Multimodal Probes for Tissue Inspection

JP2024538380A5Pending Publication Date: 2025-11-05SPECTRAWAVE INC
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Patent Information

Application Number
JP2024528512
Authority / Receiving Office
JP · JP
Patent Type
Applications
Current Assignee / Owner
Priority Date
2021-11-19
Filing Date
2022-11-18
Publication Date
2025-11-05

AI Technical Summary

Technical Problem

Existing multimodal characterization systems face challenges in optimizing illumination and detection designs for multiple optical modalities, leading to suboptimal information quality in one or more modalities, particularly in intravascular characterization for coronary artery disease diagnosis.

Method used

A multimodal probe design utilizing a combination of single-mode and multi-mode optical fibers, with optimized waveguide arrangements and beam redirectors, allows for simultaneous imaging and spectroscopy, minimizing specular reflections and maximizing diffuse light collection, while maintaining a small diameter suitable for intravascular use.

Benefits of technology

The probe achieves high-resolution imaging and molecular characterization with improved sensitivity and fidelity, reducing manufacturing costs and probe size, while minimizing performance loss and maximizing signal collection efficiency.

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Abstract

Aspects of the present disclosure relate to the use of optical detection schemes that enable multiple imaging subsystems simultaneously optimized to acquire multiple characterization modalities. A feature described is an offset illumination and detection arrangement for a multimodal imaging probe. The imaging probe includes multiple waveguides disposed within a torque transfer coil and terminating distally at longitudinally spaced locations. A first waveguide may have focusing optics for concentrated illumination and / or detection. Any number of other waveguides for illumination and / or detection that do not have focusing optics may also be disposed. The present disclosure enables a high fidelity multimodal imaging system.
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Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent Application No. 63 / 281,383, filed November 19, 2021, the disclosure of which is hereby incorporated by reference in its entirety herein.

[0002] FIELD OF THE DISCLOSURE The present disclosure relates generally to methods for detecting and characterizing objects within a body cavity using optical waveguides. [Background technology]

[0003] In many applications, multiple sample characterization modalities are used to characterize a sample. Multimodal characterization can be performed using different forms of electromagnetic (e.g., optical) radiation from a single waveguide (e.g., optical fiber) or multiple waveguides. It can be difficult to optimize the illumination and detection design of multiple optical modalities. Thus, the quality of information (e.g., images) in at least one of the multiple modalities of a multimodal system often suffers. Summary of the Invention [Means for solving the problem]

[0004] Coronary artery disease (CAD) is the leading cause of death in the United States and worldwide, with over one million percutaneous coronary interventions (PCI) performed annually to combat CAD. Unfortunately, one in five patients who undergo PCI procedures will experience a major adverse cardiovascular event (MACE) within two years due to failure of the PCI site or the formation of new coronary lesions due to rupture of high-risk vulnerable plaques. Being able to optimize PCI treatment and identify patients and plaques at high risk for future rupture can help physicians manage and prevent the main causes of future MACE. To optimize such procedures, intravascular characterization can be performed to examine the arterial wall using small diameter probes (e.g., probes with an outer diameter of less than 500 μm, e.g., probes with an outer diameter of less than 1000 μm). Intravascular characterization informs physicians and contributes to clinical decision-making. Thus, intravascular characterization systems that can utilize multiple modalities (e.g., using the same intravascular probe) are of greater benefit to clinicians as these can provide more information for decision-making. Furthermore, one modality (e.g., an interference imaging modality) may improve one specific clinical endpoint (e.g., PCI optimization), while another modality (e.g., spectroscopy) may serve a different clinical purpose (e.g., detection of vulnerable plaque).

[0005] Intraluminal characterization (e.g., arterial wall characterization) can be performed using electromagnetic radiation. In some cases, performing more than one characterization method (e.g., multimodal characterization) may improve characterization. However, challenges exist with multimodal characterization. For example, some modalities require single-mode waveguides (e.g., single-mode optical fibers), whereas some require multimode waveguides (e.g., multimode optical fibers). In some cases, a combination may even be desirable, depending, for example, on which modalities are being used. Furthermore, one modality may require focused illumination or detection, or both, whereas another may only require maximizing the illumination or detection area. In some cases, the amount of light detected should be minimized / maximized or optimally controlled to exploit the dynamic range of the detector. Some modalities require a predictable phase change (e.g., 180°), whereas some do not. Some modalities rely on coherence preservation (e.g., coherent imaging systems), whereas others do not (e.g., spectroscopy). Some modalities use specular reflection to create contrast, while others can use diffuse reflection to create contrast (e.g., diffuse reflectance spectroscopy). In some modalities, it is desirable to separate or control the distance and / or position between the illumination and detection regions (e.g., to control the depth of sensing or to minimize specular reflection). In some modalities, it may be advantageous to control the angle of incidence of the radiation to the sample (to reduce surface reflections, e.g., from a protective probe sheath, e.g., from the sample, etc.).

[0006] Exemplary systems include imaging and spectroscopy modalities. In imaging modalities used to investigate structural samples (e.g., interferometric imaging systems), focused illumination and detection may be desirable, such as to provide high resolution information. In spectroscopy modalities used to examine molecular (e.g., chemical) samples (e.g., NIRS systems), it may be desirable to use focused illumination, where the use of focused detection is undesirable as it may minimize collection efficiency. Thus, to perform multimodal characterization using such imaging modalities and such spectroscopy modalities, unique multimodal probes can be used to optimize the performance of each modality. Ultimately, many factors must be considered when designing a multimodal characterization probe, and the present disclosure is based on this recognition.

[0007] For arterial wall characterization, a key challenge stems from size constraints to design a probe that can fit inside the vessel and characterize it. Thus, many designs have been introduced to address this issue, introducing specialized sheaths containing complex distal probe optics and optical fibers. The present disclosure provides, among other things, a simplified, performance-optimized probe for multimodal characterization resulting from unexpected observations and subsequent experimentation and analysis. The present disclosure also provides a waveguide arrangement with improved manufacturability, thereby reducing manufacturing costs.

[0008] According to some embodiments, the multimodal system may be comprised of a multimodal probe for intracavity characterization, the multimodal probe having a proximal end and a distal end, the distal end of which may be optically coupled to a sample. The multimodal probe may be arranged such that electromagnetic radiation (e.g., light) transmitted to the sample may travel through a first waveguide (e.g., a single mode fiber) and backscattered electromagnetic radiation received after interaction with the sample (e.g., a coronary artery) may travel through two or more waveguides (e.g., a single mode fiber and a multimode fiber). In some embodiments of the present disclosure, the multimodal probe may include at least two optical waveguides within a torque transmission coil (e.g., a drive shaft) that is used to circumferentially rotate a distal portion of the probe (e.g., to image the interior of a body cavity (e.g., an artery)).

[0009] In some embodiments, a single waveguide may be used for illumination and detection, while the same or another waveguide is used for detection. In some embodiments, the distal ports of the waveguides (e.g., where the electromagnetic radiation is optically transmitted to the sample) are optimally offset longitudinally or circumferentially, such as to optimize source-detector separation for optical measurements (e.g., scattering measurements, e.g., anisotropy measurements, e.g., absorption measurements).

[0010] The multimodal probe can include distal optics optimized for each modality of the multimodal characterization system. In some embodiments, the illumination waveguide is optically coupled to the distal focusing optics (e.g., to focus light onto the sample), such as to optimize the resolution of the characterization modality. In some embodiments, the collection waveguide is not optically coupled to the distal focusing optics, such as to maximize the light collected for the characterization modality.

[0011] In some embodiments, single-mode waveguides can be used to transmit single-mode light to or from a sample for imaging modalities (e.g., optical coherence tomography (OCT), e.g., confocal microscopy). In some embodiments, multimode waveguides can be used to transmit multimode light to or from a sample for reflectance intensity modalities (e.g., diffuse spectroscopy, fluorescence spectroscopy, Raman spectroscopy).

[0012] In some embodiments, a source-to-detector offset between the illumination and collection waveguides can optimize collection of diffusely reflected light (e.g., compared to specularly reflected light) (e.g., for probing below the surface of a sample). In some embodiments, the central axis of the illumination beam of a given characterization modality can be deflected (e.g., reflected) toward the sample (e.g., away from the central axis of the characterization probe). In some embodiments, the angle of incidence of radiation (e.g., for illumination) impinging on the sample from a first waveguide is controlled relative to the angle of the central axis of the collection region of another waveguide. In some embodiments, the central axis of the incident beam in optical transmission through one waveguide (e.g., illumination waveguide) is vertically offset from the central axis of the incident beam in optical transmission through another waveguide (e.g., collection waveguide).

[0013] In some embodiments, each modality can use a unique light source, multiple light sources, or the same light source. In some embodiments, the light source can use a narrow wavelength band, a broad wavelength band, and / or can be wavelength swept or wavelength tunable. In some embodiments, the duty cycles of multiple light sources can be interleaved in time to allow multi-modal characterization in a single pullback.

[0014] In some embodiments, the first characterization modality may be an imaging modality, for example, optical coherence tomography (OCT). The second characterization modality may be a spectroscopy modality, for example, near-infrared spectroscopy (NIRS). In some embodiments, the multimodal probe is a catheter, for example, a cardiac catheter, that can be used to rapidly characterize a patient's lumen (e.g., an artery) in a multimodal manner.

[0015] In some embodiments, a probe for characterization of a body cavity is provided. The probe can include a first waveguide and a second waveguide, each extending to a distal end of the probe. A first beam redirector and / or focusing optics (e.g., a combination of focusing optics and beam redirector) can be disposed in the optical path of the first waveguide to focus a first beam transmitted by the first waveguide toward a wall of the lumen (e.g., a body cavity). A second beam redirector can be disposed in the optical path of the second waveguide to direct a second beam transmitted by the second waveguide toward the wall (e.g., without focusing optics). The first beam redirector, focusing optics, and second beam redirector, when disposed in the lumen, can be disposed such that a center of the first beam points to a location on the wall more distal than a center of the second beam. In some embodiments, the first waveguide and the second waveguide may share a single beam redirector after the focusing optics disposed in the optical path of the first waveguide.

[0016] In some embodiments, the first waveguide is configured to detect a signal of a first characterization modality and the second waveguide is configured for a second characterization modality, the first characterization modality being an interferometric imaging modality (e.g., OCT).

[0017] In some embodiments, the first beam redirector is disposed distally to the second beam redirector. In some embodiments, no focusing optics are disposed in the optical path between the second waveguide and the wall of the lumen. In some embodiments, the first and second waveguides are disposed within the torque transfer coil. In some embodiments, the first beam redirector and the focusing optics are physically connected to the first waveguide and the second beam redirector is physically connected to the second waveguide.

[0018] In some embodiments, the first beam redirector or the second beam redirector is an angled optical fiber. In some embodiments, the focusing optic is a ball lens (e.g., an integrated ball lens). In some embodiments, the focusing optic is a gradient index lens. In some embodiments, the first beam redirector and the focusing optic are each (e.g., together) a curved mirror surface. In some embodiments, the injection molded part includes the first beam redirector, the second beam redirector, and the focusing optic. In some embodiments, the 3D printed part includes the first beam redirector, the second beam redirector, and the focusing optic.

[0019] In some embodiments, a protective case is disposed about the distal end of the probe. In some embodiments, the protective case comprises an optically transparent window. In some embodiments, the protective case comprises a radiopaque material.

[0020] In some embodiments, the probe includes a spectroscopic modality subsystem (e.g., NIRS, autofluorescence, fluorescence, Raman) optically connected to the second waveguide to detect light received via the second waveguide. In some embodiments, the probe includes a characterization modality subsystem optically connected to the first waveguide such that reflected intensity is detected by the first waveguide. In some embodiments, the probe includes an interferometric modality subsystem (e.g., OCT or OFDI) optically connected to the first waveguide (e.g., the first waveguide is an illumination and collection waveguide for an interferometric modality). In some embodiments, the probe includes an intensity modality subsystem (e.g., spectroscopy, NIRS, fluorescence, Raman) optically connected to the second waveguide (e.g., the second waveguide is an illumination and / or collection waveguide for an intensity modality).

[0021] In some embodiments, the second waveguide is optically connected to a light source for illuminating the sample. In some embodiments, the probe includes at least one additional waveguide. In some embodiments, the second waveguide is not associated with (e.g., optically connected to) any focusing optics at the distal end of the probe. In some embodiments, the first redirector, the focusing optics, and the second redirector are positioned such that the beams from the first waveguide and the second waveguide do not overlap circumferentially. In some embodiments, the probe is rotatable.

[0022] In some embodiments, a probe for characterization of a body cavity is provided. The probe can include a first waveguide and a second waveguide. A first beam redirector and / or focusing optics can be disposed in an optical path of the first waveguide. A second beam redirector can be disposed in an optical path of the second waveguide. In some embodiments, the first beam redirector and focusing optics are disposed to focus a center of a beam from the first waveguide at a first location (e.g., at a lumen wall) and the second beam redirector is disposed to provide a center of a beam from the second waveguide at a second location. The first location can be offset (e.g., radially offset) a distance from the second location.

[0023] In some embodiments, the first location is distal to the second location (e.g., along a wall of the body cavity). In some embodiments, the first redirector, focusing optics, and second redirector are positioned such that the beams from the first waveguide and the second waveguide do not circumferentially overlap. In some embodiments, the second waveguide is not associated with (e.g., optically connected to) any focusing optics at the distal end of the probe.

[0024] In some embodiments, the probe includes an interferometric modality subsystem (e.g., OCT or OFDI) optically coupled to a first waveguide (e.g., the first waveguide is an illumination and collection waveguide for an interferometric modality), and in some embodiments, the probe includes an intensity modality subsystem (e.g., spectroscopy, NIRS, fluorescence, Raman) optically coupled to a second waveguide (e.g., the second waveguide is an illumination and / or collection waveguide for an intensity modality).

[0025] In some embodiments, the first beam redirector and focusing optics are positioned to radially focus the beam from the first waveguide, and / or the second beam redirector is positioned to (for example) radially direct the beam from the second waveguide.

[0026] The probe may be included in an (e.g., intravascular) imaging catheter. The outer diameter of the catheter may be less than 1 mm over the lumen insertable length of the catheter. In some embodiments, the imaging catheter is part of a multimodal (e.g., intravascular) imaging system. In some embodiments, the probe is an air-filled probe. In some embodiments, the catheter is an air-filled catheter. In some embodiments, the probe is in optical communication with a rotatable combiner. The rotatable combiner may be optically coupled to a fiber optic rotary junction (FORJ), e.g., a double clad FORJ. The rotatable combiner may combine electromagnetic radiation from one or more illumination light channels and / or one or more waveguides, e.g., for transmission through the FORJ. The FORJ may be optically coupled to the probe via the rotatable combiner.

[0027] Other features and advantages of the present disclosure will be apparent from the following detailed description and drawings, and from the claims. Unless otherwise clear from the context, any two or more of the features described in this specification, including this summary section, may be combined to form an embodiment not specifically and explicitly described herein.

[0028] The drawings herein are presented for purposes of illustration and not limitation, and the foregoing and other objects, aspects, features, and advantages of the present disclosure will become more apparent and may be better understood by referring to the following description in conjunction with the accompanying drawings, in which: [Brief description of the drawings]

[0029] [Figure 1] 1 illustrates a multi-modal imaging system according to an exemplary embodiment of the present disclosure.

[0030] [Diagram 2] 1 illustrates a more detailed multi-modal imaging system according to an exemplary embodiment of the present disclosure.

[0031] [Diagram 3] 1 illustrates an electro-optical rotary junction with fixed and rotating elements for multi-modal imaging, according to an exemplary embodiment of the present disclosure.

[0032] [Figure 4] 1 shows a multi-modal imaging probe with a focusing ball lens, an angle-polished reflective surface terminating one waveguide, and an angle-polished reflective surface terminating another waveguide in accordance with an exemplary embodiment of the present disclosure.

[0033] [Figure 5A] 1 shows a multi-modal imaging probe with a focusing ball lens, an angle-polished reflective surface terminating one waveguide, and an angle-polished reflective surface terminating another waveguide in accordance with an exemplary embodiment of the present disclosure.

[0034] [Figure 5B] 1 shows a multi-modal imaging probe with a focusing grin lens, an angle-polished reflective surface terminating one waveguide, and an angle-polished reflective surface terminating another waveguide in accordance with an exemplary embodiment of the present disclosure.

[0035] [Figure 5C] In accordance with an exemplary embodiment of the present disclosure, a multimodal imaging probe is shown with a physically disconnected unit including a reflective surface and a focusing unit positioned in the optical path of one waveguide with an angle-polished reflective surface terminating another waveguide.

[0036] [Figure 5D] According to an exemplary embodiment of the present disclosure, a multimodal imaging probe is shown with physically disconnected units including reflective surfaces as well as a focusing unit positioned in the optical path of one waveguide and a reflective surface for another waveguide.

[0037] [Figure 5E]In accordance with an exemplary embodiment of the present disclosure, a multimodal imaging probe with physically disconnected units is shown that includes curved reflective surfaces for both reflection and focusing in one waveguide optical path, as well as a reflective surface in another waveguide.

[0038] [Figure 6A] 1 shows a cross-sectional view of a multi-modal imaging probe with two waveguides having overlapping beam centerlines circumferentially, but not longitudinally, only in the probe axis, in accordance with an exemplary embodiment of the present disclosure.

[0039] [Figure 6B] 1 shows a cross-sectional view of a multi-modal imaging probe with two waveguides having non-circumferentially overlapping beam centerlines only in the probe axis according to an exemplary embodiment of the present disclosure.

[0040] [Figure 6C] 1 shows a cross-sectional view of a multi-modal imaging probe with two waveguides whose beam centerlines point along the same radial direction but do not overlap, according to an exemplary embodiment of the present disclosure.

[0041] [Figure 6D] 1 shows a cross-sectional view of a multi-modal imaging probe with three waveguides, two with beam centerlines along the same radial direction and one that does not, in accordance with an exemplary embodiment of the present disclosure.

[0042] [Figure 6E] 1 shows a cross section of a multimodal imaging probe with seven waveguides, where the centerline of the illumination beam overlaps with only one of the centerlines of the other waveguide beams, according to an exemplary embodiment of the present disclosure.

[0043] [Figure 7] 1A-B show ray tracing software simulations of light propagation in a conventional probe design and a probe design according to an exemplary embodiment of the present disclosure.

[0044] [Figure 8] 1A-D show Monte Carlo simulations of photon propagation to evaluate the normalized absorption and scattering sensitivities of a conventional probe design and a probe design according to an exemplary embodiment of the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0045] definition In order to make the present disclosure easier to understand, certain terms used herein are defined below. Further definitions for the following terms and other terms may be set forth throughout the specification. In this application, unless otherwise clear from the context or otherwise specified, (i) the term "a" may be understood to mean "at least one", (ii) the term "or" may be understood to mean "and / or", (iii) the terms "comprising" and "including" may be understood to include the listed components or steps, whether presented alone or with one or more additional components or steps, (iv) the terms "about" and "approximately" may be understood to allow for standard deviations that would be understood by one of ordinary skill in the art, and (v) when ranges are given, the endpoints are included. Any numbers used in this application, with or without about / approximately, are intended to cover any normal variations that would be understood by one of ordinary skill in the art. In certain embodiments, the terms "approximately" or "about" refer to a range of values ​​that is within 25%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, or less in either direction (greater or less than) the stated reference value, unless otherwise specified or apparent from the context (except when such number would exceed 100% of possible values).

[0046] "Probe." As used herein, a "probe" refers to a device for transmitting information (e.g., a signal, e.g., electromagnetic radiation) from a proximal end (e.g., an operator end) and a distal end (e.g., a sample end). As used herein, a "longitudinal" direction refers to a direction along the longitudinal axis of the probe, an "azimuthal" or "circumferential" direction refers to a direction along the circumference of a probe, waveguide, or other essentially cylindrical structure, and a "radial" direction refers to a direction along the radius of a probe, waveguide, or other essentially cylindrical structure.

[0047] "Light Source." As used herein, a "light source" refers to a source that emits (e.g., emits) light. Light is electromagnetic radiation (EMR) (e.g., photons). As used herein, the frequency (wavelength) of the light may or may not be within the visible spectrum. The light source may emit one or more of visible light, near infrared light, infrared light, long wavelength infrared light, ultraviolet light, deep ultraviolet light, and extreme ultraviolet light. In some embodiments, the light source may emit terahertz radiation. The light source may emit x-rays, microwaves, or radio waves. The light source may be, but is not necessarily, a laser. The light source may be, for example, a source including a light source with reduced temporal coherence, for example, a light emitting diode (LED) or a superluminescent diode (SLD). The light source may be a swept source, a tunable source, or a narrowband source. In some embodiments, the light source is a swept source laser. In some embodiments, the light source is a broadband source.

[0048] "Image." As used herein, the term "image" includes any visual representation, e.g., a photograph, a video frame, streaming video, and any electronic, digital, or mathematical analog of a photograph, video frame, or streaming video, as in the case of, for example, a two-dimensional or three-dimensional image of a tissue (or other sample). Any system or device described herein, in some embodiments, includes a display for displaying an image or any other result generated by the processor. Any method described herein, in some embodiments, includes a step of displaying an image or any other result generated by the method. Any system or device described herein, in some embodiments, outputs the image to a remote receiving device (e.g., a cloud server, a remote monitor, or a hospital information system (e.g., a Picture Archiving and Communication System (PACS))). In some embodiments, the image is generated using a fluorescent imaging system, a spectroscopic imaging system, a fluorescent imaging system, and / or a reflectance imaging system. In some embodiments, the tomographic image and the spectroscopic image are co-registered to form a composite image. In some embodiments, the image is a two-dimensional (2D) image. In some embodiments, the image is a three-dimensional (3D) image. In some embodiments, the image is a reconstructed image. An image (e.g., a 3D image) may be a single image or a set of images. One or more images may be formed by an imaging technique (e.g., using light provided by a light source).

[0049] "Sample." As used herein, a "sample" refers to a substance to be characterized. Generally, any material, mixture, or substance that can be characterized by light can be used as a sample. A sample may include one or more materials. A sample may be a gas, a fluid, or a solid. A sample may be, for example, a gel (e.g., a hydrogel), an elastomer, or a composite material. A sample may be a biological sample. For example, a sample may be an organ or biological structure (e.g., tissue) or a portion thereof. A sample may be an in vivo organ or an in vivo tissue. For example, a sample may be an in vivo artery or a portion thereof. A sample may include one or more features of interest. For example, a feature of interest may be, for example, arterial plaque (e.g., vulnerable plaque, e.g., having a fibrous cap).

[0050] "Spectroscopy." As used herein, "spectroscopy" refers to any form of characterization of a sample with a light source of a particular range of wavelengths. The light source may have a narrowband (e.g., less than 2 nm) wavelength range (e.g., 1210.01-1210.02 nm, e.g., 1210 nm-1212 nm), a broadband wavelength range (e.g., 1160 nm-1280 nm), or two or more non-contiguous bands of wavelengths (e.g., 1205 nm-1215 nm and 1260 nm-1360 nm). For example, "visible spectroscopy" may refer to characterizing (e.g., imaging) a sample at visible wavelengths (e.g., 550 nm). As another example, "near-infrared spectroscopy / NIRS" may refer to characterizing (e.g., imaging) a sample at NIRS wavelengths (e.g., 1210 nm). In some embodiments, an image may be generated by scanning any light source over any area of ​​the sample, and this process may still be referred to as spectroscopy. This is because the image relates to the absorption and scattering properties of the sample in a particular wavelength range.

[0051] "Optical" is not limited to referring to visible light. For example, an optical channel may be constructed to transmit light having a frequency (wavelength) outside the visible spectrum, such as infrared or ultraviolet light. Similarly, "light detection," "optical modalities," and other similar terms may utilize light (electromagnetic radiation) outside the visible spectrum, such as infrared or ultraviolet light. Two components that are "optically connected" may be directly optically connected or may have one or more additional optical components (e.g., waveguide(s), lens(es), beam splitter(s), multiplexer(s)) and / or free space disposed between them along the optical path.

[0052] "Specular reflection." As used herein, specular reflection refers to a mirror-like reflection, i.e., light reflected from the surface of a sample at the same angle as the incident light, but on the opposite side of the plane perpendicular to the surface. In a real optical characterization system, the incident light may be a perfectly collimated beam, a focused beam, or a beam with finite beam divergence. Thus, in real cases, specular reflection refers to the axis of the beam.

[0053] "Diffuse Reflection." As used herein, diffuse reflection refers to light that emerges in many directions from the surface of a sample after being scattered. Most surfaces exhibit a combination of diffuse and specular reflection.

[0054] Intraluminal characterization generally involves rapidly rotating a probe to image the inner circumference of an internal object, as is done in a typical catheter-based intravascular characterization system. Such characterization probes typically consist of optical waveguides that transmit light between an optical system and the sample.

[0055] Characterization probes can be designed to optimize a single characterization modality or multiple characterization modalities. For example, a characterization probe may be designed to evaluate structural properties of a sample (e.g., by imaging with OCT). A characterization probe may be designed to evaluate molecular properties of a sample (e.g., by performing spectroscopy using NIRS). A characterization probe may be designed to evaluate multiple properties of a sample using multiple characterization modalities (e.g., OCT imaging and NIRS). Such probes require careful optimization to provide high sensitivity and fidelity characterization in both modalities.

[0056] Interferometric imaging, such as OCT, is best performed using focused light. Diffuse spectroscopy, on the other hand, can be optimized in various ways. For example, optimization may include optical arrangements that favor detection of light that has interacted with subsurface molecules (e.g., diffuse reflection) rather than light that has only interacted with the surface (e.g., specular reflection). Another optimization may include optical arrangements that favor sensing of deep tissues (e.g., by controlling the distance from the source to the detector). Another optimization may include whether to use focused illumination or detection based on signal collection efficiency. Finally, in the context of intracavity characterization in a medical setting, all these optimizations must be performed under significant constraints on the probe design (e.g., size, robustness, manufacturability, cost, etc.).

[0057] The present disclosure provides, among other things, optimal optical arrangements for performing imaging and spectroscopy. For example, certain embodiments minimize loss of performance in structural imaging and achieve state-of-the-art interferometer sensitivity (e.g., greater than 90 dB, greater than 100 dB, or greater than 110 dB) while maximizing the collection ratio of desired (e.g., diffuse) and undesired (e.g., specular) signals for spectroscopy. Additionally, certain embodiments maximize manufacturability by reducing the complex optics of the probe, minimizing the cost of goods for the probe. Additionally, certain embodiments of the present disclosure allow for optimization (e.g., minimization) of the size of the probe.

[0058] Previous spectroscopic probe designs have placed focusing optics at the end of each waveguide to optimize source-detector separation. This design is costly since the focusing optics are an expensive part of the final probe design. Additionally, focusing optics on the collection fiber narrow the field of view of the fiber, reducing collection efficiency. In some embodiments, focusing optics are placed only in the light path of the illumination waveguide. Additionally, it was believed that the optimal orientation of the illumination and detection waveguides is designed such that the distal port of the collection fiber is located more distal than the distal port of the illumination fiber. In some embodiments, the illumination waveguide is oriented such that the illumination beam hits the sample more distal than the collection beam, and the central axes of both beams are angled between the sample and the distal end of the probe. This orientation significantly reduces specular reflections (e.g., reflections from the sample or sheath) detected by the collection fiber, allowing for maximum light collection.

[0059] In some embodiments, the multimodal probe may be used in combination with a multimodal characterization system (e.g., an OCT / NIRS characterization system). In some embodiments, the multimodal characterization system may be used for intraluminal characterization (e.g., coronary artery characterization). In some embodiments, the multimodal probe may be a catheter, e.g., a cardiac catheter that can be used to rapidly characterize a patient's lumen (e.g., an artery) in a multimodal manner. In some embodiments, the catheter may be air-filled. For example, the interior volume of the catheter's sheath and / or the volume between the sheath and the body cavity may be substantially devoid of any fluid. For example, an air-filled catheter may be configured such that there is no intervening fluid (e.g., blood or saline) in the optical path of the catheter (e.g., between the optics in the probe and the body cavity) during characterization of the body cavity. In some embodiments, optimizations achieved may be specific to the air-filled catheter (e.g., to reduce specular reflections, e.g., to optimize overlap of the illumination and collection beams, e.g., to optimize the signal of each optical modality). In some embodiments, the catheter may be filled with fluid (e.g., a flushing fluid (e.g., saline) or blood). In some embodiments, the probe may be filled with air. For example, an air-filled probe may be configured such that there is no intervening fluid (e.g., blood or saline) in the optical path of the probe (e.g., between the optics in the probe and the body cavity) during characterization of the body cavity.

[0060] 1 shows an exemplary embodiment of a multimodal characterization system for coronary artery imaging. The multimodal characterization system includes a console 100, a physician monitor 102, a technician monitor 104, and a tray 106. Connected to the system is a catheter interface unit 110 that interfaces with the console via an electrical-optical transmission cable 108 and a patient interface catheter 112.

[0061] 2 shows a block diagram of an exemplary embodiment of a multimodal characterization system. The multimodal system / apparatus includes a stationary optical unit 200. The stationary optical unit 200 may include one or more of an OCT light source 202, a spectroscopic light source 204, a beam splitter 206 forming a reference channel, a beam combiner (e.g., WDM) 208 combining the two light sources, a spectroscopic reference detector 210 for detecting a reference measurement, an interferometer 212, an OCT detector 214, a computing device 216, and a transceiver device 218. The stationary optical unit 200 may function in optical connection with a rotating optical unit 222 via a single channel fiber optic rotary junction (FORJ). The rotating optical unit 220 may include, for example, one or more of a rotating device housing 224, an illumination / collection optical channel (e.g., at least one tandem single mode fiber) 226, a collection optical channel (e.g., at least one tandem multimode fiber) 228, and a collection photodetector 230. The optical channel extending to the sample may be covered by a transparent sheath 232 for protection and safety considerations. The sheath 232 may remain stationary during operation, as in the case of, for example, an intravascular characterization catheter. The collection-detector device 230 may include a spectroscopic detector 234, as well as a conditioning circuit 236 (e.g., to improve the SNR of the detection signal), and a transmitter 238 (e.g., a slip ring, an RF transmitter, or an optical transmitter). The transmitter 238 may be a transceiver. In some embodiments, the collection optical detector may be located in the fixed optical unit, for example, by placing a dual-channel FORJ or a rotatable combiner. In some embodiments, the collection optical detector is located in the fixed optical unit in combination with a rotatable combiner located in the rotating optical unit. The rotatable combiner may combine the electromagnetic radiation (e.g., the illumination optical channel and the second waveguide to the third waveguide) for transmission through the double-clad FORJ.An example of such an arrangement is described in International (PCT) Patent Application No. PCT / US2014 / 013330, filed January 28, 2014, the disclosure of which is incorporated herein by reference in its entirety.

[0062] 3 is a cross-sectional view illustrating an exemplary embodiment for a rotation unit that enables high fidelity, high speed, multimodal rotational characterization. The rotation unit 300 may include a rotation device housing 310 for housing the FORJ 308 (e.g., a portion thereof), an interconnect 312, a circuit board 314, an illumination optical channel 316, a collection optical channel 318 that terminates on a light detection device 320 (e.g., a photodetector, optionally including optics), and a multi-optical channel probe 322 for transmitting and receiving light from the sample. The stationary unit may be operatively optically connected to the rotation unit 300 via a stationary optical fiber 302 that is operatively connected to the FORJ 308. To transmit torque to the rotation unit 300, a motor 304 that remains stationary relative to the rotation unit may be used to drive a drive belt 306. In some embodiments, a direct drive motor may be arranged without a drive belt. Inside the rotating device housing 310 there may be a wireless transmitter 324 (e.g., a radio transceiver) connected to a circuit board 314 to transmit data and / or receive information from the rotating unit to a wireless RF transceiver 326 on the stationary unit. At least a portion of the rotating unit may be mounted to a linear translation stage 328 to allow for back and forth translational motion. A probe housing 330 may be designed to house the optical probe 322 and function in conjunction with a stationary housing 332 for the rotating device, e.g., to remain rotationally stationary while the internal optical probe 322 is rotated and translated as part of the rotating unit 300. The illustrated housings and devices may be round (e.g., circular) or rectangular, for example.

[0063] In some embodiments of the present disclosure, a multimodal probe may include at least two optical waveguides. In some embodiments, the waveguides are disposed within a torque transfer coil that is used to circumferentially rotate the distal probe optics (e.g., to image the interior of a body cavity (e.g., an artery)). In some embodiments, a single waveguide may be used for illumination and detection of a first modality, while another waveguide, either the same or physically separate, may be used for detection of another modality. In some embodiments, any number of waveguides (e.g., three waveguides) may be disposed within the torque transfer coil of the probe. In some embodiments, multiple waveguides may be used for illumination (e.g., to provide illumination for different modalities), while two or more waveguides may be used for detection (e.g., one for at least one of the modalities). In some embodiments, a single waveguide may perform illumination, while two or more waveguides are used for detection (e.g., to detect scattered light from different locations or depths). In some embodiments, a single waveguide may perform illumination while the same and another waveguide may detect backscattered light in a different mode (e.g., optical mode). In some embodiments, a multimode fiber may be used to transmit and / or receive multimode light (e.g., for reflected intensity measurements (e.g., wavelength-dependent intensity measurements)). In some embodiments, a single mode fiber may be used to transmit and / or receive light (e.g., for interferometric measurements). In some embodiments, a dual-clad optical fiber may be used to transmit and / or receive both single mode and multimode light.

[0064] The multi-modality probe should have a proximal end and a distal end, the distal end being optically connected to the sample. In some embodiments, the distal port of the waveguide (e.g., where light is optically transmitted to the sample) is offset longitudinally or circumferentially from another waveguide to optimize the separation distance from the source to the detector for diffuse spectroscopy (e.g., NIRS). In some embodiments, the waveguide has distal focusing optics in its optical path to focus the light to optimize the resolution for the characterization modality (e.g., OCT). In some embodiments, the focusing optics is a ball lens (e.g., fused to the waveguide during manufacture). In some embodiments, the focusing optics is a gradient index (GRIN) lens (e.g., GRIN fiber). In some embodiments, the focusing optics is physically connected (e.g., bonded or fused) to the waveguide. In some embodiments, the focusing optics is part of an injection molded part, a 3D printed part, or a machined part. In some embodiments, the focusing optics is a curved surface (e.g., a curved reflector). In some embodiments, the focusing optic can be a metalens. In some embodiments, aberration correcting optics are disposed within the optical path of the waveguide. In some embodiments, the focusing optic is shaped (e.g., formed) to correct for aberrations. In some embodiments, the focusing optic is part of a larger unit that is physically connected with other optics or components (e.g., a beam redirector).

[0065] The probe is typically inserted into the cavity and rotated along its axis to characterize the inner wall of the cavity approximately parallel to the probe. Thus, in some embodiments, a waveguide in the probe is provided with a beam redirector (e.g., a mirror) in its optical path to direct the beam into the cavity. In some embodiments, the beam is redirected approximately perpendicular (e.g., 90 degrees) to the waveguide. In some embodiments, the beam redirector can redirect the beam anywhere between 90 degrees and 45 degrees (e.g., 75 degrees) from the axis of the probe (e.g., to reduce specular reflection). In some embodiments, the redirection of the beam can be achieved by total internal reflection (e.g., an angled glass surface in air). In some embodiments, the beam redirector is an angled waveguide (e.g., an angle-polished waveguide, e.g., an angle-polished optical fiber). In some embodiments, the beam redirector is a reflective surface (e.g., a mirror). In some embodiments, the collection waveguide lacks distal focusing optics and includes only a beam redirector, such as to maximize collected light for a characterization modality (e.g., fluorescence). In some embodiments, the source-to-detector offset between the illumination and collection waveguides is sufficient to optimize collection of diffusely reflected light (e.g., compared to specularly reflected light). In some embodiments, the collection waveguide is positioned longitudinally offset from the illumination waveguide.

[0066] In some embodiments, the illumination and collection beams impinge on the sample in the same circumferential direction (e.g., the centers of the beams may overlap circumferentially). In some embodiments, a first beam may be directed in a first circumferential direction, while a beam in another waveguide may be directed in another circumferential direction (e.g., directed at the same longitudinal position). Offsetting the two waveguide beams circumferentially or longitudinally helps control the source-detector separation, which is important for optimizing the collection of diffuse light (e.g., for diffuse reflectance spectroscopy (DRS)). In some embodiments, the waveguide may be positioned at the center of the probe or off-center while still being positioned in the torque transmission coil. In some embodiments, two waveguides may be positioned in the torque coil, with the first waveguide positioned "in front" of the second waveguide relative to the "line of sight" direction of the beam in the second waveguide (e.g., the second waveguide offset distally from the first waveguide). In some embodiments, the waveguides may be positioned side-by-side to view the sample at the same circumferential angle. In some embodiments, a first waveguide may be used to transmit light at a first location in the lumen, while a second waveguide may detect light at a second location, and a third waveguide may detect light at a third location (e.g., to measure a depth-dependent attribute of the sample). In some embodiments, any combination of multiple waveguides may be arranged such that the beams are positioned or directed at different locations on the lumen wall (e.g., to measure various sample depths or locations). In some embodiments, the beam divergence of the waveguide (e.g., multiple waveguides) may be engineered (e.g., by controlling the numerical aperture of the waveguide) to increase or decrease the overlap of the beams from each waveguide inside the probe. In some embodiments, the angle of incidence of the beams on a particular waveguide (e.g., multiple waveguides) may be engineered (e.g., by adjusting the polish angle of the waveguide at the glass-air interface) to increase or decrease the overlap of the beams from each waveguide inside the probe. In some embodiments, a distal opening may be located (eg, in the protective case) to affect illumination of the profile.In some embodiments, the distal aperture may be positioned to affect detection (eg, to reduce specular reflections, eg, to further separate the illumination and detection regions).

[0067] 4 is a cross-sectional view of a multimodal probe according to an exemplary embodiment of the present disclosure. A torque transfer coil 400 houses two optical waveguides: a first waveguide 402 for transmitting and detecting a first modality, and a second waveguide 404 for detecting a second modality. The first waveguide is fused to a ball lens focusing optic 406 to impart focusing power and is polished at a controlled angle 408 to optimize the beam central axis position 410 and the beam central axis angle from the longitudinal axis (e.g., perpendicular to the longitudinal axis) 412 of the probe. The focusing power of the beam of the first waveguide can be further designed and optimized by changing the polishing curvature of the angle polished surface or by changing the curvature of the ball lens (e.g., either longitudinal and / or circumferential). The second waveguide does not have focusing optics, but is polished at a controlled angle 414 to optimize the position of the beam central axis 416 and the angle of the beam central axis from the longitudinal axis of the probe (e.g., perpendicular to the longitudinal axis) 418. The acceptance angle 420 of the second waveguide can be further designed and optimized by changing the numerical aperture of the fiber or by changing the curvature of the angle polish. The distance 422 from the distal port of the first waveguide to the distal port of the second waveguide can be designed or optimized.

[0068] 5A is a cross-sectional view of a multimodal probe according to an exemplary embodiment of the present disclosure. A torque transfer coil 500 houses multiple optical waveguides. A first waveguide 510 includes fused ball lens focusing optics for transmitting and detecting a first modality, and multiple waveguide groups 504 for detecting at least a second modality, each optically coupled (e.g., physically coupled) to a beam redirecting prism 506. The probe is covered with a protective sheath 508 that is transparent to the modalities.

[0069] 5B is a cross-sectional view of a multimodal probe according to an exemplary embodiment of the present disclosure. A torque transfer coil 500 houses multiple optical waveguides. A first waveguide 510 includes angled optics 512 (e.g., cut or polished) for transmitting and detecting the first modality, and a group of collection waveguides 514 for detection (e.g., of the second modality) that are angle cut or polished for beam redirection 506. The collection waveguides are offset longitudinally to allow optimization for different source and detector separations. The probe is covered by a protective sheath 508 that is transparent to the modalities.

[0070] 5C is a cross-sectional view of a multimodal probe according to an exemplary embodiment of the present disclosure. A torque transfer coil 500 houses multiple optical waveguides. A first waveguide 516 is in optical communication with a first focusing optic (e.g., lens) 520 and a second beam redirector 522 (e.g., mirror, dielectric mirror) disposed on a substrate 518 and arranged in cooperation to transmit and detect at least a first modality. There is a second waveguide 514 for transmitting at least a second modality, angle cut or polished for beam redirection. The probe is covered with a protective sheath 508 that is transparent to the modalities.

[0071] 5D is a cross-sectional view of a multimodal probe according to an exemplary embodiment of the present disclosure. A torque transfer coil 500 houses multiple optical waveguides. A first waveguide 524 is in optical communication with a first beam redirector 526 (e.g., mirror, dielectric mirror) and a first focusing optic 528 (e.g., lens). A second waveguide 530 is in optical communication with a second beam redirector 532, where the first beam redirector, the second beam redirector, and the first focusing optic are disposed on a substrate 534. The probe is covered with a protective sheath 508 that is transparent to the modality.

[0072] FIG. 5E is a cross-sectional view of a multimodal probe according to an exemplary embodiment of the present disclosure. A torque transfer coil 500 houses multiple optical waveguides. A first waveguide 524 is in optical communication with a first beam redirector 526 (e.g., a 3D printed surface, e.g., a molded surface) and a first curved focusing optic 528 (e.g., a 3D printed curved surface, e.g., a molded surface) (e.g., a one-piece printed or molded component). A second waveguide 530 is in optical communication with a second beam redirector 532 (e.g., a 3D printed surface, e.g., a molded surface), and the first beam redirector, the second beam redirector, and the first focusing optic are disposed on a substrate 534 (e.g., a 3D printed substrate, e.g., a molded substrate). The probe is covered with a protective sheath that is transparent to the modality 508.

[0073] 6A is a cross-sectional view of a multimodal probe according to an exemplary embodiment of the present disclosure, in which the beam axes of a first (colored) (e.g., illumination and detection waveguides) and a second (empty) (e.g., detection waveguide) are overlapped in a circumferential direction. The filled arrow indicates the first waveguide beam axis (e.g., field of view axis) in the circumferential direction, and the unfilled, dashed-peripheral arrow indicates the second beam axis (e.g., field of view axis) in the circumferential direction. In this orientation, the beam axis of the first waveguide is distal to the beam axis of the second waveguide.

[0074] 6B is a cross-sectional view of a multimodal probe according to an exemplary embodiment of the present disclosure, in which the beam axes of a first waveguide (colored) (e.g., illumination and detection waveguides) and a second waveguide (empty) (e.g., detection waveguide) do not overlap in the circumferential direction. The filled arrow indicates the first waveguide beam axis (e.g., field of view axis) in the circumferential direction, and the unfilled, dashed perimeter arrow indicates the second beam axis (e.g., field of view axis) in the circumferential direction. In this orientation, the beam axis of the first waveguide is distal to the beam axis of the second waveguide.

[0075] 6C is a cross-sectional view of a multimodal probe according to an exemplary embodiment of the present disclosure, in which the beam axes of a first waveguide (colored) (e.g., illumination and detection waveguides) and a second waveguide (empty) (e.g., detection waveguide) do not overlap in the circumferential direction. The filled arrow indicates the first waveguide beam axis (e.g., field of view axis) in the circumferential direction, and the unfilled, dashed perimeter arrow indicates the second beam axis (e.g., field of view axis) in the circumferential direction. In this orientation, the beam axis of the first waveguide is distal to the beam axis of the second waveguide.

[0076] FIG. 6D is a cross-sectional view of a multimodal probe according to an exemplary embodiment of the present disclosure, showing a first waveguide (colored) (e.g., illumination and detection waveguides), a second waveguide (empty) (e.g., detection waveguide), and a third waveguide (shaded) (e.g., illumination or detection waveguide), where the second and third waveguides are at different source-to-detector distances from the first waveguide (e.g., to identify depth-dependent optical properties). The filled arrow indicates the first waveguide beam axis (e.g., field of view axis) in the circumferential direction, and the unfilled, dotted-periphery arrow indicates the second beam axis (e.g., field of view axis) in the circumferential direction. In this orientation, the beam axis of the first waveguide is more distal than the beam axis of the second waveguide.

[0077] FIG. 6E is a cross-sectional view of a multimodal probe according to an exemplary embodiment of the present disclosure, in which the beam axes of the first waveguides (colored) (e.g., illumination and detection waveguides) and the secondary waveguides (empty) do not overlap circumferentially. The secondary waveguides are arranged around the first waveguide inside the torque transfer coil. The distance from the light source to the detector can be controlled between each secondary waveguide and the first waveguide to display different regions (e.g., to identify depth-dependent optical properties). The filled arrows indicate the circumferential first waveguide beam axis (e.g., field of view axis) and the unfilled, dotted perimeter arrows indicate the circumferential beam axis (e.g., field of view axis) of each of the detection waveguides. In this orientation, the beam axis of the first waveguide is distal to the beam axis of the second waveguide.

[0078] Figure 7A shows a ray tracing software simulation of light propagation in a previous probe design, and Figure 7B shows a probe design according to an exemplary embodiment of the present disclosure.

[0079] 8A-8D show Monte Carlo simulations of photon propagation to evaluate the normalized absorption and scattering sensitivity of a conventional probe design as well as a probe design according to an exemplary embodiment of the present disclosure. FIGS. 8A-8B show that both designs can achieve similar performance in sensitivity for various optical properties (absorption and scattering) relevant to biological tissue. FIGS. 8C-8D show that when scattering is normalized, the design without focusing optics on the detection fiber has an improved relative sensitivity to absorption compared to the design with focusing optics on the detection fiber. The overall light collection and absorption sensitivity are important to optimize a spectroscopic device. As shown, the design in this exemplary embodiment of the present disclosure increases the detectable light as well as the sensitivity to absorption from the sample.

[0080] In some embodiments, a protective case (e.g., a metal can) is disposed near the distal end of the probe (e.g., to protect the distal optics or the waveguide). In some embodiments, the distal optics of the probe are positioned to allow light to pass through a window inside the protective case (e.g., the protective case). In some embodiments, the protective case includes a radiopaque material (e.g., a radiopaque can). In some embodiments, a radiopaque marker is disposed on the can (e.g., near the distal end of the can).

[0081] It is contemplated that the systems, devices, methods, and processes of the present disclosure encompass variations and modifications developed using information from the embodiments described herein. Modifications and / or variations of the systems, devices, methods, and processes described herein may be made by those skilled in the art.

[0082] Throughout the description, when articles, devices, and systems are described as having, including, or comprising particular components, or processes and methods are described as having, including, or comprising particular steps, it is believed that in addition there are articles, devices, and systems according to particular embodiments of the disclosure that consist essentially of or consist of the recited components, and there are processes and methods according to particular embodiments of the disclosure that consist essentially of or consist of the recited processing steps.

[0083] It should be understood that the order of steps or the order for performing certain actions is not important so long as operability is not lost. Additionally, two or more steps or actions may be performed simultaneously. As will be appreciated by those skilled in the art, the terms "on," "under," "up," "down," "below," and "on" are relative terms and may be interchanged to refer to different orientations of layers, elements, and substrates included in the present disclosure. For example, in some embodiments, a first layer of a second layer means that the first layer is directly on and in contact with the second layer. In other embodiments, the first layer of a second layer may include another layer therebetween.

[0084] Specific embodiments of the present disclosure have been described above. However, it should be specifically noted that the present disclosure is not limited to these embodiments, but rather additions and modifications to those explicitly described in the present disclosure are also intended to be included within the scope of the present disclosure. Furthermore, it should be understood that the features of the various embodiments described in the present disclosure are not mutually exclusive and may exist in various combinations and permutations, which may be possible without departing from the spirit and scope of the present disclosure even if such combinations or permutations are not expressed. Although the present disclosure has been described in detail with particular reference to specific embodiments thereof, it will be understood that variations and modifications may occur within the spirit and scope of the invention as claimed.

Claims

1. 1. A probe for characterizing a body cavity, comprising: a first waveguide and a second waveguide, each extending to a distal end of the probe; a first beam redirector and focusing optics disposed in the optical path of the first waveguide, the first beam transmitted by the first waveguide being capable of being focused toward a wall of the lumen; a second beam redirector disposed in the optical path of the second waveguide, such that a second beam transmitted by the second waveguide can be directed toward the wall; The probe, wherein the first beam redirector, the focusing optics, and the second beam redirector, when provided in the lumen, are positioned so that the center of the first beam points to a position on the wall more distal than the center of the second beam.

2. 10. The probe of claim 1, wherein the first waveguide is configured to detect signals of a first characterization modality and the second waveguide is configured for a second characterization modality, the first characterization modality being an interferometric imaging modality.

3. The probe of claim 1 , wherein the first beam redirector is positioned more distally than the second beam redirector.

4. The probe of claim 1 , wherein no focusing optics are disposed in the optical path between the second waveguide and the wall of the lumen.

5. The probe of claim 1 , wherein the first and second waveguides are disposed within a torque transmission coil.

6. 2. The probe of claim 1, wherein the first beam redirector and the focusing optics are physically connected to the first waveguide and the second beam redirector is physically connected to the second waveguide.

7. The probe of claim 1 , wherein the first beam redirector or the second beam redirector is an angled optical fiber.

8. The probe of claim 1 , wherein the focusing optic is a ball lens.

9. The probe of claim 1 , wherein the focusing optic is a gradient index lens.

10. The probe of claim 1 , wherein the first beam redirector and the focusing optic are each curved mirror surfaces.

11. The probe of claim 1 , wherein an injection molded portion includes the first beam redirector, the second beam redirector, and the focusing optics.

12. The probe of claim 1 , wherein a 3D printed portion comprises the first beam redirector, the second beam redirector, and the focusing optics.

13. The probe of claim 1 , further comprising a spectroscopic modality subsystem optically connected to the second waveguide for detecting light received via the second waveguide.

14. The probe of claim 1 , wherein the second waveguide is optically connected to a light source for illuminating the sample.

15. The probe of claim 1 , comprising a characterization modality subsystem optically connected to the first waveguide such that a reflected intensity is detected by the first waveguide.

16. The probe of claim 1 , wherein the second waveguide is not associated with any focusing optics at the distal end of the probe.

17. The probe of claim 1 , further comprising an interferometric modality subsystem optically connected to the first waveguide.

18. The probe of claim 1 , further comprising an intensity modality subsystem optically connected to the second waveguide.

19. 2. The probe of claim 1, wherein the first redirector, the focusing optics, and the second redirector are arranged such that the beam from the first waveguide and the beam from the second waveguide do not overlap circumferentially.

20. The probe of claim 1 , wherein the probe is in optical communication with a rotatable combiner.