Oscillating scanning ultra-flexible miniature catheter, system, and imaging methods for endomicroscopy

Abstract

An oscillating scanning imaging system, including: a drive shaft including a proximal end and a distal end; an optical waveguide including a proximal end and a distal end, the proximal end of the optical waveguide being disposed within the proximal end of the drive shaft, and the distal end of the optical waveguide extending beyond the distal end of the drive shaft; an optical probe head coupled to the distal end of the optical waveguide; and an oscillating motor coupled to the drive shaft.

Description

OSCILLATING SCANNING ULTRA-FLEXIBLE MINIATURE CATHETER, SYSTEM, AND IMAGING METHODS FOR ENDOMICROSCOPYCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present application is based on and claims priority from U.S. Patent Application Ser. No. 63 / 517,200, filed on August 2, 2023, the entire disclosure of which is incorporated herein by reference.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

[0002] N / ABACKGROUND

[0003] Sensorineural hearing loss (SNHL) - hearing loss caused by defects of the inner ear - affects hundreds of millions of people around the world. The current standard of care for hearing disorders such as SNHL includes diagnostic and treatment procedures. Diagnostic procedures include performing imaging (e.g. CT and / or MRI); assessing behavioral metrics (e.g. pure tone audiometry (Frequency x Level) and / or word recognition ability); and / or assessing physiological metrics (e.g. auditory brainstem response and / or distortion product otoacoustic emissions). Assuming an accurate diagnosis can be made, treatment procedures include providing the subject with a hearing aid and / or a cochlear implant. However, problems with current diagnostic approaches include poor or insufficient imaging resolution, inconsistent measurements, lack of reliability in certain patient populations, and / or lack of sensitivity for certain important types of pathologies. Although being able to obtain high-quality images of the cochlea would provide more accurate diagnoses, there currently are no imaging tools available for imaging the inner ear in humans at the cellular level. In addition to being useful in the inner ear, such tools would also be useful for imaging other narrow or convoluted structures.SUMMARY

[0004] Accordingly, various embodiments of the disclosure provide an oscillatingscanning ultra-flexible miniature catheter and systems for endomicroscopy of small and / or anatomically complex structures, such as the cochlea, cardiovascular spaces (e.g., coronary artery), respiratory tract (e.g., bronchus), brain vasculature, reproductive tract, digestive tract (e.g., esophagus, duodenum, colon). The catheter can be used to implement a number of optical imaging modalities, including: optical coherence tomography (OCT) and variants thereof including dynamic OCT and multichannel OCT, to name a few; fluorescence imaging; fluorescence lifetime imaging; spectroscopy; and multimodality imaging (including any combination of modalities including but not limited to those listed above).

[0005] Certain embodiments of the catheter include a multi-component sheath structure including a tip of the catheter that is flexible and soft, which permits the catheter to be inserted into structures such as the human cochlea, e.g. through the round window, and navigate turns inside the cochlea safely and ensure that the optical imaging probe can rotate smoothly inside the sheath. The optical probe head is designed such that the components have small size constraints to ensure that the catheter is small enough to be inserted into small and / or complex structures such as the human cochlea and navigate turns inside the structures and to ensure that the imaging resolution and imaging depth meet the requirements for visualization of the cellular structure of the inserted target via OCT technology. In certain embodiments, the disclosure provides an endoscope system include the imaging tool and a probe scanning device (PSD), which drives the imaging tool to perform rotational oscillations to scan the light beam to the luminal tissue for OCT imaging and drives the imaging tool to perform longitudinal movement to obtain 3D dimensional image acquisition of the luminal tissue.

[0006] In one embodiment, the disclosure provides an oscillating scanning imaging system, including: a drive shaft including a proximal end and a distal end; an optical waveguide including a proximal end and a distal end, the proximal end of the optical waveguide being disposed within the proximal end of the drive shaft, and the distal end of the optical waveguide extending beyond the distal end of the drive shaft; an optical probe head coupled to the distal end of the optical waveguide; and an oscillating motor coupled to the drive shaft.

[0007] Some embodiments of the system may further include a controller in communication with the oscillating motor, wherein the controller may be configured to rotate the oscillating motor in at least one of a single direction in a continuous manner or alternating directions in an oscillatory manner.

[0008] Some embodiments of the system may further include a controller in communication with the oscillating motor, wherein the controller may be configured to: rotate the oscillating motor in a first rotational direction and rotate the oscillating motor in a second rotational direction opposite the first rotational direction. In some embodiments of the system, the controller, when rotating the oscillating the motor in the first rotational direction, may be further configured to: rotate the oscillating motor at least one rotation in the first rotational direction, and, when rotating the oscillating the motor in the second rotational direction, may be further configured to: rotate the oscillating motor at least one rotation in the second rotational direction. In some embodiments of the system, the controller, when rotating the oscillating the motor at least one rotation in the first rotational direction, may be further configured to: rotate the oscillating motor two or more rotations in the first rotational direction, and, when rotating the oscillating the motor at least one rotation in the second rotational direction, may be further configured to: rotate the oscillating motor two or more rotations in the second rotational direction, wherein the number of rotations in the second rotational direction is equal to the number of rotations in the first rotational direction.

[0009] Some embodiments of the system may further include a fiber coil module, wherein the optical waveguide may be coupled to the fiber coil module. In some embodiments of the system, the fiber coil module may include a fiber hook, wherein the optical waveguide may be coupled to the fiber hook, and wherein the fiber hook may be configured to at least one of rotate or translate to facilitate controlled twisting of the optical waveguide. In some embodiments of the system, the fiber hook may be coupled to at least one of a linear bearing, a linear bearing spring, or a ball bearing to facilitate at least one of rotation or translation of the fiber hook. In some embodiments of the system, the fiber coil module may further include a plurality of fiber coil modules arranged in series, wherein the optical waveguide may be coupled through the plurality of fiber coil modules.

[0010] Some embodiments of the system may further include a fiber collar coupled to the distal end of drive shaft, wherein the optical waveguide may be inserted through and fixed to a central opening of the fiber collar. In some embodiments of the system, the distal end of the optical waveguide from the fiber collar to the optical probe head may include a fixed distance. In some embodiments of the system, the fixed distance may be between 20 mm and 30 mm. In some embodiments of the system, the fixed distance may be 25 mm and may be within a tolerance of 0.1 mm.

[0011] Some embodiments of the system may further include a longitudinal scanningdevice coupled to the drive shaft and in communication with the controller. In some embodiments of the system, the controller may be configured to control at least one of the oscillating motor or the longitudinal scanning device to perform at least one of a two- dimensional rotational scan, a two-dimensional linear scan, or a three-dimensional scan.

[0012] In some embodiments of the system, the distal end of the optical waveguide extending beyond the distal end of the drive shaft may include a bare portion of the optical waveguide, wherein the bare portion of the optical waveguide may be disposed within a flexible sheath. Some embodiments of the system may further include a lubricant disposed within the flexible sheath. Some embodiments of the system may further include a rounded cap coupled to a distal end of the flexible sheath. In some embodiments of the system, the rounded cap may include an oval rounded cap. In some embodiments of the system, a distal end of the flexible sheath may further include a rounded cap. In some embodiments of the system, the rounded cap may include an oval rounded cap.

[0013] Some embodiments of the system may include a rotary junction coupled to the proximal end of the optical waveguide and the proximal end of the drive shaft, wherein the optical waveguide and the optical probe head may be rotatably disposed within the flexible sheath.

[0014] In some embodiments of the system, the optical probe head may include a spacer at a proximal end thereof, wherein the distal end of the optical waveguide may be coupled to a proximal end of the spacer. In some embodiments of the system, the spacer may include a conical shape having a narrow proximal end adjacent the optical waveguide. In some embodiments of the system, the narrow proximal end may have a diameter of 250 pm or less, wherein the spacer may include a wide distal end having a diameter of 380 pm or less. In some embodiments of the system, the optical probe head may further include a reflector to reflect light from the optical waveguide away from a central axis of the optical waveguide. In some embodiments of the system, the reflector may include a freeform surface configured to correct for an optical aberration caused by the sheath. In some embodiments of the system, the optical probe head may further include a reflector cap at a distal end thereof, and wherein the reflector may be disposed within the reflector cap. In some embodiments of the system, the optical probe head may further include a reflector cap at a distal end thereof, and wherein the reflector cap may include an optically reflective surface formed therein. In some embodiments of the system, the reflector cap may be 3D printed.

[0015] In some embodiments of the system, the reflector may include a prism,wherein a reflective surface of the prism may include a reflective coating including gold. In some embodiments of the system, the reflector may include a polished glass rod, wherein a reflective surface of the prism polished glass rod may include a metallic coating. Some embodiments of the system may further include a GRIN lens disposed within a distal end of the spacer adjacent to the prism. In some embodiments of the system, the optical waveguide may include a single mode fiber, wherein the narrow proximal end of the spacer may include a multimode fiber disposed therein adjacent to the distal end of the optical waveguide. In some embodiments of the system, the multimode fiber may have a core diameter of 20 pm or less, a cladding diameter of 125 um or less, and a length of 220 pm or less.

[0016] In some embodiments of the system, the optical probe head may have a length of 1.7 mm which defines a maximum rigid length of the imaging tool.

[0017] In some embodiments of the system, the drive shaft may be disposed within a low friction sheath adjacent to the flexible sheath. In some embodiments of the system, an inside surface of the low friction sheath may include a Teflon coating.

[0018] In some embodiments of the system, the sheath may have a diameter of 600 pm or less, wherein the optical probe head may have a length of 1.7 mm or less which defines a maximum rigid length of the imaging tool, wherein a distal portion of the imaging tool may be inserted to a depth of at least 20 mm into the cochlea. In some embodiments of the system, the distal portion of the imaging tool may be inserted into a curved sample having a radius of curvature of at least 2 mm. In some embodiments of the system, the distal portion of the imaging tool may include the bare portion of the optical waveguide, the optical probe head, and the flexible sheath.

[0019] In some embodiments of the system, a distal portion of the imaging tool may have a bending stiffness of less than 7.58* 10'8Nm2, wherein the distal portion of the imaging tool may include the bare portion of the optical waveguide, the optical probe head, and the flexible sheath.

[0020] Some embodiments of the disclosure provide an oscillating scanning imaging method, including: inserting an oscillating scanning imaging tool into a luminal sample, the tool including: a drive shaft including a proximal end and a distal end, an optical waveguide including a proximal end and a distal end, the proximal end of the optical waveguide being disposed within the proximal end of the drive shaft, and the distal end of the optical waveguide extending beyond the distal end of the drive shaft, an optical probe head coupled to the distal end of the optical waveguide, and an oscillating motor coupled to the drive shaft;and obtaining, using the tool, optical data from the luminal sample.

[0021] In some embodiments of the method, the luminal sample may include the inner ear of a subject. In some embodiments of the method, inserting the oscillating scanning imaging tool into the inner ear of the subject may further include: inserting the oscillating scanning imaging tool into at least one of the cochlea, the saccule, the utricle, or the semicircular canal of the subject. In some embodiments of the method, the distal end of the optical waveguide extending beyond the distal end of the drive shaft may include a bare portion of the optical waveguide, wherein the bare portion of the optical waveguide may be disposed within a flexible sheath, and wherein inserting the oscillating scanning imaging tool into the luminal sample may further include: inserting the flexible sheath containing the bare portion of the optical waveguide into the luminal sample. In some embodiments of the method, the sheath may have a diameter of 600 pm or less, wherein the optical probe head may have a length of 1.7 mm or less which defines a maximum rigid length of the imaging tool, and wherein inserting the flexible sheath containing the bare portion of the optical waveguide into the luminal sample may further include: inserting the flexible sheath containing the bare portion of the optical waveguide to a depth of at least 20 mm into the luminal sample. In some embodiments of the method, inserting the flexible sheath containing the bare portion of the optical waveguide into the luminal sample may further include: inserting the flexible sheath containing the bare portion of the optical waveguide into the luminal sample comprising a curved portion having a radius of curvature of at least 2 mm.

[0022] In some embodiments of the method, obtaining optical data from the luminal sample may further include: obtaining three-dimensional imaging data from the luminal sample to identify at least one of a morphology or a dimension of the scala tympani to facilitate insertion of a cochlear implant.

[0023] In some embodiments of the method, the oscillating scanning imaging tool may further include an oscillating scanning module configured to rotate or oscillate the optical probe, and obtaining optical data may further include: obtaining the optical data while rotating or oscillating the optical probe using the oscillating scanning module. In some embodiments of the method, obtaining the optical data while rotating or oscillating the optical probe may further include: obtaining the optical data while rotating the optical probe in a single direction in a continuous manner. In some embodiments of the method, obtaining the optical data while rotating or oscillating the optical probe may further include: obtaining the optical data while oscillating the optical probe in alternating directions. In some embodimentsof the method, the oscillating scanning imaging tool may further include a longitudinal scanning device, and obtaining optical data may further include: obtaining the optical data while using at least one of the oscillating scanning module or the longitudinal scanning device to perform at least one of a two-dimensional rotational scan, a two-dimensional linear scan, or a three-dimensional scan.

[0024] Some embodiments of the disclosure may provide an oscillating scanning imaging tool, including: a drive shaft including a proximal end and a distal end; an insertion handle including a proximal end and a distal end, the distal end of the insertion handle surrounding the distal end of the drive shaft; an optical waveguide including a proximal end and a distal end, the proximal end of the optical waveguide being disposed within the proximal end of the drive shaft, and the distal end of the optical waveguide extending beyond the distal end of the drive shaft and beyond the distal end of the insertion handle; an optical probe head coupled to the distal end of the optical waveguide; and an oscillating motor coupled to the drive shaft.

[0025] In some embodiments of the imaging tool, the distal end of the insertion handle may further include an insertion stop, wherein the insertion stop may include an enlarged portion which is configured to limit a distance by which the distal end of the optical waveguide may be inserted into a sample. Some embodiments of the imaging tool may further include a handheld device coupled to the insertion handle. Some embodiments of the imaging tool may further include at least one of an oscillatory scanning module or a longitudinal scanning device disposed within the handheld device. In some embodiments of the imaging tool, the oscillatory scanning module may be configured to rotate the probe in at least one of a single direction in a continuous manner or alternating directions in an oscillatory manner. In some embodiments of the imaging tool, at least one of the oscillatory scanning module or the longitudinal scanning device may be configured to perform at least one of a two-dimensional rotational scan, a two-dimensional linear scan, or a three- dimensional scan.

[0026] Some embodiments of the disclosure provide an endoscope system including the disclosed imaging tool. In some embodiments, the endoscope system may be configured to be used in the inner ear, including at least one of the cochlea, the utricle, the saccule, or the semicircular canal. In some embodiments, the endoscope system may be configured to be used in at least one of the inner ear, cardiovascular spaces, the respiratory tract, brain vasculature, the reproductive tract, or the digestive tract. In some embodiments of theendoscope system, the optical waveguide may be coupled to at least one of an OCT imaging system, a fluorescence imaging, a fluorescence lifetime imaging system, a spectroscopy system, or and a multimodality imaging system.BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Various objects, features, and advantages of the disclosed subject matter can be more fully appreciated with reference to the following detailed description of the disclosed subject matter when considered in connection with the following drawings, in which like reference numerals identify like elements.

[0028] FIG. 1 shows a diagram of an OCT system that can be used with constructions of the disclosed probe.

[0029] FIG. 2A shows a diagram of a protective sheath for a probe according to certain constructions of the present disclosure.

[0030] FIG. 2B shows a photograph of a protective sheath for a probe according to certain constructions of the present disclosure, where the inset in the lower right corner highlights the cap; disposed within the protective sheath is a probe such as that shown in FIGS. 3 and 4.

[0031] FIG. 3 shows a diagram of an imaging probe according to certain constructions of the present disclosure.

[0032] FIG. 4 shows a photograph of an imaging probe according to certain constructions of the present disclosure.

[0033] FIG. 5 shows diagrams (FIGS. 5A and 5B) and photographs (FIGS. 5C and 5D) of an optical probe head of an imaging probe according to certain constructions of the present disclosure.

[0034] FIG. 6 shows a diagram of an imaging probe disposed within a protective sheath according to certain constructions of the present disclosure.

[0035] FIG. 7A shows an apparatus that was used to measure the amount of force needed to deflect a cochlear implant or a silicone sheath containing an 80 pm SMF and FIG. 7B shows graphs of data collected with the apparatus of FIG. 7 A indicating that the cochlear implants (CI samples 1-3) required more force to deflect by 20° than the silicone sheath (Our cochlear catheter).

[0036] FIG. 8 shows an apparatus for conducting an insertion force test (left panel) on a spiral phantom (first inset, center panel) which mimics the cochlea. The second inset (rightpanel) shows the rounded cap at the distal end of the protective sheath which helps the sheath advance smoothly through the cochlea.

[0037] FIG. 9 shows a graph of the amount of force required to insert either cochlear implants (CI samples 1-3) or a silicone sheath containing an 80 pm SMF (Our cochlear catheter) as a function of depth within the phantom of FIG. 8.

[0038] FIGS. 10A and 10B show results of rotation tests to quantify distortion effects associated with the probe at high rotational speeds (3000 rpm).

[0039] FIGS. 11 A and 1 IB show a diagram of the optical components of a construction of the disclosed probe (FIG. 11 A) which was used to perform optical simulations (FIG. 1 IB).

[0040] FIGS. 12A shows a photo and a schematic of an OCT imaging target that was used to characterize the lateral resolution of the disclosed probe, Fig 12B, 12C show results of characterization of image quality using a construction of the disclosed probe.

[0041] FIG. 13 shows an alternative version of an optical probe head which includes an angle polished reflector (R) disposed within a reflective tube (RT) (FIGS. 13A and 13B) where the RT includes an imaging window (FIG. 13C) and the angled reflective surface is coated (e.g. with a metal such as gold) (FIG. 13D).

[0042] FIG. 14 shows alternative version of an optical probe head with a distal cap that has an optically reflective surface (R) formed therein.

[0043] FIG. 15 shows a construction of an optical probe head with a multi -part spacer component shown in an exploded view (top) and an assembled view (bottom).

[0044] FIG. 16 shows an alternative version of an optical probe which includes an insertion handle.

[0045] FIG. 17 shows an alternative version of an optical probe which includes an insertion handle which is adjustable and bendable.

[0046] FIG. 18 shows an alternative version of an optical probe which includes an ergonomic insertion handle.

[0047] FIG. 19 shows an endoscope system with a probe scanning device (PSD).

[0048] FIG. 20 shows a schematic of an endoscope, a probe scanning device, and an imaging system in use in a clinical scenario involving imaging the inner ear.

[0049] FIG. 21 shows an embodiment of a rotational scanning module which includes a mechanical system that convers rotation of a motor to rotational oscillation.

[0050] FIG. 22 shows an embodiment of an endoscope system with a handhelddevice, where the inset shows a close-up view of an optical probe with an insertion handle.

[0051] FIG. 23 shows a cross-sectional detail view of the body of the handheld device and scanning modules.

[0052] FIG. 24 shows a schematic diagram demonstrating use of an endoscope system with a handheld device and an imaging system in a clinical scenario of imaging the inner ear.

[0053] FIG. 25 shows a diagram in which a probe insertion module is a linear stage that is connected to a rigid tube of the probe.

[0054] FIG. 26 shows a diagram in which a probe insertion module is a motor-driven wheel-based friction drive system that engages a rigid tube of the probe.

[0055] FIG. 27 shows a diagram of a reflector with a freeform surface.

[0056] FIGS. 28A-28C show an embodiment of a fiber collar that connects the SMF of the imaging probe to the driveshaft.

[0057] FIG. 29 shows a schematic of another embodiment of the probe scanning device.

[0058] FIG. 30 shows the rotation position of the probe scanning device rotational scanning module in 1 second doing direction switch after each rotation at a speed of 10 rotations / s.

[0059] FIG. 31 shows the rotation position of the PSD rotational scanning module in 1 second doing direction switch after every 16 rotations at a speed of 16 rotations / s.

[0060] FIGS. 32A-32D show embodiments of the fiber coil module used in the rotational scanning module: FIG. 32A shows a simplified diagram of the fiber core module; FIG. 32B shows a more detailed view of the fiber core module; FIG. 32C shows a more detailed view of the area covered by the dashed rectangle in FIG. 32B; and FIG. 32D shows a PSD with multiple fiber coil modules.

[0061] FIG. 33 shows the drawing of the rotational scanning module which incorporates the fiber coil module and uses a belt system to transfer rotation from the motor to the fiber coil module.

[0062] FIG. 34 shows a diagram of an oscillating scanning imaging system in communication with a computer system.DETAILED DESCRIPTION

[0063] In accordance with some embodiments of the disclosed subject matter, mechanisms (which can include apparatus, systems, and methods) for providing anoscillating scanning ultra-flexible miniature catheter for endomicroscopy are provided. Embodiments of the apparatus include an imaging probe disposed within a protective sheath.

[0064] In particular, various embodiments of the disclosure provide an oscillating scanning ultra-flexible miniature catheter and systems for endomicroscopy of small and / or anatomically complex structures, such as the cochlea, cardiovascular spaces (e.g., coronary artery), respiratory tract (e.g., bronchus), brain vasculature, reproductive tract, digestive tract (e.g., esophagus, duodenum, colon). The catheter can be used to implement a number of optical imaging modalities, including: optical coherence tomography (OCT) and variants thereof including dynamic OCT and multichannel OCT to name a few; fluorescence imaging; fluorescence lifetime imaging; spectroscopy; and multimodality imaging (including any combination of modalities including but not limited to those listed above).

[0065] In particular embodiments, the disclosure may provide an oscillating scanning optical coherence tomography catheter apparatus for endomicroscopy of small and / or anatomically complex structures such as the human cochlea and other parts of the human inner ear which can be used to diagnose conditions such as sensorineural hearing loss (SNHL) and other sensory deficit of the auditory system in humans. Embodiments of the disclosed procedures will allow visualization of cellular and neuronal structures that may be damaged and / or destroyed in patients with SNHL. In various embodiments, embodiments of the disclosed imaging tool can be used to perform 3D imaging of the cochlea prior to cochlear implant insertion surgery, providing 3D reconstruction of the morphology and / or dimensions of the scala tympani so it can facilitate the determination and insertion of the regular cochlear implant. While the cochlea is mentioned herein as an exemplary structure that can be examined using embodiments of the disclosed device, the size and flexibility feature of the device makes it suitable to image various luminal (e.g. hollow or tube-shaped) samples such as other inner ear structures including the vestibular end organs and can be used for imaging through the oval window to image the sensory epithelium of the saccule and / or the utricle or could be used for imaging inside the semicircular canals.

[0066] The disclosed device is designed to provide in vivo imaging from inside the cochlea to visualize structures such as the Organ of Corti. The cochlea can be entered via the round window (which is approximately 2 mm) and a probe such as those disclosed herein can be advanced through the scala tympani, which has a diameter ranging from 0.8-1.2 mm. The insertion length of the probe in some embodiments may range from 20-30 mm, where an initial 360° loop through the scala tympani may require a length of approximately 18.5 mm;in other embodiments the insertion length may be such that the probe may be inserted at least 25 mm into the cochlea. The disclosed probe is configured to be capable of conforming to the varying radius of curvatures that are presented within the cochlea, for example from approximately 6 mm in the outer portions down to 2 mm in the inner portions of the scala tympani. The imaging optics of the disclosed device are configured to provide cellular-level imaging data on structures such as hair cells (with dimensions of 7-12pm x 10-70pm), auditory nerve fibers (with dimensions from 0.5pm - 2pm).

[0067] In various embodiments, meeting the above requirements is made possible by the use of high-resolution OCT (OCT), which has a lateral resolution of 2-3 pm and axial resolution of 1.5-2 pm and a depth of focus (DOF) of approximately 600 pm. To further aid in the insertion of the probe into the deepest portions of the cochlea, the disclosed device includes a rigid portion having a maximum length 1.7 mm or less and a rigid diameter of 600 pm or less. As discussed below, the disclosed probe has mechanical properties similar to those of established cochlear implants, including comparable flexibility and insertion force.

[0068] As disclosed in Yin et al. ("pOCT imaging using depth of focus extension by self-imaging wavefront division in a common-path fiber optic probe", Opt. Express, 2016 Mar. 7;24(5):5555-5564, incorporated herein by reference in its entirety), an OCT probe divides an illumination wavefront into multiple circular propagation modes that are projected as coaxial foci over an extended focal depth range to provide high depth of focus and later resolution in a range of 3-5 pm and axial resolution of approximately 2 pm over an approximately 1 mm depth range. FIG. 1 shows an OCT system that can be used with embodiments of the disclosed OCT imaging probe In FIG. 1, the arrow next to the probe indicate the rotation of the probe and the following abbreviations are applicable: SC, supercontinuum laser; COL, collimator; DM, dichroic mirror; SSF, spectral shape filter; BD, beam dump; BS, beam splitter; BE, beam expander, M, mirror; G, grating; FL, focusing lens, LSC, line scan camera; RJ, rotary junction; PB, pull-back stage; MC, motion controller; and PC, personal computer

[0069] FIG. 2A shows a diagram of a protective sheath for a probe according to certain embodiments of the present disclosure. The protective sheath, which may have a diameter of 600 pm or less, may have as many as four parts, including (from left to right in FIG. 2A): 1. a connector between the sheath and a rotary junction; 2. a low friction plastic sheath (sheath 1) made of a material (e.g. HDPE, Pebax) that has relatively low friction relative to a driveshaft (e.g. having a Teflon coating on the inside surface thereof) rotatablydisposed within the sheath; 3. a flexible sheath (sheath 2) made from material (e.g. silicone) that is ultra-flexible and soft; and / or 4. a cap on the silicone sheath that has a specific shape which could reduce insertion trauma of the human cochlea (e.g. a 3D-printed hemispherical cap having a diameter of 600 pm or less). In general, the rounded cap encompasses a number of rounded (e.g., curved / smooth) shapes such as an oval (e.g., parabolic) rounded cap to help reduce trauma when the device is inserted. Furthermore, the rounded cap may be a separate element that is attached to the sheath or the rounded cap may be formed as an integral part of the sheath itself. FIG. 2B shows a photograph of a particular embodiment of a protective sheath for a probe according to the present disclosure, where the inset in the lower right corner highlights the cap structure. Disposed within the protective sheath is a probe such as that shown in FIGS. 3 and 4, where the distal end of the drive shaft is shown in the lower left corner of FIG. 2B and the optical probe head is disposed within the distal portion of the sheath, where the "bare" or exposed portion of the optical fiber (i.e. a portion that does not include an overlying drive shaft) plus the optical probe head is at least approximately 2.5 cm / 25 mm in length.

[0070] FIG. 3 shows a diagram of an imaging probe according to certain embodiments of the present disclosure. The imaging probe may include one or more of the following components (from right to left): 1. an optical probe head; 2. a single-mode fiber which connects the optical probe head to the rotary junction with a fiber connector; 3. a driveshaft that secures the single-mode fiber and provides rotation of the probe; and / or 4. a metal tube that connects the fiber connector and the proximal end of the driveshaft and protects the fiber between them. FIG. 4 shows a photograph of a particular embodiment of an imaging probe according to the present disclosure, where the driveshaft, bare optical fiber, and optical probe head have all been labeled. In this particular example, the bare section of the optical fiber extending beyond the distal end of the driveshaft to the optical probe head (corresponding to the portion labeled "SMF" in FIG. 3) is approximately 25 mm (+ / - 3 mm), although longer or shorter lengths are possible.

[0071] FIGS. 5A-5D show diagrams (FIGS. 5A and 5B) and photographs (FIGS. 5C and 5D) of embodiments of an optical probe head of an imaging probe according to the present disclosure. FIG. 5A shows an exploded-view diagram of the optical probe head which depicts (from left / proximal to right / distal) the relative positions of the single mode fiber (SMF), multi-mode fiber (MMF), spacer, GRIN lens (which is inserted into a distal end of the spacer), a reflector prism, and a reflector cap (which houses the reflector prism and attachesto the distal end of the spacer). The spacer may include a cylindrical neck region at its proximal end and a cylindrical distal portion, where the neck region has a smaller diameter than the distal portion, and wherein the two cylindrical portions are joined by a tapered region therebetween. The SMF is inserted into a proximal end of the spacer, in the proximal portion of the narrow neck region, while the MMF is inserted further into the narrow neck region of the spacer, adjacent to a distal end of the SMF (see FIG. 3). FIG. 5B shows a side view diagram of the optical probe head in the assembled state, with indications of distances and lengths of various components (discussed further below). FIG. 5C shows a photograph of a side view of the optical probe head with a line indicating the total length (1.7 mm) of an embodiment of the probe head and which shows a side view of the prism which highlights the angled reflective surface. FIG. 5D shows a photograph of a side view of the optical probe head with a line indicating the width (380 pm) of an embodiment of the probe head and which is rotated approximately 90° (along its long axis) compared to the view in FIG. 5C which as a result shows a view of the outer face of the prism and which therefore does not show the angled reflective surface.

[0072] Due to the use of lubricant (e.g. mineral oil) in the sheath to facilitate rotation of the optical imaging probe (see below), in various embodiments the prism includes a reflective coating (e.g. is coated with a material such as a metal, for example silver, gold, and / or aluminum) to make the angled surface of the prism reflective independent of whether there is an index of refraction mismatch between the glass and the surrounding media. In various embodiments, the distal surface of the MMF may be angle polished at a certain degree, for example 8°, and the proximal end surface of the GRIN may also be angle polished at the same degree to compensate for the beam direction shift caused by the refraction at the distal surface of the MMF. By adding complementary angle polishing to these components, the back reflection from the two facing surfaces can be suppressed with a result that the SNR of the probe is improved. In certain embodiments, the prism and GRIN lens may be made of materials that are closely matched to one other in refractive index such that the interface between the prism and GRIN lens do not generate a strong back-reflection.

[0073] In various embodiments, the optical probe head includes the following parts and may be connected as described herein (see FIGS. 5A-5D): 1. a single-mode fiber (SMF) may be optically coupled to a multimode fiber (MMF) within the narrow neck region of the spacer; 2. the SMF and MMF may in turn be optically coupled to a hollow tube (e.g. the tapered portion of the spacer) that works to let the light beam expand within its hollowinternal space; 3. a GRIN lens may be secured in the distal end of the spacer (e.g. in the distal cylindrical portion of the spacer); 4. a reflector that is disposed at the distal end of the GRIN lens / spacer that reflects the light to the side direction of the catheter. The reflector in this apparatus can be a prism or a glass rod polished at a particular angle (e.g. between 30°-60°) at the distal end; and / or 5. the optical probe may also have a reflector cap which secures the reflector and helps maintain alignment between the reflector and the GRIN lens and spacer.

[0074] In various embodiments, the components disclosed herein may have particular size limitations which are selected to achieve the required performance for human intracochlear imaging (see FIG. 5B). In one particular embodiment these sizes may include: 1. the MMF may have a core diameter of 20 pm and a cladding diameter of 125 um or less and the length of the MMF may be 220 pm or less; 2. the spacer tube may include a tapered portion joining a relatively narrower cylindrical neck region at the proximal end and a relatively larger cylindrical distal region, where the outer diameter of the neck region may be 250 pm or less and the outer diameter of the distal region may be 380 pm or less, where the distance between the MMF and GRIN lens (which corresponds to the tapered portion) may be 670 pm; 3. the GRIN lens may have a diameter of 250 pm and the length of the GRIN lens may be 220 pm; 4. the reflective prism may have a length, width, and height of 180 pm; and / or 5. the polished glass rod may have a diameter of 250 pm. In those embodiments in which the neck of the spacer has a diameter of less than 250 pm and / or the distal region has a diameter of less than 380 pm, certain components such as the MMF, the GRIN lens, and the polished glass rod may be made proportionately smaller as well so that the components complement one another.

[0075] The sizes are features of the optical probe head design and may have small tolerance ranges. Various embodiments of the optical probe head may have different dimensions which may depend in part on considerations such as the anatomical structure into which a probe containing the optical probe head will be inserted.

[0076] FIG. 6 shows a diagram of an imaging probe disposed within a protective sheath according to certain constructions of the present disclosure. During the assembly of the catheter, lubricant (e.g. mineral oil; see FIG. 6) may be injected into the silicone sheath to ensure the rotation of the optical imaging probe inside of the sheath. The single-mode fiber may extend from the driveshaft for a particular length, which may be 25 mm (+ / - 3 mm) in certain embodiments of the apparatus (see FIG. 2B). Including this "bare" section of the SMF between the distal end of the driveshaft and the spacer increases the overall flexibility of theprobe by permitting the portion near the end of the probe to flex without the constraint of the relatively stiff drive shaft.

[0077] In use, light from the micro-optical coherence tomography imaging system propagates into the optical imaging probe through the connector between the probe and the rotary junction. When the light beam propagates in the core of the MMF, a few light transmission modes will be generated because of the reflection of the core-cladding interface of the MMF. After the beam expands within the spacer and is focused onto the GRIN lens and reflected onto the reflector, the light will be delivered to the tissue of interest inside the human cochlea, passing through the lubricant and the protective sheath. The few-mode light beam will be focused along the optical axis in the region of interest and will generate an extended focusing depth range. The back reflection from the illuminated region will be collected by the same optical imaging probe as it propagates back to the micro-optical coherence tomography imaging system and generates images of the tissue.

[0078] In various embodiments, the catheter is designed to be flexible. The imaging depth of the probe may be 500 pm with an average material imaging resolution between 4-5 pm. A stiffness test was conducted to measure the flexibility of the probe compared to several cochlear implant samples. Cochlear implants were used as points of reference when assessing the properties of the present device because the implanted portion of the cochlear implant system is already established as being sufficiently small and stiff to permit insertion in the cochlear space. Thus, if the present device has properties that are comparable to those of known cochlear implants, which are themselves capable of being inserted into the cochlea, then it should be possible to insert the present device into the cochlea without too much difficulty. Accordingly, an apparatus (FIG. 7A) was used to measure the amount of force needed to deflect a cochlear implant (CI samples 1-3) or a silicone sheath containing an 80 pm SMF (Our cochlear catheter) by 20°. As seen in FIG. 7B, substantially less force was required to deflect the silicone sheath by 20° than any of the cochlear implant devices that were tested, indicating that the disclosed device is more than sufficiently flexible to be insertable into the cochlea.

[0079] Flexibility (stiffness) of cochlear implants has been shown to correlate to the trauma caused by the insertion, with a more flexible implant causing less trauma. Various embodiments of the disclosed device have similar or smaller bending stiffness to commercial cochlear implants and thus are similarly suitable for insertion into the inner ear. Measured data of the bending stiffness value of embodiments of OCT catheter and commercial cochlearimplants (shown in Fig. 7B) demonstrates the force needed to deflect the sample to 30 degrees at different distance from the clamped point. Bending stiffness can be calculated from the measured data using the following equation:F x L3E x l = -3m

[0080] Where E x I is the bending stiffness (E: Modulus of elasticity, I: Moment of inertia). F is the force applied to the sample at the point with a distance of L to the fixation point, and m is the deflection distance. The measured bending stiffness of certain embodiments of the probe at the flexible distal portion (i.e. the ~25 mm extending part with the bare fiber part of the probe and the flexible silicone sheath) may fall in the range of 4 41* IQ-8Nm2to 6.81*10'8Nm2. For comparison, the bending stiffness of certain cochlear implant samples falls in the range of 1.12*10'8Nm2to 7.58* 10'8Nm2. Thus, in some embodiments the distal portion of the disclosed imaging tool has a bending stiffness of less than 7.58* 10-8Nm2.

[0081] FIG. 8 shows an apparatus for conducting an insertion force test (left panel) on a spiral phantom (first inset, center panel) which mimics the cochlea. The second inset (right panel) shows the rounded cap at the distal end of the protective sheath which helps the sheath advance smoothly through the cochlea. FIG. 9 shows a graph of the amount of force required to insert either cochlear implants (CI samples 1-3) or a silicone sheath containing an 80 pm SMF (Our cochlear catheter) as a function of depth within the phantom. As seen in FIG. 9, while the cochlear catheter required an increasing amount of force as it traveled deeper into the phantom, it still required less force than two out of the three cochlear implants that were tested, indicating that it is capable of being inserted into the cochlea without requiring application of an unusually large amount of force.

[0082] FIGS. 10A and 10B show results of rotation tests to quantify distortion effects associated with the probe at high rotational speeds (3000 rpm). FIG. 10A shows the path of rotation for the probe which collects 30 frames per rotation. Based on the data, it was determined that the average degrees of rotation of travel per frame was 12.0056° with a standard error of 0.514 milliradians; the non-uniform rotational distortion (NURD) was 0.61236° per frame; the average deviation from the rotational path was 6.124 pm; the off- center rotational distortion was 4.2789 pm; and the average measured angular speed was 3001.3977 rpm. FIG. 10B shows a diagram interpreting the results of FIG. 10A where the consequences of the standard error of 0.514 milliradians are shown at points 0.8 mm and 1.5 mm from the probe are depicted.

[0083] FIGS. 11 A and 1 IB show a diagram of the optical components of a construction of the disclosed probe (FIG. 11 A) which was used to perform optical simulations (FIG. 1 IB). The optical components include a SMF (with a 3.5 pm core and 80 pm cladding), a MMF (with a 20 pm core and 125 pm cladding), a spacer (a 3D printed tube), a 250 pm GRIN lens, and a reflector including a 180 pm prism. The diagram in FIG.11 A also shows the locations of other optically-relevant components including the sheath, the layer of mineral oil within the sheath, and the perilymph adjacent to the sheath. The depth of focus (DOF) of the setup of FIG. 11 A is approximately 600 pm, the imaging range is approximately 0.42 mm - 0.98 mm, and the average lateral resolution is approximately 4.6 pm. FIG. 1 IB (left vertical panel) shows a simulation of a beam emitted from the optical setup of FIG. 11 A (with the beam having an increasing distance from the probe going from top to bottom in the diagram) along with two cross-sectional views of the beam at different points corresponding to the peaks of mode 1 at 0.433 mm and mode 2 at 0.762 mm (upper and lower right panels, respectively).

[0084] FIGS. 12A, 12B, and 12C show results of characterization of image quality using a construction of the disclosed probe. FIG. 12A shows an OCT phantom (left panel) and the lateral resolution grids of the phantom (right panel). FIG. 12B shows a close-up image corresponding to a depth of 425 pm. The first column of FIG. 12C shows a series of images from the phantom of FIG. 12A with particular images being encircled by dashed boxes corresponding to various depths as indicated in the "Depth" column, along with an average X-profile through the respective image. The last column of FIG. 12C shows the determined resolution at the particular depth, which was best (i.e. has the lowest value, 3 pm) in the 350-500 pm range, which is close to the target lateral resolution of 2-3 pm.

[0085] Accordingly, disclosed herein are embodiments of an ultra-flexible miniature micro-OCT catheter that can be inserted into the human cochlea through the round window and can be used to obtain cellular level micro-OCT images. Characterization results disclosed herein show that the catheter has comparable mechanical properties, including flexibility and insertion force, to commercially available cochlear implants. Imaging of OCT phantoms shows that a catheter which includes the disclosed micro-OCT system can achieve ~2 pm axial resolution and <5 pm lateral resolution within an approximately 500 pm focusing range.

[0086] Variations

[0087] The following are variations on one or more of the components disclosed herein.

[0088] In some embodiments, a polished glass rod may be used as a reflector in place of the reflector prism shown in FIG. 5A. As shown in FIGS. 13A and 13B, in one particular embodiment the optical probe head is similar to that shown in FIGS. 5A and 5B except that in place of a reflector prism and reflector cap, the probe head instead includes an angle-polished reflector (R) which is placed in a reflector tube (RT). In one procedure for forming the embodiment shown in FIGS. 13A and 13B, a 250 pm glass rod was first inserted into the 3D printed RT after which the rod was cleaved slightly longer than the RT. The RT with the glass rod was aligned and attached to the main body of the probe at the distal end (connected to the GRIN lens). After this, the glass rod required a manual cleave, a vertical polish, and then a 45° polish. On the RT, an eye-shaped opening (FIG. 13C) was included on the side opposite the angled surface to allow the light beam to come out from the probe and focus on the tissue. As noted above, mineral oil is used between the probe and sheath to make sure the probe can rotate smoothly within the silicone sheath. The mineral oil also acts as an index matching oil, preventing aberrations of the light beam that can lead to poor imaging. However, given that the optics are bathed in mineral oil, it is not feasible to use total internal reflection of the polished surface to direct light to the side of the probe and therefore the polished surface is coated (e.g. with a metal such as silver, gold, and / or aluminum) in order to be reflective (FIG. 13D). In another embodiment, the optical probe head has a 3D printed cap that includes an optically reflective surface (R) formed therein (FIG. 14).

[0089] FIG. 15 shows an embodiment of an optical probe head with a multi-part spacer component shown in an exploded view (top) and an assembled view (bottom). In this embodiment, the spacer is fabricated as two separate components in order to improve the alignment of the optical components. A first alignment tube (Alignment tube - 1) includes the SMF and MMF and this first alignment tube is inserted into a complementary opening in the proximal portion of the spacer (FIG. 15, top panel). A second alignment tube (Alignment tube - 2) houses the reflector and brings the reflector into position so that it is adjacent the GRIN lens. As shown in the top panel of FIG. 15, in this embodiment a glass rod is inserted into the second alignment tube prior to polishing and the alignment tube and glass rod are polished as a single unit to produce the reflector component shown in the assembled form in the bottom panel of FIG. 15. In this particular embodiment, the first and second alignment tubes and the spacer are 3D printed.

[0090] Insertion Handle

[0091] In various embodiments, an endoscope system may be provided for probing the inner ear which includes an insertion handle surrounding the protective sheath close to the distal end of the protective sheath. In certain embodiments, the insertion handle may be designed to be handled by a clinician (e.g., a surgeon) by hand or with various insertion assistance tools, including but not limited to a surgical tweezer or a robotic device, which also helps to make the insertion of the probe into the inner ear easier and less invasive. In some embodiments, the insertion handle is also designed to protect the protective sheath from being deformed due to the pressure from the handling.

[0092] In certain embodiments, the insertion handle further includes an insertion stop at its distal end which may be a circular or rounded component projecting around the insertion handle (FIG. 16). During insertion of the endoscope into the cochlea, the insertion stop will block further insertion of the probe by pressing against the round window.

[0093] In some embodiments, the insertion handle may be rigid (e.g., made from stainless steel) and maintain a particular shape (e.g., straight or with a particular curved shape) and its length may vary depending on the way it is being handled (FIG. 16). In other embodiments, the insertion handle may be adjustable and bendable (e.g., made from memory alloy), so that the insertion direction may be adjusted by adjusting the angle of the insertion handle and the handling method (FIG. 17). In still other embodiments, the insertion handle may have an ergonomic handle, which may be made for example from rubber, for easy handling of the endoscope by operators such as surgeons (FIG. 18).

[0094] In certain embodiments, an endoscope system for probing the inner ear may further include a probe scanning device (PSD; FIG. 19). The probe scanning device, which may be connected to the proximal end of the endoscope, may be connected to the imaging system via one or both of electric wires and / or optical fibers. The probe scanning device may further include a rotational scanning module and a longitudinal scanning module (FIG. 19).

[0095] More generally, the endoscope system may include any of the imaging tools disclosed herein. The endoscope system may be configured to be used in the inner ear, including to probe at least one of the cochlea, the utricle, the saccule, or the semicircular canal. In various embodiments, the endoscope system may be coupled (e.g., via an optical waveguide) to an OCT imaging system.

[0096] In various embodiments, the protective sheath of the probe may be connected to a static part of the probe scanning device, such as its shell or a sheath holder that is specifically incorporated into the device. The proximal end of the driveshaft may beconnected to either or both of the rotational scanning module and / or the longitudinal scanning module. The fiber inside the driveshaft may be connected to the fiber inside the driveshaft of the rotational scanning device or to the moving part of the longitudinal scanning module.

[0097] In some embodiments, the rotational scanning module can either rotate continuously in one direction or perform rotational oscillating scanning in two directions. The driveshaft and the fiber fixed within the driveshaft can thus rotate and / or perform linear movement within the protective sheath, such that the optical probe can then rotate and / or perform linear movement within the flexible sheath.

[0098] In certain embodiments, the driveshaft between the probe scanning device and the optical probe head may have a 1 : 1 spinning ratio and a limited time delay, such that when the rotational scanning module is operating in a fast rotational oscillating mode, the optical probe head will rotate accordingly without significant or noticeable delay.

[0099] Thus, in particular embodiments the rotational scanning module and longitudinal scanning module can work together to perform one or more of (FIG. 20):

[0100] A. 2D rotational scan of the cochlea at a single depth (meaning that a rotational scan is obtained only at a depth determined by the distance by which the probe has been inserted into the inner ear lumen);

[0101] B. 2D linear scan of the inner ear lumen along a certain longitudinal distance at a specific radial angle / direction; and / or

[0102] C. 3D scan of the inner ear lumen by performing a partial or complete rotational scan of the inner ear lumen along a certain longitudinal distance.

[0103] In one embodiment, the rotational scanning module may include a stepped motor that can reverse its rotation direction rapidly. Thus, the motor can drive the rigid driveshaft along with the optical fiber and the probe head to spin continuously in one direction. Alternatively, the motor can drive the rigid driveshaft along with the optical fiber and the probe head to rotate in one direction for a certain amount (e.g., between 0-360 degrees or more) and reverse the rotation direction and rotate for a certain amount (e.g., between 0-360 degrees or more). Using this procedure, the optical probe can scan inside the luminal inner ear structures in a rotational oscillating manner (FIG. 19).

[0104] In another embodiment, the rotational scanning module may be a mechanical system that can convert continuous rotation of a motor into rotational oscillation movement, as shown in FIG. 21. In various embodiments, the rotational scanning system may reside onthe longitudinal scanning module (as depicted in FIG. 21) so the two components can work together to drive the driveshaft and probe head to scan the luminal structure of the inner ear.

[0105] In a further embodiment, an endoscope system for probing the inner ear may further include a handheld device, where the handheld device may further include a rigid tube (similar to certain embodiments of the insertion handle described above) at its distal end along with a rigid driveshaft (FIG. 22). The rigid tube may be connected to the flexible sheath at its distal end and to the handheld device body at its proximal end. In certain embodiments, the rigid driveshaft may enclose the optical fiber inside, where a bare portion of the optical fiber may extend from the rigid driveshaft into the flexible sheath. The rigid tube and the rigid driveshaft may be made from particular materials, such as ceramic and stainless steel, respectively, or may be specifically treated, such as being coated with PTFE on their inner surface and outer surface, respectively, so that the rigid driveshaft can rotate in the rigid tube with low friction. The handheld device may be lightweight so it can be easily handled by the surgeon to perform endoscope insertion.

[0106] In various embodiments, the endoscope tip may be about 25 mm while the rigid tube may be between about 20 mm and 30 mm, while the handheld device body may be between about 100 mm and 150 mm.

[0107] In some embodiments, the handheld device may further include a rotational scanning module and a longitudinal scanning module (FIG. 23). The rotational scanning module can either rotate in one direction continuously or perform rotational oscillating scanning in two directions. The rigid driveshaft and the fiber fixed in the rigid driveshaft can thus rotate and / or perform linear movement in the rigid tube, and as a result the optical probe can therefore rotate and / or perform linear movement in the flexible sheath.

[0108] In various embodiments, the rotational scanning module and longitudinal scanning module in the handheld device can work together to perform:

[0109] A. 2D rotational scan of the cochlea at a single depth (meaning that a rotational scan is obtained only at a depth determined by the distance by which the probe has been inserted into the inner ear lumen);

[0110] B. 2D linear scan of the inner ear lumen along a certain longitudinal distance at a specific radial angle / direction; and / or[OHl] C. 3D scan of the inner ear lumen by performing a partial or complete rotational scan of the inner ear lumen along a certain longitudinal distance.

[0112] In one embodiment, the handheld device may further include a probe insertion module inside its body (FIG. 25). In such embodiments, the rigid tube may be connected to the probe insertion module and can move back and forth relative to the handheld device body.

[0113] In another embodiment, the probe insertion module may include a linear stage that is connected to the rigid tube via rigid mechanical connections, as shown in FIG. 25.

[0114] In yet another embodiment, the probe insertion module may be a mechanical system driven by a rotational motor, where the linear movement of the rigid tube is achieved by mechanical connections, such as a friction drive system (FIG. 26), slider-crank linkage, etc.

[0115] In another embodiment of the endoscope, the 3D printed reflector (see FIG.14) has at least one freeform optical surface that can contribute to focusing and / or modulating the light beam so any astigmatism caused by the flexible sheath can be compensated and / or the depth of focus of the light beam can be extended. It may also include a protective, shaperestoring cap which complements the shape of the 3D printed reflector to bring the entire catheter back to a cylindrical profile for improved rotation performance. FIG. 27 shows an example of an embodiment of such a reflector, where one of its surfaces is a freeform reflective surface that has different curvatures in its meridian plane and its equatorial plane, so that the focusing powers are different at different directions. Thus, it can compensate for the astigmatism of various components including the flexible sheath. FIG. 27 also shows the protective cap and the complementary shape of each component. The complementary shape helps the probe to rotate more smoothly within the flexible sheath without getting stuck at when the flexible sheath is curved.

[0116] In various embodiments, the whole endoscope may be integrated into a handheld probe as shown (e.g., FIG. 22). Using this device, the surgeon will hold the handheld device and insert the flexible tip into the cochlea through the round window. The insertion can be performed manually or in an automated manner with a controlled speed.

[0117] In some embodiments, the scanning device may be about 10-15 cm in length, about 5 cm in diameter, and in a range of about 300-400 g in weight (although embodiments which include automatic insertion mechanisms may be heavier).

[0118] Fiber Collar

[0119] In various embodiments, the optical imaging probe may be connected to the driveshaft via a fiber collar (FIGS. 28A-28C). In some embodiments, the fiber collar can serve as an adaptor which enables a relatively thin fiber to be used with a driveshaft that ismade to accommodate larger optical fibers. As discussed below, the fiber collar can help center the fiber within the driveshaft so that it is properly centered during rotation and the fiber collar can also be attached to the fiber at a particular location along the length of the fiber so that a defined length of fiber extends from the distal end of the fiber collar.

[0120] In certain embodiments, the fiber collar, which may be tapered, may be a 3D printed structure (FIG. 28A) which may be made using rigid materials such as two-photon polymerization resins (e.g., IP-Q, Nanoscribe, Germany). During the fabrication process of the optical imaging probe, the optical imaging probe or fiber will be connected to the fiber collar using epoxy or other adhesive, with the length of the optical imaging probe extending from the fiber collar controlled within a particular clearance or tolerance, for example + / - 0.5 mm (or other tolerance amount) (FIG. 28C). The particular length of fiber extending toward the distal end of the probe can vary depending on the application, for example a range of between 20-30 mm, or in one particular embodiment 25 mm, for use in the cochlea. Thus, the length of the optical imaging probe secured in the flexible sheath, as well as the length of the segment of the endoscope to be inserted into the cochlea, can be precision-controlled within a tolerance or clearance, e.g., within between + / - 0.1 mm and 0.5 mm. The fiber collar with the attached fiber and optical probe tip may be inserted into the distal end of the drive shaft (FIG. 28B). The fiber collar may be tapered as shown in order to fit snugly within the drive shaft so that rotation of the drive shaft causes rotation of the fiber and optical probe tip.

[0121] The fiber collar is designed such that the fiber (and by extension the probe) is concentrically aligned with the drive shaft. With proper centering alignment, the driveshaft and the probe tip will rotate about the same axis, thus improving the overall performance of the probe.

[0122] Rotational and Oscillatory Scanning

[0123] The disclosure provides various embodiments of rotational scanning modules (e.g., FIGS. 1, 19, 21, 23, 25, 26, 29) for rotating and / or oscillating the optical fiber and probe while optionally moving the probe longitudinally in order to obtain scans of a sample. In various embodiments the rotational scanning modules may provide continuous rotation of a fiber in a single rotational direction, which requires the use of a rotary junction to optically couple the rotating fiber that connects to the probe to the stationary fiber that connects to the imaging system (e.g., OCT system).

[0124] In some embodiments, however, the intensity of light moving through the system can be harmful to a rotary junction, e.g., due to having to focus the light to a smallcross-sectional area into a thin fiber as would be used for samples such as the cochlea. For example, the fluid that is used to help optically couple the rotating fiber to the stationary fiber may be damaged in the presence of the high light intensities.

[0125] Accordingly, in some embodiments the rotational scanning module may be operated in an oscillatory fashion to collect sample data. In an oscillatory scanning mode, the system performs one or more rotations in a first rotational direction and then performs one or more rotations in the opposite rotational direction, with the result that the optical fiber is briefly twisted during the course of oscillatory scanning but eventually returns to its original configuration so that a rotary junction is not required.

[0126] In one particular embodiment, the rotational scanning module may include a motor-driven scanning device including a fiber coil module (FIG. 29). The fiber coil module, which is represented schematically in various diagrams by a loop of fiber (e.g., see FIGS. 19, 21, 23, and 29), is coupled to the probe fiber and is driven by a belt and pulley transmission for rotation and / or oscillation, along with a single-axis stage for linear movement. The fiber may be arranged and stored within the fiber coil module, which allows the fiber to be turned two or more rotations in the same direction during an oscillatory scan of a sample. Turning the fiber in two or more rotations in the same direction before reversing directions has an advantage over simply alternating one rotation in each direction, as it reduces the time spent on acceleration and deceleration each time the rotational direction is changed.

[0127] In various embodiments, the particular type of motor that is used can support different rotational scanning patterns and / or scanning rates. In one configuration, using a stepped motor from Faulhaber Group (AM2224R3-0250) allows a rate of 10 rotations per second (10 Hz) to be achieved when oscillating after each rotation (i.e., repeatedly rotating one turn in a forward direction followed by one turn in a reverse direction).

[0128] FIG. 30 shows a graph of rotational position vs. time when a fiber is oscillated in an alternating “one clockwise-one anticlockwise” pattern for a period of 1000 ms, completing more than 10 oscillations. In another configuration in which the fiber is permitted to twist inside the fiber coil module, the same stepped motor can achieve a rate of 16 highspeed rotations per second when oscillating after a full 16 rotations.

[0129] FIG. 31 shows a graph of rotational position vs. time when a fiber is turned multiple times (8 times in this example) in the same direction before reversing and rotating in the opposite rotational direction; the fiber is rotated 8 times to return to a base state (indicated by 0 rotations on the y-axis in FIG. 31) and continues to be rotated an additional 8 times pastthe base state in the other direction (labeled as -8 rotations in FIG. 31). In various embodiments, using a more powerful motor can help achieve higher scanning speeds, both in the one clockwise-one anticlockwise rotating pattern, or in the multiple (up to 25) clockwisemultiple (up to 25) anticlockwise oscillatory rotating pattern (e.g., using the DM52100R stepped motor from Faulhaber Group), which would allow a total of 50 rotational scans to be performed per second. In other embodiments, faster and / or more powerful motors may be used to rotate the drive shaft / fiber faster (e.g., 100-1000 times per second or more) and for more rotations before reversing.

[0130] In another embodiment, the fiber coil module may be composed in part of an uninterrupted optical fiber path designed such that, after spinning, the twisting pattern of the fiber is controlled so that signal loss is no more than 10% and the fiber is not damaged or broken as a result of the twisting forces. FIGS. 32A-32D and FIG. 33 show embodiments of a fiber coil module that maintains tension on the optical fiber while allowing the fiber to twist in a controlled manner that permits light transmission (e.g., by maintaining a minimum radius of curvature on the fiber) and avoids damage to the fiber.

[0131] In various embodiments, the fiber coil module may include one or more of a fiber cage, a fiber hook, a linear bearing, a spring system for the linear bearing, and / or a ball bearing with a linear shaft mounted on it (FIGS. 32A-32D). The fiber may be directed laterally from the OCT system to the fiber coil module and from the fiber coil module to the probe output in a controlled manner by the fiber cage, which guides the fiber through turns and maintains a minimum radius of curvature on the fiber to minimize bending losses. The fiber may then connect to the fiber hook which, like the fiber cage, maintains a minimum radius of curvature to minimize bending losses. The fiber twisting control is achieved by the linear shaft mounted on the ball bearing to permit the fiber hook to freely rotate.

[0132] A linear bearing is installed on the shaft using a spring mechanism which maintains the fiber under tension while also allowing for rotation / translation to absorb excess rotational energy from the operation of the rotational scanning module. The oscillating / rotational mechanism may be driven by a stepped motor similar to the one described in connection with FIG. 29, although in this case a belt system may be used to drive the rotation from the motor to the optical fiber twist control module (FIG. 33). Thus, the fiber hook may be maintained in tension by the linear bearing and associated spring system, while the ball bearing and linear shaft cooperate with the linear bearing and spring to permit the fiber hook to rotate with the fiber to facilitate multiple twists of the fiber in a singlerotational direction. In various embodiments, the fiber coil module may permit the optical fiber to be rotated multiple times (e.g., up to 10, up to 20, up to 30, up to 40, up to 50, etc.) in teach direction without significant bending losses in the light transmission and without damage to the fiber.

[0133] In some embodiments, the optical fiber may be rotated between 200-1000 times or more in a single rotational direction before the direction is reversed. In various embodiments, this degree of rotation can be achieved while still maintaining high light throughput and minimizing damage to the fibers by joining together multiple fiber coil modules in series (FIG. 32D). While FIG. 32D shows a system with two fiber coil modules, in various embodiments the imaging system may include any number of fiber coil modules, e.g., up to 5, up to 10, up to 20, etc. As noted above, a faster and / or more powerful motor may be used to rotated the drive shaft / fiber in order to provide rotational speeds of 100-1000 Hz or more in conjunction with a greater number of rotations in one direction before reversing direction.

[0134] Thus, various embodiments of the disclosure provide an oscillating scanning ultra-flexible miniature catheter and systems for endomicroscopy of small and / or anatomically complex structures, such as the cochlea, cardiovascular spaces (e.g., coronary artery), respiratory tract (e.g., bronchus), brain vasculature, reproductive tract, digestive tract (e.g., esophagus, duodenum, colon). The catheter can be used to implement a number of optical imaging modalities, including: optical coherence tomography (OCT) and variants thereof including dynamic OCT and multichannel OCT to name a few; fluorescence imaging; fluorescence lifetime imaging; spectroscopy; and multimodality imaging (including any combination of modalities including but not limited to those listed above)

[0135] While examples above refer to the use of a single mode fiber, in various embodiments the procedures and systems disclosed herein may be carried out using a variety of different fibers including without limitation: multimode fibers; few mode fibers; multicore fibers; double clad fibers; and / or multi-fiber bundles.

[0136] In certain embodiments, the type of fiber that is used may be determined in part based on the particular imaging modality that is employed, as would be understood by a skilled person. For example, dynamic OCT may use a single mode fiber, while fluorescence imaging may use a single mode fiber plus a multimode fiber or a multi core fiber or fiber bundle.

[0137] Computer System

[0138] FIG. 34 shows a diagram of an oscillating scanning imaging system in communication with a computer system. The lower portion of FIG. 34 shows an embodiment of a computer system 500 or controller that can be used to send control information to an oscillating scanning imaging system 100 (e.g. via wired or wireless communication 505) in accordance with embodiments of the disclosed subject matter. Oscillating scanning imaging system 100 may include one or more of an oscillating motor, a longitudinal scanning module or device, and / or an imaging unit (e.g., an OCT interferometry system), each of which may be in communication with and controlled by computer system 500.

[0139] As shown in FIG. 34, in some embodiments, computer system 500 can include a processor 510, a user interface and / or display 540, one or more communication systems 530, and memory 520. In some embodiments, processor 510 can be any suitable hardware processor or combination of processors, such as a central processing unit (CPU), a graphics processing unit (GPU), a microcontroller (MCU), a field programmable gate array (FPGA), an application-specific integrated circuit (ASIC), a dedicated image processor, etc. In some embodiments, input(s) and / or display 540 can include any suitable display device(s), such as a computer monitor, a touchscreen, a television, etc., and / or input devices and / or sensors that can be used to receive user input, such as a keyboard, one or more physical buttons with dedicated functions, one or more physical buttons with software programmable functions, a mouse, a touchscreen, a microphone, a gaze tracking system, motion sensors, etc.

[0140] In some embodiments, communications systems 530 can include any suitable hardware, firmware, and / or software for communicating information over a communication network and / or any other suitable communication networks. For example, communications systems 530 can include one or more transceivers, one or more communication chips and / or chip sets, etc. In a more particular example, communications systems 530 can include hardware, firmware and / or software that can be used to establish a Wi-Fi connection, a Bluetooth connection, a cellular connection, an Ethernet connection, an optical connection, etc.

[0141] In some embodiments, memory 520 can include any suitable storage device or devices that can be used to store instructions, values, etc., that can be used, for example, by hardware processor 510 to process image data generated by one or more optical detectors, to present content using input(s) / display 540, to communicate with an external computing device via communications system(s) 530, etc. Memory 520 can include any suitable volatile memory, non-volatile memory, storage, any other suitable type of storage medium, or anysuitable combination thereof. For example, memory 520 can include RAM, ROM, EEPROM, one or more flash drives, one or more hard disks, one or more solid state drives, one or more optical drives, etc. In some embodiments, memory 520 can have encoded thereon a computer program for carrying out one or more embodiments of the disclosed procedures.

[0142] Various embodiments may be carried out with a system that includes a memory (such as memory 520) in communication with a processor (such as processor 510), the memory having stored thereon a set of instructions which, when executed by the processor, cause the processor to carry out steps of various embodiments of the procedures disclosed herein. In some embodiments, the memory may include any suitable computer readable media which can be used for storing instructions for performing the functions and / or processes described herein. For example, in some embodiments, computer readable media can be transitory or non-transitory. For example, non-transitory computer readable media can include media such as magnetic media (such as hard disks, floppy disks, etc.), optical media (such as compact discs, digital video discs, Blu-ray discs, etc.), semiconductor media (such as RAM, Flash memory, electrically programmable read only memory (EPROM), electrically erasable programmable read only memory (EEPROM), etc.), any suitable media that is not fleeting or devoid of any semblance of permanence during transmission, and / or any suitable tangible media. As another example, transitory computer readable media can include signals on networks, in wires, conductors, optical fibers, circuits, or any suitable media that is fleeting and devoid of any semblance of permanence during transmission, and / or any suitable intangible media.

[0143] Thus, while the invention has been described above in connection with particular embodiments and examples, the invention is not necessarily so limited, and that numerous other embodiments, examples, uses, modifications and departures from the embodiments, examples and uses are intended to be encompassed by the claims attached hereto.

Claims

CLAIMSWhat is claimed is:

1. An oscillating scanning imaging system, comprising: a drive shaft including a proximal end and a distal end; an optical waveguide including a proximal end and a distal end, the proximal end of the optical waveguide being disposed within the proximal end of the drive shaft, and the distal end of the optical waveguide extending beyond the distal end of the drive shaft; an optical probe head coupled to the distal end of the optical waveguide; and an oscillating motor coupled to the drive shaft.

2. The system of claim 1, further comprising a controller in communication with the oscillating motor, wherein the controller is configured to rotate the oscillating motor in at least one of a single direction in a continuous manner or alternating directions in an oscillatory manner.

3. The system of claim 1, further comprising a controller in communication with the oscillating motor, wherein the controller is configured to: rotate the oscillating motor in a first rotational direction, and rotate the oscillating motor in a second rotational direction opposite the first rotational direction.

4. The system of claim 3, wherein the controller, when rotating the oscillating the motor in the first rotational direction, is further configured to: rotate the oscillating motor at least one rotation in the first rotational direction, and wherein the controller, when rotating the oscillating the motor in the second rotational direction, is further configured to: rotate the oscillating motor at least one rotation in the second rotational direction.

5. The system of claim 4, wherein the controller, when rotating the oscillating the motor at least one rotation in the first rotational direction, is further configured to: rotate the oscillating motor two or more rotations in the first rotational direction, and wherein the controller, when rotating the oscillating the motor at least one rotation in the second rotational direction, is further configured to: rotate the oscillating motor two or more rotations in the second rotational direction, wherein the number of rotations in the second rotational direction is equal to the number of rotations in the first rotational direction.

6. The system of any one of claims 1-5, further comprising a fiber coil module, wherein the optical waveguide is coupled to the fiber coil module.

7. The system of claim 6, wherein the fiber coil module comprises a fiber hook, wherein the optical waveguide is coupled to the fiber hook, and wherein the fiber hook is configured to at least one of rotate or translate to facilitate controlled twisting of the optical waveguide.

8. The system of claim 7, wherein the fiber hook is coupled to at least one of a linear bearing, a linear bearing spring, or a ball bearing to facilitate at least one of rotation or translation of the fiber hook.

9. The system of any one of claims 6-8, wherein the fiber coil module further comprises a plurality of fiber coil modules arranged in series, wherein the optical waveguide is coupled through the plurality of fiber coil modules.

10. The system of any one of claims 1-5, further comprising a fiber collar coupled to the distal end of drive shaft, wherein the optical waveguide is inserted through and fixed to a central opening of the fiber collar.

11. The system of claim 10, wherein the distal end of the optical waveguide from the fiber collar to the optical probe head comprises a fixed distance.

12. The system of claim 11, wherein the fixed distance is between 20 mm and 30 mm.

13. The system of claim 12, wherein the fixed distance is 25 mm and is within a tolerance of 0.1 mm.

14. The system of claim 2, further comprising a longitudinal scanning device coupled to the drive shaft and in communication with the controller.

15. The system of claim 14, wherein the controller is configured to control at least one of the oscillating motor or the longitudinal scanning device to perform at least one of a two- dimensional rotational scan, a two-dimensional linear scan, or a three-dimensional scan.

16. The system of any one of claims 1-5, wherein the distal end of the optical waveguide extending beyond the distal end of the drive shaft comprises a bare portion of the optical waveguide, and wherein the bare portion of the optical waveguide is disposed within a flexible sheath.

17. The system of claim 16, further comprising a lubricant disposed within the flexible sheath.

18. The system of claim 16, further comprising a rounded cap coupled to a distal end of the flexible sheath.

19. The system of claim 18, wherein the rounded cap comprises an oval rounded cap.

20. The system of claim 16, wherein a distal end of the flexible sheath further comprises a rounded cap.

21. The system of claim 20, wherein the rounded cap comprises an oval rounded cap.

22. The system of claim 1, further comprising a rotary junction coupled to the proximal end of the optical waveguide and the proximal end of the drive shaft, wherein the optical waveguide and the optical probe head are rotatably disposed within the flexible sheath.

23. The system of claim 1, wherein the optical probe head comprises a spacer at a proximal end thereof, wherein the distal end of the optical waveguide is coupled to a proximal end of the spacer.

24. The system of claim 23, wherein the spacer comprises a conical shape having a narrow proximal end adjacent the optical waveguide.

25. The system of claim 24, wherein the narrow proximal end has a diameter of 250 pm or less and wherein the spacer comprises a wide distal end having a diameter of 380 pm or less.

26. The system of claim 24, wherein the optical probe head further comprises a reflector to reflect light from the optical waveguide away from a central axis of the optical waveguide.

27. The system of claim 26, wherein the reflector comprises a freeform surface configured to correct for an optical aberration caused by the sheath.

28. The system of claim 26, wherein the optical probe head further comprises a reflector cap at a distal end thereof, and wherein the reflector is disposed within the reflector cap.

29. The system of claim 26, wherein the optical probe head further comprises a reflector cap at a distal end thereof, and wherein the reflector cap comprises an optically reflective surface formed therein.

30. The system of claim 29, wherein the reflector cap is 3D printed.

31. The system of claim 28, wherein the reflector comprises a prism, andwherein a reflective surface of the prism comprises a reflective coating comprising gold.

32. The system of claim 28, wherein the reflector comprises a polished glass rod, and wherein a reflective surface of the prism polished glass rod comprises a metallic coating.

33. The system of claim 31, further comprising a GRIN lens disposed within a distal end of the spacer adjacent to the prism.

34. The system of claim 24, wherein the optical waveguide comprises a single mode fiber, wherein the narrow proximal end of the spacer comprises a multimode fiber disposed therein adjacent to the distal end of the optical waveguide.

35. The system of claim 34, wherein the multimode fiber has a core diameter of 20 pm or less, a cladding diameter of 125 um or less, and a length of 220 pm or less.

36. The system of claim 1, wherein the optical probe head has a length of 1.7 mm which defines a maximum rigid length of the imaging tool.

37. The system of claim 16, wherein the drive shaft is disposed within a low friction sheath adjacent to the flexible sheath.

38. The system of claim 37, wherein an inside surface of the low friction sheath comprises a Teflon coating.

39. The system of claim 16, wherein the sheath has a diameter of 600 pm or less, wherein the optical probe head has a length of 1.7 mm or less which defines a maximum rigid length of the imaging tool, and wherein a distal portion of the imaging tool can be inserted to a depth of at least 20 mm into the cochlea.

40. The system of claim 39, wherein the distal portion of the imaging tool can be inserted into a curved sample having a radius of curvature of at least 2 mm.

41. The system of claim 39, wherein the distal portion of the imaging tool comprises the bare portion of the optical waveguide, the optical probe head, and the flexible sheath.

42. The system of claim 16, wherein a distal portion of the imaging tool has a bending stiffness of less than 7.58*10'8Nm2, wherein the distal portion of the imaging tool comprises the bare portion of the optical waveguide, the optical probe head, and the flexible sheath.

43. An oscillating scanning imaging method, comprising: inserting an oscillating scanning imaging tool into a luminal sample, the tool comprising: a drive shaft including a proximal end and a distal end, an optical waveguide including a proximal end and a distal end, the proximal end of the optical waveguide being disposed within the proximal end of the drive shaft, and the distal end of the optical waveguide extending beyond the distal end of the drive shaft, an optical probe head coupled to the distal end of the optical waveguide, and an oscillating motor coupled to the drive shaft; and obtaining, using the tool, optical data from the luminal sample.

44. The method of claim 43, wherein the luminal sample comprises the inner ear of a subject.

45. The method of claim 44, wherein inserting the oscillating scanning imaging tool into the inner ear of the subject further comprises: inserting the oscillating scanning imaging tool into at least one of the cochlea, the saccule, the utricle, or the semicircular canal of the subject.

46. The method of claim 43, wherein the distal end of the optical waveguide extending beyond the distal end of the drive shaft comprises a bare portion of the optical waveguide,wherein the bare portion of the optical waveguide is disposed within a flexible sheath, and wherein inserting the oscillating scanning imaging tool into the luminal sample further comprises: inserting the flexible sheath containing the bare portion of the optical waveguide into the luminal sample.

47. The method of claim 46, wherein the sheath has a diameter of 600 pm or less, wherein the optical probe head has a length of 1.7 mm or less which defines a maximum rigid length of the imaging tool, and wherein inserting the flexible sheath containing the bare portion of the optical waveguide into the luminal sample further comprises: inserting the flexible sheath containing the bare portion of the optical waveguide to a depth of at least 20 mm into the luminal sample.

48. The method of claim 47, wherein inserting the flexible sheath containing the bare portion of the optical waveguide into the luminal sample further comprises: inserting the flexible sheath containing the bare portion of the optical waveguide into the luminal sample comprising a curved portion having a radius of curvature of at least 2 mm.

49. The method of claim 43, wherein obtaining optical data from the luminal sample further comprises: obtaining three-dimensional imaging data from the luminal sample to identify at least one of a morphology or a dimension of the scala tympani to facilitate insertion of a cochlear implant.

50. The method of claim 43, wherein the oscillating scanning imaging tool further comprises an oscillating scanning module configured to rotate or oscillate the optical probe, and wherein obtaining optical data further comprises: obtaining the optical data while rotating or oscillating the optical probe using the oscillating scanning module.

51. The method of claim 50, wherein obtaining the optical data while rotating or oscillating the optical probe further comprises: obtaining the optical data while rotating the optical probe in a single direction in a continuous manner.

52. The method of claim 50, wherein obtaining the optical data while rotating or oscillating the optical probe further comprises: obtaining the optical data while oscillating the optical probe in alternating directions.

53. The method of claim 50, wherein the oscillating scanning imaging tool further comprises a longitudinal scanning device, and wherein obtaining optical data further comprises: obtaining the optical data while using at least one of the oscillating scanning module or the longitudinal scanning device to perform at least one of a two- dimensional rotational scan, a two-dimensional linear scan, or a three-dimensional scan.

54. An oscillating scanning imaging tool, comprising: a drive shaft including a proximal end and a distal end; an insertion handle including a proximal end and a distal end, the distal end of the insertion handle surrounding the distal end of the drive shaft; an optical waveguide including a proximal end and a distal end, the proximal end of the optical waveguide being disposed within the proximal end of the drive shaft, and the distal end of the optical waveguide extending beyond the distal end of the drive shaft and beyond the distal end of the insertion handle; an optical probe head coupled to the distal end of the optical waveguide; and an oscillating motor coupled to the drive shaft.

55. The imaging tool of claim 54, wherein the distal end of the insertion handle further comprises an insertion stop, wherein the insertion stop comprises an enlarged portion which is configured to limit a distance by which the distal end of the optical waveguide may be inserted into a sample.

56. The imaging tool of claim 54, further comprising a handheld device coupled to the insertion handle.

57. The imaging tool of claim 56, further comprising at least one of an oscillatory scanning module or a longitudinal scanning device disposed within the handheld device.

58. The imaging tool of claim 57, wherein the oscillatory scanning module is configured to rotate the probe in at least one of a single direction in a continuous manner or alternating directions in an oscillatory manner.

59. The imaging tool of claim 57, wherein at least one of the oscillatory scanning module or the longitudinal scanning device are configured to perform at least one of a two- dimensional rotational scan, a two-dimensional linear scan, or a three-dimensional scan.

60. An endoscope system comprising the imaging tool of claims 54-59.

61. The system of claim 60, wherein the endoscope system is configured to be used in the inner ear, including at least one of the cochlea, the utricle, the saccule, or the semicircular canal.

62. The system of claim 60, wherein the endoscope system is configured to be used in at least one of the inner ear, cardiovascular spaces, the respiratory tract, brain vasculature, the reproductive tract, or the digestive tract.

63. The system of claim 60, wherein the optical waveguide is coupled to at least one of an OCT imaging system, a fluorescence imaging, a fluorescence lifetime imaging system, a spectroscopy system, or and a multimodality imaging system.

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