Intravascular optical devices

Abstract

For both peripheral venous clots and clots that may lead to stroke, it is important for the physician to know the composition of the clot before selecting a thrombectomy device. The present invention relates to an intravascular device (10) having an elongated member (20), an optical fiber (30), and at least one optically interactive element (40). At least a portion of the elongated member is inserted into a portion of a patient's vasculature. At least a portion of the optical fiber is disposed within the elongated member. The optical fiber transmits optical wavelength radiation. The intravascular device emits the optical wavelength radiation from the elongated member in a radiation beam that is scattered and / or reflected by the portion of the vasculature. The emission of the radiation beam involves interaction of the transmitted optical wavelength radiation with at least one optically interactive element. The intravascular device collects at least a portion of the scattered and / or reflected optical wavelength radiation and couples at least a portion of the scattered and / or reflected optical wavelength radiation into the optical fiber, including utilizing at least one optically interactive element.

Description

[Technical Field]

[0001] The present invention relates to an intravascular device, an intravascular microcatheter and guidewire device, an intravascular inspection system, an intravascular inspection method using an intravascular inspection system, and a computer program element. The intravascular device may be, for example, a guidewire, a catheter, or a microcatheter. [Background technology]

[0002] The general background of the present invention is blood clots, and in particular the provision of information to support treatment, for example by thrombolysis or thrombectomy. Ischemic stroke is a common cause of death and a leading cause of acquired neurological disability in developed countries. In high-income countries, increasing life expectancy is expected to lead to a significant increase in the number of people affected by stroke.

[0003] WO 2016 / 205576 A1 describes a beam-shaping optical system suitable for use with optical coherence tomography, including a beam-shaping insert having a polymer material, the beam-shaping insert integrally defining a beam-shaping element. The beam-shaping element has a reflective element disposed on a curved surface. A light source generates an electromagnetic beam. An optical fiber has a core and a cladding, and the optical fiber has an optical fiber end having a first end optically coupled to the light source and a fiber end. The fiber end is configured to emit the electromagnetic beam toward the beam-shaping element. The reflective element has a reflectivity greater than about 98% for both a first wavelength band of the electromagnetic beam and a second wavelength band of the electromagnetic beam.

[0004] Thrombectomy, or physical removal of a blood clot, has been shown to be superior to thrombolysis in the treatment of acute stroke. This has led to the development of various thrombectomy devices. Currently available devices include stent retrieval devices such as Johnson & Johnson's Embotrap, Stryker's Trevo ProVue, Covidien's Solitaire, and Penumbra's Penumbra line of aspiration thrombectomy devices. Because the therapeutic time window is short, achieving the correct treatment the first time is crucial during thrombectomy. Selecting the wrong treatment device can result in additional attempts to remove the clot, thereby lengthening the procedure time. Each thrombectomy attempt can take 5 to 10 minutes. Therefore, selecting the wrong device, thereby requiring the use of a subsequent different device, can lead to increased medical complications and increased treatment costs.

[0005] A complicating factor in thrombectomy is that clots have different compositions, which pose different risks during thrombectomy. See, for example, T. Andersson, "The importance of clot properties in endovascular stroke therapy," https: / / neuronewsinternational.com / the-importance-of-clot-properties-in-endovascular-stroke-therapy / (2015). These challenges include: i) red blood cell-rich clots can be fragile and pose a risk of clot fragmentation; ii) fibrin-rich clots can have a consistency that makes them difficult to grasp with thrombectomy devices; and iii) approximately 15% of clots resist thrombectomy.

[0006] The ability to determine which therapeutic device to use to treat a clot is also advantageous for peripheral venous clots. The composition of peripheral venous clots is different from the clots that can cause ischemic stroke. If left untreated or treated with an incorrect therapeutic device, a concentrated peripheral venous clot can be transported to the lungs, for example, and cause further medical complications. Summary of the Invention [Problem to be solved by the invention]

[0007] Therefore, for both peripheral venous clots and clots that may induce stroke, it would be advantageous for physicians to know the composition of the clot before selecting a thrombectomy device. Thus, there is a need to address these and other related issues. [Means for solving the problem]

[0008] It would be advantageous to have an improved instrument for supporting intravascular examination.

[0009] The object of the present invention is solved by the subject matter of the independent claims, and further embodiments are incorporated in the dependent claims. It is noted that the below-described aspects and examples of the present invention apply to intravascular devices, intravascular microcatheter and guidewire devices, intravascular examination systems, intravascular examination methods, as well as computer program elements and computer-readable media.

[0010] According to a first aspect, an intravascular device is provided, the intravascular device comprising: an elongated member; an optical fiber; at least one light-interacting element; It has.

[0011] At least a portion of the elongated member is configured to be inserted into a portion of a patient's vasculature. At least a portion of an optical fiber is disposed within the elongated member. The optical fiber is configured to transmit optical wavelength radiation. The intravascular device is configured to emit optical wavelength radiation from the elongated member in at least two optical radiation beams that are scattered and / or reflected by the portion of the vasculature. The emission of the at least two optical radiation beams comprises interaction of the transmitted optical wavelength radiation with at least one optically interactive element. The intravascular device is configured to collect at least a portion of the scattered and / or reflected optical wavelength radiation and couple at least a portion of the scattered and / or reflected optical wavelength radiation into the optical fiber, including utilizing at least one optically interactive element.

[0012] The intravascular device may be used with an optical radiation source that generates broadband optical radiation. The broadband optical radiation may be provided simultaneously either using a broadband light source, by scanning a narrowband filter across the output of the broadband light source, or by scanning the wavelength of a monochromatic optical radiation source across multiple wavelengths so that the broadband optical radiation is coupled into and transmitted through an optical fiber. The optical radiation then exits the intravascular device and interacts with the patient's vasculature. For example, reflected and / or scattered optical radiation from a blood clot can be presented to a detection unit, such as a photodetector or spectrometer. By configuring at least two optical radiation beams to be emitted from the interventional device, different regions of the vasculature may be interrogated by the interventional device at a fixed position. Furthermore, the at least two optical radiation beams may optionally interrogate corresponding regions with different optical wavelengths. In one embodiment, a first forward-viewing optical radiation beam may be provided that emits optical wavelength radiation axially toward the distal end of the interventional device, and a second side-viewing optical radiation beam may be provided that emits or projects optical wavelength radiation radially outward relative to the longitudinal axis of the interventional device. As the interventional device is advanced through the vasculature, the first optical beam may be used to characterize the vasculature prior to the second optical beam. The second optical beam may provide improved optical measurements due to improved optical contact between the clot and the interventional device as the interventional device is moved through the clot. Additionally, by providing two optical radiation beams, for example, one extending from the end of the interventional device and the other from the sidewall of the interventional device, the physician can bend the end of the interventional device, which may be a guidewire, to explore the area as needed. The second optical radiation beam can then extend from the sidewall of the interventional device, away from the non-bendable end, and provide accurate measurements as the interventional device slides through the object being interrogated. Two or more beams of optical radiation may be emitted from the sidewall of the interventional device, or indeed two or more beams of optical radiation can be projected from the front surface of the interventional device, these beams may overlap but have different wavelength ranges.The different wavelength ranges can be provided through appropriate scanning or switching, or can have different angular orientations and have the same wavelength range or different wavelength ranges.

[0013] In one example, the at least two beams of optical radiation include a first beam of optical radiation emitted from a sidewall of the elongate member.

[0014] In one example, the at least two beams of optical radiation include a second beam of optical radiation emitted from a sidewall of the elongate member.

[0015] In one example, the wavelength range of the first optical radiation beam is different from the wavelength range of the second optical radiation beam.

[0016] In this way, different light wavelengths can be emitted and therefore different volumes can be optically probed.

[0017] In one example, a first optical radiation beam is emitted from the elongate member at a first longitudinal position of the elongate member, and a second optical radiation beam is emitted from the elongate member at a second longitudinal position of the elongate member that is different from the first longitudinal position.

[0018] Thus, for example, there can be one beam of optical radiation emitted transversely from an intravascular device having one wavelength range, and a second beam of optical radiation parallel to the first but having a second wavelength range, emitted at a different location along the length of the intravascular device, such as a guidewire. Then, as the device is moved through the clot, the clot is interrogated over one wavelength range, then over the second wavelength range, and the physician need not rotate the device, but simply move it longitudinally.

[0019] In other words, one optical radiation beam can be emitted transversely, for example 4 centimeters from the tip of the intravascular device, having one wavelength range, and a second beam can be emitted in the same direction, for example 5 centimeters from the tip of the intravascular device, and parallel to the first optical radiation beam, but having a different wavelength range. In one example, the at least two optical radiation beams include optical radiation beams emitted from the end wall of the elongated member.

[0020] Thus, a forward directed optical radiation beam can be provided.

[0021] In one example, the wavelength range of the first optical radiation beam is different to the wavelength range of the optical radiation beam emitted from the end wall of the elongate member.

[0022] In one example, the wavelength range of the second optical radiation beam is different to the wavelength range of the optical radiation beam emitted from the end of the elongate member.

[0023] In one example, at least one optically interactive element comprises a wavelength selective element.

[0024] In one example, a portion of the optical fiber at a distal end of the optical fiber is fixedly connected to the elongate member, and at least a portion of the optical fiber disposed within the elongate member other than the fixed distal end is not fixedly connected to the elongate member.

[0025] According to a second aspect, there is provided an intravascular device, the intravascular device comprising: an elongated member; an optical fiber; at least one light-interacting element; It has.

[0026] At least a portion of the elongated member is configured to be inserted into a portion of a patient's vasculature. At least a portion of an optical fiber is disposed within the elongated member. The optical fiber is configured to transmit optical wavelength radiation. The intravascular device is configured to emit optical wavelength radiation from the elongated member in an optical radiation beam that forms an annular radiation profile substantially perpendicular to a longitudinal axis of the elongated member and that is scattered and / or reflected by the portion of the vasculature. The emission of the optical radiation beam comprises interaction of the transmitted optical wavelength radiation with at least one optically interactive element. The intravascular device is configured to collect at least a portion of the scattered and / or reflected optical wavelength radiation and couple at least a portion of the scattered and / or reflected optical wavelength radiation into the optical fiber with the use of the at least one optically interactive element.

[0027] Thus, the intravascular device emits and collects optical wavelength radiation to / from different angles around the elongate member at the same longitudinal location or position. In this manner, the interventionalist does not need to torque or rotate the guidewire at a longitudinal location to interrogate the clot, as optical wavelength radiation is emitted all around the periphery of the intravascular device at that location.

[0028] According to a third aspect, there is provided an intravascular microcatheter and guidewire device, comprising: a microcatheter; an intravascular device according to the first aspect or an intravascular device according to the second aspect, It has.

[0029] At least a portion of the microcatheter is configured to be inserted into a portion of a patient's vascular system. The microcatheter has at least one optically transparent wall portion. The intravascular device is configured to slide within the microcatheter along a longitudinal axis of the microcatheter. The microcatheter and intravascular device are configured such that when the intravascular guidewire is positioned at one or more longitudinal positions along the longitudinal axis of the microcatheter, optical wavelength radiation is emitted from the microcatheter through the at least one optically transparent wall portion of the microcatheter, and scattered and / or reflected optical wavelength radiation enters the microcatheter through the at least one optically transparent wall portion of the microcatheter.

[0030] According to a fourth aspect, there is provided an intravascular inspection system, the intravascular inspection system comprising: an intravascular device according to the first aspect, or an intravascular device according to the second aspect, or an intravascular microcatheter and guidewire device according to the third aspect; a source of optical radiation; an optical radiation detector; a processing unit, It has.

[0031] The optical radiation source is configured to generate optical wavelength radiation over a broadband range and couple into the optical fiber. The optical radiation detector is configured to generate at least one detection signal based on the scattered and / or reflected optical wavelength radiation. The processing unit is configured to determine at least one spectrally resolved data set based on the at least one detection signal. The processing unit is configured to determine information about the blood clot based on the at least one spectrally resolved data set.

[0032] In this manner, optical spectroscopy can be used to provide information about a suspected occlusive structure, such as a blood clot, and the location of the suspected occlusive structure can be determined. By having more than one optical radiation beam used to probe a vascular structure, the location of the blood clot and its characteristics can be determined more efficiently and effectively. Thus, a determination can be made as to whether a blood clot is present, and if so, it is possible to distinguish between different types of blood clots, for example, to determine whether the clot is red blood cell rich, to determine whether the clot is fibrin rich, and to determine whether the clot is of the type that is resistant to thrombectomy and must be treated by thrombolysis.

[0033] In other words, the correct clot removal device for removing the clot can be determined, thereby reducing treatment time, reducing costs, and reducing patient risk by reducing the need to perform a second clot removal procedure if the incorrect type of device was initially selected.

[0034] According to a fifth aspect, there is provided a method of intravascular inspection using an intravascular inspection system according to the fourth aspect, the method comprising: - generating optical wavelength radiation over a broadband range by an optical radiation source; - coupling broadband optical wavelength radiation into the optical fiber of an intravascular device or an intravascular microcatheter and guidewire device; - collecting scattered and / or reflected optical wavelength radiation from the patient's vasculature using an intravascular device or an intravascular microcatheter and guidewire device; - generating, by an optical radiation detector, at least one detection signal based on the scattered and / or reflected optical wavelength radiation; - determining, by a processing unit, at least one spectrally resolved data set based on the at least one detected signal; - determining, by a processing unit, information about the blood clot based on at least one spectrally decomposed data set; It has.

[0035] According to another aspect, there is provided a computer program element for controlling the aforementioned apparatus and / or system, configured to perform the aforementioned method steps when the computer program element is executed by a processing unit.

[0036] According to another aspect, a computer readable medium having stored thereon a computer element as described above is provided.

[0037] According to a sixth aspect, a system, a corresponding method of using the system to determine the composition of a peripheral venous blood clot, and a corresponding computer program product are provided.

[0038] The system for determining the composition of a peripheral venous blood clot comprises: an intravascular device for measuring clot composition in the peripheral vasculature; an elongated member; an optical fiber; Including, At least a portion of the elongate member is configured to be inserted into a portion of a patient's vascular system; At least a portion of the optical fiber is disposed within the elongated member; the optical fiber is configured to transmit optical wavelength radiation; the intravascular device is configured to emit a portion of the optical wavelength radiation from the elongate member that is scattered and / or reflected by a portion of the vasculature; The intravascular device is configured to collect at least a portion of the scattered and / or reflected optical wavelength radiation and couple at least a portion of the scattered and / or reflected optical wavelength radiation into an optical fiber, and the system further comprises: a source of optical radiation; an optical radiation detector; a processing unit; Including, the optical radiation source is configured to generate optical wavelength radiation over a broad band and couple it into the optical fiber; the optical radiation detector is configured to generate at least one detection signal based on the scattered and / or reflected optical wavelength radiation; the processing unit is configured to determine at least one spectrally resolved data set based on the at least one detected signal; at least one spectrally resolved data set has a spectrum corresponding to collagen; The processing unit is configured to determine a collagen content from the spectrum corresponding to collagen, and to determine information about the clot based on the collagen content.

[0039] A corresponding method for determining collagen content of a peripheral blood clot using the aforementioned intravascular testing system for use in determining clot composition in the peripheral vasculature includes: - generating a broadband range of optical wavelength radiation with an optical radiation source; - coupling broadband optical wavelength radiation into the optical fiber of an intravascular device or an intravascular microcatheter and guidewire device; - collecting scattered and / or reflected optical wavelength radiation from the patient's vasculature using an intravascular device or an intravascular microcatheter and guidewire device; - generating, by an optical wavelength radiation detector, at least one detection signal based on the scattered and / or reflected optical wavelength radiation; - determining, by a processing unit, at least one spectrally resolved data set based on the at least one detection signal, the at least one spectrally resolved data set having a spectrum corresponding to collagen; - determining, by a processing unit, a collagen content from the spectrum corresponding to collagen, and determining information about the clot based on the collagen content; may include:

[0040] A corresponding computer program product is also provided having instructions that, when executed by a processor, cause the processor to perform the method.

[0041] Advantageously, any advantages provided by any of the above aspects apply equally to all of the other aspects, and vice versa.

[0042] The above aspects and examples will be apparent from and elucidated with reference to the embodiments described hereinafter.

[0043] Exemplary embodiments are described below with reference to the following drawings: [Brief explanation of the drawings]

[0044] [Figure 1] 1 shows a schematic example of an intravascular device. [Figure 2] 1 shows a schematic example of an intravascular microcatheter and guidewire device, and an intravascular inspection system. [Figure 3] This shows the method of intravascular examination. [Figure 4] Diffuse reflectance spectroscopy (DRS) system for clot differentiation is shown. [Figure 5] 1 shows a state-of-the-art tissue sensing guidewire where sensing occurs at the tip of the guidewire. [Figure 6] 1 shows an example of an intravascular guidewire. [Figure 7] 1 shows an example of an intravascular guidewire. [Figure 8] 1 shows an example of an intravascular microcatheter and guidewire device. [Figure 9] 1 shows an example of an intravascular guidewire. [Figure 10] 1 shows an example of an intravascular guidewire. [Figure 11] 1 shows an example of an intravascular guidewire. [Figure 12] 1 shows an example of an intravascular guidewire. [Figure 13] 1 shows an example of an intravascular guidewire. [Figure 14] The measured change in light intensity (arbitrary units) versus wavelength (nanometers) is shown for three clot analog samples. [Figure 15] Predictive ability (Predictor) versus collagen percentage (%) is shown for several measured clot analog samples. DETAILED DESCRIPTION OF THE INVENTION

[0045] FIG. 1 illustrates an example of an intravascular device 10. The device includes an elongate member 20, an optical fiber 30, and at least one optically interacting element 40. At least a portion of the elongate member is configured to be inserted into a portion of a patient's vasculature. At least a portion of the optical fiber is disposed within the elongate member. The optical fiber is configured to transmit optical wavelength radiation. The intravascular device is configured to emit the optical wavelength radiation from the elongate member in at least two optical radiation beams that are scattered and / or reflected by the portion of the vasculature. The emission of the at least two optical radiation beams involves interaction of the transmitted optical wavelength radiation with the at least one optically interacting element. The intravascular device includes utilization of the at least one optically interacting element configured to collect at least a portion of the scattered and / or reflected optical wavelength radiation and couple at least a portion of the scattered and / or reflected optical wavelength radiation into the optical fiber.

[0046] In one example, the optical wavelength radiation is generated by an optical radiation source that simultaneously emits broadband optical radiation. In one example, the optical wavelength radiation is generated by an optical radiation source that emits narrowband optical radiation, and the emitted optical wavelengths are scanned over a range of wavelengths to generate the broadband optical radiation that is transmitted by an optical fiber.

[0047] In one example, the at least one optically interactive element includes at least one optically transmissive wall portion 50 of the elongated member, where emitted optical wavelength radiation is directed out of the elongated member through the at least one optically transmissive wall portion, and a portion of the scattered and / or reflected optical wavelength radiation returns through the at least one optically transmissive wall portion. Thus, the window can protect the optical fiber and can be a wavelength-sensitive filter, thus providing a convenient way to select a probing wavelength range, where the emission windows for different beams can have different passband wavelength ranges, providing an efficient way to provide beams with different wavelength ranges. These windows can be in the side walls of the elongated member, and windows can be in the end walls of the elongated member if desired.

[0048] In one example, the intravascular device is a guidewire.

[0049] In one example, the intravascular device is a microcatheter.

[0050] In one example, the elongate member includes a radiopaque marker.

[0051] In one example, the elongate member is a tube.

[0052] In one example, the optical fiber has radiopaque markers.

[0053] In this way, the operator can determine in which particular direction or directions the optical wavelength radiation is emitted to maximize the overlap between the clot being examined and the spectroscopic sensing volume.

[0054] According to one example, the at least two beams of optical radiation include a first beam of optical radiation emitted from a sidewall of the elongate member.

[0055] In one example, the first beam of optical radiation is emitted from a sidewall of the elongate strip at least 3 centimeters from the end of the elongate strip.

[0056] In one example, a first beam of optical radiation is emitted in a direction perpendicular to the longitudinal axis of the elongate member.

[0057] In one example, the at least one optically interactive element comprises a beam splitter.

[0058] In one example, the at least one optically interactive element comprises a 45 degree beam splitter.

[0059] In one example, the at least one optically interactive element comprises a region of optical fiber that exhibits total internal reflection.

[0060] In one example, the at least one optically interactive element comprises an optical wavelength filter.

[0061] In one example, the at least one light-interacting element comprises a fiber Bragg grating.

[0062] According to one example, the at least two beams of optical radiation include a second beam of optical radiation emitted from a sidewall of the elongate member.

[0063] In one example, the second optical radiation beam is emitted from a sidewall of the elongate strip at least 3 centimeters from the end of the elongate strip.

[0064] In one example, the second optical radiation beam is emitted in a direction perpendicular to the longitudinal axis of the elongate member.

[0065] In one example, the at least one optically interactive element comprises a beam splitter.

[0066] In one example, the at least one optically interactive element comprises a 45 degree beam splitter.

[0067] In one example, the at least one light-interacting element comprises a fiber Bragg grating.

[0068] In one example, the at least one optically interactive element comprises a wavelength passband filter.

[0069] In one example, at least one optically interactive element has a wavelength selective window.

[0070] According to one example, the wavelength range of the first optical radiation beam is different from the wavelength range of the second optical radiation beam.

[0071] According to one example, a first optical radiation beam is emitted from the elongate member at a first longitudinal position of the elongate member, and a second optical radiation beam is emitted from the elongate member at a second longitudinal position of the elongate member that is different from the first longitudinal position.

[0072] According to one example, the at least two beams of optical radiation comprise beams of optical radiation emitted from end walls of the elongate member.

[0073] In one example, the optical radiation beam emitted from the end wall of the elongate member is emitted in a direction parallel to the longitudinal axis of the elongate member.

[0074] According to one example, the wavelength range of the first optical radiation beam is different from the wavelength range of the optical radiation beam emitted from the end wall of the elongate member.

[0075] According to one example, the wavelength range of the second optical radiation beam is different from the wavelength range of the optical radiation beam emitted from the end of the elongate member.

[0076] According to one example, the at least one optically interactive element comprises a wavelength selective element.

[0077] In one example, the at least one wavelength selective element comprises a fiber Bragg grating.

[0078] In one example, the at least one wavelength selective element comprises a wavelength passband filter.

[0079] In one example, at least one wavelength-selective element has a wavelength-selective window, which may be located at or within a wall of the elongate member, at the sidewall and / or front wall, and provides an efficient way of providing optical wavelength radiation used to interrogate a material via optical wavelength radiation transmitted through the element to have only a specific wavelength range.

[0080] According to one example, a portion of the optical fiber at a distal end of the optical fiber is fixedly connected to the elongate member, and at least a portion of the optical fiber disposed within the elongate member other than the fixed distal end is not fixedly connected to the elongate member.

[0081] FIG. 1 may also depict another example of an intravascular device 10. The intravascular device 10 includes an elongate member 20, an optical fiber 30, and at least one optically interacting element 40. At least a portion of the elongate member is configured to be inserted into a portion of a patient's vasculature. At least a portion of the optical fiber is disposed within the elongate member. The optical fiber is configured to transmit optical wavelength radiation. The intravascular device is configured to emit optical wavelength radiation from the elongate member in an optical radiation beam that forms an annular emission profile substantially perpendicular to a longitudinal axis of the elongate member and is scattered and / or reflected by the portion of the vasculature. The emission of the optical radiation beam involves interaction of the transmitted optical wavelength radiation with at least one optically interacting element. The intravascular device is configured to collect at least a portion of the scattered and / or reflected optical wavelength radiation and couple at least a portion of the scattered and / or reflected optical wavelength radiation into the optical fiber, including utilizing at least one optically interacting element.

[0082] In one example, the annular optical wavelength radiation is emitted from a sidewall of the elongate strip at least 3 centimeters from the end of the elongate strip.

[0083] Thus, the interventionalist can bend the tip of the guidewire as needed, for example, to provide the probing beam at the correct angle from the end of the guidewire, without affecting the lateral transmit beam or beams.

[0084] In one example, one or more of the at least one optically interacting element are rotationally symmetric about the longitudinal axis of the elongate member.

[0085] In one example, one or more of the at least one rotationally symmetric optical interacting element has a conical structure.

[0086] In one example, the at least one optically interactive element comprises at least one optically transmissive wall portion 50 of the elongated member, where emitted optical wavelength radiation is directed out of the elongated member through the at least one optically transmissive wall portion, and a portion of the scattered and / or reflected optical wavelength radiation returns through the at least one optically transmissive wall portion. Thus, the window can protect the optical fiber and can be a wavelength-sensitive filter, thus providing a convenient way to select a probing wavelength range, where different beam exit windows can have different passband wavelength ranges, providing an efficient way to provide beams with different wavelength ranges. These windows can be in the side walls of the elongated member, and windows can be in the end walls of the elongated member, if desired.

[0087] In one example, at least one optical interacting element is configured to emit an additional optical radiation beam laterally from the elongate member at a different longitudinal position relative to the annular emission profile. The optical radiation beam can have a smaller angular spread than the annular emission profile. Thus, probing the annular emission profile (or donut-shaped emission) can be used to quickly locate a clot, and then a second optical radiation beam can be moved to that position, and via rotation of the guidewire, the optical radiation beam can be used to interrogate the clot with a high signal-to-noise ratio because the signal can be limited to the clot and does not have background vasculature information.

[0088] FIG. 2 illustrates an example of an intravascular microcatheter and guidewire device 100 including a microcatheter 110 and an intravascular device 10 as described with respect to either of the two embodiments described with respect to FIG. 1. At least a portion of the microcatheter is configured to be inserted into a portion of a patient's vasculature. The microcatheter has at least one optically transparent wall portion. The intravascular device is configured to slide within the microcatheter along the longitudinal axis of the microcatheter. The microcatheter and intravascular device are configured such that, when the intravascular guidewire is positioned at one or more longitudinal positions along the longitudinal axis of the microcatheter, optical wavelength radiation is emitted from the microcatheter through the at least one optically transparent wall portion of the microcatheter, and scattered and / or reflected optical wavelength radiation enters the microcatheter through the at least one optically transparent wall portion of the microcatheter.

[0089] FIG. 3 illustrates an example of an intravascular inspection system 200. The system includes an intravascular device 10 as described with respect to either of the two embodiments described with respect to FIG. 1, or an intravascular device 100 according to claim 11, or an intravascular microcatheter and guidewire device 100 as described with respect to FIG. 2. The system 200 also includes an optical radiation source 210, an optical radiation detector 220, and a processing unit 230. The optical radiation source is configured to generate optical wavelength radiation over a broadband range and couple it into an optical fiber. The optical radiation detector is configured to generate at least one detection signal based on the scattered and / or reflected optical wavelength radiation. The processing unit is configured to determine at least one spectrally resolved data set based on the at least one detection signal. The processing unit is configured to determine information about the blood clot based on the at least one spectrally resolved data set.

[0090] In one example, the optical radiation source is configured to scan narrowband or monochromatic optical wavelength radiation over a wide band, and the at least one optical radiation signal comprises scattered and / or reflected optical radiation for each wavelength step of the scan.

[0091] In one example, the optical radiation source is configured to provide broadband optical wavelength radiation in one beam, and the detector and processing unit can be part of a spectrometer that determines a "one-shot" detection signal and a spectrally resolved data set.

[0092] In one example, the processing unit is configured to provide an output indicating that a spectrum from a blood vessel wall is detected.

[0093] In this way, a feedback loop is provided to the interventionalist, who then knows when the clot is not being interrogated and can move the guidewire either rotationally or longitudinally as necessary to interrogate the clot.

[0094] Associated with system 200 is a method of intravascular inspection using an intravascular inspection system. The method includes: - generating optical wavelength radiation over a broadband range using an optical radiation source; - coupling broadband optical wavelength radiation into the optical fiber of an intravascular device or an intravascular microcatheter and guidewire device; - collecting scattered and / or reflected optical wavelength radiation from the patient's vasculature using an intravascular device or an intravascular microcatheter and guidewire device; - generating, by an optical radiation detector, at least one detection signal based on the scattered and / or reflected optical wavelength radiation; - determining, by a processing unit, at least one spectrally resolved data set based on the at least one detected signal; - determining, by a processing unit, information about the blood clot based on at least one spectrally decomposed data set; It has.

[0095] The intravascular devices, intravascular microcatheter and guidewire devices, intravascular inspection systems, and methods of intravascular inspection will now be described in more detail with respect to specific embodiments, with reference to FIGS.

[0096] Figure 4 shows a diffuse reflectance spectroscopy (DRS) system for clot differentiation. Research has shown that DRS, among other optical analysis techniques, can be used to distinguish between different types of clots and help physicians make the best treatment decisions. As shown in "A," a light source emits optical wavelength radiation through an optical fiber. As shown in "B," the optical wavelength radiation is scattered and absorbed in the clot, and some of the scattered optical wavelength radiation is reflected back into the optical fiber. As shown in "C," the optical wavelength radiation is received and analyzed by a spectrometer. As shown in "D," an algorithm calculates physiological parameters, such as red blood cell, fibrin, and white blood cell content, which are presented to the operator. Therefore, in this system, optical wavelength radiation is used to illuminate a diffuse reflectance sample, which may be, for example, biological tissue. The new devices, systems, and methods described herein can utilize an optical radiation source that scans a narrow emission band over a wide wavelength range to generate this optical wavelength radiation, such as by scanning a tunable laser, or can have a light source that emits optical wavelength radiation across multiple optical wavelengths, or can actually consist of multiple narrowband light sources (such as infrared or visible LEDs or lasers) emitting simultaneously or sequentially. The optical wavelength radiation is scattered and / or absorbed by the sample. A portion of the backscattered optical wavelength radiation is collected and analyzed using a photodetector, resulting in a spectrum that is characteristic of the sample. Typically, these spectra exhibit a scattering background punctuated by characteristic dips caused by absorbers such as blood, water, and fat.Detailed descriptions of exemplary methods for analyzing data can be found, for example, in the following publications: R. Nachabe, BHW Hendriks, AE Desjardins, M. van der Voort, MB van der Mark, and HJCM Sterenborg, "Estimation of lipid and water concentrations in scattering media with diffuse optical spectroscopy from 900 to 1600 nm", J. Biomed. Opt. 15, (2010); Rami Nachabe, Benno HW Hendriks, Marjolein van der Voort, Adrien E. Desjardins, and Henricus JCM Sterenborg, "Estimation of biological chromophores using diffuse optical spectroscopy: benefit of extending the UV-VIS wavelength range to include 1000 to 1600 nm", Optics Express 18 (2010) p1432; and R. Nachabe, et al., "Diagnosis of breast cancer using "Diffuse optical spectroscopy from 500 to 1600 nm: comparison of classification methods" J. Biomed. Opt. 16(8): p. 087010 (2011).

[0097] FIG. 5 shows a state-of-the-art tissue-sensing guidewire placed within a blood vessel, where optical sensing is performed at the tip of the guidewire. The blood vessel and vessel wall are shown, and surrounding tissue is represented beyond the vessel wall. The "atraumatic optical radiation emitting tip" is represented by "A," the "sensing volume" is represented by "B," and the "blood clot" is represented by "C." Such systems are described, for example, in US5439000, US5601087A, US7532920B1, and US6445939B1. However, such sensing devices are suboptimal for some of the above sensing applications for several reasons: i) the tip of the guidewire tends to slide along the vessel wall, which can make it difficult to obtain good optical contact with the clot; ii) because the guidewire typically slides along the vessel wall, the sensed volume includes not only the clot but also the vessel wall and surrounding tissue, reducing the signal-to-noise ratio and making the reflected optical wavelength radiation more difficult to interpret; iii) some interventionalists prefer to use guidewires with specially shaped tips, which are sometimes tips that they shape themselves; however, such tips can interfere with optical radiation emission and collection at the tip; and iv) These include: neural guidewires are typically designed with very flexible tips to avoid damage to the vasculature, while in forward-sensing optical guidewires, the necessary optical fiber stiffens the tip, thereby limiting its flexibility; v) because clots can be heterogeneous, physicians will want to scan along the length of the clot without losing track of the guidewire's position, which is difficult when sensing occurs at the tip of the guidewire because the guidewire needs to be completely withdrawn from the clot to sense the proximal portion of the clot; and vi) for regulatory, training, or safety reasons, it would be beneficial to have the option to measure clot composition from within the neurological catheter, so that the measurement guidewire does not need to come into direct contact with the vessel wall or clot.

[0098] Thus, sensing volume may be suboptimal for state-of-the-art tissue sensing guidewires where sensing occurs at the tip of the guidewire as shown in Figure 5. Some of these obstacles are addressed by the devices, systems, and methods described herein.

[0099] Figure 6 shows an example of an intravascular guidewire. A represents a "side-emitting guidewire," B represents a "sensing volume," C represents a "clot," and D represents an "arbitrarily shaped tip." In this embodiment, optical wavelength radiation is emitted and received at the shaft of the wire at a distance from the tip (e.g., at least 3 centimeters away from the tip). Thus, the tip can be shaped, bent, or otherwise designed as desired without affecting spectroscopic sensing. Optical wavelength radiation is emitted and received substantially perpendicular to the major axis of the wire. The interventionist can "pass the clot" and, once this is achieved, perform traction and pull back along its length to scan the clot composition without losing track of the wire position. To obtain the best signal, the interventionist may have to torque (i.e., rotate) the wire to optimize overlap between the sensing volume and the clot and minimize overlap between the sensing volume, the vessel wall, and potentially other surrounding tissues. To aid in finding the correct rotation angle, the wire can incorporate radiopaque markers that indicate the sensing direction. Alternatively, if a spectrum corresponding to a vessel wall is detected, feedback may be provided to the operator in the form of a warning.

[0100] Figure 7 shows an example of an intravascular guidewire. Arrows indicate the direction toward the "optical radiation source" (represented by "A") and the "spectrometer" (represented by "B"), which are located outside the intravascular portion of the guidewire at the other end of the optical fiber. The "hollow tube" is represented by "C," the "optical fiber" by "D," the "emitted optical wavelength radiation" by "E," the "hole with transparent filling" by "F," the "crack with reflective coating" by "G," and the "tip" by "H." Typically, the wire has a hollow tube or coil with the optical fiber inside the lumen. A hole or gap in the tube at the distal end of the fiber allows optical wavelength radiation to pass in and out of the lumen. The hole or gap is typically sealed with a transparent material to ensure optimal optical contact with the outside and to prevent blood from entering. The fiber is typically fixed only at the distal end to allow the fiber to slide within the lumen to facilitate bending. Alternatively, the fiber can be placed in a groove along the side of the wire. The wire can be surrounded by additional layers (e.g., shrink tubing). These surrounding layers are also transparent to the wavelengths used for spectroscopy. Optical wavelength radiation is emitted from the fiber in a direction substantially perpendicular to the major axis of the guidewire (which is typically also the major axis of the fiber). Ideally, the same fiber is used to collect optical wavelength radiation reflected from the surrounding tissue and blood. The end of the fiber can be cleaved at an angle of approximately 45 degrees to deflect the optical wavelength radiation out / into the fiber by approximately 90 degrees. Optionally, the cleaved edge of the fiber can be coated with a reflective coating. Alternatively, a separate mirror can be utilized. Optionally, the facet of the fiber or the mirror can be shaped to focus or defocus the optical wavelength radiation.

[0101] Figure 8 shows an example of an intravascular microcatheter and guidewire device. A "transparent catheter" is represented by "A," a "side-release guidewire" by "B," a "blood clot" by "C," and a "tip of arbitrary shape" by "D." In this embodiment, a wire is combined with a microcatheter that is transparent at its distal end to the wavelengths used in spectroscopy. Once the microcatheter has passed the clot, a wire is inserted and spectroscopic measurements are made through the wall of the microcatheter without the wire leaving the microcatheter. A mechanical block can be used to prevent the tip of the wire from exiting the microcatheter. An advantage of this device is that the wire itself never comes into contact with the clot or the vessel wall, so the wire (and wire operator) requirements are lower than in embodiments without a transparent microcatheter.

[0102] FIG. 9 shows an example of an intravascular guidewire. The "side-release guidewire" is represented by "A," the two "sensing volumes" are represented by "B," the "blood clot" is represented by "C," and the "arbitrarily shaped tip" is represented by "D." In this embodiment, the neurointerventionalist does not need to rotate the wire because the sensing volume covers a 360-degree ring around the wire. This ensures that the blood clot is always within the sensing volume of the wire. Note that the sensing volume also includes the vessel wall and possibly surrounding tissue, resulting in a lower signal-to-noise ratio than in embodiments in which only the blood clot is interrogated. In this embodiment, the optical fiber is inside a hollow tube (i.e., not in a groove). Instead of a single hole / window, the tube has multiple openings or a single slit (optionally with a window). To deflect optical wavelength radiation over a 360-degree range, the tip of the fiber may have a conical shape (as shown in FIG. 10), which may be achieved, for example, by polishing. In FIG. 10, the "optical radiation source" is represented by "A," the "spectrometer" by "B," the "hollow tube" by "C," the "optical fiber" by "D," the "emitted optical wavelength radiation" by "E," the "hole or slit with transparent filler" by "F," the "cone" by "G," and the "tip" by "H." If the refractive index of the fiber and the cone angle are appropriate, total internal reflection in the cone will deflect the optical wavelength radiation from the fiber into an annular shape that diverges laterally away from the intravascular device. Thus, the sensing volume can be a "doughnut" shaped volume from which optical wavelength radiation can be scattered / reflected and collected.

[0103] FIG. 11 shows an example of an intravascular guidewire. The "optical radiation source" is represented by "A," the "spectrometer" by "B," the "hollow tube" by "C," the "optical fiber" by "D," the "emitted optical wavelength radiation" by "E," the "hole or slit with transparent filler" by "F," the "reflection cone" by "G," and the "tip" by "H." In this embodiment, a cone-shaped mirror is placed adjacent to the distal end of the fiber to generate a 360-degree ring of optical wavelength radiation around the wire (creating an annular or donut-shaped field of optical wavelength radiation). Ideally, the mirror cone angle is 45 degrees. There are also other, less efficient ways to shape the optical wavelength radiation profile; for example, a scattering medium may be placed in front of the optical fiber.

[0104] FIG. 12 shows an example of an intravascular guidewire. The "optical radiation source" is represented by "A," the "spectroscope" by "B," the "hollow tube" by "C," the "optical fiber optic" by "D," the "first sensing volume" by "E," the "hole with transparent filling" by "F," the "wavelength-selective element" by "G," the "second sensing volume" by "H," and the "tip" by "I." While side-sensing wires often offer advantages over forward-sensing wires, as discussed above, there are situations in which a forward-sensing guidewire has advantages. This is particularly the case when a physician does not want to pass a blood clot. Therefore, it would be highly beneficial if a single wire could provide both sensing options simultaneously, or if the physician could simply switch between them. Thus, measurements at both locations are simultaneous, since these regions can be probed with different wavelength ranges. However, it can be beneficial to limit optical wavelength radiation exposure and provide for actual switching, for example. Therefore, switching can actually be achieved simply by changing the spectrum of the optical wavelength radiation coupled into the fiber. Another way to provide both sensing options is to use two optical fibers in the wire, one for forward sensing and one for side sensing. However, this side and forward sensing can be provided by a single fiber. Thus, there can be one side beam and one forward beam, or two or more side beams (which can form a doughnut-shaped emission) and forward emissions, which can operate over the same wavelength range or over different wavelength ranges.

[0105] Thus, the system allows different sensing volumes to be interrogated by using different wavelengths or wavelength ranges for each sensing volume. For example, a wavelength range of approximately 450 nm to 900 nm may be used, which is primarily visible light radiation, to distinguish different types of blood clots in one sensing volume, and a wavelength range of approximately 1000 to 1600 nm may be used, which is near-infrared, or NIR, light radiation, to simultaneously distinguish different types of blood clots in a second sensing volume. Alternatively, the same or similar wavelengths may be used, e.g., wavelengths of 520 nm, 830 nm, 1270 nm, and 1450 nm may be used to distinguish different types of blood clots in one sensing volume, while wavelengths of 525 nm, 835 nm, 1275 nm, and 1455 nm may be used to simultaneously distinguish different types of blood clots in a second sensing volume. Wavelength-selective elements integrated into the wire may also be used to ensure that sensing volume E is illuminated with light-wavelength radiation having a different wavelength than sensing volume H. Different types of wavelength selective elements can be used. For example, a wavelength selective element such as a fiber Bragg grating, or FBG, can be used to couple optical wavelength radiation within a predetermined wavelength range from a fiber. A depiction of this is shown in FIG. 12.

[0106] FIG. 13 shows an example of an intravascular guidewire. The "optical radiation source" is represented by "A," the "spectroscope" by "B," the "hollow tube" by "C," the "optical fiber" by "D," the "sensing volume 1 (visible light radiation)" by "E," the "visible-transmitting IR-absorbing window" by "F," the "50:50 splitter / coupler" by "G," the "sensing volume 2 (infrared light radiation)" by "H," and the "visible-absorbing IR-transmitting window" by "I." In this embodiment, approximately half of the optical wavelength radiation is coupled into the first sensing volume, regardless of wavelength, and optical filters are then used to filter out the unwanted optical wavelength radiation. These optical filters may be integrated into the optical window or into an optical filler sealing the opening of the hollow tube. Although a 50:50 splitter / coupler has been mentioned here, other ratios may be utilized, as will be understood by those skilled in the art.

[0107] Thus, in summary, the above disclosure relates to an intravascular device having an associated optical wavelength radiation generating and spectral data generating system, the intravascular device comprising the following features: i) at least one optical fiber intended to emit optical wavelength radiation into a blood vessel or biological tissue adjacent to the blood vessel and to collect a portion of the optical wavelength radiation reflected by the tissue; ii) a portion of the optical wavelength radiation emitted and received in a direction perpendicular to a major axis of the intravascular device; iii) a portion of the optical wavelength radiation emitted and received significantly proximal to the tip of the intravascular device (significantly proximal to the tip may mean more than 3 centimeters from the tip; in cases where the intravascular device has a functional tip with a coil proximal to the length covered by the coil, the coil is a standard design element in medical guidewires to achieve desired mechanical properties; the tip of a guidewire must typically be more flexible than the shaft, and therefore the coil is used to provide the desired "flexibility"); iv) a tip optimized for mechanical properties and not optimized for its optical or sensing properties; v) a tip optimized for different optical properties; The microcatheter may have one or more of the following: vi) emitting and receiving optical wavelength radiation from / to the tip, which may include the use of wavelength-selective elements so that wavelengths are emitted / received in different sensing volumes; vii) emitting and receiving optical wavelength radiation from / to the lateral direction, which may include the use of wavelength-selective elements to emit / receive different optical wavelengths in different sensing volumes; vii) emitting / receiving optical wavelength radiation from / to the lateral direction in an annular or donut shape so that guidewire rotation or torque is not required to provide rotational sensitivity; viii) an intravascular microcatheter that is optically transparent at a predetermined length from the tip, with a lumen suitable for receiving a guidewire so that the intravascular device can measure from within the catheter through the catheter wall; and ix) a (radiopaque) marker (or other feedback mechanism) to assist in torqueing the intravascular device to maximize overlap between the clot and the spectroscopic sensing volume.

[0108] An intravascular device for use in determining clot composition in the peripheral vasculature shares many of the features described above with reference to Figure 1. In contrast, however, it is not necessary to include the aforementioned light-interacting element 40 or to provide the aforementioned two light beams. Thus, with reference to Figure 1, an intravascular device for determining clot composition in the peripheral vasculature may include: an elongated member 20; an optical fiber 30; and At least a portion of the elongate member 20 is configured to be inserted into a portion of the patient's vascular system; At least a portion of the optical fiber 30 is disposed within the elongated member 20; the optical fiber is configured to transmit optical wavelength radiation; the intravascular device is configured to emit a portion of the optical wavelength radiation from the elongate member that is scattered and / or reflected by a portion of the vasculature; The intravascular device is configured to collect at least a portion of the scattered and / or reflected optical wavelength radiation and couple at least a portion of the scattered and / or reflected optical wavelength radiation into an optical fiber.

[0109] 1. An apparatus for use in determining clot composition in the peripheral vasculature, optionally comprising:

[0110] In one example, the optical wavelength radiation is generated by an optical radiation source that simultaneously emits broadband optical radiation.

[0111] In one example, optical wavelength radiation is generated by an optical radiation source that emits narrowband optical radiation, and the emitted optical wavelengths are scanned across a range of wavelengths to generate broadband optical radiation that is transmitted by an optical fiber.

[0112] In another example, the intravascular device is a guidewire.

[0113] In another example, the intravascular device is a microcatheter.

[0114] In another example, the elongate member includes a radiopaque marker.

[0115] In another example, the elongate member is a tube.

[0116] In another example, the optical fiber has radiopaque markers.

[0117] In another example, optical wavelength radiation may be emitted axially from the end walls of the elongate members, as illustrated with reference to FIG.

[0118] In another example, optical wavelength radiation may be emitted radially from the elongated member in the form of a conical emission profile, such as may be provided by a beam redirector in the form of a region of optical fiber exhibiting total internal reflection, or a beam redirector in the form of a mirror or beam splitter positioned transverse to the longitudinal axis of the optical fiber 30.

[0119] In another example, optical wavelength radiation may be emitted radially from the elongate member in the form of an annular emission profile, for example, by providing the optical fiber 30 with a beam redirector in the form of a distal tip having a conical shape as illustrated with reference to FIG. 10, or by providing a beam redirector in the form of a reflective cone as described with reference to FIG. 11.

[0120] In another example, the radial emission may be in a direction perpendicular to the longitudinal axis of the elongate member.

[0121] In another example, the radial emission may be provided at least 3 centimeters from the end of the elongate member.

[0122] In another example, an intravascular device for use in determining clot composition in the peripheral vasculature may be incorporated into a microcatheter 110, as illustrated with reference to FIG. 2. The optical fiber 30 may be provided with a beam redirector, as described above, to emit optical wavelength radiation radially from the elongate member. At least a portion of the microcatheter 110 of FIG. 2 is configured to be inserted into a portion of a patient's vasculature. The microcatheter has at least one optically transparent wall portion configured to emit optical wavelength radiation. The intravascular device is configured to slide within the microcatheter along the longitudinal axis of the microcatheter. The microcatheter and intravascular device are configured such that when an intravascular guidewire is positioned at one or more longitudinal positions along the longitudinal axis of the microcatheter, optical wavelength radiation is emitted from the microcatheter through the at least one optically transparent wall portion of the microcatheter, and scattered and / or reflected optical wavelength radiation enters the microcatheter through the at least one optically transparent wall portion of the microcatheter.

[0123] An intravascular examination system 200 for use in determining clot composition in the peripheral vasculature will now be described with reference to FIG. 3 . The system includes an intravascular device for use in determining clot composition in the peripheral vasculature, as described above. The intravascular device for use in determining clot composition in the peripheral vasculature may optionally be included in a microcatheter, as described above with reference to FIG. 2 . The system 200 for use in determining clot composition in the peripheral vasculature also includes an optical radiation source 210, an optical radiation detector 220, and a processing unit 230. The optical radiation source is configured to generate optical wavelength radiation over a broadband range and couple it into an optical fiber. The optical radiation detector is configured to generate at least one detection signal based on the scattered and / or reflected optical wavelength radiation. The processing unit is configured to determine at least one spectrally resolved data set based on the at least one detection signal. The at least one spectrally resolved data set includes a spectrum corresponding to collagen. The processing unit is configured to determine collagen content from the spectrum corresponding to collagen and determine information about the clot based on the collagen content.

[0124] As described in more detail below, the presence of collagen in peripheral vascular clots is a sign of advanced clot differentiation and age. In these clots, fibroblasts have had time to infiltrate the clot and begin the process of forming an endothelial layer overlying the clot. In these chronic clots, t-PA and other thrombolytic agents may be unable to penetrate the clot, depending on the degree of endothelialization. Therefore, clots with significant collagen content may resist thrombolysis. In fact, attempting thrombolysis on this type of clot may put the patient at risk because the clot may be prone to migration and may cause acute downstream injury, for example, in the form of pulmonary embolism. Therefore, determining the collagen content of peripheral vascular clots in this manner may be beneficial to physicians and allow them to select the best treatment modality for each patient.

[0125] Clot differentiation

[0126] The following provides details regarding the distinction between a first clot type that is red blood cell-rich and a second clot type that is fibrin-rich, which may include determining the amount of red blood cells present and / or the amount of fibrin present. In other words, the scale between "red blood cell-rich" and "fibrin-rich" on the one hand takes into account that actual clots can exist between being red blood cell-rich and being fibrin-rich, and can exist as clots intermediate between these two.

[0127] As mentioned above, the systems described herein include an intravascular device or microcatheter for optically interrogating a portion of a patient's intravascular system. Broadband optical wavelength radiation spanning multiple optical wavelengths may be used in the optical interrogation. Thus, for example, a true broadband light source may be used. Broadband optical wavelength radiation may also be provided in the form of a tunable laser or multiple narrowband optical radiation sources, such as LEDs or lasers, that simultaneously or sequentially emit narrowband optical radiation. Thus, in one example, the optical radiation source and detector may operate as a spectrally resolved unit, where broadband optical wavelength radiation coupled into the optical fiber of the intravascular device includes a tunable laser operating over a range of wavelengths, and this optical wavelength radiation is scattered and / or reflected from the patient and detected to provide a spectrally resolved data set. In another example, a one-shot broadband optical wavelength radiation beam may be coupled into the fiber and collected and analyzed, for example, by a spectrometer, to provide a spectrally resolved data set.

[0128] The described system allows a measure of the actual morphology of a blood clot to be determined. Distinguishing between a first clot type and a second clot type can include determining at least one physiological parameter, the at least one physiological parameter including one or more of hemoglobin amount, hemoglobin oxygen saturation, scattering amount, vascular packaging parameters, water content, and the amount of at least one hemoglobin derivative. The at least one physiological parameter can be determined, for example, by fitting an optical model derived from diffusion theory to the measured spectrum. In one example, fitting the spectrum to the optical model can include taking into account a wavelength-dependent absorption coefficient and a wavelength-dependent reduced scattering coefficient. In one example, a double power law can be used to describe the wavelength dependence of the reduced scattering, with the first power law corresponding to the Mie scattering contribution and the second power law corresponding to the Rayleigh scattering contribution.

[0129] μ s '=a(ρ MR (λ / λ0) -b +(1-ρ MR )(λ / λ0) -4 )

[0130] wavenumber, i.e. cm -1 The equivalent scattering μ is expressed as s ' can be written as a function of wavelength λ as: where λ is the normalized wavelength, which in one example can be set to 800 nm, and the parameter a corresponds to the equivalent scattering amplitude at this exemplary wavelength. The equivalent scattering corresponds to the sum of Mie scattering and Rayleigh scattering, and ρ MR is defined as the ratio of Mie to Rayleigh scattering. The equivalent scattering slope of Mie scattering is denoted b and is related to particle size.

[0131] Further details on the determination of physiological parameters can be found in the following two articles: R. Nachabe, BHW Hendriks, AE Desjardins, M. van der Voort, MB van der Mark, and HJCM Sterenborg, "Estimation of lipid and water concentrations in scattering media with diffuse optical spectroscopy from 900 to 1600 nm", J. Biomed. Opt. 15, (2010), and Rami Nachabe, Benno HW Hendriks, Marjolein van der Voort, Adrien E. Desjardins, and Henricus JCM Sterenborg, "Estimation of biological chromophores using diffuse optical spectroscopy: benefit of extending the UV-VIS wavelength range to include 1000 to 1600 nm", Optics Express 18 (2010) p1432.

[0132] Determining the at least one physiological parameter can include one or more of fitting an optical model to the at least one spectrally resolved data set, applying at least one multivariate analysis tool to the at least one spectrally resolved data set, applying partial least squares discriminant analysis to the at least one spectrally resolved data set, applying a support vector machine to the at least one spectrally resolved data set, applying k-nearest neighbor analysis, and applying a deep learning algorithm to the at least one spectrally resolved data set. The at least one multivariate analysis tool can include principal component analysis (PCA). Differentiating between the first clot type and the second clot type can include utilizing a lookup table.

[0133] Similar optical analysis techniques may be used to determine collagen content in the intravascular examination system 200 described above for use in determining clot composition in the peripheral vasculature. In the system 200, a spectrally resolved data set is generated. The spectrally resolved data set has spectra corresponding to collagen. A processing unit is configured to determine the collagen content from the spectra corresponding to collagen and determine information about the clot based on the collagen content.

[0134] In peripheral vascular disease, it has been found that differentiation between recently formed (i.e., acute) and older (i.e., chronic) clots can be made based on the clot's collagen content. This is because collagen content increases as the clot ages. The age of the clot is a useful factor for physicians to use to determine which of several treatment options is most appropriate for the clot, for example, whether to perform thrombectomy or thrombolysis, and therefore which of various treatment devices to use. In one example, collagen content can be determined by fitting the optical model described above to the measured spectrum, as described for diffuse reflectance spectroscopy with reference to Equation 4 and Figure 2 of Nachabe et al., 2011. Collagen exhibits an absorption band in the wavelength range of 400 to 1700 nm, which is particularly suitable for the use of readily available optics. Particularly useful absorption bands characteristic of collagen occur at approximately 950 nm ±50 nm, 1030 nm ±50 nm, 1230 nm ±50 nm, and 1500 nm ±100 nm.

[0135] To demonstrate that collagen content can be accurately determined using diffuse reflectance spectroscopy, various clot "analog" samples were prepared from collagen and fibrin, and their spectra were measured using a spectrophotometer. The collagen in the analog samples represents collagen in the clot, and fibrin was added as a counterpart to the clot analog samples to represent fibrin that is typically also present in actual clots, and to demonstrate that collagen can be measured in the presence of a spectral signature relatively close to that of fibrin.

[0136] In contrast, Figure 14 shows the measured variation of light intensity (arbitrary units) versus wavelength (nanometers) for three clot analog samples. In the top graph of Figure 14, the spectrum of a pure collagen sample (100% collagen) was measured. In the bottom graph of Figure 14, the spectrum of a pure fibrin sample (100% fibrin) was measured. In the middle graph, 50% collagen and 50% fibrin were present. Characteristic absorption bands of collagen can be seen in Figure 14 at approximately 950 + / - 50 nm, 1030 nm + / - 50 nm, 1230 nm + / - 50 nm, and 1500 nm + / - 100 nm.

[0137] Collagen content "predictors" were then determined using the optical model described above for the spectra of FIG. 14 and for spectra of analog samples with collagen fractions of 25% and 75% and compared against the ground truth collagen fraction, as shown in FIG. 15. FIG. 15 shows the predictive ability (predictor) relative to the collagen fraction (%), i.e., ground truth, for several measured blood clot analog samples. Ideally, the value of the parameter predictor in FIG. 15 would be equal to the collagen fraction in FIG. 15. As can be seen from FIG. 15, model accuracy improves with collagen fraction.

[0138] A variety of alternative optical configurations are also suitable for measuring collagen content, including Raman spectroscopy, a molecular identification technique that uses unique spectral signatures useful for detecting collagen.

[0139] A corresponding method for determining collagen content of a peripheral vascular clot using the aforementioned intravascular examination system 200 for use in determining clot composition in the peripheral vasculature includes: - generating optical wavelength radiation over a broadband range using an optical radiation source; - coupling broadband optical wavelength radiation into the optical fiber of an intravascular device or an intravascular microcatheter and guidewire device; - collecting scattered and / or reflected optical wavelength radiation from the patient's vasculature using an intravascular device or an intravascular microcatheter and guidewire device; - generating, by an optical wavelength radiation detector, at least one detection signal based on the scattered and / or reflected optical wavelength radiation; - determining, by a processing unit, at least one spectrally resolved data set based on the at least one detection signal, the at least one spectrally resolved data set having a spectrum corresponding to collagen; - determining, by a processing unit, a collagen content from the spectrum corresponding to collagen, and determining information about the clot based on the collagen content; may include:

[0140] In another exemplary embodiment, a computer program or a computer program element is provided, characterized in that it is configured to perform, on a suitable system, the method steps of the method according to one of the previous embodiments.

[0141] Thus, the computer program element may be stored in a computing unit that may be part of an embodiment. This computing unit may be configured to perform or direct the performance of the steps of the above-mentioned method. Furthermore, the computing unit may be configured to operate components of the above-mentioned devices and / or systems. The computing unit can be configured to operate automatically and / or to execute user instructions. The computer program may be loaded into a working memory of a data processor. The data processor may thus be arranged to perform a method according to one of the above-mentioned embodiments. The computer program or the output unit may be integrated into an imaging or navigation system.

[0142] This exemplary embodiment of the present invention encompasses both computer programs that use the present invention from the beginning, and computer programs that convert existing programs into programs that use the present invention by means of an update.

[0143] Furthermore, the computer program element may be capable of providing all the steps necessary to fulfill the procedures of the exemplary embodiments of the methods described above.

[0144] According to a further exemplary embodiment of the present invention, a computer readable medium such as a CD-ROM, a USB stick, etc. is presented, the computer readable medium having stored thereon computer program elements, which computer program elements are described by the preceding sections.

[0145] The computer program may be stored and / or distributed on a suitable medium, such as an optical storage medium or a solid-state medium supplied together with or as part of other hardware, but may also be distributed in other forms, such as via the Internet or other wired or wireless telecommunications systems.

[0146] However, the computer program may also be presented over a network such as the World Wide Web and can be downloaded from such a network into the working memory of a data processor. According to a further exemplary embodiment of the present invention, a medium for making a computer program element available for downloading is provided, the computer program element being configured to perform a method according to one of the aforementioned embodiments of the present invention.

[0147] It should be noted that the embodiments of the present invention are described with reference to different subject matters. In particular, some embodiments are described with reference to method-type claims, and other embodiments are described with reference to apparatus-type claims. However, those skilled in the art will understand from the above and below description that, unless otherwise specified, any combination of features belonging to one type of subject matter, as well as any combination between features relating to different subject matters, is disclosed in the present application. However, all features can be combined to provide a synergistic effect that is greater than the simple sum of the features.

[0148] While the invention has been illustrated and described in detail in the drawings and foregoing description, such illustration and description are to be considered exemplary or explanatory and not restrictive. The invention is not limited to the disclosed embodiments. Other variations to the disclosed embodiments can be understood and effected by those skilled in the art in practicing the claimed invention, from a study of the drawings, the disclosure and the dependent claims.

[0149] In the claims, the word "comprise" does not exclude other elements or steps, and the indefinite article "a" or "an" does not exclude a plurality. A single processor or other unit may fulfill the functions of several items recited in the claims. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage. Any reference signs in the claims should not be interpreted as limiting the scope.

Claims

1. an elongate member configured to be inserted into a patient's vascular system; an optical fiber disposed within the elongated member and configured to transmit optical wavelength radiation; a reflecting cone disposed within the elongated member, the tip of the reflecting cone facing the end of the optical fiber; 1. An intravascular device comprising: the intravascular device is configured to emit optical wavelength radiation from a sidewall of the elongate member, the optical wavelength radiation forming an annular radiation profile around the elongate member due to interaction of the transmitted optical wavelength radiation with the reflection cone to be scattered and / or reflected by a portion of the vasculature; the intravascular device is configured to collect at least a portion of the scattered and / or reflected optical wavelength radiation and use the reflection cone to provide at least a portion of the scattered and / or reflected optical wavelength radiation into the optical fiber. Device.

2. The apparatus of claim 1 , wherein the optical wavelength radiation is emitted from the sidewall of the elongated member at least 3 centimeters away from the end of the elongated member.

3. 3. The device according to claim 1, further comprising a wavelength selective element.

4. The apparatus of claim 3 , wherein the wavelength selective element is at least one of a fiber Bragg grating, a wavelength passband filter, and a wavelength selective window.

5. 5. The device of claim 1, wherein a portion of the optical fiber at a distal end of the optical fiber is fixedly connected to the elongated member, and the at least a portion of the optical fiber disposed within the elongated member other than the fixed distal end is not fixedly connected to the elongated member.

6. A microcatheter, An intravascular device according to any one of claims 1 to 5; 1. An intravascular microcatheter and guidewire device comprising: at least a portion of the microcatheter is configured to be inserted into a portion of the patient's vascular system; the microcatheter having at least one optically transparent wall portion; the intravascular device is configured to slide within the microcatheter along a longitudinal axis of the microcatheter; the microcatheter and intravascular device are configured such that, when the intravascular guidewire is positioned at one or more longitudinal positions along the longitudinal axis of the microcatheter, optical wavelength radiation is emitted from the microcatheter through the at least one optically transparent wall portion of the microcatheter, and scattered and / or reflected optical wavelength radiation enters the microcatheter through the at least one optically transparent wall portion of the microcatheter. Device.

7. an intravascular device according to any one of claims 1 to 5 or an intravascular microcatheter and guidewire device according to claim 6; a source of optical radiation; an optical radiation detector; a processing unit; In an intravascular inspection system having the optical radiation source is configured to generate optical wavelength radiation over a broadband range and couple it into the optical fiber; the optical radiation detector is configured to generate at least one detection signal based on the scattered and / or reflected optical wavelength radiation; the processing unit is configured to determine at least one spectrally resolved data set based on the at least one detected signal; the processing unit is configured to determine information about the clot based on the at least one spectrally resolved data set. system.

8. 8. A method for intravascular examination using the intravascular examination system according to claim 7, generating optical wavelength radiation over a broadband range using the optical radiation source; coupling the broadband optical wavelength radiation into the optical fiber of the intravascular device or the intravascular microcatheter and guidewire device; collecting scattered and / or reflected optical wavelength radiation from the patient's vasculature using the intravascular device or the intravascular microcatheter and guidewire device; generating, by the optical wavelength radiation detector, at least one detection signal based on the scattered and / or reflected optical wavelength radiation; determining, by the processing unit, at least one spectrally resolved data set based on the at least one detected signal; determining, by the processing unit, information about the clot based on the at least one spectrally resolved data set; A method comprising:

9. an intravascular device according to any one of claims 1 to 5 or an intravascular microcatheter and guidewire device according to claim 6; a source of optical radiation; an optical radiation detector; a processing unit; 1. A system for determining the composition of a peripheral venous blood clot, comprising: the optical radiation source is configured to generate optical wavelength radiation over a broadband range and couple it into the optical fiber; the optical radiation detector is configured to generate at least one detection signal based on the scattered and / or reflected optical wavelength radiation; the processing unit is configured to determine at least one spectrally resolved data set based on the at least one detected signal; the at least one spectrally resolved data set has a spectrum corresponding to collagen; the processing unit is configured to determine a collagen content from the spectrum corresponding to the collagen, and determine information about the clot based on the collagen content. system.

10. 10. A method for determining collagen content of a peripheral vascular clot using the system for determining peripheral venous clot composition of claim 9 for use in determining clot composition in the peripheral vasculature, comprising: generating optical wavelength radiation over a broadband range using the optical radiation source; coupling the broadband optical wavelength radiation into the optical fiber of the intravascular device or the intravascular microcatheter and guidewire device; collecting scattered and / or reflected optical wavelength radiation from the patient's vasculature using the intravascular device or the intravascular microcatheter and guidewire device; generating, by the optical wavelength radiation detector, at least one detection signal based on the scattered and / or reflected optical wavelength radiation; determining, by the processing unit, at least one spectrally resolved data set based on the at least one detection signal, the at least one spectrally resolved data set having a spectrum corresponding to collagen; determining, by the processing unit, a collagen content from the spectrum corresponding to the collagen, and determining information about the clot based on the collagen content; A method comprising:

11. A computer program for controlling a system according to claim 7, arranged to carry out the method according to claim 8 when executed by a processor.

12. A computer program for controlling a system according to claim 9, arranged to carry out the method according to claim 10 when executed by a processor.

11. A computer-readable medium storing a computer program according to claim 11 or 12.

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