Multifunctional luminal organ imaging system

Abstract

A device for imaging a luminal organ is presented. The device includes: a flexible tether that includes an optical fiber with a distal end optically coupled to at least: a first and second Optical Coherence Tomography (OCT) light source, and a first and second OCT interference signal detector, where the first OCT light source produces light having a wavelength distribution centered at a first wavelength and the second OCT light source produces light having a wavelength distribution centered at a second wavelength different from the first wavelength; and a capsule that is physically coupled to a proximal end of the flexible tether, where the capsule includes a motor that is mechanically coupled to a mirror that conveys light from the first and second OCT light source to the luminal organ and conveys light from the luminal organ to the first and second OCT interference signal detector.

Description

Attorney Docket No.: C17393_P17393-02 / 0184.0317-PCTMULTIFUNCTIONAL LUMINAL ORGAN IMAGING SYSTEMRelated Application

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 703,308 entitled “Multifunctional Luminal Organ Imaging System,” filed October 4, 2024.Field

[0002] This disclosure relates generally to medical imaging of a luminal organ, such as an esophagus.Background

[0003] Over the past few decades, endoscopic optical coherence tomography (eOCT) has shown great potential for early diagnosis of esophageal cancer. One of the most salient examples is using OCT to augment the detection of dysplasia during Barrett’s esophagus (BE) surveillance, the established precursor to esophageal adenocarcinoma (EAC). Periodic screening and detecting the dysplasia associated with BE are crucial for monitoring the progression from BE to EAC and providing timely interventions. In this regard, eOCT has long been regarded as a promising imaging technology for detecting the dysplasia associated with the BE owing to its capability of realtime cross-sectional imaging of mucosal and submucosal layers with micron-scale resolution. Moreover, eOCT may greatly reduce errors associated with random biopsies that rely on conventional endoscope camera images of superficial mucosa.

[0004] The first generation of eOCT catheters for esophagus imaging utilized flexible fiber and micro-optics integrated inside an inflatable balloon. These fiber-opticcatheters can be deployed through an accessory port of a standard gastrointestinal (Gl) endoscope during a routine esophagogastroduodenoscopy procedure, providing comprehensive volumetric imaging of the esophagus by helical scanning of the optics inside a balloon. To ensure reliable imaging and optimal placement of the catheter, the balloon could be inflated until it fully contacts the surface of the esophagus. However, esophagogastroduodenoscopy requires patients to be sedated in specialized settings with special equipment and continuous monitoring of potential adverse reactions by trained medical professionals. It is time-consuming and costly and is not preferable for regular surveillance nor suitable for general screening purposes.

[0005] OCT-tethered capsule endomicroscopy (TCE) technology overcomes some, but not all, of the challenges mentioned above. Similar to wireless capsule endoscopy, the tethered capsule can be swallowed and is well tolerated by unsedated patients. Once swallowed, the capsule can acquire volumetric OCT images as it naturally progresses through the digestive system via gravity and peristalsis. Alternatively, the capsule can be pulled upwards toward the mouth using the tether, allowing for comprehensive imaging throughout the area it traverses. It is more patient-friendly and holds great promise for efficient and comfortable Gl surveillance, as it eliminates the need for sedation and can be conducted by nurses or technicians even in primary care clinics. However, TCE generally does not provide a conventional visible-light endoscopic view of the esophagus.

[0006] Conventional eOCT devices utilize a broadband light source with a center wavelength of around 1300 nm, affording an axial resolution of ~7 to 20 pm and a few millimeters of the imaging depth in tissue. These systems have successfully identified microarchitectural features associated with neoplasia in BE, such asirregular glandular morphology and increased surface signal intensity, achieving a sensitivity and specificity of 70 to 80%. However, with the current TCE technology, it remains challenging to detect early lesions mainly due to its suboptimal resolution and imaging contrast for OCT operating at 1300 nm. The recently developed ultrahigh- resolution (UHR) OCT endoscope and capsule technologies employing a broadband light source around 800 nm exhibit much improved axial resolution (~2.8 pm in air corresponding to ~2 pm in tissue) as well as enhanced imaging contrast owing to stronger light-tissue interactions around 800 nm than 1300 nm. On the one hand, it has been shown that the UHR OCT capsule is more effective for detecting features associated with esophageal neoplasia. On the other hand, the UHR OCT system compromises the imaging depth to less than 1 mm in highly scattering tissues such as esophagus and may be restrictive in some applications, such as evaluating the invasion depth of squamous cell carcinoma or EAC where a sufficient imaging depth is crucial.Summary

[0007] A device for imaging a luminal organ is presented. The device includes: a flexible tether including at least one optical fiber, where a distal end of the at least one optical fiber is optically coupled to at least: a first Optical Coherence Tomography (OCT) light source, a first OCT interference signal detector, a second OCT light source, and a second OCT interference signal detector, where the first OCT light source produces light having a wavelength distribution centered at a first wavelength, where the second OCT light source produces light having a wavelength distribution centered at a second wavelength, and where the first wavelength is different from the second wavelength; and a capsule that is physically coupled to a proximal end of the flexibletether, where the capsule includes a motor that is mechanically coupled to a mirror, where the mirror conveys light from the first OCT light source and from the second OCT light source to the luminal organ, and where the mirror conveys light from the luminal organ to the first OCT interference signal detector and to the second OCT interference signal detector.

[0008] Various optional features of the above device embodiments include the following. The capsule may further include a visible light camera and a visible light source aperture, and the flexible tether may further include a camera signal cable. The first OCT interference signal detector, the second OCT interference signal detector, and the visible light camera may be communicatively coupled to a display that displays, simultaneously, a first OCT image of the luminal organ obtained by OCT at the first wavelength, a second OCT image of the luminal organ obtained by OCT at the second wavelength, and a visible light image of the luminal organ obtained using the visible light camera. The first wavelength may be 800 nm and the second wavelength may be 1300 nm. The distal end of the flexible tether may be further optically coupled to an ablation laser, such that the mirror conveys light from the ablation laser to the luminal organ. The device may be usable to therapeutically ablate the luminal organ while imaging the luminal organ. The mirror may compensate for astigmatism induced by a wall of the capsule. The capsule may further include a dispersive element that compensates for chromatic focal shift. The luminal organ may include an esophagus. The capsule may have an outer diameter of less than 11 mm.

[0009] According to various embodiments, a system for imaging a luminal organ is presented. The system includes a first OCT system including a first light source and a first OCT interference signal detector; a second OCT system including a second OCT light source and a second OCT interference signal detector; a flexible tetherincluding at least one optical fiber, where a distal end of the at least one optical fiber is optically coupled to at least: the first OCT light source, the first OCT interference signal detector, the second OCT light source, and the second OCT interference signal detector, where the first OCT light source produces light having a wavelength distribution centered at a first wavelength, where the second OCT light source produces light having a wavelength distribution centered at a second wavelength, and where the first wavelength is different from the second wavelength; and a capsule that is physically coupled to a proximal end of the flexible tether, where the capsule includes a motor that is mechanically coupled to a mirror, where the mirror conveys light from the first OCT light source and from the second OCT light source to the luminal organ, and where the mirror conveys light from the luminal organ to the first OCT interference signal detector and to the second OCT interference signal detector.

[0010] Various optional features of the above system embodiments include the following. The capsule may further include a visible light camera and a visible light source aperture, and the flexible tether may further include a camera signal cable. The system may include a display, where the first OCT interference signal detector, the second OCT interference signal detector, and the visible light camera are communicatively coupled to the display, where the display is configured to display, simultaneously, a first OCT image of the luminal organ obtained by OCT at the first wavelength, a second OCT image of the luminal organ obtained by OCT at the second wavelength, and a visible light image of the luminal organ obtained using the visible light camera. The first wavelength may be 800 nm and the second wavelength may be 1300 nm. The system may include an ablation laser, where the distal end of the flexible tether is further optically coupled to the ablation laser, such that the mirror conveys light from the ablation laser to the luminal organ. The device may be usableto therapeutically ablate the luminal organ while imaging the luminal organ. The mirror may compensate for astigmatism induced by a wall of the capsule. The capsule may further include a dispersive element that compensates for chromatic focal shift. The luminal organ may include an esophagus. The capsule may have an outer diameter of less than 11 mm.

[0011] Combinations, (including multiple dependent combinations) of the above-described elements and those within the specification have been contemplated by the inventors and may be made, except where otherwise indicated or where contradictory.Brief Description of the Drawings

[0012] Various features of the examples can be more fully appreciated, as the same become better understood with reference to the following detailed description of the examples when considered in connection with the accompanying figures, in which:

[0013] Fig. 1 is a schematic diagram of a super-achromatic, anastigmatic optical layout for dual-wavelength OCT imaging using a tethered capsule, according to various embodiments;

[0014] Fig. 2 depicts ray-tracing simulation results of the chromatic focal shift of an example embodiment at a focal length of ~7 mm, with and without a BK7 rod spacer;

[0015] Fig. 3 depicts ray-tracing simulation results for a system that omits a curved mirror that is used in various embodiments, contrasted with the measured output beam shapes of a capsule along the axial direction that includes a curved mirror according to an example embodiment;

[0016] Fig. 4 is a schematic diagram of a capsule for imaging a luminal organ, according to various embodiments;

[0017] Fig. 5 shows photographs of an assembled capsule for imaging a luminal organ, according to an embodiment;

[0018] Fig. 6 is a schematic diagram of a system for imaging a luminal organ, including a tethered capsule and a remote system, which includes two OCT imaging systems, a visible light imaging system, and a laser ablation system, according to various embodiments;

[0019] Fig. 7 shows unwrapped en face images of 3D volumetric OCT images at 1300 nm and 800 nm obtained in an ex vivo swine study;

[0020] Fig. 8 is a photograph of the excised swine esophagus imaged as shown in Fig. 7;

[0021] Fig. 9 shows representative circumferential (polar) and unwrapped rectangular (Cartesian) cross-sectional images over one ablated spot along the dotted line shown in Fig. 7;

[0022] Fig. 10 is a photograph of a representative endoscope video camera view of a swine esophagus obtained in an in vivo study; and

[0023] Fig. 11 presents photographs of swine esophagus OCT imaging results obtained from the in vivo study.Description of the Examples

[0024] Reference will now be made in detail to example implementations, illustrated in the accompanying drawings. Wherever convenient, the same reference numbers will be used throughout the drawings to refer to the same or like parts. In the following description, reference is made to the accompanying drawings that form apart thereof, and in which is shown by way of illustration specific exemplary examples in which the invention may be practiced. These examples are described in sufficient detail to enable those skilled in the art to practice the invention and it is to be understood that other examples may be utilized and that changes may be made without departing from the scope of the invention. The following description is, therefore, merely exemplary.

[0025] Despite the promising potential of the TCE technology, its adoption by clinicians faces several challenges. One major hurdle is the substantial difference between OCT images and conventional endoscope camera images. The unique characteristics and features captured by OCT may be unfamiliar to many clinicians and requires extensive training in order to interpret and analyze OCT images effectively. Another challenge is the difficulty in tracking the imaging location due to the absence of visual guidance during TCE imaging. While OCT images may reveal abnormalities during screening, accurate colocalization of OCT images and subsequent biopsies becomes crucial for precise diagnosis, and it is challenging to rely on the location estimated from the insertion length of the tether. Laser marking has been introduced to create visible fiducial marks in the patient’s esophagus during OCT imaging and allows precise correlation between OCT images and histopathology. While the process requires a pause in scanning and imaging, typically for one to a few seconds, supplemental visual guidance could enhance the accuracy of positioning the capsule at the target location during marking.

[0026] Some embodiments provide a multifunctional luminal organ (e.g., gastrointestinal) ablative imaging capsule system that solves many existing problems of traditional TCE. Some embodiments integrate a dual-wavelength OCT imaging system operating at both 800 and 1300 nm, leveraging the advantages of both UHRimaging of superficial layers at 800 nm and deep tissue imaging at 1300 nm. The 800- nm OCT images allow for differentiating fine histopathological changes in mucosal layers with better resolution and enhanced contrast, while the 1300-nm OCT images allow for monitoring the depth of lesion invasion. The capsule of some embodiments includes a built-in miniature complementary metal oxide semiconductor (CMOS) camera, offering direct visualization of the esophagus in front of the capsule (similar to a conventional endoscope view) and permitting visual guidance for the capsule deployment, OCT imaging, and laser ablation. Some embodiments are also equipped with an ablation laser, which may be used for therapeutic treatment and / or laser marking for precise biopsies. By fully utilizing the critical functions in a single device, some embodiments provide a comprehensive and effective solution for endoscopic screening, diagnosis, and ablation treatment of the esophagus.

[0027] Further features and advantages are shown and described herein in reference to the accompanying figures.

[0028] Fig. 1 is a schematic diagram of a super-achromatic, anastigmatic optical layout 100 for dual-wavelength OCT imaging using a tethered capsule, according to various embodiments. The optical layout 100 is described presently in reference to an example, non-limiting embodiment. The optical layout 100 may be implemented in a tethered capsule to achieve both UHR / contrast imaging at 800 nm and deep tissue imaging at 1300 nm. The optical layout 100 includes two single-mode fibers, with a 630-HP fiber for OCT imaging at 800 nm and an SMF-28e fiber for deep OCT imaging at 1300 nm and laser ablation at 1470 nm. In the example embodiment, the light delivered from both fibers is expanded and focused at ~100 pm outside of the capsule wall (~7 mm from the lens surface) through a super-achromatic optics assembly composed of a pair of doublets and a BK7 rod spacer. In the example embodiment,the focused imaging beams are circumferentially scanned by a curved mirror driven by a micromotor. In the example embodiment, the curved mirror has a 48° tilt angle with respect to the micromotor rotation axis in order to minimize specular reflection by the glass wall of the capsule. The micromotor may affect the circumferential scanning at any suitable rate, e.g., a few rotations to a few hundred of rotations per second, or higher. In the example embodiment, the two fibers are separated by 125 pm, resulting in slight differences in the focal point of ~450 and ~60 pm in the lateral and axial directions, respectively.

[0029] The optical layout 100 is shown as incorporating an additional BK7 rod spacer to achieve super-achromatic performance, as shown and described in detail herein in reference to Fig. 2, and a curved mirror to compensate for astigmatism caused by the cylindrical capsule shell, as shown and described herein in reference to Fig. 3.

[0030] According to various embodiments, BK7 may be used for matching the specific chromatic doublet lenses used in the capsule of an embodiment described herein. For other types of chromatic lenses, a different glass rod, e.g., different from BK 7, may be used. Various embodiments may include diffractive optics such as diffractive optical element to compensate the chromatic aberration. Nevertheless, compared to the use of diffractive optical elements, a BK 7 rod may be more convenient and cost effective. As described presently, the use of a glass rod such as BK7 can expand the OCT imaging beam diameter for tuning and achieve a desired focal position and focused beam spot size.

[0031] Fig. 2 depicts ray-tracing simulation results of the chromatic focal shift of an example embodiment at a focal length of ~7 mm, with (204) and without (202) aBK7 rod spacer. The BK7 rod spacer greatly reduced the chromatic focal shift downto ~5.4 pm, whereas a pair of off-the-shelf achromatic doublets alone would result in ~50-pm focal shift over the 760- to 910-nm wavelength range.

[0032] One of the technical challenges for achieving a UHR is to minimize chromatic aberration over a broad spectral bandwidth. It is particularly challenging at the 800-nm wavelength range due to the much stronger material dispersion than that of 1300-nm light. For example, the ray-tracing simulation results in Fig. 2 show that the combination of carefully selected achromatic doublet pair results in a longitudinal chromatic focal shift of ~50 pm around the target ~7-mm focal length over the 760- to 910-nm spectral range. On the one hand, one method to compensate for this residual chromatic aberration would be to use a custom-designed diffractive optical element. However, it can be not only expensive for customization but also require precise alignment along the optical axis for optimal performance. On the other hand, expanding a beam inside a dispersive material can exhibit complementary dispersion (i.e. , longer wavelengths expand more than shorter wavelengths). Thus, to reduce the chromatic aberration, some embodiments include a BK7 rod spacer between the fiber and doublets to expand the beam. The chromatic focal shift may be further reduced by adjusting the length of the BK7 rod. As shown in Fig. 2, at a target focal length (~7 mm), the chromatic focal shift is reduced to ~5.4 pm by using a 2-mm-long BK7 rod spacer.

[0033] Fig. 3 depicts ray-tracing simulation results 302 for a system that omits a curved mirror that is used in various embodiments, contrasted with the measured output beam shapes 304 of a capsule along the axial direction that includes a curved mirror according to the non-limiting example embodiment. The ray-tracing simulation results 302 show a pronounced astigmatism along the axial direction that would be caused by a transparent cylindrical capsule shell without beam correction using acurved mirror. By contrast, the measured output beam shapes 304 show that a curved mirror of a properly designed radius of curvature as used in the example embodiment successfully compensates the astigmatism, achieving a nearly perfect round beam shape along the axial direction.

[0034] In general, an engineering challenge for UHR imaging is astigmatism. The glass tube of the capsule functions as a negative (diverging) cylindrical lens along the azimuthal direction (perpendicular to the longitudinal axis of the capsule) and induces astigmatism. Fig. 3 shows the simulated beam shape results 302 at the focus, as well as ±50 and ±100 pm away from the focal point along the imaging depth when using a conventional flat mirror on the micromotor for beam scanning. With a glass shell of a 11 -mm outer diameter and a 1 -mm thickness, the worst calculated astigmatism ratio (i.e., the ratio between the focused spot size in the azimuthal direction to the one in the longitudinal direction) would be ~5, which would severely degrade the lateral resolution along imaging depth. To reduce this astigmatism, some embodiments implement a customized curved mirror for beam scanning. The curvature of the mirror may be selected to prefocus the imaging beam along the azimuthal direction, effectively compensating for the diverging effect (astigmatism) of the capsule shell. That is, the curved mirror may have a cylindrical surface with a radius of curvature that cancels the diverging effect of the cylindrical shell of the capsule. Optical modelling software may be used to determine the radius of curvature based on the optical properties (inner radius, outer radius, material) of the cylindrical shell. As shown in Fig. 3, the custom curved mirror successfully alleviates astigmatism, resulting in nearly perfect round output beam shapes 304 over the entire imaging depth. The worst measured astigmatism ratio for the measured output beamshapes 304 was 1 .125, which is a pronounced improvement over the astigmatism ratio without the curved mirror.

[0035] Fig. 4 is a schematic diagram of a capsule 400 for imaging a luminal organ, according to various embodiments. As shown in Fig. 4, two single-mode fibers for the dual-wavelength OCT imaging and laser ablation and the endoscope camera with an LED illumination fiber are integrated inside a single device with an 11 -mm diameter and a 26-mm length. For the assembly procedure used in a non-limiting example embodiment, two fibers of 630-HP and SMF-28e are first inserted and secured into a glass ferrule with a 2-mm diameter with epoxy. An oval-shaped bore (127 pm x 252 pm) of the ferrule is used to accommodate both fibers in the example embodiment. In the example embodiment, the ferrule and fiber end surfaces are angle-polished with 8° to minimize back- reflections from the fiber tips. In the example embodiment, the entry surface of the BK7 rod spacer (2 mm x 2 mm, diameter x length) that face the fibers is also polished at an 8° angle. In the example embodiment, the angle-polished surfaces of both the ferrule and the BK7 rod spacer are aligned in parallel and then glued with an optical adhesive. In the example embodiment, this step reduced the back-reflections with a measured value of less than -55 dB.

[0036] In the example embodiment, the ferrule-spacer assembly are aligned with a pair of achromatic doublets inside a housing and mounted at the center of a base. In the example embodiment, the housing and bases are fabricated via high- precision three-dimensional (3D) printing, with a machining tolerance of better than 50 pm. In the example embodiment, the housing and base are designed to ensure concentricity between each component during assembling. In the example embodiment, the gap between the BK7 rod spacer and the achromatic lens pair asfurther adjusted inside the housing to precisely achieve a working distance of ~7 mm away from the last surface of the doublets.

[0037] In the example embodiment, the curved mirror as shown and described in reference to Fig. 3 is mounted on the micromotor shaft, and then the micromotor is mounted at the center of a base. In the example embodiment, two bases with the optics housing and micromotor are encased inside a glass shell enclosure that includes of a cylindrical sidewall with an 11 -mm outer diameter and a flat distal end. In the example embodiment, the distance between the two bases is fine-tuned to position the beam focus at a desired location (e.g., 100 / 160 pm for 800 / 1300 nm outside the capsule shell). In the example embodiment, and endoscope camera and an additional multimode fiber (with a 500 / 486-pm outer / core diameter and a numerical aperture of 0.51 ) for delivering a white light-emitting diode (LED) illumination light is inserted and installed in the capsule through the guiding holes on 3D-printed bases. Alternately, some embodiments may include an LED inside of the capsule. The flat end surface of the glass housing may reduce the lensing effect and ensure a clear camera view while keeping the capsule watertight. In the example embodiment, electrical drive wires for the micromotor and the camera and all the imaging and illumination fibers are enclosed and protected with a flexible torque coil securely connected to the proximal end of the capsule. In the example embodiment, the torque coil may be further covered with a thin, biocompatible, and watertight plastic sheath suitable for in vivo use.

[0038] According to some embodiments, the capsule 400 may be equipped with position memory to facilitate accurately repositioning the ablation laser beam and / or one or both OCT laser beams to any previously imaged and / or ablated location. During operation, each imaged and / or ablated position may be associated withrotational and linear coordinates, and the associations may be stored in persistent memory. The rotational coordinates may be obtained by integrating a high-resolution rotational encoder with the micromotor to precisely track the angular position of the motor’s rotor (and mechanically coupled mirror). The high-resolution rotational encoder may include a sensor that converts rotational mechanical motion and / or position into precise electrical signals. The high-resolution rotational encoder can utilize any of a variety of sensor technologies to determine the rotational position of the micromotor, including magnetics, capacitance, or optics. The linear coordinates, which indicate the position along the axis of the luminal organ, may be obtained by using a linear position stage to retract, or allow slack in, the tether. The linear position stage may effectuate motion away from the patient by retracting the tether, and gravity and peristalsis may effectuate motion deeper into the patient consistent with the slack provided by the linear position stage. The linear position stage may covert linear mechanical motion and / or position into precise electrical signals. The linear position stage may be implemented using a UTS100CC, available from Newport Corporation of Irvine, CA, USA.

[0039] The position memory may be used for any of a variety of purposes, including, but not limited to: precision guidance for biopsy, and / or targeted ablation at a specific site or across a defined area. For example, the position memory facilitates tracking the exact location of any given site over the imaged area and repositioning the laser beam back to that site.

[0040] Fig. 5 shows photographs 502, 504 of an assembled capsule for imaging a luminal organ, according to an embodiment. The non-limiting example embodiment shown in Fig. 5 was constructed as shown and described herein in reference to Figs.1 , 2, 3, and 4. The embodiment is shown with a two-m-long flexible tether inphotograph 502. The tether may include at least a mechanically strong tether like flexible metal coil, nylon string, etc. The assembled capsule had a dimension of 11 mm x 26 mm (diameter x length). While the embodiment of Fig. 5 used a glass shell enclosure various embodiments may use glass or a medical-grade transparent plastic shell.

[0041] Fig. 6 is a schematic diagram of a system 600 for imaging a luminal organ, including a tethered capsule and a remote system, the latter of which includes a UHR spectral-domain OCT (SD-OCT) system operating at 800 nm, a deep tissue imaging swept-source OCT (SS-OCT) system operating at 1300 nm, an ultracompact endoscope video camera system, and an ablation laser system (e.g., operating at 1470 nm), according to various embodiments. Two, or all three, of the imaging systems may operate simultaneously. The following notations are used in Fig. 6: CL = collimating lens, ND = neutral density filter, M = mirror, PC = polarization controller, PP = prism pair, VPHG = volume phase holographic grating, CIR = fiberoptic circulator, and BD = balanced detector. The output powers of the OCT imaging beams at the capsule may be adjusted to ~16 mW for 800 nm and ~7 mW for 1300 nm, by way of non-limiting example. Boxes 602, 604 show the measured axial point spread functions (PSFs) of the capsule when using the 800- and 1300-nm OCT imaging systems, respectively, with the axial resolution given by the ful l-width-at-half- maximum of the corresponding PSF. The system 600 is described in reference to a non-limiting example embodiment.

[0042] In the example embodiment, all the fiber-coupled light sources, includingOCT imaging beams at both 800 and 1300 nm, the ablation laser, and the illuminationLED, are delivered to the capsule and controlled through a portable console. The console also includes an endoscope camera microcontroller and recording system, amicromotor controller, an LED driver, and fiber connectors to transceive light between each imaging system and the capsule. The console may simultaneously display one, two, or all three of: the 800 nm OCT image, the 1300 nm image, and / or the visible light camera image. According to some embodiments, the OCT images may be registered with each-other and overlayed in a single display image.

[0043] In the example embodiment, the UHR SD-OCT system utilizes a supercontinuum (SuperK) light source (NKT Photonics) equipped with a Gaussian beam shaper, which provides a 3-dB spectral bandwidth of ~120 nm with a distribution centered at ~800 nm. In the example embodiment, the laser is coupled in a fiber-optic Michaelson interferometer and separated into the sample and reference arms using a 50 / 50 broadband fiber-optic coupler. In the example embodiment, the OCT interference signal is captured by a spectrometer with a line-CMOS camera (e.g., available from Wasatch Photonics) that can operate at up to 250-kHz A-line scan rate. In the example embodiment, the spectrometer accommodates a spectral bandwidth of 300 nm with a spectral resolution of ~0.15 nm / pixel, allowing for a calibrated imaging depth of 1 mm. In the example embodiment, with super-achromatic optics as shown and described herein in reference to Figs. 1 and 2, an ultrahigh axial resolution of 2.8 pm in air was achieved (box 602).

[0044] In the example embodiment, the deep-tissue imaging SS-OCT imaging system includes a vertical-cavity surface-emitting laser (VCSEL) swept laser (e.g., available from Excelitas Technologies) and a fiber-optic Mach-Zehnder interferometer. In the example embodiment, the VCSEL providse a 100-kHz A-line scan rate at a central wavelength of 1310 nm with a 3-dB spectral band- width of ~88 nm (and a 10-dB bandwidth of ~130 nm). In the example embodiment, the laser is split into the sample and reference arms using a 90 / 10 fiber-optic coupler, and the OCTinterference signal isobtained through a balanced detector. In the example embodiment, the VCSEL source incorporates an internal linear -clock (with an imaging depth of up to 6 mm in air) to trigger a high-speed DAQ card (e.g., available from AlazarTech) for synchronized data acquisition. In the example embodiment, the measured axial resolution of the SS-OCT system was ~10.7 pm in air (box 604).

[0045] In the example embodiment, the video camera system includes a compact CMOS camera (1.05 mm x 1.05 mm x 2.27 mm) and a fiber-coupled white LED (e.g., available from Thorlabs, MCWHF2) for illumination. In the example embodiment, the ultracompact CMOS sensor, along with optical lenses (e.g., and OVM 6946, available from OmniVision) provides a 120° wide field of view with a focusing range of 5 to 50 mm. The camera captures images of 400 x 400 pixels at 4.33 frames per second.

[0046] Various types of ablation lasers may be used, and the ablation laser may be used for marking and / or ablation treatment. For example, a fiber-coupled diode laser (e.g., available from Anritsu, 500 mW) may be used. As another example, a pulsed Raman fiber laser (available from IPG Photonics, 3W) may be used. The pulsed Raman laser may be more efficient and require a shorter time to ablate the tissue. Both example lasers operate at 1470 nm and can be directly coupled into the SMF-28e fiber and focused on the target tissue surface through the same capsule optics. More generally, the ablation laser wavelength may be any suitable wavelength, e.g., a wavelength with high water absorption. Non-limiting example suitable wavelengths include 950 nm, 1450 nm, 1550 nm, 1200 nm, and 970 nm. The ablation laser may be a nanosecond or femtosecond laser, e.g., outside of a water absorption peak.

[0047] Two studies that utilized embodiments as presented herein are shown and described presently in reference to Figs. 7, 8, 9, 10, and 11. In particular, an ex vivo swine imaging study is shown and described in reference to Figs. 7, 8, and 9, and an in vivo swine imaging study is shown and described in reference to Figs. 10 and 11 . Note that although the example embodiments used in the studies used ablation lasers only for marking, embodiments are not so limited. In general, embodiments may include and use lasers for clinical ablation treatment.

[0048] For the ex vivo study, an embodiment was used to image freshly dissected swine esophagi (within 30 min after sacrificing the swine). For each sample, the esophagus was first pinned on a wax block, and the capsule was gently introduced to the distal end of the esophagus following its natural path. During the deployment of the capsule, the capsule was parked at four random locations and ablated with the ablation laser for 20 s at 150 mW at each location. 3D volumetric OCT images of the esophagus were then acquired by pulling back the capsule with a motorized linear stage while circumferentially scanning the micromotor. Circumferential cross- sectional imaging was performed at 20 frames per second, and a total of 56-mm-long esophagus was imaged at the motorized stage pullback speed of 1 mm / s.

[0049] Fig. 7 shows unwrapped en face images of the 3D volumetric OCT images at 1300 nm (702) and 800 nm (704) according to the ex vivo study. The ablated spots are clearly visible in both images (dark arrows). The box shows an enlarged view of a representative ablated spot. The en face images were generated by averaging OCT signals along the depth after unwrapping each cross-sectional image. Around 7% of the field of view was blocked by the electrical wires for the camera and the motor, visible as blank lines (light arrows). The ablation laser successfully created fiducial marks on the esophageal surface, as shown in Fig. 8.The en face images provided a comprehensive overview of the entire esophagus and clearly identified the four marking positions, which appeared as dots (indicated with arrows) in both the 1300-nm OCT image 702 and the 800-nm OCT image 704.

[0050] Fig. 8 is a photograph 800 of the excised swine esophagus imaged as shown and described herein in reference to Fig. 7. The fiducial marks created by the ablation laser are visible in the photograph 800.

[0051] Fig. 9 shows representative circumferential (polar) and unwrapped rectangular (Cartesian) cross-sectional images over one ablated spot along the dotted line shown in Fig. 7. The circumferential (polar) cross-sectional images over the ablated spot as shown in Fig. 9 allow side-by-side comparison of the OCT imaging characteristics at 1300 and 800 nm. Around 7% of the field of view was blocked by the electrical wires for the camera and the motor, visible at the 11 and 5 o’clock directions in Fig. 9 (cw = camera drive / signal wire, mw = motor drive wire). The unwrapped rectangular (Cartesian) images do not exhibit pronounced nonuniform rotational distortions, since the micromotor was well protected within the capsule and did not experience much bending or other stresses during imaging. However, should nonuniform rotational distortions occur, existing methods can be applied to effectively mitigate it.

[0052] As shown in Fig. 9, the 1300-nm OCT image revealed the full-thickness layered structures of the normal swine esophagus wall extending from the stratified squamous epithelium (EP) to lamina propria (LP), muscularis mucosa (MM), submucosa (SM), and muscularis propria (MP). Additionally, the outer wall of the esophagus can be identified, demonstrating deep tissue imaging with an excellent resolution.

[0053] By contrast, the 800-nm OCT image shown in Fig. 9 exhibited much finer tissue structures in the superficial layers up to the SM layer. The superb resolution and contrast of the 800-nm OCT images allow visualization of the fine tissue microstructures that are not visible in 1300-nm OCT images. Particularly, microglandular structures in the submucosal layer and the boundaries between the layers were much more pronounced compared to the 1300-nm OCT images. These performance characteristics of the 800-nm OCT would potentially allow for distinguishing subtle changes in tissue microarchitectural features associated with esophageal neoplasia at an earlier stage.

[0054] For the in vivo swine esophagus imaging study, shown and described herein in reference to Figs. 10 and 11 , the capsule was introduced into the esophagus of a sedated swine under the visual guidance of the built-in camera and the real-time feedback from the simultaneous 800 and 1300-nm OCT imaging. During the capsule insertion, random locations were selected to simulate “suspected” areas and ablated for three seconds to create visible fiducial marks. These marks serve not as indicators of abnormality but as references for potential areas of interest. In clinical scenarios, upon detecting a genuinely abnormal area in the OCT images or video footage, e.g., as indicated by characteristics suggesting pathology or concern, an embodiment may allow for these specific areas to be ablated, creating a reference mark for further examination or treatment. The consistency of the laser marking may be affected by unstable contact of the capsule with the esophageal wall due to the peristalsis. To mitigate this issue, the study utilized a high-power pulsed Raman laser, which has demonstrated the capability of making effective marks and minimizing the impact of transient tissue contact. In practice, an embodiment may allow for immediate verification of tissue coagulation at the targeted area through subsequent OCT scans.Further, an embodiment may be used to ensure that the locations of the laser marks correspond precisely with the areas being imaged by sharing the same optics. If the subsequent OCT scan indicates that the initial marking was insufficient, a prompt remarking can be performed.

[0055] Fig. 10 is a photograph of a representative endoscope video camera view of a swine esophagus for the in vivo study. The capsule was introduced to the esophagus under the guidance of the built-in endoscope camera. As shown in Fig. 10, the ablated spots (arrow) are clearly visible in the endoscope camera video footage, allowing for accurate correlation during further examination or other procedures.

[0056] Subsequent to the ablation, the marked areas were imaged again with the capsule and biopsied at the end of the study. The OCT images were compared with the corresponding histology micrographs of the biopsied tissue samples.

[0057] Fig. 11 presents photographs of swine esophagus OCT imaging results 1000 obtained from the in vivo study. In particular, Fig. 11 shows real-time circumferential OCT images around an ablated spot captured at 1300 nm (1102) and 800 nm (1104). The laser-ablated spot is clearly visible in the camera image and OCT images as indicated with arrows. Fig. 11 also shows zoomed-in OCT images and corresponding histology micrographs 1106, 1108 of the area indicated with dotted boxes in 1102 and 1104. The top and bottom images show 1300- and 800-nm OCT images, respectively, and the corresponding histology micrograph is shown in the middle. The ablated spot is indicated with dotted circles in 1106.

[0058] The non-limiting example embodiment used in the in vivo study successfully demonstrated both deep tissue imaging at 1300 nm and UHR / contrast imaging at 800 nm. The 1300-nm OCT image revealed full-thickness layers of theswine esophagus, while the 800-nm OCT resolved micro-glandular structures buried in the subepithelium as indicated with light arrows in 2* zoomed-in images. In Fig 11 , the following notations are used: EP = stratified squamous epithelium, MEP = mature epithelium, EP = basal epithelium, LP = lamina propria, MM = muscularis mucosae, SM = submucosa, and MP = muscularis propria. The scale bars indicate 250 pm.

[0059] As shown in Fig. 11 , the ablated tissue site could be easily identified in both OCT images and the histology micrograph with good correlation (indicated with dotted circles in 1106). The histology micrograph confirmed that the lateral extent of the thermal damaged area was ~700 pm with the depth reaching ~500 pm, extending to the boundary of the MM layer while creating a cavity in the epithelial layer (where the beam was focused). These details were also clearly identifiable in the OCT images, suggesting its capability to detect and visualize microarchitectural changes and monitor the depth of invasion. The dual-wavelength OCT imaging allows for UHR / contrast imaging of superficial layers as well as deep tissue layers. As shown in 1108, the 1300-nm OCT allowed imaging of entire tissue layers of the swine esophagus. At the same time, the 800-nm OCT could resolve the microglandular structures underneath the squamous epithelium with much improved resolution and contrast. The 2* zoomed-in images of 1108 clearly identify the fine details of the microglands or ducts, as indicated with arrows, suggesting that UHR imaging at 800 nm could play a crucial role in assessing Barrett’s glands buried underneath the subepithelium and for achieving curative treatment. Notably, the 800-nm OCT images reveal sublayers in the epithelium, as seen in the gradient in histology images. This may represent the development of the epithelium layer from the basal layer with stem cells toward matured superficial layers. Conventional eOCT at 1300 nm has shown the potential to identify irregular glands. However, it remains challenging to identifydysplastic glands or changes due to its insufficient resolution and contrast. The 800- nm OCT image in 1108 shows finer microstructures of the subepithelial glands, which cannot be clearly resolved in the 1300-nm images. As illustrated by Fig. 11 , the UHR imaging capability of embodiments holds strong promise to augment clinical diagnosis and treatment assessment.

[0060] Thus, various example embodiments of a device for imaging a luminal organ are shown and described. Embodiments may be capable of dual-wavelength OCT imaging, laser ablation, and endoscope camera imaging. With dual-wavelength OCT imaging, e.g., operating at 800 and 1300 nm simultaneously, an embodiment can provide high-resolution images from the superficial mucosal layers to deeper tissue layers. The UHR OCT images at 800 nm offer enhanced visualization of fine tissue microarchitecture, potentially allowing for the detection of subtle changes associated with early esophageal neoplasia, while 1300-nm OCT imaging provides deeper penetration, which is important for evaluating lesion invasion (highly relevant to selecting the proper treatment). Furthermore, the ablation laser allows for not only precise marking of suspicious areas, facilitating subsequent targeted biopsies and improving diagnostic accuracy, but also ablation treatment, e.g., of esophageal lesions, particularly early-stage lesions. Embodiments may facilitate precise identification of lesions through high-resolution OCT imaging, and subsequent treatment with the integrated ablation laser could be conducted, selectively targeting well-defined areas of abnormal superficial tissue and minimizing damage to the adjacent or deeper healthy tissues. Unlike traditional fiber-optic-based laser ablation, which frequently demands multiple sessions, an embodiment may provide 3D scanning capabilities (circumferential and pullback). An embodiment may facilitate the ablation of as extensive area akin to conventional radiofrequency ablation, while thedepth of tissue ablation can be more precisely controlled. Thus, some embodiments may be theragnostic devices, capable of both diagnosis and treatment within a single procedure. Lastly, the endoscope camera integrated within some embodiments may further enhance their functionality. Embodiments may include a low-resolution (400 x 400 pixels) visible light camera, or a medical-grade, high-resolution visible light endoscope camera. An endoscope camera affords comprehensive tissue surface surveillance along the Gl tract, allowing for initial screening and providing real-time visual guidance for navigating and positioning the capsule. According to various embodiments, the endoscope camera may capture video in front of the capsule, allowing for estimation of the distance between the location on the camera view and the OCT view. If an abnormal area is detected in the video footage, it would be very likely identifiable in the preceding OCT cross-sectional or en face images. Further, embodiments may facilitate comprehensive scanning of the esophagus from the gastroesophageal junction to the mouth, offering a potential way to correlate recorded endoscopic and OCT images with specific locations along the tract and further registering with other imaging modalities. A more accurate correlation may be possible with the help of the laser ablation landmarks during the following rounds of imaging. The camera images may also offer clinicians a familiar functionality, similar to conventional Gl endoscopic procedures. Embodiments may not only facilitate the interpretation and analysis of OCT images, but also contribute to accelerating the clinical translation and adaption of the TCE technology. Further, some embodiments may provide more advanced endoscopic imaging functions by utilizing red, green, and blue (RGB) laser illumination instead of LED. This opens up possibilities for applications for narrow-band imaging and photodynamic therapy (e.g., using 5-aminolevulinic acid or porfimer sodium), allowing for versatile imaging and treatment using a single device.

[0061] Some embodiments successfully integrate clinically viable functions for comprehensive esophagus surveillance and ablation treatment with surface and volumetric imaging guidance and feedback. This advancement holds a strong promise in accelerating the clinical translation and adoption of the TCE technology. As described herein, embodiments may utilize two separate OCT systems for each wavelength to highlight their distinct advantages and provide synergistic, complementary benefits when combined. Integrating these two OCT wavelengths into a single device allows for more comprehensive diagnosis, potentially enhancing clinical outcomes.

[0062] Certain examples can be performed using a computer program or set of programs. The computer programs can exist in a variety of forms both active and inactive. For example, the computer programs can exist as software program (s) comprised of program instructions in source code, object code, executable code or other formats; firmware program(s), or hardware description language (HDL) files. Any of the above can be embodied on a transitory or non-transitory computer readable medium, which include storage devices and signals, in compressed or uncompressed form. Exemplary computer readable storage devices include conventional computer system RAM (random access memory), ROM (read-only memory), EPROM (erasable, programmable ROM), EEPROM (electrically erasable, programmable ROM), flash memory, and magnetic or optical disks or tapes.

[0063] Aspects of the present disclosure are described herein with reference to flowchart illustrations and / or block diagrams of methods, apparatus (systems), and computer program products according to embodiments of the disclosure. It will beunderstood that each block of the flowchart illustrations and / or block diagrams, and combinations of blocks in the flowchart illustrations and / or block diagrams, can be implemented using computer readable program instructions that are executed by an electronic processor.

[0064] These computer readable program instructions may be provided to a processor of a general-purpose computer, special purpose computer, or other programmable data processing apparatus to produce a machine, such that the instructions, which execute via the electronic processor of the computer or other programmable data processing apparatus, create means for implementing the functions / acts specified in the flowchart and / or block diagram block or blocks. These computer readable program instructions may also be stored in a computer readable storage medium that can direct a computer, a programmable data processing apparatus, and / or other devices to function in a particular manner, such that the computer readable storage medium having instructions stored therein comprises an article of manufacture including instructions which implement aspects of the function / act specified in the flowchart and / or block diagram block or blocks.

[0065] In embodiments, the computer readable program instructions may be assembler instructions, instruction-set-architecture (ISA) instructions, machine instructions, machine dependent instructions, microcode, firmware instructions, statesetting data, configuration data for integrated circuitry, or either source code or object code written in any combination of one or more programming languages, including an object oriented programming language such as Smalltalk, C++, or the like, and procedural programming languages, such as the C programming language or similar programming languages. The computer readable program instructions may execute entirely on a user's computer, partly on the user's computer, as a stand-alone softwarepackage, partly on the user's computer and partly on a remote computer or entirely on the remote computer or server.

[0066] As used herein, the terms “A or B” and “A and / or B” are intended to encompass A, B, or {A and B}. Further, the terms “A, B, or C” and “A, B, and / or C” are intended to encompass single items, pairs of items, or all items, that is, all of: A, B, C, {A and B}, {A and C}, {B and C}, and {A and B and C}. The term “or” as used herein means “and / or.”

[0067] As used herein, language such as “at least one of X, Y, and Z,” “at least one of X, Y, or Z,” “at least one or more of X, Y, and Z,” “at least one or more of X, Y, or Z,” “at least one or more of X, Y, and / or Z,” or “at least one of X, Y, and / or Z,” is intended to be inclusive of both a single item (e.g., just X, or just Y, or just Z) and multiple items (e.g., {X and Y}, {X and Z}, {Y and Z}, or {X, Y, and Z}). The phrase “at least one of” and similar phrases are not intended to convey a requirement that each possible item must be present, although each possible item may be present.

[0068] The techniques presented and claimed herein are referenced and applied to material objects and concrete examples of a practical nature that demonstrably improve the present technical field and, as such, are not abstract, intangible or purely theoretical. Further, if any claims appended to the end of this specification contain one or more elements designated as “means for [perform]ing [a function]...” or “step for [performing [a function]...”, it is intended that such elements are to be interpreted under 35 U.S.C. § 112(f). However, for any claims containing elements designated in any other manner, it is intended that such elements are not to be interpreted under 35 U.S.C. § 112(f).

[0069] While the invention has been described with reference to the exemplary examples thereof, those skilled in the art will be able to make various modifications tothe described examples without departing from the true spirit and scope. The terms and descriptions used herein are set forth by way of illustration only and are not meant as limitations. In particular, although the method has been described by examples, the steps of the method can be performed in a different order than illustrated or simultaneously. Those skilled in the art will recognize that these and other variations are possible within the spirit and scope as defined in the following claims and their equivalents.

Claims

What is claimed is:1 . A device for imaging a luminal organ, the device comprising: a flexible tether comprising at least one optical fiber, wherein a distal end of the at least one optical fiber is optically coupled to at least: a first Optical Coherence Tomography (OCT) light source, a first OCT interference signal detector, a second OCT light source, and a second OCT interference signal detector, wherein the first OCT light source produces light having a wavelength distribution centered at a first wavelength, wherein the second OCT light source produces light having a wavelength distribution centered at a second wavelength, and wherein the first wavelength is different from the second wavelength; and a capsule that is physically coupled to a proximal end of the flexible tether, wherein the capsule comprises a motor that is mechanically coupled to a mirror, wherein the mirror conveys light from the first OCT light source and from the second OCT light source to the luminal organ, and wherein the mirror conveys light from the luminal organ to the first OCT interference signal detector and to the second OCT interference signal detector.

2. The device of claim 1 , wherein the capsule further comprises a visible light camera and a visible light source aperture, and wherein the flexible tether further comprises a camera signal cable.

3. The device of claim 2, wherein the first OCT interference signal detector, the second OCT interference signal detector, and the visible light camera are communicatively coupled to a display that displays, simultaneously, a first OCT image of the luminal organ obtained by OCT at the first wavelength, a second OCT image of the luminal organ obtained by OCT at the second wavelength, and a visible light image of the luminal organ obtained using the visible light camera.

4. The device of claim 1 , wherein the first wavelength is 800 nm and the second wavelength is 1300 nm.

5. The device of claim 1 , wherein the distal end of the flexible tether is further optically coupled to an ablation laser, whereby the mirror conveys light from the ablation laser to the luminal organ.

6. The device of claim 5, whereby the device is usable to therapeutically ablate the luminal organ while imaging the luminal organ.

7. The device of claim 1 , wherein the mirror compensates for astigmatism induced by a wall of the capsule.

8. The device of claim 1 , wherein the capsule further comprises a dispersive element that compensates for chromatic focal shift.

9. The device of claim 1 , wherein the luminal organ comprises an esophagus.

10. The device of claim 9, wherein the capsule has an outer diameter of less than 11 mm.11 . The device of claim 1 , further comprising a position memory.

12. A system for imaging a luminal organ, the system comprising: a first Optical Coherence Tomography (OCT) system comprising a first light source, a first OCT reference arm, and a first OCT interference signal detector; a second OCT system comprising a second OCT light source, a second OCT reference arm, and a second OCT interference signal detector; a flexible tether comprising at least one optical fiber, wherein a distal end of the at least one optical fiber is optically coupled to at least: the first OCT light source, the first OCT interference signal detector, the second OCT light source, and the second OCT interference signal detector, wherein the first OCT light source produces light having a wavelength distribution centered at a first wavelength, wherein the second OCT light source produces light having a wavelength distribution centered at a second wavelength, and wherein the first wavelength is different from the second wavelength; and a capsule that is physically coupled to a proximal end of the flexible tether, wherein the capsule comprises a motor that is mechanically coupled to a mirror, wherein the mirror conveys light from the first OCT light source and from the second OCT light source to the luminal organ, and wherein the mirror conveys light from the luminal organ to the first OCT interference signal detector and to the second OCT interference signal detector.

13. The system of claim 12, wherein the capsule further comprises a visible light camera and a visible light source aperture, and wherein the flexible tether further comprises a camera signal cable.

14. The system of claim 13, further comprising a display, wherein the first OCT interference signal detector, the second OCT interference signal detector, and the visible light camera are communicatively coupled to the display, wherein the display is configured to display, simultaneously, a first OCT image of the luminal organ obtained by OCT at the first wavelength, a second OCT image of the luminal organ obtained by OCT at the second wavelength, and a visible light image of the luminal organ obtained using the visible light camera.

15. The system of claim 12, wherein the first wavelength is 800 nm and the second wavelength is 1300 nm.

16. The system of claim 12, further comprising an ablation laser, wherein the distal end of the flexible tether is further optically coupled to the ablation laser, whereby the mirror conveys light from the ablation laser to the luminal organ.

17. The system of claim 16, whereby the device is usable to therapeutically ablate the luminal organ while imaging the luminal organ.

18. The system of claim 12, wherein the mirror compensates for astigmatism induced by a wall of the capsule.

19. The system of claim 12, wherein the capsule further comprises a dispersive element that compensates for chromatic focal shift.

20. The system of claim 12, wherein the luminal organ comprises an esophagus.21 . The system of claim 20, wherein the capsule has an outer diameter of less than 11 mm.

22. The system of claim 12, further comprising a position memory.

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