E l e c t ro m a g n e t i c Navigation

Yehuda Schwarz, MD, FCCPa,b,*

KEYWORDS
 Electromagnetic navigation bronchoscopy  Peripheral lung lesion  Transbronchial needle aspiration  Fiducial markers  Stereotactic radiosurgery

Department of Pulmonology, Tel-Aviv Sourasky Medical Center, 6 Weisman Street, Tel-Aviv, 64239, Israel Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel * Department of Pulmonology, Tel-Aviv Sourasky Medical Center, 6 Weisman Street, Tel-Aviv, 64239, Israel. E-mail address: schwarz@tasmc.health.gov.il

Clin Chest Med 31 (2010) 6573 doi:10.1016/j.ccm.2009.08.005 0272-5231/10/$ see front matter 2010 Published by Elsevier Inc.

chestmed.theclinics.com

The first bronchoscopic procedure was performed in 1897 by Gustav Killian using a laryngoscope and a rigid esophageal tube to remove a foreign body from the trachea.1 During the next century, bronchoscopy evolved from being a rigid technique to one that uses a flexible bronchoscope developed by Ikeda and colleagues2 in 1968, opening new horizons in the diagnosis and treatment of pulmonary diseases. Flexible bronchoscopy is a minimally invasive procedure, obviating general anesthesia and eliminating potential associated complications. New technological developments emerged in the 80s to improve the yield in diagnosis; these innovations included videobronchoscopy, endobronchial ultrasonography (EBUS), autofluorescence bronchoscopy, and lately, narrow-band imaging.3,4 Endoscopic therapeutic procedures have also kept pace with these developments, with the introduction of laser photoresection, cryotherapy, electrocautery, and stent technology.5 The field of imaging also underwent technological transformation at the same time. The incidence of peripheral non-smallcell lung cancer (NSCL, adenocarcinoma subgroup) has also increased significantly during the last 30 years; probably because of the introduction and use of filtered cigarettes and the subsequent distal delivery of smaller cigarettes particles. Patients with pulmonary nodules and masses are routinely referred to pulmonologists, radiologists, and thoracic surgeons for evaluation and tissue diagnosis. The rapidly increasing use of chest computed tomography (CT) for screening and ruling out pulmonary embolism and various other indications has led to a significant increase

in the detection of lung nodules.6 More than 6.5 million CT scans of the chest were performed in the United States alone in 2001, highlighting the gravity of this clinical scenario.7 Choosing the invasive diagnostic procedures to perform a biopsy for tissue diagnosis in cases of small peripheral nodules or opacities remains a clinical challenge. The main options are bronchoscopy, percutaneous needle aspiration, and thoracoscopic lung biopsy. Percutaneous needle aspiration biopsy still plays an important role in the diagnosis of peripheral lung cancers, yet the associated pneumothorax (20%34%) and hemoptysis are unacceptable.811 The high incidence of pneumothorax in percutaneous techniques can be partially explained by the fact that most patients diagnosed with a peripheral lung lesion also may have some degree of emphysematous changes and poor pulmonary function from smoking. Thoracoscopic and open surgical biopsy have the obvious disadvantages of the procedures being invasive, the patients having to undergo general anesthesia, and the need to tolerate single-lung ventilation during the procedure. The rate of mortality for this procedure can be 0.5% to 5.3%.12 In patients with a high probability of lung cancer and good lung function, it is often not necessary to obtain tissue diagnosis. For all others, however, there is a need for an approach with a low complication rate, especially in those with multiple nodules and compromised lung function. Cohort studies have demonstrated that most nodules so detected are benign.13 As such, surgery, with its associated morbidity and mortality, is not

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indicated for most patients who present with incidentally discovered pulmonary nodules. Tissue diagnosis, on the other hand, is frequently essential.12 The conventional flexible bronchoscopy procedure is of limited diagnostic value in peripheral lung nodules, that is, those located at the peripheral third of the lung. Biopsy success is further compromised if the lesion is smaller than 2 cm in diameter.14 The main limitation of the bronchoscopic approach is the difficulty in reaching peripheral lesions with the biopsy tools. The tools used to obtain biopsy tissue are difficult to steer to the desired location. Once extended beyond the tip of the bronchoscope, the physician performing the bronchoscopy is faced with the difficulty of precisely localizing the lesion under fluoroscopy, whereas the alternatives of CTguided bronchoscopy and EBUS are more technically demanding and require special training. EBUS enables the operator to see the lesion but it cannot provide guidelines to the bronchoscopist for choosing the correct airway to reach a given peripheral lesion. Moderate sedation is the current practice in standard bronchoscopy and the procedure is safe in the hands of trained personnel. Because the mortality for bronchoscopy is low (1 in 4000) and the complication rate for pneumothorax with transbronchial biopsy is also much lower than all the other available approaches (<2%), it would be worthwhile to use it as the procedure of choice if the yield could be improved. The recently introduced electromagnetic navigation bronchoscopy (EMB) system (inReach system, superDimension Ltd, Herzliya, Israel) is a new technology that includes the use of virtual bronchoscopy (VB) and real-time 3-dimensional CT images, allowing the bronchoscopist to localize peripheral lung lesions and to introduce endobronchial accessories for performing biopsies of peripheral lesions. The technology uses a processor, an amplifier, and a location board. By means of low-frequency electromagnetic waves emitted from a board placed under the head of the bronchoscopy table, the monitor picks up the signal emitted by the sensor. Electromagnetic waves preclude the use of the system on patients with devices such as pacemakers and automatic cardioverter-defibrillators. The sensor is 1 mm in diameter and 8 mm in length at the tip of a flexible metal cable (the locatable guide [LG]) (Fig. 1A). Once the sensor is placed within the electromagnetic field generated by the board placed under the mattress of the bronchoscopic bed (see Fig. 1B), its position in the X, Y, and Z planes and its orientation (roll, pitch, and yaw movements) are visualized on the monitor in realtime (see Fig. 1C). The guide is mounted on a tool that allows its distal section to be steered in 8 directions, translating into 360 of steerability. The fully retractable sensor is integrated into a flexible catheter that serves as an extended working channel (EWC) of the bronchoscope (see Fig. 1D). The LG has a built-in bending mechanism for active steering that allows bending of the tip toward the selected target (see Fig. 1A). The catheter is left in place once it reaches the desired location, enabling easy access for bronchoscopic accessories. The computer software and monitor allow the bronchoscopist to view the reconstructed 3-dimensional CT scans of the patients anatomy in coronal, sagittal, and axial views, with superimposed graphic information depicting the position of the sensor probe (Fig. 2). Information on location, orientation, and movement is then superimposed on a previously acquired CT scan and displayed on a monitor in real time. Navigation bronchoscopy is performed in several steps. The first step is the planning of the procedure, which is performed by importing the CT data into the software. The software presents the CT images in axial, sagittal and coronal cuts and also provides VB images (Fig. 3A). The planner marks the main carina and major bronchial bifurcations as reference points on the VB images (see Fig. 3B) and the targeted lesions (mediastinal lymph nodes and lung nodules) on the CT images. The physician can track a lesion by following the CT images and flying though the VB images. The quality of the virtual environment is dependent on the quality of the CT scan; so it is essential to plan the procedure in great detail. To perform a transbronchial needle aspiration (TBNA), the tracheal wall on the VB images can be made transparent to place a marker as reference to a site for needle insertion (Fig. 4). The next step is the alignment of the VB images at preselected points of the carina and major bronchial bifurcations. These easily recognizable points act as anatomic landmarks during the bronchoscopy and are aligned with the VB images for the purpose of registration (Fig. 5). The software then aligns both environments (VB and endoscopy), thus enabling the sequential presentation of the CT cuts while the sensor (LG) is advanced through the patients airways. Registration errors could then be reduced by either repositioning a misplaced registration point or by eliminating the registration points with the greatest deviation. Navigation is performed by steering the LG probe with its extending working channel (EWC) to the lesion, by following the multiplanar CT images and the tip-view. The latter also provides information on the

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Fig. 1. (A) The sensor (1 mm diameter and 8 mm length) mounted at the tip of a flexible metal cablethe LG. The LG has a built-in bending mechanism for active steering in 8 directions that allows bending of the tip. Courtesy of superDimension, Inc., Minneapolis, MN; with permission. (B) The LG with the sensor is integrated into the extended working channel (EWC). The EWC is left at the desired location once it has been reached with the aid of the sensor, enabling easy access for bronchoscopic accessories. (C) The monitor and computer are placed on a trolley to receive input and visualization of the sensors position on the monitor in all orientations (X, Y, and Z planes and roll, pitch, and yaw movements) in real time. Courtesy of superDimension, Inc., Minneapolis, MN; with permission. (D) Magnetic board placed under the mattress of the bronchoscopy bed.

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Fig. 2. The monitor depicting the reconstructed 3-dimensional CT scans (coronal, sagittal, and axial views), with the position of the sensor probe at the tip-view showing a ring with an arrow giving an accurate direction to bend the LG for reaching the targeted lesion and 3-dimensional CT images of the focal sensors area.

direction in which to bend the LG to move toward the lesion (see Fig. 2). The fully retractable probe is incorporated into a flexible catheter (the EWC sheath) that is 130 cm long and 1.9 mm in diameter. Once the area of interest is reached, the LG is removed leaving the sheath in place. Various tools and endoscopic accessories can now be introduced through the catheter: these include forceps for biopsy, needle, brush or curette, radial EBUS (used by some researchers for confirmation of the proximity of the sensor to the nodule), or to place fiducials surrounding the diagnosed tumors. Schwarz and colleagues15 performed the first trial to determine the practicality, accuracy, and safety of real-time EMB in locating artificial peripheral lung lesions in a swine model. The study showed a registration accuracy of 4.5 mm on average. No adverse effects, such as pneumothorax or internal bleeding, were encountered in any animal. The authors concluded that real-time electromagnetic positioning with previously acquired CT scans is an accurate technology that can augment standard bronchoscopy to assist in reaching peripheral lung lesions and in

performing biopsies. The first human study was a prospective controlled clinical investigation that was opened in June 2003; its result was published in 2006.16 Of 15 subjects, 13 underwent EMB for peripheral lung lesions, ranging in size from 1.5 to 5 cm, that were beyond the optical reach of a bronchoscope. Four of the lesions were in the left upper lobe, 3 in the right upper lobe; 5 in the right lower lobe, and 1 in the right middle lobe. A definitive diagnosis was established in 9 (69%) of the 13 subjects. No device-related adverse events were reported during or up to 48 hours after the study. A parallel study17 was performed in Germany from July to December, 2003, which also attained diagnostic yield of 69%. There were no serious complications. Both studies concluded that real-time EMB with CT images is a feasible and safe method for obtaining biopsies of peripheral lung lesions. At the end of the 2006, a larger prospective study involving 60 patients was performed by Gildea and colleagues18; the results showed an improved yield of 74%, although 57% of lesions were smaller than 20 mm in size. Their study

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Fig. 3. (A) CT data represented by the system software in axial, sagittal, and coronal cuts and VB images. (B) Carina and major bronchial bifurcations on the VB images marked as reference points for the registration phase.

was the first to demonstrate another application of the navigation system, that is, the diagnosis of mediastinal lymph nodes. By adding lymph node sampling, they improved the overall patient diagnosis accuracy to 80.3%. Complications were limited to pneumothorax, which occurred

in 3.5% of the patients. By giving the bronchoscopist access to the peripheral lung area, it became apparent that there are cases in which the steerable probe cannot be advanced to all the lesions, as the bronchus leading to the lesion may not exist.

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Fig. 4. Targeting the mediastinal lymph nodes for TBNA. The software on-demand shows a transparent VB image of the tracheal wall, thus allowing a view of the previously marked mediastinal lymph node for aspiration. (A) R4 lymph node and (B) lymph node at the aortopulmonary window.

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Fig. 5. Registration step: during the bronchoscopy the carina and the major bronchial bifurcations are marked on the VB images at the planning step in the same position using the sensor applied lightly on the carina mucosa.

Makris and colleagues19 described their experience using the same EMB system in 40 patients with lesions between 17 to 39 mm in size. They emphasized that the average of CT-to-body divergence, which represents the radius of the expected difference in location between the tip of the sensor probe in the actual patient and where the tip is expected to be was 4.6015 mm, whereas the distance between sensor probe and the center of the lesion was 8.7608 mm. The yield they reached was 62.5% in 25 out of the 40 cases, improving if the CT-to-body divergence was less than 4 mm. The sensitivity and negative predictive value of EMB for malignancy were 57 and 25%, respectively. Eberhardt and colleagues20 reported their experience with EMB in 89 subjects in whom they reached a diagnostic yield of 67%, (independent of lesion size). They had a CT-to-body divergence of 4.6 1.8 mm (range, 1 to 31). There was no occurrence of pneumothorax. The mean navigation error was 9 6 mm. These investigators also found that size of the lesion was not

a determinant in diagnostic yield, and noted that the time needed for the electromagnetic navigation method is around 30 minutes or less. This is similar to the time for performing bronchoscopy on patients with interstitial lung diseases and for obtaining a transbronchial biopsy. The same group21 compared the added value of using the US probe to verify and correct the position of the sensor once it had reached the lesion, as indicated by the software. By doing so, they were able to correct the position of the sensor and thereby improved their yield. They concluded that combined EBUS and EMB enhance the diagnostic yield of flexible bronchoscopy in peripheral lung lesions without compromising patient safety. Specifically, combined EBUS/EMB had a significantly higher diagnostic yield (88%) compared with EBUS (69%) or EMB alone (59%; P 5 .02), with an overall pneumothorax rate of 6%. Several explanations were given by the users of the EMB for the failure to reach near 100% success, one being the absence of an airway leading to the targeted nodule, another being the

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lesion extrinsic to an airway making adequate tissue sampling difficult. Wilson and Bartlett22 performed a larger EMB retrospective consecutive study in a community bronchoscopic unit using rapid on-site cytologic evaluation (ROSE) on 248 patients referred for diagnosis of peripheral lesions or mediastinal lymph nodes (71). Pneumothorax was reported in 1.2%, mainly because of the efforts to reach a diagnosis, which occurred in 70%. Mean size of targeted peripheral lung lesion (PLL) and lymph nodes was 2.1 1.4 (SD) cm and 1.8 0.9 (SD) cm, respectively. The mean follow-up period was 6 5 (SD) months. Fifty-one percent of PLLs were in the upper lobes; EMB 1 ROSE success was 96% for PLL (34 samples per patient with forceps and needle). Lymph nodes success was 94.3% (56 samples with needle biopsy). Overall diagnosis was made in 173 patients of the 248 (70%). The investigators used fluoroscopy to verify the location of the LG and biopsy forceps. Therapeutic uses of the EMB have also been described in the literature. In year 2006, Harms and colleagues23 applied EMB technology to therapeutic objectives and described the successful placement of a brachytherapy catheter after navigation to a peripheral, unresectable lung cancer. A second article showing the applicability of EMB in therapeutics was published by Kupelian and colleagues.24 They placed metallic markers for radiation therapy for a small early-stage lung cancer using the EMB system transbronchially. They concluded that the markers placed using this less invasive method remained stable within the tumors throughout the treatment duration without any incidence of pneumothorax as compared with the 8 out of 15 in whom the transthoracic route was used and who developed the complication. Anantham and colleagues25 reported their experience with placement of 39 fiducial markers in 9 patients. The success rate was 89% (8 of 9 patients). The mean number of fiducial markers placed in each patient was 4.9 1 1.0 (range, 4 to 6). No migration was encountered in 90% of the patients. Weiser and colleagues26 published their experience in diagnosis and in placing fiducial markers in and around the lesions to enable stereotactic radiosurgery. They used ROSE and in case of a negative result, they continued surgically for additional biopsies. Krimsky and colleagues27 used the EMB system to tattoo the subpleural area of the lung nodules after malignant diagnosis and to perform a therapeutic video-assisted thoracoscopic surgery. Electromagnetic navigation bronchoscopy using overlaid CT images is a safe procedure. It improves the diagnostic yield of the flexible bronchoscopy for peripheral lesions and also allows sampling of the mediastinal lymph nodes. Also, the system affords several other advantages: there is no additional radiation, and it has a short learning curve. It can also be used for fiducial marker placement for brachytherapy or stereotactic radiosurgery. It plays a complementary role to other modalities such as an ultrathin bronchoscopy or an EBUS.

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