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

Abstract

A probe for performing endoscopic examination, comprising: a light source; a waveguide coupled to the light source; a diffraction grating, the waveguide guiding light from the light source to the diffraction grating; and a lens having a first aspherical surface and a second biconical surface, diffracted light from the diffraction grating being guided into the aspherical surface of the lens and emitted from the biconical surface of the lens toward a transparent cylindrical surface of the probe.

Description

[0001] Cross-reference to related applications

[0002] This application is based on, claims the benefit of and claims the priority of, U.S. Provisional Application No. 62 / 892,073, filed on August 27, 2019, which is hereby incorporated by reference in its entirety for all purposes.

[0003] A note about federally funded research

[0004] not applicable Background Art

[0005] Spectrally encoded confocal microscopy (SECM) is a high-speed imaging technique that can provide imaging speeds 1-2 orders of magnitude faster than video-rate reflection confocal microscopy while achieving a high degree of probe miniaturization by replacing the mechanical scanning device with a diffraction grating. However, in existing designs, asymmetric spherical aberrations caused at the probe surface (e.g., caused by the cylindrical imaging window of the SECM capsule) make it difficult to achieve diffraction-limited optical resolution. One solution is to fill the gap between the imaging window in the objective lens and the probe (e.g., capsule) with water to minimize the aberration by reducing the refractive index mismatch, thereby striving to provide diffraction-limited optical resolution (see Figure 1, panels A and B). Panel A of Figure 1 shows an objective lens of a known system having circular surfaces on both sides, wherein both circular surfaces are radially symmetric.

[0006] However, filling a probe such as a SECM capsule with water introduces a number of additional manufacturing requirements, including the need to use a water-tight epoxy to seal the components. In addition, the life of a water-filled SECM capsule is shortened (e.g., less than 1-2 months) due to the difficulty in retaining the water within the probe. Finally, bubbles within the water can appear inside the probe during a procedure, which can interfere with optimal performance (see Figure 2). Summary of the invention

[0007] Therefore, new SECM probe designs are sought that do not require filling the probe with a liquid such as water, but still provide comparable optical performance.

[0008] Therefore, the present invention provides an embodiment of a probe for performing endomicroscopy, comprising: a light source; a waveguide coupled to the light source; a diffraction grating, the waveguide guiding light from the light source to the diffraction grating; and a lens having a first aspheric surface and a second biconic surface, diffracted light from the diffraction grating being guided into the aspheric surface of the lens and emitted from the biconic surface of the lens toward a transparent cylindrical surface of the probe.

[0009] In one embodiment, the present invention provides a method for performing endoscopy using a probe. The probe includes: a light source, a waveguide coupled to the light source, a diffraction grating, and a lens having a first aspheric surface and a second biconical surface. The method includes: the waveguide guides light from the light source to the diffraction grating, and the diffraction grating guides the diffracted light to the aspheric surface of the lens and emits it from the biconical surface of the lens to the transparent cylindrical surface of the probe.

[0010] These and other embodiments, aspects, advantages and features of the present invention will be explained in part in the following description and will become apparent to those skilled in the art by reference to the following description of the present invention and by reference to the accompanying drawings or by practice of the present invention. The accompanying drawings illustrate one or more implementations, and these implementations do not necessarily represent the full scope of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] Figure 1 shows a ZEMAX simulation of a SECM objective without a biconical surface; Panel A shows the layout of the objective with ray tracing, and Panel B shows the RMS wavefront error as a function of field angle.

[0012] Figure 2 shows a water-filled SECM capsule 1 day (left), 1 week (middle), and 1 month (right) after the capsule has been filled with water, illustrating the progressive effect of water on the probe over time.

[0013] Figure 3 A SECM optical device for use in a capsule is shown and includes an objective lens having a biconical surface facing an imaging window.

[0014] Figure 4 A tethered capsule is shown, wherein SECM optics are disposed within the tethered capsule.

[0015] Figure 5 A schematic diagram of a lens generated using ZEMAX software is shown, which includes parameter listings for specific embodiments of aspheric surfaces, biconical surfaces, and lens materials.

[0016] Figure 6 Shown is the design of an objective lens with aspherical and biconical surfaces, including notches for proper alignment of the lens, shown in perspective (left) and from the side (right).

[0017] Figure 7Another design of an objective lens with an aspheric surface and a biconical surface is shown, the objective lens including two notches for properly aligning the lens, where the lens is shown from the top (upper left corner), in perspective (upper right corner), from a first side (lower left corner), and from a second side orthogonal to the first side (lower right corner).

[0018] Figure 8 A tethered capsule is shown comprising an objective lens holder having a pair of circular notches and a lens having a similar pair of circular notches, wherein two ceramic balls are inserted into the space formed by the notches to secure the lens in place in the correct orientation.

[0019] Fig. 9 A table comparing the specifications of an existing SECM-based water-immersion capsule with a SECM capsule that includes an objective lens with a bi-conical surface and does not require water immersion is shown.

[0020] Fig.10 A schematic diagram of a capsule probe with a cylindrical housing is shown, wherein the long axis of the probe is indicated together with the radius of the biconical lens of the optical component within the probe, wherein a first axis (R1) is parallel to the long axis of the probe and perpendicular to a second, shorter axis (R2).

[0021] The following detailed description includes references to the accompanying drawings, which form a part of the detailed description. The accompanying drawings show by way of illustration specific embodiments in which the device can be practiced. These embodiments are also referred to herein as "examples" or "options", which are described in sufficient detail to enable those skilled in the art to practice the present embodiment. The embodiments may be combined, other embodiments may be utilized, or structural or logical changes may be made without departing from the scope of the invention. Therefore, the following specific embodiments should not be understood in a restrictive sense, and the scope of the invention is defined by the appended claims and their legal equivalents. In this document, unless otherwise stated, the term "a / an" is used to include one or more than one, and the term "or" is used to refer to a non-exclusive "or". In addition, it should be understood that the terms or terms used herein and not otherwise defined are only for descriptive purposes and are not restrictive. DETAILED DESCRIPTION

[0022] Embodiments of an apparatus, method, and / or system for a SECM probe are disclosed herein that includes an objective lens having a biconical surface and that therefore does not require water immersion or other corrective measures to be taken to achieve diffraction-limited or near-diffraction-limited optical resolution.

[0023] Spectrally encoded confocal microscopy (SECM) is a microendoscopy technique that uses wavelength to encode physical locations on a sample to achieve fast imaging speeds. Simply put, a broadband or wavelength-swept light source is dispersed across a swath of the sample so that each wavelength or subset of wavelengths acts 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 pass, as this allows a large amount of data to be collected in parallel. Although some pill-sized tethered SECM capsules have been developed to acquire cellular-resolution images of the upper gastrointestinal (GI) tract, the imaging quality of such SECM capsules has so far been limited by issues including insufficient optical resolution, non-uniform pullback, and non-uniform rotational deformation.

[0024] Some versions of water-filled, pill-sized tethered capsules have been developed that are compatible with 100kHz, 1310nm wavelength swept source SECM imaging systems. Embodiments of tethered SECM endoscopic imaging systems and capsules utilizing a 400kHz swept source centered at 1060nm are disclosed herein. In addition to providing higher resolution due to the shorter wavelength, the new 1060nm capsule design does not require corrective measures such as water immersion (i.e., filling the capsule with a liquid such as water).

[0025] In various disclosed embodiments, by designing an objective lens 310 (e.g., the side facing the source) with a conventional aspheric surface 320 on one side of the objective lens 310 (e.g., the side facing the source) and a biconical surface 330 on the other side (e.g., the side facing the sample), Figure 3 , Figure 5 ) to correct for the asymmetric spherical aberration caused by the curved (usually cylindrical) transparent wall of the capsule, eliminating the need for water immersion or other corrective measures.

[0026] In various embodiments, the diameter of the capsule is also increased to improve physical contact with the esophagus and extend the line length of the spectral encoding that can be used, thereby producing more distinguishable wavelengths and therefore more pixels in the spectrally extended light band. In various embodiments, the imaging speed of the currently disclosed design can be increased by 5.2 times and the lateral resolution can be improved by 15% compared to other SECM capsule devices and systems using a 100kHz, 1310nm source. In addition, SECM is implemented without immersion of the capsule, simplifying manufacturability and increasing the life of the device. These advances significantly improve the clinical translatability of SECM in applications such as upper gastrointestinal diagnosis.

[0027] Typically, SECM allows for the use of compact probes such as catheters or capsules. Figure 4 )) performs reflection confocal microscopy. SECM uses wavelength division multiplexing ("WDM") to encode one-dimensional spatial information reflected from the sample. The fast scanning axis is replaced by a series of focused points in which each position is illuminated by a different wavelength of light 340, 350, 360 ( Figure 3 ) is represented. The remittance as a function of spatial position can be determined by measuring the spectrum of reflected light. A two-dimensional image can be created by scanning the wavelength-encoded axis through slow mechanical movement of the probe. Therefore, the endoscopic device implementing the present invention allows 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. Patent No. 6,831,781 and U.S. Patent Application Publication No. 2011 / 013178, each of which is incorporated herein by reference in its entirety for all purposes.

[0028] In some embodiments, the SECM system can be implemented in a swallowable tethered capsule 400 ( Figure 4 ). Figure 4 As shown, capsule 400 includes an imaging window 410 (indicated by a dashed line), 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, may include one or more of the following: a light source (e.g., a swept source laser), a rotational and / or linear scanning system, a light detector, and a computing system for controlling one or more other components and for collecting and processing data.

[0029] In various embodiments, the overall shape of capsule 400 can be smooth, with shell 460 comprising a cylindrical body with rounded (e.g., hemispherical) ends. This overall shape allows capsule 400 to be swallowed and moved through a luminal passage (such as the GI tract) with low resistance to allow it to move by gravity and / or peristaltic muscle movement, with tether 420 extending from one end of shell 460 ( Figure 4 ). The size of the capsule 400 can vary, but is typically less than 10 mm in diameter, and in some embodiments is 7 mm, and in other embodiments is 8 mm. At least a portion of the shell 460 of the capsule 400 includes an imaging window 410 that is optically transparent to a suitable wavelength (e.g., at UV, visible light, and / or IR wavelengths); typically, the imaging window 410 extends completely around the perimeter of the capsule 400 to allow rotational scanning of a sample through the capsule shell 460.

[0030] Light from a waveguide housed within tether 460 is directed toward diffraction grating 440, which is disposed at an angle relative to the waveguide (e.g., approximately a 45° angle), and light exiting diffraction grating 440 is directed to objective lens 450, which in turn focuses the light through the side of capsule 400 and toward tissue 480 ( Figure 4 ). In some embodiments, the objective lens 450 (described further below) may have: a first side facing the diffraction grating 440 and having an aspheric surface, and a second side facing the outside of the capsule 400 and tissue 480 having a biconical surface. As described further below, the biconical surface is designed to correct aberrations that may be caused by the curved / cylindrical outer surface of the capsule body (i.e., the imaging window 410) through which imaging occurs. In some embodiments, the collimating lens 430 can be placed between the output of the waveguide and the diffraction grating 440. Given that the optical components within the probe are rotatable, there is a gap between the objective lens 450 and the imaging window 410 to facilitate free rotation of the optical components within the capsule 400. In some known devices, the gap has been filled with water, food-grade oil, mineral oil, or other medical-grade or food-grade liquid (typically a liquid with a viscosity similar to water and optically transparent) to reduce aberrations from the curved imaging window 410, however, the biconical surface of the objective lens 450 disclosed herein corrects these aberrations without the need for a liquid such as water to fill the gap. Instead of filling the space within housing 460 with a liquid, such as water, the space may be filled with a gas, such as air, nitrogen, or any other suitable (eg, medically approved) gas.

[0031] As discussed further below, a spectral source (e.g., a swept source laser) can be used for SECM implementation. Light emitted from the source through the side of the capsule and emitted onto the tissue is distributed in a linear arrangement extending in a direction parallel to the long axis of the capsule, with different wavelengths of the spectral source distributed along the line. Light reflected from the sample is then transmitted through the capsule and waveguide to the SECM system 470 for construction into an image.

[0032] For luminal samples such as portions of the GI tract (e.g., the esophagus or other regions), the capsule can collect image data as it moves downward through the luminal structures (e.g., during swallowing) or in the opposite direction during capsule retrieval. As the capsule is translated (e.g., pulled upward) through the luminal sample, the optical components can rotate so as to obtain image data from the entire circumference of the luminal sample, which produces a helical scan of the sample that can be presented using polar or rectangular coordinates.

[0033] In various embodiments, the lens includes an aspheric surface and a biconical surface. The lens can be machined or injection molded from glass or plastic. The lens can be manufactured using a polymer (such as OKP4 or PMMA) by diamond turning, or using a glass material (such as D-ZK3) via injection molding. In some embodiments, injection molding of the lens is expected to significantly reduce the cost per unit, for example to $10 per unit. In other embodiments, the aspheric lens can have a radius of about 1.45 mm, but the radius may also be larger or smaller. In some embodiments, the refractive index can be between 1.5 and 1.7, and in one particular embodiment, the refractive index is 1.607 for OKP4 plastic. Figure 5 A schematic diagram of a lens generated using ZEMAX software is shown, which includes parameter listings for specific embodiments of aspheric surfaces, biconical surfaces, and lens materials.

[0034] Although the outer circumference of the lens having a biconical surface may be circular, the biconical surface of the lens includes a convex portion that is not radially symmetrical. Instead, the convex portion has two axes, such as an x-axis and a y-axis, each axis having an associated radius of curvature and a conic constant K. The axis has a larger radius of curvature and conic constant than one of the axes, so that the lens is oriented within the capsule with the axis having the larger radius of curvature and conic constant parallel to the axis of the cylindrical imaging window and the major axis of the cylindrical shell (see Fig.10 ). The overall shape of the biconical lens, defined at least in part by the radii and conic constants of the x-axis and y-axis, is selected so that it corrects for aberrations caused by the capsule shell (particularly the transparent curved imaging window), and typically the lens properties are matched for use with a particular imaging window. In some embodiments, while the radius of the x-axis is -2.676 and the conic constant of the x-axis is -27.735, and the radius of the y-axis is -2.725 and the conic constant of the y-axis is -32.572, biconical lenses with other radii and conic constants may be used.

[0035] Given that the biconical surface of the lens has an elongated, non-radially symmetrical shape, in some embodiments, the lens may 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, while the lens may include a ( Figure 6 ) or two ( Figure 7 ) notches to facilitate alignment of the lens, but other shapes and numbers of alignment features are possible. The notched lens fits into a receptacle with a complementary shape that secures the lens in the correct orientation ( Figure 8 ).exist Figure 8 In the illustrated embodiment, the objective lens holder 810 includes a circular notch 820 (such as Figure 7 ), and two spherical or cylindrical inserts (e.g., ceramic balls 840) are used to hold lens 830 in place. However, other shapes and styles of notches and inserts may be used, and in some embodiments, the lens or socket may include one or more protrusions that complement the notches or other shapes in the socket or lens, respectively.

[0036] The light source for SECM can be a broadband or wavelength swept source. Relative to the previous embodiments of SECM (especially capsule-based SECM) using a swept source with a central wavelength of 1310nm and a repetition rate of 100kHz, the use of a swept source laser with a shorter wavelength as disclosed herein and a higher repetition rate improves both optical resolution and imaging speed. In various embodiments, the capsule-based system disclosed herein provides a technology using a swept source laser, the wavelength of which is centered at a shorter wavelength (such as 1060nm, ranging from 1020nm to 1100nm) and has a faster repetition rate, such as 400kHz. In a specific embodiment, the source is a model AXP50124-3 from Axsun Technologies of Billerica, Massachusetts. Given that optical resolution is a function of wavelength, wherein a shorter wavelength provides a smaller diffraction-limited focal size and therefore has better resolution than a longer wavelength, the shorter wavelength source disclosed herein provides a higher optical resolution compared to the previously used 1300nm range laser. Furthermore, the 400 kHz repetition rate of the disclosed laser significantly reduces motion artifacts observed in previous 100 kHz laser systems.

[0037] Fig. 9 The table in presents a comparison of the specifications of the current system (right, "SECM-TCE-1060") and the previous system (left, "SECM-TCE-1310") for the optics of the capsule-based SECM system. Fig. 9As shown, the currently disclosed embodiments do not require immersion of the optical device in a liquid such as water, which, as discussed above, simplifies manufacturing and extends the life of the device. In addition, the central wavelength is significantly shorter (1060nm vs. 1290nm), which provides improved resolution. In certain embodiments, the capsule diameter is increased from 7mm to 8mm, which increases the physical contact between the capsule and surrounding tissue (such as the esophagus) and also provides an extended spectrally encoded line length, which in turn increases the number of distinguishable pixels / samples. The imaging field of view is increased from 260μm to 340μm, and the lateral resolution is improved from 1.44μm to 1.25μm, while the imaging depth is increased from 50μm to 100μm. Finally, the device using a lens with a biconical surface operates at a 90° imaging angle, compared to the 95.725° imaging angle used in previous devices. Having an imaging angle approximately perpendicular to the imaging window improves image quality because the biconical surface of the objective lens is in an optimal orientation to correct aberrations generated by the curved surface of the curved imaging window.

[0038] Fig.10 A schematic diagram of an embodiment of a capsule probe 1000 is shown, the capsule probe 1000 including a cylindrical shell 1060, wherein the major axis 1050 of the probe is shown together with the radius of the biconical lens of the optical components within the probe, wherein a first axis R1 (associated with a first radius of curvature and a first conic constant) is parallel to the major axis 1050 of the cylindrical shell 1060 of the probe 1000 and perpendicular to a second axis R2 (associated with a second radius of curvature and a second conic constant), wherein the first radius of curvature and the first conic constant are greater than the second radius of curvature and the second conic constant. A window 1070 (a transparent cylindrical surface in some embodiments) is shown with a dashed line, wherein the window 1070 is included within the cylindrical shell 1060. Also indicated is an objective lens holder 1010 comprising a circular notch 1020 in which a lens 1030 may be secured in place using two spherical or cylindrical inserts 1040 (e.g., ceramic spheres) to maintain the lens 1030 in a correct orientation in which a first axis R1 is parallel to a long axis 1050 of a cylindrical housing 1060.

[0039] Although the examples disclosed herein are generally shown in the context of capsule-based SECM, the disclosed apparatus and methods are more generally applicable for use with any probe subject to aberrations from a curved (e.g., cylindrical) imaging window. Thus, the disclosed objective lens with a biconical surface can be used in a probe such as a capsule to implement various imaging modes, including but not limited to OCT, OFDI, SD-OCT, and other scanning imaging modes.

[0040] Those skilled in the art will recognize that although the disclosed subject matter has been described above in conjunction with specific embodiments and examples, the invention is not necessarily limited thereto, and many other embodiments, examples, uses, modifications, and deviations from the embodiments, examples, and uses are intended to be included in the claims appended hereto. The entire disclosure of each patent and publication cited herein is incorporated herein by reference, as if each such patent or publication was individually incorporated herein by reference.

[0041] Various features and advantages of the invention are set forth in the following claims.

Claims

1. A probe for performing endoscopic examination, comprising: light source; a waveguide coupled to the light source; Diffraction grating, The waveguide guides light from the light source to the diffraction grating; as well as a lens having a first aspherical surface and a second biconical surface, the second biconical surface having a first axis associated with a first radius of curvature and a second axis associated with a second radius of curvature, The second axis is perpendicular to the first axis, The first radius of curvature and the second radius of curvature have the same sign, Diffracted light from the diffraction grating is guided into the aspherical surface of the lens and emitted from the biconical surface of the lens toward a transparent cylindrical surface of the probe.

2. The probe according to claim 1, characterized in that The lens is included in the housing, and Wherein the housing comprises the transparent cylindrical surface.

3. The probe according to claim 2, characterized in that The housing does not contain liquid.

4. The probe according to claim 2, characterized in that The lens is immersed in the gas within the housing.

5. The probe according to claim 4, characterized in that The gas includes air.

6. The probe according to claim 2, characterized in that The first radius of curvature is greater than the second radius of curvature.

7. The probe according to claim 6, characterized in that The lens is configured such that the first axis is oriented parallel to a long axis of the transparent cylindrical surface of the probe.

8. The probe according to claim 7, characterized in that The first axis is associated with a first cone constant and the second axis is associated with a second cone constant, and Wherein, the first cone constant is greater than the second cone constant.

9. The probe according to claim 1, characterized in that: further comprising a collimating lens disposed between the waveguide and the diffraction grating, The light from the waveguide reaches the diffraction grating through the collimating lens.

10. The probe according to claim 1, characterized in that The probe includes a tethered capsule.

11. The probe according to claim 10, characterized in that The tethered capsule had an outer diameter of 8 mm.

12. The probe according to claim 1, characterized in that The shape of the biconical surface of the lens is designed to correct spherical aberration from the transparent cylindrical surface of the probe.

13. The probe according to claim 1, characterized in that The source comprises a swept source laser.

14. The probe according to claim 13, characterized in that The swept source laser has a central wavelength of 1060 nm and a repetition rate of 400 kHz.

15. The probe according to claim 14, characterized in that The target imaging depth of the probe is 100 μm, and the lateral resolution of the probe is 1.25 μm.

16. The probe according to claim 13, characterized in that The endoscopy includes spectrally encoded confocal microscopy (SECM).

17. The probe according to claim 1, characterized in that The lens includes a notch for aligning the lens.

18. A method for performing an endoscopy, the method comprising: providing a probe, the probe comprising a light source, a waveguide, a diffraction grating, and a lens, the waveguide being coupled to the light source, the lens having a first aspheric surface and a second biconical surface, The second biconical surface has a first axis associated with a first radius of curvature and a second axis associated with a second radius of curvature, The second axis is perpendicular to the first axis, The first radius of curvature and the second radius of curvature have the same sign, directing light from the light source to the diffraction grating, and Diffracted light is guided from the diffraction grating into the aspherical surface of the lens and emitted from the biconical surface of the lens toward a transparent cylindrical surface of the probe.

19. The method according to claim 18, characterized in that The lens is included in the housing, and Wherein the housing comprises the transparent cylindrical surface.

20. The method of claim 19, wherein: The housing does not contain liquid.

21. The method of claim 19, wherein: The lens is immersed in the gas within the housing.

22. The method according to claim 21, characterized in that The gas includes air.

23. The method of claim 19, wherein: The first radius of curvature is greater than the second radius of curvature.

24. The method of claim 23, wherein: The lens is configured such that the first axis is oriented parallel to a long axis of the transparent cylindrical surface of the probe.

25. The method of claim 24, wherein: The first axis is associated with a first cone constant and the second axis is associated with a second cone constant, and Wherein, the first cone constant is greater than the second cone constant.

26. The method of claim 18, wherein: Directing light from the light source to the diffraction grating further comprises: directing light from the light source from the waveguide to a collimating lens disposed between the waveguide and the diffraction grating, Wherein, the light from the collimating lens is guided to the diffraction grating.

27. The method of claim 18, wherein: The probe includes a tethered capsule.

28. The method of claim 27, wherein: The tethered capsule had an outer diameter of 8 mm.

29. The method of claim 18, wherein: The shape of the biconical surface of the lens is designed to correct spherical aberration from the transparent cylindrical surface of the probe.

30. The method of claim 18, wherein: The source comprises a swept source laser.

31. The method of claim 30, wherein: The swept source laser has a central wavelength of 1060 nm and a repetition rate of 400 kHz.

32. The method of claim 31, wherein: The target imaging depth of the probe is 100 μm, and the lateral resolution of the probe is 1.25 μm.

33. The method of claim 30, wherein: The endoscopy comprises spectrally encoded confocal microscopy (SECM), and wherein the probe is a SECM probe.

34. The method of claim 18, wherein: The lens includes a notch for aligning the lens.

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