Systems and methods for high-resolution, high-speed capsule endoscopy

Abstract

To provide a new SECM probe design which does not require filling the probe with a liquid such as water but which nevertheless provides comparable optical performance.SOLUTION: A probe for performing endomicroscopy, comprises: a light source; a waveguide coupled to the light source; a diffraction grating 440, the waveguide directing light from the light source to the diffraction grating; and a lens 450 having a first aspheric surface and a second biconic surface. Diffracted light from the diffraction grating is directed into the aspheric surface of the lens and emitted from the biconic surface of the lens towards a transparent cylindrical surface of the probe.SELECTED DRAWING: Figure 4

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application is based on and claims the benefit of and priority to U.S. Provisional Patent Application No. 62 / 892,073, filed August 27, 2019, the entire contents of which are incorporated herein by reference for all purposes.

[0002] STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT Not applicable. [Background technology]

[0003] Spectrally encoded confocal microscopy (SECM) is a high-speed imaging technique that offers imaging speeds one to two orders of magnitude faster than video-rate reflection confocal microscopy, while enabling the probe to be significantly smaller by replacing mechanical scanning devices with diffraction gratings. However, conventional designs have difficulty achieving diffraction-limited optical resolution due to asymmetric spherical aberrations at the probe surface (e.g., resulting from the cylindrical imaging window of the SECM capsule). One solution to this problem is to fill the gap between the objective lens and the imaging window in the probe (e.g., capsule) with water, thereby reducing the refractive index mismatch and minimizing the aberrations to achieve diffraction-limited optical resolution (see Figure 1A and B). Figure 1A shows the objective lens of a known system, which has two rounded surfaces on both sides, both of which are radially symmetric.

[0004] However, filling a probe such as an SECM capsule with water imposes numerous additional manufacturing requirements, including the need to seal the components with a watertight epoxy. Furthermore, the difficulty of maintaining water within the probe reduces the lifetime of a water-filled SECM capsule (e.g., less than 1-2 months). Finally, air bubbles can appear in the water inside the probe during processing, potentially preventing optimal performance (see Figure 2). Summary of the Invention

[0005] Thus, new SECM probe designs that do not require the probe to be filled with a liquid such as water, yet still provide comparable optical performance, are desirable.

[0006] Thus, presented herein is an embodiment of a probe for performing endoscopy, the probe comprising a light source, a waveguide coupled to the light source, a diffraction grating, and a lens having a first aspherical surface and a second biconic surface, the waveguide configured to direct light from the light source to the diffraction grating, and configured such that diffracted light from the diffraction grating is directed to the aspherical surface of the lens and emitted from the biconic surface of the lens towards a transparent cylindrical surface of the probe.

[0007] In one embodiment, the present invention provides a method for performing endoscopy using a probe comprising a light source, a waveguide coupled to the light source, a diffraction grating, and a lens having a first aspherical surface and a second biconic surface, the method including directing light from the light source through the waveguide to the diffraction grating, and directing the diffracted light through the diffraction grating to the aspherical surface of the lens and out the biconic surface of the lens toward a transparent cylindrical surface of the probe.

[0008] Some of the above and other embodiments, aspects, advantages and features of the present invention are described in the following description and appended claims. These and other features and advantages will become apparent to those skilled in the art upon examination of the accompanying drawings or by practice of the invention. The accompanying drawings are for the purpose of illustrating one or more embodiments, and do not necessarily represent the full scope of the invention.

[0009] The following detailed description is described with reference to the accompanying drawings, which form a part of the detailed description. The drawings illustrate specific embodiments in which the apparatus may be implemented. These embodiments, also referred to herein as "examples" or "options," are described in sufficient detail to enable those skilled in the art to practice the embodiments. The embodiments may be combined, other embodiments may be utilized, and structural or logical changes may be made within the scope of the present invention. Therefore, the following detailed description is not to be taken in a limiting sense, and the scope of the present invention is defined by the appended claims and their legal equivalents. As used herein, the terms "a" or "an" are used to include one or more, and the term "or" is used to refer to a non-exclusive "or" unless otherwise specified. Additionally, terms or phrases employed herein and not otherwise defined should be understood to be for descriptive purposes only and not for limiting purposes. [Brief explanation of the drawings]

[0010] [Figure 1] ZEMAX simulations of an SECM objective without a biconic surface are shown. A shows the objective layout including ray tracing, and B shows the RMS wavefront error as a function of field angle. [Figure 2] A water-filled SECM capsule is shown 1 day (left), 1 week (center), and 1 month (right) after the capsule was filled with water, demonstrating the gradual effect of water on the probe over time. [Figure 3] 1 shows the SECM optical configuration used in the capsule, including an objective lens with a biconic surface facing towards the imaging window. [Figure 4] The tethered capsule with the SECM optical system inside is shown. [Figure 5] 1 shows lenses generated using ZEMAX software, including a list of parameters for specific embodiments of aspheric and biconic surfaces and lens materials. [Figure 6] 1 shows an objective lens design with aspheric and biconic surfaces, including a notch for proper alignment of the lens, and shows a perspective view (left) and a side view (right) of the lens. [Figure 7] Another design of an objective lens with aspheric and biconic surfaces, including two notches for proper alignment of the lens, is shown in an end view (top left), an oblique view (top right), a first side view (bottom left), and a second side view perpendicular to the first side (bottom right). [Figure 8] Shown is a tethered capsule containing an objective lens mount with a pair of round notches and a lens with a similar pair of round notches, with two ceramic spheres inserted into the space formed by the notches to hold the lens in place and in the correct orientation. [Figure 9] 1 is a table comparing the specifications of an existing SECM-based water immersion capsule with the specifications of an SECM capsule that includes an objective lens with a biconic surface and does not require water immersion. [Figure 10] FIG. 1 is a diagram of a capsule probe having a cylindrical housing, with the long axis of the probe shown along the radius of the biconic lens of the optical component within the probe, and a first axis (R1) parallel to the long axis of the probe and perpendicular to a shorter second axis (R2). DETAILED DESCRIPTION OF THE INVENTION

[0011] Disclosed herein are embodiments of apparatus, methods, and / or systems for SECM probes, which include an objective lens having a biconic surface, resulting in improved resolution by water immersion to achieve diffraction-limited or near-diffraction-limited optical resolution. No corrective or other corrective measures are required.

[0012] Spectrally encoded confocal microscopy (SECM) is a miniature endoscopic technique that uses wavelengths to encode physical locations on an inspected sample in order to achieve high imaging speeds. Briefly, a broadband or wavelength-swept light source is scanned across a swath (hereafter referred to as a "swath") of the sample. The SECM capsules are split into multiple wavelengths, with each wavelength or subgroup of wavelengths acting as a separate beam to illuminate the sample (Figure 3), thereby increasing the amount of data that can be collected from a sample in a single optical path, as large amounts of data can be collected in parallel. Several pill-sized, tethered SECM capsules have been developed to obtain cellular-resolution images of the upper gastrointestinal (GI) tract, but to date the imaging quality of such SECM capsules has been limited by issues such as insufficient optical resolution, non-uniform pullback, and non-uniform rotational distortion.

[0013] Some versions of the water-filled, pill-sized, tethered capsule have been developed that are compatible with 100 kHz, 1310 nm wavelength swept-source SECM imaging systems. Disclosed herein is an example of a tethered SECM endoscopic imaging system and capsule that utilizes a 400 kHz swept-source centered at 1060 nm. This new 1060 nm capsule design not only offers higher resolution due to the shorter wavelength, but also eliminates the need for corrective measures such as water immersion, i.e., filling the capsule with a liquid such as water.

[0014] In various disclosed embodiments, to correct for the asymmetric spherical aberration caused by the curved (nearly cylindrical) transparent wall of the capsule, the objective lens 310 (FIGS. 3, 5) may have a conventional aspheric surface 320 on one side (e.g., the side facing the light source) and a biconic surface 330 on the opposite side (e.g., the side facing the sample); by designing the objective lens 310 in this manner, water immersion or other correction measures are not required.

[0015] In various embodiments, the capsule diameter is increased to improve physical contact with the esophagus and increase the usable spectrally encoded line length, thereby increasing the number of distinguishable wavelengths and therefore the number of pixels within the spectrally broadened swath of light. In various embodiments, compared to other SECM capsule devices and systems using a 100 kHz, 1310 nm source, the imaging speed of the designs disclosed herein can be increased by 5.2 times and the lateral resolution can be improved by 15%. Furthermore, achieving SECM without capsule immersion simplifies manufacturability and extends the device's lifetime. These advances significantly enhance the clinical translatability of SECM for applications such as upper gastrointestinal diagnostics.

[0016] Generally, SECM enables reflection confocal microscopy via a compact probe such as a catheter or capsule (Figure 4). SECM uses wavelength division multiplexing ("WDM") to encode one-dimensional spatial information reflected from a sample. A fast-scan axis is replaced by a series of focal points, each represented by a different wavelength of light 340, 350, or 360 (Figure 3). Remittance as a function of spatial position can be determined by measuring the spectrum of the reflected light. Two-dimensional images may be generated by scanning the wavelength-encoded axis with slow mechanical movement of the probe. Thus, an endoscopic device embodying the present invention enables SECM imaging of various tissues and organs, either integrated with a standard endoscope or as a stand-alone device such as a capsule. See U.S. Pat. No. 6,831,781 and U.S. Patent Application Publication No. 2011 / 013178, the entire contents of each of which are incorporated herein by reference for all purposes.

[0017] In some embodiments, the SECM system can be constructed as a swallowable tethered capsule 400 (FIG. 4). As shown in FIG. 4, the capsule 400 includes an imaging window. The SECM system includes a window 410 (shown in dotted lines), a tether 420 including a waveguide / optical fiber, a collimating lens 430, a diffraction grating 440, an objective lens 450, and a housing 460. Tether 420 is connected to a SECM system 470, which, in various embodiments, can include one or more light sources (e.g., swept-source lasers), a rotational and / or linear scanning system, a photodetector, and a computing system for controlling one or more other components and for collecting and processing data.

[0018] In various embodiments, capsule 400 may have a smooth overall shape, with housing 460 comprising a cylindrical body with rounded (e.g., hemispherical) ends. This overall shape allows capsule 400 to be swallowed and moved with little resistance through luminal passageways, such as the digestive tract, by gravity and / or peristaltic muscle movement. Tether 420 extends from one end of housing 460 ( FIG. 4 ). Capsule 400 may vary in size, but typically has a diameter of less than 10 mm, in some embodiments, 7 mm, and in other embodiments, 8 mm. At least a portion of capsule 400's housing 460 includes an imaging window 410 that is optically transparent to appropriate wavelengths (e.g., UV, visible, and / or IR wavelengths). Typically, imaging window 410 extends completely around the outer edge of capsule 400, allowing for rotational scanning of a sample through capsule housing 460.

[0019] Light from a waveguide housed within tether 460 is directed toward a diffraction grating 440, which is set at an angle (e.g., about a 45° angle) relative to the waveguide, and light exiting diffraction grating 440 is directed toward objective lens 450, which focuses the light through the side of capsule 400 toward tissue 480 ( FIG. 4 ). In some embodiments, objective lens 450 (described further below) may have an aspheric surface on a first side facing toward diffraction grating 440 and a biconic surface on a second side facing the outside of capsule 400 and toward tissue 480. As described further below, the biconic surface is designed to correct for aberrations that may be caused by the curved / cylindrical outer surface of the capsule body portion involved in imaging (i.e., imaging window 410). In some embodiments, a collimating lens 430 may be positioned between the output of the waveguide and diffraction grating 440. Given that the optical components within the probe are rotatable, a gap exists between the objective lens 450 and the imaging window 410, which facilitates free rotation of the optical components within the capsule 400. While in certain known devices, this gap is filled with water, food-grade oil, mineral oil, or other medical or food-grade liquid (typically an optically clear liquid with a viscosity similar to water) to reduce aberrations due to the curved imaging window 410, the biconic surface of the objective lens 450 disclosed herein corrects for such aberrations without the need to fill the gap with a liquid such as water. Instead of filling the space within the housing 460 with a liquid such as water, the space may be filled with a gas such as air, nitrogen, or other suitable (e.g., medically approved) gas.

[0020] As described further below, a spectral source (e.g., a swept-source laser) can be used to implement SECM. Light from the light source emitted through the side of the capsule onto the tissue is distributed in a line-like configuration extending in a direction parallel to the long axis of the capsule, i.e., the different wavelengths of the spectral source are distributed along the line. Light reflected from the sample is then sent through the capsule and waveguide to the SECM system 470, where an image is constructed.

[0021] For luminal samples, such as portions of the GI tract (e.g., the esophagus or other regions), image data can be collected while the capsule is moving downward through the luminal structure (e.g., during swallowing) or while moving backward during capsule retrieval. While the capsule is translating (e.g., being pulled up) through the luminal sample, the optics can be rotated to obtain image data from the entire circumference of the luminal sample, generating a spiral scan of the sample that can be presented using polar or Cartesian coordinate systems.

[0022] In various embodiments, the lens includes an aspheric surface and a biconic surface. The lens may be machined or injection molded from glass or plastic. The lens may be manufactured by diamond turning using a polymer such as OKP4 or PMMA, or injection molding using a glass material such as D-ZK3. In some embodiments, injection molding the lens is expected to significantly reduce the cost per unit of product, for example, by as much as $10 per unit of product. In other embodiments, the radius of the aspheric lens may be approximately 1.45 mm, although larger or smaller radii are also possible. In certain embodiments, the refractive index may be 1.5 to 1.7, and in one particular embodiment, the refractive index is 1.607 for OKP4 plastic. Figure 5 shows a lens generated using ZEMAX software, which, in certain embodiments, includes a list of parameters for the aspheric surface, biconic surface, and lens material.

[0023] Although the periphery of a lens having a biconic surface may be circular, the biconic surface of the lens includes a raised portion that is not radially symmetric. Instead, the raised portion has two axes, e.g., an X-axis and a Y-axis, each of which has an associated radius of curvature and conic constant K. One axis has a larger radius of curvature and conic constant than the other axis, so that the lens is oriented within the capsule so that the axis with the larger radius of curvature and conic constant is parallel to the axis of the cylindrical imaging window and the longitudinal axis of the cylindrical housing (see FIG. 10 ). The overall shape of the biconic lens, defined at least in part by the X-axis and Y-axis radii and conic constants, is selected to correct aberrations introduced by the capsule housing, particularly the transparent curved imaging window, and typically to match the lens characteristics for use with the particular imaging window. In some embodiments, the X-axis radius is −2.676, the X-axis conic constant is −27.735, and the Y-axis radius is −2.725, and the Y-axis conic constant is −32.572, although biconic lenses with other radii and conic constants can be used.

[0024] Given the elongated and radially asymmetric shape of the biconic surface of the lens, in some embodiments, the lens can include one or more features, such as markings or notches, to ensure proper alignment of the lens relative to other optical components and the capsule housing. For example, the lens may include one ( FIG. 6 ) or two ( FIG. 7 ) notches on its outer edge to facilitate lens alignment, although other shapes and numbers of alignment features are possible. The notched lens fits into a receptacle with a complementary shape to secure the lens in the correct orientation ( FIG. 8 ). In the embodiment shown in FIG. 8 , the objective lens mount 810 includes a round notch 820, as shown for the lens in FIG. 7 , and the lens 830 is secured in place using two spherical or cylindrical inserts, such as ceramic spheres 840. However, other shapes and styles of notches and inserts may be used, and in some embodiments the lens or receptacle may include one or more protrusions of a shape complementary to the notch or other shape of the receptacle or lens, respectively.

[0025] The light source for the SECM can be either a broadband or wavelength-swept source. Compared to conventional forms of SECM (particularly capsule-based SECM) that use swept sources with a center wavelength of 1310 nm and a repetition rate of 100 kHz, the use of swept-source lasers with shorter wavelengths and higher repetition rates, as disclosed herein, improves both optical resolution and imaging speed. In various embodiments, the capsule-based systems disclosed herein utilize swept-source lasers centered at shorter wavelengths, such as 1060 nm (ranging from 1020 nm to 1100 nm), and with faster repetition rates, such as 400 kHz. In one specific embodiment, the light source is a Model AXP50124-3 available from Axsun Technologies (Billerica, MA). Considering that optical resolution is a function of wavelength, and that shorter wavelengths provide smaller diffraction-limited focal spot sizes and therefore better resolution than longer wavelengths, the shorter wavelength light sources disclosed herein provide higher optical resolution compared to previously used 1300 nm-range lasers. Additionally, the 400 kHz repetition rate of the disclosed laser significantly reduces the motion artifacts observed in conventional 100 kHz laser systems.

[0026] The table in Figure 9 compares the optical system specifications for a capsule-based SECM system between the present system (right, "SECM-TCE-1060") and a conventional system (left, "SECM-TCE-1310"). As shown in Figure 9, the disclosed embodiment does not require immersion of the optical system in a liquid such as water, which, as discussed above, simplifies manufacturing and extends the useful life of the device. Furthermore, the central wavelength is significantly shorter (1060 nm vs. 1290 nm), improving resolution. In certain embodiments, the capsule diameter is increased from 7 mm to 8 mm, which increases physical contact between the capsule and surrounding tissue, such as the esophagus, and also increases the spectrally encoded line length, thereby increasing the number of distinguishable pixels / samples. The imaging field of view is increased from 260 μm to 340 μm, the lateral resolution is improved from 1.44 μm to 1.25 μm, and the imaging depth is improved from 50 μm to 100 μm. Finally, instruments using lenses with biconic surfaces operate at a 90° imaging angle, compared to the 95.725° imaging angle used in conventional instruments. Having an imaging angle nearly perpendicular to the imaging window improves image quality by aligning the biconic surface of the objective lens in the best position to correct for aberrations caused by the curvature of the curved imaging window.

[0027] 10 shows an embodiment of a capsule probe 1000 including a cylindrical housing 1060, with a long axis 1050 of the probe shown along the radius of the biconic lens of the optical components within the probe, a first axis R1 (associated with a first radius of curvature and a first conic constant) parallel to the long axis 1050 of the cylindrical housing 1060 of the probe 1000 and perpendicular to a second axis R2 (associated with a second radius of curvature and a second conic constant) greater than the second radius of curvature and the second conic constant. A window 1070, shown as a dotted line, which in certain embodiments is a transparent cylindrical surface, is contained within the cylindrical housing 1060. Also shown is an objective lens mount 1010, which has a round notch 1020, and a lens 1030 which may be fixed in place using two spherical or cylindrical inserts 1040, e.g., ceramic spheres, which maintain the lens 1030 in the correct orientation so that its first axis R1 is parallel to the longitudinal axis 1050 of the cylindrical housing 1060.

[0028] Although the examples disclosed herein are generally presented in the context of capsule-based SECM, the disclosed apparatus and methods are more generally applicable for use with any probe that is susceptible to aberrations resulting from a curved (e.g., cylindrical) imaging window. Thus, the disclosed objective lenses having biconic surfaces can be used in probes such as capsules to implement a variety of imaging modalities, including, but not limited to, OCT, OFDI, SD-OCT, and other scanning imaging modalities.

[0029] Although the disclosed subject matter has been described with reference to particular embodiments and examples, the invention is not necessarily limited thereto and can be embodied in many other embodiments, examples, uses, modifications, and implementations. Those skilled in the art will recognize that variations in modes, examples, and uses are intended to be encompassed within the scope of the appended claims. Each patent document and publication cited herein is incorporated by reference as if individually incorporated by reference.

[0030] Various features and advantages of the invention are set forth in the following claims.

Claims

1. 1. A probe for performing an endoscopy, comprising: a waveguide coupled to a light source; A diffraction grating; an objective lens having a first aspheric surface and a second biconic surface; the waveguide is configured to direct light from the light source to the diffraction grating; diffracted light from the diffraction grating is directed onto the first aspheric surface of the objective lens and emitted from the second biconic surface of the objective lens towards the transparent cylindrical surface of the probe; the second biconic surface includes a first axis associated with a first radius of curvature of the second biconic surface and a second axis associated with a second radius of curvature of the second biconic surface; the second axis is perpendicular to the first axis; the second biconic surface of the objective lens is shaped to correct spherical aberration resulting from the transparent cylindrical surface of the probe; The objective lens is housed in a housing, The probe, wherein the housing comprises the transparent cylindrical surface.

2. A probe as described in claim 1, wherein the first radius of curvature and the second radius of curvature have the same positive and negative signs.

3. The probe of claim 1 , wherein the first radius of curvature is greater than the second radius of curvature.

4. The probe of claim 1 , wherein the objective lens is oriented with the first axis parallel to a long axis of the transparent cylindrical surface of the probe.

5. the first axis is associated with a first conic constant and the second axis is associated with a second conic constant; The probe of claim 1 , wherein the first conic constant is greater than the second conic constant.

6. The probe of claim 1 , wherein the objective lens is oriented perpendicular to the transparent cylindrical surface of the probe.

7. The probe of claim 1 , wherein the housing does not contain a liquid.

8. The probe of claim 7 , wherein the objective lens is immersed in a gas within the housing.

9. The probe of claim 8 , wherein the gas comprises air.

10. a collimating lens disposed between the waveguide and the diffraction grating; The probe of claim 1 , wherein light from the waveguide passes through the collimating lens to the diffraction grating.

11. The probe of claim 1 , wherein the probe comprises a tethered capsule.

12. The probe of claim 11 , wherein the tethered capsule has an outer diameter of 8 mm.

13. The probe of claim 1 , wherein the light source comprises a swept-source laser.

14. The probe of claim 13 , wherein the swept-source laser has a center wavelength of 1060 nm and a repetition rate of 400 kHz.

15. 15. The probe of claim 14, wherein the target imaging depth of the probe is 100 μm and the lateral resolution of the probe is 1.25 μm.

16. The probe of claim 1 , wherein the endoscopy method comprises spectrally encoded confocal microscopy (SECM).

17. The probe of claim 1 , wherein the objective lens has a notch for alignment of the objective lens.

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