Guide wire sensing device

Abstract

A sensing device for sensing within a blood vessel of a biological subject, the sensing device including a guidewire configured to be positioned within a blood vessel of a biological subject, the guidewire including a circumferential window positioned proximate a distal end, an optical fiber extending substantially from the proximal end of the guidewire to a position proximate the window, and a substantially conical reflector positioned proximate the window and aligned with the axis of the optical fiber, the conical reflector configured to reflect stimulation radiation emitted from the optical fiber so that the stimulation radiation passes substantially radially through the window, thereby exposing the blood vessel to the stimulation radiation, and to reflect sample radiation emitted from within the blood vessel to transmit the sample radiation to the optical fiber.

Description

Technical Field

[0001] The present invention relates to a sensing device and related methods for performing sensing in the blood vessels of a biological subject. In one detailed embodiment, it relates to a sensing device and an accompanying method that use a guide wire to perform sensing within a blood vessel, for example, to detect vulnerable atherosclerotic plaques.

Background Art

[0002] Any reference herein to any prior published document (or information derived therefrom), or to any known matter, is not to be taken as an admission, or any form of suggestion, that such prior published document (or information derived therefrom) or known matter forms part of the common general knowledge in the relevant field of endeavour of this specification, and it is desirable that it is not.

[0003] Atherosclerosis is currently a major cause of mortality and morbidity worldwide. Atherosclerotic plaques can affect various arteries in various parts of the body, leading to a number of clinical presentations. These lesions can be asymptomatic for years, can present with stable symptoms such as exertional angina, or can suddenly lead to life-threatening complications such as myocardial infarction or stroke.

[0004] Fatty plaques, composed of foam cells (lipid-filled macrophages), are the earliest lesions of atherosclerosis. These fatty plaques are harmless and completely reversible. Only a portion of them progress to more advanced stages of atherosclerosis. Further advanced plaques become irreversible and contain varying proportions of cells (including smooth muscle cells, macrophages, and T cells), extracellular matrix (including collagen, elastin, and proteoglycans), and lipids (intracellular and extracellular). Various morphological types of plaques appear depending on their composition. Some are fibrous plaques consisting of fibrous tissue and calcification without lipid-rich nuclei, while others are fibrous atheromas covered by a fibrous capsule and containing lipid-rich nuclei.

[0005] Atherosclerosis is broadly considered an inflammatory disease. Inflammatory cells play a crucial role not only in the pathogenesis of atherosclerosis progression but also in its destabilization (inflammatory cytokines and proteolytic enzymes cause the destruction of the fibrous membrane, leading to atherosclerotic rupture and complications).

[0006] The development of atherosclerotic plaques is highly diverse. Some plaques remain dormant for many years, while others develop into complex plaques that lead to rupture or erosion. Complex plaques can cause thrombosis and arterial occlusion, potentially leading to catastrophic consequences. Plaque rupture is the most common cause of coronary thrombosis.

[0007] Atherosclerotic plaques that progress rapidly and are prone to thrombosis or rupture, generally known as fragile plaques, are called "high-risk / fragile plaques." Thin-capsulated fibrous plaques (TCFAs), which are characteristic of fragile plaques, have been described as having several classic morphological features, namely a fibrous capsule <65 μm, large necrotic nuclei, increased plaque inflammation, positive vascular remodeling, increased microangiogenic neovascularization, and intraplaque hemorrhage.

[0008] However, despite extensive advances in the field of cardiovascular medicine, it remains unclear whether high-risk / vulnerable atherosclerotic plaques (plaques prone to complications) can be detected early before they rupture.

[0009] Several invasive atherosclerotic plaque imaging techniques are being developed to detect TCFA. These methods are currently far from ideal and may only detect some, if not all, of the features of fragile atherosclerotic plaques. For example, IVUS (intravascular ultrasound) can detect positive remodeling, but its resolution of 100 to 250 μm is insufficient to detect fibrous capsule thickness or inflammation of the plaque. IVUS-VH (Virtual Histology) uses the backscattered high-frequency signal from IVUS to detect the composition of the plaque, specifically necrotic nuclei. Meanwhile, high-resolution (10-15 μm) optical coherence tomography (OCT) has been proposed for detecting fibrous capsules, macrophages, and necrotic nuclei, but it is not suitable for detecting positive remodeling.

[0010] Other emerging methods include intravascular MRI (for detecting necrotic nuclei), angiography (for visualizing the surface appearance of atherosclerotic plaques), thermography (for detecting metabolic activity of atherosclerotic plaques), and spectroscopy.

[0011] Various types of spectroscopic imaging have been used to characterize and detect atherosclerotic plaques. Regarding the chemical composition of atherosclerosis, successful analysis using Raman spectroscopy and Fourier transform infrared spectroscopy (FT-IR) has been achieved in various ex vivo human atherosclerotic plaques.

[0012] Infrared reflection spectroscopy has been shown to differentiate various atherosclerotic plaque components based on their characteristic absorbance / reflectance properties, both in vivo and in vitro. InfraReDx, Inc. (Burlington, Massachusetts, USA) developed an intracoronary probe using this technology, later combining it with IVUS (LipiScan IVUS system). The SPECTACL (SPECTroscopic Assessment of Coronary Lipid) trial was the first multicenter human study demonstrating the safety and feasibility of detecting lipid nuclei-containing atherosclerotic plaque using a NIRS (Near Infra-Red Spectroscopy) system in living patients.

[0013] UV (Ultra-Violet) fluorescence spectroscopy is used as another modality for the spectroscopic evaluation of atherosclerotic plaques. Some components of plaque, such as collagen, elastin, several extracellular lipids, and ceroids / lipofuscin, have been shown to exhibit intrinsic fluorescence when excited by ultraviolet light and visible light in the violet to blue range (325 to 475 nm). However, UV fluorescence has several drawbacks, including photon absorption and considerable tissue autofluorescence, which make the detection of plaques in this manner problematic.

[0014] International Publication No. 2005 / 052558 describes a method and apparatus for classifying cancerous tissue using Raman and background fluorescence spectral features. Spectra may be acquired at near-infrared wavelengths. Principal component analysis and linear discriminant analysis of reference spectra may be used to recognize the Raman and background fluorescence spectral features of the test tissue and to obtain a classification function that indicates the likelihood of the test tissue being abnormal. This method and apparatus are applicable to the screening of skin cancer or other diseases.

[0015] U.S. Patent Publication No. 2015 / 0080686 describes a device for detecting atherosclerotic plaque. The device includes an electronic processing unit which, in response to exposure of at least a portion of an artery to radiation at a first infrared wavelength, determines the level of fluorescence sensed by a sensor at a second infrared wavelength, and uses that fluorescence level to determine a fluorescence index. The fluorescence index indicates the presence, absence, or extent of atherosclerotic plaque.

[0016] Therefore, this disclosure requires the introduction of an exogenous fluorescent agent into the artery for this method to work effectively. Furthermore, the device employed includes a catheter containing one or more optical fibers extending between its proximal and distal ends.

[0017] However, none of the above mechanisms provide a system for easily detecting fragile atherosclerotic plaques or other characteristics within blood vessels.

[0018] U.S. Patent Publication 2019 / 0059734 describes an optical coherence tomography (OCT) system comprising a sample arm, a reference arm, and an OCT probe. The probe irradiates a body cavity and the fluid contained within it with light from a sample beam transmitted through a double-clad fiber (DCF). A first detector detects the reference beam and the light reflected within the body cavity and propagating through the core of the DCF to generate an OCT interference signal. Light backscattered by the body cavity and the fluid contained within it propagates through the cladding of the DCF and is detected by a second detector to generate an intensity signal. A processor analyzes the intensity signal and triggers the retraction of the probe, initiating recording of an OCT image of the body cavity in response to the intensity of the backscattered light reaching a predetermined threshold.

[0019] Chinese Patent No. 109381167 describes a bimodal endoscope apparatus based on liquid lens self-focusing, which includes a shell set in a rotating scanning cavity, and a reflector inside the shell, and the OCE signal and fluorescence signal received by the rotating scanning cavity, excitation light and output sample reflection by single-mode optical fiber and multimode fiber respectively, are for panoramic scanning. The present invention integrates OCE and FLE technology, enabling real-time high-resolution varifocal imaging of the internal structure and function of living organisms, providing accurate and effective morphological structural information images for accurate monitoring and early detection of gastrointestinal diseases, and a quantitative optical system that simultaneously provides extremely high sensitivity and high specificity, related to two-dimensional and three-dimensional bimodal fluorescence imaging.

[0020] International Publication No. 2017 / 147845 describes a small, motor-integrated opto-acoustic integrated self-rotating endovascular imaging probe. This opto-acoustic integrated self-rotating endovascular imaging probe comprises a stainless steel tube, a light-transmitting and sound-transmitting housing housed in a sheath on the stainless steel tube, a monomode optical fiber introduced into the light-transmitting and sound-transmitting housing by the stainless steel tube, a GRIN lens positioned within the light-transmitting and sound-transmitting housing corresponding to the monomode optical fiber, an annular ultrasonic transducer housed in a sheath on the GRIN lens, and an electromagnetic motor positioned inside the light-transmitting and sound-transmitting housing. A reflective inclined surface is provided at the end of the motor rotor at the GRIN lens. The reflective inclined surface is provided with a mirrored layer with high acoustic impedance. During retraction, IVUS images are obtained, and photodetection with corresponding synchronized registration is performed simultaneously. Therefore, an integrated optical-acoustic image of the vascular wall structure and composition with synchronized registration is obtained, enabling more comprehensive and accurate intravascular imaging.

[0021] The article "An all-fiber-optic endoscopy platform for simultaneous OCT and fluorescence imaging" by Jessica Mavadia, Jiefeng Xi, Yongping Chen, and Xingde Li in Biomedical Optics Express 3(11):2851, 1 November 2012, describes an all-fiber-optic endoscopy platform for simultaneous OCT and fluorescence imaging. This design requires the use of double-clad fiber (DCF) within the endoscope to deliver the OCT source and fluorescence excitation light, while simultaneously collecting the backscattered OCT signal through a single-mode core and the fluorescence emission through the large internal cladding of the DCF. Circumferential beam scanning was performed by rotating a 45° reflector using a small DC motor at the distal end of the endoscope. In addition, by utilizing a specially designed DCF coupler and wavelength division multiplexer (WDM), both imaging modalities are seamlessly integrated, resulting in a fully fiber optic dual-modality imaging system.

[0022] "Shanshan Liang, Arya Saidi, Joe Jing and Gangjun Liu, Journal of Biomedical Optics 17(7):070501, July 2012" describes "Intravascular atherosclerotic imaging with combined fluorescence and optical coherence tomography probe based on a double-clad fiber." The combined probe describes a multimodality fluorescence and optical coherence tomography probe using a double-clad fiber (DCF) combiner. This probe consists of a DCF combiner, a grin lens, and a micromotor at the distal end. An integrated wavelength-swept light source optical coherence tomography and fluorescence intensity imaging system was developed using the combined probe for the early diagnosis of atherosclerosis. This system allows for real-time data acquisition and processing as well as image display. In fluorescence imaging, inflammation in atherosclerosis and necrotic nuclei formed with Cy5.5 bound to annexin V were imaged. The capabilities of this combined system were demonstrated by ex vivo imaging of arteries in New Zealand white rabbits.

[0023] However, all of the above methods rely on imaging within blood vessels, which in turn leads to several problems. For example, positioning the imaging device within a blood vessel to image a target point can be problematic, and it is often necessary to position the device, performing a pullback and moving the imaging device past the target feature at a constant speed to fully image it. In addition, the optical system of such devices typically needs to focus on the feature, which in turn leads to complex configurations that require rotation of the imaging device, or the focusing lens or reflector, in order to scan the imaging field and thereby image the entire feature.

[0024] U.S. Patent No. 7,328,058 describes an intravascular imaging device for detecting and characterizing early-stage unstable coronary artery atherosclerotic plaques. This detector works by identifying and locating a radiopharmaceutical that binds to the plaque and emits beta rays.

[0025] Therefore, this method requires a beta-emitting radiopharmaceutical, and in fact uses an optical fiber with a concave cone-shaped mirror at its tip to collect light from a tubular scintillating phosphor imaging plate surrounding the optical fiber. A highly sensitive photomultiplier tube is used to detect the low levels of light from the imaging plate. Thus, it is understandable that this is a remarkably complex mechanism, and in fact is implemented as a catheter placed on a guidewire, which is not always practically user-friendly. In addition, it requires the use of a beta-emitting radiopharmaceutical, which is generally undesirable.

[0026] U.S. Patent Publication No. 2009 / 0175576 ​​describes an optical fiber tip comprising a core and a recess formed within the core at the distal end of the optical fiber tip, wherein the recess has a vertex within the core.

[0027] However, this manufacturing technique limits the types of tip configurations that can be produced, resulting in extremely delicate mechanisms that are unsuitable for many applications.

[0028] U.S. Patent No. 10,517,669 describes a catheter device comprising a balloon structure and a lateral-emitting laser lumen within the balloon for creating a lesion in the pulmonary vein (PV) in the treatment of atrial fibrillation. One or more electrodes are attached to the balloon so as to contact the pulmonary vein when the balloon is inflated, and may be used in measurement mode, treatment mode, or both. This mechanism is intended for vascular irradiation only and cannot perform optical detection techniques, and it must be implemented as part of the catheter.

[0029] U.S. Patent Publication No. 2010 / 0094138 describes an apparatus, system, and method for measuring the depth of a material layer such as an atherosclerotic layer. A bundle of fiber optics stored in a balloon catheter projects a laser dot towards a conical mirror, and this conical mirror reflects the dot perpendicularly onto the surface of the atherosclerotic plaque. The laser dot is reflected from the atherosclerotic layer and returns with a substantially Gaussian-distributed intensity profile. The conical mirror directs the reflected image back towards the bundle of fiber optics, and this bundle of fiber optics delivers the image to a sensor. The depth of the atherosclerotic layer can be determined by comparing the diameter of the image intensity profile with a pre-obtained normalized dataset.

[0030] However, once again, this is actually a complex mechanism implemented as a catheter that is placed on a guidewire, and in practice, it is not necessarily easy to use.

[0031] U.S. Patent Publication No. 2021 / 0041366 discloses a spectroscopic probe for a Raman spectroscopy system and a method for preparing a filter for the probe. Also described is a method for forming a SERS substrate that can optionally be used with the probe. The spectroscopic probe is formed using a double-clad optical fiber probe tip, a double-clad optical fiber (DCF) having a single-mode core, a multimode inner cladding, and an outer cladding, and a microfilter fixed to the distal end of the optical fiber probe tip. The microfilter has a short-pass filter or a band-pass filter configured to align with the DCF core to filter the silica Raman background generated by laser excitation in the single-mode core, and a long-pass filter configured to suppress Rayleigh scattering from the sample while allowing Raman scattering wavelengths to pass through the inner cladding. However, due to its forward-facing design, this forward-looking probe cannot continuously scan the arterial wall / lumen. SUMMARY OF THE INVENTION [Means for solving the problem]

[0032] In terms of one broad form, one aspect of the present invention aims to provide a sensing device for sensing in the blood vessels of a biological subject, comprising: a guidewire configured to be positioned within the blood vessels of a biological subject, the guidewire comprising: a circumferential window positioned near the distal end; an optical fiber substantially extending from the proximal end of the guidewire to a position near the window; and a substantially conical reflector positioned near the window and aligned with the axis of the optical fiber, the conical reflector configured to reflect the stimulus radiation emitted from the optical fiber so that the stimulus radiation passes substantially radially through the window, thereby exposing the blood vessel to the stimulus radiation; and the conical reflector configured to reflect the sample radiation emitted from within the blood vessel and transmit the sample radiation to the optical fiber; as well as a radiation source coupled to the optical fiber and configured to emit stimulus radiation through the optical fiber; a detector configured to detect the sample radiation received through the optical fiber; and one or more processing devices configured to analyze the detected sample radiation; and a processing device configured to generate an index indicating the result of the analysis.

[0033] In one embodiment, at least one of the reflector and the distal end of the optical fiber is embedded in a support material.

[0034] In one embodiment, the reflector includes a reflective surface coating.

[0035] In one embodiment, the reflector includes at least one of: a curved conical surface; a curved conical surface configured to collimate the stimulus radiation; a surface that is at least partially parabolic; and a flat conical surface.

[0036] In one embodiment, the reflector is configured to generate an annular beam of stimulated radiation having a longitudinal width of at least one of the following: greater than 10 μm; greater than 50 μm; less than 200 μm; and about 100 μm.

[0037] In one embodiment, the optical fiber is at least one of: a multimode optical fiber; and a double-clad optical fiber.

[0038] In one embodiment, the optical fiber is a double-clad optical fiber, and the apparatus includes a beam expander coupled to the distal end of the double-clad fiber, the beam expander being configured to expand the stimulated radiation by diffraction so that the beam of stimulated radiation has a diameter similar to or smaller than the diameter of the reflector.

[0039] In one embodiment, the beam expander includes a multimode fiber spliced ​​into a double-clad optical fiber.

[0040] In one embodiment, the radiation source includes a laser diode.

[0041] In one embodiment, the radiation source generates radiation in the range of 600 nm to 900 nm.

[0042] In one embodiment, the apparatus includes a filter configured to filter the sample radiation before it reaches the detector.

[0043] In one embodiment, the filter is a long-pass filter configured to: transmit radiation having a wavelength longer than the wavelength of the stimulating radiation; transmit radiation having a wavelength 20 nm or more longer than the wavelength of the stimulating radiation; and suppress the stimulating radiation.

[0044] In one embodiment, the device includes a coupler configured to connect a detector and a radiation source to an optical fiber.

[0045] In one embodiment, the apparatus includes a reader that comprises at least a detector and a radiation source.

[0046] In one embodiment, the device includes a connector that physically disconnects the optical fiber from the reader.

[0047] In one embodiment, the device includes a second detector configured to detect backscattered stimulus radiation.

[0048] In one embodiment, the guide wire includes a metal sheath that is flexible in the transverse direction but rigid in the longitudinal direction and under rotational movement around the longitudinal axis.

[0049] In one embodiment, the guidewire includes at least one of: a radiopaque, non-traumatic tip; and a moldable section at the distal end.

[0050] In one embodiment, the guidewire includes at least one working length from 1.5 to 2.0 m; 1.75 to 1.9 m; and approximately 1.85 m; and at least one outer diameter from 300 μm to 400 μm; 325 μm to 375 μm; and approximately 350 μm.

[0051] In one embodiment, one or more processing devices are configured to analyze sample radiation by determining sample radiation characteristics based on a signal received from a detector; using the sample radiation characteristics to determine whether a feature is present within a blood vessel; and generating an index if the feature is present.

[0052] In one embodiment, the sample radiation characteristics represent at least one of the following: the measured intensity of the sample radiation; a value derived from the measured intensity of the sample radiation; and a change in the measured intensity of the sample radiation.

[0053] In one embodiment, one or more processing units are configured to analyze sample radiation by: determining the intensity of sample radiation based on a signal from a detector; comparing the intensity to a threshold; and generating an index if the intensity exceeds the threshold.

[0054] In one embodiment, one or more processing devices include: normalizing the measured intensity of sample radiation based on at least one of the measured intensity of backscattered stimulus radiation and the measured intensity of background radiation; and selecting a threshold based on at least one of the measured intensity of backscattered stimulus radiation, the measured intensity of background radiation, and a composite value based on the measured intensity of backscattered stimulus radiation and the measured intensity of background radiation.

[0055] In one embodiment, the device includes an output configured to produce at least one of: tactile feedback; an audible output indicating an indicator; and a visual output indicating an indicator.

[0056] In one embodiment, sample radiation is emitted as a result of at least one of the following: Raman scattering; fluorescence; and autofluorescence.

[0057] In one embodiment, the sample radiation is emitted from atherosclerotic plaque within a blood vessel.

[0058] In one embodiment, the index indicates at least one of: the presence of fragile atherosclerotic plaques; and the degree of fragility of the fragile atherosclerotic plaques. A sensing method comprising positioning a guidewire within a blood vessel of a biological subject, wherein the guidewire includes: a circumferential window positioned close to the distal end of the guidewire; an optical fiber substantially extending from the proximal end of the guidewire to a position close to the window; and a substantially conical reflector positioned close to the window and aligned with the axis of the optical fiber, the reflector being configured to: reflect stimulatory radiation emitted from the optical fiber so that the stimulatory radiation passes substantially radially through the window, thereby exposing the blood vessel to the stimulatory radiation; and to reflect sample radiation emitted from within the blood vessel, thereby transmitting the sample radiation to the optical fiber; emitting stimulatory radiation through the optical fiber using a radiation source coupled to the optical fiber; detecting the sample radiation received through the optical fiber using a detector; and using one or more processing devices to: analyze the detected sample radiation; and generate an index indicating the result of the analysis.

[0059] In one embodiment, the method includes moving a guidewire within a blood vessel.

[0060] In one embodiment, the method includes analyzing the sample radiation in one or more processing units by: determining the sample radiation characteristics based on a signal received from a detector; using the sample radiation characteristics to determine whether a feature is present within a blood vessel; and generating an index if the feature is present.

[0061] In one embodiment, the sample radiation characteristics represent at least one of the following: the measured intensity of the sample radiation; a value derived from the measured intensity of the sample radiation; and a change in the measured intensity of the sample radiation.

[0062] In one embodiment, the method includes analyzing sample radiation in one or more processing devices by determining the intensity of sample radiation based on a signal from a detector, comparing the intensity to a threshold, and generating an index if the intensity exceeds the threshold.

[0063] In one embodiment, the method includes, in one or more processing units, normalizing the measured intensity of a sample radiation based on at least one of the measured intensity of backscattered stimulus radiation and the measured intensity of background radiation; and selecting a threshold based on at least one of the measured intensity of backscattered stimulus radiation, the measured intensity of background radiation, and a composite value based on the measured intensities of backscattered stimulus radiation and background radiation.

[0064] In one embodiment, the method includes: moving a guidewire within a blood vessel until an index is generated; and identifying the location of fragile atherosclerotic plaques based on the position of the guidewire.

[0065] In one embodiment, the method includes: disconnecting the guidewire from the reader in response to the output of an indicator; inserting a catheter into a blood vessel on the guidewire; and performing a procedure using the catheter.

[0066] In terms of a broad range of embodiments, one aspect of the present invention aims to provide a guidewire for a sensing device that performs sensing in the blood vessels of a biological subject, configured to be positioned within the blood vessels of a biological subject, the guidewire comprising: a circumferential window positioned near the distal end; an optical fiber substantially extending from the proximal end of the guidewire to a position near the window; a substantially conical reflector positioned near the window and aligned with the axis of the optical fiber, the reflector configured to reflect stimulus radiation emitted from the optical fiber so that the stimulus radiation passes through the window substantially radially, thereby exposing the blood vessel to the stimulus radiation; and a conical reflector configured to reflect sample radiation emitted from within the blood vessel and transmit the sample radiation to the optical fiber.

[0067] In one embodiment, at least one of the reflector and the distal end of the optical fiber is embedded in a support material.

[0068] In one embodiment, the reflector includes a reflective surface coating.

[0069] In one embodiment, the reflector includes at least one of: a curved conical surface; a curved conical surface configured to collimate the stimulus radiation; a surface that is at least partially parabolic; and a flat conical surface.

[0070] In one embodiment, the reflector is configured to generate an annular beam of stimulated radiation having a longitudinal width of at least one of the following: greater than 10 μm; greater than 50 μm; less than 200 μm; and about 100 μm.

[0071] In one embodiment, the optical fiber is at least one of: a multimode optical fiber; and a double-clad optical fiber.

[0072] In one embodiment, the optical fiber is a double-clad optical fiber, and the device includes a beam expander coupled to the distal end of the double-clad fiber, the beam expander being configured to expand the stimulating radiation by diffraction such that the beam of stimulating radiation has a diameter similar to that of the reflector.

[0073] In one embodiment, the beam expander includes a multimode fiber spliced ​​into a double-clad optical fiber.

[0074] In one embodiment, the guide wire includes a connector that physically disconnects the optical fiber from the reader.

[0075] In one embodiment, the guide wire includes a metal sheath that is flexible in the transverse direction but rigid in the longitudinal direction and under rotational movement around the longitudinal axis.

[0076] In one embodiment, the guidewire includes at least one of a radiopaque, non-traumatic tip and a moldable section at the distal end.

[0077] In one embodiment, the guidewire includes at least one working length from: 1.5 to 2.0 m; 1.75 to 1.9 m; and approximately 1.85 m, and at least one outer diameter from: 300 μm to 400 μm; 325 μm to 375 μm; and approximately 350 μm.

[0078] The broad embodiments of the present invention and their respective features can be used together and / or independently, and it will be understood that references to separate broad forms are not intended to be limiting. Furthermore, it will be understood that the features of the Method can be performed using the System or Apparatus, and the features of the System or Apparatus can be implemented using the Method.

[0079] Hereinafter, various embodiments and examples of the present invention will be described with reference to the accompanying drawings, in which: [Brief explanation of the drawing]

[0080] [Figure 1A] Figure 1A is a schematic diagram of one embodiment of a sensing device that performs sensing within the blood vessels of a biological subject; [Figure 1B] Figure 1B is a schematic diagram showing one embodiment of the tip of the guide wire shown in Figure 1A; [Figure 2] Figure 2 is a flowchart of one embodiment of a method for performing sensing within the blood vessels of a biological subject; [Figure 3] Figure 3A is a schematic diagram of an alternative embodiment of the guide wire tip in Figure 1A; Figure 3B is a schematic detail diagram of an alternative embodiment of the conical reflector; [Figure 4] Figure 4A is a schematic diagram of a further alternative embodiment of the guide wire tip in Figure 1A; Figure 4B is a schematic end view of an example of a double-clad optical fiber; Figure 4C is a schematic perspective cut of the double-clad optical fiber in Figure 4B; [Figure 5] Figure 5 is a schematic diagram of an alternative embodiment of a reader for a sensing device that performs sensing within the blood vessels of a biological subject; [Figure 6A] Figures 6A and 6B are flowcharts of specific examples of methods for performing sensing within the blood vessels of a biological subject; [Figure 6B] Same as above. [Figure 7-1] Figures 7A to 7C are schematic diagrams of examples of ray tracing simulations of a conical reflector in which the number of surface elements approximating a concavely curved conical reflector is gradually increased. Figures 7D to 7F are schematic diagrams of examples of surface elements approximating a concavely curved conical reflector for the ray tracing simulations in Figures 7A to 7C, respectively. [Figure 7-2] Figures 7G to 7I are schematic diagrams of examples of ray tracing simulations when the length of the beam expansion section is gradually increased. Figure 7J is a graph showing the relationship between the return power of the sample emission and the increase in beam expansion length; and [Figure 8]Figure 8 is a scanning electron microscope image of one embodiment of a conical reflector. [Modes for carrying out the invention]

[0081] An embodiment of the sensing device is described below with reference to Figures 1A and 1B.

[0082] In this example, the device 100 includes a guide wire 110 connected to a reader 120, which incorporates electronic circuitry that enables sensing using the guide wire 110.

[0083] The distal end 111 of the guidewire 110, shown in more detail in Figure 1B, is inserted into a blood vessel of a biological subject during use to enable sensing. The guidewire includes a circumferential window 114 positioned close to the distal end 111, and the optical fiber 112 extends substantially from the proximal end of the guidewire to a position close to the window. A substantially conical reflector 115 is positioned close to the window 114. In one detailed embodiment, the conical reflector 115 is located radially inward of the window 114 and is aligned with the axis of the optical fiber 112, with the end of the optical fiber 112 located near or in contact with the conical reflector 115.

[0084] To maintain the physical relationship between the distal end of the optical fiber 112 and the reflector 115, they may be embedded in a support material that is transparent to stimulating and sample radiation, such as a silicone bowl-shaped section 113 or similar. However, it will be understood that other suitable mechanisms may be available.

[0085] When in use, the conical reflector 115 is configured to reflect the stimulus radiation (indicated by the solid arrow) emitted from the optical fiber 112, so that the stimulus radiation passes substantially radially through the window 114, exposing the blood vessel to the stimulus radiation. In addition, the conical reflector 115 is configured to reflect the sample radiation (indicated by the dotted arrow) emitted from within the blood vessel, so that the sample radiation is returned to the optical fiber 112. Specifically, in one embodiment, the window 114 extends substantially around the entire circumference of the guidewire 110, so that, in combination with the conical shape of the reflector 115, the stimulus radiation is emitted around the entire circumference of the guidewire, while at the same time receiving sample radiation from within the blood vessel around the entire circumference of the guidewire. The properties of the window vary and may include a material that transmits radiation, or it may be an opening that optionally includes a mesh or support that provides physical support while minimizing obstruction to the transmitted radiation.

[0086] In this example, the reader 120 includes a radiation source 121 and a detector 122, optically coupled to an optical fiber 112. The radiation source 121 is configured to emit a stimulating radiation through the optical fiber 112, while the detector 122 is configured to detect a sample radiation received through the optical fiber 112. The radiation source 121 and the detector 122 can be in any suitable form depending on the nature of the sensing being performed, but in one embodiment they include a laser diode and a photodiode. The radiation source 121 is generally configured to produce a stimulating radiation having a specific wavelength or wavelength range (commonly referred to as the stimulating wavelength), while the detector 122 may be configured to detect a sample radiation having a specific wavelength or wavelength range different from the stimulating wavelength (commonly referred to as the sample wavelength). In this context, it should be noted that the terms stimulating wavelength and sample wavelength encompass radiation spanning a wavelength range or including multiple wavelengths, and are not necessarily intended to be limited to specific wavelengths.

[0087] The properties of the induction wavelength and sample wavelength vary depending on the sensing being performed, and may depend, for example, on the stimulating and luminescent properties of the feature being detected. For instance, when detecting atherosclerotic plaque, stimulating radiation with a stimulating wavelength in the range of 600 nm to 900 nm may be used, while sample radiation in the form of autofluorescence is detected at even longer sample wavelengths. However, it will be understood that other suitable ranges may be available, and that in some situations, sample radiation may be detected at wavelengths shorter than the stimulating radiation wavelength.

[0088] One or more processing units 123 configured to analyze detected sample radiation and generate an index indicating the results of the analysis can also be provided. The processing units 123 are typically any electronic processing unit, such as a microprocessor, microchip processor, logic gate configuration, FPGA (Field Programmable Gate Array), or any other electronic device, system, or mechanism, optionally accompanied by implementation logic such as firmware. While the system may use multiple processing units and processing is performed by one or more devices, for the sake of ease of illustration, the following embodiments refer to a single device; however, it will be recognized that a reference to a single processing unit encompasses multiple processing units and vice versa, and it is desirable to understand that processing is distributed among those devices as appropriate. The processing units 123 typically form part of the reader, but this is not essential, and it may be possible to use remote processing units 123, or alternatively, to distribute processing between processing units 123 inside and outside the reader 120.

[0089] The nature of the analysis performed varies depending on the preferred implementation and the nature of the feature being detected. For example, if the feature emits radiation at a characteristic wavelength, this may involve sensing the intensity of the sample radiation emitted at the characteristic wavelength and comparing it to a threshold to determine whether the feature is present.

[0090] The following describes one example of the operation of the sensing device, with reference to Figure 2.

[0091] In this example, in step 200, the guidewire 110 is positioned within the blood vessel, and sensing is initiated by causing the radiation source 121 to generate stimulating radiation. The stimulating radiation is transmitted along the guidewire via the optical fiber 112, reflected by the reflector 115, and emitted transversely from the guidewire 110 through the window 114, thereby exposing the inside of the blood vessel and any features within it to the stimulating radiation. Any radiation obtained, whether reflected or emitted, can then be returned to the detector 122 via the window 114, the conical reflector 115, and the optical fiber 112, which can then be received by the detector 122 in step 220.

[0092] For example, if a blood vessel contains features such as fragile atherosclerotic plaque, when exposed to stimulating radiation, the plaque will autofluoresce at different, longer wavelengths, resulting in the sample radiation being transmitted to and received by the detector 122. In fragile atherosclerotic plaque, the stimulating radiation may be in the wavelength range of 600-900 nm, but other wavelength ranges may be used. It will be understood that sample radiation may be emitted as a result of mechanisms other than autofluorescence, including fluorescence and Raman scattering. Therefore, it will be understood that other suitable wavelength ranges may be used to detect other features.

[0093] In step 230, the processing unit 123 can analyze the detected radiation to determine whether it is a feature of interest, such as a feature of fragile atherosclerotic plaque. Thus, the processing unit can compare the intensity and / or wavelength of any detected sample radiation to a threshold or characteristic wavelength to determine whether the sample radiation exhibits a feature of interest. In addition, and / or alternatively, the sample radiation may be analyzed over multiple wavelengths, which can be done, for example, by examining the spectrum of the sample radiation and comparing it to a reference spectrum exhibiting different features, making it possible to detect and / or identify the features.

[0094] In the context of atherosclerotic plaque, an appropriate stimulation wavelength and analysis of sample emission resulting from the autofluorescence of the atherosclerotic plaque can be used to determine whether the atherosclerotic plaque is vulnerable. Techniques for performing such sensing and analysis are described in more detail in U.S. Patent No. 20150080686, which is incorporated herein by cross-reference in its entirety.

[0095] Therefore, in this example, the device can be used to analyze the intensity of infrared fluorescence emitted by atherosclerotic plaques, which can then be used to determine the degree of vulnerability of the plaques, thus enabling healthcare professionals to identify suitable treatment strategies, such as stent placement on the plaques. In this example, fluorescence sensing is performed using a stimulation wavelength, and fluorescence detection is performed at a different sample wavelength that is longer than the stimulation wavelength. This makes it possible to expose the tissue that will be identified by the fluorescence using the stimulation radiation, and in more detail, to prevent false results from being produced by the stimulation radiation.

[0096] Furthermore, it will be understood that stimulation radiation and sample radiation can be distinguished in other ways, for example, by using time-resolved techniques. In detail, there is usually a slight time delay of the order of a few nanoseconds between tissue exposure and the subsequent generation of fluorescence. Therefore, sensing devices can be adapted, for example, using gated sensing devices, to detect only radiation after the radiation source has stopped emitting radiation, thereby ensuring that the detected radiation includes only radiation resulting from fluorescence.

[0097] If the target feature is detected, in step 240 instructions, such as visual and / or audible warnings, can be optionally generated and presented via the optional output device 130, enabling appropriate action, such as performing a procedure. If the target feature is not detected, the process can then be continuously repeated by continuing to move the guidewire along the blood vessel until the examination of the blood vessel is complete and / or until the target feature is detected.

[0098] In the mechanism described above, the use of a conical reflector and a circumferential window makes it possible to expose the entire circumferential region of the blood vessel to the stimulating radiation, and by collecting the sample radiation across this entire region, it becomes possible to monitor all segments of the blood vessel in a continuous process by moving the guidewire continuously (or substantially continuously).

[0099] As a result, this avoids the need to rotate the imaging device or reflector to scan the inside of blood vessels, which is required in conventional prior art methods, and reduces the complexity of the sensing mechanism and its operation. For example, this avoids the need to incorporate a rotation mechanism into the system and / or the need for the user to manually move and rotate the device. Synchronizing rotation and retraction in this way is an extremely difficult task, considering the possibility that one or both movements (depending on the configuration) may be disrupted by changes in friction and shear between the proximal and distal ends.

[0100] Furthermore, the guidewire does not need to be held statically within the vessel to allow scanning or other similar processes to be performed; instead, detection can be performed while the guidewire is continuously moved within the vessel. This means the operator simply positions the guidewire within the vessel to activate the reader, and then moves the guidewire along the vessel until features are detected and corresponding indices are determined. This thus reduces not only the complexity of the scanning process but also the time required to perform sensing, providing a direct and effective mechanism for identifying features within vessels. In this regard, it should be noted that this form of sensing leverages the knowledge that physical procedures, such as stents or balloons, have radial symmetry, meaning that there is no practical advantage in locating features in the circumferential / radial direction. Conversely, the longitudinal location within the vessel is necessary information, and therefore this mechanism uses the circumferential exposure of substantially the entire annular portion of the vessel to locate features longitudinally, while avoiding the complexity of circumferential / radial location determination.

[0101] In addition, by avoiding imaging, the complexity of the required signal processing is reduced, which in turn makes it possible to generate instructions in virtually real time as the guidewire is moved along the blood vessel. This also avoids the potential limitation on the speed at which sensing can be performed using prior art, which is the need to collect image data with the required spatial resolution necessary for useful diagnosis. Furthermore, as mentioned earlier, in conventional mechanisms, the speeds of lateral and rotational movement may be interdependent to ensure that the entire inner surface of the blood vessel is scanned, whereas the above mechanism offers greater flexibility in terms of the speed of movement along the blood vessel. This not only allows for the collection of measurements more quickly and with less dependence on the speed of movement, but also enables improved feature detection by allowing the user to stop and then move back or forward along features without difficulty.

[0102] Therefore, this allows an operator, such as a clinician or surgeon, to simply insert the guidewire into the blood vessel and gradually move it along the vessel as sensing is performed. If a feature is detected, instructions such as an audible or visual warning can be generated, allowing the operator to stop moving the guidewire, and then the procedure can be performed by using the guidewire position to locate the feature within the blood vessel.

[0103] It should be noted that the above mechanism is performed using a guidewire, which is significantly different from a mechanism using a catheter.

[0104] For example, a guidewire can be placed without any additional placement mechanism, whereas a catheter can only be placed using an additional device to position the catheter within the blood vessel. As a result, the workflow that can be achieved using a catheter-based system may be inefficient overall, due to the need to repeatedly insert and remove the catheter in order to insert the stent catheter.

[0105] In addition, guidewires possess sufficient flexibility and, in some cases, a degree of maneuverability, allowing them to be easily positioned within arteries. Conversely, catheters also require a guidewire to position them within arteries, resulting in the guidewire obstructing the lateral view of the radial reflector on one side, leading to signal loss from a portion of the artery. This means that the catheter-based approach has several drawbacks that make it unsuitable for practical applications.

[0106] In addition, as those skilled in the art will understand, guidewires typically have a smaller diameter than catheters. For example, a standard coronary artery guidewire typically has a diameter of 350 μm, while conventional sensing catheter systems typically have a diameter on the order of 1 mm (in the case of Infraredox Incorporated mentioned above) or 600 μm (described as an endoscopic probe in Komachi Y, Sato H, Matsuura Y, Miyagi M, Tashiro H, “Micro-optical fiber probe for use in an intravascular Raman endoscope,” (2005) Opt Lett 30:2942-2944). This means that it may not be possible to simply implement prior art teachings with guidewires.

[0107] In this regard, several prior art mechanisms utilize multiple optical fibers, which generally do not conform to the standard 350 μm coronary artery guidewire size. NIR spectroscopy, being based on the level of reflected light, may not typically be considered a low-light-level technique. However, if measurements are performed in blood without relying on vascular flushing, vascular occlusion, or tissue compression, the signal level will decrease. Thus, the longitudinal retraction speed is limited to 0.5 mm / s, which is insufficient for practical applications.

[0108] Therefore, all of these examples of spectroscopic measurements of low-level light signals are currently performed in catheters or endoscopic devices with relatively large diameters, and thus, based on these examples, it is clear that these spectroscopic techniques cannot be practically implemented in guidewires.

[0109] In contrast, the above mechanism stipulates a certain degree of flexibility and small size for implantation as a guidewire, and that it can be used to perform spectroscopic measurements of low-level optical signals, i.e., measurements of light intensity at different wavelengths.

[0110] The following describes several further features.

[0111] The guidewire can take any suitable form, but typically includes a metal sheath that is flexible transversely but rigid longitudinally and under rotational movement around the longitudinal axis. In one embodiment, the guidewire is a coiled or braided wire or slotted tube made of stainless steel and / or nitinol (nickel-titanium), and optionally coated with a polymer, such as silicone or polytetrafluoroethylene (PTFE), to enhance lubricity. Hydrophilic coatings may also be used to reduce friction during placement and to allow for easier movement within tortuous vessels.

[0112] A guidewire typically includes a tip 118 at the distal end 111 of a catheter used to allow the guidewire to move along a blood vessel. The tip can be made to have various configurations, including a "J" curve, a tip of various angles, or a straight tip, to help navigate the anatomical structures of various blood vessels. More typically, however, the tip 118 is a radiopaque, non-traumatic tip, or a tip that includes radiopaque features and includes a morphable section at the distal end. This makes it possible to adjust the shape of the tip to facilitate navigation through the blood vessel, and at the same time, the radiopaque nature makes it possible to sense the location of the tip within the blood vessel using sensing mechanisms, such as X-rays or similar. It will be understood that when locating the position of features, it will be necessary to consider the offset between the radiopaque features and the window, however, in another embodiment, a metallic mirror coating on a conical reflector may serve a dual purpose of providing a radiopaque area. This could potentially improve the estimation of the longitudinal position of the signal location, and this could potentially be enhanced by increasing the thickness of the mirror coating beyond the thickness required for a highly reflective mirror, which should be an advantage for radiopaqueness.

[0113] The guidewire typically includes working lengths of 1.5 to 2.0 m, 1.75 to 1.9 m, and more typically approximately 1.85 m, while simultaneously including outer diameters of 300 μm to 400 μm, 325 μm to 375 μm, and more typically approximately 350 μm. The guidewire 110 may also include a handle 117 that allows for insertion and manipulation of the guidewire 110.

[0114] A connector can be provided that includes male and female connector portions 116, 126, which physically separate the guidewire 110 and the optical fiber 112 from the reader 120, thereby making the guidewire 110 detachable from the reader 120. This can be used to feed a catheter or other surgical instrument onto the guidewire 110, allowing for the performance of procedures as needed, such as positioning a stent within a blood vessel. The connector may also include a gripping mechanism and / or a removable handle, which serves to align the fibers on both sides of the connector and assist in handling, in particular, rotating, the guidewire.

[0115] In one embodiment, the reader 120 and the handle 117 can be combined into a single component, and the connector can be positioned between the reader 120 and the rest of the guidewire, allowing the handle 117 and reader 120 to be detached from the guidewire. The connector 116 may be intended to rotate freely so that the guidewire can be rotated without requiring the reader 120 to rotate. This can assist in manipulating the guidewire within the subject and at the same time avoid the need to rotate the reader 120, which can be problematic if the reader is of considerable size. In this case, since the connector 116 does not have the ability to transmit rotational force, the handle 117 can be positioned between the connector 116 and the tip of the guidewire, allowing the guidewire to be rotated using the handle. In this situation, the handle 117 may be removable, for example, by sliding the handle away from the guidewire or by gripping the guidewire with the handle, allowing devices such as catheters, stents, or similar devices to pass along the guidewire as described above.

[0116] Typically, the radiation source includes a laser diode, but other suitable sources may be used. Radiation source 121 generates stimulating radiation in the range of 600 nm to 900 nm at a power level below the thermal damage threshold of blood vessels. In one detailed embodiment, radiation source 121 generates stimulating radiation at one or more of the wavelength ranges 600 nm to 900 nm, 650 nm to 850 nm, 700 nm to 850 nm, 750 nm to 850 nm, 800 nm to 850 nm, 650 nm to 800 nm, 700 nm to 800 nm, 750 nm to 800 nm, 650 nm to 700 nm, 650 nm to 750 nm, 650 nm to 800 nm, or 700 nm to 750 nm. However, other ranges may be used depending on the preferred implementation and the nature of the features to be detected, so it will be understood that wavelengths below 500 nm may be used, for example.

[0117] The power level of the radiation source may also be adjusted to ensure its safety. For example, by adjusting the radiation source using measurements of the intensity of backscattered sample radiation, it may be possible to maintain a safe intensity on tissue and prevent excessive fluctuations in sensitivity as vessel diameter changes.

[0118] The properties of the detector will vary depending on the preferred implementation and may include photodetectors, photomultiplier tubes, infrared cameras, spectrometers, or similar devices.

[0119] To enable sensing at a specific sample wavelength, the apparatus typically includes a filter 124 configured to filter the sample radiation before it reaches the detector 122. In one embodiment, the filter 124 is a long-pass filter configured to transmit radiation having a wavelength 20 nm greater than the wavelength of the stimulating radiation.

[0120] In one embodiment, sensing is performed at wavelengths longer than the wavelength of the stimulating radiation, specifically in the wavelength ranges of 600nm-1150nm, 650nm-1150nm, 700nm-1150nm, 750nm-1150nm, 800nm-1150nm, 850nm-1150nm, 900nm-1150nm, 950nm, 1150nm, 1000nm-1150nm, 1050nm-1150nm, 1100nm-1150nm, 600nm-1100nm, 650nm-1100nm, 650nm-1100nm, 700nm-1100nm, and 750nm. 1100nm, 800nm~1100nm, 850nm~1100nm, 900nm~1100nm, 950nm~1100nm, 1000nm~1100nm, 1050nm~1100nm, 600nm~1050nm, 650nm~1050nm, 700nm~1050nm, 750nm~1050nm, 800nm~1050nm, 850nm~1050nm, 900nm~1050 nm, 950nm~1050nm, 1000nm~1050nm, 600nm~1000nm, 650nm~1000nm, 700nm~1000nm, 750nm~1000nm, 800nm ~1000nm, 850nm~1000nm, 900nm~1000nm, 950nm~1000nm, 600nm~950nm, 650nm~950nm, 700nm~950nm, 750nm 950nm, 800nm~950nm, 850nm~950nm, 900nm~950nm, 600nm~900nm, 650nm~900n m, 700nm~900nm, 750nm~900nm, 800nm~900nm, 850nm~900nm, 600nm~850nm, 65 0nm~850nm, 700nm~850nm, 750nm~850nm, 800nm~850nm, 600nm~800nm, 650nm~ 800nm, 700nm~800nm, 750nm~800nm, 600nm~750nm, 650nm~750nm, 700nm~750nm The sensing is performed in one or more of the following ranges: 600nm–700nm, 600nm–650nm, or 650nm–700nm. However, it will be understood that other sensing wavelengths may be usable, depending on the preferred implementation and the nature of the features to be detected.

[0121] It will be understood that a wavelength range includes the numerical values ​​at each endpoint of the range. For example, the wavelength between 600 nm and 900 nm includes the wavelengths of 600 nm and 900 nm. Furthermore, if a range of values ​​is provided, it will be understood that values ​​interposing between the upper and lower limits of that range are included within that range up to one-tenth of the lower limit unit unless the context clearly specifies otherwise, and that any other listed or interposing values ​​within that range are included within that range. The fact that the upper and lower limits of these even smaller ranges may be independently included within those even smaller ranges is, by presupposition, encompassed within the invention any limits that are specifically excluded within that listed range. If a listed range includes one or both limits, the range excluding either of those included limits is also included within that range.

[0122] In this embodiment, the use of a multimode optical fiber allows multiple transmission modes to be transmitted through a common core, enabling the optical fiber to transmit stimulatory radiation to the target tissue and return sample radiation to the detector. A multimode fiber typically has an overall diameter of up to 250 μm with a 110 μm core, a 125 μm cladding, and an outer polymer buffer, although other suitable mechanisms may be used.

[0123] The apparatus typically includes a coupler 125 configured to couple the detector 122 and the radiation source 121 to an optical fiber 110. In this example, the coupler 125 is a multimode fiber coupler, which transmits laser light from the radiation source 121 to the multimode fiber 112 via the radiation source-side optical fiber 121.1 extending from the radiation source 121, and transmits sample radiation from the optical fiber 112 to the detector-side multimode optical fiber 122.2 extending to the detector. Multimode fibers are not only suitable for couplers that enable efficient delivery of stimulating radiation and collection of sample radiation, and that provide reasonably efficient separation of light between the delivery path and the collection path, but are also robust in structure. Multimode fibers also enable efficient coupling of stimulating radiation to the fiber, however, it will be understood that other mechanisms may be usable, and embodiments using double-clad optical fibers and associated couplers will be described in more detail below.

[0124] During use, the processing unit 123 controls the radiation source 121 and analyzes the signal from the detector 122 to identify features within the subject. The processing unit 123 can also be connected to an input device, such as a touchscreen, keypad, input buttons, or similar, to control the operation of the reader, for example, to start the measurement process, or to connect the reader 120 to an output device 130 or similar.

[0125] The processing unit 123 may also be connected to an interface 127, which can be used to connect the processing unit 123 to peripheral devices such as communication networks, databases, other storage devices, output devices 130, remote devices such as computer systems, smartphones, tablets, or the like. Although a single external interface 127 is shown, this is for illustrative purposes only, and in practice, multiple interfaces using various methods (e.g., Ethernet, serial, USB, wireless, or the like) may be provided. In a preferred embodiment, interface 127 is used to enable wireless connection of the reader to output device 130, although this is not essential, and other mechanisms may be used.

[0126] In addition, and / or alternatively, the operation of the reader 120 can be controlled by a remote device, such as a computer system, smartphone, tablet, or similar. In this example, it will be understood that the analysis of the results may also be performed entirely or partially on the remote device, reducing the amount of processing required within the reader, and that the output may be presented by the remote device, for example, by using a built-in display or similar. In this example, the processing unit 123 within the reader 120 typically performs the minimal function of controlling the radiation source 121 based on signals from the remote device and uploading signals from the detector 122 to the remote device for analysis. It will also be understood that any division of tasks between the processing unit and the remote device may be used depending on the preferred implementation.

[0127] In one embodiment, the reflector includes a reflective surface coating and, more specifically, may include a conical inset having a reflective surface coating, although other mechanisms such as an air gap between the conical surface and the rest of the structure that allows for total internal reflection may be used. When a reflective surface is used, surface imperfections can lead to scattering of stimulus radiation and / or sample radiation, so it is preferable to minimize imperfections and thereby maximize the signal intensity and thus the ability to accurately detect features. As a result, in one embodiment, the conical insert is manufactured using two-photon stereolithography based on photopolymerization of a material comprising a photoinitiator and a monomer. A two-photon photoinitiator is a chemical species or combination of chemicals that can efficiently absorb two photons to generate an excited state from which radicals or ions can be produced to initiate polymerization of the monomer. Exemplary materials include acrylate monomers and photoinitiators such as 4,4'-dialkylaminotransstilbene, bisdonner-type bis(styryl)benzene or bis(phenyl)polyene, fluorenes, and ketocoumarin derivatives. Furthermore, the surface may be subjected to laser polishing as an additional and / or alternative processing step.

[0128] In one specific example, the reflector is manufactured using ORMOSIL polymer (Organic Modified Silicate, SZGel, SZ2080 Silica-Zirconia Hybrid). This can be used as a non-photosensitive type to avoid the adverse effects of photoinitiators on optical performance, although it may also contain the photosensitizer Irgacure 369 photoinitiator. ORMOSIL can provide improved dimensional stability compared to other methods. Avoiding photoinitiators is also preferable for medical devices, as photoinitiators can generate free radicals and contribute to cytotoxicity, although this may not be necessary given that the reflector can be encapsulated.

[0129] A conical reflector can have a surface that is a flat conical surface similar to that shown in Figure 1B. In this example, the flat conical surface has a radius that increases at a constant rate in the axial direction. The mechanism in this form generates an annular radiation beam with substantially a constant longitudinal width. However, this is not essential, and the conical surface can be a curved conical surface, an example of which is shown in Figure 3A.

[0130] In this example, similar reference numerals, incremented by 200, are used to indicate the mechanism and similar features shown in Figure 1B, so these will not be described in detail.

[0131] Therefore, the guidewire includes a circumferential window 314, and the optical fiber 312 extends substantially from the proximal end of the guidewire to a position close to the conical reflector 315.

[0132] In this example, the conical reflector 315 is curved inward (angular shape) to more tightly focus the stimulation radiation beam, thus reducing the spread of the stimulation radiation over the tissue, improving spatial resolution, and helping to focus the sample radiation onto the facets of the optical fiber 312. In this example, the window 314 also extends longitudinally to allow more sample radiation to enter the window 314, which is focused onto the optical fiber 312, thereby increasing the amount of sample radiation received, which in turn helps to improve the signal intensity of the detected sample radiation. To achieve a significant increase in the amount of light collected, it is preferable to extend the reflector beyond the diameter of the optical fiber so that the reflector has a diameter larger than the diameter of the optical fiber. This can be used to maximize the signal intensity of the detected sample radiation, which can help ensure that weak autofluorescence can be detected and distinguished from background radiation. It should be noted that such a mechanism is incompatible with the catheter-based mechanisms of prior art.

[0133] In one embodiment, this would require the use of a substantially parabolic profile and / or a curved conical surface configured to collimate the stimulating radiation and to ensure uniform exposure of the vessel wall regardless of the distance between the vessel wall and the reflector. However, it will be understood that if wider dispersion of the stimulating radiation is desired, an outwardly curved (semi-ellipsoidal) reflector may be used. In practice, tapering of a conical reflector in this manner can be carried out using the two-photon polymerization process described above.

[0134] Combining an increase in mirror diameter with an increase in the curvature of the conical surface leads to at least a 100% increase in light-gathering efficiency compared to a flat conical surface, which in turn helps ensure that the sample signal originating from autofluorescence within the artery can be detected, overcoming background radiation resulting from other emission and reflection within the artery.

[0135] The following describes another example of a reflector configuration, referring to Figure 3B.

[0136] In this example, the conical reflector 315 has a diameter d larger than the diameter of the optical fiber 312, which helps to increase the signal intensity of the detected sample radiation, as described above. In this example, an expansion region 319 is provided between the end of the optical fiber 312 and the conical reflector 315 to allow the beam to expand by diffraction, which also helps to focus the sample radiation reflected back from the reflector onto the optical fiber. In this example, the distal end of the expansion region 319 has the same diameter as the conical reflector, while the proximal end can have a diameter greater than or equal to the diameter of the optical fiber 312.

[0137] Using ray tracing simulations, we demonstrated how the combination of increasing mirror diameter and increasing curvature of the conical surface leads to increased light-gathering efficiency. In this regard, Figures 7A to 7C illustrate exemplary ray tracing for the corresponding reflector mechanism in Figures 7D to 7F, where a curved conical reflector is approximated using a gradually increasing number of surface elements. These simulations show how the number of photons captured by the optical fiber increases as the number of surface elements approximating an ideal curved mirror surface increases. The power received by the detector effectively doubles for the four-element case compared to the baseline case with a single cone angle. In the simulations, all rays come from the same point source on the wall of the vessel (located above the area of ​​the optical system shown in these examples), but have randomly selected propagation angles covering a wider range than the range the mirror sees. Figures 7D to 7F are simplified 2D examples of the conical surface relative to the fiber end face. Here, for convenience, only the upper half of the conical cross-section is shown.

[0138] Furthermore, the use of beam-expanding sections of appropriate length enhances focusing on the end face of the optical fiber. In this regard, Figures 7G to 7I illustrate the effect of gradually increasing the beam-expanding section, and the resulting sample radiation return power is shown in Figure 7J. This highlights that beam-expanding sections with lengths of 0.3 mm to 0.5 mm, preferably 0.4 mm, provide optimal return power for sample radiation, although it should be understood that this value may vary depending not only on the reflector diameter, cone angle, and curvature, but also on the numerical aperture of the optical fiber.

[0139] Both simulations demonstrate that substantial improvements in focusing efficiency can be achieved by increasing the mirror diameter, curving the mirror surface, and selecting an appropriate beam extension length.

[0140] Generally, the reflector 315 may typically have a diameter d of at least 80 μm, which corresponds to the smallest "standard" diameter optical fiber that might actually be used in a guidewire. The maximum diameter of the reflector 315 may typically be constrained by the diameter of the guidewire, and may be up to 350 μm. The height h of the conical reflector 315 may be approximately half the conical diameter d in the case of a flat conical surface, and may be slightly larger or smaller if a curved or parabolic reflector is used.

[0141] A specific example of the manufactured reflector is shown in Figure 8.

[0142] In addition, the angle of the cone α can determine the angle at which light emerges from the guidewire. In one embodiment, this may be a 90° angle of cone, resulting in emission substantially perpendicular to the longitudinal axis of the guidewire. However, other angles may be used depending on the preferred implementation, for example, to allow for further relaxed manufacturing tolerances or different levels of spatial resolution along the arterial wall.

[0143] In one detailed embodiment, the reflector is configured such that the stimulus radiation is emitted from the optical fiber at an angle offset by 90°. This causes the emitted sampling radiation to be reflected from the blood vessel wall and return straight to the reflector, and is therefore detected as sample radiation, which may be able to overwhelm the signal resulting from autofluorescence within the blood vessel. As a result, cone angles between 45° and 135° may be used, and in one embodiment, cone angles offset from 90°, more preferably from 85° to 95°, are used.

[0144] Typically, reflectors 115, 315 are configured to produce an annular beam of stimulated radiation having at least one longitudinal width of greater than 10 μm, greater than 50 μm, less than 200 μm, or about 100 μm, although it will be understood that other widths may be usable depending on the preferred implementation.

[0145] In the above example, multimode optical fiber is used. However, this is not essential, and double-clad optical fiber can be used as an alternative. This example will be described below with reference to Figures 4A to 4C.

[0146] In this example, similar reference numerals, incremented by 300, are used to indicate the mechanism and similar features shown in Figure 1B, so these will not be described in detail.

[0147] Therefore, the guidewire includes a circumferential window 414 and a conical reflector 415 positioned radially inward from the window 414 and rearward from the tip 418. In this example, a double-clad optical fiber 412 extends substantially from the proximal end of the guidewire to a beam expander 419 positioned close to the conical reflector 415. Again, the distal end of the optical fiber 412, the beam expander 419, and the conical reflector 415 are held in place by a support material 413, for example, a bowl-shaped portion made of silicone.

[0148] The double-clad optical fiber 412 includes a single-mode core 412.1, a first multimode cladding layer 412.2, and a second outer cladding layer 412.3. The single-mode core 412.1 and the first multimode cladding layer 412.2 have a diameter of 125 μm or less, and the total diameter of the optical fiber, including the polymer outer cladding layer 412.3, is a maximum of 250 μm.

[0149] During use, the single-mode core 412.1 is used to propagate the stimulating radiation from the radiation source 121, while the multimode cladding layer 412.2 is used to transmit the sample radiation back to the detector 122. In this example, the beam expander 419 includes a standard multimode fiber similar to the one described above, spliced ​​to the end of the double-cladding fiber 412. The beam expander 419 operates to allow the single-mode laser light to be expanded by diffraction so that the size of the radial reflector matches the beam of the stimulating radiation. The size of the beam expander 419 will depend on the desired spatial extent in the lumen and the diameter of the reflector available for collecting the sample radiation, but is typically approximately up to 1.5 mm in length.

[0150] In this example, the reader 120 includes a double-clad fiber coupler 125, which transmits the stimulus radiation from the single-core single-mode radiation source side optical fiber 121.1 to the inner core 412.1 and the backscattered sample radiation from the inner cladding 412.2 of the double-clad fiber to the multimode detector side optical fiber 122.2.

[0151] The use of double-clad fiber 412 enables efficient delivery of stimulating radiation and collection of backscattered sample radiation. The double-core fiber 412 also has a robust structure and is compatible with fiber coupler 125, which provides efficient separation of light between the delivery path and the focusing path.

[0152] In this example, the beam expander 419 plays a crucial role in adapting the double-core fiber for radial emission and signal collection, primarily by ensuring that the largest possible range of sample radiation is collected by the surface of the conical reflector and returned to the inner core of the fiber. In addition, the beam expander ensures that spatially small stimulation radiation sources are efficiently reflected and potentially focused into an annular beam of stimulation radiation, which is emitted from the entire circumference of the guidewire 110.

[0153] Again in this example, the radial reflector 415 may be flat or curved, but in either case, it should provide a sufficiently defined spatial location (along the longitudinal axis of the blood vessel) for detecting sample radiation, such as autofluorescence, and in principle should have better spatial resolution than that obtained using multimode fibers, due to the ability to focus a smaller radiation source size into a narrower annular beam.

[0154] Although the above examples have focused on the use of multimode or double-clad optical fibers, it should be understood that other forms of fibers, such as microstructured optical fibers, photonic crystal fibers, or similar materials, can be used, and that the reference to multimode or double-clad optical fibers should not be considered limiting.

[0155] In the above embodiment, the reader includes a single detector 122 configured to detect sample radiation. However, the intensity of the received sample radiation can vary depending on several factors, including the scattering of radiation within blood vessels as well as the presence of features. For example, stimulation radiation and sample radiation are likely to be strongly scattered in the blood. In one embodiment, such scattering can be addressed by monitoring the distance of the guidewire from the blood vessel wall using, for example, a technique similar to the technique described in U.S. Patent No. 7,539,530,B2, the contents of which are incorporated herein by cross-reference. In addition, and / or alternatively, it may be necessary to flush the blood from the measurement window during measurement, which can be achieved using a contrast agent used to visualize arteries, such as VISIPAQUE®.

[0156] In a further alternative, a second detector is provided to detect backscattered stimulus radiation, which can then be used to calibrate the measurement results of the received sample radiation, an example of which is shown in Figure 5.

[0157] In this example, we use similar reference numerals incremented by 400 to indicate the mechanism and similar features shown in Figure 1A, so we will not explain them in detail.

[0158] Therefore, in this example, the reader 520 includes a radiation source 521, a radiation source-side source optical fiber 521.1, a processing unit 523, a fiber coupler 525, a connector 526, an interface 527, and an optional input 528. The single detector in Figure 1A is replaced by first and second detectors 522.1, 522.2, which are coupled to detector-side optical fiber 522.3 via a filter / beam splitter mechanism 524.1 and lens 524.2, and they operate to split the incident radiation into sample radiation directed toward the first and second detectors 522.1 and backscattered stimulation radiation, respectively. This makes it possible to calibrate the intensity received by the sample radiation using the backscattered stimulation radiation, for example by using the ratio of stimulation radiation to sample radiation, and by using this ratio, the amount of scattering occurring within the blood vessels is taken into account in the analysis. For example, this ratio may take into account changes in the size of the blood vessels, thereby 1 / R 2 A coefficient is introduced (where R is the vascular radius).

[0159] Background signals may also arise from Raman scattering generated from the silica glass inside the optical fiber. In this example, a microfilter mechanism similar to that described in the concurrently pending U.S. Patent Application Publication No. 2021 / 0041366 may be employed to remove such Raman scattering from the double-clad optical fiber. In this example, this filter mechanism may be integrated as part of the beam expander 419 in the double-clad fiber mechanism described above with reference to Figures 4A to 4C.

[0160] Alternatively, in another embodiment, the intensity of background radiation at a third wavelength can be measured, which represents background radiation emitted from other tissue components irradiated with the annular beam, such as fluorescence or autofluorescence emitted from healthy tissue and / or stable plaque, or similar. In this case, the signal of interest can be the ratio between the sample radiation and the background radiation. In one embodiment, any NIRAF signal resulting from unstable plaque is clinically significant, so the detection threshold is determined by the noise level of the background signal. For example, if the variation in background radiation intensity is 10%, then a ratio greater than 1.3 (corresponding to a threshold of SNR > 3) may be required for the event to be significant.

[0161] The processing apparatus 523 is typically configured to analyze the received sample radiation by determining the characteristics of the sample radiation and using this to evaluate whether the sample radiation indicates the presence or absence of a feature. For example, a feature may emit radiation at a characteristic frequency, in which case the presence of that feature can be identified by using the detection of the sample radiation at that frequency.

[0162] In one detailed embodiment, the processing apparatus 523 is configured to analyze sample radiation by determining sample radiation characteristics, such as the measured intensity of sample radiation, a value obtained from the measured intensity of sample radiation, or a change in the measured intensity of sample radiation. The sample radiation characteristics are then used to determine whether features exist in the blood vessels, and if so, an index is generated if features are present.

[0163] Therefore, for example, the intensity of sample radiation at a specific wavelength can be used to evaluate features, such as the presence of vulnerable atherosclerotic plaques. In this example, the processing unit typically determines the intensity of sample radiation based on the signal received from the detector and then compares that intensity to a threshold. If the intensity of sample radiation exceeds the threshold, this can indicate the presence of a feature and / or a quantification of the feature, such as the degree of vulnerability of atherosclerotic plaques. The threshold may be an absolute value, for example, a value obtained from the analysis of multiple features, or it may be a relative value, and / or it may be derived based on the measurement of background radiation or backscattered stimulus radiation.

[0164] This then allows for the generation of corresponding instructions, for example, audible, tactile, and / or visual warnings, or optionally, the spectrum of the received sample radiation. In one embodiment, a numerical index representing the risk associated with any detected feature may be displayed, for example, by using a value scaled between 1 and 10 to indicate the degree of risk. In this regard, the intensity of the received signal may depend on the size and / or extent of the intrathecal hemorrhage, with a higher intensity of the received signal meaning either the plaque is larger or more fragile, either of which represents a greater risk to the subject, so it becomes possible to provide such an index by scaling the intensity.

[0165] In addition, and / or alternatively, the change in intensity determined as the guidewire moves may be used to compare healthy portions of the blood vessel with portions containing features. Thus, for example, as the guidewire moves from a region of healthy blood vessels to a region of blood vessels containing fragile atherosclerotic plaques, there will be a stepwise change in the intensity of the detected sample radiation. In one embodiment, the degree of change, for example, the ratio of sample radiation from the healthy portion of the blood vessel to the portion containing the features, can be used to assess the presence of the features.

[0166] It is understandable that the speed at which the guidewire moves within the blood vessel can "blur" the spatial resolution. However, this can be explained by adjusting the sampling rate in terms of the detection threshold, which is done, for example, by using a small signal to provide a high sampling rate. However, this means that a compromise in sampling rate, spatial resolution, and sensitivity may be necessary in this process, as high noise levels lead to decreased sensitivity, and vice versa for slower sampling. In addition, this may need to be adjusted to take into account changes in vessel diameter, the presence of stable plaque, or other factors. Thus, in one embodiment, the system may use additional data, such as expected vessel diameter, to control signal sampling and signal threshold, thereby optimizing the analysis performed to suit this scenario. In addition and / or alternatively, further processing may be required, for example, by using the rate of change in spatial intensity which can take into account the speed at which the guidewire moves through the blood vessel.

[0167] As mentioned earlier, different amounts of scattering can occur within blood vessels, in which case the measured results of backscattered stimulus radiation can be used when analyzing sample radiation. For example, the measured intensity of backscattered stimulus radiation can be used to normalize the measured intensity of sample radiation, or the threshold used when analyzing sample radiation can be changed. For example, if the measured intensity of backscattered stimulus radiation increases, this suggests that additional scattering is occurring, and therefore the threshold required to identify the presence of the feature can be changed. In this regard, the threshold can be a specific value of the measured index, such as the ratio of the intensity of the measured sample radiation from the feature to the background radiation from healthy tissue, or something similar.

[0168] In practice, it will be understood that the techniques used may depend on various factors, such as the nature of the features, the intravascular environment, or similar factors. In one embodiment, to best account for this, there is a technique that measures the intensity across the entire spectrum, i.e., at many wavelengths. This can then be analyzed using multivariate techniques and / or machine learning techniques, making it possible to perform feature detection using the most appropriate technique.

[0169] As described above, the apparatus may include outputs such as a display device, computer monitor, touchscreen, tablet, speaker, or similar, which can be configured to produce audible, visual, or tactile outputs indicating features. For example, a monitor or display can be used to show an intensity map derived from the measured sample radiation. This map can be further registered against the background of the radiopaque tip position and projected onto the corresponding area of ​​the fluoroscopic image, allowing the clinician to visualize the location of features. In addition, and / or alternatively, other forms of data representation, such as audible signals, may be used, which has the advantage of allowing the clinician to identify features without the clinician's attention being diverted from managing the guidewire by having to observe a screen.

[0170] Below, an embodiment of a preferred process for performing feature sensing is described with reference to Figures 6A and 6B. For illustrative purposes, this example is described with reference to the apparatus in Figure 5, although it will be understood that a broadly similar process can be performed using the mechanisms of other apparatuses described herein.

[0171] In this example, in step 600, the operator inserts the guidewire 110 into the subject's blood vessel and uses input 528 to initiate the measurement procedure, thereby causing the processing unit 523 to activate the radiation source 521 in step 605.

[0172] At this point, the operator begins moving the guidewire along the vessel in step 610, which is done, for example, by retracting the guidewire to pass over any hazardous vessels that contain features such as fragile atherosclerotic plaque.

[0173] In step 615, the radiation is received by the first and second detectors 522.1, 522.2, and the signals from the detectors are used by the processing unit 523 to determine the intensity of the sample radiation and the backscattered stimulating radiation, and / or background radiation in step 620. In step 625, the processing unit 523 is used to normalize the intensity of the sample radiation based on the intensity of the backscattered stimulating radiation. This attempts to adjust the magnitude of the sample radiation intensity to account for the amount of scattering within the blood vessels, which in turn may affect the intensity of the received sample radiation.

[0174] In one embodiment, the above method detects any sample radiation that has an intensity significantly higher than the intensity of background radiation detected from healthy tissue or similar material. By simultaneously measuring background radiation, variations in vessel diameter and tissue characteristics can be taken into account. In addition, and / or alternatively, the measured intensity of sample radiation may be combined with measured values ​​of backscattered stimulation radiation intensity and compared to a composite reading based on the measured intensity of background radiation, including autofluorescence from healthy tissue and / or stable plaque.

[0175] In step 630, the normalized sample radiation intensity is compared to a threshold, and the processing device 523 uses the results of the comparison to determine whether a feature is present in the blood vessel. If not, the process returns to step 610, and the operator continues to move the guidewire along the blood vessel.

[0176] However, if a feature exists, step 640 generates and presents instructions, for example, by updating the display and / or sounding an alarm. This allows the operator to initiate the procedure in step 650 by disconnecting the guidewire from the reader in step 645.

[0177] Since the above process can be carried out substantially continuously, it will be understood that in practice, it is not necessary to statically hold the guidewire within the blood vessel; instead, detection can be carried out substantially continuously as the guidewire moves within the vessel. This therefore provides a simple, effective, and timely mechanism for identifying features within blood vessels.

[0178] The above method can be used to perform feature detection in a wide range of situations. This tends to be most useful, for example, in situations where sample emission is caused by exogenous fluorescence or autofluorescence resulting from the fluorescence of the feature without additional exogenous markers. In one preferred mechanism, the device is configured to detect sample emission emitted from atherosclerotic plaques in blood vessels, and the resulting indicator indicates the presence, extent, or vulnerability of the plaques.

[0179] The above method can be more directly adopted by providing a flexible and small-sized device that is implanted as a guidewire, and can be used to perform spectroscopic measurements of low-level optical signals, i.e., measurements of the intensity of light at different wavelengths.

[0180] Another form of spectroscopy that has been evaluated for spectroscopic measurements within blood vessels is near-infrared reflectance spectroscopy, which is described in paragraph 0012. The InfraReDx NIR spectroscopy system consists of a 3.2F imaging catheter (1.07 mm in diameter) with mechanical retraction and rotation. The catheter includes a rotating core and a sealed outer sheath equipped with a guidewire as well as optical fibers that deliver and collect NIR light (as described in Waxman S, “Near infrared spectroscopy for plaque characterization,” J Interv Cardiol 2008, 21:452-458). The use of multiple optical fibers is generally incompatible with the standard coronary artery guidewire size of 350 μm. NIR spectroscopy is not usually considered a low-light-level technique because it is based on the level of reflected light. However, if measurements are performed in blood without relying on vascular flushing, vascular occlusion, or tissue compression, the signal level will be reduced. Therefore, the longitudinal retraction speed is limited to 0.5 mm / s.

[0181] Based on these examples of spectroscopic measurements of low-level light signals, while these are all currently implemented in catheters or endoscopic devices with relatively large diameters, it is clear that these spectroscopic techniques are not practically feasible in guidewires having any of the devices disclosed in the prior art discussed above, because these patents do not show how to (a) miniaturize the device to the size of a standard coronary artery guidewire, and (b) provide sufficient focusing efficiency for the level of sensitivity (and thus scanning speed) required in practical applications.

[0182] Throughout this specification and the accompanying claims, unless otherwise required by context, the phrase “contains,” and its variations “contains” or “contains,” shall be understood to mean that they include the described complete set, or group of complete sets or steps, but not to exclude other complete sets, or groups of complete sets. As used herein, unless otherwise specified, the terms “approximately” or “about” mean ±20%.

[0183] Those skilled in the art will understand that numerous variations and modifications will become apparent. It is desirable that all such variations and modifications that become apparent to those skilled in the art be considered to fall within the broad spirit and scope of the invention as described above.

Claims

1. a) A guidewire configured to be positioned within the blood vessels of a biological subject: i) A circumferential window positioned close to the distal end; ii) An optical fiber substantially extending from the proximal end of the guide wire to a position close to the window; and, iii) A substantially conical reflector positioned in close proximity to the window and having an axis aligned with the axis of the optical fiber: (1) Reflect the stimulating radiation emitted from the optical fiber so that the stimulating radiation passes substantially radially through the window, thereby exposing the blood vessel to the stimulating radiation; and, (2) A conical reflector configured to reflect the sample radiation emitted from within the blood vessel and transmit the sample radiation to the optical fiber; A guide wire comprising the reflector and the distal end of the optical fiber embedded in a support material, b) A radiation source coupled to the optical fiber and configured to emit stimulating radiation through the optical fiber; c) A detector configured to detect sample radiation received through the optical fiber; and, d) One or more processing devices: i) Analyze the detected sample radiation; and, ii) A processing apparatus configured to generate an index indicating the results of the analysis, A sensing device that performs sensing in the blood vessels of a biological subject, including [specific components / features].

2. The sensing device according to claim 1, wherein the support material is transparent to the stimulus radiation and the sample radiation.

3. The sensing device according to claim 1 or 2, wherein the reflector satisfies at least one of the following conditions. a) Including a reflective coating, b) including at least one of the following: i) A curved conical surface; ii) A curved conical surface configured to collimate the stimulus radiation; iii) A surface that is at least partially parabolic; and, iv) Flat conical surface, c) Having a diameter larger than the diameter of the optical fiber, d) The optical fiber is configured to emit stimulating radiation at an angle offset by 90°. e) An angle of cone: i) Between 45° and 135°; and, ii) Offset from 90° Cone angle, f) Configured to generate an annular beam of stimulation radiation having at least one of the following longitudinal widths i) Larger than 10 μm; ii) Larger than 50 μm; iii) Less than 200 μm; and, iv) It is approximately 100 μm.

4. The sensing device according to any one of claims 1 to 3, wherein the optical fiber satisfies at least one of the following conditions. a) Multimode optical fiber; b) Double-clad optical fiber; and c) A double-clad optical fiber, wherein the apparatus includes a beam expander coupled to the distal end of the double-clad optical fiber, the beam expander is configured to expand the stimulating radiation by diffraction so that the beam of the stimulating radiation has a diameter similar to or smaller than the diameter of the reflector, and the beam expander may include a multimode fiber spliced ​​to the double-clad optical fiber.

5. The sensing device according to any one of claims 1 to 4, wherein the radiation source satisfies at least one of the following conditions. a) Including a laser diode, b) Generate radiation in the range of 600 nm to 900 nm.

6. The filter includes a filter configured to filter the sample radiation before it reaches the detector, and optionally the filter is a) Transmitting radiation having a wavelength greater than the wavelength of the stimulus radiation; b) Transmitting radiation having a wavelength 20 nm or more greater than the wavelength of the stimulating radiation; and, c) Suppressing stimulating radiation, A sensing device according to any one of claims 1 to 5, which is a long-pass filter configured to perform at least one of the following:

7. a) A coupler configured to connect the detector and the radiation source to the optical fiber. b) A reader including at least the detector and the radiation source, c) A connector for physically separating the optical fiber from the reader, and d) A second detector configured to detect backscattered stimulus radiation, A sensing device according to any one of claims 1 to 6, comprising at least one of the following.

8. The aforementioned guide wire, a) A metal sheath that is flexible in the transverse direction but rigid in the longitudinal direction and under rotational movement around the longitudinal axis. b) Radiopaque, non-traumatic tip, c) A moldable section at the distal end, d) i) 1.5 to 2.0 m; ii) 1.75 to 1.9 m; and, iii) Approximately 1.85 m; At least one of the working lengths, and e) i) 300 μm to 400 μm; ii) 325 μm to 375 μm; and, iii) approximately 350 μm; At least one of the outer diameters, A sensing device according to any one of claims 1 to 7, comprising at least one of the following.

9. a) Determining the sample emission characteristics based on the signal received from the detector, wherein the sample emission characteristics exhibit at least one of the following: i) Measured intensity of sample radiation; ii) Values ​​derived from the measured intensity of the sample radiation; and iii) Changes in the measured intensity of the sample radiation, b) Using the radioactive properties of the sample, determine whether a feature exists within the blood vessel; and, c) If a feature exists, generate an index. The sensing device according to any one of claims 1 to 8, wherein one or more processing devices are configured to analyze the sample radiation by means of the sensing device.

10. The one or more processing devices: a) Determining the intensity of sample radiation based on the signal from the detector; b) Comparing the intensity with a threshold; and, c) If the intensity exceeds the threshold, generate an index. The system is configured to analyze the sample radiation, and optionally, i) The measured intensity of the sample radiation, (1) The measured intensity of the backscattered stimulus radiation; and, (2) Measured intensity of background radiation, Normalize based on at least one of the following; and ii) The threshold: (1) The measured intensity of the backscattered stimulus radiation; (2) Measured intensity of background radiation; and, (3) A composite value based on the measured intensity of backscattered stimulus radiation and the measured intensity of background radiation, Select based on at least one of the following: A sensing device according to any one of claims 1 to 9, satisfying at least one of the following conditions.

11. a) Tactile feedback; b) Audible output indicating the aforementioned indicator; and, c) Visual output showing the above indicator, A sensing device according to any one of claims 1 to 10, comprising an output configured to generate at least one of the following:

12. a) The sample radiation is i) Raman scattering; ii) Fluorescence; and, iii) Autofluorescence, As a result of at least one of the following, b) The sample radiation is emitted from atherosclerotic plaques within blood vessels. A sensing device according to any one of claims 1 to 11, satisfying at least one of the following:

13. The aforementioned indicators are: a) The presence of fragile atherosclerotic plaques; and, b) Degree of vulnerability of fragile atherosclerotic plaque, A sensing device according to any one of claims 1 to 12, wherein at least one of the following is shown.

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