title: 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.
abstract: BACKGROUND
  High-intensity focused ultrasound is a valuable tool for minimally invasive tumour ablation. However, due to the air content in ventilated lungs, lung tumours have never been treated with high-intensity focused ultrasound. Lung flooding enables efficient lung sonography and tumour imaging in ex vivo human and in vivo porcine lung cancer models. The current study evaluates the effectiveness of lung flooding and sonography-guided high-intensity focused ultrasound for lung tumour ablation in ex vivo human and in vivo animal models.
  
  
  METHODS
  Lung flooding was performed in four human lung lobes which were resected from non-small cell lung cancers. B-mode imaging and temperature measurements were simultaneously obtained during high-intensity focused ultrasonography of centrally located lung cancers. The tumour was removed immediately following insonation and processed for nicotinamide adenine dinucleotide phosphate-diaphorase and H&E staining. In addition, the left lungs of three pigs were flooded. Purified BSA in glutaraldehyde was injected centrally into the left lower lung lobe to simulate a lung tumour. The ultrasound was focused transthoracically through the flooded lung into the simulated tumour with the guidance of sonography. The temperature of the tumour was simultaneously measured. The vital signs of the animal were monitored during the procedure.
  
  
  RESULTS
  A well-demarcated lesion of coagulation necrosis was produced in four of four human lung tumours. There did not appear to be any damage to the surrounding lung parenchyma. After high-intensity focused ultrasound insonation, the mean temperature increase was 7.5-fold higher in the ex vivo human tumour than in the flooded lung tissue (52.1 K ± 8.77 K versus 7.1 K ± 2.5 K). The transthoracic high-intensity focused ultrasound of simulated tumours in the in vivo model resulted in a mean peak temperature increase up to 53.7°C (±4.5). All of the animals survived the procedure without haemodynamic complications.
  
  
  CONCLUSIONS
  High-intensity focused ultrasound with lung flooding produced a thermal effect in an ex vivo human lung carcinoma and in vivo simulated lung tumours in a porcine model. High-intensity focused ultrasound is a potential new strategy for treating lung cancer.
authors.forename: Frank
authors.initials: F
authors.lastname: Wolfram
authors.forename: Carsten
authors.initials: C
authors.lastname: Boltze
authors.forename: Harald
authors.initials: H
authors.lastname: Schubert
authors.forename: Sabine
authors.initials: S
authors.lastname: Bischoff
authors.affiliation: Department of Thoracic and Vascular Surgery, SRH Wald-Klinikum Gera, Teaching Hospital of Friedrich-Schiller-University of Jena, Strasse des Friedens 122, D-07548 Gera, Germany. Thomas.lesser@wkg.srh.de.
authors.forename: Thomas Günther
authors.initials: TG
authors.lastname: Lesser
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000601:surgery; D004195:Disease Models, Animal; D005260:Female; D057086:High-Intensity Focused Ultrasound Ablation / Q000379:methods*; D006801:Humans; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery*; D013552:Swine; D013696:Temperature; D014463:Ultrasonography