Medical Ultrasound

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Medical Ultrasound

• Spring 2008

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Chapter 8. Ultrasound Contrast Agent
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General bubble Model

• Surface tension

pipgpv Liquid pressure at bubble wall
pL Liquid pressure at bubble wall
p? Surface tension pressure
p0 Hydrostatic pressure in body of the liquid
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General bubble Model

• Rayleigh-Plesset Equation

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Shelled bubble Model
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Shelled bubble Model
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Shelled bubble Model resonance frequency
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Shelled bubble Model damping
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Shelled bubble Model scattering cross section
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Shelled bubble Model Speed of Sound
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History of UCA

• Contrast agents can improve the image quality of
  sonography either by decreasing the reflectivity
  of the undesired interfaces or by increasing the
  backscattered echoes from the desired regions.
• In the former approach, the contrast agents are
  taken orally, and for the latter effect, the
  agent is introduced vascularly.
• In the upper GI tract, sonographic assessment is
  limited by the gas-filled bowel, which produces
  shadowing artifacts. Ingestion of degassed water
  has been used to improve ultrasound imaging of
  the GI tract, but with inconsistent results.
  Alternatively, investigators have studied oral
  ultrasound contrast agents designed to adsorb and
  displace stomach and bowel gas. One such agent is
  SonoRx from Bracco, consisting of
  simethicone-coated cellulose. This agent recently
  was approved for clinical use by the FDA.
  Ingestion in dosages of 200 to 400 mL results in
  a homogeneous transmission of sound through the
  contrast-filled stomach.

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History of UCA

• Vascular enhancing ultrasound agents were first
  introduced by Gramiak and Shah in 1968, when they
  injected agitated saline into the ascending aorta
  and cardiac chambers during echocardiographic
  examinations.
• Strong echoes were produced within the heart, due
  to the acoustic mismatch between free air
  microbubbles in the saline and the surrounding
  blood. However, microbubbles produced by
  agitation are both large and unstable, diffusing
  into solution in less than 10 seconds.

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Ultrasound Contrast Agent

• Required Condition
• Strong reflection
• Small compared to capillary vessel
• Stable
• Safety
• Definity, Optison FDA warning

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Ultrasound Contrast Agent

• Commercially available UCA
• Albunex and Optison (Molecular Biosystems)
• Echovist and Levovist (Schering)
• EchoGen (Sonus Pharmaceuticals)
• Definity (Du Pont Merck)
• Imagent (Alliance Pharmaceutical)
• Sonazoid (Nycomed-Amersham)
• SonoVue (Bracco Diagnostics)
• Quantison (Quadrant)
• Biosphere (Ponit Biomedical)
• AI-700 (Acusphere)

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Ultrasound Contrast Agent

• Stabilization
• Shelled microbubble
• Albumin type of protein
• Albunex, Optison
• Lipid
• Definity

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Ultrasound Contrast Agent

• Strong reflection
• Resonance frequency
• Imaging machine
• 310 MHz
• Albunex strong resonance
• at 4MHz

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Ultrasound Contrast Agent

• Ultrasound Contrast Agent

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UCA techniques

• Contrast-enhanced Doppler imaging.
• Color amplitude imaging (CAI) shows the amplitude
  of the Doppler signal from moving blood flow,
  while color Doppler imaging (CDI) depicts the
  mean frequency shifts of the Doppler signal
  (i.e., mean flow velocity).
• CAI is a relatively new ultrasound technique with
  increased dynamic range and flow sensitivity in
  comparison to conventional CDI.
• The sensitivity of Doppler ultrasound should be
  increased markedly in conjunction with the use of
  vascular contrast agents.

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UCA techniques

• Contrast harmonic imaging
• CHI is a novel technique, opening the possibility
  of measuring blood perfusion or capillary blood
  flow-a clinically important task.
• It utilizes the nonlinear properties of contrast
  agents by transmitting at the fundamental
  frequency but receiving at the second harmonic.

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UCA techniques

• Intermittent imaging
• Contrast microbubbles can be destroyed by intense
  ultrasound and the scattered signal level can
  increase abruptly for a short time during
  microbubble destruction, resulting in sudden
  increase in echogenicity (acoustical "flash").
• Intermittent imaging with high acoustic output
  utilizes the unique property of contrast
  microbubbles to improve blood-to-tissue image
  contrast by imaging intermittently at very low
  frame rates instead of the conventional 30 frames
  per second.
• The frame rate is usually reduced to about one
  frame per second, or it is synchronized with
  cardiac cycles so that enough contrast
  microbubbles can flow into the imaging site where
  most microbubbles have been destroyed by the
  previous acoustic pulse. Because bubbles are
  destroyed by ultrasound, controlling the delay
  time between frames produces images whose
  contrast emphasizes regions with rapid blood flow
  or regions with high or low blood volume.

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UCA techniques

• ECHOCARDIOLOGY
• One of the most important clinical uses of
  ultrasound contrast is in cardiology, where it
  will potentially compete with thallium nuclear
  scans.
• The phase III trial of Albunex showed that
  Albunex was effective in improving left
  ventricular endocardial definition in 83 of
  patients and achieving LV chamber opacification
  in 81 of cases. Chamber opacification and
  improved endocardial border delineation in
  gray-scale are important clinical objectives,
  since accurate assessment of the LV volume allows
  the cardiac output to be calculated more
  precisely and therefore better determines heart
  function. Cardiac shunts and valve regurgitations
  are often evaluated with CDI, which also improves
  with injections of Albunex, but this agent is
  pressure-sensitive and does not recirculate. It
  is effectively a one-pass-only agent, limiting
  its clinical efficacy.

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UCA techniques

• ECHOCARDIOLOGY
• Newer agents such as Optison, Definity, and
  Sonazoid have overcome the stability problems of
  Albunex and can produce myocardial perfusion
  images in humans. This is clinically significant,
  since visualization of the myocardial flow
  permits direct assessment of underperfused or
  unperfused regions (i.e., areas of ischemia or
  infarction) in patients with a history of chest
  pain. Myocardial imaging using ultrasound
  contrast agents provides an assessment of the
  coronary arteries and of the coronary blood flow
  reserve, as well as collateral blood flow that
  may exist.

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UCA Images
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UCA Images
Harmonic Imaging
Intermittent Imaging