Importance of a Bubble Study

A bubble study, also called a bubble exam, is performed to evaluate for the presence of a right-to-left shunt (RLS). RLS is known to be a risk factor for stroke as it provides a conduit for a venous clot to travel to the brain. A patent foramen ovale (PFO) is the most common source of RLS.1 A bubble study can be performed using transcranial Doppler (TCD) ultrasound, as well as using transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE).  While TTE and TEE are excellent for vizualizing heart structures, TCD is much more sensitive at detecting RLS.2  A bubble study is indicated following a stroke or transient ischemic attack (TIA), especially when there is no obvious cause (cryptogenic), with a history of migraines, and a history of deep vein thrombosis (DVT) with anticoagulation.3

What is a Patent Foramen Ovale?

In a normal heart, deoxygenated blood from the body enters the right atrium from both the inferior and superior vena cava, then goes to the right ventricle, and from there, to the lungs for reoxygenation.  Once oxygenated, blood flows back through the left atrium to the left ventricle where it exits the heart and is sent to the body.

A PFO is an abnormal connection between the right and left sides of the heart.  Before birth, we have a small hole between the right and left atria in the heart, called the foramen ovale.  The lungs are not yet functional, and oxygenated blood is coming from the mother via the placenta.  The foramen ovale acts as a shunt, allowing the blood coming from the body through the right side of the heart to skip the lungs and go directly to the left side of the heart and back to the body.  After birth with our lungs are functioning, the foramen ovale should close. If it does not close all the way, it can leave a flap-like opening, now called a patent foramen ovale, or PFO.  This occurs in approximately 25% of the population, and in up to 40% of those with cryptogenic stroke.4

PFOs can allow blood clots, or other emboli from the lower body venous system, that enter the right atrium from the inferior vena cava to be directly shunted to the arterial distribution of the upper body and brain, bypassing the lungs. These blood clots that would have been filtered out by the lungs, can lodge in downstream arteries and possibly lead to strokes.  Therefore, when a PFO is identified as the source of a cryptogenic stroke, it can be surgically closed to prevent further adverse events.

Using TCD to Identify a Right-to-Left Shunt (RLS)

Transesophageal echocardiography (TEE) is the current gold standard for PFO testing, though transthoracic echocardiography (TTE) is the current standard of care as the test most commonly performed.  Both exams have the ability to visualize cardiac structures, but have low sensitivity for the identification of RLS.  Simply put, if TTE and TEE are negative for PFO, it does not necessarily mean that a PFO does not exist. TCD has been shown to be a highly sensitive method (>95%) for the detection of PFO.5

Valsalva Maneuver

An additional benefit of TCD is that it can be performed during a Valsalva maneuver.  A Valsalva maneuver is when the patient takes a breath in and holds it while tightening their abdominal muscles for approximately ten seconds, then releases.  The purpose of this maneuver is to increase the pressure within the right atrium, forcing the flap, if present, open to shunt blood directly from the right atrium to the left atrium.  Some PFOs may not have adequate right atrial pressure to open with the patient at rest, though during Valsalva may demonstrate a significant opening due to the increased right atrial pressure pushing the flap open. TTE exams may include a Valsalva maneuver, though there can be a loss of the cardiac image during the movement caused from inhalation, making it unreliable during Valsalva.  A Valsalva maneuver cannot be performed during a TEE because of the transesophageal transducer and the need for patient sedation.

Performing a Bubble Study

During a TCD bubble study, an IV is placed in the arm, preferably using an antecubital vein.  TCD is used to monitor the middle cerebral arteries (MCAs) bilaterally. While the patient is being autonomously monitored by the system, nine cc’s of bacteriostatic saline, one cc of air, and a small amount of drawn back blood are agitated between two syringes to create microbubbles.  This solution is then injected into the IV.  

The first injection is at rest, with no patient participation.  The TCD waveforms are recorded for one minute following the resting injection.  A second injection is then performed, this time the patient is asked to perform a Valsalva maneuver for 10 seconds, then relax and breathe normally.  The TCD waveforms are again recorded for one minute.6

Grading Shunt Severity

If microbubbles are detected following the rest and/or Valsalva injections, then the study is positive for RLS.  Counting number of microembolic signals (MES) caused by the microbubbles gives the clinician a shunt grade which corresponds to the size of the PFO. The Spencer Logarithmic Scale (SLS) grading criteria is divided into six categories, grades zero through five with grade five being the most severe (largest in size).  Grade 0 corresponds to zero MES being detecting, meaning there is no shunt. The rest of the grades are detailed below.

Link to image source

NovaGuide Clinical Trial Results7

NovaGuide Intelligent Ultrasound compared to standard of care TTE for RLS detection


shunt detection rate 63.6% with NovaGuide, 20.9% with TTE


detection of intervenable shunts 27% with NovaGuide, 10% with TTE

Read the full results from this groundbreaking study

Download the case


  1. Ghosh AK, Jain A. Diagnosis and management of patent foramen ovale. Br J Hosp Med (Lond). 2015;76:C98–C102.
  2. Katsanos, A. H., Psaltopoulou, T., Sergentanis, T. N., Frogoudaki, A., Vrettou, A. R., Ikonomidis, I., … Tsivgoulis, G. (2016). Transcranial Doppler versus transthoracic echocardiography for the detection of patent foramen ovale in patients with cryptogenic cerebral ischemia: A systematic review and diagnostic test accuracy meta-analysis. Annals of Neurology, 79(4), 625–635. Link
  3. Stafford, M. B., Bagley, J. E., & DiGiacinto, D. (2019). Comparison of Transthoracic Echocardiography, Transesophageal Echocardiography, and Transcranial Doppler in the Detection of Patent Foramen Ovale as the Etiology for Cryptogenic Stroke. Journal of Diagnostic Medical Sonography, 35(2), 127–133. Link
  4. Kimberly Atianzar, Peter Casterella, Ming Zhang, Sameer Gafoor, Update on the Management of Patent Foramen Ovale in 2017: Indication for Closure and Literature Review, US Cardiology Review 2017;11(2):75–9.
  5. Mayerhofer, E., Kanz, D., Guschlbauer, B., Anderson, C. D., Asmussen, A., Grundmann, S., Strecker, C., & Harloff, A. (2022). Bubble Test and Carotid Ultrasound to Guide Indication of Transesophageal Echocardiography in Young Patients With Stroke. Frontiers in neurology, 13, 836609. Link
  6. Rubin, MN, Alexandrov, AV, Douville, C, Rinsky, B, Tsivgoulis, G. Novel robotic TCD ultrasound with bubbles versus standard care to detect right to left shunt: Study methods. J Neuroimaging. 2021; 31: 858– 863. Link
  7. Rubin, M., Shah, R., et al. Novel Robotic-Assisted Transcranial Doppler versus Transthoracic Echocardiography to Detect Right-to-Left Shunts. New Orleans, LA USA: International Stroke Conference - Late Breaking Abstract.
< View All Lessons