Design and Fabrication of a Motor Legged Capsule for the Active Exploration of the Gastrointestinal Tract

This paper describes a novel solution for the active locomotion of a miniaturized endoscopic capsule in the gastrointestinal (GI) tract. In particular, the authors present the design, development, and testing of a legged locomotion system embedded in a capsule (with a volume of about 4-5 cm³) and actuated by a brushless minimotor. The actuation mechanism and transmission mechanism are described in detail in order to highlight the compactness of the overall design. This device is provided with four superelastic legs, allowing large stroke advancement in the GI tract, and a CMOS frontal camera, for diagnostic purposes. A dedicated electronic board for controlling the opening angle of the legs and adjusting their speed has been developed. In order to investigate the motion ability of the device, a set of experiments has been carried out. Four different types of superelastic legs have been designed and tested with the objective to identify the best leg configuration for capsule locomotion. Experimental results demonstrate that the device can travel in the digestive tract with a typical speed ranging between 10 and 40 mm/min.     

GI tract unraveling with curved cross sections

Gastrointestinal (GI) tract examination with spiral/helical computed tomography (CT) is currently performed by slice-based inspection of axial images. CT colography is a recent advance which allows an intraluminal visualization of the colon, similar to endoscopy. Various rendering algorithms have been developed with promising results, however navigation through the complex, tortuous anatomy of the colon can be time consuming in practice. In this paper, the authors propose an electrical-field-based method to unravel the convoluted colon, that is, to digitally straighten it with curved cross sections and flatten it over a plane. In the authors' method, electrical charges are simulated along the central colon path. Curved cross sections are defined by the electrical force lines, and lead to consistent unraveling. It is demonstrated with image volumes of two patients that this technique produces a global planar view of complicated colon features with a potential for detection of polyps     

Magnetic control system targeted for capsule endoscopic operations in the stomach--design, fabrication, and in vitro and ex vivo evaluations

This paper presents a novel solution of a hand-held external controller to a miniaturized capsule endoscope in the gastrointestinal (GI) tract. Traditional capsule endoscopes move passively by peristaltic wave generated in the GI tract and the gravity, which makes it impossible for endoscopists to manipulate the capsule endoscope to the diagnostic disease areas. In this study, the main objective is to present an endoscopic capsule and a magnetic field navigator (MFN) that allows endoscopists to remotely control the locomotion and viewing angle of an endoscopic capsule. The attractive merits of this study are that the maneuvering of the endoscopic capsule can be achieved by the external MFN with effectiveness, low cost, and operation safety, both from a theoretical and an experimental point of view. In order to study the magnetic interactions between the endoscopic capsule and the external MFN, a magnetic-analysis model is established for computer-based finite-element simulations. In addition, experiments are conducted to show the control effectiveness of the MFN to the endoscopic capsule. Finally, several prototype endoscopic capsules and a prototype MFN are fabricated, and their actual capabilities are experimentally assessed via in vitro and ex vivo tests using a stomach model and a resected porcine stomach, respectively. Both in vitro and ex vivo test results demonstrate great potential and practicability of achieving high-precision rotation and controllable movement of the capsule using the developed MFN.     

Magnetic Living Hydrogels for Intestinal Localization,Retention, and Diagnosis

Natural microbial sensing circuits can be rewired into new gene networks to build living sensors that detect and respond to disease-associated biomolecules. However, synthetic living sensors, once ingested, are cleared from the gastrointestinal (GI) tract within 48 h; retaining devices in the intestinal lumen is prone to intestinal blockage or device migration. To localize synthetic microbes and safely extend their residence in the GI tract for health monitoring and sustained drug release, an ingestible magnetic hydrogel carrier is developed to transport diagnostic microbes to specific intestinal sites. The magnetic living hydrogel is localized and retained by attaching a magnet to the abdominal skin, resisting the peristaltic waves in the intestine. The device retention is validated in a human intestinal phantom and an in vivo rodent model, showing that the ingestible hydrogel maintains the integrated living bacteria for up to seven days, which allows the detection of heme for GI bleeding in the harsh environment of the gut. The retention of microelectronics is also demonstrated by incorporating a temperature sensor into the magnetic hydrogel carrier.     

Magnetically controllable gastrointestinal steering of video capsules

Wireless capsule endoscopy (WCE) allows for comfortable video explorations of the gastrointestinal (GI) tract, with special indication for the small bowel. In the other segments of the GI tract also accessible to probe gastroscopy and colonscopy, WCE still exhibits poorer diagnostic efficacy. Its main drawback is the impossibility of controlling the capsule movement, which is randomly driven by peristalsis and gravity. To solve this problem, magnetic maneuvering has recently become a thrust research area. Here, we report the first demonstration of accurate robotic steering and noninvasive 3-D localization of a magnetically enabled sample of the most common video capsule (PillCam, Given Imaging Ltd, Israel) within each of the main regions of the GI tract (esophagus, stomach, small bowel, and colon) in vivo, in a domestic pig model. Moreover, we demonstrate how this is readily achievable with a robotic magnetic navigation system (Niobe, Stereotaxis, Inc, USA) already used for cardiovascular clinical procedures. The capsule was freely and safely moved with omnidirectional steering accuracy of 1°, and was tracked in real time through fluoroscopic imaging, which also allowed for 3-D localization with an error of 1 mm. The accuracy of steering and localization enabled by the Stereotaxis system and its clinical accessibility world wide may allow for immediate and broad usage in this new application. This anticipates magnetically steerable WCE as a near-term reality. The instrumentation should be used with the next generations of video capsules, intrinsically magnetic and capable of real-time optical-image visualization, which are expected to reach the market soon.     

High-Bandwidth Plastic Optical Fiber for Fiber to the Display

Novel photonics polymer devices for broadband technologies are described, focusing on the high-bandwidth graded-index plastic optical fiber (GI POF). Based on these photonics polymer device technologies, the concept of "Fiber to the Display" is proposed, where GI POF is directly distributed to display from main server in a building or house. Therefore, real-time face-to-face communication with high-definition-television quality becomes possible, which cannot be achieved by current technologies. The authors believe that new innovative concepts of broadband society in the 21st century will be realized by "the proposal from the material side."     

Electromagnetic radiation from ingested sources in the human intestine between 150 MHz and 1.2 GHz

The conventional method of diagnosing disorders of the human gastro-intestinal (GI) tract is by sensors embedded in cannulae that are inserted through the anus, mouth, or nose. However, these cannulae cause significant patient discomfort and cannot be used in the small intestine. As a result, there is considerable ongoing work in developing wireless sensors that can be used in the small intestine. The radiation characteristics of sources in the GI tract cannot be readily calculated due to the complexity of the human body and its composite tissues, each with different electrical characteristics. In addition, the compact antennas used are electrically small, making them inefficient radiators. This paper presents radiation characteristics for sources in the GI tract that should allow for the optimum design of more efficient telemetry systems. The characteristics are determined using the finite-difference time-domain method with a realistic antenna model on an established fully segmented human body model. Radiation intensity outside the body was found to have a Gaussian-form relationship with frequency. Maximum radiation occurs between 450 and 900 MHz. The gut region was found generally to inhibit vertically polarized electric fields more than horizontally polarized fields.     

RF Localization for Wireless Video Capsule Endoscopy

RF localization science and technology started with the global positioning systems for outdoor areas, and it then transformed into wireless indoor geolocation. The next step in the evolution of this science is the transformation into RF localization inside the human body. The first major application for this technology is the localization of the wireless video capsule endoscope (VCE) that has been in the clinical arena for 12?years. While physicians can receive clear images of abnormalities in the gastrointestinal tract with VCE devices, they have little idea of their exact location inside the GI tract. To localize intestinal abnormalities, physicians routinely use radiological, endoscopic or surgical operations. If we could use the RF signal radiated from the capsule to also locate these devices, not only can physicians discover medical problems, but they can also learn where the problems are located. However, finding a realistic RF localization solution for the endoscopy capsule is a very challenging task, because the inside of the human body is a difficult environment for experimentation and visualization. In addition, we have no-idea how the capsule moves and rotates in its 3D journey in this non-homogeneous medium for radio propagation. In this paper, we describe how we can design a cyber physical system (CPS) for experimental testing and visualization of interior of the human body that can be used for solving the RF localization problem for the endoscopy capsule. We also address the scientific challenges that face and the appropriate technical approaches for solving this problem.     

A review of localization systems for robotic endoscopic capsules

Obscure gastrointestinal (GI) bleeding, Crohn disease, Celiac disease, small bower tumors, and other disorders that occur in the GI tract have always been challenging to be diagnosed and treated due to the inevitable difficulty in accessing such a complex environment within the human body. With the invention of wireless capsule endoscope, the next generation of the traditional cabled endoscope, not only a dream has come true for the patients who have experienced a great discomfort and unpleasantness caused by the conventional endoscopic method, but also a new research field has been opened to develop a complete miniature robotic device that is swallowable and has full functions of diagnosis and treatment of the GI diseases. However, such an ideal device needs to be equipped with a highly accurate localization system to be able to exactly determine the location of lesions in the GI tract and provide essential feedback to an actuation mechanism controlling the device's movement. This paper presents a comprehensive overview of the localization systems for robotic endoscopic capsules, for which the motivation, challenges, and possible solutions of the proposed localization methods are also discussed.     

Nanoassemblies Derived from Natural Flavonoid Compounds as New Antioxidant Oral Preparations for Targeted Inflammatory Bowel Disease Therapy

Possessing the largest surface area of mucosa in the body, the gastrointestinal (GI) tract can easily sufferfrom inflammatory damage under various adverse external exposures, resulting in the occurrence of inflammatory bowel disease (IBD). Excessive reactive oxygen species (ROS) usually lead to local mucosal injury, accelerate the formation of niduses, andamplify the inflammatory and immune response. Antioxidant therapy, therefore, is considered as a potential strategy against IBDs. Herein, a series of novel dihydromyricetin-based nanoassemblies with excellent antioxidant activities and high dispersion in GI tract as oral preparations are developed for the targeted IBD treatment. By changing raw materials, the current strategy can be well extended to the preparation of other insoluble natural flavonoid compound-based nanoassemblies. The well-designed dihydromyricetin-PEG 1000-based nanoassemblies (DMY-1000 NAs) with high stability and great ROS scavenging capacity in the harsh environment of GI tract hold an admirable targeted capability toward the intestinal inflamed lesions. Therefore, these biocompatible DMY-1000 NAs show promising therapeutic effects for typical IBDs including ulcerative colitis and Crohn's disease in murine models. This study not only provides a new method for constructing antioxidant therapy platforms but also illustrates their prominent therapeutic promise against IBDs.     

A scalable VideoGIS system for GPS-guided vehicles

A VideoGIS system aims at combining geo-referenced video information with traditional geographic information in order to provide a more comprehensive understanding over a spatial location. Video data have been used with geographic information in some projects to facilitate a better understanding of the spatial objects of interest. This paper presents an on-going VideoGIS project, in which scalable geo-referenced video and geographic information (GI) are transmitted to GPS-guided vehicles. The hypermedia, which contains cross-referenced video and GI, are organized in a scalable (layered) fashion. The remote users can request, through 3G mobile devices, the abundant information related to the objects of interest, while adapting to heterogeneous network condition and local CPU usage. Available bandwidth estimation technique is used in the adaptive video transmission.     

A foot-wearable interface for locomotion mode recognition based on discrete contact force distribution

The knowledge of plantar pressure distribution is important in understanding human locomotion activities, and its integration with robotic assistive devices is an important potential application. In this paper, we aim to explore the potential of using discrete contact force distribution signals for locomotion mode recognition. A foot-wearable interface comprising a pair of sensing insoles, each with four sensors at selected locations, has been designed to record discrete contact forces during locomotion. Based on the information of discrete contact force distribution, we present a locomotion mode recognition strategy with decision tree and linear discriminant analysis classifiers. To verify the measurement performance of the sensing system, experiments are carried out to investigate the system stability in long term working conditions and its adaptation to different ground surfaces. To evaluate whether discrete contact force signals can be used for locomotion mode recognition, five able-bodied subjects and one amputee subject are recruited and asked to perform six types of locomotion tasks. With the proposed recognition strategy, reliable recognition performance is obtained. The average classification accuracy is 98.8% ± 0.5% for able-bodied subjects and 98.4% for the amputee subject, which is comparable to those obtained from systems based on other sensors. These experimental results indicate that monitoring of discrete contact force distribution is valuable for locomotion mode recognition. Its use can be combined with other sensing systems to achieve better performance of locomotion mode recognition for intelligent assistive device control.     

A novel robotic colonoscopy system integrating feeding and steering mechanisms with self-propelled paddling locomotion: A pilot study

Colonoscopy is a common procedure to perform advanced therapies such as Endoscopic Submucosal Dissection (ESD), which allows for greater diagnostic specificity and sensitivity compared to other types of examination. Nevertheless, since the colonoscope can cause patient discomfort or pain due to improper manipulation, it is quite challenging for endoscopists who need to develop the necessary skills to accurately perform the procedure and minimize this discomfort. To overcome these sorts of limitations inherent in conventional colonoscopies, various studies regarding robotic and automated systems have been made. In this paper, based on the mechanics of paddling locomotion, a fully self-propelled robotic colonoscope is proposed, then integrated with assistance modules. The feeding and the steering module aim to assist the navigation of the human colon. By building on operations already familiar to endoscopists (i.e., tip deflection, push forward and pull back, hooking, etc.), the device's automatic sequences are investigated to ensure high safety and maneuverability. In addition, a Multimodal Robotic Colonoscope Interface (MRCI) is integrated with each modular mechanism, which allows endoscopists to monitor kinetic/kinematic data and implement manual control in case of unexpected emergency (i.e., deadlocked in colon, paradoxical movement, etc.). With the integrated interface, a pilot study using a porcine colon was conducted. Through an In-vitro test along a straight path, the velocity of the proposed RC was identified as 16.9 mm/s at a paddling frequency of 2 Hz with feeding force of 10 N. These results are 1.7 times faster (9.6 mm/s) than tests that only used paddling locomotion without any feeding force and steered angle. Furthermore, at a curved path with a radius of 60 mm, the RC velocity was measured at 21.5 mm/s, and experienced a radial elongation ratio of 20%. Similarly, at an inclined path of 30°, the velocity of the robot increased 25% (8.93 mm/s) compared to paddling locomotion alone (7.14 mm/s). The final results showed that the integrated system had superior results compared to previous studies based on self-propelled locomotion alone.     

Optical monitoring of tissue viability parameters in vivo: from experimental animals to clinical applications

Optical monitoring of tissue physiological and biochemical parameters in real-time is a new approach and a powerful tool for better clinical diagnosis and treatment.Most of the devices available for monitoring patients in critical conditions provide information on body respiratory and hemodynamic functions. Currently, monitoring of patients at the cellular and tissue level is very rare. Realtime monitoring of mitochondrial nicotinamide adenine dinucleotide (NADH) as an indicator of intra-cellular oxygen levels started 50 years ago. Mitochondrial dysfunction was recognized as a key element in the pathogenesis of various illnesses. We developed the "CritiView" - a revolutionary patient monitoring system providing real time data on mitochondrial function as well as microcirculatory blood flow, hemoglobin oxygenation as well as tissue reflectance.We hypothesize that under the development of body O2 insufficiency the well known blood flow redistribution mechanism will protect the most vital organs (brain and heart) by increasing blood flow while the less vital organs (gastrointestinal (GI) tract or urogenital system) will become hypoperfused and O2 delivery will diminish.Therefore, the less vital organs will be the initial responders to O2 imbalances and the last to recover after the end of resuscitation. The urethral wall represents a lessvital organ in the body and may be very sensitive to the development of emergency situations in patients. It is assumed that the beginning of deterioration processes (i.e.,internal bleeding) as well as resuscitation end-points in critically ill patients will be detected.In this paper, we review the theoretical, technological,experimental and preliminary clinical results accumulated using the "CritiView". Preliminary clinical studies suggest that our monitoring approach is practical in collecting data from the urethral wall in critical care medicine. Using CritiView in critical care medicine may shed new light on body O2 balance and the development of body emergency metabolic state.     

Accuracy of RSS-Based RF Localization in Multi-capsule Endoscopy

In this paper, we derive and analyze cooperative localization bounds for endoscopic wireless capsule as it passes through the human gastrointestinal (GI) tract. We derive the Cramer-Rao bound (CRB) variance limits on location estimators which use measured received signal strength (RSS). Using a three-dimension human body model from a full wave simulation software and log-normal models for RSS propagation from implant organs to body surface, we calculate bounds on location estimators in three digestive organs: stomach, small intestine and large intestine. We provide analysis of the factors affecting localization accuracy, including various organ environments, external sensor array topology, number of pills in cooperation and the random variations in transmit power of sensor nodes. We also do localization accuracy analysis for the case when transmit power of the sensor is random with known priori distribution. The simulation results show that the number of receiver sensors on body surface has more influence on the accuracy of localization than the number of pills in cooperation inside the GI tract, The large intestine is affected the most with the transmit power randomness.     

Analog CMOS implementation of a CNN-based locomotion controller with floating-gate devices

This paper proposes an analog CMOS circuit that implements a central pattern generator (CPG) for locomotion control in a quadruped walking robot. Our circuit is based on an affine transformation of a reaction-diffusion cellular neural network (CNN), and uses differential pairs with multiple-input floating-gate (MIFG) MOS transistors to implement both the nonlinearity and summation of CNN cells. As a result, the circuit operates in voltage mode, and thus it is expected to reduce power consumption. Due to good matching accuracy of devices, the circuit generates stable rhythmic patterns for robot locomotion control. From experimental results on fabricated chip using a standard CMOS 1.5-/spl mu/m process, we show that the chip yields the desired results; i.e., stable rhythmic pattern generation and low power consumption.     

Application of an object-oriented programming paradigm inthree-dimensional computer modeling of mechanically activegastrointestinal tissues

The aim of this study was to develop a novel three-dimensional (3-D) object oriented modeling approach incorporating knowledge of the anatomy, electrophysiology, and mechanics of externally stimulated excitable gastrointestinal (GI) tissues and emphasizing the “stimulus-response” principle of extracting the modeling parameters. The modeling method used clusters of class hierarchies representing GI tissues from three perspectives: 1) anatomical; 2) electrophysiological; and 3) mechanical. We elaborated on the first four phases of the object-oriented system development life-cycle: 1) analysis; 2) design; 3) implementation; and 4) testing. Generalized cylinders were used for the implementation of 3-D tissue objects modeling the cecum, the descending colon, and the colonic circular smooth muscle tissue. The model was tested using external neural electrical tissue excitation of the descending colon with virtual implanted electrodes and the stimulating current density distributions over the modeled surfaces were calculated. Finally, the tissue deformations invoked by electrical stimulation were estimated and represented by a mesh-surface visualization technique     

Fully automated colon segmentation for the computation of complete colon centerline in virtual colonoscopy

Virtual colonoscopy detects polyps by navigating along a colon centerline. Complete colon segmentation based on computed tomography (CT) data is a prerequisite to the computation of complete colon centerline. There are two main problems impeding complete segmentation: overdistention/underdistention of colon and the use of oral contrast agents. Overdistention produces loops in the segmented colon, while underdistention may cause the segmented colon collapse into a series of disconnected segments. Use of oral contrast agents, which have high attenuation on CT, may add redundant structures (bones and small bowels) to the segmented colon. A fully automated colon segmentation method is proposed in this paper to address the two problems. We tested the proposed method in 170 cases, including 37 "moderate" and 133 "challenging" cases. Computer-generated centerlines were compared with human-generated centerlines (plotted by three radiologists). The proposed method achieved a 90.56% correct coverage rate with respect to the human-generated centerlines. We also compared the proposed method with two existing colon segmentation methods: Uitert's method and Nappi's method. The results of these two methods were 75.16% and 72.59% correct coverage rates, respectively. Our experimental results indicate that the proposed method could yield more complete colon centerlines than the existing methods.     

An elastic caterpillar-based self-propelled robotic colonoscope with high safety and mobility

Colonoscopies are one of the best methods of screening colorectal cancer (CRC) at present. Since conventional colonoscopes have some drawbacks concerning diagnostic procedures, robotic colonoscopes have been studied for smooth intubation. However, previously developed robotic colonoscopes still suffer from disadvantages such as poor locomotion performance and the occurrence of local bleeding due to harsh clamping. In a previous study, therefore, we presented an elastic caterpillar-based robotic colonoscope actuated by an external motor through a flexible shaft to enhance safety and mobility. However, in-depth discussion was not included on theoretical and experimental evaluations for the design of each component. Moreover, the only demonstration of the design's feasibility was carried out without a steering module. Therefore, in the present study, theoretical and experimental evaluations are provided so as to select the optimal components for the robot to guarantee safety, steerability, and mobility. Based on these theoretical and experimental results, the proper components are fabricated and assembled into a robotic colonoscope. Subsequently, a mobility test is performed in an excised porcine colon. The robotic colonoscope shows reliable locomotion performance; it has forward and backward velocities of 5.0 ± 0.4 mm/s and 9.5 ± 0.9 mm/s, respectively. When facing inclined angles of 30˚ and 60˚, the robot moves forward at velocities of 6.1 ± 1.1 mm/s and 4.7 ± 0.7 mm/s, respectively. Furthermore, in order to confirm the feasibility of locomotion performance in a human colon, an additional locomotion test is performed with a lower gastrointestinal phantom mimicking a human colon. Here again, the robot shows high locomotive performance with a velocity of 3.0 ± 0.2 mm/s. Finally, to validate the feasibility of a clinical demonstration for the robotic colonoscope, an in-vivo test is implemented with a live mini pig. Conclusively, owing to a reliable mechanism and a steering module, the robot shows reliable locomotion without complications such as bleeding or perforations in the colon.     

A spatio-temporal dipole simulation of gastrointestinal magnetic fields

We have developed a simulation of magnetic fields from gastrointestinal (GI) smooth muscle. Current sources are modeled as depolarization dipoles at the leading edge of the isopotential ring of electrical control activity (ECA) that is driven by coupled cells in the GI musculature. The dipole moment resulting from the known transmembrane potential distribution varies in frequency and phase depending on location in the GI tract. Magnetic fields in a homogeneous volume conductor are computed using the law of Biot-Savart and characterized by their spatial and temporal variation. The model predicts that the natural ECA frequency gradient may be detected by magnetic field detectors outside the abdomen. It also shows that propagation of the ECA in the gastric musculature results in propagating magnetic field patterns. Uncoupling of gastric smooth muscle cells disrupts the normal magnetic field propagation pattern. Intestinal ischemia, which has been experimentally characterized by lower-than-normal ECA frequencies, also produces external magnetic fields with lower ECA frequencies.