Harmonics and Contrast Agents Flashcards

Harmonics and Contrast Agents

Introduction

• Harmonic imaging and contrast agents can improve suboptimal studies and increase the diagnostic accuracy of ultrasonic imaging and Doppler.
• Harmonic imaging involves creating an image from sound reflections at twice the transmitted sound's frequency.

Harmonic Imaging

• Harmonic frequency = Transmitted frequency x 2

Example

• If a transducer transmits a sound pulse with a frequency of 4 MHz, the harmonic frequency is 4 \text{ MHz} \times 2 = 8 \text{ MHz}.
• Transmitted frequency = Fundamental frequency: the frequency of sound produced by the transducer.
• Harmonic frequency: Twice the fundamental frequency; also known as the second harmonic frequency.
• Harmonic frequency sound waves result from nonlinear behavior.
• As a sound wave travels, a small amount of energy converts from the fundamental to the harmonic frequency.

Fundamental vs. Harmonic Images

• Fundamental Image: Created by processing reflections with the same frequency as the transmitted sound.
• Harmonic Image: Created by processing reflections that are twice the fundamental frequency.
• Harmonic imaging improves poor quality images because harmonic frequency waves undergo less distortion than fundamental sound waves.
• Two forms of harmonics in diagnostic ultrasound:
  1. Tissue harmonics
  2. Contrast harmonics

Linear vs. Nonlinear Behavior

Linear Behavior

• Systems respond evenly, proportionally, and symmetrically.
• Example: An elevator travels linearly when it takes the same amount of time to go between each floor.

Nonlinear Behavior

• Behaves unevenly, irregularly, and disproportionately; asymmetrical.
• Example: An elevator traveling nonlinearly takes varying times to go between floors.
• Harmonic frequency sound arises from nonlinear behavior!

Tissue Harmonics

• Sound waves traveling through patients have a small amount of energy converted from the fundamental to the harmonic frequency, creating tissue harmonics.
• Sound wave: a series of compressions and rarefactions.
  • Compressions: squeezed together, higher pressure and density.
  • Rarefactions: stretched apart, lower pressure and density.
• Sound travels at slightly uneven speeds through soft tissue, faster through compressions and slower through rarefactions.
• This nonlinear behavior creates tissue harmonics in biological media.
• Speed variations change the shape of the sound beam, transferring energy from the fundamental to the harmonic frequency.
• The strength of the harmonic wave grows as sound travels in tissue because Harmonic frequency = Fundamental frequency x 2.

Gradual Development of Harmonic Signal

• Fundamental imaging has artifacts in the superficial tissue due to the strong sound beam and multiple superficial anatomic layers distorting the sound beam.
• Tissue harmonic signals do not exist at extremely superficial depths; they develop deeper in the tissue.
• Harmonic signals cannot distort, thus enhancing image quality.
• Harmonics increase the signal-to-noise ratio, resulting in a higher quality image.

Nonlinear Relationship

• The relationship between sound beam strength and harmonic creation is nonlinear with tissue harmonics.
  • Weak beams do not create tissue harmonics.
  • Intermediate strength beams create only a tiny amount of tissue harmonics.
  • Strong beams create significant tissue harmonic signals.

Side Lobes and Grating Lobes

• A small portion of sound energy is directed away from the sound beam’s main axis in the form of side lobes or grating lobes.
• Beams that are most likely to create harmonics are least likely to create artifact because:
  • Harmonics are produced along these strong main sound beams.
  • Harmonics arise only in the non-distorted main sound beam.
  • Very few harmonics are created in the side lobes and grating lobes as they are so weak.

Tissue Harmonics Summary

• Created in deeper tissues.
• Not present as sound initially leaves the transducer.
• Created in tissues during transmission.
• Created by nonlinear behavior in the speed of sound (faster during compressions than rarefactions).
• Created primarily along the sound beam’s main axis.
• The sound beam contains no harmonic frequency at the surface of the skin, avoiding distortion and reducing noise.

Applications of Tissue Harmonics

• Widely used in ultrasound imaging, producing images with:
  • Better lateral resolution
  • Reduced appearance of artifacts
• Effective in reducing side lobe artifacts and weak echoes, which benefits imaging obese patients.

Pulse Inversion Harmonics

• Designed to utilize harmonic reflections while eliminating distorted fundamental reflections.
• Reflections contain fundamental and harmonic frequencies.
• Fundamental imaging creates sound that has the same frequency as the transmitted sound.
• Harmonic imaging creates images only from the harmonic, which is twice the frequency of the transmitted sound.
• Two consecutive ultrasound pulses are transmitted down each scan line.
  • The first pulse is a typical pulse.
  • The second pulse is an inverted copy that is out-of-phase with the first.
  • Wherever compression exists in the first pulse, a rarefaction exists in the second.
• Reflections from these two out-of-phase pulses are combined in the receiver.
  • Fundamental portions of the reflections (linear behavior) interfere destructively and completely cancel each other out.
  • Harmonic portions of the reflections (nonlinear behavior) are in-phase and interfere constructively, leaving only the harmonic portions.
• The remaining harmonic reflections form an image with less distortion.

Disadvantages

• Requires twice the number of pulses to create each image, doubling the time to create a single frame.
• Frame rate is cut in half, reducing temporal resolution.

Power Modulation Harmonic Imaging

• Designed to augment harmonic reflections while eliminating distorted fundamental reflections.
• Two consecutive ultrasound pulses are sent down each scan line.
  • The second pulse is twice the strength of the first pulse.
  • The first reflection, which is weaker, does not contain harmonics due to harmonics exhibiting nonlinear behavior.
  • The stronger second reflection does contain harmonics.
• The reflections from the first pulse are doubled and then subtracted from the second reflection during reception.
  • Fundamental portions of the two reflections completely cancel each other out.
  • This leaves only the harmonic portion of the second reflection.
• The remaining harmonics can form an image with less distortion than the fundamental image.

Disadvantages

• Frame rate is cut in half, reducing temporal resolution due to transmitting two pulses down each scan line.

Contrast Agents (Microbubbles)

• Gas bubbles encapsulated in a shell.
• Injected into the circulation intravenously or ingested.
• Designed to create strong reflections that “light up” blood chambers, vessels, or other anatomic regions.

Requirements

• Safe
• Metabolically inert (cannot reproduce or replicate themselves)
• Long-lasting
• Strong reflector of ultrasound
• Small enough to pass through capillaries

Microbubbles and Resonance

• Microbubbles are strong scatterers of sound waves because they can produce large oscillations or resonance from a small driving force under the right circumstances.
• Resonance: Nonlinear change in a microbubble's size due to compressions and rarefactions of a sound wave.
• Oscillation = regular variation in magnitude or position around a central point.
• Microbubbles the size of red blood cells resonate when exposed to sound in the 2 to 4 MHz range, which is within the frequencies used in diagnostic sonography.

Contrast Harmonics

• When ultrasound pulses interact with contrast agents, much stronger harmonics are generated because microbubbles act in a nonlinear manner when struck by sound waves.
• This energy is converted from fundamental frequency to the harmonic frequency during reflection.

Nonlinear Behavior

• A microbubble within a sound beam grows and shrinks in relation to pressure variations from compressions and rarefactions.
• Sound beams of adequate strength cause microbubbles to create contrast harmonics due to the nonlinear changes in bubble size; this behavior is called resonance.

Mechanical Index (MI)

• Estimates the amount of contrast harmonics produced, depending on:
  1. Frequency of the transmitted sound
  2. Rarefaction pressure of the sound wave
• The numerical value of the mechanical index and harmonic production increases with:
  1. Lower frequency sound
  2. Stronger sound waves (substantial pressure variations)
• \text{Mechanical Index} = \frac{\text{peak rarefaction pressure}}{\sqrt{\text{frequency}}}

Microbubble Behavior During Compressions and Rarefactions

• During compression (high pressure): microbubble shrinks, and the pressure inside increases.
  • Microbubble will stabilize and resist further compression, limiting how small the bubble will become.
• During rarefaction (low pressure): the microbubble expands.
  • Microbubbles expand to a greater extent than they shrink, transferring energy from the fundamental frequency to the harmonic frequency.
  • Peak rarefaction pressure (expands the bubble) is most important regarding contrast harmonics.

Nonlinear Relationship Between MI and Harmonic Creation

• Low MI sound beams = no harmonics are created because the microbubbles expand and contract evenly in a linear fashion
• Intermediate MI sound beams = ( 0.1 to 1.0) a small amount of harmonics is created
• High MI sound beams = (greater than 1.0) substantial harmonic signals are created
  • Microbubbles may expand and break apart with high MI sound beams
  • Bubbles disruption is an example of extreme nonlinear behavior
  • This behavior creates very strong harmonic reflections

Mechanical Index Values and Harmonic Production

Contrast Agent Characteristics

• Two important characteristics of contrast agents:
  1. The nature of the outer shell
  2. The gas that fills the microbubble
• The relationship between the shell and the internally trapped gas determines the contrast agent’s stability and longevity while circulating in the blood.

How Contrast Agents Work

• The shell of the microbubbles traps the gas and increases the effective life of a microbubble.
  • Gas bubbles without a shell shrink and quickly disappear as the gas dissolves in blood.
• Shells can change shape because they are designed to be flexible thus Rigid shells tend to crack or fracture hence This results in bubble disruption
• The gas trapped within the shell determines bubble stability.
  • Smaller gas bubbles are more likely to leak through the shell and shrink.
  • Larger gas bubbles find the shell less permeable and remain trapped within its boundaries.
• Contrast harmonics created by microbubbles are much stronger than tissue harmonics!

Contrast Harmonics Summary

• Created during reflection
• Created by nonlinear behavior of the microbubble
  • Resonance creates some harmonics
  • Bubble disruption creates very strong harmonics
• Related to the mechanical index (MI)
  • Low MI: Associated with no harmonics
  • Intermediate MIs: Associated with weaker harmonics as a result of resonance
  • High MIs: Associated with bubble disruption, which causes a great amount of harmonics
• Affected by the microbubble’s shell and the gas within it

Tissue Harmonics vs. Contrast Harmonics