Skip to main content

Pulmonary transit time measurement by contrast-enhanced ultrasound in left ventricular dyssynchrony


Background: Pulmonary transit time (PTT) is an indirect measure of preload and left ventricular function, which can be estimated using the indicator dilution theory by contrast-enhanced ultrasound (CEUS). In this study, we first assessed the accuracy of PTT-CEUS by comparing it with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Secondly, we tested the hypothesis that PTT-CEUS correlates with the severity of heart failure, assessed by MRI and N-terminal pro-B-type natriuretic peptide (NT-proBNP).

Methods and results: Twenty patients referred to our hospital for cardiac resynchronization therapy (CRT) were enrolled. DCE-MRI, CEUS, and NT-proBNP measurements were performed within an hour. Mean transit time (MTT) was obtained by estimating the time evolution of indicator concentration within regions of interest drawn in the right and left ventricles in video loops of DCE-MRI and CEUS. PTT was estimated as the difference of the left and right ventricular MTT. Normalized PTT (nPTT) was obtained by multiplication of PTT with the heart rate. Mean PTT-CEUS was 10.5±2.4s and PTT-DCE-MRI was 10.4±2.0s (P=0.88). The correlations of PTT and nPTT by CEUS and DCE-MRI were strong; r=0.75 (P=0.0001) and r=0.76 (P=0.0001), respectively. Bland–Altman analysis revealed a bias of 0.1s for PTT. nPTT-CEUS correlated moderately with left ventricle volumes. The correlations for PTT-CEUS and nPTT-CEUS were moderate to strong with NT-proBNP; r=0.54 (P=0.022) and r=0.68 (P=0.002), respectively.

Conclusions: (n)PTT-CEUS showed strong agreement with that by DCE-MRI. Given the good correlation with NT-proBNP level, (n)PTT-CEUS may provide a novel, clinically feasible measure to quantify the severity of heart failure.

Clinical Trial Registry: NCT01735838


  1. Sakka SG, Reuter DA & Perel A 2012 The transpulmonary thermodilution technique. Journal of Clinical Monitoring and Computing 26 347–353. (doi:10.1007/s10877-012-9378-5)

    Article  Google Scholar 

  2. Roy SB, Bhardwaj P & Bhatia ML 1965 Pulmonary blood volume in mitral stenosis. BMJ 2 1466–1469.

    Article  CAS  Google Scholar 

  3. Shors SM, Cotts WG, Pavlovic-Surjancev B, Francois CJ, Gheorghiade M, Finn JP 2003 Heart failure: evaluation of cardiopulmonary transit times with time-resolved MR angiography. Radiology 229 743–748. (doi:10.1148/radiol.2293021363)

    Article  Google Scholar 

  4. Cao JJ, Wang Y, McLaughlin J, Haag E, Rhee P, Passick M, Toole R, Cheng J, Berke AD & Lachman J, et al. 2011 Left ventricular filling pressure assessment using left atrial transit time by cardiac magnetic resonance imaging. Circulation: Cardiovascular Imaging 4 130–138. (doi:10.1161/CIRCIMAGING.110.959569)

    PubMed  Google Scholar 

  5. Brittain EL, Doss LN, Saliba L, Irani W, Byrd BF & Monahan K 2015 Feasibility and diagnostic potential of pulmonary transit time measurement by contrast echocardiography: a pilot study. Echocardiography 32 1564–1571. (doi:10.1111/echo.12906)

    Article  Google Scholar 

  6. Mischi M, Kalker TA & Korsten EH 2004 Contrast echocardiography for pulmonary blood volume quantification. IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control 51 1137–1147.

    Article  Google Scholar 

  7. Herold IH, Soliman Hamad MA, van Assen HC, Bouwman RA, Korsten HH, & Mischi M 2015 Pulmonary blood volume measured by contrast enhanced ultrasound: a comparison with transpulmonary thermodilution. British Journal of Anaesthesia 115 53–60. (doi:10.1093/bja/aeu554)

    Article  CAS  Google Scholar 

  8. Streitberger A, Modler P & Haggstrom J 2015 Increased normalized pulmonary transit times and pulmonary blood volumes in cardiomyopathic cats with or without congestive heart failure. Journal of Veterinary Cardiology 17 25–33. (doi:10.1016/j.jvc.2014.09.005)

    Article  Google Scholar 

  9. Herold IH, Russo G, Mischi M, Houthuizen P, Saidov T, van het Veer M, van Assen HC & Korsten HH 2013 Volume quantification by contrast-enhanced ultrasound: an in-vitro comparison with true volumes and thermodilution. Cardiovasc Ultrasound 11 36. (doi:10.1186/1476-7120-11-36)

    Article  Google Scholar 

  10. Choi BG, Sanai R, Yang B, Young HA, Mazhari R, Reiner JS & Lewis JF 2014 Estimation of cardiac output and pulmonary vascular resistance by contrast echocardiography transit time measurement: a prospective pilot study. Cardiovascular Ultrasound 12 44. (doi:10.1186/1476-7120-12-44)

    Article  Google Scholar 

  11. Mischi M, van den Bosch HC, den Boer JA, Verwoerd J, Grouls RJ, Peels CH, Korsten HH 2009 Intra-thoracic blood volume measurement by contrast magnetic resonance imaging. Magnetic Resonance in Medicine 61 344–353. (doi:10.1002/mrm.21824)

    Article  CAS  Google Scholar 

  12. Sheppard CW & Savage LJ 1951 The random walk problem in relation to the physiology of circulatory mixing. Physical Review 83 489–490.

    Google Scholar 

  13. Wise ME 1966 Tracer dilution curves in cardiology and random walk and lognormal distributions. Acta Physiologica et Pharmacologica Neerlandica 14 175–204.

    CAS  PubMed  Google Scholar 

  14. Mischi M, Kalker T & Korsten HHM 2003 Videodensitometric methods for cardiac output measurements. EURASIP Journal on Applied Signal Processing 5 479–489. (doi:10.1155/S1110865703211185)

    Google Scholar 

  15. Lord P, Eriksson A, Haggstrom J, Jarvinen AK, Kvart C, Hansson K, Maripuu E & Makela O 2003 Increased pulmonary transit times in asymptomatic dogs with mitral regurgitation. Journal of Veterinary Internal Medicine 17 824–829. (doi:10.1111/j.1939-1676.2003.tb02521.x)

    Article  Google Scholar 

  16. Bax JJ, Ansalone G, Breithardt OA, Derumeaux G, Leclercq C, Schalij MJ, Sogaard P, St John Sutton M & Nihoyannopoulos P 2004 Echocardiographic evaluation of cardiac resynchronization therapy: ready for routine clinical use? A critical appraisal. Journal of the American College of Cardiology 44 1–9. (doi:10.1016/j.jacc.2004.02.055)

    Article  Google Scholar 

  17. Pitzalis MV, Iacoviello M, Romito R, Massari F, Rizzon B, Luzzi G, Guida P, Andriani A, Mastropasqua F & Rizzon P 2002 Cardiac resynchronization therapy tailored by echocardiographic evaluation of ventricular asynchrony. Journal of the American College of Cardiology 40 1615–1622.

    Article  Google Scholar 

  18. Herold IH, Saporito S, Bouwman RA, Houthuizen P, van Assen HC, Mischi M & Korsten HH 2016 Reliability, repeatability, and reproducibility of pulmonary transit time assessment by contrast enhanced echocardiography. Cardiovascular Ultrasound 14 1. (doi:10.1186/s12947-015-0044-1)

    Article  Google Scholar 

  19. Taub PR, Gabbai-Saldate P & Maisel A 2010 Biomarkers of heart failure. Congestive Heart Failure 16 S19–S24. (doi:10.1111/j.1751-7133.2010.00168.x)

    Article  CAS  Google Scholar 

  20. Fruhwald FM, Fahrleitner-Pammer A, Berger R, Leyva F, Freemantle N, Erdmann E, Gras D, Kappenberger L, Tavazzi L, Daubert JC, et al. 2007 Early and sustained effects of cardiac resynchronization therapy on N-terminal pro-B-type natriuretic peptide in patients with moderate to severe heart failure and cardiac dyssynchrony. European Heart Journal 28 1592–1597. (doi:10.1093/eurheartj/ehl505)

    Article  CAS  Google Scholar 

  21. Bland JM & Altman DG 1986 Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1 307–310. (doi:10.1016/S0140-6736(86)90837-8)

    Article  CAS  Google Scholar 

  22. Evans JD 1996 Straightforward Statistics for the Behavioral Sciences. Pacific Grove, CA, USA: Brooks/Cole Publishing Company.

    Google Scholar 

  23. Malm S, Frigstad S, Sagberg E, Larsson H & Skjaerpe T 2004 Accurate and reproducible measurement of left ventricular volume and ejection fraction by contrast echocardiography: a comparison with magnetic resonance imaging. Journal of the American College of Cardiology 44 1030–1035. (doi:10.1016/j.jacc.2004.05.068)

    Article  Google Scholar 

  24. Sapin PM, Schroeder KM, Gopal AS, Smith MD & King DL 1995 Three-dimensional echocardiography: limitations of apical biplane imaging for measurement of left ventricular volume. Journal of the American Society of Echocardiography 8 576–584. (doi:10.1016/S0894-7317(05)80370-0)

    Article  CAS  Google Scholar 

  25. Streitberger A, Hocke V & Modler P 2013 Measurement of pulmonary transit time in healthy cats by use of ultrasound contrast media “Sonovue(R)”: feasibility, reproducibility, and values in 42 cats. Journal of Veterinary Cardiology 15 181–187. (doi:10.1016/j.jvc.2013.05.001)

    Article  Google Scholar 

  26. Falch DK & Stromme SB 1979 Pulmonary blood volume and interventricular circulation time in physically trained and untrained subjects. European Journal of Applied Physiology and Occupational Physiology 40 211–218. (doi:10.1007/BF00426943)

    Article  CAS  Google Scholar 

  27. Hoogslag GE, Hoke U, Thijssen J, Auger D, Marsan NA, Wolterbeek R, Holman ER, Schalij MJ, Bax JJ, Verwey HF, et al. 2013 Clinical, echocardiographic, and neurohormonal response to cardiac resynchronization therapy: are they interchangeable? Pacing and Clinical Electrophysiology 36 1391–1401. (doi:10.1111/pace.12214)

    Article  Google Scholar 

  28. Magne J, Dubois M, Champagne J, Dumesnil JG, Pibarot P, Philippon F, O’Hara G & Senechal M 2009 Usefulness of NT-pro BNP monitoring to identify echocardiographic responders following cardiac resynchronization therapy. Cardiovascular Ultrasound 7 39. (doi:10.1186/1476-7120-7-39)

    Article  Google Scholar 

  29. Swift AJ, Telfer A, Rajaram S, Condliffe R, Marshall H, Capener D, Hurdman J, Elliot C, Kiely DG & Wild JM 2014 Dynamic contrast-enhanced magnetic resonance imaging in patients with pulmonary arterial hypertension. Pulmonary Circulation 4 61–70. (doi:10.1086/674882)

    Article  Google Scholar 

Download references


The authors thank especially M Koehler and all personnel of the MRI department of the Catharina Hospital for their collaboration in performing the acquisitions. They also thank S Cai and F T A Nandiska for their support in data analysis.


This research is supported by the Dutch Technology Foundation STW, which is part of the Netherlands Organisation for Scientific Research (NWO), and which is partly funded by the Ministry of Economic Affairs. Project number: 11865.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Ingeborg H. F. Herold MD.

Rights and permissions

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Herold, I.H.F., Saporito, S., Mischi, M. et al. Pulmonary transit time measurement by contrast-enhanced ultrasound in left ventricular dyssynchrony. Echo Res Pract 3, 35–43 (2016).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

Key Words

  • pulmonary transit time
  • contrast echocardiography
  • cardiac magnetic resonance imaging
  • B-type natriuretic peptide
  • heart failure