Since Gustav Killian performed the first bronchoscopy in 1897 to remove an inhaled pork bone, bronchoscopy has developed beyond recognition.1 Gustav Killian was a laryngologist, but the bronchoscope soon find its role extending beyond the upper airway to the bronchi and lungs. Today, it has a central role in the diagnosis of benign and malignant lung conditions, and technology now even allows us to extend our reach outside the confines of the bronchial wall with transbronchial biopsies and endobronchial ultrasound (EBUS)-guided lymph node biopsies.
However, the peripheral half of the lungs remain beyond the reach of the conventional bronchoscope – as it sinuates down the bronchial tree, the bronchi become narrower and narrower until a point where vision is lost and the scope is wedged in and can not advance further. Because of this, conventional bronchoscopy is an excellent tool for diagnosing central lung conditions but not peripheral lesions.
The need to reach the peripheral lung
Lung cancer is the most common cause of death worldwide (1.59 million deaths in 2012), and the fourth most common cancer in Europe, with over 400,000 new cases diagnosed and 350,000 deaths each year.2 Early diagnosis is key to better outcomes – earlier diagnosis means earlier treatment and better outcomes, and this requires diagnosing more lesions when they are smaller.
Small peripheral lung lesions are however, becoming more common. As CT scans become more prevalent for investigating different conditions, more incidental lung nodules are identified. The National Lung Screening Trial also showed a 20% reduction in overall mortality with CT screening but with the caveat that 39.1% of participants had a positive screen, which may need investigating.3 If implemented, screening would result in a deluge of peripheral small lung lesions.
Finally, there has been a shift in the pattern of lung cancer, with central squamous cell carcinoma giving way to peripheral adenocarcinomas. All this points to the need for a safe and reliable way to diagnose small peripheral lesions.
The diagnostic yield for small (<2cm) peripheral lesions with conventional bronchoscopy is poor and the main alternatives are CT-guided biopsy, watchful waiting and surgery. However, only certain areas of the lung are accessible by CT-guided biopsy – lesions in areas such as behind the scapula, in the apex and areas around the heart and diaphragm are not accessible. It is also a procedure that carries significant risks including a high pneumothorax rate with many patients requiring a chest drain, and risk of bleeding.4
In patients with emphysematous lungs and poor lung function, the risk from a pneumothorax is so high it precludes this option for diagnosis. Watchful waiting is an alternative for low risk lesions but leads to more radiation exposure, delaying treatment, whilst waiting without a diagnosis is a psychological burden for many patients. Finally, surgery is the gold standard for diagnosis but is invasive.
Because of these limitations, there have been attempts at improving bronchoscopic diagnosis of peripheral lesions. One such is the development of the radial EBUS miniprobe, which is a thin, circumferentially scanning ultrasound probe. When a lesion is identified on the ultrasound image, it could be biopsied. However, with the loss of bronchoscopic vision in the lung peripheries, the probe is advanced blindly by trial and error into different branches of the bronchial tree in the hope of encountering the lesion at some point. The need to be able to be guided through the bronchial tree accurately to a peripheral lesion led to the development of navigation bronchoscopy.
Electromagnetic Navigation Bronchoscopy™
There are two main ways of guiding bronchoscopes and instruments through the airway. One method is through image-based guidance by using a virtual bronchoscopy image constructed from a CT, to which the operator matches the image to the real bronchoscopy view, allowing them to follow a path. However, this relies on a clear endoscopic view which can be difficult with mucus and secretions, narrowing bronchi as you advance the scope, and difficulty identifying which virtual bronchoscopic orifice corresponds to which real orifice due to similar appearances, rotation and distortion.
Electromagnetic Navigation Bronchoscopy™ (ENB™) avoids these problems by using a locatable guide within an electromagnetic field placed around the patient. This way it is possible to navigate an ultra-thin sheath throughout the entire lung and all the way to the pleura.
The first electromagnetic navigation bronchoscopy was carried out in 2006,5 and since then technology has progressed with improved ease and accuracy of registration (the process whereby a CT scan is mapped onto the patient), easier pathway calculation, more intuitive user interface to simplify navigation and a wider range of instruments to tackle more complex biopsies and improve yield. Through a generous donation by Barts Charity, St Bartholomew’s Hospital became the first hospital in Europe to offer patients the latest version 7.1 of the superDimension™ Electromagnetic Navigation Bronchoscopy System (Covidien-Medtronic, Minneapolis, USA).
How is navigation bronchoscopy done?
There are several steps in ENB: planning, registration, navigation and sampling.
In order to ensure the map through which navigation takes place is accurate, a recent planning CT scan is required. This scan is carried out to a pre-specified protocol to optimise airway segmentation. The proprietary software imports the CT scan to create a 3D reconstruction of the bronchial tree or ‘virtual bronchoscopy’. The operator then defines the target they want to navigate to and the software computes pathways to the target (Figure 1). Previously the pathway had to be manually plotted by the operator, but the latest version of the software is capable of automatic pathway finding once the nearest airway is identified.
Fig. 1: Planning: the CT scan is loaded into the application and a bronchial map is created. The target is defined by the user, and the software will automatically find the quickest path to the target.
The next step is to map the CT scan onto the patient. The latest versions of the software allows for automatic registration where the locatable guide surveys the entire bronchial tree and the software matches the locus of movement to the CT bronchial tree. Previously and in the event of failed automatic registration, manual registration can be carried out.
In this mode, the operator touches each of a number of predetermined registration landmarks with the locatable guide and the software will superimpose the scan on the patient with these anchor points. In order to compensate for respiratory movements, three sensors are placed on the surface of the patient’s chest to make adjustments to the mapping for breathing.
After registration the accuracy of the mapping is checked. The locatable guide is touched onto the carina and other landmarks to ensure they match the equivalent position on the CT scan.
Fig. 2: Central navigation – synchronised electromagnetic navigation and virtual bronchoscopy allow the user to use the intuitive image based navigation in real time to advance quickly down the correct bronchi.
Once the registration is accepted, navigation can commence. The locatable guide is placed within a sheath (the extended working channel) and advanced through the lung. In the first part of navigation through the large central airways, the ‘central navigation’ screen is displayed where the bronchoscopy image is juxtaposed against the virtual bronchoscopy, and a path through the latter guides which bronchi to advance the scope down (Figure 2).
Fig. 3: Peripheral navigation – electromagnetic localisation navigates the probe through the virtual lung map down the correct bronchi towards the target.
Once advanced to a point where the bronchi have become too narrow and the bronchoscope is wedged in, the ‘peripheral navigation’ mode is engaged. Here the locatable guide is advanced out of the bronchoscope and steered through a virtual CT and virtual bronchial tree towards the target which appears as a large green ball (Figure 3). Navigation is considered successful when the probe arrives within a centimetre of the centre of the target (Figure 4).
Fig. 4: Successful navigation – the probe is now within the lesion as can be seen on the projected CT image, and the probe tip lies within the green target sphere. The view out of the end of the probe shows the target is in front of and surrounds it.
Sampling and therapy
Once arrived at the target, the bronchoscope is locked into position, and the locatable guide is removed leaving an extended working channel that leads straight to the target. Through this channel a number of diagnostic and therapeutic instruments can be deployed. Biopsy instruments including suction catheters, aspiration needles, brushes and biopsy forceps are used. Therapeutic adjuncts include radiopaque fiducials, which are placed to guide stereotactic radiotherapy, and markers such as dye, or other contrast material used to guide surgical resection, can be placed.6
The benefits of ENB
ENB is an effective instrument to reach the peripheries of the lung safely. The diagnostic yield for conventional bronchoscopy when diagnosing small peripheral pulmonary nodules (<2cm) is as low as 14%.7 Since the first in-human series which observed a positive diagnosis in 69% of patients, the reported results have progressively improved over the years.
Two techniques have been shown to improve diagnostic yield in conjunction with ENB: radial EBUS miniprobe and rapid on-site evaluation (ROSE).
The radial EBUS miniprobe could be passed down the working channel to confirm the presence of a lesion at the end of the channel before biopsy. In a randomised study, EBUS combined with ENB was shown to result in a significantly higher diagnostic yield (88%) than either ENB (59%) or EBUS (69%) alone.8 ROSE allows an immediate cytological evaluation of the sample for diagnostic material and adequacy. In a series of 112 patients undergoing ENB with ROSE, the diagnostic yield was 87.5%.9 Both these techniques help confirm accurate biopsies before ending the procedure, allowing for reselection of biopsy sites and repeat sampling until a positive diagnosis is obtained.
The reported diagnostic yield for ENB continues to improve and in a recent retrospective study an overall diagnostic yield of 94% for peripheral lesions was reported, with a positive yield of 87% for small peripheral nodules.10
The biggest attraction for ENB is its safety profile. The procedure is safe and complications are rare. In a recent meta-analysis of 1033 nodules in 971 patients undergoing ENB biopsy, the most common complication was pneumothorax which occurred in 32 (3.1%) patients. Of these, only 17 (1.6%) required a chest drain insertion.11
Minor and moderate bleeding occurred in 0.9% patients. This compares very favourably with CT-guided lung biopsy, which has a pneumothorax rate an order of magnitude higher at 15–43%,4 and a haemoptysis rate of 12%.12
ENB has markedly improved the diagnostic yield of peripheral lung lesions by bronchoscopy, but nevertheless there is still an approximate 20% failure rate to diagnose some lesions. This is where refinements in the techniques and technology can improve the rate, to achieve the holy grail of 100% diagnosis and no complications.
Whilst the strength of ENB is the ability to navigate through the lung without relying on visual feedback, it takes a leap of faith to believe when the system reports you have arrived at the lesion, that you are actually at the lesion. This very lack of real-time visualisation is therefore also its limitation. The use of the radial EBUS miniprobe and ROSE was designed to circumvent this problem; others have used fluoroscopic or CT confirmation of the probe position prior to biopsy but they carry radiation risks and renders the procedure cumbersome, whilst still not guaranteeing a positive diagnosis.
The next generation of locatable guide will incorporate real-time visualisation of the area by incorporating ultrasound into the locatable guide and instruments. Prototypes are already being developed to allow real-time visualisation.13
The other limitation of ENB is restriction of travel within the bronchus. Once at the target site, instruments inserted will tend to travel within the bronchus, and if the target lesion lies outside the bronchus, the instruments may skirt pass it without entering it. This is borne by the higher diagnostic yield when a bronchus leads straight into a lesion,14 and similarly in radial EBUS where the yield is higher when the lesion is concentrically seen around the probe rather than adjacent to it.15
In order to circumvent this restriction, a recently launched new device CrossCountry™ (Medtronic, Minneapolis, USA) is becoming available to create a path out of the bronchus to reach these lesions.
Navigation bronchoscopy is a rapidly developing area, and a number of different platforms are currently being developed,16 and there is much work looking to improve different aspects of the technology, from the use of inspiratory-expiratory CT to better map CT anatomy to respiration, to techniques that improve tracking accuracy.
Navigation bronchoscopy has opened access of the whole lung to the bronchoscope. Until now, many peripheral and small lung nodules, which could represent cancer, could not be diagnosed safely. However, earlier diagnosis means earlier treatment, and earlier treatment means better outcomes.
Navigation bronchoscopy is able to obtain a diagnosis for lung lesions in 70–90% cases with a very safe profile, thus allowing more patients to have an earlier diagnosis and an earlier start to treatment, with a view to better outcomes. We are still at the embryonic development phase of this technology, and we expect to see many exciting developments in the coming years to push the diagnostic yield and improve safety further.
- Panchabhai TS, Mehta AC. Historical perspectives of bronchoscopy. Connecting the dots. Ann Am Thorac Soc 2015;12(5):631–41.
- Ferlay J et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer 2013;49(6):1374–403.
- National Lung Screening Trial Research Team et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 2011;365(5):395–409.
- Wahidi MM et al. American College of Chest Physicians. Evidence for the treatment of patients with pulmonary nodules: when is it lung cancer? ACCP evidence-based clinical practice guidelines (2nd edition). Chest 2007;132(Suppl 3):94S–107S.
- Schwarz Y et al. Real-time electromagnetic navigation bronchoscopy to peripheral lung lesions using overlaid CT images: the first human study. Chest 2006;129(4):988–94.
- Krimsky WS et al. Thoracoscopic detection of occult indeterminate pulmonary nodule using bronchoscopic pleural dye marking. J Community Hosp Intern Med Perspect 2014;17:4.
- Baaklini WA et al. Diagnostic yield of fiberoptic bronchoscopy in evaluating solitary pulmonary nodules. Chest 2000;117(4):1049–54.
- Eberhardt R et al. Multimodality bronchoscopic diagnosis of peripheral lung lesions: a randomized controlled trial. Am J Respir Crit Care Med 2007;176(1):36–41.
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- Loo FL et al. The emerging technique of electromagnetic navigation bronchoscopy-guided fine-needle aspiration of peripheral lung lesions: promising results in 50 lesions. Cancer Cytopathol 2014;122(3):191–9.
- Gex G et al. Diagnostic yield and safety of electromagnetic navigation bronchoscopy for lung nodules: a systematic review and meta-analysis. Respiration 2014;87(2):165–76.
- Yildirim E et al. CT-guided cutting needle lung biopsy using modified coaxial technique: factors effecting risk of complications. Eur J Radiol 2009;70(1):57–60.
- Luo X, Mori K. Beyond current guided bronchoscopy: a robust and real-time bronchoscopic ultrasound navigation system. Med Image Comput Comput Assist Interv 2013;16(Pt 1):388–95.
- Seijo LM et al. Diagnostic yield of electromagnetic navigation bronchoscopy is highly dependent on the presence of a Bronchus sign on CT imaging: results from a prospective study. Chest 2010;138(6):1316–21.
- Kurimoto N et al. Endobronchial ultrasonography using a guide sheath increases the ability to diagnose peripheral pulmonary lesions endoscopically. Chest 2004;126(3):959–65.
- Reynisson PJ et al. Navigated bronchoscopy: a technical review. J Bronchology Interv Pulmonol 2014;21(3):242–64.