Research Spotlight: Transcranial Doppler In PFO Investigation

By: Dr. Gracielly Barros & Patrick Ventorim Costa

Sep 10, 2024

This week, we’re going to spotlight relevant research by Dr. Gracielly Barros and Patrick Ventorim Costa that was conducted in Brazil. Our goal is to keep the echo community engaged and well-informed, and it's your ongoing support that makes this possible.

My Approach to Transcranial Doppler Combined With Transthoracic and Transesophageal Echocardiography to Investigate PFO

Abstract

This review article explores the combined use of Transcranial Doppler (TCD) with transthoracic (TTE) and transesophageal (TEE) echocardiography to investigate Patent Foramen Ovale (PFO), a condition found in approximately 25-27% of the adult population. PFO is a remnant of fetal circulation and the most common cause of interatrial shunt. It is associated with clinical complications such as platypnea-orthodeoxia syndrome, obstructive sleep apnea, migraine, and stroke. PFO assessment is generally performed using TTE and TEE, but TCD, a highly sensitive and less used method, is also important. TCD indirectly detects shunts in awake patients and uses the microembolic signal (MES) grading score to classify shunt severity. This technique involves injecting a contrast solution into the antecubital vein during the Valsalva maneuver to detect intracardiac shunt by observing microbubble appearance in the first cardiac cycles.

The case report illustrates the effectiveness of TCD in the initial screening of a patient with suspected PFO using TTE, TCD and TEE. The conclusion highlights that TCD is a crucial diagnostic tool, particularly relevant for the therapeutic management of patients with cryptogenic stroke. Several scientific publications are referenced, providing a theoretical foundation for the combined use of TCD, TTE, and TEE in PFO investigation.

Introduction

Patent Foramen Ovale (PFO) is a fetal circulation remnant and the most common cause of interatrial shunt, affecting approximately 25 to 27% (1 in every 4 to 5 people) of adults. It is considered an anatomical tunnel-like variation, potentially associated with clinical complications such as platypnea-orthodeoxia syndrome, obstructive sleep apnea, migraine, and, notably, stroke due to paradoxical embolism. Diagnosis is particularly crucial in young stroke patients without apparent risk factors.^1,2

Assessment of PFO typically involves transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE). Another valuable but underutilized method among echocardiographers is transcranial Doppler (TCD). This method offers a noninvasive assessment of shunt presence in awake patients with high sensitivity,³ using the microembolic signal (MES) grading score to classify the shunt severity. See Central Illustration below. A clinically meaningful diagnosis of PFO requires both anatomical characterization and physiological assessment of potential right-to-left shunting.

Traditionally, TTE serves as the primary imaging method for PFO screening due to its widespread availability and cost-effectiveness. At the same time, TEE with agitated saline enhancement remains the gold standard for demonstrating shunts through PFO and providing morphological details of the interatrial septum.

TCD with agitated saline (microbubbles) has increasingly played a role in diagnosing transient shunts by enabling real-time analysis of the presence of High-Intensity Transient Signals (HITS) in the cerebral arterial circulation, offering a semi-quantitative assessment of venous-arterial shunt severity.^4,5

Technique

The 3-to-5 Mhz sectoral ultrasound transducer is generally the most suitable and it is recommended to use the transcranial factory preset. Then, the transducer is positioned in the temporal window, with the transducer index pointed to the patient’s right, anterior to the tragus of the ear and moving in small steps, until the flow signal towards the transducer is recorded by adjusting the frequency (2.0 MHz and 2.5 MHz), gain and depth (35-60mm) settings to obtain clear images of the middle cerebral artery (MCA) (Figures 1A, 1B, 1C).

In detail, the contrast agent ideally consists of 8 mL of normal saline combined with 1 mL of air and 1 mL of the patient’s blood. The presence of red blood cells in the agitated saline solution enhances ultrasonic wave reflection, thereby improving visibility of microbubbles in TCD. The mixture is then vigorously shaken approximately 10 times using a system comprising two 10 mL syringes connected by a 3-way stopcock. The stirred solution is then administered into the antecubital vein via an 18 gauge, preferably.

During the procedure, the patient is instructed to perform the Valsalva maneuver, which involves forced expiration against a closed glottis for at least 10 seconds (strain phase), followed by relaxation (release phase). Hemodynamically, this maneuver causes a sudden increase in blood volume in the right atrium, exceeding the flow from the pulmonary veins to the left atrium, thereby promoting flow through the shunt.^6,7

Simultaneously, in an insonation of the curve is conducted using Pulsatile Doppler on the middle cerebral artery (MCA), with reduced scanning speed to allow continuous recording for 60 seconds from the start of the Valsalva maneuver. During this time period, spikes of microbubbles will be visualized, being evidenced as HITS due to reflection of the ultrasound signal (Figure 1C).

The test is considered positive when at least one early hyperintense signal is detected (up to 10 seconds after microbubble infusion). In tachycardic patients, counting cardiac cycles may be a more accurate approach, as it considers the patient’s individual heart rate.⁸ The detection of microbubbles within the first 3-5 cardiac cycles indicates an intracardiac shunt, whereas their appearance after the fifth cardiac cycle suggests a pulmonary shunt.⁹

The number of embolic spikes (HITS) recorded provides critical information; a higher number of microbubbles correlates with a larger foramen ovale passage size.^10,11 Such data is essential for determining the hemodynamic significance of PFO according to the Spencer logarithm scale (adapted from Table 1 and Figure 2).^12,13

Clinical Case

Case report demonstrating the value of TCD in the initial screening of a patient with suspected PFO. J.R.C., a 56-year-old male patient, without comorbidities, but with sequelae of ischemic stroke. The 24-hour Holter did not show atrial fibrillation. The patient sequentially underwent TTE, TCD and TEE associated with the Valsalva maneuver to evaluate the cardioembolic source.

The TTE showed an aneurysm of the interatrial septum with the early detection of a large amount of saline contrast in the left atrium (Figure 3A). TEE was performed to adequately visualize the characteristics of the interatrial septum and PFO, aiming for percutaneous closure (Figures 3B and 3C). Using the MCA spectral Doppler, a number of severe HITS were detected during the first three cardiac cycles, defining the presence of an important venous arterial shunt (Figure 4).

Conclusion

Diagnosing PFO can pose significant challenges due to various factors that can influence and result in inconclusive studies. False negatives can occur due to the presence of a redundant Eustachian valve, obstructing saline solution from reaching the interatrial septum and false positives such as pulmonary venoarterial shunts.¹⁴

TCD represents an additional, straightforward, and non-invasive diagnostic tool with high sensitivity, being particularly essential in the initial evaluation of patients with cryptogenic stroke, especially in those where identifying a right-to-left shunt through PFO may be crucial for therapeutic management.¹⁵

Thank you Dr. Barros!

Dr. Gracielly Barros has submitted this novel research she conducted and let us share it all with all of you! It highlights the continuous advancements in echo and ultrasound, reminding us of the importance of continued education.

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References

1. Johansson MC, Eriksson P, Guron CW, Dellborg M. Pitfalls in Diagnosing PFO: Characteristics of False-negative Contrast Injections During Transesophageal Echocardiography in Patients with Patent Foramen Ovales. J Am Soc Echocardiogr. 2010;23(11):1136-42. doi: 10.1016/j.echo.2010.08.004.

2. Kutty S, Sengupta PP, Khandheria BK. Patent Foramen Ovale: The Known and the to be Known. J Am Coll Cardiol. 2012;59(19):1665-71. doi: 10.1016/j. jacc.2011.09.085.

3. Mahmoud AN, Elgendy IY, Agarwal N, Tobis JM, Mojadidi MK. Identification and Quantification of Patent Foramen Ovale-Mediated Shunts: Echocardiography and Transcranial Doppler. Interv Cardiol Clin. 2017;6(4):495-504. doi: 10.1016/j.iccl.2017.05.002.

4. Barbosa MF, Abdala N, Carrete H Jr, Nogueira RG, Nalli DR, Fonseca JR, et al. Doppler Transcraniano Convencional em Voluntários Assintomáticos: Variabilidade e Valores de Referência para Parâmetros de Fluxo Sanguíneo. Arq Neuropsiquiatr. 2006;64(3B):829-38. Portuguese. doi: 10.1590/s0004-282x2006000500023.

5. D’Andrea A, Conte M, Riegler L, Scarafile R, Cocchia R, Pezzullo E, et al. Transcranial Doppler Ultrasound: Incremental Diagnostic Role in Cryptogenic Stroke Part II. J Cardiovasc Echogr. 2016;26(3):71-7. doi: 10.4103/2211-4122.187947.

6. Santos SN, Alcantara ML, Freire CMV, Cantisano AL, Teodoro JAR, Porto CLL, Amaral SI, et al. Posicionamento de Ultrassonografia Vascular do Departamento de Imagem Cardiovascular da Sociedade Brasileira de Cardiologia – 2019. Arq Bras Cardiol. 2019;112(6):809-4. doi: 10.5935/abc.20190106.

7. Rodrigues AC, Picard MH, Carbone A, Arruda AL, Flores T, Klohn J, et al. Importance of Adequately Performed Valsalva Maneuver to Detect Patent Foramen Ovale During Transesophageal Echocardiography. J Am Soc Echocardiogr. 2013;26(11):1337-43. doi: 10.1016/j.echo.2013.07.016.

8. Jauss M, Zanette E. Detection of Right-to-left Shunt with Ultrasound Contrast Agent and Transcranial Doppler Sonography. Cerebrovasc Dis. 2000;10(6):490-6. doi: 10.1159/000016119.

9. Zétola VF, Lange MC, Muzzio JA, Marchioro I, Nóvak EM, Werneck LC. Doppler Transcraniano na Prática Neurológica. Arq Neuropsiquiatr. 2006;64(1):100-3. doi: 10.1590/s0004-282x2006000100020.

10. Spencer MD, Moehring MA, Jerusum J, Gray WA, Olsen JV. Power M-Mode Transcranial Doppler for Diagnosis of Patent Foramen Ovale and Assessing Transcatheter Closure. J Neuroimaging. 2004;14(4):342-9. doi: 10.1111/ j.1552-6569.2004.tb00261.x.

11. Santos SND, Alcantara ML, Freire CMV, Cantisano AL, Teodoro JAR, Porto CLL, et al. Vascular Ultrasound Statement from the Department of Cardiovascular Imaging of the Brazilian Society of Cardiology - 2019. Arq Bras Cardiol. 2019;112(6):809-49. doi: 10.5935/abc.20190106.

12. Markus H. Microembolic Signal Detection in Cerebrovascular Disease. In: Babikian VL, Wechsler LR, Toole JF (editors). Transcanial Doppler Ultrasonography. 2nd ed. Woburn: Butterworth-Heinemann; 1999. p. 167-74.

13. Lao AY, Sharma VK, Tsivgoulis G, Frey JL, Malkoff MD, Navarro JC, et al. Detection of Right-to-left Shunts: Comparison Between the International Consensus and Spencer Logarithmic Scale Criteria. J Neuroimaging. 2008;18(4):402-6. doi: 10.1111/j.1552-6569.2007.00218.x.

14. Felix A, Alcantara ML. To Close or not to Close PFOs in Cryptogenic Stroke, an Evolving Question. Int J Cardiovasc Sci. 2020;33(4):318-20. doi: 10.36660/ ijcs.20200128.

15. Gripp E, Portela ACF, Costa FL, Rabishoffsky R. Forame Oval Patente: A Contribuição do Doppler Transcraniano em seu Diagnóstico. Arq Bras Cardiol. 2023;36(2):e20230020. doi: 10.36660/abcimg.20230020.