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.

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.