Martin L. Mayse

FIDUCIAL-BASED TRANSLATIONAL LOCALIZATION ACCURACY OF ELECTROMAGNETIC TRACKING SYSTEM AND ON-BOARD KILOVOLTAGE IMAGING SYSTEM

PURPOSE The Calypso medical four-dimensional localization system uses AC electromagnetics, which do not require ionizing radiation, for accurate, real-time tumor tracking. This investigation compared the static and dynamic tracking accuracy of this system to that of an on-board imaging kilovoltage X-ray system for concurrent use of the two systems. METHODS AND MATERIALS The localization accuracies of a kilovoltage imaging system and a continuous electromagnetic tracking system were compared. Using an in-house developed four-dimensional stage, quality-assurance fixture containing three radiofrequency transponders was positioned at a series of static locations and then moved through the ellipsoidal and nonuniform continuous paths. The transponder positions were tracked concurrently by the Calypso system. For static localization, the transponders were localized using portal images and digitally reconstructed radiographs by commercial matching software. For dynamic localization, the transponders were fluoroscopically imaged, and their positions were determined retrospectively using custom-written image processing programs. The localization data sets were synchronized with and compared to the known quality assurance fixture positions. The experiment was repeated to retrospectively track three transponders implanted in a canine lung. RESULTS The root mean square error of the on-board imaging and Calypso systems was 0.1 cm and 0.0 cm, respectively, for static localization, 0.22 mm and 0.33 mm for dynamic phantom positioning, and 0.42 mm for the canine study. CONCLUSION The results showed that both localization systems provide submillimeter accuracy. The Calypso and on-board imaging tracking systems offer distinct sets of advantages and, given their compatibility, patients could benefit from the complementary nature of the two systems when used concurrently.

Radial Probe Endobronchial Ultrasound for Peripheral Pulmonary Lesions. A 5-Year Institutional Experience

RATIONALE Technological advances have improved the ability of bronchoscopists to access peripheral pulmonary lesions for tissue sampling. Radial probe endobronchial ultrasound (EBUS) provides real-time feedback to guide biopsies of peripheral lesions, thereby potentially improving diagnostic yield over conventional bronchoscopy. OBJECTIVES We assessed the overall diagnostic yield of peripheral bronchoscopy using radial probe EBUS for peripheral pulmonary lesions, as well as factors that might influence the diagnostic yield, such as radial ultrasound view, lesion size, and ability to locate the peripheral lesion. METHODS We conducted a retrospective review of peripheral bronchoscopy cases in which radial probe EBUS was utilized to diagnose peripheral pulmonary lesions at a tertiary care university hospital. MEASUREMENTS AND MAIN RESULTS Our study cohort comprised 496 patients who underwent bronchoscopies between January 2008 and December 2012 for the diagnosis of peripheral pulmonary lesions. Radial probe EBUS was used alone for diagnostic purposes in 467 patients. A diagnosis was made on that basis in 321 (69%) of 467 patients. A diagnosis was obtained for 83 of 144 (58%) of nodules 1-2 cm in diameter, 99 of 137 (72%) of nodules 2.1-3 cm, 54 of 70 (77%) of nodules 3.1-4 cm, 41 of 47 (87%) of nodules 4.1-5 cm, and 35 of 40 (88%) of nodules larger than 5.1 cm. Of all 467 nodules, 446 (96%) were successfully identified using radial probe EBUS. When the radial probe position was within the target lesion, the diagnostic yield was 84% compared with 48% when the probe was positioned adjacent to the lesion. CONCLUSIONS Radial probe EBUS can be used to guide biopsy during peripheral bronchoscopy. This technique provides real-time ultrasound-based confirmation of target lesion localization prior to biopsy. Using radial probe EBUS, the vast majority of peripheral pulmonary nodules can be identified. Radial EBUS probe position relative to the target lesion significantly affects the diagnostic yield.

Safety of investigative bronchoscopy in the Severe Asthma Research Program.

BACKGROUND Investigative bronchoscopy was performed in a subset of participants in the Severe Asthma Research Program to gain insights into the pathobiology of severe disease. We evaluated the safety aspects of this procedure in this cohort with specific focus on patients with severe asthma. OBJECTIVE To evaluate prospectively changes in lung function and the frequency of adverse events related to investigative bronchoscopy. METHODS Bronchoscopy was performed by using a common manual of procedures. A subset of very severe asthma was defined by severe airflow obstruction, chronic oral corticosteroid use, and recent asthma exacerbations. Subjects were monitored for changes in lung function and contacted by telephone for 3 days after the procedure. RESULTS A total of 436 subjects underwent bronchoscopy (97 normal, 196 not severe, 102 severe, and 41 very severe asthma). Nine subjects were evaluated in hospital settings after bronchoscopy; 7 of these were respiratory-related events. Recent emergency department visits, chronic oral corticosteroid use, and a history of pneumonia were more frequent in subjects who had asthma exacerbations after bronchoscopy. The fall in FEV₁ after bronchoscopy was similar in the severe and milder asthma groups. Prebronchodilator FEV₁ was the strongest predictor of change in FEV₁ after bronchoscopy with larger decreases observed in subjects with better lung function. CONCLUSION Bronchoscopy in subjects with severe asthma was well tolerated. Asthma exacerbations were rare, and reduction in pulmonary function after the procedure was similar to that in subjects with less severe asthma. With proper precautions, investigative bronchoscopy can be performed safely in severe asthma.

Randomized Trial of Pleural Fluid Drainage Frequency in Patients with Malignant Pleural Effusions. The ASAP Trial

Rationale: Patients with malignant pleural effusions have significant dyspnea and shortened life expectancy. Indwelling pleural catheters allow patients to drain pleural fluid at home and can lead to autopleurodesis. The optimal drainage frequency to achieve autopleurodesis and freedom from catheter has not been determined. Objectives: To determine whether an aggressive daily drainage strategy is superior to the current standard every other day drainage of pleural fluid in achieving autopleurodesis. Methods: Patients were randomized to either an aggressive drainage (daily drainage; n = 73) or standard drainage (every other day drainage; n = 76) of pleural fluid via a tunneled pleural catheter. Measurements and Main Results: The primary outcome was the incidence of autopleurodesis following the placement of the indwelling pleural catheters. The rate of autopleurodesis, defined as complete or partial response based on symptomatic and radiographic changes, was greater in the aggressive drainage arm than the standard drainage arm (47% vs. 24%, respectively; P = 0.003). Median time to autopleurodesis was shorter in the aggressive arm (54 d; 95% confidence interval, 34‐83) as compared with the standard arm (90 d; 95% confidence interval, 70 to nonestimable). Rate of adverse events, quality of life, and patient satisfaction were not significantly different between the two arms. Conclusions: Among patients with malignant pleural effusion, daily drainage of pleural fluid via an indwelling pleural catheter led to a higher rate of autopleurodesis and faster time to liberty from catheter. Clinical trial registered with www.clinicaltrials.gov (NCT 00978939).

Bronchoscopic Implantation of a Novel Wireless Electromagnetic Transponder in the Canine Lung: A Feasibility Study

PURPOSE The success of targeted radiation therapy for lung cancer treatment is limited by tumor motion during breathing. A real-time, objective, nonionizing, electromagnetic localization system using implanted electromagnetic transponders has been developed (Beacon electromagnetic transponder, Calypso Medical Technologies, Inc., Seattle, WA). We evaluated the feasibility and fixation of electromagnetic transponders bronchoscopically implanted in small airways of canine lungs and compared to results using gold markers. METHODS AND MATERIALS After approval of the Animal Studies Committee, five mongrel dogs were anesthetized, intubated, and ventilated. Three transponders were inserted into the tip of a plastic catheter, passed through the working channel of a flexible bronchoscope, and implanted into small airways of a single lobe using fluoroscopic guidance. This procedure was repeated for three spherical gold markers in the opposite lung. One, 7, 14, 28, and 60 days postimplantation imaging was used to assess implant fixation. RESULTS Successful bronchoscopic implantation was possible for 15 of 15 transponders and 12 of 15 gold markers; 3 markers were deposited in the pleural space. Fixation at 1 day was 15 of 15 for transponders and 12 of 12 for gold markers. Fixation at 60 days was 6 of 15 for transponders and 7 of 12 for gold markers, p value = 0.45. CONCLUSIONS Bronchoscopic implantation of both transponders and gold markers into the canine lung is feasible, but fixation rates are low. If fixation rates can be improved, implantable electromagnetic transponders may allow improved radiation therapy for lung cancer by providing real-time continuous target tracking. Developmental work is under way to improve the fixation rates and to reduce sensitivity to implantation technique.

Bronchial thermoplasty: a novel technique in the treatment of severe asthma

New therapies are needed for patients with severe persistent asthma who cannot achieve control with current therapy of inhaled corticosteroids and long-acting β2-agonists. Bronchial thermoplasty is a novel intervention for asthma that delivers controlled thermal energy to the airway wall during a series of bronchoscopies, resulting in a prolonged reduction in airway smooth muscle mass. We review the method of performing bronchial thermoplasty with the Alair System, how to appropriately select and manage patients undergoing bronchial thermoplasty, and the clinical experience to date with this treatment. Randomized, controlled clinical trials with bronchial thermoplasty in subjects with severe asthma have resulted in improvements in overall asthma control as demonstrated by significant improvement in quality of life, asthma symptoms, severe exacerbations requiring corticosteroids, days lost from work/school/other daily activities due to asthma, and healthcare utilization.

The correlation of tissue motion within the lung: implications on fiducial based treatments

In radiation therapy many motion management and alignment techniques rely on the accuracy of an internal fiducial acting as a surrogate for target motion within the lung. Although fiducials are routinely used as surrogates for tumor motion, the extent to which varying spatial locations in the lung move similarly to other locations has yet to be quantitatively analyzed. In an attempt to analyze the motion correlation throughout the lung, ten primary lung cancer patients underwent IRB-approved 4DCT scans in the supine position. Deformable registration produced motion vectors for each voxel between exhalation and inhalation. Modeling was performed for each vector and all surrounding vectors within the lung in order to determine the mean 3D Euclidean distance necessary for an implanted fiducial to correlate with surrounding tissue motion to within 3 mm (left lower: 1.7 cm, left upper: 2.1 cm, right lower 1.6 cm, and right upper 2.9 cm). No general implantation rule of where to position a fiducial with respect to the tumor was found as the motion is highly patient and lobe specific. Correlation maps are presented showcasing spatial anisotropy of the motion of tissue surrounding the tumor.

Endobronchial Ultrasound-guided Transbronchial Miniforceps Biopsy of Mediastinal and Hilar Lymph Node Stations.

Linear array endobronchial ultrasound has significantly improved the diagnostic yield of transbronchial needle aspiration for the diagnosis of centrally located lesions within the thorax. Although transbronchial needle aspiration has become an accepted technique for diagnosing solid tumors within the chest, its yield for hematologic malignancies such as lymphoma and other benign conditions in which direct examination of tissue architecture are preferred is lower. Currently, surgical biopsies by mediastinoscopy or video-assisted thoracic surgery are often required to obtain adequate tissue specimens to make these diagnoses. In this retrospective study, we review our experience with patients who underwent endobronchial ultrasound-guided miniforceps biopsy of abnormalities at mediastinal and hilar lymph node stations.

MO-D-ValB-01: Characterization of Cardiac Motion in the Lung Using a Novel Electromagnetic System in An Animal Model

Purpose: Previous studies have examined the accuracy of the use of three internal ACelectromagnetic transponders and wireless tracking system (Calypso® Medical) for tumor localization in prostate cancer. This study focuses on the use of the system to investigate and characterize cardiac induced lungtissue motion to better predict three‐dimensional lungtumor position in real‐time. Method and Materials: Under an institutional approved animal study, three 1.8 mm ACelectromagnetic transponders are bronchoscopically implanted in the periphery of the lungs of five hounds. The transponders are positioned in a triangle, each spaced 1–3 cm apart. The transponder positions are sequentially measured every 50 ms at five time points. During each measurement, the subject is stressed with several respiratory patterns. Signal processing of the data involves the design and application of a Butterworth highpass filter to obtain the component of transponder movement due to cardiac motion. Results: The data for the 1st three time points of the first animal are presented. FFT spectrum analysis indicated signal frequency components of 13.05 and 123.8 cycles/minute, due to respiration and cardiac motion respectively. Cardiac‐induced lungtissue motion was detected in vivo, ranging from 0.0007cm – 0.3592cm, by applying the highpass filter to the data. The motion was smaller on the implant day compared with the other two time points. Moreover, transponder position and distance from the heart had an effect on calculated motion. Finally, breathing patterns also affected the observed motion at a statistically significant 0.1% level. Conclusion:Cardiac contractions cause quantifiable motion in surrounding lungtissues that cannot be measured with existing onboard imaging capabilities. The motion varies depending on transponder position, distance from the heart, breathing pattern, and day of measurement. Though the motion maximum was 3.6mm, this motion could cause imaging artifacts when using respiratory correlates. Research sponsored by Calypso® Medical Technologies.

Physiologic and Histopathologic Effects of Targeted Lung Denervation in an Animal Model

Parasympathetic efferent innervation of the lung is the primary source of lung acetylcholine. Inhaled long-acting anticholinergics improve lung function and symptoms in patients with chronic obstructive pulmonary disease. Targeted lung denervation (TLD), a bronchoscopic procedure intended to disrupt pulmonary parasympathetic inputs, is an experimental treatment for chronic obstructive pulmonary disease. The physiologic and histologic effects of TLD have not previously been assessed. Eleven sheep and two dogs underwent circumferential ablation of the main bronchi with simultaneous balloon surface cooling using a lung denervation system (Nuvaira, Inc., Minneapolis, MN). Changes in pulmonary air flow resistance were monitored before and following TLD. Four animals were assessed for the presence or abolishment of the sensory axon-mediated Hering-Breuer reflex before and following TLD. Six sheep were histologically evaluated 30 days post-TLD for the extent of lung denervation (axonal staining) and effect on peribronchial structures near the treatment site. No adverse clinical effects were seen in any treated animals. TLD produced a ~30% reduction in pulmonary resistance and abolished the sensory-mediated Hering-Breuer reflex. Axonal staining was consistently decreased 60% at 30 days after TLD. All treated airways exhibited 100% epithelial integrity. Damage to other peribronchial structures was minimal. Tissue 1 cm proximal and distal to the treatment was normal, and the esophagus and periesophageal vagus nerve branches were unaffected. TLD treatment effectively denervates the lung while protecting the bronchial epithelium and minimizing effects on peribronchial structures. NEW & NOTEWORTHY The feasibility of targeted lung denervation, a new minimally invasive therapy for obstructive lung disease, has been demonstrated in humans with preliminary clinical studies demonstrating improvement in symptoms, pulmonary function, and exercise capacity in patients with chronic obstructive pulmonary disease. This preclinical animal study demonstrates the ability of targeted lung denervation to disrupt vagal inputs to the lung and details its physiologic and histopathologic effects.