Angela Delsing

The Use of MDCT-Based Computer-Aided Pathway Finding for Mediastinal and Perihilar Lymph Node Biopsy: A Randomized Controlled Prospective Trial

Background: Mediastinal and perihilar lymph node samples can be acquired safely through the transbronchial approach during a bronchoscopic examination that is usually required as part of the evaluation of suspected lung cancer. Typically, needle aspiration samples are performed and needle cores can be sampled if the operator is confident that the needle is within the lymph node target, partly because of the risk of bleeding if a large blood vessel is sampled during core biopsy, especially in the perihilar region. Many bronchoscopists have difficulty assessing the three-dimensional (3D) positioning for needle sampling during these procedures, especially when relying on multidetector-row computerized tomography (MDCT) images displayed two-dimensionally seen prior to and usually during the procedure. Objective: We have developed and evaluated a process model and associated software for providing interactive 3D displays of the MDCT data for procedure planning and real-time virtual bronchoscopic pathfinding for these procedures. Methods: We undertook a prospective randomized clinical study for evaluating the computer-aided pathfinding assistance in mediastinal lymph node biopsies in 87 consenting subjects. Results: We demonstrate that the addition of this computer-aided pathfinding improved operator performance in perihilar and paratracheal lymph node sampling (100 vs. 69%) but not in subcarinal sampling (82 vs. 85%). Overall success with lymph node sampling is 92% using the computer-aided method and 77% using standard clinical practice. Conclusions: The type of computer-aided pathway assistance described here, using 3D MDCT scanning information obtained before the procedure, but interacting with real-time bronchoscopic images during the bronchoscopic procedure, should improve the confidence of most bronchoscopists in performing these procedures, with improved clinical outcomes, and will add to the personalization of medicine through imaging.

Plasma angiopoietin 2 concentrations are related to impaired lung function and organ failure in a clinical cohort receiving high-dose interleukin 2 therapy.

ABSTRACT Introduction: The pathophysiology and therapeutic options in sepsis-induced lung injury remain elusive. High-dose interleukin 2 therapy (HDIL-2) is an important protocol for advanced malignancies but is limited by systemic inflammation and pulmonary edema that is indistinguishable from sepsis. In preclinical models, IL-2 stimulates angiopoietin 2 (AngP-2) secretion, which increases endothelial permeability and causes pulmonary edema. However, these relationships have not been fully elucidated in humans. Furthermore, the relevance of plasma AngP-2 to organ function is not clear. We hypothesized that plasma AngP-2 concentrations increase during HDIL-2 and are relevant to clinical pathophysiology. Methods: We enrolled 13 subjects with metastatic melanoma or renal cell carcinoma admitted to receive HDIL-2 and collected blood and spirometry data daily. The plasma concentrations of AngP-2 and IL-6 were measured with enzyme-linked immunosorbent assay. Results: At baseline, the mean AngP-2 concentration was 2.5 (SD, 1.0) ng/mL. Angiopoietin 2 concentrations increased during treatment: the mean concentration on the penultimate day was 16.0 (SD, 4.5) ng/mL and increased further to 18.6 (SD, 4.9) ng/mL (P < 0.05 vs. penultimate) during the last day of therapy. The forced expiratory volume in 1 s decreased during treatment. Interestingly, plasma AngP-2 concentrations correlated negatively with forced expiratory volume in 1 s (Spearman r = −0.78, P < 0.0001). Plasma AngP-2 concentrations also correlated with plasma IL-6 concentrations (r = 0.61, P < 0.0001) and Sequential Organ Failure Assessment scores (r = 0.68, P < 0.0001). Conclusions: Plasma AngP-2 concentrations increase during HDIL-2 administration and correlate with pulmonary dysfunction. High-dose IL-2 may serve as a clinical model of sepsis and acute lung injury. Further investigation is warranted.

Laser fluorescence bronchoscopy for detection of fluorescent reporter genes in airway epithelia.

Current methods for detecting successful gene transfer to airway epithelia involve obtaining a sample of the target tissue. This may affect the longevity of expression of the transgene under evaluation. We describe a laser fluorescence bronchoscopic system that can detect the expression of the fluorescent protein, green fluorescence protein (GFP), in the airway of monkeys that have been transfected with adenovirus, without the need for obtaining tissue. This technique will have applications in pre-clinical and clinical studies of gene transfer to airway epithelia and other surface epithelia accessible by endoscopy.

Color analysis of the human airway wall

A bronchoscope can be used to examine the mucosal surface of the airways for abnormalities associated with a variety of lung diseases. The diagnosis of these abnormalities through the process of bronchoscopy is based, in part, on changes in airway wall color. Therefore it is important to characterize the normal color inside the airways. We propose a standardized method to calibrate the bronchoscopic imaging system and to tabulate the normal colors of the airway. Our imaging system consists of a Pentium PC and video frame grabber, coupled with a true color bronchoscope. The calibration procedure uses 24 standard color patches. Images of these color patches at three different distances (1, 1.5, and 2 cm) were acquired using the bronchoscope in a darkened room, to assess repeatability and sensitivity to illumination. The images from the bronchoscope are in a device-dependent Red-Green-Blue (RGB) color space, which was converted to a tri-stimulus image and then into a device-independent color space sRGB image by a fixed polynomial transformation. Images were acquired from five normal human volunteer subjects, two cystic fibrosis (CF) patients and one normal heavy smoker subject. The hue and saturation values of regions within the normal airway were tabulated and these values were compared with the values obtained from regions within the airways of the CF patients and the normal heavy smoker. Repeated measurements of the same region in the airways showed no measurable change in hue or saturation.