Deformable 3D/3D CT-to-digital-tomosynthesis image registration in image-guided bronchoscopy interventions.

Traditional navigational bronchoscopy procedures rely on preprocedural computed tomography (CT) and intraoperative chest radiography and cone-beam CT (CBCT) to biopsy peripheral lung lesions. This navigational approach is challenging due to the projective nature of radiography, and the high radiation dose, long imaging time, and large footprints of CBCT. Digital tomosynthesis (DTS) is considered an attractive alternative combining the advantages of radiography and CBCT. Only the depth resolution cannot match a full CBCT image due to the limited angle acquisition. To address this issue, preoperative CT is a good auxiliary in guiding bronchoscopy interventions. Nevertheless, CT-to-body divergence caused by anatomic changes and respiratory motion, hinders the effective use of CT imaging. To mitigate CT-to-body divergence, we propose a novel deformable 3D/3D CT-to-DTS registration algorithm employing a multistage, multiresolution approach and using affine and elastic B-spline transformation models with bone and lung mask images. A multiresolution strategy with a Gaussian image pyramid and a multigrid strategy within the B-spline model are applied. The normalized correlation coefficient is included in the cost function for the affine model and a multimetric weighted cost function is used for the B-spline model, with weights determined heuristically. Tested on simulated and real patient bronchoscopy data, the algorithm yields promising results. Assessed qualitatively by visual inspection and quantitatively by computing the Dice coefficient (DC) and the average symmetric surface distance (ASSD), the algorithm achieves mean DC of 0.82±0.05 and 0.74±0.05, and mean ASSD of 0.65±0.29mm and 0.93±0.43mm for simulated and real data, respectively. This algorithm lays the groundwork for CT-aided intraoperative DTS imaging in image-guided bronchoscopy interventions with future studies focusing on automated metric weight setting.

"Tool-in-lesion" Accuracy of Galaxy System-A Robotic Electromagnetic Navigation BroncHoscopy With Integrated Tool-in-lesion-Tomosynthesis Technology: The MATCH Study.

BACKGROUND: The Galaxy System (Noah Medical) is a novel robotic endoluminal platform using electromagnetic navigation combined with integrated tomosynthesis technology and augmented fluoroscopy. It provides intraprocedural imaging to correct computerized tomography (CT) to body divergence and novel confirmation of tool-in-lesion (TIL). The primary aim of this study was to assess the TIL accuracy of the robotic bronchoscope with integrated digital tomosynthesis and augmented fluoroscopy. METHODS: Four operators conducted the experiment using 4 pigs. Each physician performed between 4 and 6 nodule biopsies for 20 simulated lung nodules with purple dye and a radio pacifier. Using Galaxy's "Tool-in-Lesion Tomography (TOMO+)" with augmented fluoroscopy, the physician navigated to the lung nodules, and a tool (needle) was placed into the lesion. TIL was defined by the needle in the lesion determined by cone-beam CT. RESULTS: The lung nodule's average size was 16.3 ± 0.97 mm and was predominantly in the lower lobes (65%). All 4 operators successfully navigated to all (100%) of the lesions in an average of 3 minutes and 39 seconds. The median number of tomosynthesis sweeps was 3 and augmented fluoroscopy was utilized in most cases (17/20 or 85%). TIL after the final TOMO sweep was 95% (19/20) and tool-touch-lesion was 5% (1/20). Biopsy yielding purple pigmentation was also 100% (20/20). CONCLUSION: The Galaxy System demonstrated successful digital TOMO confirmed TIL success in 95% (19/20) of lesions and tool-touch-lesion in 5% (1/20) as confirmed by cone-beam CT. Successful diagnostic yield was achieved in 100% (20/20) of lesions as confirmed by intralesional pigment acquisition.

A Cone Beam CT Bronchoscopy Study of the Ultrathin Cryoprobe for Biopsy of Peripheral Lung Lesions.

BACKGROUND: Compared with the standard cryoprobe, the novel ultrathin 1.1 mm cryoprobe (UTCP) has improved ergonomics, shape memory, and flexibility. The performance of UTCP has demonstrated promising results in several small trials. METHODS: In this single-center, retrospective review, we examine 200 (N=200) consecutive patients referred for cone beam CT bronchoscopic biopsy of peripheral lung lesions. We utilized an extended multimodality approach, including transbronchial needle aspirate, brush, traditional forces biopsies, UTCP biopsies, and BAL. We analyzed tool in lesion, tool touch lesion, center strike rates, and diagnostic yield. We assessed for molecular adequacy and analyzed safety. RESULTS: A total of 222 lesions were biopsied. We achieved a tool in lesion or tool touch lesion confirmation for all biopsy attempts (100%) and a center strike rate of 68%. AQuIRE diagnostic yield was 90%, with 60% malignant, 30% benign lung nodules, and 10% nondiagnostic. UTCP was diagnostic in 3.6 % of peripheral lung lesions biopsies when all other modalities were nondiagnostic; thus, raising our overall diagnostic yield from 86.4% to 90.1%. Our analysis demonstrates superior adequacy for molecular analysis for histologic samples (TBBX or UTCP) versus cytologic samples (FNA) ( P <0.001). Three patients (1.5%) had a pneumothorax, and 1 patient (0.5%) had moderate bleeding. CONCLUSION: UTCP was diagnostic in 3.6% of peripheral lung lesions when all other modalities were nondiagnostic. In the setting of CBCT guidance, UTCP has a similar safety profile to standard biopsy tools. Future trials are warranted to assess UTCP and its impact on peripheral lung lesion biopsies.

High Tidal Volume, High Positive End Expiratory Pressure and Apneic Breath Hold Strategies (Lung Navigation Ventilation Protocol) With Cone Beam Computed Tomography Bronchoscopic Biopsy of Peripheral Lung Lesions: Results in 100 Patients.

BACKGROUND: A dedicated anesthesia protocol for bronchoscopic lung biopsy-lung navigation ventilation protocol (LNVP)-specifically designed to mitigate atelectasis and reduce unnecessary respiratory motion, has been recently described. LNVP demonstrated significantly reduced dependent ground glass, sublobar/lobar atelectasis, and atelectasis obscuring target lesions compared with conventional ventilation. METHODS: In this retrospective, single-center study, we examine the impact of LNVP on 100 consecutive patients during peripheral lung lesion biopsy. We report the incidence of atelectasis using cone beam computed tomography imaging, observed ventilatory findings, anesthesia medications, and outcomes, including diagnostic yield, radiation exposure, and complications. RESULTS: Atelectasis was observed in a minority of subjects: ground glass opacity atelectasis was seen in 30 patients by reader 1 (28%) and in 18 patients by reader 2 (17%), with good agreement between readers (κ = 0.78). Sublobar/lobar atelectasis was observed in 23 patients by reader 1 and 26 patients by reader 2, also demonstrating good agreement (κ = 0.67). Atelectasis obscured target lesions in very few cases: 0 patients (0%, reader 1) and 3 patients (3%, reader 2). Diagnostic yield was 85.9% based on the AQuIRE definition. Pathology demonstrated 57 of 106 lesions (54%) were malignant, 34 lesions (32%) were benign, and 15 lesions (14%) were nondiagnostic. CONCLUSION: Cone beam computed tomography images confirmed low rates of atelectasis, high tool-in-lesion confirmation rate, and high diagnostic yield. LNVP has a similar safety profile to conventional bronchoscopy. Most patients will require intravenous fluid and vasopressor support. Further study of LNVP and other ventilation protocols are necessary to understand the impact of ventilation protocols on bronchoscopic peripheral lung biopsy.

NAVIGATE 24-Month Results: Electromagnetic Navigation Bronchoscopy for Pulmonary Lesions at 37 Centers in Europe and the United States.

INTRODUCTION: Electromagnetic navigation bronchoscopy (ENB) is a minimally invasive, image-guided approach to access lung lesions for biopsy or localization for treatment. However, no studies have reported prospective 24-month follow-up from a large, multinational, generalizable cohort. This study evaluated ENB safety, diagnostic yield, and usage patterns in an unrestricted, real-world observational design. METHODS: The NAVIGATE single-arm, pragmatic cohort study (NCT02410837) enrolled subjects at 37 academic and community sites in seven countries with prospective 24-month follow-up. Subjects underwent ENB using the superDimension navigation system versions 6.3 to 7.1. The prespecified primary end point was procedure-related pneumothorax requiring intervention or hospitalization. RESULTS: A total of 1388 subjects were enrolled for lung lesion biopsy (1329; 95.7%), fiducial marker placement (272; 19.6%), dye marking (23; 1.7%), or lymph node biopsy (36; 2.6%). Concurrent endobronchial ultrasound-guided staging occurred in 456 subjects. General anesthesia (78.2% overall, 56.6% Europe, 81.4% United States), radial endobronchial ultrasound (50.6%, 4.0%, 57.4%), fluoroscopy (85.0%, 41.7%, 91.0%), and rapid on-site evaluation use (61.7%, 17.3%, 68.5%) differed between regions. Pneumothorax and bronchopulmonary hemorrhage occurred in 4.7% and 2.7% of subjects, respectively (3.2% [primary end point] and 1.7% requiring intervention or hospitalization). Respiratory failure occurred in 0.6%. The diagnostic yield was 67.8% (range: 61.9%-70.7%; 55.2% Europe, 69.8% United States). Sensitivity for malignancy was 62.6%. Lung cancer clinical stage was I to II in 64.7% (55.3% Europe, 65.8% United States). CONCLUSIONS: Despite a heterogeneous cohort and regional differences in procedural techniques, ENB demonstrates low complications and a 67.8% diagnostic yield while allowing biopsy, staging, fiducial placement, and dye marking in a single procedure.

Lung Navigation Ventilation Protocol to Optimize Biopsy of Peripheral Lung Lesions.

BACKGROUND: Computed tomography-to-body divergence caused by respiratory motion, atelectasis, diaphragmatic motion and other factors is an obstacle to peripheral lung biopsies. We examined a conventional ventilation strategy versus a lung navigation ventilation protocol (LNVP) optimized for intraprocedural 3-dimensional image acquisition and bronchoscopic biopsy of peripheral lung nodules. METHODS: A retrospective, single center study was conducted in consecutive subjects with peripheral lung lesions measuring <30 mm. Effects of ventilation strategies including atelectasis and tool-in-lesion confirmation were assessed using cone beam computed tomography images. Diagnostic yield was also evaluated. Complications were assessed through 7 days. RESULTS: Fifty subjects were included (25 per group) with 27 nodules in the conventional group and 25 nodules in the LNVP group. Atelectasis was assessed by 2 blinded readers: [reader 1 (R1) and reader 2 (R2)]. Atelectasis was more prevalent in the conventional ventilation group, both for dependent atelectasis (R1: 64% and R2: 68% vs. R1: 36% and R2: 16%, P=0.00014) and sublobar/lobar atelectasis (R1: 48% and R2: 56% vs. R1: 20% and R2: 32%, P=0.01). Similarly, the target lesion was obscured due to atelectasis more often in the conventional ventilation group (R1: 36% and R2: 36% vs. R1: 4% and R2: 8%, P=0.01). Diagnostic yield was 70% for conventional ventilation and 92% for LNVP (P=0.08). CONCLUSION: LNVP demonstrated markedly reduced dependent and sublobar/lobar atelectasis and lesions either partially or completely obscured by atelectasis compared with conventional ventilation. Future prospective studies are necessary to understand the impact of protocolized ventilation strategies for bronchoscopic biopsy of peripheral lung lesions.

Anesthesia considerations to reduce motion and atelectasis during advanced guided bronchoscopy.

Partnership between anesthesia providers and proceduralists is essential to ensure patient safety and optimize outcomes. A renewed importance of this axiom has emerged in advanced bronchoscopy and interventional pulmonology. While anesthesia-induced atelectasis is common, it is not typically clinically significant. Advanced guided bronchoscopic biopsy is an exception in which anesthesia protocols substantially impact outcomes. Procedure success depends on careful ventilation to avoid excessive motion, reduce distortion causing computed tomography (CT)-to-body-divergence, stabilize dependent areas, and optimize breath-hold maneuvers to prevent atelectasis. Herein are anesthesia recommendations during guided bronchoscopy. An FiO2 of 0.6 to 0.8 is recommended for pre-oxygenation, maintained at the lowest tolerable level for the entire the procedure. Expeditious intubation (not rapid-sequence) with a larger endotracheal tube and non-depolarizing muscle relaxants are preferred. Positive end-expiratory pressure (PEEP) of up to 10-12 cm H2O and increased tidal volumes help to maintain optimal lung inflation, if tolerated by the patient as determined during recruitment. A breath-hold is required to reduce motion artifact during intraprocedural imaging (e.g., cone-beam CT, digital tomosynthesis), timed at the end of a normal tidal breath (peak inspiration) and held until pressures equilibrate and the imaging cycle is complete. Use of the adjustable pressure-limiting valve is critical to maintain the desired PEEP and reduce movement during breath-hold maneuvers. These measures will reduce atelectasis and CT-to-body divergence, minimize motion artifact, and provide clearer, more accurate images during guided bronchoscopy. Following these recommendations will facilitate a successful lung biopsy, potentially accelerating the time to treatment by avoiding additional biopsies. Application of these methods should be at the discretion of the anesthesiologist and the proceduralist; best medical judgement should be used in all cases to ensure the safety of the patient.

Augmented Fluoroscopy: A New and Novel Navigation Platform for Peripheral Bronchoscopy.

BACKGROUND: The diagnosis of lung nodules continues to be a challenge. Confirmed diagnosis allows appropriate treatment for cancers and allows avoidance of more invasive procedures for proven noncancers. Currently, available lung biopsy technologies each have their own limitations, which affect the ability to successfully navigate to a suspicious nodule and to collect a diagnostic sample. Additional advancements in endobronchial navigation, localization, and guided biopsy are needed to obtain higher rates of definitive diagnosis for lung nodules. METHODS: This is a prospective, multicenter study that assessed the localization success rate and diagnostic yield of bronchoscopies guided only by the LungVision platform. Physicians navigated to pulmonary nodules according to a proposed pathway and verified nodule location using radial endobronchial ultrasound before the biopsy. RESULTS: Fifty-five patients were enrolled in the study. Two patients had >1 nodule that was evaluated on the day of the procedure. During bronchoscopy, the nodule localization success rate was 93%. The overall diagnostic yield measured the day of the procedure, based on the immediate rapid on-site pathology report, was 75.4%. CONCLUSION: LungVision provides reliable navigation and ability to biopsy pulmonary nodules with an acceptable success rate. The platform demonstrates a high localization rate of pulmonary nodules.

Electromagnetic Navigation Bronchoscopy With Tomosynthesis-based Visualization and Positional Correction: Three-dimensional Accuracy as Confirmed by Cone-Beam Computed Tomography.

BACKGROUND: Electromagnetic navigation bronchoscopy (ENB) aids in lung lesion biopsy. However, anatomic divergence between the preprocedural computed tomography (CT) and the actual bronchial anatomy during the procedure can limit localization accuracy. An advanced ENB system has been designed to mitigate CT-to-body divergence using a tomosynthesis-based software algorithm that enhances nodule visibility and allows for intraprocedural local registration. MATERIALS AND METHODS: A prospective, 2-center study was conducted in subjects with single peripheral lung lesions ≥10 mm to assess localization accuracy of the superDimension navigation system with fluoroscopic navigation technology. Three-dimensional accuracy was confirmed by cone-beam computed tomography. Complications were assessed through 7 days. RESULTS: Fifty subjects were enrolled (25 per site). Lesions were <20 mm in 61.2% (30/49). A bronchus sign was present in 53.1% (26/49). Local registration was completed in 95.9% (47/49). Three-dimensional target overlap (primary endpoint) was achieved in 59.6% (28/47) and 83.0% (39/47) before and after location correction, respectively. Excluding subjects with unevaluable video files, target overlap was achieved 68.3% (28/41) and 95.1% (39/41), respectively. Malignant results were obtained in 53.1% (26/49) by rapid on-site evaluation and 61.2% (30/49) by final pathology of the ENB-aided sample. Diagnostic yield was not evaluated. Procedure-related complications were pneumothorax in 1 subject (no chest tube required) and scant hemoptysis in 3 subjects (no interventions required). CONCLUSION: ENB with tomosynthesis-based fluoroscopic navigation improved the 3-dimensional convergence between the virtual target and actual lung lesion as confirmed by cone-beam computed tomography. Future studies are necessary to understand the impact of this technology on diagnostic yield.

Erratum to virtual or reality: divergence between preprocedural computed tomography scans and lung anatomy during guided bronchoscopy.

[This corrects the article DOI: 10.21037/jtd.2020.01.35.].

Prognostic performance of proteomic testing in advanced non-small cell lung cancer: a systematic literature review and meta-analysis.

OBJECTIVE: Timely assessment of patient-specific prognosis is critical to oncology care involving a shared decision-making approach, but clinical prognostic factors traditionally used in NSCLC have limitations. We examine a proteomic test to address these limitations. METHODS: This study examines the prognostic performance of the VeriStrat blood-based proteomic test that measures the inflammatory disease state of patients with advanced NSCLC. A systematic literature review (SLR) was performed, yielding cohorts in which the hazard ratio (HR) was reported for overall survival (OS) of patients with VeriStrat Poor (VSPoor) test results versus VeriStrat Good (VSGood). A study-level meta-analysis of OS HRs was performed in subgroups defined by lines of therapy and treatment regimens. RESULTS: Twenty-four cohorts met SLR criteria. Meta-analyses in five subgroups (first-line platinum-based chemotherapy, second-line single-agent chemotherapy, first-line EGFR-tyrosine kinase inhibitor (TKI) therapy, and second- and higher-line TKI therapy, and best supportive care) resulted in statistically significant (p ≤ .001) summary effect sizes for OS HRs of 0.42, 0.54, 0.41, 0.52, and 0.50, respectively, indicating increased OS by about two-fold for patients who test VSGood. No significant heterogeneity was seen in any subgroup (p > .05). CONCLUSIONS: Advanced NSCLC patients classified VSGood have significantly longer OS than those classified VSPoor. The summary effect size for OS HRs around 0.4-0.5 indicates that the expected median survival of those with a VSGood classification is approximately 2-2.5 times as long as those with VSPoor. The robust prognostic performance of the VeriStrat test across various lines of therapy and treatment regimens has clinical implications for treatment shared decision-making and potential for novel treatment strategies.

Virtual or reality: divergence between preprocedural computed tomography scans and lung anatomy during guided bronchoscopy.

Guided bronchoscopy offers a minimally invasive and safe method for accessing indeterminate pulmonary nodules. However, all current guided bronchoscopy systems rely on a preprocedural computed tomography (CT) scan to create a virtual map of the patient's airways. Changes in lung anatomy between the preprocedural CT scan and the bronchoscopy procedure can lead to a divergence between the expected and actual location of the target lesion. Termed "CT-to-body divergence", this effect reduces diagnostic yield, adds time to the procedure, and can be challenging for the operator. The objective of this paper is to describe the concept of CT-to-body divergence, its contributing factors, and methods and technologies that might minimize its deleterious effects on diagnostic yield.

Cone beam CT imaging for bronchoscopy: a technical review.

Cone beam computed tomography (CBCT) is a well-established imaging modality with numerous proven applications across multiple clinical disciplines. More recently, CBCT has emerged as an important imaging tool for bronchoscopists, primarily used during transbronchial biopsy of peripheral pulmonary lesions (PPLS). For this application CBCT has proved useful in navigating devices to a target lesion, in confirming device tool-in-lesion, as well as during tissue acquisition. In addition, CBCT is poised to play an important role in trials evaluating bronchoscopic ablation by helping to determine the location of the ablative probe relative to the target lesion. Before adopting this technology, it is key for bronchoscopists to learn some basic concepts that will allow them to have a safer and more successful experience with CBCT. Hence, in the current manuscript, we will focus on both technical and practical aspects of CBCT imaging, ranging from systems considerations, image quality, radiation dose and dose-reduction strategies, procedure room set-up, and best practices for CBCT image acquisition.

Secondary carina Y-stent placement for post-lung-transplant bronchial stenosis.

BACKGROUND: Post-lung-transplant bronchial stenosis (TBS) may cause significant morbidity and mortality. Although often transiently relieved by balloon bronchoplasty, stents may be required for long-term airway patency. We report a series of lung transplant patients in whom a silicone Y-stent was placed at the secondary carina for long-standing relief of post-transplant-airway stenosis. METHODS: Six lung transplant patients received 10 silicone Y-stents in the secondary carina over the past 18 months for post-transplant-bronchial stenosis. All patients failed other interventional therapeutic procedures including balloon bronchoplasty and/or conventional stenting before secondary carina Y-stent placement. Patient data include 12 months' follow-up after Y-stent insertion. The number of procedures and the interval between procedures was examined before and after secondary carina silicone Y-stent placement. RESULTS: There was a significantly prolonged therapeutic effect accomplished in these patients after secondary carina Y-stent placement with the exception of 1 patient. When stents were tolerated by the patient, the mean number of procedures before secondary carina Y-stent insertion was 15.6, but only 4.8 after Y-stent insertion. The number of days between procedures was 24.5 days before the Y-stent insertion and 85.8 days after the Y-stent insertion. There were no complications in any patient during secondary carina Y-stent insertion. CONCLUSIONS: Secondary carina silicone Y-stent placement in TBS decreased the number of therapeutic procedures and provided longer-lasting results in most posttransplant patients who required multiple prior procedures for TBS.

A bronchoscopic oddity: nodular tracheobronchial amyloidosis.

Tracheobronchial amyloidosis is a rare disorder of unknown cause associated with the extracellular deposition of amyloid protein in a characteristic spatial structure of ß-sheet fibrils assembled into bundles. We present a case that represents the nodular form of tracheobronchial amyloidosis, which is the least common form of pulmonary amyloidosis with less than 20 cases reported so far. Patients with tracheobronchial amyloidosis may present with symptoms of dyspnea, localized wheezing, cough, hemoptysis, or recurrent pneumonias. The mainstay of the therapy is debridement of the symptomatic luminal obstruction with neodymium-doped yttrium aluminium garnet laser therapy. Other treatment strategies include airway stenting, external beam radiation therapy, bypass tracheostomy, or open surgical resection.