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

OBJECTIVES: 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. RESULTS: 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. CONCLUSION: 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.

Assessment of MR imaging during one-lung flooding in a large animal model.

OBJECTIVE: Magnetic resonance imaging (MRI) of the lung remains challenging due to the low tissue density, susceptibility artefacts, unfavourable relaxation times and motion. Previously, we demonstrated in vivo that one-lung flooding (OLF) with saline is a viable and safe approach. This study investigates the feasibility of OLF in an MRI environment and evaluates the flooding process on MR images. METHODS: OLF of the left lung was performed on five animals using a porcine model. Before, during and after OLF, standard T2w and T1w spin-echo (SE) and gradient-echo (GRE) sequences were applied at 3 T. RESULTS: The procedure was successfully performed in all animals. On T1w MRI, the flooded lung appeared homogenous and isointense with muscle tissue. On T2w images, vascular structures were highly hypointense, while the bronchi were clearly demarcated with hypointense wall and hyperintense lumen. The anatomical demarcation of the flooded lung from the surrounding organs was superior on T2w images. No outflow effects were seen, and no respiration triggering was required. DISCUSSION: OLF can be safely performed in an MR scanner with highly detailed visualization of the pulmonary structures on T2w images. The method provides new approaches to MRI-based image-guided pulmonary interventions using the presented experimental model.

Effects of HIFU induced cavitation on flooded lung parenchyma.

BACKGROUND: High intensity focused ultrasound (HIFU) has gained clinical interest as a non-invasive local tumour therapy in many organs. In addition, it has been shown that lung cancer can be targeted by HIFU using One-Lung Flooding (OLF). OLF generates a gas free saline-lung compound in one lung wing and therefore acoustic access to central lung tumours. It can be assumed that lung parenchyma is exposed to ultrasound intensities in the pre-focal path and in cases of misguiding. If so, cavitation might be induced in the saline fraction of flooded lung and cause tissue damage. Therefore this study was aimed to determine the thresholds of HIFU induced cavitation and tissue erosion in flooded lung. METHODS: Resected human lung lobes were flooded ex-vivo. HIFU (1,1 MHz) was targeted under sonographic guidance into flooded lung parenchyma. Cavitation events were counted using subharmonic passive cavitation detection (PCD). B-Mode imaging was used to detect cavitation and erosion sonographically. Tissue samples out of the focal zone were analysed histologically. RESULTS: In flooded lung, a PCD and a sonographic cavitation detection threshold of 625 Wcm- 2(pr = 4, 3 MPa) and 3.600 Wcm- 2(pr = 8, 3 MPa) was found. Cavitation in flooded lung appears as blurred hyperechoic focal region, which enhances echogenity with insonation time. Lung parenchyma erosion was detected at intensities above 7.200 Wcm- 2(pr = 10, 9 MPa). CONCLUSIONS: Cavitation occurs in flooded lung parenchyma, which can be detected passively and by B-Mode imaging. Focal intensities required for lung tumour ablation are below levels where erosive events occur. Therefore focal cavitation events can be monitored and potential risk from tissue erosion in flooded lung avoided.

Flooded Lung Generates a Suitable Acoustic Pathway for Transthoracic Application of High Intensity Focused Ultrasound in Liver.

Background: In recent years, high intensity focused ultrasound (HIFU) has gained increasing clinical interest as a non-invasive method for local therapy of liver malignancies. HIFU treatment of tumours and metastases in the liver dome is limited due to the adjacent ultrasound blocking lung. One-lung flooding (OLF) enables complete sonography of lung and adjoining organs including liver. HIFU liver ablation passing through the flooded lung could enable a direct intercostal beam path and thus improve dose deposition in liver. In this study, we evaluate the feasibility of an ultrasound guided transthoracic, transpulmonary HIFU ablation of liver using OLF. Methods: After right-side lung flooding, ultrasound guided HIFU was applied transthoracic- transpulmonary into liver to create thermal lesions in three pigs. The HIFU beam was targeted five times into liver, two times at the liver surface and three times deeper into the tissue. During autopsy examinations of lung, diaphragm and liver located in the HIFU path were performed. The focal liver lesions and lung tissue out of the beam path were examined histologically. Results: Fifteen thermal liver lesions were generated by transpulmonary HIFU sonication in all targeted regions. The lesions appeared well-demarcated in grey color with a cigar-shaped configuration. The mean length and width of the superficial and deeper lesions were 15.8 mm (range: 13-18 mm) and 5.8 mm (range: 5-7 mm), and 10.9 mm (range: 9-13 mm) and 3.3 mm (range: 2-5 mm), respectively. Histopathological, all liver lesions revealed a homogeneous thermal necrosis lacking vitality. There were no signs of damage of the overlying diaphragm and lung tissue. Conclusions: Flooded lung is a suitable pathway for applying HIFU to the liver, thus enabling a transthoracic, transpulmonary approach. The enlarged acoustic window could enhance the ablation speed for targets in the hepatic dome.

One-lung flooding reduces the ipsilateral diaphragm motion during mechanical ventilation.

BACKGROUND: Diaphragm motion during spontaneous or mechanical respiration hinders image-guided percutaneous interventions of tumours in lung and upper abdomen. Motion-tracking methods can be applied but increase procedure complexity and procedure time. One-lung flooding (OLF) generates a suitable acoustic pathway to lung tumours and likely suppress diaphragm motion. The aim of this study was to quantify the effect of OLF on ipsilateral diaphragm motion during contralateral one-lung ventilation. METHODS: To measure the diaphragm motion, M-mode ultrasonography of the right hemidiaphragm was performed during spontaneous breathing and mechanical ventilation, as well as after right-side lung flooding, in three pigs. Diaphragm motion was analysed using magnetic resonance images during left-side lung flooding and mechanical ventilation, in four pigs. RESULTS: Double-lung ventilation increased the diaphragm movement in comparison with spontaneous breathing (17.8 ± 4.4 vs. 12.2 ± 3.4 mm, p = 0.014). Diaphragm movement on the flooded side during contralateral one-lung ventilation was significantly reduced compared to that during double-lung ventilation (3.9 ± 1.0 vs. 17.8 ± 4.4 mm, p = 0.041). By analysing the magnetic resonance images, the hemidiaphragm on the flooded side showed an average displacement of 4.2 mm, a maximum displacement of 15 mm close to the ventilated lung and no displacement at the lateral side. CONCLUSION: OLF leads to a drastic reduction of diaphragm motion on the ipsilateral side which implies that targeting and motion compensation algorithms for interventions like high-intensity focused ultrasound ablation of intrapulmonary and hepatic lesions might not be required.

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.

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.

Lung flooding enables efficient lung sonography and tumour imaging in human ex vivo and porcine in vivo lung cancer model.

BACKGROUND: Sonography has become the imaging technique of choice for guiding intraoperative interventions in abdominal surgery. Due to artefacts from residual air content, however, videothoracoscopic and open intraoperative ultrasound-guided thermoablation of lung malignancies are impossible. Lung flooding is a new method that allows complete ultrasound imaging of lungs and their tumours. METHODS: Fourteen resected tumourous human lung lobes were examined transpleurally with B-mode ultrasound before (in atelectasis) and after lung flooding with isotonic saline solution. In two swine, the left lung was filled with 15 ml/kg isotonic saline solution through the left side of a double-lumen tube. Lung tumours were simulated by transthoracic ultrasound-guided injection of 5 ml of purified bovine serum albumin in glutaraldehyde, centrally into the left lower lung lobe. The rate of tumour detection, the severity of disability caused by residual gas, and sonomorphology of the lungs and tumours were assessed. RESULTS: The ex vivo tumour detection rate was 100% in flooded human lung lobes and 43% (6/14) in atelectatic lungs. In all cases of atelectasis, sonographic tumour imaging was impaired by residual gas. Tumours and atelectatic tissue were isoechoic. In 28% of flooded lungs, a little residual gas was observed that did not impair sonographic tumour imaging. In contrast to tumours, flooded lung tissue was hyperechoic, homogeneous, and of fine-grained structure. Because of the bronchial wall three-laminar structure, sonographic differentiation of vessels and bronchi was possible. In all cases, malignant tumours in the flooded lung appeared well-demarcated from the lung parenchyma. Adenocarcinoma, squamous, and large cell carcinomas were hypoechoic. Bronchioloalveolar cell carcinoma was slightly hyperechoic. Transpleural sonography identifies endobronchial tumour growth and bronchial wall destruction. With transthoracic sonography, the flooded animal lung can be completely examined in vivo. There is no residual gas, which interferes with ultrasound. Pulmonary vessels and bronchi are clearly differentiated. Simulated lung lesions can easily be detected inside the lung lobe. CONCLUSIONS: Lung flooding enables complete lung sonography and tumour detection. We have developed a novel method that efficiently uses ultrasound for guiding intraoperative interventions in open and endoscopic lung surgery.