Enhanced real-time pose estimation for closed-loop robotic manipulation of magnetically actuated capsule endoscopes

Pose estimation methods for robotically guided magnetic actuation of capsule endoscopes have recently enabled trajectory following and automation of repetitive endoscopic maneuvers. However, these methods face significant challenges in their path to clinical adoption including the presence of regions of magnetic field singularity, where the accuracy of the system degrades, and the need for accurate initialization of the capsule's pose. In particular, the singularity problem exists for any pose estimation method that utilizes a single source of magnetic field if the method does not rely on the motion of the magnet to obtain multiple measurements from different vantage points. We analyze the workspace of such pose estimation methods with the use of the point-dipole magnetic field model and show that singular regions exist in areas where the capsule is nominally located during magnetic actuation. Since the dipole model can approximate most magnetic field sources, the problem discussed herein pertains to a wider set of pose estimation techniques. We then propose a novel hybrid approach employing static and time-varying magnetic field sources and show that this system has no regions of singularity. The proposed system was experimentally validated for accuracy, workspace size, update rate and performance in regions of magnetic singularity. The system performed as well or better than prior pose estimation methods without requiring accurate initialization and was robust to magnetic singularity. Experimental demonstration of closed-loop control of a tethered magnetic device utilizing the developed pose estimation technique is provided to ascertain its suitability for robotically guided capsule endoscopy. Hence, advances in closed-loop control and intelligent automation of magnetically actuated capsule endoscopes can be further pursued toward clinical realization by employing this pose estimation system

Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins.

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by heterozygous point mutations or genomic deletion copy-number variants (CNVs) of FOXF1 or its upstream enhancer involving fetal lung-expressed long noncoding RNA genes LINC01081 and LINC01082. Using custom-designed array comparative genomic hybridization, Sanger sequencing, whole exome sequencing (WES), and bioinformatic analyses, we studied 22 new unrelated families (20 postnatal and two prenatal) with clinically diagnosed ACDMPV. We describe novel deletion CNVs at the FOXF1 locus in 13 unrelated ACDMPV patients. Together with the previously reported cases, all 31 genomic deletions in 16q24.1, pathogenic for ACDMPV, for which parental origin was determined, arose de novo with 30 of them occurring on the maternally inherited chromosome 16, strongly implicating genomic imprinting of the FOXF1 locus in human lungs. Surprisingly, we have also identified four ACDMPV families with the pathogenic variants in the FOXF1 locus that arose on paternal chromosome 16. Interestingly, a combination of the severe cardiac defects, including hypoplastic left heart, and single umbilical artery were observed only in children with deletion CNVs involving FOXF1 and its upstream enhancer. Our data demonstrate that genomic imprinting at 16q24.1 plays an important role in variable ACDMPV manifestation likely through long-range regulation of FOXF1 expression, and may be also responsible for key phenotypic features of maternal uniparental disomy 16. Moreover, in one family, WES revealed a de novo missense variant in ESRP1, potentially implicating FGF signaling in the etiology of ACDMPV