MR imaging of pulmonary lung nodules during one lung flooding: first morphological evaluation using an ex vivo human lung model

  • Frank WolframEmail author
  • Joachim Böttcher
  • Thomas Günther Lesser
Research Article
Part of the following topical collections:
  1. Basic Science - Preclinical imaging



Magnetic resonance imaging in pulmonary oncology is limited because of unfavourable physical and physiological conditions in ventilated lung. Previous work showed operability of One Lung Flooding using saline in vivo in MR units, and that valuable conditions for ultrasound and thermal-based interventions exist. Therefore, this study investigates the morphological details of human lung during Lung Flooding to evaluate its further value focusing on MR-guided interventions.

Materials and methods

MR imaging was performed on 20 human lung lobes containing lung cancer and metastases. Lobes were intraoperatively flooded with saline and imaged using T1w Gradient Echo and T2 Spin Echo sequences at 1.5 T. Additionally, six patients received pre-operative MRI.


During lung flooding, all lung tumours and metastases were visualized and clearly demarked from the surrounding lung parenchyma. The tumour mass appeared hyperintense in T1w and hypointense in T2w MR imaging. Intra-pulmonary bronchial structures were well differentiated in T2w and calcification in T1w MR sequences.


Superior conditions with new features of lung MRI were found during lung flooding with an unrestricted visualization of malignant nodules and clear demarcation of intra-pulmonary structures. This could lead to new applications of MR-based pulmonary interventions such as laser or focused ultrasound-based thermal ablations.


MRI One lung flooding Lung imaging Lung cancer MR intervention HIFU 



Adeno carcinoma


Bronco alveolar carcinoma


Contrast-to-noise ratio


Colorectal carcinoma


Computer tomography


Flip angle


Fraction inspired oxygen


Focused ultrasound surgery


Gradient echo


Half-Fourier acquisition single-shot turbo spin echo sequence


High-intensity focused ultrasound


Invasive mammary ductal carcinoma


Lung cancer


Large-cell carcinoid


Left upper lobe


Left lower lobe


Lung metastasis


Maximum intensity projection


Magnet resonance imaging


Non-small cell lung cancer


One lung flooding


Positron emission tomography


Pancreatic ductal carcinoma




PerFluoroCarbonate liquid


Renal cell carcinoma




Right middle lobe


Right upper lobe


Right lower lobe


Region of interest


Specific absorption rate


Squamous carcinoma


Echo time


Repetition time


Author contributions

FW and TGL developed the study design and conception. TGL performed clinical selection of cases and performed surgical resection. FW performed ex vivo lung preparation. Acquisition of MR data and statistics were performed by JB and FW. FW, JB, and TGL were drafting the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests, neither financial nor non-financial. This research was supported by the FUS Foundation, Charlottesville, VA, USA (FUS325) and the SRH Waldklinikum Gera, Germany.

Ethic approval

All surgical procedures were performed at the clinic for thoracic and vascular surgery of the SRH Wald-Klinikum Gera, Germany. The use of human tissue for this study was approved by the ethics committee of the Medical Association of Thuringia (TLLV) and patients were informed prior to surgery. This article does not contain any studies with animals performed by any of the authors.

Supplementary material

10334_2020_826_MOESM1_ESM.avi (263 kb)
Supplementary file1 (AVI 263 kb)


  1. 1.
    Wielpütz M, Kauczor H (2012) MRI of the lung: state of the art. Diagn Interv Radiol 18(4):344–353PubMedGoogle Scholar
  2. 2.
    Kurihara Y, Matsuoka S, Yamashiro T, Fujikawa A, Matsushita S, Yagihashi K, Nakajima Y (2014) MRI of pulmonary nodules. Am J Roentgenol AJR 202(3):1CrossRefGoogle Scholar
  3. 3.
    Flors L, Mugler J, de Lange E, Miller G, Mata J, Tustison N, Ruset I, Hersman F, Altes T (2016) Hyperpolarized gas magnetic resonance lung imaging in children and young adults. J Thorac Imaging 31(5):285–295CrossRefGoogle Scholar
  4. 4.
    S. Obruchkov, M. Noseworthy (2016) (1)H-MR imaging of the lungs at 3.0 T. Quant Imaging Med Surg 6(1), 67–75.Google Scholar
  5. 5.
    Wild J, Marshall H, Bock M, Schad L, Jakob P, Puderbach M, Molinari F, Van Beek E, Biederer J (2012) MRI of the lung (1–3). Insights Imaging 3(4):345–353CrossRefGoogle Scholar
  6. 6.
    Wolfson M, Shaffer T (2005) Pulmonary applications of perflourchemical liquids: ventilation and beyond. Pediatric Resp Rev 1:117–127CrossRefGoogle Scholar
  7. 7.
    Weigel J, Steinmann D, Emerich P, Stahl C, Elverfeldt DV, Guttmann J (2001) High-resolution three-dimensional 19F-magnetic resonance imaging of rat lung in situ: evaluation of airway strain in the perfluorocarbon-filled lung. Physiol Meas 32(2):251–262CrossRefGoogle Scholar
  8. 8.
    Huang M, Basse P, Yang Q, Horner J, Hichens T, Ho C (2004) MRI detection of tumor in mouse lung using partial liquid ventilation with a perfluorocarbon-in-water emulsion. Magn Reson Imaging 22(5):645–652CrossRefGoogle Scholar
  9. 9.
    Chenoune M, De Rochefort L, Bruneval P, Lidouren F, Kohlhauer M, Seemann A, Ghaleh B, Korn M, Dubuisson R, Ben Yahmed A, Maître X, Isabey D, Ricard J, Kerber R, Darrasse L, Berdeaux A, Tissier R (2014) Evaluation of lung recovery after static administration of three different perfluorocarbons in pigs. BMC Pharmacol Toxicol 1:15–53Google Scholar
  10. 10.
    Lesser T, Klinzing S, Schubert H, Kosmehl M (2008) Consequences of one-lung flooding: a histological and immunological investigation. Eur J Med Res 13(9):432–438PubMedGoogle Scholar
  11. 11.
    Klinzing S, Lesser T, Schubert H, Bartel M, Klein U (2000) Wet to Dry ratio of lung tissue and surfactant outwash after one lung flooding. Eur J Med Res 200:27–33Google Scholar
  12. 12.
    Klinzing S, Lesser T, Schubert H, Bartel M, Klein U (2000) One lung flooding for video-assisted thoracoscopic surgery in animal experiments on pigs. Resp Exp Med 199:333–337CrossRefGoogle Scholar
  13. 13.
    Wolfram F, Boltze C, Schubert H, Bischoff S, Lesser T (2014) Effect of lung flooding and high-intensity focused ultrasound on lung tumours: an experimental study in an ex vivo human cancer model and simulated in vivo tumours in pigs. Eur J Med Res 19(1):1CrossRefGoogle Scholar
  14. 14.
    Lesser T, Schubert H, Güllmar D, Reichenbach J, Wolfram F (2016) One-lung flooding reduces the ipsilateral diaphragm motion during mechanical ventilation. Eur J Med Res 21(9):1Google Scholar
  15. 15.
    Herrmann K, Krämer M, Reichenbach J (2016) Time efficient 3D radial UTE sampling with fully automatic delay compensation on a clinical 3T MR scanner. PLoS ONE 11(3):1CrossRefGoogle Scholar
  16. 16.
    Watanabe H, Kanematsu M, Goshima S, Kondo H, Kajita K, Kawada H, Noda Y, Moriyama N (2012) Detection of focal hepatic lesions with 3-T MRI: comparison of two-dimensional and three-dimensional T2-weighted sequences. Jpn J Radiol 30(9):721–728CrossRefGoogle Scholar
  17. 17.
    Young-Joo J, Soon Gu C, Kun Young L, Joon Mee K, WooLee J (2017) Association between relative liver enhancement on gadoxetic acid enhanced magnetic resonance images and histologic grade of hepatocellular carcinoma. Medicine 96(30):1Google Scholar
  18. 18.
    Renz D, Scholz O, Böttcher J, Maurer M, Denecke T, Schwarz C, Pfeil A, Streitparth F, Huppertz A, Mehl A, Poellinger A, Staab D, Hamm B, Mentzel H (2015) Comparison between magnetic resonance imaging and computed tomography of the lung in patients with cystic fibrosis with regard to clinical, laboratory, and pulmonary functional parameters. Invest Radiol 50(10):733–742CrossRefGoogle Scholar
  19. 19.
    Schmidt H, Tscholakoff D, Hricak H, Higgins C (1985) MR image contrast and relaxation times of solid tumors in the chest, abdomen, and pelvis. J Comput Assist Tomogr 9(4):738–748CrossRefGoogle Scholar
  20. 20.
    Lesser T, Petersen I, Pölzig F, Wolfram F (2018) Lung flooding enables ultrasound-guided transthoracic needle biopsy of small pulmonary nodules with high sensitivity. Ultrasound Med Biol 44(7):1556–1562CrossRefGoogle Scholar
  21. 21.
    Wolfram F, Güllmar D, Böttcher J, Schubert H, Bischoff S, Reichenbach J, Lesser T (2019) Assessment of MR imaging during one-lung flooding in a large animal model. MAGMAGoogle Scholar
  22. 22.
    Lesser T, Klinzing S, Schubert H, Klein U, Bartel M (1998) Lung flooding—a new method for complete lung sonography. Resp Exp Med 198:83–91CrossRefGoogle Scholar
  23. 23.
    Klinzing S, Lesser T, Schubert H, Bloos F, Klein U, Bartel M (1999) Hemodynamics and gas exchange during experimental one-lung fluid flooding in pigs. Resp Exp Med 199(2):87–94CrossRefGoogle Scholar
  24. 24.
    Lesser T, Schubert H, Bischoff S, Wolfram F (2013) Lung flooding enables efficient lung sonography and tumour imaging in human ex vivo and porcine in vivo lung cancer models. Eur J Med Res 18(23):1Google Scholar
  25. 25.
    Wolfram F, Reichenbach J, Lesser T (2013) An ex vivo human lung model for ultrasound guided HIFU therapy using lung flooding. Ultrasound Med Biol 40(3):496–503CrossRefGoogle Scholar
  26. 26.
    Wang Y, Liu B, Cao P, Wang W, Wang W, Chang H, Li D, Li X, Zhao X, Li Y (2018) Comparison between computed tomography-guided percutaneous microwave ablation and thoracoscopic lobectomy for stage I non-small cell lung cancer. Thorac Cancer 9(11):1376–1382CrossRefGoogle Scholar
  27. 27.
    C. Fink, M. Puderbach, J. Biederer, M. Fabel, O. Dietrich, H. Kauczor, M. Reiser, S. Schönberg (2007) Lung MRI at 1.5 and 3 T: observer preference study and lesion contrast using five different pulse sequences. Invest Radiol 42(6), 377–383.Google Scholar
  28. 28.
    Scadeng M, Rossiter H, Dubowitz D, Breen E (2007) High-resolution three-dimensional magnetic resonance imaging of mouse lung in situ. Invest Radiol 41(1):50–57CrossRefGoogle Scholar
  29. 29.
    Koumellis P, van Beek E, Woodhouse N, Fichele S, Swift A, Paley M, Hill C, Taylor C, Wild J (2005) Quantitative analysis of regional airways obstruction using dynamic hyperpolarized 3He MRI-preliminary results in children with cystic fibrosis. J Mag Res Im 22(3):420–426CrossRefGoogle Scholar
  30. 30.
    Cameron I, Ord V, Fullerton G (1984) Characterization of proton NMR relaxation times in normal and pathological tissues by correlation with other tissue parameters. Magn Reson Imaging 97(106):97–106CrossRefGoogle Scholar
  31. 31.
    Liu X, Madhankumar A, Miller P, Duck K, Hafenstein S, Rizk E, Slagle Webb B, Sheehan J, Connor J, Yang Q (2016) MRI contrast agent for targeting glioma: interleukin-13 labeled liposome encapsulating gadolinium-DTPA. Neuro Oncol 18(5):691–699CrossRefGoogle Scholar
  32. 32.
    Takayama Y, Nishie A, Sugimoto M, Togao O, Asayama Y, Ishigami K, Ushijima Y, Okamoto D, Fujita N, Yokomizo A, Keupp J, Honda H (2016) Amide proton transfer (APT) magnetic resonance imaging of prostate cancer: comparison with Gleason scores. MAGMA 29(4):671–679CrossRefGoogle Scholar
  33. 33.
    Dadakova T, Gellermann J, Voigt O, Korvink J, Pavlina J, Hennig J, Bock M (2015) Fast PRF-based MR thermometry using double-echo EPI: in vivo comparison in a clinical hyperthermia setting. MAGMA 28(4):305–314CrossRefGoogle Scholar
  34. 34.
    Streicher M, Schäfer A, Reimer E, Dhital B, Trampel R, Ivanov D, Turner R (2012) Effects of air susceptibility on proton resonance frequency MR thermometry. MAGMA 25(1):41–47CrossRefGoogle Scholar

Copyright information

© European Society for Magnetic Resonance in Medicine and Biology (ESMRMB) 2020

Authors and Affiliations

  1. 1.Department of Thoracic and Vascular Surgery, SRH Wald-Klinikum GeraTeaching Hospital of Friedrich-Schiller University of JenaGeraGermany
  2. 2.Institute of Diagnostic and Interventional Radiology, SRH Wald-Klinikum GeraTeaching Hospital of Friedrich-Schiller University of JenaGeraGermany

Personalised recommendations