Tissue Harmonics

As sound travels through tissue, some energy shifts from the fundamental frequency to higher harmonic frequencies

-Nonlinear process

What creates Tissue Harmonics?

uneven speed distortion of the wave.

Sound Travels Faster through Compressions or Rarefactions?

Compressions

As the wave travels Deeper, Harmonic strength Increases or Decreases?

Increases

Harmonic Frequency Formula

Fundamental x Harmonic number

EX: If Fundamental is 3 and Harmonic is 3, then the HF is

6

The 2 requirements for Tissue Harmonic Generation

1. Relatively high sound intensity

2. Sufficient travel distance through tissue for nonlinear distortion to develop

Methods used to Isolate Harmonic Frequencies

– Bandwidth filtering

– Pulse inversion harmonics

– Coded harmonics

– Differential harmonics

If the fundamental image is poor the

2nd Harmonic data often provides a clearer image

Higher harmonics (3rd, 4th, etc.) are rarely used because of:

Lower amplitude

– Outside transducer range

– More attenuation in tissue

Harmonics are Strongest at the

Focus

Artifact

Elements in an image that do not accurately represent the anatomy or tissue characteristics

– Errors in the image

Artifacts are common in superficial tissues

– Caused by:

■ Strong beams near surface

■ Distortion from multiple superficial layers

Harmonic signals form deeper in tissue result in More or Less noise?

less noise & higher signal-to-noise-ratio

Harmonics pass through tissue without distortion

Lobe artifacts occur when sound travels off the axis of the beam

Main

Side Lobes:

Single-crystal transducers

Grating Lobes:

Array transducers

Lobes impact on imaging?

– Cause blurred or misplaced echoes

– Reduce lateral resolution

Harmonic imaging Suppresses or Improves side lobes & grating lobes?

Suppresses

Beams that create Harmonics are More or Least likely to create Artifacts?

Least likely

How Harmonics Affect Lobe artifacts

Side & grating lobes send sound off-axis, creating false echoes

– Harmonics form only along the main beam axis

■ Ignores off-axis echoes

■ Result:

– Improved lateral resolution

– Cleaner images with fewer distortion & less noise

Higher Harmonic frequencies provide:

– Shorter wavelengths

– Shorter pulses

– Better Axial Resolution

– Less divergence in the far field

– Better Lateral Resolution

Ways artifacts are Helpful

– Help differentiate between fluid filled vs solid structures

■ Posterior acoustic enhancement

■ Posterior acoustic shadowing

– Artifact that can help identify the presence of air/gas

■ Comet tail

– Can be seen in bile ducts, an abscess, leaking valve

Helpful Artifacts are Increased or Decreased by using Harmonics?

Increased

Pulse Inversion Harmonics

Technique that captures pure harmonic signals

– Separates harmonic frequencies

– Cancels out fundamental frequency

Originally: Bandwidth Filters

Filters were used to separate harmonic & fundamental frequencies

■ Filtering was only moderately effective

Modern Technique – Pulse Inversion:

Sends two pulses: one positive & one inverted (negative)

– When combined, the fundamental cancels out

– harmonic remains

– Provides cleaner, distortion free image

Transmission Method

Two consecutive pulses are sent down each scan line:

■ 1st Pulse: Standard, typical pulse (+)

■ 2nd Pulse: Inverted (-, out-of-phase)

Wave Behavior:

Compressions in 1st pulse align with rarefactions in 2nd pulse

– This phase opposition cancels the fundamental & enhances harmonic separation

Reflections from the transmitted pulses are processed in the receiver During or After pulse inversion harmonics?

During

Combining Reflections:

Both positive & negative reflections are merged

■ Interfere destructively

■ Cancel each other out

– Fundamental components are eliminated

– Isolates the harmonic reflection

Pulse Inversion Harmonics Result in

Cancels out fundamental echoes

– Only harmonic reflections remain

– Produces an image with less distortion & better clarity

Pulse Inversion Harmonics Cons

– Requires two pulses per line, so each frame takes longer to build

– Reduces temporal resolution

Pulse Inversion Harmonics Pro

Improves spatial resolution

Power Modulation Harmonics

Imaging technique designed to:

– Increase harmonic signals

– Eliminates fundamental signals

Power Modulation Harmonics

Technique Overview:

– Two pulses are sent along each scan line:

1st Pulse: Weaker (standard strength)

■ 2nd Pulse: Stronger (twice the strength of the first)

The weaker pulse produces

minimal harmonics

The stronger pulse generates

harmonic information

The weaker returning signal is doubled and subtracted from the

stronger returning signal

Power Modulation Harmonics

■ Reception Process:

– Reflections from the first pulse are what?

Doubled

Contrast Harmonics

Occurs when a contrast agent (microbubbles) is injected into the bloodstream to enhance imaging

How Contrast Harmonics Work?

Microbubbles act as strong reflectors and resonate in response to sound waves

■ Their oscillation produces harmonic frequencies

■ These harmonics are used to differentiate blood flow and enhance vascular structures

Contrast Agents:

Have different acoustic footprint than blood or tissue

■ Caused by big impedance mismatch

Contrast Agents is designed to

Create strong reflections

■ Microbubbles “Light- up” blood chambers, vessels, & other areas

Contrast treatment for

– Inflammation ■ Identifies areas of inflammation through changes in vascular activity and endothelial cells ■ Applications include Crohn’s disease, atherosclerosis, and coronary artery disease

– Cancer ■ Microbubbles can be designed to attach to receptors associated with tumors ■ Helps visualize new blood vessel growth (angiogenesis) associated with cancer

– Drug Delivery ■ Medications can be carried within or attached to microbubbles ■ Ultrasound can break apart the bubbles, releasing medication at a specific location

– Gene Delivery ■ Microbubbles help transport genetic material to selected tissues ■ Ultrasound promotes the entry of DNA into targeted cells

Untargeted Microbubbles:

Circulate freely through the bloodstream

– Enhance visualization of blood volume and tissue perfusion

– Help characterize lesions and distinguish tissue boundaries

Targeted Microbubbles

Designed to bind to specific molecular markers

– Help identify disease-related changes or particular cell types

– Primarily used in research and investigational imaging

Contrast Agents must meet the following criteria:

– Safe for patient use

– Biocompatible and safely cleared from the body.

– Long lasting enough for imaging sequences

– Strong reflector of ultrasound

– Small enough to pass through capillaries

Outer shell

Surrounds & stabilizes gas core

– Influences microbubble stability and circulation time

– Flexible materials withstand repeated acoustic pressure changes

– Shell composition affects how the body interacts with the microbubble

Common Outer Shell Materials

– Lipids

– Albumin

– Polymers

– Galactose-based formulations

Gas Core

Responsible for strong ultrasound reflections (echogenicity)

– Gas composition influences microbubble stability and lifespan

Common Gases for Gas Core

■ Air

■ Nitrogen

■ Perfluorocarbons

■ Sulfur Hexafluoride

More or Less soluble gases dissolve or escape more quickly

More

Less or More soluble gases remain trapped longer, extending imaging time

Less

Nonlinear oscillation produces

Contrast Harmonics

contrast harmonics are created during

Reflection

When exposed to compression, the bubble

Shrinks

When exposed to rarefaction, the bubble

Expands

Expansion may exceed contraction? Yes or No

Yes

What is most important with regard to contrast harmonics?

Peak rarefaction pressure

The amount of harmonic energy produced depends on the

Mechanical Index (MI)

High Mechanical Index (MI):

Causes bubbles to expand & rupture

– This bubble disruption produces the strongest harmonic reflections

What is Mechanical Index?

A value established by AIUM guidelines that indicates the likelihood of cavitation (bubble activity) in tissues.

What does Mechanical Index depend on?

Frequency of transmitted sound

– Rarefaction pressure (negative pressure of the sound wave)

MI increases with:

Lower frequency sound

– Higher pressure amplitudes (stronger sound waves)

Greater pressure variation =

more potential for harmonic generation

Mechanical Index Formula

= Peak Rarefaction pressure / Square root of Frequency

Low Mechanical Index (MI) beams Characteristics

– Lower acoustic pressure

– Microbubbles can oscillate nonlinearly

– Harmonic signals can be detected while bubbles remain intact

– Useful for continuous contrast imaging

■ When MI < 0.1

Increasing Mechanical Index beams

Greater acoustic pressure

– More pronounced microbubble oscillation

– Increased potential for bubble disruption

High Mechanical Index (MI) beams

Greater acoustic pressure produces larger microbubble oscillations

■ MI greater than 1.0

– Microbubbles may rupture or become disrupted

– Disruption can produce brief, strong acoustic signals

– Bubble destruction reduces contrast persistence

– Can be used intentionally in destruction–replenishment imaging

Contrast harmonics produced by microbubbles are much stronger or weaker than tissue harmonics.

Stronger