Integration of adjunct imaging for peripheral lung nodule sampling: a comprehensive review

Introduction

Lung cancer is the leading cause of cancer-related mortality worldwide. Diagnosis at an earlier stage is one way to improve the lung cancer-related morbidity and mortality. Lung cancer screening with an annual low dose computed tomography (CT) scan in high risk individuals has been proven to impart a mortality benefit, by increasing the proportion of cases diagnosed at an earlier stage. With the increased adoption of lung cancer screening, it is anticipated that physicians will be called upon to evaluate an increasing number of lung nodules and masses detected on screening scans. Similarly, there has also been an increase in incidentally detected lung nodules, on scans done for unrelated reasons. A significant number of these nodules will need to be biopsied to obtain a tissue diagnosis.

The two non-surgical techniques for biopsying lung nodules are CT-guided transthoracic or bronchoscopic transbronchial biopsies. While CT-guided transthoracic technique has a high diagnostic yield, it is also associated with an approximately 20% risk of pneumothorax. On the one hand while conventional bronchoscopic transbronchial biopsies are associated with a lower complication rate, their diagnostic yield is poor. Recent innovations in guided bronchoscopic modalities and integration of advanced intra-procedural imaging modalities can allow us to increase the diagnostic yield of transbronchial biopsies while retaining their favorable safety profile. Two main challenges need to be overcome for a successful transbronchial biopsy. Firstly, navigating through multiple generations of successively smaller airways to get in the vicinity of the lesion. Secondly, obtaining real-time confirmation that the lesion has been reached. The latter can also be used for fine movements, ensuring that the tool is adequately inserted in to the lesion. Navigational bronchoscopy platforms such as electromagnetic navigational bronchoscopy and robotic bronchoscopy assist with the first, while advanced imaging modalities such as radial endobronchial ultrasound (R-EBUS), 2-dimensional (2D) fluoroscopy and tomosynthesis, cone-beam CT, O-arm and augmented fluoroscopy, can help overcome the latter challenge. Our comprehensive and detailed review article highlights the unique aspects of different adjunct imaging modalities including nuances of its technical facets along with a summation of other characteristics such as size, footprint, cost, compatibility, and radiation exposure. We believe adding newer mobile modalities such as the GE-OEC arm and Siemens CIOS Spin is important to enable users to make an educated decision.

R-EBUS

R-EBUS probe is 1.4 mm in diameter (1) (Figure 1, Olympus Corporation, Tokyo, Japan). When advanced through the working channel of a bronchoscope into the lung, it leverages its unique mechanical properties to produce a 360-degree ultrasonographic view of the adjacent airway and lung parenchyma. The characteristic ultrasonographic images help operator differentiate normal lung parenchyma from lesional tissue (Figure 2) (2). Additionally, the ultrasonographic view can also help establish the relationship between the R-EBUS probe and the lesion. A concentric R-EBUS view, where the lesional tissue characteristics are seen in all quadrants of the ultrasonographic image, indicates that the R-EBUS probe is completely surrounded by the lesion. An eccentric R-EBUS view, where a circumferential lesional tissue view is not seen on the ultrasonographic image, indicates that the R-EBUS probe is adjacent to the lesion, as opposed to being embedded in the lesion. A concentric R-EBUS view indicates a higher probability of biopsy instruments capturing lesional tissue and has been consistently shown to be a marker of increased diagnostic yield (3). Once lesional tissue has been identified the R-EBUS probe is withdrawn, and biopsy instruments are deployed for tissue sampling.

Figure 1 Radial EBUS. (A) Radial EBUS probe. (B) Close-up view of the radial EBUS probe tip. EBUS, endobronchial ultrasound.

Figure 2 Radial EBUS imaging. (A) Radial EBUS view of concentric lesional tissue surrounded by normal lung. (B) Radial EBUS view of eccentric lesional tissue. Images courtesy of Dr. Hasnain Bawaadam. EBUS, endobronchial ultrasound.

The R-EBUS is compatible with and complements multiple bronchoscopic platforms. It can be used with flexible bronchoscopes (including slim bronchoscopes with working channels as small as 1.7 mm). When used with flexible bronchoscopes, it can also be potentially coupled with commercially available guide sheaths (4). Guide-sheaths are small plastic tubes that are advanced through the bronchoscope’s working channel, towards the lesions. The R-EBUS probe is then inserted through the guide sheath, allowing for adjustment of the guide-sheath positioning until the most satisfactory ultrasonographic view has been rendered. At this point the R-EBUS is withdrawn, leaving the guide sheath in place. The guide sheath acts as an extended working channel, a conduit allowing the passage of biopsy instruments. The guide sheath is thought to improve the probability of biopsy instruments sampling the same spot where the R-EBUS probe had earlier rendered the most satisfactory lesional tissue images. Fluoroscopy can better define the relationship between the lesion, guide sheath, R-EBUS probe and the biopsy instruments; thereby potentially improving the diagnostic yield and safety outcomes. R-EBUS is also compatible with navigational platforms such as electromagnetic navigational bronchoscopy and robotic bronchoscopy (5-7). When used with these systems, R-EBUS can not only confirm accurate navigation to the lesion but can also allow for fine tuning until a concentric (or as close as possible) view has been obtained. The latter is an independent marker of increased diagnostic yield.

In a meta-analysis of 57 studies (7,872 lesions), the diagnostic performance of R-EBUS was studied and demonstrated pooled diagnostic yield of 70.6% (8). Factors associated with increased diagnostic yield were: lesion size >2 cm, malignant etiology, presence of a CT-bronchus sign, and concentric R-EBUS view. The overall complication rate was only 2.8%. Some important limitations of R-EBUS are: unlike linear EBUS scope, the R-EBUS probe does not allow for the deployment of the biopsy instruments under simultaneous ultrasound guidance. Once the lesion has been visualized on the R-EBUS, the probe must be removed before advancing the biopsy instruments. Therefore, patient or operator-related movements of the bronchoscopic platform (with regards to the surrounding structures), during R-EBUS probe removal and insertion of the biopsy instruments, can cause the latter to miss the lesion. Secondly, various factors such as blood clots in the airways, secretions, and atelectasis, can lead to false-positive findings (9). Thirdly, its use can be challenging for lesions that are neither inside the airway nor adjacent. In these cases, the operator first has to create a pathway or a tunnel through the airway wall using a needle, before the R-EBUS probe can be advanced through the airway wall towards the lesion. Lastly, there is a learning curve associated with the operation of R-EBUS probe. Moreover, it is a delicate instrument and must be handled with care during operation and cleaning, to minimize the chances of malfunction.

In summary, R-EBUS is a versatile, widely available tool that not only increases the diagnostic yield of conventional bronchoscopy but can also be easily coupled with advanced navigational platforms such as robotic bronchoscopy. There is a learning curve associated with its use, and the operator must be cognizant of its limitations to minimize the risk of false-negative results.

2D fluoroscopy and IllumiSite

This portion of the review article delves into the intricacies of using Medtronic IllumiSite^® Fluoroscopic Navigation System (Figure 3A,3B) for peripheral lung nodule biopsy. It combines electromagnetic navigation, augmented fluoroscopy and fluoroscopic sweep which contributes to the precision and safety of peripheral lung nodule biopsies. The augmented fluoroscopy is attained using a fluoroscopic sweep (Figure 3C) and can utilize R-EBUS (Figure 3D), enabling precise nodule localization while improving biopsy accuracy (10,11).

Figure 3 IllumiSite^® Navigation Platform System. (A) IllumiSite^® Navigation Platform. (B) Target visible as green ball on virtual peripheral navigation view. (C) Fluoroscopic sweep being performed with the benefit of minimizing CT-body divergence. (D) R-EBUS image demonstrating lesional tissue presence in 360-degree plane. CT, computed tomography; R-EBUS, radial endobronchial ultrasound.

The IllumiSite^® system helps with nodule localization and biopsy safety by employing augmented fluoroscopy. The real-time overlay of the pre-operative three-dimensional (3D) model onto the 2D fluoroscopic imaging forms a synchronized visual aid, crucial for navigating the bronchial tree and enhancing the diagnostic yield of biopsies (12,13).

The procedural execution of the IllumiSite^® Fluoroscopic Navigation System comprises two detailed phases. The ‘Planning’ phase calls for the analysis of the patient’s CT scans to generate a personalized 3D model of the lungs, which acts as a roadmap for the physicians. The model helps chart the safest and most efficient route to the nodule, maximizing procedural accuracy and patient safety.

The ‘Execution’ phase sees the bronchoscope, equipped with the IllumiSite^® system, being introduced into the patient’s airway. As the bronchoscope advances towards the nodule following the pre-planned pathway, the augmented fluoroscopy provides dynamic imaging of the bronchial anatomy. The synchronized overlay of the 3D model on the 2D fluoroscopic imaging, in real-time, significantly improves the accuracy of nodule localization and allows for immediate procedural adjustments. A vital step in the procedure is the fluoroscopic sweep. This real-time fluoroscopic screening from multiple angles helps in localizing the nodule and adjusting the pathway, especially when accessing complex or hard-to-reach areas of the lung (13,14).

An essential procedural step is the integration of R-EBUS before biopsy. A R-EBUS probe is inserted through the bronchoscope’s working channel. It provides a 360-degree ultrasound image (Figure 3C), which in combination with the augmented fluoroscopic imaging, offers dual confirmation of the nodule’s exact location (15). Upon confirmation, biopsy tools are introduced, and tissue samples are obtained from the nodule under fluoroscopic guidance (16).

The implications of integrating augmented fluoroscopy in the IllumiSite^® system are profound. Not only does it enhance navigation through the bronchial tree and the precision of nodule localization, but it also minimizes complications linked to bronchoscopy and permits real-time procedural adjustments. By boosting diagnostic yields, this advanced system holds the potential to for earlier detection and intervention in lung cancer which subsequently would translate into improved patient prognosis (5).

The IllumiSite^® Fluoroscopic Navigation System is an innovative technique for the biopsy of peripheral lung nodules, which embodies the fusion of augmented fluoroscopy and R-EBUS. It offers an enriched understanding of lung anatomy and improved precision in nodule localization, which result in safer and more effective biopsies. The integration of electromagnetic navigation, augmented fluoroscopy, and the fluoroscopic sweep in the IllumiSite^® Navigation System is poised to transform bronchoscopic procedures, offering better outcomes in lung cancer diagnosis and staging.

Mobile cone beam computed tomography (m-CBCT) unit

m-CBCT provide intraoperative CT imaging in mobile form. There are atleast two mobile 3D fluoroscopy systems that are currently approved for use in the pulmonary space: The CIOS Spin and the GE-OEC C-arm. The CIOS Spin (Siemens Medical Solutions, Malvern, PA, USA) is a hybrid mobile 2D/3D C-arm platform that can be easily moved in and out of bronchoscopy suites and shared amongst different specialties (Figure 4). It relies on complementary metal-oxide-semiconductor detector technology. It possesses a 16 cm³ field of view (FOV). This produces a matrix size of 512×512×512 pixels (or more appropriately, 512 “voxels” which are 3D pixels). What makes this system unique is the ability to provide 3D imaging in a mobile platform. It has several distinctive features for the 3D imaging component: with a spin time of 30 seconds, the data is acquired from a 196-degree isocentric cone beam CT scan which takes up to 400 2D images to build a 3D dataset. The computer then compiles this data into the matrix described above and turns it into a CT-like image with simultaneous display of three projections (transversal, coronal, and sagittal) for immediate, intraoperative review (Figure 5A,5B). The integrative version of CIOS Spin and the Ion Endoluminal System can perform intraoperative corrections based on acquired 3D images. This allows the user to make fine adjustments and adjust for CT to body divergence while updating biopsy target (17).

Figure 4 Image of 3D mobile cone beam unit—CIOS Spin (Siemens Medical Solutions, Malvern, PA, USA) around a compatible table that allows for the spin around the patient during procedure. 3D, three dimensional.

Figure 5 Intra-procedural CIOS Spin. (A) Intra-procedural CIOS Spin view. The Siemens CIOS Spin system is a hybrid mobile 2D/3-dimensional C-arm system. Left, the viewing console houses two screens that can display 2D fluoroscopic images and 3-dimensional reconstructed images. Right, the ion system control panel shows transferred images from the CIOS Spin that allows the proceduralist to make both catheter and target adjustments based on needle to lesion relationship after C-arm spin acquired 3-dimensional reconstructed-images. (B) Intra-procedural CIOS Spin images. Right upper lobe nodule in a 74-year-old woman with coronal (left), sagittal (middle) and axial (right) images generated by the 3-dimensional component of the CIOS Spin showing the catheter-needle within target lesion. 2D, 2-dimensional.

OEC 3D imaging system from GE Healthcare (GE HealthCare Technologies Inc., Chicago, USA) is the other mobile CBCT released globally and cleared by US FDA (K203346) for a wide range of intraoperative imaging needs including imaging of pulmonary lesions. OEC 3D imaging system is a precise and efficient 2D/3D C-arm featuring a lightweight isocentric carbon fiber-based gantry and performing 200 degrees of orbital sweep within 30 seconds. OEC 3D has a large 3D FOV of 19 cm × 19 cm × 19 cm and provides high resolution 512×512×512 voxel DICOM 3D images. This mobile CBCT system allows users to select 200 or 400 projections (X-ray shots) to complete the orbital spin which creates CT-like images (in ~30 seconds) and display on a volume viewer with five image perspectives. The five image perspectives include the 3-multiplanar (axial, sagittal & coronal) views along with the maximum intensity projection (MIP) as well as a volume rendering (VR) view. The MIP view resembles a 3D radiograph, and the VR helps clearly visualize the biopsy catheters as well as the tool tip (Figure 6). The volume viewer also allows the pulmonologist to directly interact through the touch control interface to select a “lung” preset & “multi-oblique” mode for precise localization of tool-in-lesion confirmation or to mitigate CT to body divergence during biopsy procedures (18).

Figure 6 GE OEC-C arm imaging system. (A) Image of the GE OEC-C arm system unit with viewing console for proceduralist to view 3-dimensional images acquired during the spin intraoperatively. (B) The viewing console that displays the 3-dimensional reconstructed images showing the catheter-needle within target lesion (images reproduced with permission from GE HealthCare Technologies Inc., Chicago, USA).

Both systems deliver high quality CBCT images at a very low dose of radiation and have workstations that can be plugged into standard wall outlets of conventional bronchoscopy rooms (18-20). The footprint is similar to most conventional C-arm fluoroscopy systems and have easy maneuverability in space constrained endobronchial suites.

The combination of mobile CBCT with the newer commercially available navigational and robotic systems has been described in several small case series and case studies, clearly demonstrating that the improvement in diagnostic yields would not have occurred without this image guidance, which helps correct the CT-to-body divergence (21-25).

In a pioneering study by Dr. Reisenauer and team at Mayo in 2022, the integration of the CIOS m-CBCT (CIOS Spin, Siemens Healthineers) with shape-sensing robotic-assisted bronchoscopy (SSRAB) (Ion Endoluminal System, Intuitive Surgical) was examined (20). This initial, forward-looking study aimed to evaluate m-CBCT’s effectiveness in confirming tool placement within lesions, measuring CT-to-body discrepancies and determining diagnostic accuracy along with radiation levels. Correspondingly, research by Sadoughi et al. brought to light the efficacy of combining ultrathin bronchoscopy, R-EBUS, 2D fluoroscopy, and 3D imaging with the mobile CIOS unit for diagnosing small peripheral lung nodules (26). These encouraging findings underscore the potential of new mobile hybrid 2D/3D C-arm fluoroscopy systems in enhancing airway navigation and providing real-time, multi-dimensional verification of biopsy tools at the targeted lesions.

Conventional-ceiling-mounted cone beam computed tomography (c-CBCT) unit

CBCT is a newer CT modality widely used in interventional radiology, neurosurgery, vascular surgery, interventional cardiology and more recently has emerged as a valuable tool for secondary confirmation in the bronchoscopic biopsy of peripheral pulmonary nodules (PPNs) (21). CBCT provides real-time multiplanar confirmation with 3D reconstruction to confirm accurate biopsy tool position within the target lesion. CBCT is compact and can be mounted to the ceiling on a moving C-arm, allowing for efficient use of space in the procedure room and eliminating the need for additional floor or table-mounted equipment (Figure 7). Conveniently, many interventional radiology operating rooms are already equipped with c-CBCT. C-arm CBCT employs a flat panel detector system made from cesium iodide scintillators to produce CT-like cross sectional multiplanar and 3D images. Image acquisition involves the projection of a cone-shaped (wide collimation) X-ray beam from the X-ray source onto the flat panel detector. CBCT performs volumetric data acquisition in a single rotation of the source and detector by rotating the C-arm approximately 200 degrees around the patient in a circular trajectory and acquiring a series of 2D X-ray projection images at specific angular intervals, with the patient remaining stationary during the examination. Image acquisition times range from 4–10 seconds and cover a volume of 24×24×18.5 cm³ resulting in an isotropic volumetric dataset of 0.5 mm voxels in a 512×512 matrix. These reconstructed images can be reformatted into coronal, sagittal, and axial views for reviewing on a separate work station (Figure 8) (27). CBCT can also provide standard fluoroscopy images and identify lesions not visible on fluoroscopy, such as ground glass opacities or cystic lesions. Common trade names for CBCT include DynaCT (Siemens Healthineers, Germany), Innova CT (GE Healthcare, USA), and XperCT (Philips Healthcare, The Netherlands).

Figure 7 Image of ceiling-mounted CBCT with robotic bronchoscopy in catheterization laboratory. CBCT, cone beam computed tomography.

Figure 8 Cone beam CT images providing real-time 3D confirmation of biopsy tool in target lung lesion. CT, computed tomography; 3D, three dimensional.

Radiation dose during CBCT-guided bronchoscopy primarily depends upon the number of CBCT acquisitions performed during each procedure, which has been reported to range from 1–3 per patient (27,28). Radiation dose for a single CBCT is related to the number of projection images acquired and the dose per projection image. Dose reduction techniques such as collimation can significantly reduce radiation exposure, allowing for repeated CBCT imaging. Comparing radiation exposure among studies is challenging due to variable reporting methods, but it appears CBCT radiation dosage is similar to those of low-dose CT done as part of the National Lung Screening Trial (28).

Several studies have highlighted the advantages of c-CBCT in the bronchoscopic biopsy of PPNs. When used with electromagnetic navigation bronchoscopy (ENB) and R-EBUS, CBCT improved the diagnostic yield by 23% (ENB-CBCT 74.5% vs. ENB 51.6%) (24). The first publication using CBCT with shape-sensing robotic navigation bronchoscopy showed an overall diagnostic yield of 86% (20). A larger single-center study using CBCT with shape-sensing robotic navigation bronchoscopy and R-EBUS resulted in an overall diagnostic yield of 91.4% (29). A systematic review and meta-analysis of 95 studies analyzing the diagnostic yield of navigation bronchoscopy for the diagnosis of PPNs showed in a subgroup analysis based on navigation technique that the diagnostic yield was highest at 77.3% when CBCT was used (30).

A new 3D imaging and navigation platform, the Philips Lung suite, further provides augmented fluoroscopy for c-CBCT. After the initial CBCT spin to confirm biopsy tool position, the target is manually outlined by the operator using the Lung suite software during a process known as segmentation. The updated 3D target segmentation is then visualized in an overlay with live fluoroscopy images (Figure 9). This enables the operator to adjust biopsy tool position with the 3D target overlayed on live fluoroscopy in multiple fluoroscopic planes, reducing the need for repeat CBCT spins. In a single center retrospective study, intraprocedural CBCT with augmented fluoroscopy was shown to be an effective method of secondary confirmation for ENB with 83.7% diagnostic yield (31). These findings underscore the clinical utility of c-CBCT in improving the diagnostic yield of bronchoscopic PPN biopsies. The ability of CBCT to confirm biopsy tool position improves navigation success and enables selectively targeted biopsies of lesions not easily visible on fluoroscopy.

Figure 9 Cone beam CT with augmented fluoroscopy. (A-C) 3D target segmentation using CBCT images. Note navigation bronchoscope (red arrow) distance from target lesion (blue dotted segmentation). (D) 3D target (blue) overlayed on live fluoroscopy with biopsy tool in target after adjustments of bronchoscope position were made. CT, computed tomography; CBCT, cone beam computed tomography; 3D, three dimensional.

These findings underscore the clinical utility of c-CBCT in improving the diagnostic yield of bronchoscopic PPN biopsies. The ability of CBCT to confirm biopsy tool position improves navigation success and enables selectively targeted biopsies of lesions not easily visible on fluoroscopy.

O-arm CT (OACT)

The O-arm^TM O2 Imaging System (Medtronic) is another intraoperative imaging modality increasingly used for peripheral bronchoscopy. OACT is a mobile X-ray system designed for 2D and 3D imaging system traditionally used for spinal, orthopedic trauma, and neurosurgical procedures. Given its wider application, it may be more accessible and affordable in certain healthcare systems. The system consists of a gantry that can be opened into a C-shape to allow for positioning and travel. Once in position, it can be closed to form an O-shaped gantry which can still be adjusted in a craniocaudal direction. The system can provide 2D fluoroscopic imaging using a flat panel detector. Due to the closed gantry, the panel can acquire multiple projection views over 360 degrees to generate 3D imaging. The system does have presets for standard and high definition and can be collimated based on patient thickness. The tube voltage and current can be further adjusted manually to reduce radiation exposure and based on imaging needs.

During the procedure, the patient is intubated and positioned in a supine position with the arms tucked to reduce the overall footprint. With the gantry in an open position (in C shape), the O-arm is moved into position over the patient. The gantry is closed to completly encircle the patient (Figure 10A). Before registering with the navigation platform, we would typically perform a scout 2D fluoroscopy image in anterior-posterior (AP) and lateral views to isocenter the area of interest. This minimizes the need for any movement that may interfere with the registration later in the case. During the navigation process and deployment of radial-EBUS or biopsy tools, the 2D fluoroscopy images can be taken as needed. The flat panel detector can be moved in a 360-degree fashion to obtain images at any desired angle. Moreover, the 2D images can be connected to the navigation platform to use any software integration with the navigation platform like any other C arm. Once the catheter or probe is navigated to the target lesion, a 3D spin can be performed to confirm the tool in lesion or adjust the catheter position as desired (Figure 10B). A breath-hold maneuver is advisable to reduce interference and improve image acquisition. Upon completion of the procedure, the gantry can be reopened and removed.

Figure 10 Medtronic O-arm imaging system. (A) The room set-up with O-arm CT. The gantry is in closed position with the robotic bronchoscopy docked. (B) 3D reconstruction images of O-arm CT images demonstrating tool-in-lesion. CT, computed tomography.

The OACT has been reported for intraoperative lung nodule localization with video-assisted thoracoscopy (32). In recent years, a multicenter case series (33) demonstrated the feasibility of use with an electromagnetic navigation platform. In this series successful tool in lesion confirmation was obtained in 6/6 cases; however, the overall diagnostic yield was only at 33%. A high tool in lesion confirmation (97%) using the O-arm imaging with shape-sensing robotic bronchoscopy was also reported in a retrospective study (34). Overall diagnostic yield was similar to other navigation studies at about 77%. The diagnostic yield rose to 86% if pathology with suspicious cells were included in the diagnostic yield definition. The average number of spins was two with radiation dose exposure at 7.2 (3.9–14.3) mSv. The subgroup analysis of the last 15 cases showed that after optimization of the protocol, this was reduced to 5.3 (2.2–5.4) mSv during the last 15 cases.

The above studies demonstrate the feasibility of using OACT for real-time imaging to help adjust for CT to body divergence and tool in lesion confirmation. The reported average effective radiation dose per 3D spin is slightly higher than other reported Cone beam imaging, though further optimization of the protocol can minimize this to as low as 3.3 mSv per spin on low dose mode with minimal effect on imaging quality. It does carry a significant footprint, but owing to its mobile nature and accessibility, it remains a very useful alternative intraoperative platform for peripheral bronchoscopy.

Augmented fluoroscopy—BodyVision

LungVision^TM (BodyVision Medical Ltd., Ramat Ha Sharon, Israel) uses artificial intelligence (AI) to augment images obtained via intra-operative C-arm based tomography (CABT) to offer local registration of the peripheral target lesion and its relationship to a previously performed CT scan. With this platform, digital tomosynthesis is conducted by performing a sweep arc with a conventional C-arm fluoroscopy around a patient’s chest with continuous image acquisition to gather volumetric data by capturing multiple projections from different angles. The AI integrates these fluoroscopic images with pre-procedural CT images to create augmented images in three-dimensions via machine learning. The reconstructed images offer a more detailed, precise, and accurate view of the targeted area.

Throughout the procedure, the AI can constantly adjust for CT to body diversion (CTBD) by updating the position of the target lesion so that the platform can provide real-time localization of the bronchoscope and tools in relation to the target lesion in three dimensions (35-38). The resultant generated augmented images include an overlay of both the pathway to the lesion and the lesion itself on the standard fluoroscopic screen (28,39). The updated position of the target lesion is maintained even as the C-arm is moved in different angulations and with digital zooming, without losing the augmented fluoroscopic overlay. With this, the operator can make fine adjustments to the bronchoscope to better align biopsy instruments with the target lesion, thus potentially increasing localization success and diagnostic yield (36,40). Additionally, the continuous positional data allows for multi-directional sampling and more thorough biopsy (11,41). Of note, LungVision^TM can be used as an advanced imaging confirmation tool, a stand-alone navigation platform, or combined with another navigation or robotic platform.

Prior to starting the procedure, a pre-procedural CT scan with slice thickness of 1.5 mm is imported into proprietary planning software to reconstruct the tracheobronchial tree and identify the target lesion. A location board with radio-opaque markers is placed on the procedure table underneath the patient. After the patient is anesthetized, if another navigational platform is used in combination, it is docked to the patient. Fluoroscopic registration begins by obtaining a series of fluoroscopic images with the patient at isocenter, centered on patient’s main carina, to correlate the pre-procedural CT scan with the patient’s position during the procedure. While the images are being processed, inspection bronchoscopy and registration of navigation bronchoscopy equipment can ensue. Once CT-body registration is completed, an initial CABT spin is performed with the target lesion at isocenter (typically −50° to +50°). During this step, it is important to ensure that the spin is performed at a steady pace and the clarity of the radio-opaque markers on the fluoroscopy screen is maintained during the spin. Once the images from the spin are reconstructed, the target nodule is segmented and projected on the standard fluoroscopy screen. This overlay is maintained in 3D during every movement of the C-arm and the table.

Once navigation to the nodule is completed, another fluoroscopy spin is performed with the nodule at isocenter. This helps define the 3D relationship of the nodule with the bronchoscope and sampling tools. Fine adjustments to the bronchoscope and sampling tools are made to allow for needle penetration into the lesion via the airway wall under real-time guidance and confirmation. The localization of the target lesion can also be confirmed with R-EBUS. If needed, another spin can be performed to ensure the presence of “tool-in-lesion” articulation. Once the tool location and projected trajectory is confirmed, tissue sampling is repeated under augmented fluoroscopy guidance (Figure 11).

Figure 11 LungVision^TM imaging system. (A) Interface on the LungVision^TM platform demonstrating the updated location of the target lesion after a CABT spin. (B) Augmented fluoroscopic images with the target lesion highlighted (yellow outline) on the standard fluoroscopic screen. (C) Radial EBUS image showing an eccentric view of the target lesion while using the LungVision^TM platform. (D) Rapid on-site evaluation confirms the presence of malignant cells. Courtesy of Ajay Wagh at the University of Chicago, Chicago, IL, USA. CABT, C-arm based tomography; EBUS, endobronchial ultrasound.

A single-center study using LungVision^TM to navigate and sample pulmonary lesions with intra-operative co-relation using CBCT in 51 patients demonstrated lesion localization success of 96.1% with the platform. The average distance between lesion localization shown by LungVision^TM augmented fluoroscopy and location measured by CBCT was 5.9 mm (range, 2.1–10.0 mm). The diagnostic yield at the index procedure was 78.4%. Diagnostic accuracy assessed at 12 months follow-up was 88.2%. Average CTBD was 14.5 mm (range, 2.6–33.0 mm) from pre-procedural CT to intra-procedural CBCT images. The median lesion diameter was 18.0 mm (range, 7.0–48.0 mm) (35). In a prospective, multi-center study, Cicenia et al. used the LungVision^TM augmented fluoroscopy platform to navigate to target lesions in 55 patients and demonstrated localization success of 93%, with an overall diagnostic yield of 75.4% based on rapid on-site pathology report (36).

In a retrospective study, Aboudara et al. demonstrated a 25% absolute increase in diagnostic yield (79%) when using the superDimension iLogic 7.2 ENB platform (superDimension, Medtronic) combined with fluoroscopic tomosynthesis (F-ENB) when compared with using standard navigation with the superDimension iLogic 7.2 ENB platform alone (54%) (P<0.05). The median divergence was 12 mm in this study (37). A case report described a combined modality approach of using Monarch^TM robotic bronchoscopy platform for navigation and the LungVision^TM platform image guidance and confirmation of tools during peripheral lung nodule sampling (42). Another retrospective study which involved 45 patients undergoing navigation bronchoscopy with the Monarch^TM robotic platform, R-EBUS, and the LungVision^TM system for intra-procedural real-time guidance yielded an immediate diagnostic yield of 84% and final diagnostic accuracy of 91% (43). Pertzov et al. reported overall diagnostic yield of 81.8% and 72.2% for lesions smaller than 20 mm, when using the LungVision^TM platform for peripheral pulmonary lesion sampling. Median lesion size was 25 mm (range, 18–28 mm) (44).

Given the current costs and limited access to CBCT, alternative advanced imaging technologies such as augmented fluoroscopy with the integration of AI may prove to be a more economical option while providing similar success with lesion confirmation and combating the effects of CTBD. Additionally, the smaller footprint of this technology may make it more easily incorporated with another navigational platform in the bronchoscopy suite.

Conclusions

In summary, the above article not only reviews multiple modalities of augmented imaging that are now commercially available to enhance the diagnostic yield during navigation bronchoscopy, but also examines the factors influencing the selection of these systems by institutions, including needs assessment, capital availability, operational space, potential for co-sharing, and predicted utility (Table 1).

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the Guest Editors (Jonathan Kurman and Bryan S. Benn) for the series “Diagnostic & Therapeutic Bronchoscopy” published in AME Medical Journal. The article has undergone external peer review.

Peer Review File: Available at https://amj.amegroups.com/article/view/10.21037/amj-23-119/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://amj.amegroups.com/article/view/10.21037/amj-23-119/coif). The series “Diagnostic & Therapeutic Bronchoscopy” was commissioned by the editorial office without any funding or sponsorship. H.B. is a consultant for Intuitive Surgical. E.H. is a consultant for Biodesix, Olympus and Intuitive Surgical. U.G. is a consultant for Noah Medical. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All clinical procedures described in this study were performed in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patients/participants for the publication of this article and accompanying images.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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