NEUROIMAGING / NEUROSONOLOGY

TCD/TCCD bubble test

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

Indications

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

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
grade	number of HITS	evaluation
I	0	negative test
II	1-10	low-grade shunt
III	> 10	medium-grade shunt
IV	“shower” or “curtain”	high-grade shunt
permanent 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)