Systems and methods for performing retrograde tethered capsule endoscopy

Abstract

A system for performing retrograde tethered capsule endoscopy includes a capsule including at least one outwardly spiraling thread, a drive shaft coupled to the capsule and configured to rotate the capsule, and an optical system disposed within the capsule and configured to acquire ambient image information.

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims priority to U.S. Provisional Application No. 63 / 394,940, filed August 3, 2022, the entire contents of which are incorporated herein by reference.

[0002] (Statement regarding federally funded research) Not applicable. [Background technology]

[0003] Optical coherence tomography (OCT) is a non-invasive optical diagnostic tool that provides high-resolution microscopic images of tissue. For the light in an OCT device to penetrate tissue sufficiently, a probe must be delivered inside the human body. Various designs of OCT devices have been developed to probe the human body, but further development is required to gain access for OCT imaging in different parts of the body. Summary of the Invention

[0004] Therefore, new devices, systems, and methods for performing retrograde tethered capsule endoscopy are desirable.

[0005] Various embodiments of the present invention provide a retrograde tethered capsule endomicroscopy (R-TCE) catheter that can image the lower gastrointestinal (GI) tract using optical coherence tomography (OCT) imaging by inserting a tethered capsule containing micro-optics into the anus. Implementations of this catheter can be used to diagnose lower GI disorders such as Crohn's disease and screen for colorectal cancer, including adenomas.

[0006] An embodiment of the R-TCE catheter includes a hard capsule body with a silicone outer thread layer connected to the distal end of a long, semi-rigid drive shaft. The drive shaft is surrounded by a smooth outer sheath. A central channel in the drive shaft contains a flexible inner sheath that houses and protects insulated electrical wires and optical fibers. The drive shaft drives the capsule via a motor at its proximal end, which is attached to a separate drive system, the Retrograde Tethered Capsule Endomicroscopy Drive System (R-TCE-DS). The drive system rotates the drive shaft, converting rotational motion and force into the threaded capsule. The thread converts rotational motion into axial motion, advancing the capsule into the lower gastrointestinal tract. Removal of the device is achieved by switching the drive system to rotate in the opposite direction. The hard capsule body at the distal end of the drive shaft contains micro-optics, including a ball lens connected to an optical fiber, a reflecting prism, and a micromotor that rotates the prism. Electrical wiring is soldered to the motor and powers it through terminals on the catheter cap. A rotating prism allows the OCT light to reach the entire periphery of the capsule wall, thus creating a 360° image that can be viewed on an imaging system.

[0007] The catheter cap at the proximal end of the drive shaft contains the optical and electrical terminations and a locking mechanism for connection to the drive system. The inner catheter cap is threaded onto the drive shaft, and the outer catheter cap is added later. The proximal-most end of the inner catheter cap houses the optical and electrical terminations of the fiber and wires, and a bearing (e.g., ball bearing) can be placed at the distal end of the inner cap to isolate rotation between the inner cap and drive shaft / capsule after the outer cap is attached. The fiber is epoxied into an SC / APC connector, the ferrule is polished to a smooth finish, and the electrical wire is soldered into a spring-loaded contact pin. The outer catheter cap is epoxied around the inner catheter cap, and a locking mechanism connected to the drive system allows the inner cap to rotate and holds the outer cap in place.

[0008] In one embodiment, the present invention provides a system for performing retrograde tethered capsule endoscopy, including: a capsule including at least one outwardly spiraling thread; a drive shaft coupled to the capsule and configured to rotate the capsule; and an optical system disposed within the capsule and configured to acquire ambient image information.

[0009] In another embodiment, the present invention provides a method for performing retrograde tethered capsule endoscopy, comprising: providing a capsule including at least one outwardly spiraling thread and an optical system disposed within the capsule; rotating a drive shaft coupled to the capsule; and acquiring ambient image information using the optical system disposed within the capsule.

[0010] In yet another embodiment, the present invention provides a method of polyp detection comprising: acquiring an image of a sample using a processor; determining a correlation of the derivative (COD) for the image using the processor; determining a scattering coefficient for the image using the processor; determining an angular scattering coefficient for the image using the processor; and predicting a type of polyp in the sample by training a classifier based on the differential bandwidth correlation, the scattering coefficient, and the angular scattering coefficient.

[0011] Various objects, features, and advantages of the disclosed subject matter may be more fully understood by reference to the following detailed description of the disclosed subject matter considered in conjunction with the following drawings, in which like reference numerals identify like elements. [Brief explanation of the drawings]

[0012] [Figure 1] Schematics of the R-TCE and OFDI console are shown, with the inset showing the capsule without external threads for clarity. [Figure 1A] A close-up image of the capsule is shown, showing (from left to right) the respective diameters of the outer sheath (2.1971 mm), outer silicone layer (13 mm), outer imaging window (11 mm), and silicone thread (16 mm). [Figure 2] FIG. 1 is a schematic diagram of the R-TCE optical detection subsystem. [Figure 3] FIG. 2 is a schematic diagram of a distal scanning subsystem. [Figure 4] FIG. 1 is a schematic diagram of an internal capsule subsystem. [Figure 5] FIG. 1 is a schematic diagram of an external capsule subsystem. [Figure 6] FIG. 2 is a schematic diagram of a drive shaft subsystem. [Figure 7] FIG. 1 is a schematic diagram of a catheter cap. [Figure 8A-C]

[0049] Figures 8A and 8B show various aspects of a retrograde tethered capsule endoscopy device. Figure 8A shows a schematic diagram of the retrograde tethered capsule endoscopy device. Figure 8B shows a cross section of the tether portion. Figure 8C shows an enlarged view of the capsule. Here, SMF is single-mode fiber, dc is the drive cable, s is the tether sheath, dcca is the drive cable-capsule connection, t is the silicone thread, bl is the ball lens, mnt is the motor mount, m is the motor, w is the imaging window, p is the prism, and O / E connector is the optical / electrical connector. [Figure 9] An enlarged view of the capsule is shown, where SMF is single-mode fiber, dc is the drive cable, s is the tether sheath, dcca is the drive cable-capsule connection, t is the silicone thread, bl is the ball lens, mnt is the motor mount, m is the motor, w is the imaging window, p is the prism, and O / E connector is the optical / electrical connector. [Figure 10A-B] Figure 10A is a photograph (top) and a schematic (bottom) of a guidewire-based distal tip prototype, and Figure 10B is a photograph (top) and a schematic (bottom) of a tapered spring-based distal tip prototype. [Figure 11] FIG. 1 is a schematic diagram of an R-TCE capsule being treated by etching plasma to improve the antifouling performance of the capsule surface. [Figure 12] The R-TCE OCT treatment system is shown. [Figure 13] 1 shows an R-TCE OCT treatment system with one waveguide and one ball lens for delivering two types of electromagnetic radiation to tissue. [Figure 14] 1 shows an R-TCE OCT treatment system with two waveguides and one focusing / collimating lens, which focuses the OCT laser and collimates the treatment light. [Figure 15]1 shows an R-TCE OCT treatment system with one waveguide and one focusing / collimating lens, which focuses the OCT laser and collimates the treatment light. [Figure 16] 1 illustrates an R-TCE OCT treatment system having one waveguide and one adjustable lens, which can be adjusted to focus either the OCT laser or the treatment light depending on whether the system is operating in either mode. [Figure 17] Histology images of laser-ablated colon tissue (porcine colon). The image on the left was stained with nitroblue tetrazolium chloride (NBTC) to show inactive cells. The image on the right was stained with H&E to show the area of tissue removed by the laser. [Figure 18] The frontal projection of a sample containing normal and tubular adenoma tissues (left panel) and the standard deviation of correlation of derivative bandwidth (COD) (right panel) show the clear separation of normal and tubular adenoma tissues. [Figure 19] The scattering coefficients of the colon polyp determined by A-line fitting are displayed as frontal projections. [Figure 20] A 50 pixel square extracted from the μs map is shown. [Figure 21] Figure 20 shows a 50 pixel square extracted from the μs map (shown in Figure 20), as well as a low-pass filtered version extracted from the logarithm of the Fourier transform (circle in the middle image) and a ring extracted from the logarithm of the same Fourier transform (right image). [Figure 22] FIG. 10 shows the angular scattering index generated using a 50×50 pixel scan square and dynamic fitting with an elliptical aperture and ring. [Figure 23] FIG. 1 is a diagram of an R-TCE system in communication with a computer system. DETAILED DESCRIPTION OF THE INVENTION

[0013] According to some embodiments of the disclosed subject matter, mechanisms (which may include devices, systems, and methods) for performing retrograde tethered capsule endoscopy are provided.

[0014] One method of delivering light to the tissue of interest is via a tethered capsule. Tethered capsules typically contain micro-optics that direct light laterally to focus on the tissue wall surrounding the capsule. The micro-optics are rotated by a micromotor located within the housing, allowing circumferential data to be collected from the tissue surrounding the capsule. Power for the motor can be provided via the tether by a small, well-insulated wire that can be encapsulated within the tether. The catheter wire can terminate in an electrical connector that connects to a compact imaging system (CIS). All external components that directly contact the patient are generally made of biocompatible materials. Such micro-optics for use with coherent imaging (e.g., optical coherence tomography, OCT, or variations such as OFDI) allow the tether on the tethered capsule device to be relatively thin and flexible, since the tether only needs to accommodate an optical fiber and a few thin wires.

[0015] Tethered capsules are placed in the upper gastrointestinal tract (e.g., esophagus, stomach, duodenum), but for various reasons, this technique has not yet been used in other tissues, including the lower gastrointestinal tract (e.g., colon, rectum). While tethered capsules can be delivered to the relatively straight upper gastrointestinal tract using gravity and involuntary muscle movements (e.g., by having the patient swallow the capsule), delivering a tethered capsule to the lower gastrointestinal tract through the subject's mouth is impractical. Because the entire gastrointestinal tract is approximately 18 feet (5.5 meters) long, it takes a relatively long time for a capsule at the end of the tether to reach the lower gastrointestinal tract. Furthermore, the tether, including the optical fiber, may have difficulty surviving the many bends and curves along the entire length of the gastrointestinal tract, preventing easy retrieval of the capsule by pulling it backward through the entire tract.

[0016] While it is possible to access the lower gastrointestinal tract via the anus, many of the current procedures involve colonoscopy and require sedation, making these procedures more complex and expensive than when performed with a tethered capsule. The complexity of accessing the lower gastrointestinal tract via the anus is due, in part, to the need for a probe to be actively moved through tissue, as the capsule, attached to a thin, flexible tether, does not move passively or through involuntary movements, as occurs with swallowing. While tethered capsules include relatively small capsules attached to the end of a thin, flexible tether, current probes for accessing the lower gastrointestinal tract, such as conventional endoscopes, are relatively thick and can cause discomfort as they are guided and maneuvered through tissue, requiring the patient to be sedated.

[0017] Accordingly, various embodiments disclosed herein provide a retrograde tethered capsule endoscopy (R-TCE) catheter (see FIGS. 1 and 1A), which is a tethered capsule configured to move through tissue in an active manner to provide access to the lower gastrointestinal tract via the anus. The motive force for the movement of the R-TCE capsule is provided by one or more outwardly spiral threads on the capsule combined with a rotational drive system coupled to the capsule by a semi-rigid drive shaft. According to one embodiment, the semi-rigid drive shaft includes two coiled layers (which may be fabricated from 304 stainless steel), one layer wound in a right-handed direction and the other layer wound in a left-handed direction. When the drive system rotates the capsule in a first rotational direction, engagement of the capsule's spiral threads with the tissue moves the capsule forward and into the tissue (e.g., the anus and lower gastrointestinal tract). When the rotational direction of the drive system is reversed, engagement of the capsule's spiral threads with the tissue similarly moves the capsule in the opposite direction, back out of the tissue. This arrangement allows for a relatively thin and flexible tether to drive the capsule in either direction and advance it with minimal discomfort, thereby enabling R-TCE procedures to be performed on unsedated subjects.

[0018] In various embodiments, the R-TCE catheter includes a hard capsule body with an elastic outer portion (e.g., made of silicone) that includes an outer thread layer, where the capsule is connected to the distal end of a long, semi-rigid drive shaft. The drive shaft may be surrounded by a smooth outer sheath. The drive shaft's central channel may include a flexible, string-like inner sheath that houses and protects components such as insulated electrical wires and optical fibers. In certain embodiments, the capsule is sized and shaped for insertion into the anus. The drive shaft functions to drive the capsule via a motor at its proximal end (i.e., the end closer to the operator and further from the subject) that is attached to a separate drive system, the Retrograde Tethered Capsule Endomicroscope Drive System (R-TCE-DS) (see Figure 1). The R-TCE-DS rotates the drive shaft, converting rotational motion and force into the threaded capsule. Upon contact with GI tissue, the thread converts rotational motion and force into axial motion (e.g., forward or reverse motion along the long axis), which propels the capsule through the lower GI tract. To remove the device, the drive system switches to rotating in the reverse direction. The catheter material that contacts the patient is biocompatible or food grade. While the thread shown in the embodiment of Figures 1 and 1A has a right-handed orientation, in other embodiments, the thread may be left-handed.

[0019] In some embodiments, the drive system (R-TCE-DS) can be connected to a compact imaging system (e.g., an OCT-based system, see FIG. 1 ), so that endoscopic imaging using R-TCE can be performed similar to upper gastrointestinal OCT capsule endoscopy. In use, the capsule can be administered to a subject, and once inserted, it moves through the lower gastrointestinal tract via a threaded screw action driven by the R-TCE-DS.

[0020] As the capsule passes through the colon, electromagnetic radiation (e.g., near-infrared light) from the imaging system can be scanned over the tissue surrounding the capsule (e.g., the colon wall) by the rotation of the shaft of a micromotor enclosed inside the capsule (note that the rotation of the micromotor shaft is separate from the rotation of the drive shaft subsystem). The light returned from the tissue carries information about the tissue's internal structure and can then be recorded, processed, and displayed in real time by the imaging system. The capsule's advancement and imaging can be manually controlled by the capsule operator via the R-TCE-DS and the imaging system.

[0021] In certain embodiments, a retrograde tethered capsule endoscopy (R-TCE) catheter includes a ball lens (BL)-based optical system and a distal scanning (DS) mechanism, where the R-TCE may be "self-propelled" through the lower intestinal tract (see Figures 1 and 1A). In various embodiments, the R-TCE may be referred to as "self-propelled," whereby rotation of the R-TCE in a particular rotational direction generated by a drive system advances the capsule into or out of a subject's tissue without the need for a tether to drive the capsule forward. Whether the capsule advances into or out of tissue depends not only on the handedness of the helical thread on the exterior of the capsule, but also on the direction of rotation.

[0022] (Optical Coherence Tomography (OCT)) In various embodiments, the R-TCE catheter is designed for use with an existing imaging system (CIS), such as an MGH OCT imaging system. The MGH OCT imaging console can be electrically isolated from the catheter by using a cell-driven motor power unit to drive the micromotor distal scanning optics, or can serve as a direct power supply to the motor power unit. The console also generates lower optical power at the same wavelength on tissue, 1310±50 nm, with a maximum of 35 mW. This results in an estimated tissue radiant exposure of 0.01 mJ / cm.2 The device is approved for use in other tests. In various embodiments, the electromagnetic radiation delivered to the sample by the imaging system can include light having wavelengths in the ultraviolet, visible, and / or infrared regions of the spectrum. The electromagnetic radiation may be transmitted from the CIS / imaging system via an optical waveguide, including an optical fiber, such as a single-mode fiber. In various embodiments, the imaging system can have a relatively short spectral bandwidth (approximately 60 nm or less) compared to conventional OCT imaging consoles used for esophageal imaging, which typically provide an imaging depth of approximately 6 mm. The shorter spectral bandwidth can be selected to enable 3D-OCT imaging of larger luminal structures, such as the colon, and provide a longer range of imaging depth (12 mm imaging depth).

[0023] (OCT Retrograde Tethered Capsule Endoscopy (R-TCE)) In certain embodiments, a catheter may be designed for intraluminal navigation and imaging of the human lower gastrointestinal tract. The R-TCE catheter includes a hard capsule (e.g., made of PMMA) with an outer threaded layer (e.g., made of silicone) connected to the distal end of a long, semi-rigid drive shaft, which may be surrounded by a smooth outer sheath. The drive shaft's central channel is provided with a flexible, string-like inner sheath that houses and protects insulated electrical wires and optical fibers. The size and shape of the capsule and tether (see Figure 1A) allow for its insertion into the anus. The drive shaft allows the capsule to be driven via a motor at its proximal end. The R-TCE device connects to a drive system (R-TCE-DS) with a catheter cap that houses the optical and electrical terminals. The drive system rotates the drive shaft, which converts rotational motion and force into the threaded capsule, allowing for the conversion of rotational motion into axial motion for capsule navigation within the colon. The drive system is then reversed for device removal. Patient-contact catheter materials are generally biocompatible and / or food-grade, and the devices are tested for low pH resistance, tensile strength, and leakage in accordance with the relevant FDA guidance: "Medical Devices; Gastroenterology-Urology Devices; Classification of the Colon Capsule Imaging System" and "Medical Devices; Gastroenterology-Urology Devices; Endoscopes and accessories."

[0024] As described above, in various embodiments, the catheter is connected to a drive system, and the retrograde TCE drive system (R-TCE-DS) is connected to an IRB-approved imaging console that facilitates endoscopic imaging in a manner similar to imaging procedures suitable for previously approved protocols. In use, the capsule is administered to a subject, and once inserted, the capsule travels through the lower gastrointestinal tract, propelled by a spiral motion driven by the R-TCE-DS. Advancement of the drive shaft is manually controlled by the capsule operator via the R-TCE-DS and the imaging system.

[0025] (R-TCE Optical Probe Subsystem (OPS)) In certain embodiments, the optical components of the R-TCE Optical Probe Subsystem (OPS) 200 can include an optical single-mode fiber 210 terminating in a glass spacer 220 and / or a ball lens 230 (see FIG. 2). The optics are secured within an optical probe housing 240 or "hypotube," while the remaining length of the fiber is enclosed within the drive shaft subsystem. At the proximal end of the OPS 200, an SC / APC optical connector is epoxied, and the fiber is threaded through the drive shaft subsystem and polished. The SC connector is epoxied to the inner cap and assembled to the catheter cap. Electromagnetic radiation (e.g., near-infrared light) from the optical fiber can be reflected by a prism attached to the angled shaft weight of the micromotor and then focused by a ball lens to a point just beyond the outer surface of the capsule. The light beam emerging from the OPS 200 (e.g., from the ball lens) illuminates an angled reflector mounted on a micromotor that sits at the most distal end within the distal scanning subsystem (see Figure 1A).

[0026] (R-TCE Distal Scanning Subsystem (Dist-SS)) In various embodiments, the components of the R-TCE Dist-SS 300 may include a prism 310, a prism mount 320, a micromotor 340, and a motor centering piece 330, and / or electrical wires (see FIG. 3). The R-TCE Dist-SS 300 functions by using a prism that reflects light at a 90-degree angle. The prism 310 is attached to the shaft of the micromotor 340 by the prism mount 320. In certain embodiments, the micromotor 340 rotates at a rate of 20 Hz to 40 Hz, rotating the prism 310 and causing the light beam to scan in a circular pattern. The micromotor 340 is powered and controlled through four electrically insulated wires that terminate distally on the sides of the micromotor 340 and are protected with a layer of epoxy. Each wire threads through the drive shaft subsystem and solders to spring-loaded contact pins on the proximal side, which together form an electrical connector within the catheter cap.

[0027] (R-TCE internal capsule subsystem) In certain embodiments, the internal capsule subsystem 400 can include a proximal base 410, an imaging window 430, a distal cap 440, and / or a base weight 420 (see FIG. 4). The capsule's diameter and length (see FIG. 1A) are comparable to FDA-approved commercially available capsule endoscopes (Givens G2, Ormum Capsule Endoscope, SmartPill) and colonoscopes (Olympus), which are widely used in clinical practice for gastrointestinal tract probing. The internal rigid capsule consists of three parts for assembling the catheter: the proximal base 410, the imaging window 430, and the distal cap 440. These components form a sealed rigid capsule containing the optomechanical components for OCT imaging. The base 410 holds the base weight 420, which anchors and centers the OPS 200. This surrounds the optics and connects to the imaging window 430, which has high optical clarity. The capsule's exterior contours allow for easy passage through the lower gastrointestinal tract. The distal portion of the imaging window 430 houses the distal scanning subsystem 300, which is centered at the distal end to ensure proper light propagation. A distal cap 440 seals the capsule end with biomedical grade epoxy.

[0028] (R-TCE External Capsule Subsystem (ECS)) In some embodiments, the R-TCE outer capsule subsystem 500 surrounds a hard inner capsule (see FIG. 5 ). This subsystem 500 is made of silicone and can include one or both outer thread sections 510, 520, which function to translate rotational forces from the drive shaft and drive system into axial forces and translation of the capsule through the colon. In certain embodiments, the threads are attached as proximal and distal layers 510, 520, with a gap 530 between them that can be imaged. The proximal thread layer 510 has a tapered shape that acts as strain relief, gradually transitioning in diameter from a larger diameter encompassing the capsule's outer surface to a smaller diameter encompassing the drive shaft's outer surface (see FIG. 1A for exemplary diameter values). In certain embodiments, the R-TCE outer capsule subsystem 500 can also include a hydrophilic coating to increase the device's lubricity and minimize tissue damage and patient discomfort.

[0029] (R-TCE drive shaft subsystem) In various embodiments, the R-TCE drive shaft subsystem 600 includes a tether collar 650 connecting the drive shaft and inner sheath to the proximal base, an inner sheath 630 housing four wires and fibers, a bidirectional drive shaft 620, and / or an outer sheath 610 that isolates the device rotation from surface contact with tissue (see FIG. 6). The tether collar 650, made of brass, can be secured inside the capsule to improve interface strength.

[0030] (R-TCE Catheter Cap (Catheter Cap, CC)) The R-TCE catheter cap 700 at the proximal end of the drive shaft contains the optical and electrical terminations and a locking mechanism for connection to the drive system. The inner catheter cap is threaded onto the drive shaft, and then the outer catheter cap is added. The proximal-most end of the inner catheter cap houses the optical and electrical terminations of the fiber and wires, and a ball bearing is placed at the distal end of the inner cap to isolate rotation to only the inner cap and drive shaft / capsule once the outer cap is attached. The fiber has an SC / APC connector. The outer catheter cap is epoxied around the inner catheter cap, and a locking mechanism coupled to the drive system can be added to allow the inner cap to rotate and hold the outer cap in place.

[0031] The R-TCE catheter cap 700 can serve as a mechanical, optical, and / or electrical connection to the drive system (R-TCE-DS). In some embodiments, the R-TCE catheter cap 700 can include one or more electrical pins 710, an SC / APC fiber connector 720 that centers and terminates to the OPS 200, inner caps 730, 735, outer caps 740, 745, a bearing 750, a hypotube 760, two springs 770, and / or a ring lock 780 (see FIG. 7).

[0032] (inner cap) In some embodiments, the internal cap 730, 735 can house and protect the optical and electrical connections. The proximal end of the drive shaft subsystem can be epoxied to the inside of the internal cap 730, 735, where a channel separates the electrical wires while maintaining the central optics. The electrical wires can be secured in separate housings that can be soldered onto four separate electrical pins. The optical fibers and electrical wires can be secured with a hypotube 760 having notches for separating the wires. The hypotube 760 can be epoxied to the fiber-terminated, angle-polished drive shaft and SC connector 720. Both the electrical pin 710 and the optical connector 720 are epoxied into the proximal face of the internal cap 730, 735. The internal cap 730, 735 is rigidly connected to the drive shaft subsystem and therefore rotates with the device.

[0033] (external cap) In various embodiments, outer caps 740, 745 surround inner caps 730, 735 and can isolate rotational motion for ease of use. The inner caps 730, 735 can rotate within the outer caps 740, 745 and can be stabilized and centered by bearings 750. A ring lock 780, loaded by two springs 770, serves as the locking mechanism and extends into a release button at the top of the outer caps 740, 745. In addition to the ring lock 780, the grooved exterior surfaces of the outer caps 740, 745 facilitate locking and proper alignment of the catheter caps within the drive system.

[0034] In use, the R-TCE catheter uses optical coherence tomography (OCT) to image the lower gastrointestinal (GI) tract by inserting a tethered capsule containing micro-optics into the anus. Various embodiments of the R-TCE device can be used to diagnose diseases in the lower GI tract (e.g., Crohn's disease and / or colon cancer), quantify inflammation, screen for adenomas, detect cancer in the lower GI tract, and / or perform colon cancer screening.

[0035] As disclosed herein, in certain embodiments, the hard capsule body on the distal end of the drive shaft contains micro-optics, which may include various focusing elements such as a ball lens or prism connected to an optical fiber, and an angled reflector (e.g., a mirror or reflective prism) coupled to a micromotor to rotate the prism. In some embodiments, an ellipsoidal reflector can be used to direct light from the optical fiber to the tissue.

[0036] In various embodiments, an anti-reflective coating can be applied to the ball lens to reduce numerous image artifacts from the capsule wall. In some embodiments, electrical wires can be soldered to the motor and powered from terminations on the catheter cap. In use, rotating the angled reflector allows electromagnetic radiation (e.g., OCT light) from the fiber optic to reach the entire circumference of the tissue surrounding the capsule, creating a 360-degree image that can be displayed on a Computational Imaging System (CIS).

[0037] Generally, these threads (e.g., silicone threads) may not be completely optically transparent, thus enabling depth imaging with low light loss in certain embodiments that provide an imaging window gap. In certain embodiments, one or more threads of the capsule may include a gap that provides a circumferential imaging window that aligns with the imaging optics to allow image data to be obtained from the tissue in an unobstructed manner. In other embodiments, the thread may extend the entire length of the capsule, and other methods, such as post-processing of image data or adjusting the refractive index of the thread material to more closely match the refractive index of the tissue, may be used to compensate for possible distorting effects due to the thread.

[0038] In various embodiments, the R-TCE capsule can be made from a hard material surrounded by an elastic outer layer containing one or more helical threads. While silicone is a suitable material for making threads due to its biocompatibility and elasticity, other elastic and biocompatible materials can be used instead of or in addition to silicone to form the outer layer of the R-TCE capsule. In particular, the threads can be integrally formed as part of the capsule body, which can be formed from a hard material or from an elastic or semi-elastic material. In some embodiments, an imaging window can be formed in the elastic outer layer by providing a thin central section (i.e., a gap in the thread) that does not contain one or more threads, or by providing the elastic outer layer as two separate sections, including a proximal layer and a distal layer (see Figure 5). In particular embodiments, the one or more threads spiral around the capsule and protrude 1 to 5 mm from the surface of the capsule and / or elastic outer layer, and according to one embodiment, can protrude 3 mm (see Figure 1A). The R-TCE capsule may include one, two, three, or other number of outwardly protruding threads to facilitate movement of the capsule as it is rotated. The threads can be shaped and angled at various angles to best match the type of tissue being traversed and to advance at a suitable axial velocity with each rotation of the capsule. Generally, one or more of the threads can be or include ridges that protrude outward from the capsule sufficiently so that the threads engage tissue to propel the capsule as it is rotated.

[0039] In certain embodiments, the rigid portion of the R-TCE capsule may have an outer diameter between 8 and 15 mm, and in one particular embodiment, an outer diameter of 11 mm (see FIG. 1A). In some embodiments, the outer layer in the thread-free areas may have a thickness of 0.5 to 3 mm, and in one embodiment, a thickness of 1 mm. In various embodiments, the portion of the outer layer containing the thread may have a thickness of 1 to 5 mm, and in one particular embodiment, a thickness of 3 mm. Finally, the diameter of the outer sheath is 2 to 3 mm, and in one particular embodiment, 2.1971 mm. See FIG. 1A for exemplary diameters of various components of certain embodiments of the R-TCE capsule.

[0040] In various embodiments, the balloon may be mounted near the strain relief, such that the balloon is adjacent to the capsule, e.g., under or at the bottom of the silicone cap (see FIG. 8A). The balloon may be configured to expand within the colon to provide improved image quality. In particular, the balloon can be inflated (e.g., with a gas such as air or a liquid such as saline) during operation (e.g., during pullback imaging) centered on the capsule within the colon, allowing complete image data to be obtained from a 360° view of the surrounding tissue with a single pullback. In further embodiments, an infusion tube may be mounted next to the drive shaft to deliver water / saline to the imaging window to remove debris.

[0041] Figure 8B shows a cross-section of the tether between the balloon and the proximal end in the position shown in Figure 8A. The cross-section shows the drive cable with single-mode fiber (SMF) and motor power wires disposed therein, the balloon inflation channel (for delivery of gas or liquid inflation fluid), the water delivery channel (for flushing debris from the imaging window), and the suction channel.

[0042] FIG. 8C shows a close-up of the capsule as shown in FIG. 8A, where dc is the drive cable, s is the strain relief, dcca is the drive cable-capsule connection, t is the silicone thread, bl is the ball lens, mnt is the motor mount, m is the motor, w is the imaging window, and p is the prism.

[0043] Figure 9 illustrates an R-TCE catheter with a balloon, where the diagram provides approximate sizes or size ranges for the balloon axial length (7 cm), balloon diameter (0-6 cm), and capsule diameter (1.2 cm). The diagram in Figure 9 also shows the relative positions of the catheter cap, aspiration / infusion tubing with coupling and connecting wrap, drive shaft, balloon, infusion outlet, and capsule (reproductions of various components are not to scale). Finally, the enlarged view in Figure 9 shows details of the capsule design.

[0044] In various embodiments, the balloon can be inflated to a diameter less than, equal to, or greater than the outer diameter of the R-TCE catheter. In the embodiment shown in Figure 8A, the balloon is approximately 7 cm axially and has an outer diameter greater than the outer diameter of the R-TCE capsule. In various embodiments, the outer diameter of the inflated balloon matches the focal length of the R-TCE capsule optic (see Figure 1A), so that the balloon uniformly stretches the tissue outward to a distance consistent with the focal length.

[0045] The use of external threads (e.g., silicone threads) on the exterior of the capsule can convert rotational motion into axial motion, thereby facilitating OCT imaging within the lower GI tract, which has not been previously possible. The capsule can also be equipped with a balloon, which can facilitate visualization of the colon wall, which has a relatively large diameter compared to the capsule's size. Furthermore, the R-TCE includes an internal sheath, or a rotating drive shaft, that houses a tether, similar to those used in upper GI capsules.

[0046] (Attaching the capsule tip) In some embodiments, the R-TCE capsule can include an extension at its distal end to help prevent the capsule from getting stuck in tight bends in tissue (e.g., the colon). In various embodiments, the extension can be the 25-50 mm distal tip of a wire, such as a guidewire (see Figures 10A and 10B). In use, when the distal tip contacts the mucosal wall, it deflects the capsule, changing its angle to allow transverse movement and continuing to follow the course of the lumen. The distal tip can be a straight, commercially available GI guidewire, as shown in Figure 10A, or a tapered, spring-shaped tip, as shown in Figure 10B. Here, the mechanical properties of the distal tip can be selected by the length, thickness, flexibility, or spring properties of the guidewire tip, such as shape, dimensions (vertical), number of coils, and flexibility. As shown in Figure 10, the distal tip can be relatively straight (see Figure 10A) or tapered / conical (see Figure 10B).

[0047] Multi-use catheters typically undergo high-level disinfection (HLD) before their first use and after each use according to standard sterilization protocols (e.g., those established in the GI unit at Massachusetts General Hospital (MGH)). In one embodiment, this protocol is the same as that for endoscopes and esophageal manometry study catheters (ESMO) in the GI unit at MGH, both of which are removed through the upper gastrointestinal tract.

[0048] (Plasma treatment) In some embodiments, R-TCE capsules can be pretreated to reduce fouling during use, making subsequent cleaning and sterilization easier. In various embodiments, hard capsules made of polymethyl methacrylate (PMMA) can be treated with O2 / CF4 plasma (see arrows in Figure 11) to modify the R-TCE capsule wall by etching. Plasma treatment increased the hydrophilicity of the surface with O2 gas, while increased the hydrophobicity of the surface with CF4, both of which improved antifouling performance. Plasma-treated PMMA capsules with CF4 content between 20% and 40% achieved both good antifouling properties and hydrophilicity.

[0049] (excision) In various embodiments, the R-TCE device can be used in the colon to treat precancerous lesions, including colon polyps, using OCT-guided laser ablation. In such embodiments, the device includes an OCT imaging system and a therapeutic laser integrated into the imaging system. In certain embodiments, the OCT system can include an OCT imaging console and an OCT therapeutic capsule, where the capsule can include a single waveguide (e.g., a single-mode fiber or a multimode fiber) or multiple waveguides (e.g., a multicore fiber) that deliver therapeutic light to the OCT capsule. The capsule can further include optical components that transmit the light toward the capsule to the identified lesion, and can share an OCT imaging component, such as those therapeutic optical components described herein.

[0050] FIG. 12 illustrates an R-TCE OCT treatment system based on R-TCE as disclosed above, with an additional treatment laser in the imaging console or a separate treatment console. Thus, in certain embodiments, the R-TCE OCT treatment system can include a first electromagnetic radiation source as part of the imaging console (e.g., the OCT imaging console of FIG. 12 ) and a second electromagnetic radiation source as part of the treatment / ablation device (e.g., the treatment console of FIG. 12 ). One embodiment of the treatment capsule includes a waveguide, a ball lens, and a rotating reflector for delivering light, where the ball lens focuses both the OCT light and the treatment light (both shown as dotted lines) onto the tissue (see FIG. 13 ).

[0051] Another embodiment of the treatment capsule includes a second waveguide (in addition to the OCT waveguide) for delivering therapeutic electromagnetic radiation, a focusing / collimating optical module, and a rotating reflector for delivering light (see FIG. 14). The focusing / collimating optical module focuses the OCT light (dotted line) for imaging and collimates the therapeutic light (solid line) to cover a large area of tissue for ablation. Yet another embodiment of the treatment capsule (see FIG. 15) includes a single waveguide that delivers OCT and / or therapeutic light to a focusing / collimating lens, where the lens focuses the OCT laser (dotted line) and collimates the therapeutic light (solid line).

[0052] Additionally, another embodiment of the treatment capsule includes a single waveguide (for both OCT light and therapeutic light), an adjustable lens, and a rotating reflector for delivering light (see FIG. 16 ), where the focusing power of the adjustable lens can be controlled. When the capsule performs OCT imaging, the adjustable lens can focus the OCT laser (dotted line) on the tissue, which can occur before the target lesion is identified and the therapeutic laser is activated. When therapeutic light delivery is desired, the adjustable lens focuses / collimates the therapeutic light (dashed line) onto the tissue. The spot size of the treatment laser can also be adjusted by the adjustable lens, ablating areas of various sizes depending on the lesion characteristics of the tissue.

[0053] In various embodiments, the R-TCE OCT treatment capsule can be used to screen for colon polyps in OCT mode. Once one or more polyps are identified and located, the system records the polyp coordinates, and the rotating reflector stops at those coordinates. The treatment laser can then be activated for a period of time with a specific illumination pattern, including, for example, continuous illumination, repetitive pulsed illumination, etc., to ablate the tissue site.

[0054] In certain embodiments, laser-induced tissue ablation can be "non-thermally limited," meaning that tissue ablation begins where the therapeutic laser is focused (e.g., the impact zone), and the size of the ablated tissue region depends on heat transfer to the tissue, which can be controlled by the duration of laser irradiation. That is, a portion of the sample beyond the impact zone is ablated, and ablation is not limited to the region where the laser radiation contacts the tissue. In other embodiments, laser-induced tissue ablation can be "thermally limited," meaning that once the laser is turned on, tissue ablation begins instantaneously, and heat is not transferred outside the irradiated region, such that the size of the ablation is determined by the size of the laser spot on the tissue.

[0055] In various embodiments, the wavelength of the therapeutic laser can be within the high water-absorption spectrum between 1400 nm and 2000 nm. The therapeutic laser light can be absorbed by tissue, generating heat that can denature proteins within cells or thermally ablate cells.

[0056] Figure 17 shows histological images of laser-ablated colon tissue (pig colon). The image on the left was stained with nitroblue tetrazolium chloride (NBTC) to show inactive cells. The image on the right was stained with H&E to show the tissue area ablated by the laser.

[0057] (Computer-Aided Polyp Detection) In various embodiments, the R-TCE system can be used to obtain data that can be used for computer-aided polyp detection based on other data processing procedures, differential bandwidth correlation, scattering coefficient, angular scattering, and texture analysis.

[0058] In some embodiments, three independent data processing approaches can be combined in a data fusion step to generate a classifier. These approaches include determining correlation of differential bandwidth (COD), determining scattering coefficients for each A-line, and determining angular scattering of the sample. Finally, a classifier (such as ResNet101) can be trained to predict polyp type based on the processed data. In various embodiments, one or more other classifiers can be used, including squeezenet, googlenet, inceptionv3, mobilenetv2, xception, resnet18, resnet50, resnet101, inceptionresnetv2, efficientnetb0, and / or alexnet. In other embodiments, after identifying boundaries around the point cloud corresponding to identifiable classifications, the 3D point cloud can be used to plot u_s, ASI, and standard deviation (STD) of the COD bandwidth. The classification of an unknown sample can be identified using its position in u_s, ASI, and STD, as well as the location of the boundaries.

[0059] (differential bandwidth correlation) The OCT signal contains information about the spectrum of the light beam, and spectroscopic processing methods allow for the resolution of this depth-dependent spectrum. Using additional processing techniques, such as COD bandwidth, we can assign a scattering size to each tissue pixel at depth by taking the spectrum at each point, performing a normalization operation (e.g., numerical differentiation), and then performing an autocorrelation and comparing it to a known reference size. The results can then be displayed in two or three dimensions.

[0060] In contrast to traditional COD analysis, the present procedure uses some similar variations in calculating the local standard deviation of the COD bandwidth using a reference square (of any size) that scans either the B-scan image or the en face view of the average COD bandwidth. At each position during the scan, the standard deviation is calculated. This standard deviation provides information about how fast the modulation frequency changes. It has been shown that there are clear differences between normal and adenomatous tissue (see Figure 18).

[0061] (scattering coefficient μ s ) The OCT signal exhibits both scattering and attenuation as a function of depth into the sample, which is determined by the scattering and absorption coefficients (μ, respectively). s , μ a ), which can be displayed on an en face map as a single value for each A-line (Figure 19 shows an en face map of the scattering coefficient). To obtain the scattering and absorption coefficients, the linear OCT image must first be corrected to compensate for the intensity attenuation caused by the confocal gate. Then, μ can be calculated through curve fitting of the A-lines or other methods. s It is possible to extract a coefficient, μ, which can have higher contrast than the frontal projection produced by simply adding A-lines, but still have the same high contrast as the frontal projection. s This is particularly useful for obtaining maps of the scattering coefficients generated in this manner, which have previously been shown to correlate with normal and malignant colonic tissue.

[0062] (Angular scattering coefficient) Pit patterns on tissue surfaces have different structures depending on the tissue type and have previously been shown to be useful for distinguishing normal and cancerous tissue. Consistent with this, Fourier domain displays of tissue types show differences in frequency content, including, but not limited to, normal tissue, tubular adenomas, hyperplastic polyps, sessile serrated adenomas, and sessile serrated polyps. To extract this information from the Fourier domain spectrum, in one embodiment, a scanning square (shown by the intersection of lines in FIG. 20 ) can be used to extract subregions of the image. The amplitude spectrum (or logarithm of the Fourier transform) of the subregion can then be calculated, and the energy ratios at low and high spatial frequencies in the subregion can then be determined to generate an index value that can be used to distinguish different polyps.

[0063] In various embodiments, a high-contrast en face representation of the data can be used to extract spatial frequencies. In some embodiments, a high-contrast en face representation is obtained by generating en face projections (e.g., by simply summing a well-defined number of pixels from a plane). However, these projections may have low contrast and may not always have their viewing direction oriented perpendicular to the tissue plane. Therefore, in some embodiments, a better option is to use μ s map is generated, and then the scanning square is μ s A patch-wise approach is to use these maps such that the orthogonal orientation of each sub-region within the scan square is corrected by moving across the map. These resulting orientation-corrected patches can then be processed using Fourier domain operations.

[0064] In certain embodiments, a dual-aperture approach to this can be taken, where a small circle (low-frequency mask) in Fourier space can be used to pass low spatial frequencies while masking the high ones (see the center diagram in FIG. 21 ), and a ring (i.e., a high-frequency mask made of radial bands, shown on the right in FIG. 21 ) can be used to pass only the high spatial frequencies, where the ratio of the energy of the low spatial frequency components divided by the energy of the high spatial frequency components can be determined. This ratio of the energy concentrated at low / high spatial frequencies gives the angular scattering index (ASI), as shown in FIG. 22 . Calculating this index is similar to procedures that have been used for cancer (but not polyp) detection, but there are some substantial differences. One difference is that previous approaches use dynamically assigned elliptical apertures in Fourier space, which likely accounts for the fact that some images do not appear orthogonal to the surface, while accounting for how the spatial frequencies for the irradiated tissue are tilted relative to the OCT beam. The present procedure, on the other hand, uses static apertures and rings in Fourier space to specify the energy used to determine the indices. In this procedure, each patch can be flattened by first determining its surface orthogonal vector to control the tissue orientation.

[0065] In various embodiments, the angular or radial energy distribution of either the inner or outer aperture can be used to detect the degree of spatial frequency homogeneity. In yet other embodiments, a triple aperture can be used instead of the dual aperture approach described above, in which case the triple aperture can measure energy in the low-frequency center (as described above) as well as the inner and outer rings (e.g., the radial band in the right diagram of FIG. 21 can be divided into two parts, the inner and outer rings). The ratio of the energy in the outer ring to the energy in the inner ring can be used as a separate parameter indicating the concentration of energy in the third band. This additional information is important only if hyperplastic and normal tissue morphologies may be superficially similar when viewed in real space but may have different spatial frequencies, and these differences in spatial frequency can be distinguished in Fourier space.

[0066] In another embodiment, similar information can be extracted from B-scans by first attenuation correcting the OCT signal using the method reported by Cheng (see J Biomed Opt, 2019.24(9), pp. 1-17, cited herein), followed by a two-dimensional Fourier transform to look for the energy distribution in vertically sliced bands.

[0067] (Data Fusion and Machine Learning) In some embodiments, a deep learning network may be used with multiple patches or the entire image as training and validation data in two ways: early fusion and late fusion. In early fusion, three channels (scattering coefficient map, angular scattering coefficient, and COD bandwidth) are input into a pre-trained network (e.g., ResNet101), excluding either multiple polyps or multiple patches for validation. In late fusion, each channel is fed into the network individually, and the final classification is determined using either a weighted probability or a decision tree. Instead of or in addition to the above channels, first- and second-order intensity statistics, including gray-level co-occurrence matrices and features, can also be used.

[0068] Upon predicting the polyp type, the system can communicate information regarding the polyp type to a clinician or other interested party, who can decide on a course of treatment or other action to take based on the predicted polyp type.

[0069] (Computer System) In various embodiments, the R-TCE system 100 (which may include one or more of a drive system, an imaging system / console, and / or a treatment system / console) may include a controller, such as a processor 130, a memory 160, a power source 140 (e.g., a battery, such as a rechargeable battery), and / or a communication system 150 (e.g., a wireless communication modality, such as Bluetooth®, or a suitable wired communication mechanism) (see FIG. 23). In some embodiments, the R-TCE system 100 may be self-contained and programmed to perform the various procedures disclosed herein without requiring input or control from an external source. In other embodiments, the R-TCE system 100 may be programmed to perform the various procedures disclosed herein that are initiated upon receipt of a signal from an external source. In still other embodiments, the R-TCE system 100 may not have the capability to perform the various procedures, but instead may perform the procedures based on a sequential series of individual instructions sent to the R-TCE system 100 from an external source.

[0070] Thus, in various embodiments, software for controlling the R-TCE system may reside on R-TCE system 100 itself, on an external device, and / or distributed between R-TCE system 100 and one or more external devices. In particular embodiments, the external device includes a standalone computer system 500, which may include a portable device such as a tablet, laptop computer, or smartphone, in communication 505 (e.g., wired or wireless) with R-TCE system 100 (see FIG. 8). This software may be provided as an application ("app") for execution on the device, with the app providing instructions to R-TCE system 100 (e.g., issued via Bluetooth or other wireless or wired communication) to perform the various procedures disclosed herein.

[0071] The bottom portion of FIG. 23 illustrates an embodiment of a computer system 500 that can be used to transmit control information to R-TCE system 100 (e.g., via wired or wireless communication 505) in accordance with some embodiments of the disclosed subject matter. As shown in FIG. 23 , in some embodiments, computer system 500 can include a processor 510, a user interface and / or display 540, one or more communication systems 530, and memory 520. In some embodiments, processor 510 can be any suitable hardware processor or combination of processors, such as a central processing unit (CPU), a graphics processing unit (GPU), a microcontroller (MCU), a field programmable gate array (FPGA), an application specific integrated circuit (ASIC), a dedicated image processing device, etc. In some embodiments, one or more input and / or display units 540 can include any suitable one or more display devices, such as a computer monitor, a touchscreen, a television, etc., and / or input devices and / or sensors that can be used to receive user input, such as a keyboard, one or more physical buttons with dedicated functions, one or more physical buttons with software with programmable functions, a mouse, a touchscreen, a microphone, an eye tracking system, a motion sensor, etc.

[0072] In some embodiments, communications system 530 may include any suitable hardware, firmware, and / or software for communicating information over a communications network and / or other suitable communications network. For example, communications system 530 may include one or more transceivers, one or more communications chips and / or chipsets, etc. In more particular examples, communications system 530 may include hardware, firmware, and / or software that can be used to establish Wi-Fi connections, Bluetooth connections, cellular connections, Ethernet connections, optical connections, etc.

[0073] In some embodiments, memory 520 can include any suitable storage device or devices that can be used to store instructions, values, etc., for use by hardware processor 510, such as to process image data generated by one or more optical detectors, present content using one or more input / displays 540, communicate with external computing devices via one or more communication systems 530, etc. Memory 520 can include any suitable volatile memory, non-volatile memory, storage, any other suitable type of storage medium, or any suitable combination thereof. For example, memory 520 can include RAM, ROM, EEPROM, one or more flash drives, one or more hard disks, one or more solid-state drives, one or more optical drives, etc. In some embodiments, memory 520 can be coded with a computer program for executing one or more embodiments of the disclosed procedures.

[0074] Various embodiments are implemented in a system including a memory (e.g., memory 520) in communication with a processor (e.g., processor 510), the memory including a set of instructions stored thereon that, when executed by the processor, cause the processor to perform steps of various embodiments of the procedures disclosed herein. According to some embodiments, the memory may include any suitable computer-readable medium that can be used to store instructions for implementing the functions and / or processes disclosed herein. For example, in some embodiments, the computer-readable medium may be transitory or non-transitory. For example, non-transitory computer-readable medium may include magnetic media (hard disks, floppy disks, etc.), optical media (compact discs, digital video discs, Blu-ray Discs, etc.), semiconductor media (RAM, flash memory, electrically programmable read-only memory (EPROM), electrically erasable programmable read-only memory (EEPROM), etc.), any suitable medium that is not transitory or permanent in transmission, and / or any suitable tangible medium. As another example, a primary computer-readable medium may include a signal on a network, in an electrical wire, in a conductor, in an optical fiber, in a circuit, or any suitable medium that is not transitory or permanent during transmission, and / or any suitable tangible medium.

[0075] (Example) The following provides non-limiting examples according to various embodiments of the present disclosure. (Structure and operation of the R-TCE device, power to the distal micromotor) Electrically, the micromotor of the R-TCE device is powered by a motor power unit (MPU) integrated within the CIS. A motor power subassembly inside the CIS device transmits power through electrical wires. The MPU subassembly is powered by a DC power supply housed within the CIS case. The waveform sent to the capsule catheter micromotor via the insulated wires is less than 10.0 V. The bandwidth of the waveform is limited to approximately 10 kHz. The capsule catheter leakage current complies with the IEC 60601-1 standard.

[0076] (electrical insulation) The R-TCE device contains a very thin wire that runs through the lumen of the inner sheath and supplies power from the motor power unit to the micromotor. There are three layers of material between the wire and the outer surface of the inner sheath. The wire itself is insulated with a non-conductive perfluoroalkoxy alkane (PFA) material. Surrounding the PFA-coated wire is an insulating, multi-layered inner sheath. The inner sheath is made of an inner PTFE-coated layer and an outer PMMA layer. The inner sheath is enclosed within the drive shaft, and an outer sheath, which comes into contact with the patient, fits over the drive shaft. The outer sheath is made of the same material as the inner sheath.

[0077] The non-conductive capsule body serves as the primary insulating layer for the micromotor and the electrical wires at the distal tip of the catheter. The solder joints between the electrical wires and the micromotor within the capsule body are covered with non-conductive epoxy, which also provides a second insulating layer.

[0078] (Capsule Design) In one embodiment, the basic capsule design includes a rigid capsule body housing the micro-optics, a micromotor to rotate the micro-optics, and a tether connecting to the imaging console. A variation disclosed herein is a retrograde TCE capsule (see Figures 1 and 1A). The R-TCE has an outer silicone layer with flexible / elastic threads, which provides the additional functionality of self-propulsion for navigating the colon while minimizing local tissue trauma. The capsule is 27 mm long, including the outer layer. The inner rigid capsule has a diameter of 11 mm, and the outer flexible silicone layer has a diameter of 16 mm at the end of the threads (see Figure 1A). The unthreaded outer layer is 1 mm thick. Finally, the diameter of the outer sheath is 2.1971 mm.

[0079] Design control procedures are followed for all capsules. The design of the motor power unit includes verification and validation procedures to ensure the device is electrically and mechanically safe during manufacturing and use, as well as a failure mode analysis. Failure mode and effect analysis conducted in accordance with NFPA-99 "Standard for Health Care Facilities" and IEC 60601-1 guidelines for medical electrical equipment poses a low electrical risk to the patient or user.

[0080] (specification) [Table 1]

[0081] (Safety testing) Below is a table showing several tests that are performed on catheters to ensure the aforementioned safety features before they are put into clinical use. [Table 2]

[0082] The catheter may be introduced for clinical use only if all of the above tests meet the prescribed criteria. Each capsule should be labeled with a unique identifier, HLDI date, and expiration date.

[0083] (Environmental requirements) The catheter is designed to withstand normal shipping and operating conditions, but should be handled with care during shipping and installation. Knocking or dropping the catheter may damage the capsule, rendering it unusable for clinical use. The catheter is designed to operate at room temperature (10°C to 35°C) and relative humidity (RH) of 10 to 90%.

[0084] (Pre-procedure testing and calibration) As disclosed herein, each capsule is thoroughly disinfected before its first use and after each use. After disinfection, each catheter is tested and calibrated before use. After passing visual and tactile inspections for integrity, the capsule is connected to a system for image quality confirmation. If the catheter fails any of these tests, it cannot be used for clinical imaging diagnostics.

[0085] (Optical and electrical connection procedures) 1. Connect the drive system (R-TCE-DS) to the CIS and turn on the power to the CIS. 2. Ensure the drive system catheter cap interface returns to the home position, which should occur automatically when the R-TCE-DS is powered on (via the CIS). 3. Align the capsule catheter cap with the drive system catheter cap. The button protruding from the capsule's outer catheter cap should correspond to the top position of the catheter cap and be aligned with the drive system accordingly. 4. Gently push the catheter cap into the drive system until you hear a click, indicating it is locked in place. If inserted correctly, the catheter cap should not be able to be rotated or easily pulled out.

[0086] (Handling procedures during clinical procedures) 1. Ensure that the drive shaft is free of knots and twists by straightening it and handing it over to the capsule operator. 2. The capsule operator can hold the catheter at any position on the drive shaft or capsule with his / her fingers to avoid applying too much pressure. 3. The catheter can be handed to the subject, who can hold the drive shaft at any position on the tether or capsule with their fingers to avoid applying too much pressure. 4. The capsule operator can control the capsule position throughout the procedure via the drive shaft, which can withstand bending but must not be subjected to significant torque due to the fragility of the optical fiber inside. 5. The position of the capsule can be estimated using the position marks on the outer sheath.

[0087] (Navigation by capsule) 1. During the procedure, the live image on the CIS should be monitored. If the image begins to "collapse" (stops spinning, then spins quickly for a few seconds) or stops completely, the operator should start counting or watching the clock. This indicates that the capsule is not rotating or advancing. 2. If the problem persists for 15 seconds, rotation will be halted and appropriate action will be taken, which may include manually rotating the drive shaft to release the torque or reversing the drive system to fully extract the capsule.

[0088] (Optical and Electrical Disconnect Procedures) 1. Stop the laser in the imaging system and turn off the power to the micromotor power supply unit. 2. Gently release the locking mechanism and pull the capsule catheter cap away from the driver.

[0089] Thus, while the invention has been described above with reference to particular embodiments and examples, the invention is not necessarily so limited, and numerous other embodiments, examples, uses, modifications, and departures from the embodiments, examples, and uses are intended to be encompassed by the claims appended hereto.

Claims

1. a capsule including at least one outward spiral thread; a drive shaft coupled to the capsule and configured to rotate the capsule; an optical system disposed within the capsule and configured to acquire ambient image information; 1. A system for performing retrograde tethered capsule endoscopy, comprising:

2. further comprising an optical waveguide disposed within the drive shaft; The system of claim 1 , wherein the optical system comprises a lens disposed within the capsule and optically coupled to the optical waveguide.

3. the optical system further includes an angled reflector aligned with the lens; The system of claim 2 , wherein the angled reflector is configured to rotate electromagnetic radiation emitted from the lens in a circumferential pattern around the capsule.

4. The system of claim 3 , wherein the capsule further comprises a circumferential imaging window aligned with the angled reflector.

5. The system of claim 4 , wherein the at least one outward spiral thread is absent within the circumferential imaging window.

6. the capsule includes a hard capsule inner body and an elastomeric outer shell; The system of claim 5 , wherein the elastomeric sheath includes the at least one outwardly spiraling thread.

7. the elastomeric outer shell includes a proximal layer and a distal layer attached to the hard capsule inner body; The system of claim 6 , wherein the circumferential imaging window is between the proximal layer and the distal layer.

8. The system of claim 6 , wherein the elastomeric sheath comprises silicone.

9. further comprising an imaging system; The system of claim 3 , wherein the imaging system is coupled to the optical system using the optical waveguide.

10. the imaging system includes an interferometric imaging system; The system of claim 9 , wherein the ambient image information is acquired using the interferometric imaging system.

11. The system of claim 1 further comprising a drive system coupled to the drive shaft.

12. the drive shaft comprises a semi-rigid drive shaft; 12. The system of claim 11, wherein the drive system is configured to rotate the semi-rigid drive shaft to rotate the capsule in a first rotational direction and a second rotational direction opposite the first rotational direction.

13. the drive system is coupled to the semi-rigid drive shaft using a catheter cap; The system of claim 12 , wherein the catheter cap provides at least one of optical and electrical coupling to the capsule.

14. the catheter cap includes an outer cap and an inner cap disposed within the outer cap and having a bearing therebetween; The system of claim 13 , wherein the inner cap rotates within the outer cap via the bearing, thereby rotating the semi-rigid drive shaft.

15. the angled reflector is rotated using a micromotor; Power is supplied to the micromotor via wires in the drive shaft. The system of claim 3.

16. 16. The system of claim 15, wherein the lens comprises at least one of a ball lens or a prism configured to direct light from the light guide to the angled reflector.

17. The system of claim 9 further comprising a balloon surrounding the drive shaft adjacent the capsule.

18. The system of claim 17 , wherein the balloon is configured to be inflated during operation of the imaging system.

19. The system of claim 4 , further comprising an infusion tube configured to deliver fluid to the imaging window to remove debris.

20. further comprising a first electromagnetic radiation source for imaging and a second electromagnetic radiation source for ablation; each of the first electromagnetic radiation source and the second electromagnetic radiation source is optically coupled to the optical system; the first electromagnetic radiation source is configured to acquire ambient image information of a sample; the second electromagnetic radiation source is configured to ablate the sample; The system of claim 1 .

21. 21. The system of claim 20, wherein the optical system includes a lens configured to at least one of focus the electromagnetic radiation from the first electromagnetic radiation source and collimate the electromagnetic radiation from the second electromagnetic radiation source.

22. further comprising an optical waveguide disposed within the drive shaft; 22. The system of claim 21, wherein each of the first and second electromagnetic radiation sources uses the optical waveguide to deliver the electromagnetic radiation to the optical system.

23. the lens comprises an adjustable lens; 23. The system of claim 22, wherein the adjustable lens is configured to adjust a focusing ability based on whether the first electromagnetic radiation source or the second electromagnetic radiation source delivers electromagnetic radiation to the optical system.

24. further comprising a first optical waveguide and a second optical waveguide disposed within the drive shaft; the first electromagnetic radiation source delivers electromagnetic radiation to the optical system using the first optical waveguide; 22. The system of claim 21, wherein the second electromagnetic radiation source delivers electromagnetic radiation to the optical system using the second optical waveguide.

25. The system of claim 1 , wherein the capsule is pre-treated with plasma to reduce fouling during use.

26. The capsule comprises polymethyl methacrylate (PMMA) and is etched using O ２ / CF ４ 26. The system of claim 25, wherein the system is pretreated with plasma.

27. providing a capsule including at least one outwardly spiral thread and an optical system disposed within said capsule; Rotating a drive shaft connected to the capsule; acquiring ambient image information using the optical system disposed within the capsule; A method for performing retrograde tethered capsule endoscopy.

28. Providing a capsule further includes providing the capsule including an optical waveguide disposed within the drive shaft; 28. The method of claim 27, wherein the optical system comprises a lens disposed within the capsule and optically coupled to the optical waveguide.

29. Providing the capsule further includes providing the capsule, wherein the optical system further includes an angled reflector aligned with the lens; 30. The method of claim 28, further comprising rotating the angled reflector to direct electromagnetic radiation emitted from the lens toward a periphery of the capsule.

30. Providing a capsule further includes providing the capsule further including a circumferential imaging window aligned with the angled reflector; 30. The method of claim 29, wherein the at least one outward spiral thread is not within an area of the circumferential imaging window.

31. Providing a capsule further includes providing the capsule including a hard capsule inner body and an elastomeric outer shell; 31. The method of claim 30, wherein the elastomeric sheath includes the at least one outwardly spiraling thread.

32. Providing a capsule further includes providing the capsule, wherein the elastomeric outer shell includes a proximal layer and a distal layer attached to the hard capsule inner body; 32. The method of claim 31 , wherein the circumferential imaging window is between the proximal layer and the distal layer.

33. acquiring the ambient image information further includes acquiring the ambient image information using an imaging system; the imaging system includes an interferometric imaging system; 30. The method of claim 29, wherein the imaging system is coupled to the optical system using the optical waveguide.

34. Providing a capsule further includes providing the capsule further including a drive system coupled to the drive shaft; the drive shaft comprises a semi-rigid drive shaft; 28. The method of claim 27, further comprising rotating the semi-rigid drive shaft with the drive system to rotate the capsule in a first rotational direction and a second rotational direction opposite the first rotational direction.

35. providing a capsule further includes providing the capsule wherein the drive system is coupled to the semi-rigid drive shaft using a catheter cap; 35. The method of claim 34, wherein the catheter cap provides at least one of optical and electrical coupling to the capsule.

36. Providing a capsule further includes providing the capsule, wherein the catheter cap includes an outer cap and an inner cap disposed within the outer cap and having a bearing therebetween; 36. The method of claim 35, further comprising rotating the semi-rigid drive shaft by rotating the inner cap within the outer cap via the bearing.

37. rotating the angled reflector further comprises rotating the angled reflector using a micromotor; 30. The method of claim 29, wherein power is supplied to the micromotor via wires in the drive shaft.

38. obtaining ambient image information further includes using the lens to direct light from the light guide to the angled reflector; 38. The method of claim 37, wherein the lens comprises at least one of a ball lens or a prism.

39. providing a capsule includes providing the capsule including a balloon surrounding the drive shaft adjacent the capsule; The method further comprises inflating the balloon while the imaging system is in operation.

34. The method of claim 33, comprising:

40. providing a capsule includes providing the capsule with an infusion tube; 31. The method of claim 30, further comprising delivering a fluid to the imaging window to remove debris.

41. Providing a capsule further includes providing the capsule including a first electromagnetic radiation source for imaging and a second electromagnetic radiation source for ablation; each of the first electromagnetic radiation source and the second electromagnetic radiation source is optically coupled to the optical system; The method further comprises: acquiring ambient image information of a sample using the first electromagnetic radiation source; ablating the sample using the second electromagnetic radiation source.

28. The method of claim 27.

42. Providing a capsule further includes providing the capsule wherein the optical system includes a lens; The method further comprises: focusing the electromagnetic radiation from the first electromagnetic radiation source using the lens; or and collimating the electromagnetic radiation from the second electromagnetic radiation source using the lens.

43. Providing a capsule further includes providing the capsule including an optical waveguide disposed within the drive shaft; 43. The method of claim 42, further comprising using the optical waveguide to deliver the electromagnetic radiation from each of the first and second electromagnetic radiation sources to the optical system.

44. Providing a capsule further includes providing the capsule wherein the lens includes an adjustable lens; 44. The method of claim 43, further comprising adjusting a focusing ability of the adjustable lens based on whether the first electromagnetic radiation source or the second electromagnetic radiation source delivers electromagnetic radiation to the optical system.

45. Providing a capsule further includes providing the capsule further including a first optical waveguide and a second optical waveguide disposed within the drive shaft; The method further comprises: using the first optical waveguide to deliver electromagnetic radiation from the first electromagnetic radiation source to the optical system; 43. The method of claim 42, comprising using the second optical waveguide to deliver electromagnetic radiation from the second electromagnetic radiation source to the optical system.

46. further comprising pre-treating the capsule with plasma to reduce fouling during use; The capsule comprises polymethyl methacrylate (PMMA) and is etched using O ２ / CF ４ 28. The method of claim 27, wherein the pretreatment is by plasma.

47. ablating the sample further includes directing electromagnetic radiation from the second electromagnetic radiation source toward an impact region of the sample for a specified duration to perform non-thermal limited ablation; 42. The method of claim 41, wherein a portion of the sample beyond the impact region is ablated.

48. ablating the sample further includes directing electromagnetic radiation from the second electromagnetic radiation source toward an impact region of the sample to perform thermal limited ablation; 42. The method of claim 41, wherein the portion of the sample beyond the impact area is not ablated.

49. acquiring an image of the sample using a processor; determining, with the processor, a derivative bandwidth correlation (COD) for the image; determining, with the processor, a scattering coefficient for the image; determining angular scattering coefficients for the images using the processor; A method of polyp detection, using the processor to predict the type of polyp in the sample by training a classifier based on the differential bandwidth correlation, the scattering coefficient, and the angular scattering coefficient.

50. 50. The method of claim 49, wherein determining a differential bandwidth correlation (COD) further comprises determining the differential bandwidth correlation (COD) for each of a plurality of reference squares of the image, and determining a local standard deviation of the differential bandwidth correlation (COD) for each of the plurality of reference squares of the image.

51. the image includes a plurality of A-lines; 50. The method of claim 49, wherein determining a scattering coefficient further comprises determining a scattering coefficient for each of the plurality of A-lines of the image.

52. 52. The method of claim 51 , wherein determining a scattering coefficient for each of the plurality of A-lines of the image further comprises determining the scattering coefficient for each of the plurality of A-lines of the image using curve fitting.

53. Determining the angular scattering coefficient further comprises: generating a scattering coefficient map based on the image; generating a plurality of sub-regions of the scattering coefficient map; orienting each of the plurality of subregions of the scattering coefficient map so that it is perpendicular to a surface of the sample; determining energy associated with low and high spatial frequency regions in each of the plurality of sub-regions of the scattering coefficient map; 50. The method of claim 49, comprising generating an angular scattering index for each of a plurality of sub-regions of the scattering coefficient map by generating a ratio of the energy associated with the low spatial frequency regions and the high spatial frequency regions in each of the plurality of sub-regions of the scattering coefficient map.

54. Determining energy associated with low and high spatial frequency regions in each of the plurality of sub-regions of the scattering coefficient map further comprises: generating a Fourier domain amplitude spectrum for each of the plurality of sub-regions of the scattering coefficient map; for each of the plurality of sub-regions of the scattering coefficient map, determining the energy associated with the low spatial frequency region by applying a low frequency mask to the Fourier domain amplitude spectrum; 54. The method of claim 53, comprising, for each of the plurality of sub-regions of the scattering coefficient map, determining the energy associated with the high spatial frequency region by applying a high frequency mask to the Fourier domain amplitude spectrum.

55. 50. The method of claim 49, wherein the classifier comprises ResNet101.

56. 50. The method of claim 49, wherein acquiring an image of a sample further comprises acquiring the image of the sample using an R-TCE system.

57. 50. The method of claim 49, wherein the sample comprises colon tissue.

58. 50. The method of claim 49, further comprising predicting the type of polyp thereby specifying a treatment.

59. 50. The method of claim 49, further comprising forwarding information regarding the type of the polyp to a clinician.

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