System and method for oct-guided treatment of patient

Abstract

To provide an imaging system for a patient comprising an imaging probe and an imaging assembly.SOLUTION: An imaging probe comprises: an elongate shaft comprising a proximal end, a distal portion, and a lumen extending between the proximal end and the distal portion; a rotatable optical core having the proximal end and a distal end, wherein at least a portion of the rotatable optical core is located within the lumen of the elongate shaft; and an optical assembly proximate the distal end of the rotatable optical core, the optical assembly configured to direct light to tissue and collect reflected light from the tissue. An imaging assembly is constructed and arranged to optically couple to the imaging probe. The imaging assembly is configured to emit light into the imaging probe and receive the reflected light collected by the optical assembly. The system is configured to provide treatment information used by an operator to plan a treatment and / or predict a treatment outcome.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] (Related Applications) This application claims the benefit of U.S. Provisional Application No. 62 / 850,945, titled "OCT-Guided Treatment of a Patient," filed on May 21, 2019, the contents of which are incorporated herein by reference in their entirety.

[0002] This application claims the benefit of U.S. Provisional Application No. 62 / 906,353, titled "OCT-Guided Treatment of a Patient," filed on September 26, 2019, the contents of which are incorporated herein by reference in their entirety.

[0003] This application claims the benefit of U.S. Provisional Application No. 63 / 017,258, titled "Imaging System," filed on April 29, 2020, the contents of which are incorporated herein by reference in their entirety.

[0004] This application is related to U.S. Provisional Application No. 62 / 148,355, titled "Micro-Optic Probes for Neurology," filed on April 16, 2015, the contents of which are incorporated herein by reference in their entirety.

[0005] This application is related to U.S. Provisional Application No. 62 / 322,182, titled "Micro-Optic Probes for Neurology," filed on April 13, 2016, the contents of which are incorporated herein by reference in their entirety.

[0006] This application is related to International PCT Patent Application No. PCT / US2016 / 027764, titled "Micro-Optic Probes for Neurology", filed on April 15, 2016, and published under Publication No. WO2016 / 168605 on October 20, 2016, the content of which is incorporated herein by reference in its entirety.

[0007] This application is related to U.S. Patent Application No. 15 / 566,041, titled "Micro-Optic Probes for Neurology", filed on October 12, 2017, and published under U.S. Publication No. 2018-0125372 on May 10, 2018, the content of which is incorporated herein by reference in its entirety.

[0008] This application is related to U.S. Provisional Application No. 62 / 212,173, titled "Imaging System Includes Imaging Probe and Delivery Devices", filed on August 31, 2015, the content of which is incorporated herein by reference in its entirety.

[0009] This application is related to U.S. Provisional Application No. 62 / 368,387, titled "Imaging System Includes Imaging Probe and Delivery Devices", filed on July 29, 2016, the content of which is incorporated herein by reference in its entirety.

[0010] This application is related to International PCT Patent Application No. PCT / US / 2016 / 049415, titled "Imaging System Includes Imaging Probe and Delivery Devices", filed on August 30, 2016, and published under Publication No. WO2017 / 040484 on March 9, 2017, the content of which is incorporated herein by reference in its entirety.

[0011] This application is related to U.S. Patent Application No. 15 / 751,570, titled "Imaging System Includes Imaging Probe and Delivery Devices", filed on February 9, 2018, and U.S. Patent No. 10,631,718, published on April 28, 2020, the content of which is incorporated herein by reference in its entirety.

[0012] This application is related to U.S. Patent Application No. 16 / 820,991, titled "Imaging System Includes Imaging Probe and Delivery Devices", filed on March 17, 2020, and published under Publication No. ____________ on ____________, the content of which is incorporated herein by reference in its entirety.

[0013] This application is related to U.S. Provisional Application No. 62 / 591,403, titled "Imaging System", filed on November 28, 2017, the content of which is incorporated herein by reference in its entirety.

[0014] This application is related to U.S. Provisional Application No. 62 / 671,142, titled "Imaging System", filed on May 14, 2018, the content of which is incorporated herein by reference in its entirety.

[0015] This application is related to International PCT Patent Application No. PCT / US2018 / 062766, titled "Imaging System", filed on November 28, 2018, and published under Publication No. WO2019 / 108598 on June 6, 2019, the content of which is incorporated herein by reference in its entirety.

[0016] This application is related to U.S. Provisional Application No. 62 / 732,114, titled "Imaging System with Optical Pathway", filed on September 17, 2018, the content of which is incorporated herein by reference in its entirety.

[0017] This application is related to International PCT Patent Application No. PCT / US2019 / 051447, titled "Imaging System with Optical Pathway", filed on September 17, 2019, and published under Publication No. WO2020 / 061001 on March 26, 2020, the content of which is incorporated herein by reference in its entirety.

[0018] This application is related to U.S. Provisional Application No. 62 / 840,450, titled "Imaging Probe with Fluid Pressurization Element", filed on April 30, 2019, the content of which is incorporated herein by reference in its entirety.

[0019] This application is related to International PCT Patent Application No. PCT / US2020 / 030616, titled "Imaging Probe with Fluid Pressurization Element", filed on April 30, 2020, and published under Publication No. _____________ on ________________, the content of which is incorporated herein by reference in its entirety.

[0020] (Field of the Invention) The present invention generally relates to imaging systems using optical coherence tomography (OCT), and more particularly to systems that provide guidance for therapeutic treatment of patients.

Background Art

[0021] Imaging probes for imaging various locations within a patient's body, such as intravascular probes for imaging a patient's heart, are commercially available. Current imaging probes have limitations in their ability to reach specific anatomical locations due to their size and stiffness. In addition, because current imaging probes are inserted over a guidewire, the placement of the probe can become unstable and the use of one or more delivery catheters through which the imaging probe is inserted is limited. Therefore, there is a need for imaging systems with small-diameter, highly flexible imaging probes, and systems with one or more delivery devices compatible with these improved imaging probes.

Summary of the Invention

[0022] According to one aspect of the concepts of the present invention, an imaging system for a patient includes an imaging probe, an optical assembly, and an imaging assembly. The imaging probe includes an elongated shaft having a proximal end, a distal end, and a lumen extending between the proximal end and the distal end, and a rotatable optical core having a proximal end and a distal end, and at least a portion of the rotatable optical core is disposed within the lumen of the elongated shaft. The optical assembly is disposed proximate to the distal end of the rotatable optical core and is configured to direct light toward tissue and collect reflected light from the tissue. The imaging assembly is configured and arranged to be optically coupled to the imaging probe, to irradiate the imaging probe with light, and to receive the reflected light collected by the optical assembly. The system is configured to provide treatment information that can be used by an operator to plan a treatment and / or predict a treatment outcome.

[0023] In some embodiments, the imaging probe further includes a damping fluid disposed between the elongated shaft and the rotatable optical core and configured to reduce non-uniform rotation of the optical assembly. The imaging probe may further include a fluid pressurizing element configured to increase the pressure of the damping fluid to reduce the presence of air bubbles proximate to the optical assembly.

[0024] In some embodiments, the treatment information is based on OCT data collected by the imaging probe. The system may further include a second imaging device configured to collect non-OCT data. The treatment information may further be based on the non-OCT data. The second imaging device may be configured to collect non-OCT data including angiography data.

[0025] In some embodiments, the system is configured to evaluate the severity of a disease. The evaluation may include a quantitative evaluation and / or a qualitative evaluation.

[0026] In some embodiments, the system is configured to accurately capture thrombi of 5 μm or greater, 10 μm or greater, or 30 μm or greater.

[0027] The technology described herein, together with its attributes and attendant advantages, will be best understood in view of the following detailed description, taken in conjunction with the accompanying drawings, in which representative embodiments are shown by way of example.

[0028] (Incorporation by reference) All publications, patents, and patent applications mentioned herein are hereby incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.

Brief Description of the Drawings

[0029]

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Best Mode for Carrying Out the Invention

[0030] Next, refer in detail to the present embodiments of the present technology illustrated in the accompanying drawings. The same reference numerals are used to refer to the same components. However, the description is not intended to limit the present disclosure to specific embodiments, but should be construed to include various modifications, equivalents, and / or alternatives of the embodiments described herein.

[0031] The terms "comprising" (and any form of "comprising" such as "comprise" and "comprises"), "having" (and any form of "having" such as "have" and "has"), "including" (and any form of "including" such as "includes" and "include"), or "containing" (and any form of "containing") as used herein mean the presence of the stated feature, integer, step, operation, element, and / or component, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and / or groups thereof.

[0032] Furthermore, in this specification, terms such as first, second, third, etc. may be used to describe various limitations, elements, components, regions, layers, and / or sections, but it will be understood that these limitations, elements, components, regions, layers, and / or sections are not to be limited by these terms. These terms are only used to distinguish one limitation, element, component, region, layer, or section from another. Thus, a first limitation, element, component, region, layer, or section described below may, without departing from the teachings of the present application, be referred to as a second limitation, element, component, region, layer, or section.

[0033] Furthermore, when a component is "above," "attached to," "connected to," or "coupled to" another component, it will be further understood that the component may be directly above or over the other component, or connected or coupled to the other component, or that one or more intervening components may be present. On the other hand, when a component is "directly above," "directly attached to," "directly connected to," or "directly coupled to" another component, there are no intervening components. Other words used to describe the relationship between components should be interpreted similarly (e.g., "between" vs. "directly between," "adjacent" vs. "directly adjacent," etc.).

[0034] Furthermore, when the first component is "in," "above," and / or "within" the second component, it will be understood that the first component may be disposed within the internal space of the second component, within a portion of the second component (e.g., within the wall of the second component), on the outer surface and / or inner surface of the second component, or in one or more combinations thereof.

[0035] As used herein, when the term "proximal" is used to describe that a first component or location is proximal to a second component or location, it is considered to include one or more locations near the second component or location, as well as locations within, above, and / or inside the second component or location. For example, a component disposed proximal to an anatomical site (e.g., the location of a target tissue) shall be considered to include not only components disposed proximal to the anatomical site, but also components disposed within, above, and / or inside the anatomical site.

[0036] Spatially relative terms such as "beneath", "below", "lower", "above", "upper", etc. are used to describe the relationship of a feature to a component and / or another component, and / or, for example, to describe a feature as shown in the figures. Further, it will be understood that spatially relative terms are intended to encompass different orientations of the device in use and operation in addition to the orientation shown in the figures. For example, if the device in the figure is inverted, components described as "beneath" and / or "below" other components or features will be oriented "above" the other components or features. The device can be oriented in other directions (e.g., rotated 90 degrees or otherwise), and the spatially relative descriptors used herein will be interpreted accordingly.

[0037] As used herein, terms such as "reduce", "reducing", "reduction", etc. shall include a reduction in amount including reduction to zero. Reducing the likelihood of occurrence shall include preventing occurrence. Correspondingly, the terms "prevent", "preventing", and "prevention" shall each include the acts of "reduce", "reducing", and "reduction", respectively.

[0038] As used herein, the term "and / or" shall be construed as specifically disclosed for each of two particular features or components, with or without the other. For example, "A and / or B" shall be construed as specifically disclosed for each of (i) A, (ii) B, and (iii) A and B, as if each were individually described herein.

[0039] As used herein, the term "one or more" may mean one, two, three, four, five, six, seven, eight, nine, ten, or any number up to and including more.

[0040] The terms "and combinations thereof" and "and combinations of these" may each be used in this specification after a list of items to be included, either singly or in combination. For example, a component, process, and / or other item selected from a group consisting of A, B, C, and combinations thereof shall be deemed to include one or more sets of components consisting of one or more of item A, two or more of item B, and / or three or more of item C.

[0041] In this specification, unless otherwise expressly stated, "and" may mean "or", and "or" may mean "and". For example, if a feature is described as having A, B, or C, the feature may have A, B, and C, or any combination of A, B, and C. Similarly, if a feature is described as having A, B, and C, the feature may have only one or two of A, B, or C.

[0042] In this specification, when a quantifiable parameter is described as being "between" a first value X and a second value Y, the parameter shall be deemed to include a length of X or more, a length of Y or less, and / or a value of X or more and Y or less. For example, a length between 1 and 10 shall be deemed to include a length of 1 or more (including values of 10 or more), a length of 10 or less (including values of 1 or less), and / or a value of 1 or more and 10 or less.

[0043] The expression "configured (or set) to" used in this disclosure may be exchanged and used, for example, depending on the situation, with expressions such as "suitable for", "having the ability to", "designed for", "adapted to", "created for", "capable of". Also, the expression "configured (set) to do" does not only mean "specially designed to do" in terms of hardware. Depending on the situation, the expression "a device configured to do" may in some cases mean that the device "can" operate with other devices or components.

[0044] In this specification, the terms "about" or "approximately" shall refer to ±30%.

[0045] In this specification, the term "threshold value" refers to a maximum level, a minimum level, and / or a range of values correlated with a desired state or an undesired state. In some embodiments, a system parameter is maintained above a minimum threshold value, below a maximum threshold value, within a range of threshold values, and / or outside a range of threshold values so as to cause a desired effect (e.g., effective treatment) and / or prevent or otherwise reduce (hereinafter, "prevent") an undesired event (e.g., a device and / or clinically adverse event). In some embodiments, a system parameter is maintained above a first threshold value (e.g., above a first temperature threshold value for providing a desired therapeutic effect to tissue) and below a second threshold value (e.g., below a second temperature threshold value for preventing undesired tissue damage). In some embodiments, the threshold value is determined to have a safety margin in consideration of patient variability, system variability, tolerance, and the like. In this specification, "exceeding the threshold value" is related to the parameter exceeding the maximum threshold value, falling below the minimum threshold value, being within the range of threshold values, and / or being outside the range of threshold values.

[0046] In this specification, "room pressure" shall mean the pressure of the environment surrounding the systems and devices of the concepts of the present invention. Positive pressure includes a pressure higher than room temperature, or simply a pressure higher than other pressures such as a positive differential pressure across components of a fluid path such as a valve. Negative pressure includes a pressure below room pressure, or a pressure smaller than other pressures such as a negative differential pressure across components of a fluid path such as a valve. Negative pressure may include a vacuum, but does not mean a pressure below room pressure. The term "vacuum" as used herein is used to refer to a complete or partial vacuum, or any negative pressure described herein.

[0047] As used herein to describe a non-circular geometric shape, the term "diameter" should be interpreted as the diameter of a virtual circle that approximates the geometric shape being described. For example, when describing a cross-section such as the cross-section of a component, the term "diameter" shall represent the diameter of a virtual circle having the same cross-sectional area as the cross-section of the component being described.

[0048] As used herein, the terms "major axis" and "minor axis" of a component respectively represent the length and diameter of a virtual cylinder of the minimum volume that can completely enclose the component.

[0049] As used herein, the term "functional component" should be construed to include one or more components configured and arranged to perform a function. The functional component may include a sensor and / or a transducer. In some embodiments, the functional component is configured to supply energy and / or treat tissue (e.g., a functional component configured as a treatment element). Alternatively or additionally, the functional component (e.g., a functional component configured with a sensor) may be configured to record one or more parameters such as a patient's physiological parameters, a patient's anatomical parameters (e.g., tissue shape parameters), a patient's environmental parameters, and / or system parameters. In some embodiments, the sensor or other functional component is configured to perform a diagnostic function (e.g., collect data used to perform a diagnosis). In some embodiments, the functional component is configured to perform a therapeutic function (e.g., provide therapeutic energy and / or a therapeutic agent). In some embodiments, the functional component includes one or more components configured and arranged to perform a function selected from the group consisting of supplying energy, extracting energy (e.g., cooling components), supplying a drug, operating system components or a patient's tissue, recording or otherwise sensing parameters such as a patient's physiological parameters or system parameters, and combinations of one or more of these. The functional component is configured with a fluid and / or a fluid supply system. The functional component may include a reservoir such as an expandable balloon or other fluid holding reservoir. The functional assembly may include an assembly configured and arranged to perform a function such as a diagnostic and / or therapeutic function. The functional assembly may include an expandable assembly. The functional assembly may include one or more functional components.

[0050] As used herein, the term "transducer" should be construed to include any component or combination of components that receives energy or some input and generates an output. For example, a transducer may include electrodes that receive electrical energy and distribute that electrical energy to tissue (e.g., based on the size of the electrodes). In some configurations, a transducer converts an electrical signal into any output such as light (e.g., a transducer composed of a light-emitting diode or a light bulb), sound (e.g., a transducer comprising a piezoelectric crystal configured to supply ultrasonic energy), pressure (e.g., an applied pressure or force), thermal energy, cryogenic energy, chemical energy, mechanical energy (e.g., a transducer comprising a motor or a solenoid), magnetic energy, and / or a different electrical signal (e.g., a signal different from the input signal to the transducer). Alternatively or additionally, a transducer may convert a physical quantity (e.g., a change in a physical quantity) into an electrical signal. A transducer may include any component configured to supply energy and / or an agent to tissue, such as, for example, a transducer configured to supply electrical energy (e.g., a transducer comprising one or more electrodes), light energy (e.g., a transducer comprising a laser, a light-emitting diode, and / or optical components such as a lens or a prism), mechanical energy (e.g., a transducer comprising components that manipulate tissue), sound energy (e.g., a transducer comprising a piezoelectric crystal), chemical energy, electromagnetic energy, magnetic energy, and any combination of one or more of these.

[0051] As used herein, the term "fluid" refers to any flowable material such as a liquid, a gas, a gel, or a material that can be propelled through a lumen and / or an opening.

[0052] As used herein, the term "material" refers to a single material or a combination of two, three, four, or more materials.

[0053] As used herein, the term "lesion" constitutes a segment of a blood vessel (e.g., an artery) in an undesirable state. The lesions used herein include segments of blood vessels with stenosis (e.g., strictures) of the blood vessels and / or, regardless of the presence or absence of stenosis, segments of blood vessels containing accumulations of calcium, lipids, cholesterol, and / or other plaques.

[0054] It should be understood that certain features of the invention that are described in the context of separate embodiments for clarity may be provided in combination in a single embodiment. Conversely, for brevity, the various features of the invention that are described in the context of a single embodiment may also be provided separately or in any suitable sub-combination. For example, it will be understood that all features (whether independent or dependent) recited in any of the claims can be combined in any way.

[0055] Although at least some of the drawings and descriptions of the present invention are simplified to focus on components relevant to a clear understanding of the present invention, it should be understood that other components that may be understood by those skilled in the art to possibly constitute a part of the present invention have been excluded for clarity. However, since such components are well known in the art and do not necessarily facilitate a better understanding of the present invention, no description of such components is provided herein.

[0056] The terms defined in this disclosure are used only to describe particular embodiments of this disclosure and are not intended to limit the scope of this disclosure. Terms provided in the singular are intended to include the plural as well, unless the context clearly indicates otherwise. All terms used herein, including technical or scientific terms, have the same meaning as commonly understood by one of ordinary skill in the relevant technical field, unless otherwise specifically defined herein. Terms defined in commonly used dictionaries should be interpreted as having the same or similar meaning as their meaning in the context of the relevant art and should not be interpreted as having an idealized or exaggerated meaning, unless expressly defined otherwise herein. In some cases, the terms defined in this disclosure should not be construed as excluding embodiments of this disclosure.

[0057] Provided herein is an imaging system for a patient comprising an imaging probe and an imaging assembly. The imaging probe includes an elongated shaft having a proximal end, a distal end, and a lumen extending between the proximal end and the distal end, a rotatable optical core having a proximal end and a distal end, at least a portion of which is disposed within the lumen of the elongated shaft, and an optical assembly disposed proximate to the distal end of the rotatable optical core and configured to direct light toward tissue and collect reflected light from the tissue.

[0058] The imaging system of the concepts of the present invention can be used to provide image data representing arteries, veins, and / or other body conduits and to image one or more devices inserted into those conduits. The imaging system may provide image data related to diseased tissue, such as blood vessels including stenoses, lesions, myocardial bridges, and / or other vascular stenoses (referred to herein as "stenoses") and / or blood vessels including aneurysms, as well as healthy tissue. The system may be configured to provide treatment information. The treatment information is used by an operator to plan a treatment and / or to predict treatment results.

[0059] Referring now to FIG. 1, there is shown a schematic diagram of an imaging system that includes an imaging probe, an independent retraction assembly, and a rotation assembly that are consistent with the concepts of the present invention. The imaging system 10 is configured and arranged to collect image data and generate one or more images based on the recorded data. For example, the imaging system 10 includes an optical coherence tomography (OCT) imaging system configured and arranged to collect image data at an imaging location (e.g., a segment of a blood vessel during a pullback procedure). The imaging system 10 includes an imaging probe 100 that is a catheter-based probe, and a rotation assembly 500 and a retraction assembly 800 that are operably attachable to the imaging probe 100. Further, the imaging system 10 may include a console 50 configured to be operably connected to the imaging probe 100 via the rotation assembly 500 and / or the retraction assembly 800. The imaging probe 100 may be introduced into a conduit, such as a patient's blood vessel, using one or more delivery catheters, such as the illustrated delivery catheter 80. Additionally or alternatively, the imaging probe 100 may be introduced via an introduction device such as an endoscope, an arthroscope, a balloon dilator, or the like. In some embodiments, the imaging probe 100 is configured to be introduced into a conduit selected from the group consisting of arteries, veins, arteries within or adjacent to the heart, veins within or adjacent to the heart, arteries within or adjacent to the brain, veins within or adjacent to the brain, peripheral arteries, peripheral veins, via a natural body opening into a conduit such as the esophagus, a surgically created opening into a body cavity such as the abdomen, and one or more combinations thereof. The imaging system 10 may further include a plurality of imaging devices (second imaging device 15). The imaging system 10 may further include a device (treatment device 16) configured to treat a patient. The imaging system 10 may further include a fluid injector, such as injector 20. The fluid injector may be configured to inject one or more fluids, such as an injection fluid, an image contrast agent (e.g., a radiopaque contrast agent, hereinafter "contrast agent"), and / or other fluids (e.g., implant 21). The imaging system 10 may further include an implant (e.g., implant 31).The implant may be implanted into a patient via a delivery device such as an implant delivery device 30 and / or a delivery catheter 80.

[0060] In some embodiments, the imaging probe 100 and / or other components of the imaging system 10 may have a configuration and arrangement similar to those of the components as described in U.S. Patent Application No. 15 / 566,041, filed on October 12, 2017, titled "Micro-Optical Probe for Neurology," which is co-pending with the applicant, and the content thereof is hereby incorporated by reference in its entirety for all purposes. The imaging probe 100 may be configured and arranged to collect image data from a patient site such as an intravascular cardiac site, an intracranial site, or other sites accessible via the patient's vasculature. In some embodiments, the imaging system 10 may have a configuration and arrangement similar to those of the system and its method of use as described in U.S. Patent Application No. 15 / 751,570, filed on February 9, 2018, titled "Imaging System Comprising an Imaging Probe and a Delivery Device," which is co-pending with the applicant, and the content thereof is hereby incorporated by reference in its entirety for all purposes.

[0061] The delivery catheter 80 includes a shaft 81 which is an elongated shaft having a lumen 84 therein, and a connector 82 disposed at its proximal end. The connector 82 may be a Touhy or valved connector, such as a valved connector configured to prevent the outflow of fluid from the associated delivery catheter 80 (with and / or without a separate shaft disposed within the connector 82). The connector 82 may include a port 83 configured and arranged to allow the introduction of fluid into and / or the removal of fluid from the delivery catheter 80. In some embodiments, the injection fluid as described herein is introduced through one or more ports 83 to remove blood or other undesirable substances (e.g., from a position proximate to the optical assembly 115 to a position distal to the optical assembly 115) from a position proximate to the optical assembly 115, for example. The port 83 may be disposed on the side of the connector 82 and may include a luer fitting, a cap, and / or a valve. The shaft 81, the connector 82, and the port 83 may each be composed of standard materials and may have a configuration similar to commercially available introducers, guide catheters, diagnostic catheters, intermediate catheters, and microcatheters used in interventional procedures. The delivery catheter 80 may be a catheter configured to supply the imaging probe 100 to a position within the brain, within the heart, and / or other positions within the patient.

[0062] The imaging system 10 may include two or more delivery catheters 80, for example, three or more delivery catheters 80. The plurality of delivery catheters 80 may include at least a vascular introducer and another delivery catheter 80 that can be inserted into the patient after the vascular introducer is placed through the patient's skin. The two or more delivery catheters 80 may be collectively configured such that a set of inner diameter (ID) and outer diameter (OD) is such that the first delivery catheter 80 slidably receives the second delivery catheter 80 (for example, the second delivery catheter OD is less than or equal to the first delivery catheter ID), and the second delivery catheter 80 slidably receives the third delivery catheter 80 (for example, the third delivery catheter OD is less than or equal to the second delivery catheter ID). In these configurations, advancing the first delivery catheter 80 to a first anatomical location and advancing the second delivery catheter 80 to a second anatomical location distal or far from (hereinafter, "distal") the first anatomical location through the first delivery catheter, etc., can be appropriately performed as needed using delivery catheters 80 with sequentially smaller diameters. In some embodiments, the delivery catheter 80 may have the same configuration and arrangement as similar components described in the applicant's co-pending U.S. Patent Application No. 15 / 751,570, entitled "Imaging System Comprising an Imaging Probe and a Delivery Device," filed on February 9, 2018, the content of which is hereby incorporated by reference in its entirety for all purposes.

[0063] The imaging probe 100 includes an elongated body (the elongated shaft 120 in this specification) composed of one or more elongated shafts and / or tubes. The shaft 120 includes a proximal end portion 1201, a distal end portion 1209, and a lumen 1205 extending therebetween. In some embodiments, the lumen 1205 may be a plurality of coaxial lumens within one or more elongated shafts, for example, lumens such that one or more lumens are adjacent to each other to form a single lumen 1205. In some embodiments, at least a portion of the shaft 120 constitutes a torque shaft. In some embodiments, a portion of the shaft 120 has a braided structure. In some embodiments, a portion of the shaft 120 includes a helically cut tube (for example, a helically cut metal tube). In some embodiments, the pitch of the helical cut may be varied along the length of the cut so as to vary the rigidity of the shaft 120 along the cut. A portion of the shaft 120 may include a tube composed of a nickel-titanium alloy. The shaft 120 operably surrounds an optical core 110 (for example, the optical core 110 is disposed within the lumen 1205), which is a rotatable optical fiber having a proximal end portion 1101 and a distal end portion 1109. The optical core 110 may include a dispersion-shifted optical fiber such as a depressed cladding dispersion-shifted optical fiber (for example, a non-zero dispersion-shifted (NZDS) fiber). Further, the shaft 120 includes a distal portion 1208 having a window portion 130 that is a transparent window (for example, a window portion that is relatively transparent to light of one or more frequencies passing through the optical core 110). An optical assembly 115 is operably attached to the distal end portion 1109 of the optical core 110. The optical assembly 115 is disposed within the window portion 130 of the shaft 120. The optical assembly 115 may include a GRIN lens optically coupled to the distal end portion 1109 of the optical core 110.The optical assembly 115 may have a configuration and arrangement similar to that of the optical assembly 115 as described in the applicant's co-pending international PCT patent application number PCT / US2018 / 062766, titled "Imaging System," filed on November 28, 2018, and the applicant's co-pending international PCT patent application number PCT / US2019 / 051447, titled "Imaging System with an Optical Path," filed on September 17, 2019. The entire content of each of these is hereby incorporated by reference in its entirety for all purposes. The connector assembly 150, which is a connector assembly, is disposed at the proximal end of the shaft 120. The connector assembly 150 operably attaches the imaging probe 100 to the rotation assembly 500 as described herein. The connector assembly 150 surrounds an optical connector 161 fixedly attached to the proximal end of the optical core 110 and is operably attached to the optical connector 161. The retraction connector 180, which is a second connector, is disposed on the shaft 120. The connector 180 may be removably attached and / or adjustably disposed along the length of the shaft 120. The connector 180 may be disposed along the shaft 120 proximate to the proximal end of the delivery catheter 80 by a clinician or other user of the system 10, etc., after the imaging probe 100 has been inserted into the patient via the delivery catheter 80. The shaft 120 may include a portion that accommodates slack in the shaft 120 between the locations of the connector assembly 150 and the connector 180, a proximal portion of the shaft 120 (e.g., the proximal portion of the imaging probe 100), and a service loop 185.

[0064] The imaging probe 100 may include one or more visualizable markers 131a-b (referred to herein as marker 131) along its length (e.g., along the shaft 120). The marker 131 may be a marker selected from the group consisting of a radiopaque marker, an ultrasonic reflection marker, a magnetic marker, a ferromagnetic material, and one or more combinations thereof. In some embodiments, the marker 131 is located at a position (e.g., within the distal portion 1208 and / or at least a proximal position) to assist the user of the imaging system 10 in performing a pull-back procedure (referred to herein as the "pull-back procedure" or "pull-back"), for example, to position the distal tip 119 at a distal position from the proximal end of the implant after the pull-back is completed (e.g., so that the imaging probe 100 can be safely advanced through the implant after the pull-back).

[0065] In some embodiments, the imaging probe 100 includes a gel 118 (e.g., a gel injected in the manufacturing process or otherwise installed) that is a viscous damping material disposed within the shaft 120 and surrounding the distal portions of the optical assembly 115 and the optical core 110. The gel 118 may be a non-Newtonian fluid, such as a shear-thinning fluid. In some embodiments, the gel 118 has a static viscosity greater than 500 centipoise and a shear viscosity less than the static viscosity. In these embodiments, the ratio of the static viscosity to the shear viscosity of the gel 118 may be between 1.2:1 and 100:1. The gel 118 may have a similar composition and arrangement as the gel described with reference to U.S. Patent Application No. 15 / 566,041, co-pending of the applicant with the title "Micro-Optical Probe for Neurology" filed on October 12, 2017, and International PCT Patent Application No. PCT / US2018 / 062766, co-pending of the applicant with the title "Imaging System" filed on November 28, 2018, the contents of each of which are hereby incorporated by reference in their entirety for all purposes.

[0066] The imaging probe 100 may include a distal tip 119 that is a distal tip portion. In some embodiments, the distal tip 119 is configured to improve the "operability" of the imaging probe 100 (e.g., improve the "trackability" and / or "maneuverability" of the imaging probe 100) within, for example, a serpentine path (e.g., within the blood vessels of the brain or heart having a serpentine path), such as a spring tip including a spring tip configured as such. In some embodiments, the spring tip 119 has a length between 5 mm and 100 mm (e.g., a spring having a length between 5 mm and 100 mm). In some embodiments, the spring tip 119 may be a spring tip that can be shaped by the user (e.g., at least a portion of the spring tip 119 may be malleable). The imaging probe 100 may be rotated (e.g., via the connector 180) to adjust the direction of the non-linear shape portion of the spring tip 119 (e.g., adjust the trajectory of the spring tip 119 in the patient's vascular system). Alternatively or additionally, the spring tip 119 may include a cap, plug, or other component configured to seal the distal opening of the window 130. In some embodiments, the spring tip 119 may include a radiopaque marker configured to enhance the visibility of the imaging probe 100 under X-ray or fluoroscopy. In some embodiments, the spring tip 119 may include a relatively short lumen guidewire path to enable "quick exchange" translation of the imaging probe 100 on a guidewire of the system 10 (such as the guidewire 31).

[0067] In some embodiments, at least the distal portion of the imaging probe 100 (e.g., the distal portion of the shaft 120 surrounding the optical assembly 115) has an outer diameter of 0.030 inches or less, such as 0.025 inches or less, 0.020 inches or less, and / or 0.016 inches or less.

[0068] In some embodiments, the imaging probe 100 may be configured and arranged for use in an intravascular nerve procedure (e.g., a procedure in which blood, vasculature, and other tissues proximate to the brain are visualized, and / or a procedure in which a device temporarily or permanently disposed proximate to the brain is visualized). The imaging probe 100 configured for use in a nerve procedure may have an overall length of at least 150 cm, for example, a length of about 300 cm.

[0069] Alternatively or additionally, the imaging probe 100 may be configured and arranged for use in an intravascular cardiac procedure (e.g., a procedure in which blood, vasculature, and other tissues proximate to the heart are visualized, and / or a procedure in which a device temporarily or permanently disposed proximate to the heart is visualized). The imaging probe 100 configured for use in a cardiovascular procedure may have an overall length of at least 120 cm, for example, an overall length of about 280 cm (e.g., such that the proximal end of the probe 100 can be disposed outside the sterile area). In some embodiments, for example, for placement outside the sterile area, the imaging probe 100 may have a length greater than 220 cm and / or less than 320 cm.

[0070] The rotary assembly 500 includes a connector assembly 510 operably attached to a rotary joint 550. The rotary assembly 500 further includes a power element 530 that is a motor or other source of rotational energy. The power element 530 is operably attached to the rotary joint 550 via a linkage assembly 540. In some embodiments, the linkage assembly 540 includes one or more gears, belts, pulleys, or other power transmission mechanisms. The power element 530 may drive (e.g., rotate via the linkage assembly 540) the rotary joint 550 (and the core 110) at a speed of at least 100 revolutions per second, such as at least 200 revolutions per second, 250 revolutions per second, 400 revolutions per second, 500 revolutions per second, or between 20 revolutions per second and 1000 revolutions per second. The power element 530 may include a mechanism selected from the group consisting of a motor, a servo, a stepper motor (e.g., a stepper motor with a gearbox), a linear actuator, a hollow core motor, and combinations thereof. In some embodiments, the rotary assembly 500 is configured to rotate the optical assembly 115 and the rotatable optical core 110 together.

[0071] The connector assembly 510 is operably attached to the connector assembly 150 of the imaging probe 100, enabling the optical connector 161 to operably engage with the rotary joint 550. In some embodiments, the connector assembly 510 operably engages with the connector assembly 150. In some embodiments, the connector assembly 510 operably engages with the connector assembly 150 such that it can rotate freely within the assembly where the rotary joint 550 and the optical connector 161 are engaged.

[0072] The retraction assembly 800 includes a connector assembly 820 that is operably attached to a reference point, such as a connector 82 of the delivery catheter 80, to establish a reference for the retraction assembly 800 with respect to the patient. The connector assembly 820 may be attached to a reference point such as a patient introduction device, an operating table, and / or other fixed or semi-fixed reference points. A puller 850, which is a retraction element, is releasably attached to the connector 180 of the imaging probe 100, for example via a carrier 855. The retraction assembly 800 retracts at least a portion of the imaging probe 100 (e.g., the portion of the imaging probe 100 distal from the attached connector 180) with respect to the established reference. In some embodiments, the retraction assembly 800 is configured to retract at least a portion of the imaging probe 100 (e.g., at least a portion of the optical assembly 115 and the shaft 120) at a speed between 5 mm / second and 100 mm / second, such as 60 mm / second. In some embodiments, the retraction assembly 800 is configured to retract at least a portion of the imaging probe 100 at a speed of at least 60 mm / second, at least 80 mm / second, at least 100 mm / second, and / or at least 150 mm / second. Additionally or alternatively, the retraction procedure may be performed over a time period between 0.5 seconds and 25 seconds, such as about 20 seconds (e.g., over a distance of 100 mm at 5 mm / second). The service loop 185 of the imaging probe 100 may be disposed between the retraction assembly 800 and / or at least the connector assembly 820 and the rotation assembly 500, such that the rotation assembly 500 can retract the imaging probe 100 with respect to the patient while remaining stationary (e.g., while attached to a portion of the operating table and / or the console 50).

[0073] The retraction assembly 800 further includes a power element 830 that is a linear drive device. In some embodiments, the power element 830 may include a linear actuator, a worm drive operably attached to a motor, a pulley system, and / or other linear force transmission mechanisms. The plier 850 may be operably attached to the power element 830 via a linkage assembly 890. In some embodiments, the linkage assembly 890 may include one or more components of a "retraction assembly" as described with reference to FIGS. 1A and 2A. Alternatively or additionally, the linkage assembly 890 may include one or more components of an enclosed retraction connector as described with reference to FIG. 1B. One or more components of the linkage assembly 890 may establish a reference frame (e.g., an internal retraction reference) between the plier 850 and the power element 830 such that the power element 830 applies a retraction force to the plier 850 via the linkage assembly 890 and the plier 850 retracts relative to the distal portion of the linkage assembly 890 (e.g., relative to the distal end of the sheath portion 895 as described with reference to FIG. 1A). In some embodiments, the distal ends of the linkage assembly 890 and the connector assembly 820 are fixed relative to each other, and the plier 850 translates linearly between them in response to the force applied from the power element 830.

[0074] The console 50 includes an imaging assembly 300, a user interface 55, a processor 52, and one or more algorithms 51. The processor 52 may include one or more memory storage components such as one or more memory circuits that store software routines, algorithms (e.g., algorithm 51), and other operating instructions of the system 10, as well as data acquired by the imaging probe 100, the second imaging device 15, and / or other components of the system 10. The imaging assembly 300 may be configured to provide light to the optical assembly 115 (e.g., via the optical core 110) and collect light from the optical assembly 115 (e.g., via the optical core 110). The imaging assembly 300 may include a light source 310. The light source 310 may include one or more light sources such as one or more light sources configured to provide light of one or more wavelengths to the optical assembly 115 via the optical core 110. The light source 310 is configured to provide light to the optical assembly 115 (via the optical core 110) such that image data including information about a cross-section, longitudinal direction, and / or volume related to the patient site to be imaged or the implanted device can be collected. The light source 310 may be configured to provide light such that the collected image data includes characteristics of tissue within the patient site being imaged, and may, for example, quantify, qualify, or otherwise provide information related to a patient's disease or disorder present within the patient site being imaged. The light source 310 may be configured to supply broadband light having a center wavelength in the range of 350 nm to 2500 nm, in the range of 800 nm to 1700 nm, in the range of 1280 nm to 1310 nm, or in the range of about 1300 nm (e.g., light supplied in a sweep range from 1250 nm to 1350 nm). The light source 310 may have a sweep rate of at least 50 kHz. In some embodiments, the light source 310 may have a sweep rate of at least 100 kHz, for example, at least 200 kHz, 300 kHz, 400 kHz, and / or 500 kHz. These faster sweep rates provide a number of advantages, for example, to provide a higher frame rate and to accommodate rapid retraction and rotation speeds.For example, a higher sweep rate enables the required sampling density (e.g., the amount of the lumen surface area swept by the rotating beam) to be achieved in a shorter time, which is advantageous in most situations and particularly advantageous when there is relative movement between the probe and the surface / tissue being imaged, such as the arteries of a beating heart. The bandwidth of the light source 310 may be selected to achieve the desired resolution. The desired resolution may vary depending on the needs of the intended use of the imaging system 10. In some embodiments, the bandwidth is about 5% to 15% of the central wavelength. This enables a resolution of 20 μm to 5 μm. The light source 310 may be configured to supply light at a power level that meets the ANSI Class 1 (“eye-safe”) limit, although higher power levels may be employed. In some embodiments, the light source 310 irradiates light in the 1.3 μm band at a power level of about 20 mW. As the central wavelength of the supplied light increases, light scattering in the tissue decreases, but water absorption increases. The light source 310 may supply light at a wavelength close to 1300 nm to balance these two effects. The light source 310 may be configured to supply light at a shorter wavelength (e.g., light at about 800 nm) to cross a patient site being imaged that contains a large amount of fluid. Alternatively or additionally, the light source 310 may be configured to supply light at a longer wavelength (e.g., light at about 1700 nm) that reduces high levels of scattering within the patient site being imaged. In some embodiments, the light source 310 is a tunable coherent light source (e.g., the light source 310 emits a single wavelength that varies repetitively over time), and / or a broadband light source. The light source 310 may be a single spatial mode light source or a multimode light source (e.g., a multimode light source with spatial filtering).

[0075] The light source 310 may have a relatively long effective coherence length, such as a coherence length of 10 mm or more, for example, at least 50 mm in length, at all frequencies within the bandwidth of the light source. In order to generate detectable interference fringes, the light returning from a distant imaging object (e.g., tissue) must maintain phase coherence with the returning reference light. Thus, due to this coherence length capability, the system 10 may achieve a longer effective scan range. In the case of a swept light source laser, the instantaneous linewidth becomes very narrow (i.e., when the laser is swept, it outputs a very narrow frequency band that varies at the sweep rate). Similarly, in the case of a broadband light source, the detector arrangement needs to be able to select a very narrow linewidth from the spectrum of the light source. The coherence length is inversely proportional to the linewidth. If the scan range is long, larger or more distant objects can be imaged (e.g., more distant tissue can be imaged). In current systems, the coherence length is short. The coherence length is correlated with a reduction in the image capture range and artifacts (ghosts) arising from objects outside the effective scan range.

[0076] The console 50 may comprise one or more algorithms, such as an algorithm 51 configured to adjust (e.g., automatically and / or semi-automatically) one or more operating parameters of the imaging system 10, such as operating parameters of the console 50, the imaging probe 100, and / or the delivery catheter 80. The console 50 may further comprise a processor 52, which is a processing assembly configured to execute the algorithm 51 and / or to execute any type of data processing, such as the digital signal processing described with reference to FIG. 4. Additionally or alternatively, the algorithm 51 may be configured to adjust the operating parameters of another device, such as the injector 20 or the implant delivery device 30 described herein. In some embodiments, the algorithm 51 is configured to adjust the operating parameters based on one or more sensor signals, such as sensor signals provided by the sensor-based functional components of the inventive concept described herein. The algorithm 51 may adjust operating parameters selected from a group consisting of rotational parameters, such as the rotational speed of the optical core 110 and / or the optical assembly 115, retraction parameters, such as the retraction speed, distance, start position, end position, and / or retraction start timing (e.g., when retraction is initiated) of the shaft 120 and / or the optical assembly 115, position parameters, such as the position of the optical assembly 115, line interval parameters, such as the number of lines per frame, image display parameters, such as scaling of the display size relative to the vessel diameter, configuration parameters of the imaging probe 100, parameters of the implant 21, such as saline, with respect to the contrast ratio configured to determine the appropriate refractive index, light source 310 parameters, such as the power and / or frequency of the light being irradiated, and combinations of one or more of these.In some embodiments, algorithm 51 is configured to adjust retraction parameters, such as parameters that trigger the start of retraction, such as retraction that is initiated based on parameters selected from the group consisting of lumen cleaning (wherein the lumen proximate to the optical assembly 115 is sufficiently cleared of blood or other substances that would interfere with image creation), receiving an indicator signal (e.g., a signal indicating that sufficient cleaning fluid has been supplied) from the injector 20, a change in the collected image data (e.g., a change in the image is detected that correlates to the proper drainage of blood from around the optical assembly 115 based on the collected image data), and one or more combinations thereof. In some embodiments, algorithm 51 is configured to identify the attached imaging probe 100 (e.g., automatically identify via RF or other embedded ID) and adjust configuration parameters of the imaging system 10 related to the imaging probe 100, such as when adjusting parameters of the imaging system 10, such as arm path length parameters, dispersion parameters, and / or other parameters as described above.

[0077] The imaging system 10 may include a bus 58 that is one or more interconnecting cables. The bus 58 may operably connect the rotation assembly 500 to the console 50, the retraction assembly 800 to the console 50, and / or the rotation assembly 500 to the retraction assembly 800. The bus 58 may include one or more optical transmission fibers, electrical transmission cables, fluid conduits, and combinations of one or more thereof. In some embodiments, the bus 58 may include at least one optical transmission fiber that optically couples the rotation joint 550 to the imaging assembly 300 of the console 50. Additionally or alternatively, the bus 58 includes at least power and / or data transmission cables that transmit power and / or power information to one or more of the power elements 530 and 830.

[0078] The second imaging device 15 may be an imaging device such as an X-ray, a single-plane or bi-plane fluoroscope such as a fluoroscope, a CT scanner, an MRI, a PET scanner, an ultrasonic imaging device, and one or more imaging devices selected from the group consisting of combinations of one or more of these. In some embodiments, the second imaging device 15 is a device configured to perform rotational angiography.

[0079] The treatment device 16 may be an occlusion treatment or other treatment device selected from the group consisting of a balloon catheter configured and arranged to expand a stenosis or other constriction of a blood vessel, a drug-eluting balloon, a suction catheter, a sonolysis device, an atelectomy device, a thrombus removal device such as a stent retriever device, a Trevo® stent retriever device, a Solitaire® stent retriever device, a Revive® stent retriever device, an Eric® stent retriever device, a Lazarus® stent retriever device, a stent delivery catheter, a microblade implant, an embolization system, a WEB® embolization system, a Luna® embolization system, a Medina® embolization system, and combinations of one or more of these. In some embodiments, the imaging probe 100 is configured to collect data related to the treatment device 16 (e.g., the position, orientation, and / or other configuration data of the treatment device 16) after the treatment device 16 has been inserted into the patient.

[0080] The injector 20 may be a power injector, a syringe pump, a peristaltic pump, or other fluid delivery device configured to inject a contrast agent such as a radiopaque contrast agent and / or other fluid. In some embodiments, the injector 20 is configured to supply a contrast agent and / or other fluid (e.g., a contrast agent, saline, and / or dextran). In some embodiments, the injector 20 delivers fluid with a flushing procedure as described herein. In some embodiments, the injector 20 supplies a contrast agent or other fluid via a delivery catheter 80 having an ID between 5Fr and 9Fr, a delivery catheter 80 having an ID between 0.53 inches and 0.70 inches, or a delivery catheter 80 having an ID between 0.0165 inches and 0.027 inches. In some embodiments, the contrast agent or other fluid is supplied via a small delivery catheter (e.g., for distal injection) on the order of 4Fr. In some embodiments, the injector 20 supplies a contrast agent and / or other fluid through the lumen of one or more delivery catheters 80 while one or more smaller delivery catheters 80 are also present within the lumen. In some embodiments, the injector 20 is configured to supply two different fluids, such as a first fluid supplied from a first reservoir and containing a contrast agent at a first concentration, and a second fluid supplied from a second reservoir and having less or no contrast agent, simultaneously and / or sequentially.

[0081] The injectant 21 may be a fluid selected from the group consisting of an optically transparent material, saline, a visualizable material, a contrast agent, dextran, an ultrasonic reflective material, a magnetic material, and combinations thereof. The injectant 21 may be a contrast agent and saline. The injectant 21 may contain at least 20% contrast. During the collection of the image data, for example, the injectant 21, which is one or more fluids, is supplied (e.g., so as to be propelled by an injector 20 or other fluid delivery device) to remove blood or other somewhat opaque materials (hereinafter, non-permeable materials) in the vicinity of the optical assembly 115 (e.g., to remove non-permeable materials between the optical assembly 115 and the delivery catheter and / or non-permeable materials between the optical assembly 115 and the blood vessel wall), so that the light distributed from the optical assembly 115 reaches all the tissues and other objects to be imaged and returns reflectively. An injection procedure may be performed, such as to enable this. In embodiments of these injection procedures, the injectant 21 may be an optically transparent material such as saline. The injectant 21 may be one or more visualizable materials as described herein.

[0082] As an alternative to or in addition to use in the injection procedure, the injectant 21 may be a material configured to be seen by a second imaging device 15 that constitutes, for example, a fluoroscope or other X-ray device, an ultrasonic reflective material configured to be seen by a second imaging device 15 that constitutes an ultrasonic imaging device, and / or a magnetic material configured to be seen by a second imaging device 15 that constitutes an MRI.

[0083] The implant 31 may be an implant (e.g., a temporary or chronic implant) for treating one or more of vascular occlusions or aneurysms. In some embodiments, the implant 31 is one or more implants selected from the group consisting of a flow diverter, a Pipeline® flow diverter, a Surpass® flow diverter, an embolization coil, a stent, a Wingspan® stent, a covered stent, an aneurysm treatment implant, and combinations of one or more thereof.

[0084] The implant delivery device 30 may comprise a catheter or other tool used to supply the implant 31, for example, when the implant 31 has a self-expanding or balloon-expandable portion. In some embodiments, the imaging system 10 comprises an imaging probe 100, one or more implants 31, and / or one or more implant delivery devices 30. In some embodiments, the imaging probe 100 is configured to collect data related to the implant 31 and / or the implant delivery device 30 (e.g., the anatomical location, orientation, and / or other configuration data of the implant 31 and / or the implant delivery device 30) after the implant 31 and / or the implant delivery device 30 have been inserted into a patient.

[0085] In some embodiments, one or more system components, such as console 50, delivery catheter 80, imaging probe 100, rotation assembly 500, retraction assembly 800, treatment device 16, injector 20, and / or implant delivery device 30, further include one or more functional components (referred to herein as "functional components"), such as the illustrated functional components 59, 89, 199, 599, 899, 99a, 99b, and / or 99c. Each functional component may be composed of at least two functional components. Each functional component may be one or more components selected from the group consisting of sensors, transducers, and combinations thereof. The functional component may be a sensor configured to generate a signal. The functional component may be a physiological sensor, a pressure sensor, a strain gauge, a position sensor, a GPS sensor, an acceleration sensor, a temperature sensor, a magnetic sensor, a chemical sensor, a biochemical sensor, a protein sensor, a flow sensor such as an ultrasonic flow sensor, a gas detection sensor such as an ultrasonic bubble detector, a sound sensor such as an ultrasonic sensor, and sensors selected from the group consisting of combinations thereof. The sensor may be a pressure sensor such as a blood pressure sensor, a blood gas sensor, a flow sensor such as a blood flow sensor, a temperature sensor such as a temperature sensor for blood or other tissue, and a physiological sensor selected from the group consisting of combinations thereof. The sensor may be a position sensor configured to generate a signal related to the shape of a vascular path (e.g., the shape of a 2D or 3D vascular path). The sensor may be a magnetic sensor. The sensor may be a flow sensor. The system may further include an algorithm configured to process signals generated by the sensor-based functional components. Each functional component may include one or more transducers. Each functional component may include one or more transducers selected from the group consisting of a heater such as a heating element configured to provide sufficient heat to excise tissue, a cooler such as a cooling element configured to provide cryogenic energy to excise tissue, a sound transducer such as an ultrasonic transducer, a vibration transducer, and combinations thereof.

[0086] In some embodiments, the imaging probe 100 includes a fluid propulsion element and / or a fluid pressurization element (referred to herein as a "fluid pressurization element"), such as an FPE 1500, which is not shown and will be described with reference to FIGS. 12 and 12A-C. The fluid propulsion element may be configured to prevent and / or reduce the presence of air bubbles in the gel 118 proximate the optical assembly 115. The fluid propulsion element can be fixedly attached to the optical core 110. The fluid propulsion element rotates in response to rotation of the optical core 110 to generate a pressure increase in the gel 118 configured to reduce the presence of air bubbles from a position proximate the optical assembly 115. Such one or more fluid pressurization elements can reduce the likelihood of air bubble formation within the gel 118, reduce the size of air bubbles within the gel 118, and / or move any air bubbles formed within the gel 118 away from locations that would adversely affect the collection of image data by the optical assembly 115 (e.g., move the air bubbles away from the optical assembly 115). In some embodiments, the fluid propulsion element of the imaging probe 100 is configured in the same configuration and arrangement as the fluid propulsion element described in U.S. Provisional Patent Application No. 62 / 840,450, filed Apr. 30, 2019, titled "Imaging Probe with Fluid Pressure Element," which is co-pending and assigned to the applicant, the entire content of which is hereby incorporated by reference in its entirety for all purposes. S

[0087] ​Referring now to FIG. 1A, a schematic view of an imaging system is illustrated. This system, in accordance with the concepts of the present invention, comprises an imaging probe operably attached to a patient interface module, and an independent retraction module operably attached to the patient interface module and the imaging probe. The imaging system 10 may comprise a patient interface module 200. The patient interface module 200 comprises a housing 201 which is a housing surrounding at least a part of a rotation assembly 500 and at least a part of a retraction assembly 800. The imaging system 10 may further comprise a retraction module 880 which is a second separable component. The retraction module 880 may comprise a housing 881 which is a housing surrounding at least a part of the retraction assembly 800. The retraction module 880 and the patient interface module 200 may be operably attached to each other via a linkage assembly 890 which is the connector assembly described herein. The retraction module 880 and the patient interface module 200 may be configured and arranged to enable positioning at different locations (by virtue of each having a separate housing) (for example, the linkage assembly 890 connecting the modules 880 and 200 may have a length of at least 15 cm such that it can separate two remote positions by at least 15 cm). For example, the patient interface module 200 may be disposed on or near a surgical bed rail. Also, the retraction module 880 may be disposed near the patient's vascular access site (for example, within 30 cm of the vascular access site where the imaging probe 100 enters the patient). The linkage assembly 890 may comprise a linkage 891 slidably received within a sheath 895. The linkage 891 is operably attached to a bracket 850, and the proximal end 893 of the linkage 891 may have a connection point 842. The power element 830 may comprise a connector 835 configured to releasably attach to the connection point 842. The components shown in FIG. 1A may be of a similar nature to the components described with reference to FIG. 1, and of a similar configuration and arrangement as described elsewhere in this specification.

[0088] As described with reference to FIG. 2B, the retraction module 880 may include a connector assembly 820b that is operably attached to the connector 82 of the delivery catheter 80. As described with reference to FIG. 2A, the connector assembly 845 may include a connector 840 that is operably attached to the connector assembly 820a of the patient interface module 200.

[0089] Referring now to FIG. 1B, a schematic diagram of the imaging system is shown. The system includes an imaging probe operably attached to a module having a first connector for attachment to a rotational power element and a second connector for attachment to a retraction power element so as to conform to the concepts of the present invention. The imaging system 10 may include a patient interface module 200 as described herein. The imaging system 10 may further include a module 410 that is a connector module. The module 410 includes a housing 411 that is a housing surrounding at least a portion of the retraction assembly 800, the service loop 185 of the imaging probe 100, the connector assembly 150', and the connector 840'. The module 410 may be configured to operably attach both the imaging probe 100 and a linkage, the puller 850', to the patient interface module 200. The components shown in FIG. 1B may be similar components as described with reference to FIG. 1 and similar configurations and arrangements as described elsewhere in this specification. The module 410 may be operably attached to a delivery catheter 480. The delivery catheter 480 may have a similar configuration and arrangement as the delivery catheter 80 described with reference to FIG. 1. The delivery catheter 480 may include a window portion 485 that is at least optically transparent. The window portion 485 may be disposed at or near the distal portion of the delivery catheter 480. The window portion 485 may be made of a material that is transparent to the imaging modality utilized by imaging the imaging probe 100 such that, for example, the imaging probe 100 can image through the window portion 485 when the optical assembly 115 is retracted into the window portion 485. In some embodiments, the module 410, the delivery catheter 480, and the imaging probe 100 collectively form a catheter assembly 4100.

[0090] Referring now to FIG. 2A, a perspective view of a connector attached to a patient interface that conforms to the concepts of the present invention is shown. The patient interface module 200 is configured to provide rotation to the rotatable optical core of the imaging probe and to provide power to translate at least a portion of the imaging probe as described herein. The patient interface module 200 includes a rotation assembly 500 and at least a portion of a retraction assembly 800. The housing 201 surrounds the patient interface module 200. The patient interface module 200 may include one or more user interface elements such as buttons 205a, 205b, which are one or more input portions, and an illustrated indicator 206, which is one or more output portions. The patient interface module 200 includes a connector assembly 510, which is a first physical connector assembly for operably connecting to the connector assembly 150 as described herein. Additionally, the patient interface module 200 may further include a connector assembly 820a, which is a second physical connector assembly for operably connecting to the connector 840 as described herein. The connector assemblies 150 and 840 may each be bayonet connectors configured and arranged to be at least partially inserted into the connector assemblies 510 and 820a, respectively. The connector assemblies 150 and 840 may then be rotated (e.g., rotated about 45°) to lock their connections to the connector assemblies 510 and 820a, respectively, as described herein. The connector assemblies 150 and / or 840 may be connectors in a number of forms, such as bayonet or other locking connectors.

[0091] Referring now to FIG. 2B, a perspective view of a retraction assembly is illustrated that is consistent with the concepts of the present invention. The retraction module 880 is operably attached as part of the imaging probe 100 of the concepts of the present invention to provide a pulling force to the probe and, as described herein, pull at least a portion of the probe proximally relative to a patient (e.g., relative to a patient introduction device). The retraction module 880 may be of a similar configuration and arrangement as the retraction module 880 as described in the applicant's co-pending international PCT patent application number PCT / US2018 / 062766, entitled "Imaging System," filed Nov. 28, 2018, the contents of which are hereby incorporated by reference in their entirety. The retraction module 880 may be operably attached to the distal end of a linkage 891 (not shown). The linkage assembly 890 may be slidably received through the retraction module 880. The sheath 895 may be fixedly attached to the proximal end of the module 880. The linkage 891 is slidably received along the length of the module 880 and is operably attached at its distal end to the puller 850.

[0092] The retraction module 880 may include a housing 881 that is composed of two parts, having an upper housing portion 881a and a lower housing portion 881b. The module 880 may include a puller 850 (not shown but disposed below the carrier 855 and described herein) that is a translation cart. The puller 850 may be designed to translate within the module 880. The module 880 may include a spring 852 (not shown) that is a biasing element. The spring 852 may provide a biasing force to the puller 850, such as biasing the puller 850 distally.

[0093] The upper receiving portion 881a may have a holding port 884 that is a first cavity and a trench 889 that is a second cavity. The holding port 884 and the trench 889 may be separated by a holding wall 888 that is a protrusion. The physical connector assembly 820b may include the holding port 884 of the receiving portion 881a having the wall 888 and a clip 885 that is a holding mechanism. The clip 885 may be configured to releasably engage a proximal end of a delivery catheter, such as the sheath connector 82 of the delivery catheter 80, for example, when the connector 82 is a Tuohy Borst connector. The physical connector assembly 820b may further include a spring 886 (not shown) that is a biasing element. The spring 886 may provide a biasing force to maintain the clip 885 in an engaged position with respect to the connector 82.

[0094] The retraction module 880 may further include a carrier 855. The carrier 855 may be operably attached to the puller 850, for example, via a groove 889a of the receiving portion 881a. The carrier 855 may translate within the trench 889 in response to the puller 850 (which translates in response to the linkage 891). The carrier 855 may be operably attached to a part of the imaging probe 100, such as the retraction connector 180. The retraction connector 180 may include a "torquer" or other device attached to the shaft 120 of the imaging probe 100. The sheath 895 of the linkage assembly 890 may provide a reference frame between the connector 840 and the retraction module 880 such that when the proximal end of the linkage 891 is drawn into the connector 840, the distal end of the linkage 891 is drawn toward the sheath 895 (i.e., toward the proximal end of the retraction module 880). This relative movement transmits the power applied at the connector 840 to the puller 850 (e.g., via the power element 830 as described herein). Subsequently, the puller 850 transmits the power to the imaging probe 100, and the imaging probe 100 is drawn relative to the patient.

[0095] During operation, the imaging probe 100 may be advanced manually (e.g., by a user) through the patient's vasculature. The retraction module 880 may be attached to the patient (e.g., attached to the delivery catheter 80 via the connector 82 when the delivery catheter 80 is inserted into the patient and in a position relatively fixed to the patient). The connector 180 may be operably connected to the imaging probe 100 and disposed proximate to the delivery catheter 80 (e.g., the torquing connector 180 may be clamped to the imaging probe 100 proximate to the delivery catheter 80). The connector 180 (not shown) may be operably disposed within the carrier 855. Power may be applied to the distal end of the linkage 891. The carrier 855 is retracted into the trench 889 to retract the imaging probe 100 relative to the patient. After being retracted, the connector 180 may be removed from the carrier 855 (e.g., lifted). The carrier 855 and the imaging probe 100 may be advanced independently again. For example, the carrier 855 can be advanced again through the biasing force of the spring 852 since the advancement of the proximal end of the linkage 891 is allowed. The imaging probe 100 may be advanced manually again by the user. Subsequent retraction can be performed by repositioning the connector 180 within the carrier 855 after both have been advanced again. The carrier 855 may include a capture portion such as a "cup-like" shape, a hook, or other capturable part so that the carrier 855 can only apply a retracting force to the connector 180. In this configuration, when the carrier 855 translates in the distal direction, the connector 180 automatically disengages from the carrier 855 (e.g., the connector 180 drops out of the cup portion of the carrier 855).

[0096] Referring now to FIG. 3, a perspective view of a connector attached to a patient interface module that conforms to the concepts of the present invention is shown. The patient interface module 200 may have the same configuration and arrangement as the patient interface module 200 described with reference to FIG. 2A. The patient interface module 200 includes a connector assembly 510, which is a first physical connector assembly for operably connecting to the connector assembly 150'. The patient interface module 200 may also include a connector assembly 820a, which is a second physical connector assembly for operably connecting to the connector 840'. The connector assemblies 150' and 840' may each include bayonet connectors configured and arranged to be at least partially inserted into the connector assemblies 510 and 820a, respectively.

[0097] As described herein, the system 10 may be configured and arranged to provide improved imaging of a patient's anatomical structure (e.g., one or more blood vessels of the patient) and to provide improved imaging of implants, catheters, and / or other devices disposed within the patient (e.g., disposed within a blood vessel of the patient). In some embodiments, the system 10 is configured to provide information for use in performing a treatment (e.g., an intervention), e.g., by a clinician. The information is based at least in part on optical coherence tomography data. For example, OCT and other data collected by the system 10 may be used in the planning of a treatment and / or prediction of treatment outcomes (e.g., a plan and / or prediction performed by the system 10, a user of the system 10, or a combination of the two) that affect the treatment to be provided to the patient (herein, "OCT-guided treatment" and / or "OCT-guided therapy").

[0098] As described herein, the imaging probe 100 may have at least one of a size (e.g., diameter and / or length), scan range, flexibility, and / or imaging ability configured to provide improved imaging. The imaging probe 100 may have a size and / or flexibility configured to enable imaging of narrow lesions within a blood vessel. As used herein, a narrow lesion may be a lesion in which the resulting lumen (i.e., the lumen within the lesion) has a diameter (e.g., the minimum diameter along the length of the lesion) of less than 2 mm (0.080 inches). Since commercially available OCT catheters are arranged to image lesions having such small-diameter lumens, the injection medium applied proximally is effectively blocked from propagating distally of the lesion. Thus, the use of this commercially available device is hindered. However, the imaging probe 100 can be configured and arranged to image these narrow lesions, e.g., lesions in which the resulting lumen is as small as 1.5 mm (0.060 inches), 1.3 mm (0.053 inches), 1.1 mm (0.043 inches), and / or 0.9 mm (0.036 inches). For example, the distal portion of the imaging probe 100 may have an outer diameter of 2.6F (0.034 inches) or less, e.g., 1.7F (0.022 inches) or less, so that in a "pre-treatment" imaging procedure (e.g., a procedure performed prior to intervention in a stenosis or other treatment), the system 10 can be used to image a potential blood vessel (e.g., an artery) having a narrow lesion. As described herein, currently available OCT imaging systems may be too large to provide useful data (e.g., cannot pass through narrow lesions and sufficient blood clearance cannot be obtained). Also, in other types of imaging systems such as angiography, accurate enough results may not be obtained when imaging narrow lesions (e.g., may falsely indicate that treatment is not necessary, such as when providing FFR information).In some embodiments, the system 10 is used to perform a pre-treatment imaging procedure (e.g., of a narrow lesion) to collect data for OCT-guided therapy that enables data provided by the system 10 (e.g., using at least images from the probe 100) to be used by an operator (e.g., a clinician) to make decisions regarding future treatments to be performed. In these embodiments, the system 10 may be used to image the same anatomical location after treatment (in a "post-treatment" imaging procedure).

[0099] In some embodiments, the system 10 is configured to perform a pre-treatment imaging procedure (e.g., of a narrow lesion) and provide OCT-guided therapy due to the following characteristics of the system 10: the distal portion of the probe 100 (e.g., including the optical assembly 115) has a diameter of 2.6 Fr (0.034 inches) or less, e.g., 2.0 Fr (0.026 inches) or less, e.g., 1.7 Fr (0.022 inches) or less.

[0100] In some embodiments, the system 10 is configured to perform a pre-treatment imaging procedure (e.g., of a narrow lesion) and provide OCT-guided therapy due to the following characteristics of the system 10: the optical assembly 115 is rotated (e.g., via the rotation assembly 500) at a speed of 180 revolutions per second or more, e.g., at least 200, 250, 400, and / or 500 revolutions per second.

[0101] In some embodiments, system 10 is configured to perform pre-treatment imaging procedures (such as of a narrow lesion) and provide OCT-guided therapy due to the following characteristics of system 10: The scan range of system 10 is at least 7 mm in radius, for example, at least 11 mm in radius. The long scan range of system 10 provides a number of advantages, such as the ability to image from the imaged blood vessel into any side branch of that vessel, the ability to image large blood vessels when the optical assembly 115 is eccentrically positioned within the blood vessel lumen (e.g., close to a part of the vessel wall), and / or the ability to image generally large blood vessels such as the left main aorta, carotid arteries, and large peripheral arteries.

[0102] In some embodiments, system 10 is configured to provide pre-treatment imaging procedures (such as of a narrow lesion) and provide OCT-guided therapy due to the following characteristics of system 10: A retraction distance of 7.5 cm or more, for example, at least 10 cm or at least 15 cm of retraction. The retraction may be performed at a speed of at least 25 mm / second and / or within a time of 4 seconds or less (e.g., a complete retraction of at least 7.5 cm, 10 cm, and / or 15 cm in 4 seconds or less). The operable retraction speed of the imaging probe 100 may be determined through the relationship between the rotational speed of the optical assembly 115 and the desired frame density of the OCT image data (e.g., frames / mm) such that the retraction speed is the rotational speed divided by the frame density. The imaging probe 100 may have a rotational speed greater than 180 Hz, such as at least 200 Hz or at least 250 Hz. The imaging probe 100 may have a frame interval of 0.2 mm or less (i.e., a frame density of at least 5 frames / mm). The imaging probe 100 may have a laser scan frequency of at least 200 kHz.

[0103] In some embodiments, system 10 is configured to perform pre-treatment imaging procedures (such as, for example, in narrow lesions) and provide OCT-guided treatment based on the following characteristics of system 10: The retraction speed (the translational speed of the optical assembly 115 during retraction) is at least 50 mm / s. In these embodiments, the rotational speed of the optical assembly 115 may be at least 180 Hz, 200 Hz, and / or 250 Hz. In these embodiments, the inter-frame spacing may be a minimum of 0.2 mm.

[0104] In some embodiments, system 10 is configured to perform pre-treatment imaging procedures (such as, for example, in narrow lesions) and provide OCT-guided treatment based on the following characteristics of system 10: The number of lines per frame is at least 400, for example at least 800 lines / frame, and the frame has continuous image data of approximately 360° (i.e., one full rotation of the optical assembly 115 provides the image data for one frame). In some embodiments, system 10 is configured to capture frames at a speed sufficient to enable downsampling of the frames (such as downsampling performed before analog-to-digital conversion of the data and / or other bandwidth-limited data processing).

[0105] In some embodiments, system 10 is configured to perform pre-treatment imaging procedures (such as, for example, in narrow lesions) and provide treatment under OCT guidance based on the following characteristics of system 10: A scan frequency of at least 50 kHz, for example at least 200 kHz, 350 kHz, and / or 500 kHz. In these embodiments, the number of lines per frame can be at least 400 lines / frame, or at least 800 lines / frame (for example, the number of lines per frame is equal to the scan frequency divided by the rotational speed of the optical assembly 115).

[0106] In some embodiments, system 10 has a laser scan frequency of 200 kHz or more, a retraction speed of 60 mm / second or 100 mm / second or more, and / or a rotation speed of 250 Hz or more. System 10 can be configured to image at least 50 mm of a blood vessel, for example, in 0.5 seconds or less, with 800 or more scan lines per rotation, a pitch of about 400 μm, and / or a frame density of at least 2.5 frames / mm and / or at least 5.0 frames / mm. In some embodiments, system 10 is configured to perform retraction during a quiescent portion of the cardiac cycle to minimize motion artifacts. In some embodiments, system 10 has a rotation speed of up to 400 kHz, such as not less than 250 kHz, 300 kHz, or 350 kHz.

[0107] In some embodiments, system 10 is configured to perform a pre-treatment imaging procedure (e.g., for a narrow lesion) and provide OCT-guided therapy based on the following characteristics of system 10: The processor 52 is configured to identify reflections generated at the splice interface between the optical assembly 115 and the optical core 110 (e.g., via algorithm 51). The optical interface between the optical assembly 115 (e.g., an optical assembly 115 comprising a GRIN lens) and the optical core 110 (e.g., an optical core 110 comprising an NZDS fiber) may have a relatively large index mismatch and provide clearly distinguishable reflections. This reflection may provide a reference point for the OCT image data collected by system 10. In some embodiments, the algorithm 51 may identify the interface with or without rotating the optical core 110.

[0108] Referring now to FIG. 4, a flowchart of a method for planning a patient treatment procedure in accordance with the concepts of the present invention is shown. The method 1000 of FIG. 4 is described using the system 10 described with reference to FIGS. 1-3.

[0109] In step 1100, a patient is selected for potential treatment.

[0110] In step 1200, an OCT probe such as imaging probe 100 is inserted into the patient.

[0111] In step 1300, OCT data as described herein is collected. In some embodiments, non - OCT data, such as physiological data of the patient recorded by one or more physiological sensors of system 10 and / or angiographic data collected by system 10, is also collected.

[0112] In step 1400, treatment information is generated by system 10 and / or a user of system 10 (e.g., a clinician of the patient who performs the data collection procedure of method 1000 or a clinician of the patient who performs subsequent treatment on the patient based on the treatment information generated via method 1000). In some embodiments, the treatment information provided by system 10 is based on a combination of OCT data and non - OCT data.

[0113] Referring now to FIG. 5, a flowchart of a method for planning a treatment procedure, a method for performing a treatment, and a method for evaluating a treatment, which is consistent with the concepts of the present invention, is shown. The method 1000 of FIG. 5 is described using the system 10 described with reference to FIGS. 1 - 3.

[0114] In step 1100, a patient is selected for potential treatment.

[0115] In step 1200, an OCT probe such as imaging probe 100 is inserted into the patient.

[0116] In step 1300, OCT data as described herein is collected. In some embodiments, non - OCT data (e.g., at least angiographic data) is also collected in step 1300 as described herein.

[0117] In step 1400, treatment information is generated by the system 10 and / or a user of the system 10 (e.g., a clinician of a patient who executes the data collection procedure of method 1000, or a clinician of a patient who executes subsequent treatment for the patient based on the treatment information generated via method 1000), etc.

[0118] In step 1500, a treatment procedure as described herein is executed on the patient.

[0119] In step 1600, OCT data as described herein is collected. In some embodiments, non - OCT data (e.g., at least angiography data) is also collected in step 1600 as described herein.

[0120] In step 1700, additional treatments, such as a treatment executed based on the OCT data collected in step 1600, are executed.

[0121] Referring now to FIG. 6, a flowchart of another method of planning a patient's treatment procedure that is consistent with the concepts of the present invention is shown. The method 1000 of FIG. 6 is described using the system 10 described with reference to FIGS. 1 - 3. The method of FIG. 6 describes the use of the system 10 to create image data from one or more arteries of a patient's heart. It should be considered within the spirit and scope of the present application that similar methods can be applied to other blood vessels and / or other locations of a patient's anatomical structure (e.g., arteries and / or veins of a patient's brain or peripheral vascular system).

[0122] In step 1100, a patient is selected. In some embodiments, the user may input one or more patient parameters into the system 10, for example, via the user interface 55 of the console 50. The one or more patient parameters may be selected from the group consisting of the patient's weight, the presence of one or more patient diseases (e.g., in addition to cardiovascular diseases such as diabetes if applicable), gender, age, height, TIMI score, stent implant, past coronary interventions such as bypass grafts, and combinations of one or more of these.

[0123] In step 1101, the system 10 is used to capture non - OCT imaging data of the selected patient, for example, via the second imaging device 15 described herein. As used herein, "non - OCT data" includes, but is not limited to, angiography image data, ultrasound image data, MRI image data, PET scan image data, and / or other non - OCT imaging data. In some embodiments, the non - OCT data includes two or more of angiography image data, ultrasound image data, MRI image data, PET scan image data, and / or other non - OCT imaging data. In some embodiments, the non - OCT data includes angiography image data and one or more of ultrasound image data, MRI image data, PET scan image data, and / or other non - OCT imaging data.

[0124] This non - OCT data may be stored in the memory of the system 10, such as in the memory of the processor 52 of the console 50. For example, angiography images of one or more blood vessels can be obtained using the injection of a contrast agent. The angiography data is stored in the memory of the system 10. Alternatively or additionally, the user may manually input relevant patient data (e.g., data similar to and / or extracted from angiography data or other non - OCT data) into the console 50 (e.g., via the keyboard of the user interface 55 or other user input components 57). Step 1101 may be performed (e.g., repeated in whole or in part) in any of the steps of the method of FIG. 6 described herein.

[0125] In step 1102, for diagnosis by a user (e.g., a patient's clinician), one or more arteries, veins, and / or other conduits (referred to herein as "arteries" or "arteries") that may require interventional treatment are selected, such as arteries. In some embodiments, the selected blood vessel (e.g., the selected artery or the selected vein) is manually input into the system 10 by, for example, a user of the system 10. In some embodiments, the selected blood vessels include arteries selected from the group consisting of the left circumflex artery (LCx), the right coronary artery (RCA), the left anterior descending artery (LAD), and combinations of one or more of these. In some embodiments, the data is input into the system 10 by the user during a processing step such as step 1310 described herein. For example, while the system 10 (e.g., algorithm 51) performs one or more background calculations, the system 10 may be configured to accept user input such that the overall treatment time is shortened (e.g., while the system 10 is processing data, the user makes the necessary and / or other data inputs).

[0126] In step 1200, the imaging probe 100 is inserted into a selected blood vessel (in this specification, appropriately referred to as the "selected blood vessel", "imaged blood vessel", "selected artery", "imaged artery", "selected vein", or "imaged vein"). When two or more arteries are selected for diagnosis, the following steps may be repeated for each selected artery. The placement of the probe 100 (e.g., positioning of the optical assembly 115) is performed to effectively obtain images required for one or more various calculations (e.g., flow rate calculation) performed by the system 10. The anatomical position where the retraction is initiated (e.g., the position of the optical assembly 115 at the start of retraction) is selected to be a position distal to (i.e., beyond) the distal end of the lesion in the artery (e.g., the most distal part of the lesion). The position where the retraction ends (e.g., the position of the optical assembly 115 at the end of retraction) is selected to be a position within the most distally positioned delivery catheter 80 into which the imaging probe 100 is inserted (e.g., the distal portion of the delivery catheter 80).

[0127] In step 1300, a retraction is performed while pulling the probe 100 through the lumen of the selected artery, and imaging data including OCT data is recorded.

[0128] In step 1310, the OCT recorded data is analyzed. In some embodiments, both OCT data and non - OCT data (e.g., angiography data) are analyzed (e.g., the OCT data is analyzed in combination with the non - OCT data). Steps 1311, 1312, and / or 1313 (or a part thereof) may be performed sequentially, simultaneously, and / or interleaved when the recorded data is analyzed by the system 10.

[0129] In step 1311, the recorded OCT data is analyzed by system 10. In some embodiments, the OCT data may be analyzed to identify one or more of the following: the boundaries of the lumen, side branches, healthy (e.g., non-diseased) portions of the lumen, diseased portions of the lumen, the type of disease imaged, the position of the guide wire within the image, and combinations of one or more of these. In some embodiments, the guide wire is removed from the OCT data. In some embodiments, system 10 identifies healthy sections of the imaged artery based on the OCT data. The healthy sections may be determined by identifying visible intima, media, and / or adventitial layers within the OCT data. In some embodiments, the myocardial mass may be estimated based on the diameter of one or more identified healthy sections of the imaged artery. In some embodiments, the estimation of the myocardial mass may be performed based on both OCT data and non-OCT data (e.g., angiographic data).

[0130] System 10 may have a weighting function (e.g., algorithm 51 has a weighting function). The weighting function is configured to prioritize data in one or more calculations (e.g., prioritize data types) so as to preferentially bias calculations based on, for example, OCT data versus non-OCT data, or vice versa. In some embodiments, system 10 identifies the presence of disease proximate to one or more side branches of the imaged artery (e.g., via algorithm 51). For example, if a disease is detected in proximity to a side branch (e.g., if the disease is detected within the side branch), the weighting function may be configured to prioritize angiographic data associated with the diseased side branch (e.g., bias the calculations in a direction to preferentially weight angiography more than OCT data).

[0131] System 10 may be configured to calculate the branch angle of a branch from an imaged artery (e.g., via algorithm 51). In some embodiments, the branch angle is used by algorithm 51 to calculate the side branch vessel diameter. System 10 may be configured to reconstruct at least a portion of the side branch from OCT data (e.g., from an image slice of the OCT data) and / or from non-OCT data (e.g., from angiography data). In some embodiments, system 10 is configured to calculate the relationship between the branch angle and the diameter of the size of the side branch (e.g., the size of the side branch relative to the size of the imaged artery). In these embodiments, if the relationship between the branch angle and the branch diameter is outside the expected range, system 10 may "flag" this anomaly (e.g., identify the anomaly and store the relevant information), as in step 1330 described herein, and / or be configured to alert the user of this anomaly.

[0132] In some embodiments, system 10 is configured to identify a portion of the OCT data that represents the minimum lumen diameter (e.g., a portion of healthy tissue having the minimum lumen diameter). Further, system 10 may be configured to identify two to five sections of the OCT data along the length of the lumen imaged during pullback (e.g., sections arranged at equal intervals along the length of the imaged lumen). The identified sections may be used to estimate the non-diseased vessel size (e.g., lumen diameter) of the selected artery. In some embodiments, at least one of the identified sections includes a proximal section and at least one of the sections includes a distal section (e.g., a proximal section and a distal section respectively proximate to the proximal and distal ends of the imaged lumen). In some embodiments, the proximal section and / or the distal section are within 10% of the proximal and distal ends respectively of the length of the imaged lumen. In some embodiments, the weighting function is configured to apply a weight (i.e., a weighting factor) to each section based on the reliability of the OCT data of that section. The reliability may be determined in several ways, for example, the percentage of the clear lumen detected within one frame (e.g., for high reliability, at least 75% of the circumference should be clear), and / or the amount of change in the lumen area from frame to frame (e.g., discontinuous frames should be given a lower weight). The reliability may also be obtained from the deviation of the circularity of the cross-section of the imaged vessel.

[0133] In some embodiments, system 10 identifies a diseased region (e.g., via algorithm 51) based on the OCT data and / or non-OCT data. In some embodiments, for example, when system 10 identifies the plaque composition of a diseased segment of an artery, the type of disease may be identified by system 10.

[0134] In step 1312, non-OCT data (e.g., angiography data) is analyzed. In some embodiments, the non-OCT data is analyzed to identify one or more of the following: the geometric shape of a blood vessel (e.g., curves, tapers, and / or trajectories), the location of a collateral (e.g., the size and location of one or more collateral branches of a diagnosed aorta), the length of a blood vessel, the diameter of a blood vessel; and combinations of one or more of these. In some embodiments, the non-OCT data may be analyzed to estimate myocardial mass, collateral blood vessels, the size of the cardiac region (myocardium) supplied by an artery (e.g., a selected artery), and combinations of one or more of these. In some embodiments, the non-OCT data analyzed in step 1312 includes angiography image data and one or more of ultrasound image data, MRI image data, PET scan image data, and / or other non-OCT image data. In some embodiments, the non-OCT data includes angiography data that is converted by system 10 into QCA data. In some embodiments, the non-OCT data includes PET scan data that system 10 converts into myocardial injury data (e.g., when system 10 adjusts the blood vessel size of the damaged region).

[0135] In step 1313, OCT data and non-OCT data (e.g., angiography data) are registered (e.g., associated with each other). In some embodiments, the data may be registered using the location, size, and shape of one or more collateral branches of a selected artery. In some embodiments, system 10 may have a digital model of one or more expected branches of the major blood vessels of the heart, such as the LCx, RCA, and / or LAD arteries. In some embodiments, the digital model is used by system 10 to register the data.

[0136] In step 1320, based on the analyzed data (e.g., the collected and / or analyzed OCT data and / or non-OCT data), cardiovascular hemodynamics are calculated. In some embodiments, system 10 is configured to estimate the microvascular resistance distal to a selected artery.

[0137] In some embodiments, the measured size of the imaged artery is adjusted by system 10 (e.g., the size of the imaged artery determined at step 1310 is adjusted by algorithm 51). System 10 may adjust the measured size of the imaged artery based on Murray's law. For example, system 10 may estimate a constant shear stress in all non-diseased regions of the imaged artery. This adjustment may minimize the error function of the flow rate calculated by system 10 using Murray's law. In some embodiments, the flow rate calculation is adjusted using a weighting function based on the reliability of the analyzed data. For example, if Murray's law proposes an adjustment to the measured size and the reliability of the imaged cross-section is relatively low, system 10 may be configured to adjust the flow rate calculation based on the adjustment proposed by Murray's law. Also, if the reliability is high, one or more adjustments based on Murray's law may be ignored by system 10.

[0138] The size of the myocardium to be supplied may be estimated by system 10 (e.g., using algorithm 51) based on the selected arterial vessel type and / or the calculated size. In some embodiments, the estimated size of the myocardium may be compared to an estimated size calculated based on non-OCT data (e.g., angiography data) as described in step 1312. In some embodiments, if the non-OCT-based estimate and the OCT-based estimate differ, the user is warned by system 10 (e.g., via user display 56 of interface 55 or other user output components). In some embodiments, system 10 accepts user input for adjusting the estimate (e.g., via user input 57 of user interface 55). In some embodiments, the OCT-based estimate is given a higher weight (e.g., by a weighting function of system 10) than the angiography-based estimate (e.g., the OCT-based estimate is preferred by system 10). In some embodiments, the data displayed in step 1330 may include a color map (e.g., a color map displayed on display 56). In some embodiments, the color map may indicate the estimated myocardium size supplied by the selected artery (e.g., the amount of myocardial tissue supplied by the selected artery). In some embodiments, the coronary microvascular resistance is estimated by system 10 (e.g., via algorithm 51) for all or at least a portion of the heart outside the imaging region.

[0139] In some embodiments, the pressure of the entire cardiovascular system of the heart (the "coronary artery tree") is calculated. In some embodiments, a fractional flow reserve (FFR) is calculated (e.g., calculated from the minimum pressure). The FFR may be calculated for a selected artery, e.g., for each selected artery (e.g., each artery selected and imaged using OCT). In some embodiments, the system 10 may be configured to warn the user (via the user interface 55) when one or more of the following are detected: when significant collateral blood flow (e.g., blood flow exceeding the threshold of the system 10) is detected; when the myocardial estimate varies significantly (e.g., the variation exceeds the threshold of the system 10) between the OCT-based estimate and the non-OCT-based estimate (e.g., angiography-based estimate) of the myocardium; when the TIMI score indicates damage to the myocardial tissue; when an area of no flow is detected by angiography (e.g., indicating an occlusion); and in cases of one or more combinations thereof.

[0140] In step 1330, OCT data and / or non-OCT data (e.g., angiography data) are displayed (e.g., on display 56). In some embodiments, the data are displayed in an overlay arrangement, such as after a plurality of data sets are registered in step 1320 (e.g., the OCT data are overlaid on the angiography data and / or other non-OCT data). In some embodiments, a graph of the lumen diameter is displayed. The lumen diameter may be the hydraulic diameter (e.g., four times the value obtained by dividing the area of the lumen by the surrounding area). In some embodiments, one or more branches (or portions thereof) of the selected artery are displayed. In some embodiments, the user may add to system 10 data indicating the presence of a disease, e.g., proximate to the displayed OCT data, such as at the proximal end of the lumen, the distal end of the lumen, or within a branch (e.g., the user may visually determine the presence of a disease via information provided by the second imaging device 15 and manually input relevant disease type and / or disease location data into system 10). In some embodiments, the calculated vessel size is displayed together with the OCT image and / or non-OCT image (e.g., angiography image). In some embodiments, system 10 enables the user to edit the displayed calculated value (e.g., to enable user-directed manual adjustment of the calculated value of system 10).

[0141] In step 1400, a user of system 10 may plan a treatment based on the displayed data. In some embodiments, the user indicates the length and location of a "treatment region" evaluated by system 10 (e.g., the user clicks on the displayed image to indicate the treatment region). In some embodiments, system 10 displays the estimated vessel diameters at the proximal and distal ends of the selected treatment region. In some embodiments, the vessel diameters are estimated by system 10 using Green's theorem (e.g., via algorithm 51). In some embodiments, system 10 displays one or more pieces of information related to the selected treatment region, such as any warnings related to the treatment region and / or plaque composition within the treatment region. In some embodiments, the post-treatment hemodynamics (e.g., FFR) may be estimated assuming that the planned treatment (e.g., stent implantation) opens the treated vessel to the estimated diameters at the proximal and distal ends of the selected treatment region (e.g., two diameters may be used to indicate the tapering of the vessel). In some embodiments, the post-treatment hemodynamics may be estimated based on the calculated pre-treatment hemodynamics and the proposed treatment. In some embodiments, the user may change the proposed treatment region, and system 10 may update the hemodynamics based on the new treatment region. In some embodiments, the user may indicate two or more treatment regions (e.g., two or more non-contiguous treatment regions), and the post-treatment hemodynamics may be estimated for each treatment region.

[0142] As described herein, system 10 may be configured to calculate flow characteristics through one or more blood vessels imaged using probe 100 (e.g., via one or more pullbacks). System 10 may be configured to calculate blood hemodynamics (e.g., flow field and / or pressure drop) through the imaged blood vessels (e.g., an artery in which treatment has been or is to be performed). In some embodiments, system 10 calculates coronary blood flow and pressure loss using a full 3D Navier-Stokes simulation of the blood vessels imaged using probe 100. As shown in FIG. 7 and described herein, system 10 may be configured to include a number of geometric and other features of the imaged region in its analysis, such as when all significant morphological features are represented. System 10 may directly measure the pressure within the blood vessel and, as described herein, calculate the FFR at locations along the length of the blood vessel. Regions where a rapid change in FFR occurs (e.g., regions identified by system 10) may be used to justify an intervention (e.g., stent placement).

[0143] FIG. 7 shows a full Navier-Stokes simulation of the flow through an artery and the FFR calculated along the length of the artery.

[0144] The use of the full 3D Navier-Stokes equations can be computationally intensive and may require an undesirably long time. In some embodiments, system 10 utilizes a two-dimensional (2D) scheme that gives sufficiently accurate results for the calculation of FFR and requires less time than a full three-dimensional (3D) Navier-Stokes based approach.

[0145] In some embodiments, the system 10 may be configured to use the 3D Navier-Stokes equations in a subset of the flow field, such as when small morphological features affect the flow rate. Examples of these include bifurcations with significant stenosis, and positions downstream of the stenosis, such as positions for predicting the transition to turbulent flow. The lengths of these short blood vessels can be calculated relatively quickly, and the calculated flow rate resistance can be modeled as a resistance element of the 2D scheme.

[0146] The system 10 may be configured to utilize a 2D scheme that uses the distance to the lumen area calculated from OCT data, as well as flow shape parameters for predicting pressure loss, flow separation, and viscous wall shear stress.

[0147] When the flow in the pipe is fully developed, the relationship between the flow rate and the pressure loss is as follows.

Equation

[0148] Q = volumetric flow rate R = radius of the pipe (1 / 2 of the pipe diameter) μ = viscosity of the blood dP / dx = pressure loss in the pipe along the pipe direction

[0149] In some embodiments, to improve the speed of the calculations performed by the system 10, μ is set to be constant (e.g., 3 centipoise). In other words, the shear thinning effect of the blood is ignored. For correlation with the measured FFR, the system 10 may be configured to adjust μ according to the hematocrit, but in general use, μ is kept constant.

[0150] FIG. 8 shows the velocity distribution in the pipe. This profile depicts a parabola, with the highest velocity at the center.

[0151] When the diameter of a blood vessel changes, the velocity profile changes from a parabola to another shape. In some embodiments, system 10 utilizes a one-dimensional (1D) method and uses only these two continuous parameters along the length of the blood vessel to calculate the pressure drop, the diameter of the blood vessel, and the deviation from the parabolic shape. System 10 calculates other continuous values along the length based on these two parameters. These values include the Reynolds number, the degree of turbulent flow, the rate of change of the pressure gradient, the wall shear stress, and the like.

[0152] As shown in FIG. 9, in the region where the blood vessel diameter increases rapidly, the velocity near the wall decreases. The shear stress μdU / dy (evaluated at the wall) decreases, thereby reducing the viscous pressure loss component.

[0153] In some embodiments, system 10 performs a 1D solution that includes a fourth-order axisymmetric equation representing velocity. U(y)=a+by+cy 2 +dy 3 +ey 4

[0154] The coefficients a, b, c, d, e are calculated along the length from the upstream velocity profile and the rate of change of pressure. The coefficients of the higher-order terms (the third and fourth terms) may be provided with boundaries to stabilize the solution. This limitation significantly speeds up the calculation while minimizing the reduction in accuracy.

[0155] In some embodiments, system 10 uses the 1D method to calculate the wall shear from the shape function.

[0156] In some embodiments, system 10 calculates the direct shear stress from the velocity gradient in the wall using a 2D method. For example, in the 2D method, the polar coordinate form of the Navier-Stokes equations may be used to simplify the calculations. All terms of low Reynolds number may be used. The viscous dissipation term may be avoided (e.g., not used). Since the equation is captured in a steady state, time-dependent terms are not used. Also, in this single-phase flow, gravity may be ignored as it is not important.

[0157]

Number

[0158] The pressure gradient is solved in the radial and axial directions in the same way as the velocity equation. Also, the continuity equation is solved considering the radial flow rate. The radial flow velocity is not important and may be ignored with respect to the wall shear.

[0159]

Number

[0160] System 10 may include any number of efficient "flow solvers". In some embodiments, system 10 includes a finite volume solver. 2D discretization may be performed. Smaller cells may be used in regions of rapidly changing geometry. The flow rate may be changed stepwise downstream from the parabolic flow at the inlet. After the equation is solved with the assumed pressure gradient and the entire flow field is calculated at that pressure, system 10 may recalculate the pressure with the updated flow field. System 10 may be configured to iterate the solution until the force balance in each finite volume converges to a predetermined tolerance.

[0161] In some embodiments, one or more steps are performed to speed up the calculations. For example, in regions where the shape of the blood vessel does not change, the length and width of the cells may be increased. Alternatively or additionally, the pressure drop may be automatically determined from the calculated pressure field, such as when the pressure drop includes both viscous and momentum losses. In some embodiments, system 10 may calculate an initial pressure field from the 1D equations based on the change in area along the length to reduce the calculation time. The Kirkeeide equation (Kirkeeide, R. L. (1991). Coronary obstructions, morphology and physiological significance. In Quantitative Coronary Arteriography (pp. 229-244). Kluwer Academic 1) is particularly suitable for this application. Regions with reduced cross-sectional area are treated as "constrictions" in his model. Each individual "constriction" is considered a reduced cross-section separated from the next by a few diameters, usually 5-10 diameters. If the constraints are closer than this, their interaction may be estimated. The Banerjee equation (Banerjee, M. K., Nag, D., Ganguly, R., & Datta, A. (2008). Stenotic interaction on hemodynamic parameters in double stenoses. International Journal of Computational Fluid Dynamics, 22(9), 609-622. doi:10.1080 / 10618560802372033) may be used to estimate the interaction.

[0162] System 10 may be configured to calculate the transition from laminar flow to turbulent flow from system 10 based on a correlation related to the divergence angle of the vessel wall, adverse pressure gradients, Reynolds number, and deviation of the flow profile from the parabolic shape. In all calculations, the variations due to the heartbeat may be ignored (e.g., in the case of coronary artery vessel analysis). In this embodiment, the main concern is the free time of the diastolic wave where the likelihood of turbulent flow is highest.

[0163] When the transition to turbulent flow is determined by System 10, another turbulent flow model may be used. The 2D Navier-Stokes equations may be solved, or an artificially high viscosity may be used. The K-epsilon model may be used to calculate the length of the turbulent section. When the dissipation term falls below a predetermined threshold of System 10, the entire cross-section returns to laminar flow. In the 1D model, tests for the transition to turbulent flow with increasing pressure loss can also be performed.

[0164] In the 2D model, when an unsteady solution occurs due to separation at the wall, reverse flow is not calculated and the Navier-Stokes equations are not used. Instead, the pressure loss of fully developed turbulent flow is used. The default length of this section is 5 diameters, and it is shortened or lengthened according to whether the shape is converging or diverging and the Reynolds number of the flow rate. After this region, System 10 enters the next section assuming a parabolic velocity of laminar flow.

[0165] The transition to turbulent flow or the separation of the flow along the wall generally means that an intervention (e.g., stent implantation) needs to be performed. Therefore, in order to calculate the judgment of whether to implant a stent, it is more important to correctly calculate the transition to turbulent flow than to accurately calculate the pressure loss in the turbulent section.

[0166] For the purposes of these calculations, System 10 may be configured to convert a non-circular cross-section into a circular cross-section. For the diameter of the circular cross-section, the hydraulic diameter, which is 4 times the value obtained by dividing the outer perimeter of the cross-section by the area, is used.

[0167] To calculate the FFR, System 10 may set the arterial pressure to 90 mmHg and the venous pressure to 30 mmHg. This pressure difference becomes the driving force for the flow. The FFR at any position is calculated as the local static pressure divided by the arterial pressure.

[0168] Referring now to FIG. 10, a schematic of blood vessel flow is shown. If there is a disease in a collateral, the system 10 calculates the non-imaging branch resistance R d due to the disease. This resistance value may be calculated based on the calculated shape of the disease. Also, this resistance value may be estimated from the algebraic equation of the corkscrew. The microvascular bed resistance R v of each collateral in the OCT image is placed in series with the R d of the diseased branch. Collaterals with a diameter of 1 mm or less may be ignored as they do not significantly contribute to the flow. If the vascular anastomosis (e.g., the anastomosis of the imaged blood vessels, or the anastomosis proximal to the imaged blood vessels, the vascular anastomosis in this specification) is not imaged, if there is another image of the vascular anastomosis (e.g., angiography), the resistance is assigned to R d1 based on that, and if not, based on the standard shape of the anastomosis. At the distal end of the image, the microvascular resistance R v2 and the disease resistance R d2 (if there is a disease distal to the imaged area) are assigned. R d2 may be estimated from angiography or from a more distal OCT pullback.

[0169] System 10 may assume that, for example, in the case of an artery on the right side of the heart (computationally), the initial flow rate at the vessel ostium is 3 ml / s, and in the case of a vessel on the left side of the heart, the initial flow rate at the vessel ostium is 4 ml / s. System 10 may determine an initial flow rate estimate by starting from the vessel ostium and dividing the flow rate of the vessel ostium based on the resistance of the branches in a state where no resistance is applied to the imaged region. The imaged region may be decomposed not only into a distal end portion and a proximal end portion but also into sections divided in each side branch. Next, the Kirchhoff and Bernoulli equations may be applied to each section, and the resistance in the flow may be calculated. Thereafter, the flow rate of each section is calculated from the analytical solution equation. Thereafter, the resistance may be adjusted according to the flow rate, and the flow rate may be recalculated from the Kirchhoff equation until a converged solution is obtained. If the calculated flow rate exceeds 6 ml / s, these high flow rates are not physiological (i.e., not expected), so the flow rate may be limited to a maximum of 6 ml / s. The high flow rate estimate may be due to a slight miscalculation of the microvascular resistance. Since this slight error is related to the FFR value when determining treatment (such as stent placement), it does not have a significant impact on the FFR result.

[0170] The flow rate and pressure in each side branch are the output of this calculation performed by System 10. The calculated pressure is used by a Navier-Stokes 2D solver with linear interpolation of the pressure between each side branch. In the non-image part, the equations regarding Kirchhoff and Bernoulli's R d may be used. In System 10, a 1D solver may optionally be used.

[0171] To create an image using the probe 100, it is necessary to wash out the blood from the blood vessel to be imaged. Currently available OCT catheters have a diameter that occludes most of the blood vessel, making it difficult to determine whether to intervene (e.g., place a stent). The probe 100 of the concept of the present invention may have a significantly reduced diameter (e.g., a distal portion of 0.030 inches or less, 0.023 inches or less, 0.020 inches or less, and / or 0.016 inches or less). When combined with a 0.014-inch guide wire, the probe 100 and the guide wire occupy a portion of the blood vessel of 0.044 inches or less.

[0172] A value of FFR of 0.8 is generally accepted as a value at which the blood vessel should not be treated (e.g., stented). To determine whether to place a stent in an artery, OCT needs to safely and effectively image the blood vessels above and below this cutoff FFR. When the cutoff FFR is 0.8, the MLA is 3.07 mm 2 (see Waksman, R., Legutko, J., Singh, J., Orlando, Q., Marso, S., Schloss, T.,... Torguson, R. (2013). FIRST: Fractional Flow Reserve and Intravascular Ultrasound Relationship Study. Journal of the American College of Cardiology, 61(9), 917-923. doi:10.1016 / j.jacc.2012.12.012). In the case of a round blood vessel, this correlates with a blood vessel having a diameter of 1.98 mm. Currently, the smallest size of commercially available OCT catheters is 2.6F. Using this device and a 0.014 guide wire, most of the blood vessel (1.23 mm) will be occupied by the combined device. Occluding the blood vessel with such a large catheter and guide wire makes it difficult to flush the blood from the blood vessel to obtain a clear image, and the image processing procedure becomes complicated.

[0173] System 10 may incorporate (e.g., take into account) the disease of the artery to be investigated (e.g., at least imaged). If there is disease distal or proximal to the imaged region, its resistance to flow needs to be estimated from angiographic data that is not as accurate as, for example, the OCT data provided by System 10. The probe 100 and the retraction assembly 800 may be configured to provide a retraction of up to 10 cm, thereby enabling imaging from the vessel inlet to a position beyond the lesion region for most coronary artery lesions (e.g., all lesions on the left side and most lesions on the right side). System 10 may be configured to perform retraction at a faster rate than, for example, commercially available systems. System 10 (e.g., the retraction assembly 800) may be configured to perform retraction at a rate of 50 mm / second (i.e., 10 cm in 2 seconds) with a frame interval of 0.2 mm. Two seconds is approximately the maximum time that a safe amount of contrast agent (e.g., correlated to about 14 ml) can clear the vessel. Thus, the probe 100 can capture continuous images between the distal position of the lesion and the vessel inlet for almost all coronary artery lesions. A frame interval of 0.2 mm provides sufficient resolution for imaging stenoses to accurately calculate FFR.

[0174] System 10 may be configured to provide a long scan range, such as a scan range of up to 8.7 mm, to facilitate the identification of collateral branches. A typical coronary artery has a diameter not exceeding 5 mm (e.g., the left main is typically 5 mm in diameter). System 10 may identify collateral branches (e.g., via algorithm 51) by, for example, the detected wall being significantly farther away from the surrounding wall. Without a long scan range (e.g., a scan range that only reaches the wall), the detection of collateral branches is more difficult.

[0175] Moreover, the long scan range provided by the system 10 improves the ability to estimate the diameter of the side branches. By imaging significantly long side branches (at least 2 mm), the direction of the side branches can be found, and as a result, the diameter of the side branches can be estimated more accurately. The size of the side branches is correlated with the angle of the branches. The larger the side branch, the smaller the angle with respect to the main blood vessel. Since diseases tend to occur at the bifurcation, by imaging beyond the bifurcation to determine the disease-free diameter of the side branch, the system 10 can estimate the size of the vascular bed supplied by the side branch and improve the microvascular resistance assigned to that side branch.

[0176] The diameter of the imaging probe 100 is small enough to enable imaging of stenosed or diameter-reduced blood vessels in the pre-treatment procedure. The probe 100 may have a diameter of 1.7F (0.022 inches) or less. An imaging probe having a diameter of 2.2 Fr (0.029 inches) or less enables pre-treatment OCT imaging (for example, it can be used to image a portion where the diameter of the blood vessel has become small). In some embodiments, the system 10 has a frame rate of 250 Hz, allowing for a rapid retraction of an extended length that can be used to obtain information about the lesion and information about the blood vessel entrance in one retraction. Also, in some embodiments, the system 10 provides a scan range of 6 mm or more, enabling the detection and size estimation of side branches.

[0177] Fibrotic tissue, calcium, and lipid each have distinct attenuation and brightness values (e.g., when imaged by the imaging probe 100 of system 10). Calcium is imaged via OCT as regions of low backscattering coefficient and low attenuation. Lipid exhibits high attenuation and high backscattering. Fibrotic tissue shows low attenuation and high backscattering (see Xu, C., Schmitt, J. M., Carlier, S. G., & Virmani, R. (2008). Characterization of atherosclerosis plaques by measuring both backscattering and attenuation coefficients in optical coherence tomography. Journal of Biomedical Optics, 13(3), 034003. doi:10.1117 / 1.2927464; also see Yabushita, H., Bouma, B. E., Houser, S. L., Aretz, H. T., Jang, I., Schlendorf, K. H.,... Tearney, G. J. (2002). Characterization of Human Atherosclerosis by Optical Coherence Tomography. Circulation, 106(13), 1640-1645. doi:10.1161 / 01.cir.0000029927.92825.f6). Normal tissue without disease can be identified by three characteristic layers: the media, adventitia, and intima (see Tearney, G. J., Regar, E., Akasaka, T., Adriaenssens, T., Barlis, P., Bezerra, H. G.,... Weisz, G. (2012).Consensus Standards for Acquisition, Measurement, and Reporting of Intravascular Optical Coherence Tomography Studies. Journal of the American College of Cardiology, 59(12), 1058-1072. doi:10.1016 / j.jacc.2011.09.079)。

[0178] In some embodiments, calcium and / or lipid deposits are automatically identified by system 10, such as by using 1D (e.g., A-line classification), 2D, and / or 3D methods to analyze the OCT data. Machine learning approaches such as deep learning (e.g., convolutional networks) and / or supervised classification (e.g., support vector machines or random forests) may be used (e.g., by algorithm 51 of system 10) to automatically classify tissue types within the OCT images. Image features such as optical backscattering, optical attenuation, layer analysis, and texture analysis may be used. In some embodiments, automatic and / or manual detection of calcium layers, lipid layers, and normal tissue layers may improve the calculation of flow (e.g., FFR) and / or treatment planning (e.g., determination of the appropriate location for a stent to be implanted).

[0179] Estimation of microvascular resistance, e.g., based on the size of non-lesion vessels, can be performed by system 10. Identification of non-lesions would be useful for the calculation of microvascular resistance. In some embodiments, the user may manually identify and / or correct the identified non-lesions, e.g., via user interface 55. In some embodiments, if very few non-lesions are identified in the OCT image (e.g., if no normal sections are present or only a limited number are found), algorithm 51 of system 10 may use information from one or more lesions to estimate microvascular resistance.

[0180] When treating cardiovascular diseases, stents may be placed across all disease regions. Ideally, the stent begins and ends in normal tissue. The stent placement algorithm (e.g., algorithm 51 of system 10) may consider not only the FFR but also one or more characteristics of the vessel wall. In some embodiments, the stent placement algorithm 51 does not permit the user to place the proposed stent at a location that starts or ends in diseased tissue (e.g., during the planning process, only placement of the stent spanning from healthy tissue to healthy tissue is permitted), and / or the algorithm 51 warns the user that the ends of the selected stent are in a diseased portion of the vessel. According to research, leaving a stent in lipids can cause embolism, which is dangerous. In some embodiments, if lipids are detected at one or more locations to be covered by the stent, the algorithm 51 based on stent placement prevents or warns the user about placing either end of the stent in the lipids.

[0181] If calcium occupies most of the circumference of the wall, it may be difficult to fully expand the vessel with a stent. In some embodiments, if a significantly calcified section is identified by the algorithm 51, the user is warned that placing a stent to open the stenosis may not be sufficient. In some embodiments, after significant calcification is identified, the system 10 provides (e.g., proposes) an alternative treatment method such as an atherectomy procedure (e.g., rotational atherectomy procedure). In some embodiments, when circumferential calcification is identified, this information is used when calculating the post-treatment FFR value when simulating the results after stent implantation. Circumferential calcification may prevent the stent from fully expanding. The calcium distribution information can provide a more detailed estimated lumen area to be achieved by stent placement and can provide improved guidance to the user.

[0182] In some embodiments, for example, when algorithm 51 is configured to estimate the size of the side branches of the imaged blood vessels, the non-diseased blood vessel size of the imaged blood vessels is calculated. Sections of the imaged area that are significantly below this diameter may be checked for disease. If no disease is seen in these areas, the blood vessel may be in spasm and a stent should not be implanted. In such a case, system 10 may warn the user that there may be spasm. In some embodiments, when spasm is identified by system 10, the FFR with and without spasm is calculated and both values may be displayed to the user by system 10 (e.g., so that the user can determine whether to implant a stent based on the displayed information).

[0183] Improved retraction of the concepts of the present invention (e.g., longer length and / or increased speed) increases the length of the imaged blood vessel (e.g., a larger length of the selected blood vessel can be imaged than by other imaging devices). In some cases, it is difficult to clear the blood, so the blood vessel wall cannot be detected over the entire length of the retraction. System 10 may be configured to define the clear portion of the retraction, and the ends of the defined length may be checked for the presence of normal tissue. If the tissue at the ends is diseased, the angiography data may be analyzed to determine the degree of proximal and distal stenosis of the clear portion of the retraction. Then, R d is calculated for these areas outside the defined retraction. The user may also be notified that there may be disease outside the imaged area and prompted to enter a minimum diameter. The use of the minimum diameter entered by the user is less accurate for more detailed lumens (calculated from OCT data), but allows some input with limited information. If a portion of the retraction is unclear (e.g., due to poor blood clearance), the user may re-image the blood vessel. In some embodiments, two images are combined by system 10 to create a hybrid image.

[0184] In some embodiments, the distal end of the delivery catheter 80 is readily distinguishable in the OCT data (e.g., when the imaging assembly 115 is retracted into the delivery catheter 80 during a retraction procedure). The system 10 may assume, for example, that the vascular inlet is proximal to the distal end of the delivery catheter 80 when the system 10 positions the delivery catheter 80 at a standard distance (e.g., a distance of about 5 mm) from the vascular inlet. If there is a disease at the inlet of the imaged blood vessel, the user may input the minimum diameter of the inlet. The display of the blood vessel may indicate the expected size and location of the inlet. The system 10 may also be capable of allowing the user to input the size of a stenosed inlet.

[0185] In some embodiments, the system 10 may include a digital model of one or more expected branches of the major blood vessels of the heart, as described with reference to step 1313 of method 1000 of FIG. 6. Identification of the major branches of the imaged blood vessel is performed starting from the vascular inlet. For example, if the LCx is imaged, the LAD is expected to be within 5-15 mm from the vascular inlet (see Abedin, Z., & Goldberg, J. (1978). Origin and length of left main coronary artery: Its relation to height, weight, sex, age, pattern of coronary distribution, and presence or absence of coronary artery disease. Catheterization and Cardiovascular Diagnosis, 4(3), 335-340. doi:10.1002 / ccd.1810040318). Also, if the LAD is imaged, the LCx is expected to be in the same region. If the branch detection-based algorithm 51 fails to detect a branch in this region (if the branch is actually missed), the user may be warned or the user may be able to input the size and location of the branch.

[0186] In some embodiments, non-OCT data (e.g., angiography data) may be analyzed by the system 10 (e.g., by the algorithm 51 of the system 10) to determine microvascular resistance. The estimation of microvascular resistance may be adjusted by the system 10 for selected blood vessels. For blood vessels of the same size, the microvascular resistance of the right side of the heart is lower. Instead of or in addition to determining microvascular resistance based on the branch diameter, non-OCT data may be analyzed by the algorithm 51 of the system 10 and a vascular area may be assigned to each branch. The right side of the heart can be more complex because it may or may not supply the left side of the heart (e.g., depending on whether the patient is right or left dominant). Automatic and / or manual algorithms (e.g., algorithm 51) enable the entire heart to be assigned to specific blood vessels. This method is most accurate when both the left and right sides are imaged, but this is not always done.

[0187] In some embodiments, system 10 obtains OCT image data by placing the optical assembly 115 of probe 100 within a selected blood vessel. This data may include blood vessel information such as blood vessel shape information, blood vessel position information (e.g., regarding anatomical landmarks). The second imaging device 15 may comprise a fluoroscope positioned outside the selected blood vessel. This fluoroscope may collect non - OCT data similar or dissimilar to the OCT data collected by probe 100. The angiography data may include, for example, data representing the entire coronary artery tree at a relatively low resolution (e.g., a resolution of 150 μm to 250 μm) captured simultaneously with the OCT data. The OCT data may include data at a higher resolution (e.g., a resolution of about 10 μm) captured at a rate of 250 frames per second. The OCT data may be used to create a 3D model of the selected blood vessel over a relatively long period of time (e.g., from 0.5 seconds to 4.0 seconds). Either the OCT data or the non - OCT data may be used for the calculation of flow rate. Algorithm 51 may use techniques incorporating 3D models as described herein, such as native 3D (e.g., using OCT data) or constructed 3D (e.g., cat scan and / or biplane angiography data).

[0188] In some embodiments, algorithm 51 analyzes data (e.g., OCT data captured over time) and creates a set of 2D images (e.g., a series of 2D snapshots at well - defined points, or image frames). Algorithm 51 can reduce the 2D information to a single descriptive numerical value such as hydraulic diameter or a similar variable. This single descriptive numerical value is very effective for calculating flow loss and / or pressure loss. This calculation depends on the detection of a well - defined lumen contour, and algorithm 51 may incorporate image analysis techniques, machine learning techniques, or a combination thereof. Algorithm 51 may convert time information to distance using various techniques to reduce error. For example, high - speed retraction (e.g., at least 50 cm / sec), gated retraction, angiographic registration, landmark registration (e.g., collateral registration) and the like. Algorithm 51 may include collateral information in the model, for example, in the form of additional resistance elements and / or flow modification factors. Additional information may be included in a 1D or 2D linear model (e.g., OCT data and / or non - OCT data) if it includes, for example, curvature from angiographic images. In some embodiments, system 10 avoids using externally derived vessel shape (e.g., curvature or other shape information from angiographic data) when calculating flow and / or pressure (e.g., based only on OCT data) in order to, for example, shorten the calculation time.

[0189] In some embodiments, system 10 captures data in the form of r, theta, and t. Here, r is the radial distance from the zero point, and theta is the angle relative to a defined zero angle. r and theta are useful when converted to rectangular coordinates x and y. t is the time point of a particular snapshot (such as an image frame). System 10 may calculate the local derivatives (slopes) of x and y.

[0190]

Number

[0191] (or other similar methods) System 10 may calculate the area and perimeter of the blood vessel cross-section using x, y, x', and y'.

[0192] [Number]

[0193] Here, N is the number of points on the circumference.

[0194] [Number]

[0195] This is simply the sum of the "small hypotenuses" around the shape.

[0196] When the OCT data is collected, system 10 calculates these results, from which system 10 may calculate the hydraulic diameter D H .

[0197] [Number]

[0198] This converts to the simple diameter of a circular cross-section. This can be used to obtain an accurate flow rate calculation using only 1D numerical values.

[0199] System 10 may add length by converting the time point of each snapshot into distance. For example, in the zero-order case, the retraction speed is used to convert into distance. In the first-order case, the start of retraction is gated at a portion of the cardiac cycle with less movement (e.g., at the T wave of an electrocardiogram), and the retraction speed is used to capture a relevant section of the blood vessel length at about 50% or less of the cardiac cycle (e.g., 30 mm to 60 mm at a retraction speed of 100 mm / second). In the second-order case, gated retraction may be used with semi-automatic or fully automatic simplified coregistration (angiographic images of a single plane) (see FIG. 11). When capturing three sequences (sequences ii to iv as shown in FIG. 11), the radiopaque markers of the probe 100 are identified at the start and end of retraction, and the angiographic image (frame) at the time closest to each trigger (e.g., a T wave trigger correlated with a point in the cardiac cycle where the tissue is relatively immobile) is identified. It should be noted that in sequences (ii) and (iv), there is no flowing contrast agent (e.g., the blood vessel wall is not visible, but the radiopaque markers are visible). In sequence (iii) captured during retraction, the blood vessel wall is visible, but the X-ray opaque markers may be unclear. In this sequence, in order to minimize out-of-plane problems, for example, the optimal projection plane can be used standardly to obtain shape curvature information. The distance traversed between the radiopaque markers in sequences (ii) and (iv) is the retraction distance (e.g., a distance of 50 mm). System 10 may map this known retraction distance linearly, for example, along the arterial shape. Time t 1m If a landmark is detected in the OCT image at time t 1m , System 10 may apply further correction such that the distance moved is t times the retraction speed.

[0200] In some embodiments, system 10 acquires non - OCT data including angiography data from a second imaging device 15 (e.g., a device 15 equipped with a fluoroscope). The non - OCT data may include consecutive image frames showing the progression of a contrast agent through a blood vessel (e.g., through a coronary artery). System 10 can determine the change in the position of the contrast agent from frame to frame, via algorithm 51, to estimate the speed of blood flow through the blood vessel, also known as the TIMI frame count or TIMI score. Here, TIMI is an abbreviation for thrombolysis in myocardial infarction. This frame count speed may be relative to a position within the coronary artery tree, such as the flow at the vessel inlet. System 10 may be used in an analysis using a resistor model of the coronary artery. For example, instead of a pressure estimate (e.g., an input pressure of 90 mmHg), a TIMI - based speed is input into the resistor model. The input flow rate is the product of the TIMI speed and the cross - sectional area of the blood vessel near the vessel inlet. The inlet pressure is increased or decreased so that the flow rate matches the TIMI speed. In this method, the resistance of the microvessels does not change. System 10 may calculate the FFR by dividing the local pressure by the inlet pressure.

[0201] In some embodiments, system 10 is configured to identify (e.g., via algorithm 51) which particular blood vessel is the imaged blood vessel (e.g., based on one or more detected collateral branches and / or geometric information of the blood vessel (e.g., information on shape, trajectory, and / or size)). This identification of the blood vessel may be performed autonomously by system 10 and / or confirmed by the user of system 10. In some embodiments, system 10 identifies and / or confirms the blood vessel using non - OCT data (e.g., using angiography data acquired from a second imaging device 15 equipped with a fluoroscope).

[0202] The system of the concept of the present invention has mainly been described for imaging and creating treatment information for arteries, particularly coronary arteries. However, all blood vessels and other body conduits should be considered within the spirit and scope of this application and its claims.

[0203] In some embodiments, the system 10 is configured to compensate for the movement of the heart. For example, a retraction synchronized to start during a part of the cardiac cycle with minimal movement of the heart tissue (e.g., via an electrocardiogram-based trigger) may be performed (e.g., in a time zone of 0.3 seconds or less, or 0.2 seconds or less).

[0204] In some embodiments, the imaging probe 100 has a unique identifier such as an RFID that can be read by the console 50 (e.g., when the imaging probe 100 is attached to the patient interface module 200 (PIM200)). In some embodiments, the system 10 includes a first imaging probe 100a and a second imaging probe 100b each identified by a unique identifier used to distinguish the two probes. In these embodiments, the probes 100a and 100b may have similar or dissimilar structures. For example, the probes 100a and 100b may have a similar structure (e.g., the same structure), but each probe model may result in a different configuration of system parameters (e.g., an automatic configuration established when the probe 100 is attached to the PIM200). In some embodiments, when the probe 100a is attached to the PIM200, the system 10 can calculate the FFR value (e.g., in response to a user request), but when the probe 100b is attached to the PIM200, the FFR function of the system 10 is disabled. In other words, even if the only difference between the FFR-compatible probe 100a and the non-FFR-compatible probe 100b is the information contained in the RFID or other model identification component of the probe 100, an FFR-compatible probe 100 is required to enable the FFR function of the system 10.

[0205] In some embodiments, if the system 10 and / or the probe 100 is effective for FFR calculation, one or more parameters of the system 10 may be different (e.g., may be changed) from those of a non-FFR compatible system and / or probe. For example, the FFR compatible system may be configured to rotate the optical core 110 at a faster speed than a non-FFR system, e.g., at least 1.5 times faster, or at least 2 times faster. The faster rotation of the core 110 enables a faster retraction speed, a longer retraction distance, and / or a combination thereof, without degrading the resolution of the collected image data. Additionally or alternatively, the faster rotation of the core 110 enables the light source 310 to provide a higher output power without increasing tissue exposure. In some embodiments, the FFR compatible probe 100 may have more markers 131 than the non-FFR probe 100, for example, to enhance image-based tracking and / or to improve registration accuracy (e.g., registration with an image from a fluoroscopic image and / or other imaging modalities).

[0206] In some embodiments, the FFR-compatible probe 100 may be configured to extend beyond the distal end of a delivery catheter, e.g., the delivery catheter 480 described with reference to FIG. 1B herein. In some embodiments, the probe 100 is configured to extend beyond a guidewire lumen, such as the rapid-exchange guidewire distal end of a delivery catheter. In these embodiments, the probe 100 may be configured to capture distal image data from the distal end of a guidewire through which the delivery catheter has been advanced, such that the image data does not include any guidewire data (known as the shadow of the guidewire). In some embodiments, extending the probe 100 beyond the distal end of the delivery catheter enables imaging of a blood vessel with a smaller device (e.g., the probe 100 having a smaller diameter than the delivery catheter) and minimizes disruption of the flow within the imaged blood vessel. Additionally or alternatively, the absence of a guidewire shadow in the image data enables improved imaging, improved lumen reconstruction, and / or improved calculation of blood flow dynamics in the blood vessel.

[0207] In some embodiments, vascular identification information regarding one or more blood vessels to be imaged is captured by the system 10, e.g., to associate a blood vessel image, flow rate, and / or other data with that identification information. In some embodiments, a user inputs vascular identification information, and the system 10 is configured to perform an assessment of the accuracy of the identification information provided by the user. For example, if the system 10 determines that the vascular information input by the user is inaccurate or at least potentially inaccurate, a warning may be provided to the user. Alternatively or additionally, the system 10 may be configured to identify a blood vessel, e.g., to save time, when the system 10 automatically inputs a blood vessel name without user input. This automatic identification may be confirmed and / or adjusted by the user. In some embodiments, the vascular identification performed by the system 10 is based on OCT data, non-OCT data (e.g., angiographic information), or both.

[0208] In some embodiments, the system 10 is used to image a blood vessel (e.g., create OCT data) both before and after a treatment procedure (e.g., after a stent has been implanted at a lesion). For example, the system 10 may be configured to create pre-treatment and post-treatment FFR data. In some embodiments, the system 10 compares information generated based on image data (e.g., OCT data and / or non-OCT data) collected before treatment with information generated based on image data (e.g., OCT data and / or non-OCT data) collected after the treatment has been performed. This comparison may cause the system 10 to alert the user to potential inaccuracies or other problems with the information provided by the system 10. In some embodiments, the probe 100 and other components of the system 10 are configured to collect at least OCT data and generate a pre-treatment FFR value used to make a treatment decision (e.g., whether to implant a stent or treat in some other way).

[0209] In some embodiments, the system 10 is configured to provide information related to the plaque content of a lesion.

[0210] In some embodiments, information generated by the system 10 based on OCT data and / or non-OCT data (e.g., at least angiography data) is used as a "training set" for a CT approach.

[0211] In some embodiments, the information generated by the system 10 is determined using OCT data and / or non-OCT data that has been processed using machine learning or other artificial intelligence. In some embodiments, the information generated by the system 10 is determined using a cloud-based approach.

[0212] As described herein, system 10 may be configured to generate information (e.g., at least FFR values) used to determine whether and / or how to treat prior to treatment. Imaging probe 100 may be configured to have a small outer profile (e.g., a distal portion having a diameter of less than 0.034 inches) for accessing narrow lesions, as described herein. System 10 may provide high-resolution morphological images and other high-resolution morphological information such as that generated using at least OCT data collected by probe 100. In some embodiments, the high-resolution information generated by system 10 is based on OCT data and non-OCT data (e.g., at least angiography data).

[0213] In some embodiments, system 10 is configured to generate FFR information based on an OCT-derived lumen profile. The FFR information may be based on collateral information. The FFR information may be based on combined information of OCT and non-OCT (e.g., angiography). The generated FFR information may be used to determine whether to treat (e.g., by a patient's clinician) (e.g., whether to implant a stent or treat the lesion in some other way).

[0214] In some embodiments, system 10 generates OCT image data (e.g., morphological and / or lumen) and FFR data. This combination of information is used (e.g., by a clinician) in the planning of a treatment procedure, including the decision of whether to treat. The information provided may be based on non-OCT image data (e.g., angiographic data) described herein. The information provided may include morphological characteristics of the region of interest (e.g., lesion), including the presence of calcium and / or lipids. The information provided may be used to determine which type of treatment to perform (e.g., whether to perform atherectomy), and / or which size (e.g., diameter and / or length) of stent to implant. The information provided may include a prediction of the post-treatment outcome (e.g., prediction of the post-treatment FFR). For example, system 10 may be used to reduce the delta FFR of the entire lesion and / or to achieve a desired FFR value (e.g., a value of 0.90 or greater).

[0215] In some embodiments, system 10 is used to treat a plurality of lesions (e.g., one or more contiguous lesions).

[0216] System 10 may model one or more lesions (e.g., each image using imaging probe 100 and / or second imaging device 15 of system 10), such as determining which lesion to treat first by utilizing computational hemodynamics. System 10 may be configured to provide information related to which lesion to treat among one or more lesions, such as when system 10 models the contribution of each lesion to the flow rate, to provide information to the clinician for determining which lesion to treat and / or in what order to treat.

[0217] In some embodiments, system 10 is configured to evaluate the results of treatment of one or more lesions, for example, when system 10 provides a quantitative or qualitative "score" of treatment success (e.g., efficacy and / or safety achieved by stent placement and / or other treatment procedures). As described herein, such evaluation may include not only post-treatment FFR calculations (e.g., including FFR values and / or delta FFR values), but also post-treatment evaluation of the device (e.g., evaluation of dilation, placement, and / or position) and / or morphological parameter evaluation.

[0218] As described herein, system 10 is configured to predict the results of treatment of one or more lesions, for example, when system 10 provides a quantitative or qualitative "score" of predicted treatment success (e.g., efficacy and / or safety predicted to be achieved by stent placement and / or other proposed treatment procedures). As described herein, such information may include not only predicted post-treatment FFR calculations (e.g., including FFR values and / or delta FFR values), but also predicted post-treatment evaluation of the device (e.g., prediction of dilation, placement, and / or position) and / or prediction of morphological parameters. In some embodiments, when the prediction falls below a threshold (e.g., a safety level determined by the user or system 10), system 10 warns the clinician of potential problems. For example, system 10 may be configured to predict the likelihood of an acute event (e.g., an undesirable acute event).

[0219] In some embodiments, system 10 is configured to provide a contour image of a blood vessel lumen and / or other information, as described herein, when system 10 collects OCT data and non-OCT data to generate information. In some embodiments, system 10 utilizes one or more algorithms, such as an algorithm using artificial intelligence (e.g., algorithm 51), to improve the contour information of the blood vessel and / or other information determined by system 10. In some embodiments, algorithm 51 is configured to modify the blood vessel information (e.g., to enable the user to modify and / or automatically modify it). In some embodiments, system 10 is configured to alert the user of blood vessel information determined by algorithm 51 to have a low "confidence level" when, for example, system 10 identifies that some of the calculated blood vessel information may not be accurate enough (e.g., when the confidence level is below a threshold). By identifying such potential problems, rapid correction and / or accuracy verification by the user becomes possible. The correction and / or verification (referred to herein as "correction") may be achieved in various ways, such as frame by frame, in the L mode (e.g., vertical display) and / or other 2D views; and / or 3D views.

[0220] In some embodiments, system 10 is configured to identify one or more branches of the imaged blood vessel when, for example, algorithm 51 is configured to identify branches. Algorithm 51 may identify branches using artificial intelligence and / or user input. In some embodiments, system 10 is configured to identify branches based on both OCT data and non-OCT data (e.g., angiography data). In some embodiments, system 10 is configured to alert the user of computationally determined branch information determined by algorithm 51 to have a low confidence level, as described herein. In some embodiments, the inlet diameter of the branch is calculated by system 10. Alternatively or additionally, the inlet diameter of the branch may be input and / or modified by the user.

[0221] In some embodiments, system 10 is configured to provide 3D lumen information as described herein. In these embodiments, system 10 may have a retraction that is triggered based on a patient's physiological parameters such as, for example, the cardiac cycle and / or respiration. For example, triggering retraction during a low-motion phase of the cardiac cycle may be used to limit motion artifacts and improve the accuracy of implant and / or vascular information.

[0222] In some embodiments, system 10 assumes that the flow rate and / or other physiological conditions are constant in healthy blood vessels.

[0223] In some embodiments, system 10 is configured to warn the user when retraction is insufficient (e.g., when the OCT data collected during retraction is insufficient), such as when system 10 identifies that the entire length of the lesion has not been captured.

[0224] In some embodiments, system 10 is configured to image tandem lesions and / or bifurcation lesions.

[0225] The final position of the retraction (e.g., the most proximal position) may be, for example, within the delivery catheter 80 into which the probe 100 is inserted to collect entrance information of the imaged blood vessel. In some embodiments, the system 10 is configured to analyze the OCT data to determine that the retraction has ended at a position within the delivery catheter 80 (e.g., the distal portion of the delivery catheter 80 has been imaged). In some embodiments, the system 10 is configured to warn the user if the final retraction position (before or after retraction) is not within the delivery catheter 80 (e.g., distal to the distal end of the delivery catheter 80). For example, such a warning may be executed to prevent (if before retraction) or to indicate that an insufficient amount of entrance information is or has been included in the OCT data. In some embodiments, the system 10 is configured to automatically identify the imaged delivery catheter 80 (e.g., model information and / or structural information regarding the delivery catheter 80). In some embodiments, the system 10 is configured to “crop” the image of the delivery catheter 80 from the provided blood vessel image (e.g., reduce the file size, provide a simplified lumen view, etc.). In some embodiments, the system 10 is configured to evaluate the positioning of the guide within the imaged blood vessel if the system 10 is configured to warn the user when an “improper seating” of the guide is suspected.

[0226] In some embodiments, the system 10 comprises preset configuration information, such as an “image acquisition recipe” that includes one or more imaging parameter values (e.g., retraction distance and / or speed, flush parameters, rotation speed, frame density, and / or other usage parameters of the probe 100) that correlate to specific situations, such as imaging of a particular artery or other blood vessel.

[0227] In some embodiments, system 10 is configured to evaluate a flush procedure that is performed while OCT data is being collected (e.g., during pullback). For example, system 10 may provide quantitative and / or qualitative information regarding the flush procedure to alert a clinician if the evaluation falls below a threshold of acceptability (e.g., if system 10 applies low reliability to the image data collected due to an inappropriate flush procedure). In some embodiments, FFR and / or other calculated information is not provided unless an appropriate flush is determined by system 10.

[0228] In some embodiments, system 10 is configured to evaluate the presence of vasospasm (e.g., during pullback or other image data collection periods). For example, system 10 may detect the presence of vasospasm via algorithm 51 and alert the user. Alternatively or additionally, system 10 may apply low reliability to the image data collected due to the detected presence of vasospasm. In some embodiments, if system 10 determines that vasospasm is present, FFR and / or other calculated information is not provided.

[0229] In some embodiments, system 10 is configured to evaluate the presence of a thrombus (e.g., during pullback or other image data collection periods). For example, system 10 may detect the presence of a thrombus via algorithm 51 and alert the user. Alternatively or additionally, system 10 may apply low reliability to the image data collected due to the detected presence of a thrombus. In some embodiments, if system 10 determines that a thrombus is present, FFR and / or other calculated information is not provided.

[0230] In some embodiments, system 10 is configured to evaluate the presence of vascular dissociation and / or other vascular damage (e.g., during retraction or other image data collection periods). For example, system 10 may detect the presence of vascular damage via algorithm 51 and alert the user. Alternatively or additionally, system 10 may apply low reliability to the collected image data due to the detected presence of vascular damage. In some embodiments, if system 10 determines that there is vascular damage, FFR and / or other calculated information is not provided.

[0231] In some embodiments, system 10 is configured to evaluate the presence of myocardial bridging (e.g., during retraction or other image data collection periods). For example, system 10 may detect the presence of myocardial bridging via algorithm 51 and alert the user. Alternatively or additionally, system 10 may apply low reliability to the collected image data due to the detected presence of myocardial bridging. In some embodiments, if system 10 determines that there is myocardial bridging, FFR and / or other calculated information is not provided.

[0232] In some embodiments, system 10 is configured to collect at least OCT data, for example, when both OCT data and non - OCT data (e.g., angiography data) are recorded. Subsequently, dynamic flow calculations, such as flow calculations performed at low resolution (e.g., to reduce calculation time), may be performed. Simultaneously or later, image correction, such as lumen and / or collateral correction (e.g., automatically by system 10 and / or manually by the user), may be performed. After the correction, additional dynamic flow calculations, such as flow calculations at high resolution, may be performed.

[0233] Referring to FIGS. 12 and 12A, there are shown a schematic view of the distal portion of an imaging probe and a delivery catheter in accordance with the concepts of the present invention, and an enlarged view of the components within circle M2. The imaging probe 100 and the delivery catheter 80 may have the same structure and arrangement as the imaging probe 100 and the delivery catheter 80 described with reference to FIG. 1. The delivery catheter 80 has a lumen 84 into which the imaging probe 100 is slidably inserted. In the embodiments shown in FIGS. 12-12A, the FPE1500, which is a fluid pressurizing mechanism S has a helical protrusion extending radially from the optical core 110. During operation, when the optical core 110 rotates, the FPE1500 S rotates integrally, and a fluid flow is generated in the vicinity of the FPE1500 S and a pressure gradient is generated within the gel 118 (e.g., across the FPE1500 S ). Modeling of examples of fluid hemodynamics is described herein with reference to FIGS. 12B-12C.

[0234] In some embodiments, the FPE1500 S is composed of a helical coil such as a spring attached along a portion of the length of the optical core 110 (e.g., so as to surround the core 110). The FPE1500 S may be attached to the optical core 110 via an adhesive or other adhesive. In some embodiments, the FPE1500 S is formed on and / or with the core 110, formed in the core 110 (e.g., via a material removal process), fused onto the core 110, and / or otherwise manufactured to adhere to or with the core 110. In some embodiments, the FPE1500 S is composed of a material selected from the group consisting of metals; plastics; stainless steels; nickel-titanium alloys; nylons; polyetheretherketones (PEEK); polyimides; and combinations thereof. In some embodiments, the FPE1500 SIt may be formed directly on the optical core 110 by using, for example, a vapor deposition technique and / or a 3D printing technique. In some embodiments, a selectively curable material is applied to the optical core 110 and cured in a spiral pattern to form the FPE1500 S is formed. For example, a high-strength UV curable adhesive may be applied to the surface of the optical core 110 and selectively cured using a rotating focused UV beam. In some embodiments, the FPE1500 S may be composed of a material selected to minimize deformation of the FPE1500 S while a pressure gradient is applied. For example, a pressure gradient is generated over the length of the FPE1500 S during rotation to prevent deformation. A shorter FPE1500 S requires a harder material than a longer FPE1500 S configured to generate the same pressure gradient.

[0235] The FPE1500 S has a radial height H1 which is the distance from the surface of the optical core 110 to the outer edge of the FPE1500 S . The optical core 110 has a diameter D1. The inner cavity 1205 of the shaft 120 has an inner diameter D2. In some embodiments, the diameters D1 and D2 vary along the length of the probe 100, and the following dimensions relate to segments of the probe 100, such as the distal segment shown in FIG. 12A (e.g., the proximal and adjacent segments of the optical assembly 115). The probe 100 has a gap C1 between the FPE1500 S (e.g., the outer diameter of the FPE1500 S ) and the inner wall of the shaft 120. The gap C1 is the difference between the diameters D1 and D2 and the FPE1500 SIt is related to both the height H1. C1 is equal to subtracting H1 from half of the difference between D1 and D2. In some embodiments, the gap C1 is a gap of 100 μm or less, 75 μm or less, for example, between 10 μm and 75 μm. In some embodiments, the height H1 is 5% or more and 95% or less of half of the difference between D1 and D2 (for example, the height H1 that occupies at least 5% and / or 95% or less of the space between the outer surface of the core 110 and the inner wall of the shaft 120). In some embodiments, the optimal height H1 is, for example, the damping fluid viscosity (for example, the viscosity of the gel 118), the desired rotational speed of the optical core 110, the desired pressure gradient, and / or FPE1500 S depends on factors such as the gap between the inner wall of the shaft 120 (for example, a narrow gap generates a higher pressure). In some embodiments, FPE1500 S The coil outer shape of has a width W1 as shown in the figure. The width W1 may be a width of 1% to 95% of the diameter D1. Also, FPE1500 S may have a pitch P1 as shown in the figure. The pitch P1 may be a pitch such that the gap between adjacent coils is 0.5 to 20 times the diameter D1. In some embodiments, adjacent coils do not contact each other. In some embodiments, the pitch P1 is along the length of FPE1500 S uniform.

[0236] In some embodiments, the gel 118 is a highly viscous shear-thinning fluid as described with reference to FIG. 1. In some embodiments, the maximum functional gap C1 (for example, the maximum allowable gap C1 such that the rotation of FPE1500 S generates sufficient fluid pressure in the inner cavity 1205) is proportional to the viscosity of the gel 118. For example, the higher the viscosity of the gel 118, the larger the maximum gap C1. In some embodiments, the gap C1 is, as described herein, FPE1500 Sis proportional to the pressure difference that can occur within the gel 118 by rotation. For example, the smaller the gap C1, the greater the pressure difference that can be generated. In some embodiments, the gap C1 and the height H1 are minimized to limit turbulent flow, recirculation, and / or other unwanted fluid flows proximate to the optical core 110. In some embodiments, the gel 118 is a Newtonian (non-shear thinning) fluid. The dimensions C1, H1, D1, and D2 may be optimized for different properties of the gel 118.

[0237] In some embodiments, the FPE 1500 S comprises a coating (not shown). The coating may be a sheath such as a heat-shrinkable tube and / or a painted or sprayed coating. The coating is S configured to improve the coupling of the FPE 1500 S to the optical core 110 and / or to control the dimensions of the FPE 1500 S (e.g., to limit undesirable variations in the height H1, to hold the FPE 1500 S securely to the optical core 110). Additionally or alternatively, the coating may be configured to change the surface properties of either or both of the optical core 110 and the FPE 1500 S . In some embodiments, the coating has a thickness that does not significantly affect the fluid thrust and / or other fluid pressure (referred to herein as "fluid pressure") performance of the FPE 1500 S . Alternatively or additionally, the FPE 1500

[0238] In some embodiments, the FPE 1500 SThe pressure of the gel 118 within the lumen 1205 caused by the rotation of [the relevant part] applies a functional torsional shear force to the inner wall of the lumen 1205. The shaft 120 may have a torsional resistance greater than the functional torsional shear force exerted by the gel 118. In some embodiments, the gel 118 exerts a torque of about 0.004 N-cm, and the shaft 120 has a torsional resistance of at least 0.01 N-cm, for example 0.03 N-cm. Additionally or alternatively, the FPE 1500 S When the optical core 110 is rotated, it exerts a "winding-up" stress on the optical core 110, and the FPE 1500 S may be driven within the gel 118. The optical core 110 is configured and arranged so as not to be adversely affected (e.g., not damaged or malfunction in other ways) by the shear stress induced by the rotation of the core 110 and the FPE 1500 S within the gel 118, as well as the shear stress induced by the pulling-back operation within the gel 118. In some embodiments, the additional winding-up stress on the optical core 110 caused by the FPE 1500 S functions as a NURD reduction mechanism, similar to the NURD reduction caused by the gel 118, as described in the co-pending international PCT patent application number PCT / US2018 / 062766 of the applicant with the title "Imaging System" filed on November 28, 2018, the content of which is hereby incorporated by reference in its entirety for all purposes.

[0239] Additionally referring to FIGS. 12B and 12C, a schematic view of the distal portion of the imaging probe showing the fluid flow pattern consistent with the concept of the present invention, and a fluid flow simulation are respectively shown. The movement of the gel 118 is depicted by the fluid flow arrow FF in FIG. 12B and the paths FP P and FP D in FIG. 12C. The shear 110 and the FPE 1500 S is the FPE 1500 that rotates within the page Sis depicted to rotate with the upper end thereof. Along with the illustrated axial movement, the fluid flow also includes a rotational component as shown in FIG. 12C. At least the distal portion of the distal end 1209 and / or the shaft 120 may be sealed if the distal end 119 comprises a cap or plug configured as a seal member (plug 1209a shown in FIG. 12B). As shown, FPE1500 S When rotating FPE1500, the fluid proximate to the optical core 110 flows distally towards the high-pressure region HP. As the pressure within the high-pressure region HP increases to match the pressure of the distally flowing fluid, a closed-loop recirculation pattern appears as shown. FPE1500 S The fluid propelled distally by FPE1500 encounters the pressure within the high-pressure area HP and redirects proximally along the surface of the lumen 1205 (e.g., along the path of least resistance). This fluid flow pattern creates a "dead-head" pressure profile (e.g., with no net fluid flow), FPE1500 S and maintains the pressure gradient from the low-pressure area LP to the high-pressure area HP along FPE1500. As shown in FIG. 12C, the fluid path FP D is proximate to the optical core 110 and depicts the fluid flow towards the high-pressure region HP on the distal side. The fluid path FP P is proximate to the surface of the lumen 1205 and depicts the fluid flow towards the low-pressure area LP proximally.

[0240] The applicant has conducted various studies using the systems, devices, and methods of the concepts of the present invention. Some results of these studies are described herein. Images and other graphics related to these studies are shown in FIGS. 13 - 23.

[0241] Figure 13 shows the principle of imaging of the system 10 in the blood vessels within the skull. While injecting a contrast agent using a 5F intermediate catheter for a short period of time, the probe 100 retreats while rapidly rotating its internal optical system, and as a result, a spiral scanning pattern is obtained. With a narrow interval pattern (e.g., 60 μm) and an axial resolution close to 10 μm, volumetric microscopy of the arterial wall, neurovascular devices, and intraluminal objects is obtained.

[0242] Figure 14 shows in vivo imaging in a forelimb flexion model of the porcine brachial artery. In (A), the dotted line shows the meandering path through which the probe 100 passes within the blood vessel. In (B), the microscope of the system 10 shows the external elastic lamina (arrowhead) and the layers of the blood vessel wall (arrows). Following the bright intima, there is a dark media and a bright adventitia (insert). The asterisk indicates the entrances of two side branches with diameters of 0.2 mm and 0.7 mm. In (C), the arrow indicates the eccentric position of the probe 100 within the arterial lumen. The image shows uniform illumination and the absence of NURD artifacts. The scale bar is 1 mm (B - C), and 0.5 mm in the insert.

[0243] Figure 15 shows three - dimensional in vivo images of the system 10 with a stent implanted in the porcine maxillary artery. (A) is a perspective view of the blood vessel. (B) is a three - dimensional cross - sectional view of the system 10 (up is distal, down is proximal). Malposition of the flow diverter (arrow) and thrombi of different sizes (purple) are seen on the surface of the flow diverter. In (C), the cross - sectional image of the system 10 shows the implanted branch (indicated by the asterisk) and some thrombus formations (arrowheads) on the surface of the flow diverter. (D) shows an incomplete junction (3 o'clock direction) and multiple thrombi (arrowheads) on the surface of the device at the proximal end of the flow diverter. The scale bar is 1 mm. Color scheme for three - dimensional rendering: red is the arterial wall, purple is the thrombus, and silver is the metal strut.

[0244] In FIG. 16, a comparison between a cross-sectional image of the system 10 and a corresponding CBCT slice is shown. (A) shows that a thrombus (arrow) in a side branch is visible on the image of the system 10. (B) shows that on the image of the system 10 between 1 o'clock and 8 o'clock, a positional abnormality of the flow diverter with a severity of up to about 400 μm is visible. A small thrombus formed on the strut of the flow diverter and having a thickness of 30 to 220 μm is indicated by an arrow. (C) shows a thrombus at the entrance of a large side branch. The presence of the thrombus and the positional abnormality of the device may not be detected in the corresponding cone beam CT image. The scale bar is 1 mm. The asterisk (*) in the CT image indicates the position of the side branch.

[0245] In FIG. 17, (A) to (C) are shown. (A) is a view of the volumetric microscopy data of the system 10 with an endoscope, showing that side branches such as small perforations placed by FDS are visible. (B) shows that there is no thrombus in the side branch (arrow) located on the left side of the image, and the FDS is firmly in close contact with the parent artery. (C) shows that the strut of the FDS embedded by a thrombus can be seen in the second branch (indicated by an asterisk) located on the right side. The scale bar is 1.0 mm. Color scheme for three-dimensional endoscope rendering: red is the arterial wall, purple is the thrombus, and silver is the metal strut.

[0246] Figure 18 shows (A)-(E). (A) is volumetric microscopy data of system 10 showing ICSs partially overlapping at the distal end of the FDS. (B) is microscopy of system 10 showing individual vascular layers (arrows) with a bright intima, a low-scattering media, and an adventitia. The internal elastic lamina (IEL) and the external elastic lamina (EFL) are indicated by green arrows. In (C), it is visible that a thrombus detached from the surface of the device is floating in a large branch, indicated by an asterisk. In (D), a thrombus with a thickness of 100 μm to 200 μm is indicated by an asterisk and is distributed on the surface of the FDS. In (E), at the proximal end of the FDS, it is visible that a semi-occlusive thrombus has formed corresponding to a significant positional abnormality (at least 500 μm). The scale bar is 1.0 mm. Color scheme for three-dimensional endoscopic rendering: red is the arterial wall, purple is the thrombus, silver is the struts of the stent of the flow diverter, and gray is the struts of the stent of the neurovascular.

[0247] Figure 19 shows intracranial plaques from an ex vivo segment of the MCA artery. (A) shows an image of a fibrous plaque by system 10 and the corresponding trichrome staining (B) and Movat staining (C). Fibrous tissue is characterized by system 10 as a region of uniform signal due to an increase in backscattering and a decrease in the optical attenuation coefficient. In (D), an image of a necrotic core plaque by system 10 and the corresponding H&E (E) and Movat staining (F) are shown. A necrotic core plaque is characterized in the image of system 10 as a region within an atherosclerotic plaque with an unclear boundary and a high optical attenuation coefficient. The asterisk indicates dissection of the vessel wall. The scale bar is 1.0 mm.

[0248] Figure 20 shows intracranial fibrocalcific plaques in segments of the intradural vertebral artery. In (A), two fibrocalcific plaques (each indicated by C) are visible within the image. (B) is a magnified view of the lower left portion of the vessel in (A). There is a calcified plaque with a thickness ranging from 100 μm to 300 μm in the 11 o'clock direction. There is a second plaque with a maximum thickness of 900 μm in the lower left. The calcified tissue is characterized by a region with low signal, being non-uniform and having clear boundaries because the backscattering coefficient and absorption coefficient of light are low. The scale bar is 1 mm.

[0249] Figure 21 shows a bench model of the circle of Willis customized for the patient. To reduce the complexity of the inlets and outlets of the flow path, the branches of the middle cerebral artery and the anterior cerebral artery were joined on both sides. For a similar purpose, individual branch arteries such as the ophthalmic artery and the superior cerebral artery were removed.

[0250] Figure 22 classifies images of blood clearance tests into three different categories: (A) a state where blood obscures the field of view, (B) a state with partial clearance, and (C) a state with complete clearance. In each case, the contrast agent injection rate was increased in increments of 0.5 ml / sec from a value of 1 ml / sec until a state of complete clearance was detected. The scale bar is 1 mm.

[0251] Figure 23 shows an image of System 10 of the common carotid artery of a pig with a maximum diameter of 5.9 mm after deployment of the Precise Pro Rx carotid stent system (Cordis). In (A), the portion where the stent was placed is indicated by an arrow. (B) shows a three-dimensional rendering of the image of System 10. (C) is a cross-sectional image of System 10, showing the field of view of the imaging technique of System 10. Even when the probe 100 is in an eccentric position within the artery, System 10 can visualize the entire stent and the arterial wall with sufficient brightness and illumination, as shown in (D). The arrowhead indicates the external elastic lamina (EEL). The scale bar is 1.0 mm.

[0252] In the current clinical setting, endovascular treatment of stroke and other cerebrovascular disorders is performed using non-invasive imaging techniques. However, with this technology, it is not possible to obtain sufficient resolution to adequately evaluate the underlying vessel pathology, the relationship between the device and the vessel, small penetrating arteries, platelet aggregation associated with the device, etc. Intravascular volumetric microscopy imaging performed using the optical probe and other system components of the concept of the present invention enables the patient's clinician to visualize the microstructure of the vessel wall and the interaction with the neurovascular device, and its use will have a great impact on the treatment of cerebrovascular diseases. System 10 is configured to rapidly acquire volumetric microscopy data with a resolution approaching 10 microns in a highly tortuous vascular structure. System 10 uses a combination of in vitro, ex vivo, and in vivo models to demonstrate the feasibility and effectiveness of cerebrovascular microscopy. These research results indicate the potential for System 10 to be used for imaging intracranial arteries and guiding neurovascular treatment.

[0253] Endovascular treatment of ruptured cerebral aneurysms has a lower mortality rate and dependency rate compared to surgery, and a similar trend has been reported for the treatment of unruptured aneurysms. Self-expanding microstents and flow diverters designed for cerebral blood vessels have a strut as small as 25 μm, enabling the treatment of wide-neck and complex aneurysms. In X-ray-based imaging systems, since the X-ray attenuation of these devices is limited, X-ray-opaque markers are placed along these treatment devices, but currently, the entire device cannot be properly imaged. This limitation is very important because effective treatment and prevention of complications with disabilities require pathologically accurate placement and alignment of the device. Despite the remarkable progress of minimally invasive treatment, endovascular treatment still has limitations mainly related to the insufficient visualization of the interface between the device and the blood vessel. Neurovascular treatment devices need to be placed particularly accurately to achieve the ultimate goal (e.g., completely excluding the aneurysm from the circulatory system). Furthermore, endovascular thrombectomy (EVT) has become the standard treatment for patients with ischemic stroke due to large vessel occlusion. To evaluate vascular damage after EVT, non-invasive imaging techniques such as magnetic resonance (MR) vessel wall imaging have been proposed, but the resolution is insufficient to directly visualize the underlying pathology (e.g., intracranial atherosclerotic disease or dissection), endothelial damage, and / or perforating artery thrombosis.

[0254] The use of system 10 for performing volumetric microscopy, which has the ability to visualize in vivo the overall neurovascular device and the fine structure of the vessel wall, has a significant impact on endovascular neurosurgery. The optical imaging technology provided by system 10 has a resolution close to the micron scale and can be incorporated into a small optical fiber probe, making it a promising candidate for successful introduction into the clinical setting where patients receive treatment. Over the past decade, intracoronary optical coherence tomography (OCT) has become an increasingly common treatment method for enabling the accurate measurement of the coronary artery lumen morphology, disease severity, and intracoronary stents. System 10 may be configured to provide an assessment of disease severity, such as a quantitative and / or qualitative assessment of disease severity. In addition to applications in the coronary artery, system 10 can revolutionize the diagnosis and management of cerebrovascular pathologies, for example, by providing the flexibility required for the imaging probe 100 to advance within the anatomical structure of the tortuous cerebrovascular vessels, by the ability of the imaging probe 100 to perform imaging with a high degree of flexion, and / or by the compatibility of the components of system 10 with standard neurovascular clinical workflows. Additionally, the increased field of view of system 10 (i.e., the diameter of the acquired image) is sufficient to characterize large and complex carotid and intracranial aneurysms. In the applicant's research, these cerebrovascular requirements were achieved using system 10.

[0255] Results In various studies, the system 10 was used to perform volumetric microscopy by combining in vitro, in vivo, and ex vivo cerebrovascular models. The imaging probe 100 used comprises a 0.016-inch wire-shaped catheter that can be delivered from a standard neurovascular microcatheter. The probe 100 is designed to have an outer shape equivalent to that of the latest guide wire and has a non-invasive and X-ray opaque tip. The optical system of the probe 100 has a function of collecting near-infrared light backscattered by the blood vessel wall and objects inside the tube. The system 10 performs volumetric imaging of the surrounding arteries and implanted devices with a resolution close to 10 μm by the high-speed rotation of the optical assembly 115 and the retraction of the probe 100 within the blood vessel, as shown in FIG. 13. The system 10 may acquire data in 2 - 3 seconds with a frame rate of 250 images per second in a field of view (i.e., image diameter) of at least 14 mm from a meandering arterial segment of 50 mm or more.

[0256] Clearance of blood vessels in an in vitro circulation model of the circle of Willis Since red blood cells scatter light and reduce its coherence properties, it is necessary to move arterial blood from the vascular lumen for data acquisition by System 10. To test the ability to inject a sufficient amount of contrast agent to form an appropriate optical window, a simulated usage experiment was conducted in a patient-specific bench model of the complete arterial circle of Willis with reference to FIG. 21. Importantly, this model includes communicating arteries that may mix with the injected contrast agent and interfere with image acquisition by System 10. Porcine blood was circulated using a pulsatile pump, and an optimal contrast agent injection protocol was identified at the positions of the internal carotid artery (ICA), middle cerebral artery (MCA), basilar artery (BA), and vertebral artery (VA). At these locations, the imaging probe 100 was sent to the target anatomical structure, and the contrast agent was injected with an automatic injector via a 5F intracranial support catheter (5F Navien, Medtronic Neurovascular, Irvine CA). Omnipaque (GE Healthcare) radiopaque contrast agents with different concentrations were tested, and 240, 300, and 350 mgl / mL were used with viscosities of 3.4, 6.3, and 10.4 cp at 37°C, respectively. The injection was performed using an automatic pump (Medrad Mark 7 Arterion Injection System, Bayer Healthcare) with a pressure limit of 300 psi from the 0.058-inch lumen of the intracranial support catheter.

[0257] Clearance as a function of contrast agent injection rate was analyzed by classifying the results into three categories of "blood obscuring the field of view", "partial clearance", and "complete clearance" using the imaging metrics of system 10 (see Fig. 22). The flow rate of the contrast agent was increased in increments of 0.5 ml / sec from 1 ml / sec until complete clearance was obtained, and the optimal injection protocol was determined for each anatomical site. Omnipaque 350, which has an optimal viscosity for efficiently expelling blood from the field of view, was confirmed to be the preferred contrast agent. Complete clearance of the ICA was obtained by injecting at 5 ml / sec and was observed approximately 2 - 3 seconds after injection. Similarly, clearance of the MCA and VA was obtained at a rate of 3 ml / sec. For the BA, a 5F catheter was placed at the height of the BA inlet, and an injection of 5 ml / sec was required to overcome the inflow from both VAs. When injecting the contrast agent at a more distal position of the BA, sufficient clearance may be obtained at a rate of 4 ml / sec. When the data acquisition time of system 10 is 2 seconds, it was shown that a minimum injection of 4 seconds is required to clear the artery, and as a result, 20 ml of contrast agent was injected into the ICA at 5 ml / sec and 12 ml into the MCA at 3 ml / sec.

[0258] Imaging of the increase in in vivo vascular tortuosity In a porcine model with flexed forelimbs (n = 8), a severe flexion state with a curvature similar to that of the human ICA siphon was observed in the brachial artery. The imaging probe 100 was tested on both sides of the brachial artery (n = 16), and an image dataset of the system 10 with an effective imaging length of 65 mm ± 13 mm was obtained. The performance of the probe 100 was evaluated by assessing image artifacts such as non-uniform rotational distortion (NURD), which generally affects modern endovascular surgery in tortuous anatomical structures. NURD is defined as an artifact caused by increased friction of the rotating catheter component, appears as circumferential (rotational) smearing, and causes distortion that misinterprets and measures images. In the degree of flexion of the brachial artery (n = 16), no NURD artifacts were observed in the dataset of the system 10. Figure 14 shows an example of image processing of the system 10. It can be seen from the angiogram that the degree of vascular flexion is increasing. Imaging without distortion by the system 10, which shows the vessel wall with uniform illumination, enables accurate visualization of individual tissue layers, the external elastic layer (EEL), detailed lumen morphology, and the inlets of two branches (see Figures 14B-C).

[0259] In Vivo Imaging of Neurovascular Stents and Flow Diversions By obtaining a dataset of the internal maxillary artery (IMAX, n = 16) in pigs implanted with a flow diverting stent (FDS) and a self-expanding intracranial stent (ICS, n = 15), a comparison was made between digital subtraction angiography (DSA), contrast cone beam CT (CBCT), and imaging of the system 10. Three expert image readers (n = 3) analyzed the presence or absence of thrombosis and positional abnormalities using two outcome measures with different imaging diagnostic methods. Each evaluator analyzed a total of 480 images, including angiograms, cross-sectional images of the system 10, and CBCT. Fleiss' kappa statistic was used to evaluate the degree of agreement among different evaluators. For the evaluation of acute thrombosis along the surface of the FDS, agreement degrees of 0.90 (system 10), 0.67 (CBCT), and 0.49 (angiography) were obtained. For the diagnosis of device positional abnormalities, values of 0.87 (system 10), 0.67 (CBCT), and 0.18 (angiography) were obtained. In the repeated analysis of the ICS device, the agreement degrees for visualizing thrombosis were 0.81 (system 10), 0.39 (CBCT), and 0.71 (angiography). For the positional abnormalities of the ICS, values of 0.78 (system 10), 0.45 (CBCT), and 0.41 (angiography) were obtained.

[0260] An example of the image data after the embedding of FDS is shown in FIG. 15. In the volumetric microscopy of the system 10, the accumulation of thrombus and the presence of an incomplete placement of the device are illustrated (see FIG. 15B). The occlusion of the collateral branch and the abnormal position of the end of the FDS covered by multiple thrombi were detected (see FIGS. 15C-D). The image of the system 10 and the corresponding CBCT data are shown in FIG. 16 (the left is the image of the system 10 and the right is the CBCT data). The collateral thrombosis (see FIG. 16A), the abnormal position of the device, and small thrombi of about 5 μm, 10 μm, or 30 μm (see FIG. 16B) are sufficiently captured by the OCT image provided by the system 10 (identified, for example, by the system 10 or by a clinician viewing an image generated by the system 10), and are often not seen (e.g., not identifiable) in the corresponding CBCT cross-section (such as shown in FIGS. 16A-C). FIGS. 17 and 18 show further examples of the ability of the image of the system 10 to depict the neurovascular device in vivo. The endoscopic data rendering shows branches such as two perforators indwelled by the FDS (see FIG. 17). FIGS. 17B-C show whether there is a thrombus at the inlet of the blood vessel using the image of the system 10. The accurate visualization of the individual layers of the blood vessel wall, the accumulation of thrombus at the level of the collateral branches connected by the ICS, and small thrombi with a thickness of 100 μm are accurately captured by the image of the system 10 (see FIGS. 18B-D). FIG. 18E shows a state where a part of the blood vessel is occluded as a result of a significant thrombus occurring at the proximal end of the abnormally positioned FDS.

[0261] Imaging of the aorta To examine the ability of the system 10 to image the large carotid artery, stent placement in the common carotid artery was performed on a subgroup of non-human animals (n = 5). The diameter of the stented segment was 5.5 mm ± 0.3 mm on average and 5.9 mm at maximum. In all cases, the extended field of view of the system 10 provided sufficient illumination to accurately evaluate the interaction between the stent and the blood vessel at the strut level (see FIG. 23).

[0262] Imaging of intracranial atherosclerosis At autopsy of patients 70 years of age and older with a history of vascular disease, fragments of intracranial arteries with disease (n = 10) were obtained. The specimens were immersed in saline, and multiple images of the system 10 were acquired to obtain the full length of each artery (n = 15). After imaging with the system 10, a subset of vascular segments containing representative examples of three major plaque types was identified by a board-certified vascular pathologist using previously established criteria. Representative examples of fibrotic plaques, plaques arising from calcification of fibrous tissue, and atherosclerotic plaques with necrotic cores were seen (n = 3). The tissues were processed by histopathological techniques and stained with Sudan black, hematoxylin-eosin (H&E), von Gieson, Movat pentachrome, and trichrome reagents. The stained slices were analyzed by a vascular pathologist blinded to the image results of the system 10 to characterize the plaques and tissue types. Agreement was seen in all cases (n = 3). Examples of intracranial plaques are shown in FIGS. 19 and 20. FIG. 19A shows a fibrous plaque in the M1 segment of the MCA of a 97-year-old cadaver. By previously established criteria, the fibrous plaque was identified on the images of the system 10 as a thick area of the arterial wall showing increased backscattering of light and uniform intensity. On histopathological evaluation, this plaque was classified as being composed mostly of fibrous tissue (see FIGS. 19B-C). FIG. 19D shows a second plaque containing a necrotic core (NC). In the images of the system 10, the NC is identified as an area of poor signal with ill-defined borders within an atherosclerotic plaque covered by a fibrous cap. The necrotic tissue shows strong optical attenuation, resulting in a rapid decrease in the image intensity signal and shadowing of the area of the vascular wall located behind. Histopathologically, this plaque was classified as a fibrous plaque with an NC and underlying medial degeneration (see FIGS. 19E-F). Finally, a fibrotic plaque was identified in the distal segment of the intradural vertebral artery harvested from an 86-year-old cadaver. In the images of the system 10, the fibrotic-sclerotic plaque is characterized by a heterogeneous area with little signal with well-defined borders containing evidence of fibrous and calcified tissue. FIG. 20B shows a fibrocalcific plaque with a circumferential distribution of 87 degrees and a maximum thickness of approximately 900 μm.Calcified tissue has low backscattering and attenuation coefficients in the near-infrared region. As a result, System 10 can accurately visualize both its thickness and circumferential distribution. In histopathological evaluation, most of this plaque was classified as calcified, showing medial degeneration and positive remodeling beneath it.

[0263] Discussion Imaging performed using System 10 may provide sufficient spatial resolution to visualize the details of neurovascular devices at the strut level that are not visible in current clinical imaging diagnostics. Previous studies have shown the potential application of intravascular imaging technology to the neurovasculature, but due to the mechanical properties of existing imaging catheters for coronary arteries, application to tortuous cerebral vasculature has been impossible. Data published in the applicant's research indicates that System 10 enables volumetric microscopy of intracranial arteries. In studies using patient-specific in vitro models of the circle of Willis, contrast agent injection protocols were presented that enable imaging with System 10 at different neurovascular anatomical locations. The optimized injection protocol established for imaging with System 10 is not different from what is routinely done to obtain rotational angiography in neurointerventional surgery, and in fact, these two different diagnostic images can be acquired simultaneously. In an in vivo non-human animal model, evidence was gathered that the imaging probe 100 is suitable for imaging highly tortuous blood vessels comparable to the highly tortuous conditions encountered in the human ICA. In volumetric microscopy using System 10, the inter-operator agreement rate was very high in the quantification of intraluminal thrombi and the evaluation of the interaction between neurovascular devices and the arterial wall compared to current imaging diagnostics such as DSA and CBCT. Furthermore, when replacing the criteria of existing intravascular imaging with imaging using System 10, it was found that it has the ability to visualize the microstructure of the blood vessel wall and characterize intracranial arteriosclerosis. Thus, the applicant's research results pave the way for the clinical application of System 10 for intracranial imaging in the human clinical environment.

[0264] Preclinical evidence is increasing to support the speculation that cerebrovascular microscopy, which has the ability to evaluate vascular wall diseases and neurovascular devices, will have a major impact on the endovascular treatment of cerebrovascular diseases. In recent years, in a rabbit aneurysm model, it has been shown that in order to achieve early and complete aneurysm occlusion, it is critically important to fully juxtapose the flow-diverting stent, but histological evidence of misplacement was not accurately captured by DSA at optimal criteria. Communication abnormalities between the aneurysm neck and the flow-diverting device are not visible by non-invasive methods but are captured by intravascular OCT and have been shown to be predictors of subsequent early aneurysm occlusion. Similarly, gaps in the reconstruction of intravascular devices at the aneurysm neck observed in the images of System 10 and not detected by CBCT have been shown to correlate with subsequent lack of occlusion. MRVM is a method suitable for imaging the intracranial vascular wall in ischemic stroke and intracranial hemorrhage, but its accuracy is greatly affected by limited spatial resolution and voxel size. In recent studies, even in cases where angiography showed complete recanalization and thrombus was not visible on CT angiography or MRVW, endothelial injury of the penetrating arteries at the base of the brain, residual thrombus, and ongoing thrombus in the lesion after EVT could be confirmed by high-resolution intravascular imaging.

[0265] System 10 enables volumetric microscopy of the arterial wall at a resolution close to 10 μm. In the applicant's research, it has been shown in animal models that System 10 can accurately identify intracavitary thrombi and neurovascular devices at the strut level. These results, combined with evidence regarding imaging of tortuous anatomical structures, suggest that System 10 can be clinically used for pre- and post-operative evaluation of neurovascular devices, whereby corrective measures such as local administration of GP IIb / IIIa inhibitors, angioplasty, or additional stent placement may be deployed. Also, when angiographic findings are ambiguous, the excellent resolution of System 10 allows visualization of vascular anatomy and stent-vessel interactions that cannot be captured by non-invasive imaging techniques. By accurately understanding the types of intracranial atherosclerotic plaques, not only can treatment strategies be determined, but also the size, placement, and interaction between the perforating arteries and residual stenoses of stents can be improved to enhance the treatment of intracranial arteries. System 10 provides more information, guides imaging, and enables individualized antithrombotic management after EVT. The excellent resolution of the images of System 10 provides the ability to study the healing response of blood vessels and aneurysms to implanted devices at an unprecedented level, and the thickness of the tissue on the surface of the device and vascular remodeling can be evaluated with the accuracy and precision of in vivo microscopy techniques. Thus, by using the cerebrovascular microscopy provided by System 10, there is great potential to monitor device healing, evaluate endothelial overgrowth and intimal hyperplasia, and provide insights for optimal antiplatelet therapy after endovascular treatment in the clinical setting. In pre-clinical settings, System 10 provides knowledge useful for the development of a new generation of neurovascular devices.

[0266] Limitations of the study The ability to inject a contrast agent to obtain a clear optical window for neurovascular imaging was investigated in a bench model of the Circle of Willis. Considerable efforts were made to reproduce the patient's circulation, including pulsatile blood flow, physiological flow rates, vessel inner diameters, and capillary resistance. However, the use of in vitro models may not be able to capture the wide range of anatomical variations and disease states encountered in the patient's cerebrovascular system. In the applicant's research, high-viscosity agents were effective in moving blood well to obtain a clear view. In the human clinical setting, due to other factors such as intracranial arterial diseases, aging, and resulting reduced blood flow, it is possible to use low-viscosity agents such as saline and low-viscosity contrast agents. In such situations, injection at a lower rate may also be possible, providing sufficient clearance for image acquisition by System 10. Furthermore, the use of low-molecular-weight dextran has been studied for successful coronary artery imaging and its safety when used intracranially, and is also being explored for use in imaging by System 10 in the future.

[0267] Patient-specific vascular model of the Circle of Willis Using a patient-specific vascular model that includes the entire Circle of Willis, optimal blood clearance protocols were investigated at anatomically different locations such as the ICA, MCA, intradural VA, and basilar artery (see Figure 21). This model has also been used in similar previous studies. In the applicant's research, multiple sensors were used to continuously measure the flow rate and pressure of the ICA, MCA, and BA to enable the reproduction of clinically appropriate values. Porcine blood was maintained at 37°C and circulated using a pulsatile pump. The outlet resistance was adjusted to obtain physiologically representative flow rates through each branch of the model. Blood pressure and flow rate were continuously monitored and adjusted to maintain physiological values of approximately 250 ml / min for the ICA, 140 ml / min for the MCA, and 160 ml / min for the BA.

[0268] Animal model and preparation In the applicant's research, a Yorkshire pig model weighing 40 - 70 kg (n = 8) was used. All procedures were performed under general anesthesia. The animals were pre - anesthetized by subcutaneous injection of glycopyrrolate (0.01 mg / kg). Anesthesia was induced by intramuscular injection of tiletamine (Telazol, 4.4 mg / kg), ketamine (2.2 mg / kg), and xylazine (2.2 mg / kg) and maintained by artificial respiration with 1 - 3% isoflurane. During the procedure, vital parameters such as heart rate, respiratory rate, invasive blood pressure, oxygen saturation, end - tidal CO2, and body temperature were continuously monitored and recorded.

[0269] Using a flexed forelimb model, a model with increased vascular tortuosity was created. This technique can impart severe flexion to the brachial artery, resulting in a radius of curvature similar to that encountered in the human ICA. After surgically exposing the right femoral artery, a 10F introducer sheath was inserted for vascular access, and a 0.058 - inch Navien (registered trademark: Medtronic) was navigated to the proximal segment of the brachial artery to deploy the imaging probe 100 to the target anatomical structure.

[0270] Subsequently, a 0.058-inch intracranial support catheter was navigated into the internal maxillary artery (IMAX). Sixteen (n = 16) FDSs were placed on both sides of the IMAX. Pipeline FDS (manufactured by Medtronic) was used in half of the arteries (n = 8), and Sirpass FDS (manufactured by Stryker Neurovascular) was placed in the remaining half (n = 8) using conventional endovascular surgical techniques. After placing the FDSs, ICSs were placed in each IMAX, resulting in partially overlapping segments. Five Wingspan stents (manufactured by Stryker Neurovascular), six Neuroform stents (manufactured by Stryker Neurovascular), and four Solitaire AB stents (manufactured by Medtronic) were placed, for a total of 15 stents. Note that there was one case where an ICS could not be placed because the artery at the distal end of the FDS was occluded by a thrombus. Additionally, the Precise Pro Rx carotid stent system (Cordis) was placed in a subset of the common carotid arteries (n = 5).

[0271] Acquisition of Imaging Data In the brachial arteries of all animals other than humans (n = 16), imaging with the system 10 was performed from both sides. Contrast agent (Omnipaque) was injected using a 5F intermediate catheter to displace blood from the arterial lumen. Images of the endovascular system 10 were obtained in all IMAX arteries after placing the FDS and ICS devices, and a total of 31 imaging sessions were performed. Sixteen (n = 16) of these image datasets were obtained after placing the FDS. The other datasets (n = 15) were obtained after placing the ICS that partially overlapped with the FDS. Similarly, digital subtraction angiography (DSA), non-subtraction cine angiography, and full-scale small FOV cone beam CT images (Philips Healthcare) were obtained for each blood vessel using standard imaging techniques, and 31 imaging sessions were performed for each treatment method.

[0272] Analysis of Neurovascular Devices Using the distal and proximal ends of the FDS and ICS as reference markers, image data registration of different treatment methods was performed. Regions of interest (ROIs) with a length of 5 mm were set at the proximal and distal ends of all devices. At each ROI, the positions containing the largest thrombus and the positions containing the most severe positional abnormalities were collated between DSA, the system 10, and the cross-sectional images of the reconstructed CBCT. All images were binarized to classify the presence or absence of thrombus and positional abnormalities of the device. The results of the analysis of 160 angiography images, 160 images of the system 10, and 160 CBCT cross-sectional images by three experienced neurointerventional physicians under blind conditions.

[0273] Ex vivo segment of the intracranial artery To histopathologically compare the images of intracranial artery atherosclerotic plaques by the system 10, arterial segments were collected from cadavers over 70 years old with a smoking history and coronary artery and / or peripheral artery disease. The intracranial vascular systems of three cadavers were examined, and arteries that were thought to contain atherosclerotic diseases were collected (n = 10). Among them, the distal segments of the ICA (n = 2), the proximal and distal segments of the MCA (n = 4), the BA (n = 2), and the intradural segments of the VA (n = 2) were included. The specimens were fixed in 10% formalin solution before collection, and then immersed in physiological saline for 10 image acquisitions. Multiple data sets sampling the entire length of each artery were obtained. Skilled image readers of the system 10 identified regions of interest (ROIs) containing atherosclerotic diseases using previously established criteria for fibrous plaques, fibrocalcific plaques, and necrotic core plaques (n = 3). Each ROI of different specimens was marked using the visible light indicator emitted by the image probe 100. Subsequently, the corresponding tissue samples were embedded in paraffin, sectioned at 5 μm, and stained with Sudan black, hematoxylin and eosin, van Gieson, Movat pentachrome, and trichrome.

[0274] Statistical analysis Unless otherwise specified, the data are presented as mean ± standard deviation. Fleiss' kappa statistic was used to evaluate and quantify the degree of agreement (inter-operator variability) among three different image evaluators who classified the DSA, CBCT, and images of the system 10.

[0275] Three-dimensional rendering by system 10 The cross-sectional images were segmented according to previously established criteria (13) using software called ImageJ (36). The thrombus in the lumen, the struts of the neurovascular device, and the contour of the vessel wall were manually traced and labeled. The data of the system 10 were displayed in color such that red represented the vessel wall, purple represented the intraluminal thrombus, and silver represented the metal struts. After performing automatic registration between frames to correct for motion artifacts caused by the mechanical scanning of the catheter, the segmented data set was imported into DICOM visualization software (OsiriX MD v10.0.2, Pixmeo SARL, Bernex, Switzerland) for volume rendering. For visualization, a perspective volume rendering method using cross-sections and a fly-through method using different opacity tables were used, similar to previous studies (14, 37).

[0276] It should be understood that the above-described embodiments function only as examples, and further embodiments are contemplated. Any feature described herein in connection with any one embodiment can be used alone or in combination with other features described, and can also be used in combination with one or more features of any other embodiment, or any combination of any other embodiments. Furthermore, equivalents and modifications not described above may be adopted without departing from the scope of the invention defined in the appended claims.

Claims

1. 1. An imaging system for a patient comprising an imaging probe and an imaging assembly, The imaging probe comprises: an elongate shaft having a proximal end, a distal end, and a lumen extending between the proximal end and the distal end; a rotatable optical core having a proximal end and a distal end, the rotatable optical core being at least partially disposed within the lumen of the elongate shaft; an optical assembly disposed proximate a distal end of the rotatable optical core, the optical assembly configured to direct light toward tissue and collect reflected light from the tissue; Equipped with the imaging assembly constructed and arranged to be optically coupled to the imaging probe and configured to project light into the imaging probe and receive reflected light collected by the optical assembly; the distal portion of the elongate shaft has an outer diameter of 0.034 inches or less; the imaging system further comprises a console having a light source; the light source has a coherence length of 10 mm or more so that the scanning range of the imaging probe is 6 mm or more; the imaging system is configured to collect image data from the reflected light; the imaging system further comprising a second imaging device configured to collect non-OCT data; Imaging system.

2. The imaging system described in Claim 1, wherein the image data is OCT data.

3. The imaging system described in claim 2, wherein the non-OCT data includes angiography data.

4. An imaging system as described in claim 2, wherein the OCT data and the non-OCT data are displayed on a display.

5. The imaging system of claim 2, wherein the imaging system is capable of registering or associating both the OCT data and the non-OCT data.

6. The imaging system of claim 5, wherein the imaging system is capable of registering or associating both the OCT data and the non-OCT data using the position of the side branch.

7. The imaging system of claim 1, wherein the imaging system is configured to provide treatment information based on the image data.

8. The imaging system of claim 7, wherein the imaging system is configured to provide the treatment information based on the image data and the non-OCT data.

9. The imaging system of claim 1, wherein the imaging probe further comprises a damping fluid disposed between the elongated shaft and the rotatable optical core and configured to reduce non-uniform rotation of the optical assembly.

10. The imaging system of claim 9, wherein the imaging probe further has a fluid pressurizing element configured to increase the pressure of the damping fluid to reduce the presence of air bubbles in proximity to the optical assembly.

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