Doctor of Philosophy

dissertationClosed-loop control of wireless capsule endoscopes is an active area of research because it would drastically improve screening of the gastrointestinal tract. Traditional endoscopic procedures are unable to view the entire gastrointestinal tract and current commercial wireless capsule endoscopes are limited in their effectiveness due to their passive nature. This dissertation advances the field of active capsule endoscopy by developing methods to localize the full six-degree-of-freedom (6-DOF) pose of a screw-type magnetic capsule while it is being propelled through a lumen (such as the small intestines) using an external rotating magnetic dipole. The same external magnetic dipole is utilized for both propulsion and localization. Hardware was designed and constructed to enable testing of the magnetic localization and propulsion methods, including a robotic end-effector used as the external actuator magnet, and a prototype capsule embedded with Hall-effect sensors. Due to the use of a rotating magnetic field for propulsion, at any given time, the capsule can be in one of three regimes: synchronously rotating with the applied field, in "step-out" where it is free to move but the external field is rotating too quickly for the capsule to remain synchronously rotating, or completely stationary. We show that it is only necessary to distinguish whether or not the capsule is synchronously rotating (i.e., a single localization method can be used for a capsule in either the step-out or stationary regimes). Two magnetic localization methods are developed. The first uses nonlinear least squares to estimate the capsule's pose when it has no (or approximately no) net motion (e.g., to find the initial capsule pose or when it is stuck in an intestinal fold). The second method estimates the 6-DOF capsule pose as it synchronously rotates with the applied magnetic field using a square-root variant of the Unscented Kalman filter. A simple process model is adopted that restricts the capsule's movement to translation along and rotation about its principle axis. The capsule is actively propelled forward or backward, but it is not actively steered, rather, steering is provided by the lumen. The propulsion parameters that transform magnetic force and torque to the capsule's spatial velocity and angular velocity are estimated with an additional square-root Unscented Kalman filter to enable the capsule to navigate heterogeneous environments such as the small intestines. An optimized localization-propulsion system is described using the two localization algorithms and prior work in screw-type magnetic capsule propulsion with a single rotating dipole field. The capsule's regime is determined and the corresponding localization method is employed. Based on the capsule's estimated pose and the current estimates of its propulsion parameters, the actuator magnet's pose relative to the capsule is optimized to maximize the capsule's forward propulsion. Using this system, our prototype magnetic capsule successfully completed U-shaped and S-shaped trajectories in fresh bovine intestines with an average forward velocity of 5.5mm/s and 3.5 mm/s, respectively. At this rate it would take approximately 18-30 minutes to traverse the 6 meters of a typical human small intestine

Localization method for a magnetic capsule endoscope propelled by a rotating magnetic dipole field

Abstract — Previous research on the localization of wireless capsule endoscopes with magnetic fields and sensors has typi-cally utilized incremental methods. This paper provides a non-iterative solution to determine the six degree-of-freedom (6-DOF) position and orientation of a wireless capsule endoscope being actuated by a rotating magnetic dipole. Non-iterative solutions in the past have only been used to locate immobile objects. We experimentally demonstrate that our algorithm calculates the 6-DOF position and orientation of capsules that are truly stationary as well as those that are operated in the “step-out ” regime, where the magnetic field is rotated too quickly for the capsule to rotate synchronously, but the capsule does undergo chaotic movement. I

Complex Compound Inheritance of Lethal Lung Developmental Disorders Due to Disruption of the TBX-FGF Pathway

International audiencePrimary defects in lung branching morphogenesis, resulting in neonatal lethal pulmonary hypoplasias, are incompletely understood. To elucidate the pathogenetics of human lung development, we studied a unique collection of samples obtained from deceased individuals with clinically and histopathologically diagnosed interstitial neonatal lung disorders: acinar dysplasia (n = 14), congenital alveolar dysplasia (n = 2), and other lethal lung hypoplasias (n = 10). We identified rare heterozygous copy-number variant deletions or single-nucleotide variants (SNVs) involving TBX4 (n = 8 and n = 2, respectively) or FGF10 (n = 2 and n = 2, respectively) in 16/26 (61%) individuals. In addition to TBX4, the overlapping similar to 2 Mb recurrent and nonrecurrent deletions at 17q23.1q23.2 identified in seven individuals with lung hypoplasia also remove a lung-specific enhancer region. Individuals with coding variants involving either TBX4 or FGF10 also harbored at least one non-coding SNV in the predicted lung-specific enhancer region, which was absent in 13 control individuals with the overlapping deletions but without any structural lung anomalies. The occurrence of rare coding variants involving TBX4 or FGF10 with the putative hypomorphic non-coding SNVs implies a complex compound inheritance of these pulmonary hypoplasias. Moreover, they support the importance of TBX4-FGF10-FGFR2 epithelial-mesenchymal signaling in human lung organogenesis and help to explain the histopathological continuum observed in these rare lethal developmental disorders of the lung