TCD/TCCD bubble test

David Goldemund M.D.
Updated on 06/05/2024, published on 13/01/2023


  • the TCD/TCCD bubble test (bubble study) is designed for the detection of right-to-left shunts, particularly Patent Foramen Ovale (PFO)
  • a cost-effective, safe, and non-invasive imaging modality ideal for screening purposes

Bubble study procedure

  • the test simulates a paradoxical embolism
    • an embolus (thrombus, gas, fat) passes through an intracardiac defect (or any other A-V shunt) and enters the systemic circulation, incl. the brain
  • with the patient in the supine position, a blue cannula (22G) is inserted into the cubital vein and connected to a 3-way stopcock via a flexible tube
  • two 20 mL syringes are connected: one containing 8 mL of saline solution + 1 mL of blood and the other containing 1 mL of air (final mixture = 8:1:1) (Zetola, 2019)
    • this air dose is safe; in animal models, a threatening air dose is a bolus of > 20 mL or 11 mL/min [Tsivgoulis, 2010]
    • some authors mix NS with blood immediately, while others mix NS + air first and then draw 1 mL of blood to stabilize the mixed suspension
  • mix the contents of both syringes (perform at least 10 exchanges between syringes)
  • inject the bolus of agitated solution (10 mL) while monitoring the flow in the MCA (ideally in both MCA and ACA)
    • in cases of an impenetrable temporal window, the terminal ICA may be examined transorbitally, or HITS may be detected in the extracranial portion of the CCA/ICA
    • bilateral monitoring with a fixation frame increases sensitivity
  • the suspension is applied twice, first during normal breathing and then during the Valsalva maneuver (which increases the pressure in the right atrium and thus the functionality of the shunt)
    • the quality of the Valsalva maneuver should be checked beforehand (verify ↓ PSV in MCA > 30% during the maneuver)
    • initiate the Valsalva maneuver approx. 5s after administration of the suspension
    • repeated testing increases sensitivity
TCD/TCCD bubble test

Definition of HITS

  • if bubbles pass from the right atrium into the left atrium via the PFO (or other shunts) and then enter the monitored cerebral artery, they manifest as High-Intensity Transient Signals (HITS) on the TCD/TCCD due to the reflection of the ultrasound signal
  • characteristics of HITS:
    • unidirectional
    • accompanied by a typical audible sound
    • duration < 300 milliseconds (usually 2-100ms)
    • amplitude >3 dB above the background (3-60 dB)
    • when insonated simultaneously at different depths, the HITS shift in time (as the bubbles travel through the artery)
  • always record the timing of the first HITS
    • HITS recorded in the first 30 seconds of monitoring indicate the presence of a right-to-left shunt
    • PFO: usually < 12s
    • extracardiac shunts: >15-20s

Test evaluation

Assessment of the right-to-left shunt severity
number of HITS
negative test
low-grade shunt
> 10
medium-grade shunt
“shower” or “curtain”
high-grade shunt
 latent – shunt is present only during and after the Valsalva maneuver
TCD/TCCD bubble test with proof of right-to-left shunt (grade II-IV)

Specificity and sensitivity

  • the sensitivity and specificity of both TCD and TCCD are reported to be > 90%
    • repeated/bilateral testing increases both sensitivity and specificity
  • false-positive results:
    • the test is not PFO specific; it can be positive in the presence of any right-to-left communication (intraventricular septal defects, intrapulmonary AV shunt, etc.).
    • false-positive results may be obtained if the monitoring duration is too long (some bubbles may be detected after passing through the pulmonary circulation) → see the timing of the HITS above
    • certain modifications of the bubble test can increase the sensitivity, such as mixing the air suspension with blood to stabilize the microbubbles, as previously described)

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TCD/TCCD bubble test