Tethered optical imaging capsule for scalable esophageal imaging

Abstract

An apparatus for imaging a cavity. The apparatus comprises an enclosure, comprising a distal end, a proximal end, and a transparent portion therebetween. The proximal end comprises at least one electrical connection, and the transparent portion is transparent to an illumination signal; and a flexible tether, operably connected to the electrical connection of the proximal end of the enclosure. The enclosure further comprises an image acquisition device, an illumination source, and an annular reflector, wherein the illumination source is configured to generate the illumination signal comprising illumination beams, the annular reflector being configured to direct at least some of the illumination beams through the transparent portion of the enclosure at the cavity, thereby generating a reflected signal comprising reflected beams, the annular reflector being further configured to direct at least some of the reflected beams at the image acquisition device, the image acquisition device being configured to capture one or more images based on the reflected signal.

Description

TETHERED OPTICAL IMAGING CAPSULE FOR SCALABLE ESOPHAGEAL IMAGINGRELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 604430, filed on November 30, 2023. The entire teachings of the above application(s) are incorporated herein by reference.GOVERNMENT SUPPORT

[0002] This invention was made with government support under R01CA252216 from the National Institute of Health. The government has certain rights in the invention.BACKGROUND OF THE INVENTION

[0003] In 2020, global esophageal cancer incidence surpassed 600,000 new cases, leading to approximately 540,000 deaths. Esophageal adenocarcinoma (EAC), common in Western regions, often has a late diagnosis with a <20% 5-year survival rate. In the U.S., EAC incidence rates have markedly increased over earlier decades, with 2023 forecasts suggesting an estimated -21,500 new cases of esophageal cancer, leading to -16,000 deaths. Premalignant conditions like Barrett’s esophagus (BE), dysplasia, and intramucosal carcinoma are highly treatable with endoscopic eradication therapy (EET), including endoscopic resection, radiofrequency ablation (RFA), and cryoablation. However, a majority of EAC patients present without any preceding diagnosis of a premalignant lesion resulting in missed opportunities for early treatment.

[0004] Screening is a potential solution to identify individuals at elevated risk of developing EAC. However, screening the general population is not recommended due to the low incidence of EAC and risk of overdiagnosis. In patients with a combination of risk factors, esophagogastroduodenoscopy (EGD) has been regarded as the gold standard method forscreening. EGD enables detailed visual examination, acquisition of biopsies, and endoscopic therapy. However, EGD is not well suited for large-scale screening due to its prohibitive cost.

[0005] Unsedated transnasal endoscopy (uTNE) is a less invasive BE screening method with 98% sensitivity and 100% specificity. However, uTNE requires a skilled operator and endoscopic equipment. Alternative unsedated screening methods include nonendoscopic sponge and balloon devices that collect cellular material for immunohistochemistry or other molecular assays. Previous studies have shown promising test accuracy, and future studies aim to assess sponge devices in larger randomized control trials (e.g., BEST4). Other approaches include multi-cancer detection blood tests and breath testing for volatile organic compounds. However, these techniques have either limited sensitivity or specificity, and additional studies in the target screening population are needed.

[0006] Swallowable imaging capsules are alternatives to uTNE and nonendoscopic sponges / balloons. Wireless video capsules have been explored as a potential screening tool, but the rapid transit time and inability to perform a detailed esophageal examination are limitations. By attaching a tether or string to the capsule, positional control is improved and more detailed examination can be performed. However, these capsules are still limited by low image resolutions, slow frame rates, and no ability to map the esophageal mucosa. Other techniques include tethered optical coherence tomography (OCT) capsules. OCT can visualize subsurface and depth-resolved microstructural features with superior imaging depth compared to standard video imaging. However, OCT has difficulty in estimating the location of the gastroesophageal junction and in measuring the length of BE using OCT features alone.SUMMARY OF THE INVENTION

[0007] In an example embodiment, the present invention is an apparatus for imaging a cavity. The apparatus comprises an enclosure, comprising: a distal end, a proximal end, and a transparent portion therebetween. The proximal end comprises at least one electrical connection, and the transparent portion is transparent to an illumination signal; and a flexible tether, operably connected to the electrical connection of the proximal end of the enclosure. The enclosure further comprises an image acquisition device, an illumination source, and an annular reflector, whereinthe illumination source is configured to generate the illumination signal comprising illumination beams, the annular reflector being configured to direct at least some of the illumination beams through the transparent portion of the enclosure at the cavity, thereby generating a reflected signal comprising reflected beams, the annular reflector being further configured to direct at least some of the reflected beams at the image acquisition device, the image acquisition device being configured to capture one or more images based on the reflected signal.

[0008] In another example embodiment, the present invention is an apparatus for imaging of a cavity. The apparatus comprises an enclosure, comprising: a distal end, a proximal end, and a transparent portion therebetween, wherein: the transparent portion is transparent to an illumination signal, the distal end is opaque to the illumination signal, at least the transparent portion of the enclosure is expandable, and the proximal end comprises at least one electrical connection; and a flexible tether, operably connected to the electrical connection of the proximal end of the enclosure. The enclosure further comprises an image acquisition device and an illumination source. The illumination source is configured to generate the illumination signal comprising illumination beams, the illumination signal being directed through the transparent portion of the enclosure at the cavity, thereby generating a reflected signal comprising reflected beams, the image acquisition device being configured to capture one or more images based on the reflected signal.

[0009] In another example embodiment, the present invention is a method of imaging a luminal organ or a surgical cavity using any of the apparatuses described herein to acquire one or more images of the cavity.BRIEF DESCRIPTION OF THE DRAWINGS

[0010] The foregoing will be apparent from the following more particular description of example embodiments of the invention, as illustrated in the accompanying drawings in which like reference characters refer to the same parts throughout the different views. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating embodiments of the present invention.

[0011] FIGs. 1A, IB, and 1C. (A) 3D rendering of the omniview capsule. (B) Flowchart describing the generation of panorama images. (C) Capsule imaging of a subject with shortsegment BE showing a darker (red-colored) distal region, corresponding to columnar epithelium, and a brighter (pink-blue) proximal region corresponding to squamous epithelium. Superficial vasculature is visualized throughout the pullback. Bubbles are seen in folded regions of the esophagus (arrowheads). The magnified region shows an area of columnar epithelium with a distinct mucosal pattern (arrows), which was biopsied on EGD and confirmed to contain intestinal metaplasia.

[0012] FIGs. 2A through FIG. 2G. Capsule imaging of a subject with prior diagnosed intramucosal carcinoma. (A) A panorama of a 10 cm length pullback shows an irregular SCJ and an island of columnar mucosa (arrows) containing IM. The island was visualized during EGD (inset). (B) through (D) Annular images at three longitudinal positions are denoted by white dotted lines in (A). The 0° angle corresponds to the top of the panorama. Gastric folds can be seen in (B), and (C) shows the presence of superficial vasculature in the squamous epithelium. The island has a characteristic pit pattern texture shown in (d). (E) through (G) Unwarped images corresponding to the three annular images above.

[0013] FIG. 3A through FIG. 3F. (A) Capsule imaging of a 16 cm pullback in a subject with long segment NDBE scheduled for surveillance endoscopy. A 16 cm pullback shows large areas of CE extending proximally. Seattle protocol biopsies confirmed the presence of IM. The SCJ is highlighted by a contour; G denotes the approximate position of the top of gastric folds. Prague C and M are measured from G. (B) EGD image showing an irregular SCJ. Different points along the SCJ are numbered from 1 to 6. (C) Magnified area of panorama showing the SCJ with corresponding numbered points, matching those in (B). (D) EGD image at a more proximal location, showing an island of BE. (E) Magnified view of the island. (F) The corresponding island is seen on capsule imaging.

[0014] FIG. 4A through FIG. 4F. (A) Capsule imaging of a 10 cm pullback in a subject with a history of high-grade dysplasia and intramucosal carcinoma (B) through (F) Magnified regions of panorama show islands of columnar epithelium (top) and corresponding islands on EGD (bottom). Targeted biopsies were obtained from the islands shown in panels (E) and (F), which showed high-grade dysplasia. Small repeated specks were from debris on the imaging window and reflector (arrow, (C)).

[0015] FIG. 5 is a screen capture demonstrating simultaneous video and panorama viewing. A video frame is rendered as annular and unwarped images. Each frame of the video is registered to a longitudinal position on the panorama. The user can scroll through the video, and a scrollbar overlay on the panorama shows the current position of the video frame.

[0016] FIG. 6A through FIG. 6E. (A) An example embodiment of an apparatus described herein. A laptop functions as an image-processing and / or display module. (B) through (E) are annular and unwarped images of a simulated inner cavity.

[0017] FIG. 7A and FIG. 7B show an example embodiment of an apparatus described herein employing an expandable enclosure.

[0018] FIG. 8A and FIG. 8B show an alternative example embodiment of an apparatus described herein employing an expandable enclosure.

[0019] FIG. 9 is a schematic diagram of an example embodiment of an apparatus described herein.DETAILED DESCRIPTION OF THE INVENTION

[0020] A description of example embodiments of the invention follows.

[0021] Presented herein is an omniview tethered video capsule technology - a novel device capable of comprehensive, 360° imaging of the esophagus. Unlike white light video capsules that capture at low frame rates, the omniview capsule generates a continuous, virtual chromoendoscopic video scan of the esophagus within 10-20 seconds, enabling detailed visualization of morphological features. The captured video frames can be digitally assembled into a scaled panorama for quantitative mapping of the esophagus. Here, we report first-inhuman results, demonstrating the initial feasibility of unsedated omniview capsule imaging in patients with BE and dysplasia.

[0022] Accordingly, in a 1stexample embodiment, the present invention is an apparatus (e.g., 100, FIG. 1) for imaging a cavity. In a 1staspect of the 1stexample embodiment, the apparatus comprises an enclosure (e.g., 101, FIG. 1), comprising: a distal end (e.g., 102, FIG. 1), a proximal end (e.g., 103, FIG. 1), and a transparent portion (e.g., 104, FIG. 1) therebetween. The proximal end comprises at least one electrical connection (e.g., 105, FIG. 1) and the transparentportion is transparent to an illumination signal. The device further comprises a flexible tether (e.g., 107, FIG. 1), operably connected to the electrical connection of the proximal end of the enclosure. The enclosure further comprises an image acquisition device (e.g., 109, FIG. 1), an illumination source (e.g., I l l, FIG. 1), and an annular reflector (e.g., 113, FIG. 1), wherein the illumination source is configured to generate the illumination signal comprising illumination beams, the annular reflector being configured to direct at least some of the illumination beams through the transparent portion of the enclosure at the cavity, thereby generating a reflected signal comprising reflected beams, the annular reflector being further configured to direct at least some of the reflected beams at the image acquisition device, the image acquisition device being configured to capture one or more images based on the reflected signal.

[0023] In a 2ndaspect of the 1stexample embodiment, the illumination source comprises one or more first light sources (e.g., I l la, FIG. 1) configured to generate light at a first wavelength, and one or more second light sources (e.g., 111b, FIG. 1) configured to generate light at a second wavelength. The remaining features and example features are as described above with respect to the 1staspect of the 1stexample embodiment.

[0024] In a 3rdaspect of the 1stexample embodiment, the first wavelength is 415 nm and the second wavelength is 540 nm. The remaining features and example features are as described above with respect to the 1stand 2ndaspects of the 1stexample embodiment.

[0025] In a 4thaspect of the 1stexample embodiment, the annular reflector is a conical reflector. The remaining features and example features are as described above with respect to the 1stthrough 3rdaspects of the 1stexample embodiment.

[0026] In a 5thaspect of the 1stexample embodiment, the image acquisition device is configured to acquire two or more images per unit time. The remaining features and example features are as described above with respect to the 1stthrough 4thaspects of the 1stexample embodiment.

[0027] In a 6thaspect of the 1stexample embodiment, the two or more images partially overlap. The remaining features and example features are as described above with respect to the 1stthrough 5thaspects of the 1stexample embodiment.

[0028] In a 7thaspect of the 1stexample embodiment, the tether is further adapted to connect to an image-processing and / or display module (e.g., 115, FIG. 1 or 901, FIG. 9). The remainingfeatures and example features are as described above with respect to the 1stthrough 6thaspects of the 1stexample embodiment.

[0029] In an 8thaspect of the 1stexample embodiment, the apparatus further comprises the image-processing module configured to digitally process the one or more images acquired by the image acquisition device into one or more panoramic images. The remaining features and example features are as described above with respect to the 1stthrough 7thaspects of the 1stexample embodiment.

[0030] In a 9thaspect of the 1stexample embodiment, the cavity is a cavity of a luminal organ or a surgical cavity. The remaining features and example features are as described above with respect to the 1stthrough 8thaspects of the 1stexample embodiment.

[0031] In a 2ndexample embodiment, the present invention is a method of imaging a luminal organ or a surgical cavity. In a 1staspect of the 2ndexample embodiment, the method comprises providing an apparatus (e.g., 100, FIG. 1) as described with respect to any of the aspects of the 1stexample embodiment; and causing the apparatus to acquire one or more images of the cavity.

[0032] In a 2ndaspect, the method further comprises linearly translating the enclosure through the cavity. The remaining features and example features are as described above with respect to the 1staspect of the 2ndexample embodiment.

[0033] In a 3rdaspect, the method further includes registering the acquired optical image relative to at least one static landmark. The remaining features and example features are as described above with respect to the 1stand 2ndaspects of the 2ndexample embodiment.

[0034] In a 4thaspect, the cavity is a cavity of a luminal organ or a surgical cavity. The remaining features and example features are as described above with respect to the 1stthrough 3rdaspects of the 2ndexample embodiment.

[0035] In a 3rdexample embodiment, the present invention is an apparatus (e.g., 700, FIGS. 7A-7B or 800, FIGS. 8A-8B) for imaging of a cavity. In a 1staspect of the 3rdexample embodiment, the apparatus comprises an enclosure (e.g., 701, FIGS. 7A-7B or 801, FIGS. 8A- 8B), comprising a distal end (e.g., 702, FIGS. 7A-7B or 802, FIGS. 8A-8B), a proximal end (e.g., 703, FIGS. 7A-7B or 803, FIGS. 8A-8B), and a transparent portion (e.g., 704, FIGS. 7A- 7B or 804, FIGS. 8A-8B) therebetween. The transparent portion is transparent to an illumination signal, the distal end is opaque to the illumination signal, at least the transparent portion of theenclosure is expandable, and the proximal end comprises at least one electrical connection (e.g., 705, FIGS. 7A-7B or 805, FIGS. 8A-8B); and a flexible tether (e.g., 707, FIGS. 7A-7B or 807, FIGS. 8A-8B), operably connected to the electrical connection of the proximal end of the enclosure. The enclosure further comprises an image acquisition device (e.g., 709, FIGS. 7A-7B or 809, FIGS. 8A-8B) and an illumination source (e.g., 711, FIGS. 7A-7B or 811, FIGS. 8A-8B), wherein the illumination source is configured to generate the illumination signal comprising illumination beams, the illumination signal being directed through the transparent portion of the enclosure at the cavity, thereby generating a reflected signal comprising reflected beams, the image acquisition device being configured to capture one or more images based on the reflected signal.

[0036] In a 2ndaspect of the 3rdexample embodiment, the distal end is expandable. The remaining features and example features are as described above with respect to the 1staspect of the 3rdexample embodiment.

[0037] In a 3rdaspect of the 3rdexample embodiment, the illumination source comprises one or more first light sources (e.g., 71 la, FIGS. 7A-7B or 811a, FIGS. 8A-8B) configured to generate light at a first wavelength, and one or more second light sources (e.g., 711b, FIGS. 7A- 7B or 811b, FIGS. 8A-8B) configured to generate light at a second wavelength. The remaining features and example features are as described above with respect to the 1stand 2ndaspects of the 3rdexample embodiment.

[0038] In a 4thaspect of the 3rdexample embodiment, the first wavelength is 415 nm and the second wavelength is 540 nm. The remaining features and example features are as described above with respect to the 1stthrough 3rdaspects of the 3rdexample embodiment.

[0039] In a 5thaspect of the 3rdexample embodiment, the enclosure further comprises an annular reflector (e.g., 713, FIGS. 7A-7B or 813, FIGS. 8A-8B) configured to direct at least some of the illumination beams to the cavity and to direct at least some of the reflected beams at the image acquisition device. The remaining features and example features are as described above with respect to the 1stthrough 4thaspects of the 3rdexample embodiment.

[0040] In a 6thaspect of the 3rdexample embodiment, the annular reflector is a conical reflector. The remaining features and example features are as described above with respect to the 1stthrough 5thaspects of the 3rdexample embodiment.

[0041] In a 7thaspect of the 3rdexample embodiment, the image acquisition device is configured to acquire two or more images per unit time. The remaining features and example features are as described above with respect to the 1stthrough 6thaspects of the 3rdexample embodiment.

[0042] In a 8thaspect of the 3rdexample embodiment, the two or more images partially overlap. The remaining features and example features are as described above with respect to the 1stthrough 7thaspects of the 3rdexample embodiment.

[0043] In an 9thaspect of the 3rdexample embodiment, the tether is further adapted to connect to an image-processing and / or display module (e.g., 901, FIG. 9). The remaining features and example features are as described above with respect to the 1stthrough 8thaspects of the 3rdexample embodiment.

[0044] In a 10thaspect of the 3rdexample embodiment, the apparatus further comprises the image-processing module configured to digitally process the one or more images acquired by the image acquisition device into one or more panoramic images. The remaining features and example features are as described above with respect to the 1stthrough 9thaspects of the 3rdexample embodiment.

[0045] In a 11thaspect of the 3rdexample embodiment, the cavity is a cavity of a luminal organ or a surgical cavity. The remaining features and example features are as described above with respect to the 1stthrough 10thaspects of the 3rdexample embodiment.

[0046] In a 4thexample embodiment, the present invention is a method of imaging a cavity. In a 1staspect, the method comprises providing an apparatus (e.g., 700, FIGS. 7A-7B or 800, FIGS. 8A-8B) according to any aspect of the 3rdexample embodiment; and causing the apparatus to acquire one or more images of the cavity.

[0047] In a 2ndaspect, the method further comprises expanding at least the expandable portion of the enclosure. The remaining features and example features are as described above with respect to the 1staspect of the 4thexample embodiment.

[0048] In a 3rdaspect, the method further comprises linearly translating the enclosure through the cavity. The remaining features and example features are as described above with respect to the 1stand 2ndaspects of the 4thexample embodiment.

[0049] In a 4thaspect, the method further comprises registering the acquired optical image relative to at least one static landmark. The remaining features and example features are as described above with respect to the 1stthrough 3rdaspects of the 4thexample embodiment.

[0050] In a 5thaspect, the cavity is a cavity of a luminal organ or a surgical cavity. The remaining features and example features are as described above with respect to the 1stthrough 4thaspects of the 4thexample embodiment.

[0051] EXEMPLIFICATION

[0052] Methods

[0053] Omniview tethered capsule device

[0054] Figure 1 displays a 3D rendering of the 12 mm diameter, 27 mm long capsule. The sealed outer housing was comprised of biocompatible plastic endcaps and a glass imaging window. The housing contained indigo and green LEDs, a conical reflector, and a 1920 x 1080p endoscope camera with a 60 frames / second rate. LED wavelengths of 415 nm and 540 nm were chosen to emulate narrow-band imaging (NBI). The capsule connected via a standard USB port on a consumer-grade laptop. A separate, external LED driving circuit (not shown) powered the LEDs. The camera cable and LED wires were enclosed by a ~2.6 mm diameter flexible polymer sheath, forming the tether. Distance markings at 5 cm intervals on the tether were used to estimate the position of the capsule from the incisors.

[0055] Image processing and analysis

[0056] The omniview capsule produced 360° images spanning a ~2 mm wide by ~37 mm circumference annulus (Fig. lb). Extracted video frames were unwarped into rectangular strips and registered to estimate the frame-to-frame displacement. Unwarped frames were then stitched into a scaled panorama, which provided an unwarped, en face overview of the esophagus. The number of pixels in each panorama was determined by the length of the esophagus imaged; a standard 10 cm pullback was ~30 megapixels. A user could therefore digitally zoom into the panorama to visualize mucosal features, such as pit patterns and vascular morphology, at high magnification (FIG. 1C). Panorama images were segmented into squamous and columnar epithelium using a k-means clustering algorithm. The squamocolumnar junction (SCJ) wasestimated on segmented images using a well-known border-finding algorithm. Post-processing was performed using MATLAB, Python, and Image!

[0057] Patient recruitment and imaging procedure

[0058] Patients undergoing surveillance EGD for NDBE or endoscopic eradication therapy for prior diagnosed dysplasia were invited to participate in the study. Exclusion criteria were individuals with dysphagia, odynophagia, or other concurrent medical conditions that precluded capsule imaging or EGD. Capsule imaging was performed 1-2 hours prior to the EGD. The capsule imaging procedure was similar to that of a previously described study. Briefly, capsule imaging was performed in a simulated office setting, with the patient unsedated and sitting upright. The subject was asked to swallow the capsule with sips of water (< 50 mL). Real-time capsule video feedback was used to confirm successful swallowing. Once the capsule traversed the gastric folds, the tether was retracted at ~l-2 cm / sec while recording video over 10-20 cm. To acquire additional pullbacks, the subject was asked to perform dry or wet swallows to reposition the capsule near the gastroesophageal junction (GEJ), and the pullback was repeated. Subjects then received same-day EGD, where a video recording of the procedure was captured. During the endoscopy, Prague numbers were obtained, and Seattle protocol was performed on patients undergoing surveillance. For patients with prior diagnosed dysplasia who had not yet achieved complete eradication of intestinal metaplasia (IM), targeted biopsies of dysplastic- appearing regions were taken under NBI, and radiofrequency ablation was performed.

[0059] Results

[0060] FIGs. 2 illustrate omniview capsule imaging in a 70-year-old male patient with prior diagnosis of intramucosal carcinoma (IMC). A 10 cm length pullback showed an irregular SCJ with ~1 cm of columnar epithelium extending beyond the top of the gastric folds (FIG. 2A). An island of columnar epithelium containing biopsy-confirmed IM was seen ~3 cm proximal to the GEJ on capsule imaging, as well as on EGD (FIG. 2A, inset). The GEJ was estimated as the most proximal extent of the folded structures seen at the distal end, presumed to be the top of the gastric folds (FIG. 2B). The SCJ appeared as a border between differently-colored regions of columnar epithelium (CE) and squamous epithelium (SE), with superficial vasculature structures visualized from the 12 o’clock position to the 4 o’clock position (FIG. 2C). A magnified view of the island showed a metaplastic pit pattern texture distinct from the gastric columnar epithelium(FIG. 2D). Unwarped versions of the three annular images rendered a view similar to magnification endoscopy (FIG. 2E through FIG. 2F). Annular and unwarped frames could also be viewed alongside the panorama by interactively scrolling through an image stack.

[0061] Capsule images allowed for quantitative mapping of esophageal morphology. FIGs. 3 show capsule imaging over a 16 cm pullback length of a 73 -year-old male with long-segment NDBE. Long segments of CE extending proximally were visualized on the panorama (FIG. 3A). Prague estimates assessed on capsule imaging were C1.2M3.8. However, EGD Prague estimates were C2M4. The discrepancy in Prague estimates may arise from the deflated state of the esophagus during capsule imaging or due to rounding or estimation error of markings on the tether or endoscope. Although absolute Prague estimates did not match, the morphology of the SCJ seen on capsule imaging was easily registered to the appearance on EGD (FIG. 3B and FIG 3C). An island of CE was seen on both EGD (FIG. 3D and FIG. 3E) and capsule imaging (FIG. 3F).

[0062] Capsule imaging can document areas of mucosal irregularity and identify areas of potential dysplasia. FIGs. 4 shows a 10 cm pullback in a 72-year-old male with a history of highgrade dysplasia and IMC receiving endoscopic therapy. Capsule imaging showed an irregular SCJ (FIG. 4A) with multiple columnar islands showing intensified tubulovillous mucosal patterns (FIGs. 4B-4F). All islands seen on capsule imaging were also seen on EGD. Targeted biopsies were acquired from the two most proximal islands (FIGs. 2E-2F), which were later confirmed to contain high-grade dysplasia. The capsule Prague numbers were C0.2M1.4, while EGD-derived numbers were C1M4. A potential explanation for the large discrepancy in M is overestimation of the maximal extent of BE during EGD, as subsequent review of the EGD recording revealed difficulty in distinguishing the contiguous BE segment from BE islands due to their proximity. This suggests capsule imaging may excel at mapping of BE islands, especially for those that are small and closely-spaced. Capsule images can also provide estimates of the area of columnar epithelium. We estimated the area of the contiguous BE segment extending from the top of the gastric folds, G, to the maximal extent, M. We also estimated the areas of the BE islands. The area of the contiguous BE segment was 256.2 mm2, and the total area including the sum of all islands was 421.2 mm2, which represented ~11% of the total imaged area.

[0063] Discussion

[0064] This first-in-human study demonstrates the feasibility of an omniview tethered video capsule for esophageal imaging in unsedated subjects. Capsule imaging can be performed with a simple, office-based procedure, similar to demonstrations of previously described tethered capsules. Initial findings suggested capsule imaging could detect areas of suspected BE and dysplasia. Patients with positive findings on capsule imaging can be referred for follow-up EGD for confirmatory diagnosis or endoscopic eradication therapy. However, a larger prospective study in the target screening population is required to assess accuracy for the detection and diagnosis of BE.

[0065] The omniview capsule provided morphological information complementary to immunohistochemistry or other molecular assays. A recent update to the American College of Gastroenterology guidelines introduced a conditional recommendation for the use of a swallowable, nonendoscopic sponge combined with a biomarker as an alternative to endoscopy for BE screening. Compared to methods that require specimens, imaging data has simpler transportation and storage requirements. Capsule imaging enables simple and quantitative morphometry that can be longitudinally tracked over time. Potential metrics include Prague numbers, the area of columnar epithelium, SCJ shape, and irregularity of mucosal and vascular patterns. However, the accuracy and repeatability of quantitative metrics require further validation. Quantitative endoscopy, including Al-based methods, has been previously proposed but was limited to upper endoscopy. Al methods used in endoscopy can be adapted to capsule imaging for detection or diagnosis, as well as for data quality control.

[0066] Initial results underscored the potential for discordance with EGD-derived measurements. Discordances are likely from a combination of current limitations of the capsule design (e.g., inability to insufflate the esophagus) and inherent variability in estimating BE length during endoscopy. However, algorithms to fuse data and compute average / consensus estimates from multiple pullbacks obtained during a single imaging session may reduce error.

[0067] The primary limitation of the study presented herein was its small sample size. However, the study described herein aimed to present the key capabilities of new capsule technology and highlight the potential utility for BE screening. Future studies with larger numbers of subjects will be performed to estimate diagnostic accuracy. The current capsulecannot obtain specimens for follow-up analyses. However, patients can be referred for follow-up EGD or other cytology-based techniques if suspected pathology is seen on capsule imaging.

[0068] The teachings of all patents, published applications and references cited herein are incorporated by reference in their entirety.

[0069] While this invention has been particularly shown and described with references to example embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the invention encompassed by the appended claims.

Claims

CLAIMSWhat is claimed is:

1. An apparatus for imaging a cavity, the apparatus comprising: an enclosure, comprising: a distal end, a proximal end, and a transparent portion therebetween, wherein: the proximal end comprises at least one electrical connection, and the transparent portion is transparent to an illumination signal; and a flexible tether, operably connected to the electrical connection of the proximal end of the enclosure; wherein the enclosure further comprises an image acquisition device, an illumination source, and an annular reflector, wherein the illumination source is configured to generate the illumination signal comprising illumination beams, the annular reflector being configured to direct at least some of the illumination beams through the transparent portion of the enclosure at the cavity, thereby generating a reflected signal comprising reflected beams, the annular reflector being further configured to direct at least some of the reflected beams at the image acquisition device, the image acquisition device being configured to capture one or more images based on the reflected signal.

2. The apparatus of Claim 1, wherein the illumination source comprises one or more first light sources configured to generate light at a first wavelength, and one or more second light sources configured to generate light at a second wavelength.

3. The apparatus of Claim 2, wherein the first wavelength is 415 nm and the second wavelength is 540 nm.

4. The apparatus of any one of Claims 1-3, wherein the annular reflector is a conical reflector.

5. The apparatus of any one of Claims 1-4, wherein the image acquisition device is configured to acquire two or more images per unit time.

6. The apparatus of any one of Claims 5, wherein the two or more images partially overlap.

7. The apparatus of any one of Claims 1-6, wherein the tether is further adapted to connect to an image-processing and / or display module.

8. The apparatus of Claim 7, further comprising the image-processing module configured to digitally process the one or more images acquired by the image acquisition device into one or more panoramic images.

9. The apparatus of Claims 1-8, wherein the cavity is a cavity of a luminal organ or a surgical cavity.

10. A method of imaging a luminal organ or a surgical cavity, comprising: providing an apparatus of any one of Claims 1 through 9; and causing the apparatus to acquire one or more images of the cavity.

11. The method of Claim 10, further comprising linearly translating the enclosure through the cavity.

12. The method of Claims 10 or 11, further including registering the acquired optical image relative to at least one static landmark.

13. The method of any one of Claims 10-12, wherein the cavity is a cavity of a luminal organ or a surgical cavity.

14. An apparatus for imaging of a cavity, the apparatus comprising:an enclosure, comprising: a distal end, a proximal end, and a transparent portion therebetween, wherein: the transparent portion is transparent to an illumination signal, the distal end is opaque to the illumination signal, at least the transparent portion of the enclosure is expandable, and the proximal end comprises at least one electrical connection; and a flexible tether, operably connected to the electrical connection of the proximal end of the enclosure; wherein the enclosure further comprises an image acquisition device and an illumination source, wherein the illumination source is configured to generate the illumination signal comprising illumination beams, the illumination signal being directed through the transparent portion of the enclosure at the cavity, thereby generating a reflected signal comprising reflected beams, the image acquisition device being configured to capture one or more images based on the reflected signal.

15. The apparatus of Claim 14, wherein the distal end is expandable.

16. The apparatus of Claim 14-15, wherein the illumination source comprises one or more first light sources configured to generate light at a first wavelength, and one or more second light sources configured to generate light at a second wavelength.

17. The apparatus of Claim 16, wherein the first wavelength is 415 nm and the second wavelength is 540 nm.

18. The apparatus of any one of Claims 14-17, wherein the enclosure further comprises an annular reflector configured to direct at least some of the illumination beams to the cavity and to direct at least some of the reflected beams at the image acquisition device.

19. The apparatus of Claim 18, wherein the annular reflector is a conical reflector.

20. The apparatus of any one of Claims 14-19, wherein the image acquisition device is configured to acquire two or more images per unit time.

21. The apparatus of any one of Claims 20, wherein the two or more images partially overlap.

22. The apparatus of any one of Claims 14-21, wherein the tether is further adapted to connect to an image-processing and / or display module.

23. The apparatus of Claim 22, further comprising the image-processing module configured to digitally process the one or more images acquired by the image acquisition device into one or more panoramic images.

24. The apparatus of Claims 14-23, wherein the cavity is a cavity of a luminal organ or a surgical cavity.

25. A method of imaging a cavity, comprising: providing an apparatus of any one of Claims 1 through 8; and causing the apparatus to acquire one or more images of the cavity.

26. The method of Claim 25, further comprising expanding at least the expandable portion of the enclosure.

27. The method of Claims 25 or 26, further comprising linearly translating the enclosure through the cavity.

28. The method of any one of Claims 25-27, further comprising registering the acquired optical image relative to at least one static landmark.

29. The method of any one of Claims 25-28, wherein the cavity is a cavity of a luminal organ or a surgical cavity.

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