Method and system for determining hemodynamic parameters

Abstract

A method may be performed by a system including a processor in communication with an extraluminal imaging device and an intravascular pressure measurement device. The method includes acquiring a contrast agent angiography image in a blood vessel having a contrast agent; based on the contrast agent angiography image, generating a reconstructed geometric object of the blood vessel and estimating blood flow in the blood vessel; implementing a physical model of blood distribution using the reconstructed geometry, determining output parameters based on the blood pressure value and the blood flow volume; and generating a harmonic hemodynamic parameter based on the output parameter. The harmonized hemodynamic parameter is adjusted based on measurements taken at various vascular conditions.

Description

Technical Field

[0001] This disclosure relates to methods and systems for assessing hemodynamic function. More specifically, the present invention relates to methods and systems for determining hemodynamic parameters using intravascular pressure measurement devices in conjunction with medical imaging. Background Technology

[0002] Coronary artery disease can be diagnosed by assessing the impact of coronary artery stenosis on blood flow. Coronary artery stenosis is associated with thickening and narrowing of the coronary arteries and can occur in the blood vessels that carry blood to the heart. Coronary artery stenosis can occur in both large and narrow coronary arteries and can lead to angina, which manifests as chest pain in patients.

[0003] To identify and characterize coronary artery stenosis, various hemodynamic parameters (sometimes referred to as "hemodynamic quantities") can be used. For example, the fractional flow reserve (FFR) determines the ratio between the maximum achievable blood flow through a blockage (stenotic area) in a given coronary artery and the theoretical maximum blood flow through the same coronary artery assuming no blockage. Another hemodynamic parameter helpful in assessing coronary artery status is the coronary flow reserve (CFR). CFR values ​​provide an estimate of the total blood flow in the epicardial vessels and microvessels.

[0004] The microvascular resistance index (IMR) is a hemodynamic parameter reflecting the function of coronary microvessels associated with the smallest vessels. Estimating the IMR can help determine blood flow characteristics in the microvessels. Currently known methods for measuring IMR provide inaccurate and / or imprecise results. Summary of the Invention

[0005] According to one aspect of the disclosed technology, a method executable by a system is provided, the system including a processor communicating with an intravascular pressure measurement device and an extravascular imaging device. The method includes: acquiring a first set of contrast-enhanced angiographic images of a blood vessel containing a contrast agent via the extravascular imaging device; generating a reconstructed geometry of the blood vessel based on the first set of contrast-enhanced angiographic images; estimating a first blood flow in the blood vessel based on the first set of contrast-enhanced angiographic images; acquiring a first set of blood pressure values ​​via the intravascular pressure measurement device; realizing a first physical model of blood distribution in the blood vessel using the reconstructed geometry; determining a first set of output parameters by the processor based on the first set of blood pressure values ​​and the first blood flow; and generating harmonic hemodynamic parameters based on the first set of output parameters.

[0006] The method acquires a first set of contrast-enhanced angiographic images and a first set of blood pressure values ​​during a congested state of the blood vessel, the blood vessel containing a congesting agent. In at least one embodiment, the first set of blood pressure values ​​may be acquired as a function of position within the blood vessel. The first set of blood pressure values ​​may be a function of position within the blood vessel. The method may further include acquiring a first set of pressure-measuring angiographic images of the blood vessel via the extravascular imaging device. The first set of blood pressure values ​​may be registered with the first set of pressure-measuring angiographic images. The method may further include determining a first set of output parameters based on the first set of blood pressure values ​​registered with the first set of pressure-measuring angiographic images. The method may further include, when the blood vessel contains a congesting agent: acquiring a second set of contrast-enhanced angiography images of the blood vessel containing the contrast agent and congesting agent using the extravascular imaging device; estimating a second blood flow in the blood vessel based on the second set of contrast-enhanced angiography images; acquiring a second set of blood pressure values ​​within the blood vessel containing the congesting agent using the intravascular pressure measurement device; determining a second set of output parameters based on the second set of blood pressure values ​​and the second blood flow using the processor by implementing a second physical model of blood distribution in the blood vessel and using the reconstructed geometry; and wherein generating the harmonic hemodynamic parameters further includes: adjusting the harmonic hemodynamic parameters based on the first set of output parameters and the second set of output parameters. The second set of blood pressure values ​​may be a function of the position within the blood vessel. The method further includes acquiring a second set of pressure-measuring angiography images of the blood vessel using the extravascular imaging device and registering the second set of blood pressure values ​​with the second set of pressure-measuring angiography images. The method further includes determining the second set of output parameters by the processor based on the second set of blood pressure values ​​registered with the second set of pressure-measuring angiography images.

[0007] The method may further include, when the blood vessel contains a vasodilator: acquiring a second set of blood pressure values ​​as a function of the position within the blood vessel containing the vasodilator using the intravascular pressure measurement device, and acquiring a second set of pressure measurement angiography images of the blood vessel using the extravascular imaging device; acquiring a second set of contrast agent angiography images of the blood vessel containing both contrast agent and vasodilator using the extravascular imaging device; estimating a second blood flow in the blood vessel based on the second set of contrast agent angiography images; determining a second set of output parameters based on the second set of blood pressure values ​​by implementing a second physical model of blood distribution in the blood vessel and using the reconstructed geometry object, the second set of blood pressure values ​​being registerable with the second set of pressure measurement angiography images; and wherein generating the harmonic hemodynamic parameters further includes: adjusting the harmonic hemodynamic parameters based on the first set of output parameters and the second set of output parameters.

[0008] The method may further include, after stent placement in the vessel or after another percutaneous coronary intervention: acquiring a third set of contrast-enhanced angiographic images of the vessel containing the stent and contrast agent via the extravascular imaging device; estimating a third blood flow in the vessel based on the third set of contrast-enhanced angiographic images; acquiring a third set of blood pressure values ​​within the vessel via the intravascular pressure measurement device; realizing a third physical model of blood distribution in the vessel using the reconstructed geometry; determining a third set of output parameters based on the third set of blood pressure values ​​and the third blood flow via the processor; and wherein the harmonized hemodynamic parameters are also based on the third set of output parameters. The third set of blood pressure values ​​may be measured as a function of position within the vessel and / or as a function of position within the vessel. The method further includes acquiring a third set of pressure-measuring angiographic images of the vessel via the extravascular imaging device and registering the third set of blood pressure values ​​with the third set of pressure-measuring angiographic images. The method further includes determining the third set of output parameters via the processor based on the third set of blood pressure values ​​registered with the third set of pressure-measuring angiographic images. The third set of contrast-induced angiography images, the third set of blood pressure values, and the third set of pressure-measuring angiography images can be acquired during the period when the blood vessels are congested and contain a congesting agent. At least a third time period elapses after acquiring the third set of contrast-induced angiography images and before acquiring the third set of pressure-measuring angiography images and the third set of blood pressure values.

[0009] The method may further include: acquiring a fourth set of contrast-enhanced angiographic images of a blood vessel containing a stent and a contrast agent using the extravascular imaging device; estimating a fourth blood flow in the blood vessel based on the fourth set of contrast-enhanced angiographic images; acquiring a fourth set of blood pressure values ​​in the blood vessel using the intravascular pressure measurement device; realizing a fourth physical model of blood distribution in the blood vessel using the reconstructed geometry object; determining a fourth set of output parameters based on the fourth set of blood pressure values ​​and the fourth blood flow using the processor; and wherein adjusting the harmonic hemodynamic parameters is also based on the fourth set of output parameters. The fourth set of blood pressure values ​​may be measured as a function of the location within the blood vessel and / or as a function of the location within the blood vessel. The method further includes acquiring a fourth set of pressure-measuring angiographic images of the blood vessel using the extravascular imaging device and registering the fourth set of blood pressure values ​​with the fourth set of pressure-measuring angiographic images. The method may further include determining the fourth set of output parameters by the processor based on the fourth set of blood pressure values ​​registered with the fourth set of pressure-measuring angiographic images.

[0010] In some embodiments, the acquisition of the fourth set of blood pressure values ​​and the fourth set of pressure measurement angiography images is performed after at least a fourth time period following the acquisition of the fourth set of contrast agent angiography images.

[0011] Acquiring the first set of blood pressure values ​​and acquiring the first set of pressure measurement angiographic images of the blood vessel can be performed simultaneously. In at least one embodiment, acquiring the second set of blood pressure values ​​and acquiring the second set of pressure measurement angiographic images of the blood vessel can be performed simultaneously. Acquiring the third set of blood pressure values ​​and acquiring the third set of pressure measurement angiographic images of the blood vessel can be performed simultaneously. In at least one embodiment, acquiring the fourth set of blood pressure values ​​and acquiring the fourth set of pressure measurement angiographic images of the blood vessel can be performed simultaneously.

[0012] The method may further include: determining a second set of output parameters by the processor based on a second set of blood pressure values ​​containing a vasodilator but without a contrast agent (in other words, acquired after a second time period following the acquisition of a first set of contrast-induced angiography images) and a second blood flow determined based on a second set of contrast-induced angiography images acquired when the blood vessel contains both contrast agent and vasodilator; and wherein generating the harmonized hemodynamic parameters further includes adjusting the harmonized hemodynamic parameters based on the first set of output parameters and the second set of output parameters. The method also includes acquiring a second set of pressure measurement angiography images of the blood vessel and registering the second set of blood pressure values ​​with the second set of pressure measurement angiography images of the blood vessel.

[0013] The method may further include, after a stent is installed in the blood vessel, determining a third set of output parameters by the processor based on the following factors: a third set of blood pressure values ​​acquired simultaneously with the acquisition of a third set of pressure measurement angiography images after at least a third time period following the acquisition of the second set of contrast-induced angiography images, and a third blood flow determined based on the third set of contrast-induced angiography images acquired when the blood vessel contains contrast agent; and wherein the adjustment of the harmonized hemodynamic parameters is also based on the third set of output parameters.

[0014] The method may further include determining a fourth set of output parameters by the processor based on a fourth blood flow rate and a fourth blood pressure value, the fourth blood flow rate being determined based on a fourth set of contrast-enhanced angiography images acquired when the blood vessel contains both contrast agent and vasopressor, the fourth set of blood pressure values ​​being registered with a fourth set of pressure-measured angiography images acquired when the blood vessel contains vasopressor but not contrast agent (after at least a fourth time period following the acquisition of the fourth set of contrast-enhanced angiography images); and wherein the adjustment of the harmonized hemodynamic parameters is also based on the fourth set of output parameters.

[0015] The first set of output parameters may include a pressure estimate along the centerline of the blood vessel. The first physical model may be a three-dimensional, two-dimensional, one-dimensional, or zero-dimensional physical model. The first, second, third, and / or fourth physical models may be three-dimensional, two-dimensional, one-dimensional, or zero-dimensional models. The first, second, third, and / or fourth physical models may be hybrid physical models. The first physical model may be a machine learning model. The second, third, and / or fourth physical models may be machine learning models.

[0016] The method may further include generating a harmonic pressure field as a function of location within the blood vessel. The method also includes generating and displaying a combined output image comprising harmonic pressure values ​​determined based on the first set of output parameters, superimposed on the reconstructed geometry to represent the harmonic pressure field. The method further includes generating and displaying a combined output image comprising a visual representation of the harmonic pressure values, superimposed on the reconstructed geometry to represent the harmonic pressure field. Estimating a first blood flow in the blood vessel is also based on the reconstructed geometry of the blood vessel. Adjusting the harmonic hemodynamic parameters may also be based on the first blood flow. The adjustment of the forty-year harmonic hemodynamic parameters is also based on at least one of the first blood flow, the second blood flow, the third blood flow, and the fourth blood flow. In at least one embodiment, the first set of blood pressure values ​​includes proximal blood pressure values ​​and distal blood pressure values. The method may also include displaying the harmonic hemodynamic parameters on a display.

[0017] Based on the first set of output parameters, the second set of output parameters, the third set of output parameters, and / or the fourth set of output parameters, a harmonic pressure field as a function of the location in the blood vessel can be generated. The method further includes generating the harmonic pressure field as a function of the location in the blood vessel based on the fourth set of output parameters. The method may also include generating the harmonic pressure field as a function of the location in the blood vessel based on at least one of the first set of output parameters, the second set of output parameters, the third set of output parameters, and the fourth set of output parameters.

[0018] The harmonized hemodynamic parameters may be at least one of the following: microvascular resistance index, fractional flow reserve, coronary flow reserve, diastolic pressure ratio, absolute flow rate, absolute resistance, and absolute resistance ratio.

[0019] According to another aspect of the disclosed technology, a system is provided, comprising: an extravascular imaging device configured to generate a first set of contrast-enhanced angiographic images of a blood vessel containing a contrast agent; an intravascular pressure measurement device configured to measure blood pressure values ​​within the blood vessel, the blood pressure values ​​being measurable as a function of position, and to generate intravascular pressure data; and a processor configured to: generate a reconstructed geometric object of the blood vessel based on the first set of contrast-enhanced angiographic images; estimate a first blood flow in the blood vessel based on the first set of contrast-enhanced angiographic images; implement a first physical model of blood distribution in the blood vessel using the reconstructed geometric object; determine a first set of output parameters based on the first blood flow and the first set of blood pressure values, the first set of blood pressure values ​​being registerable with the first set of pressure-measuring angiographic images; and generate harmonic hemodynamic parameters based on the first set of output parameters.

[0020] In at least one embodiment, the system further includes a display configured to display the harmonized hemodynamic parameters and an image representing the harmonized pressure field. The processor may also be configured to: estimate a second blood flow in the blood vessel based on a second set of contrast-enhanced angiography images acquired when the blood vessel contains a contrast agent and a vasodilator; determine a second set of output parameters based on a second set of blood pressure values ​​acquired by the intravascular pressure measurement device, the second set of blood pressure values ​​being registerable with a second set of pressure-measuring angiography images acquired by the extravascular imaging device, by implementing a second physical model of the blood distribution in the blood vessel and using the reconstructed geometry; and adjust the harmonized hemodynamic parameters based on the first set of output parameters and the second set of output parameters.

[0021] The processor can also be configured to: estimate a third blood flow in the blood vessel based on a third set of contrast-enhanced angiography images acquired when the blood vessel contains a contrast agent; determine a third set of output parameters based on a third set of blood pressure values ​​acquired by the intravascular pressure measurement device, the third set of blood pressure values ​​being able to be registered with a third set of pressure measurement angiography images acquired by the extravascular imaging device; and further adjust the harmonized hemodynamic parameters based on the third set of output parameters.

[0022] The processor can also be configured to: estimate a fourth blood flow in the blood vessel based on a fourth set of contrast-enhanced angiography images acquired when the blood vessel contains a contrast agent; determine a fourth set of output parameters based on a fourth set of blood pressure values ​​acquired by the intravascular pressure measurement device, the fourth set of blood pressure values ​​being able to be registered with a fourth set of pressure measurement angiography images acquired by the extravascular imaging device; and further adjust the harmonized hemodynamic parameters based on the fourth set of output parameters.

[0023] According to another aspect of the disclosed technology, a processor is provided that communicates with an extravascular imaging device and an intravascular data acquisition device, the extravascular imaging device being configured to acquire at least one angiographic image of a blood vessel, and the intravascular data acquisition device being configured to acquire blood pressure values ​​within the blood vessel, wherein the processor is configured to: receive from the extravascular imaging device a first set of contrast-treated angiographic images of a blood vessel containing a contrast agent; receive from the intravascular data acquisition device a first set of blood pressure values, which may be a function of the position within the blood vessel, and receive from the extravascular imaging device a first set of pressure-measured angiographic images of a blood vessel without a contrast agent; generate a reconstructed geometry of the blood vessel and a first blood flow rate based on the contrast-treated angiographic images; implement a first physical model of blood distribution in the blood vessel using the reconstructed geometry; determine a first set of output parameters based on the first set of blood pressure values ​​that can be registered with the first set of pressure-measured angiographic images and based on the first blood flow rate; and generate harmonic hemodynamic parameters based on the first set of output parameters.

[0024] The processor can also be configured to: determine a second set of output parameters based on a second set of contrast-enhanced angiography images and a second set of blood pressure values, wherein the second set of blood pressure values ​​can be registered with a second set of pressure-measured angiography images acquired when the blood vessel contains a vasodilator; and wherein the processor generates the harmonized hemodynamic parameters based on the second set of output parameters. The processor can also be configured to: determine a third set of output parameters based on a third set of contrast-enhanced angiography images and a third set of blood pressure values, wherein the third set of blood pressure values ​​can be registered with a third set of pressure-measured angiography images acquired when the blood vessel contains a stent; and wherein the processor generates the harmonized hemodynamic parameters based on the third set of output parameters.

[0025] The processor can also be configured to: determine a fourth set of output parameters based on a third set of contrast-enhanced angiography images and a fourth set of blood pressure values, wherein the fourth set of blood pressure values ​​can be registered with a fourth set of pressure-measured angiography images acquired when there is a stent and a vasodilator in the blood vessel; and wherein the processor generates the harmonized hemodynamic parameters based on the fourth set of output parameters.

[0026] According to another aspect of the disclosed technology, a method is provided that can be executed by a system including a processor communicating with an extravascular imaging device and an intravascular pressure measurement device, the method comprising: acquiring contrast-enhanced angiography images when the vessel contains a contrast agent; acquiring pressure-measuring angiography images, separately and for the same vessel, in the absence of a contrast agent (or at a significantly low contrast agent concentration), acquiring pressure values ​​within the vessel (which can be measured by measuring proximal and distal blood pressure and can be measured as a function of position); reconstructing the geometry of the vessel and applying a physical model to the reconstructed geometry, the reconstructed geometry being registerable with the intravascular pressure values; and generating harmonized hemodynamic parameters and adjusting the harmonized hemodynamic parameters based on at least two vascular states selected from: pre-PCI rest, pre-PCI hyperemia, post-PCI hyperemia, and post-PCI rest.

[0027] According to one aspect of the disclosed technology, the method described herein includes acquiring contrast-enhanced angiography images in a blood vessel containing a contrast agent, acquiring pressure-measuring angiography images simultaneously with measuring blood pressure values; generating a reconstructed geometry of the blood vessel and estimating blood flow in the blood vessel based on the contrast-enhanced angiography images; determining output parameters based on blood pressure values ​​and blood flow that can be registered with the pressure-measuring angiography images by using the reconstructed geometry; and generating harmonic hemodynamic parameters based on the output parameters. The harmonic hemodynamic parameters are adjusted based on measurements taken under various vascular conditions. Attached Figure Description

[0028] Further features and advantages of this disclosure will become apparent from the following detailed description, taken in conjunction with the accompanying drawings, wherein:

[0029] Figure 1A A portion of a blood vessel, such as a coronary artery with a guidewire, is shown according to at least one embodiment of the present disclosure.

[0030] Figure 1B A portion of the coronary tree, including two coronary arteries, is shown.

[0031] Figure 1C It shows a narrow Figure 1A The coronary arteries;

[0032] Figure 1D A support structure is shown. Figure 1A The coronary arteries;

[0033] Figure 2 A system for determining and indicating a patient's condition according to at least one embodiment of the present disclosure is illustrated schematically;

[0034] Figure 3 This schematically illustrates a method that can be used according to at least one embodiment of the present disclosure. Figure 2 Intracavitary data acquisition equipment for the system;

[0035] Figure 4A The images shown are contrast-enhanced angiography images acquired according to at least one embodiment of the present disclosure;

[0036] Figure 4B The diagram illustrates the generation of a product in the segmentation step according to at least one embodiment of the present disclosure. Figure 4A Mask of angiographic images;

[0037] Figure 5A A method for determining a patient condition indication according to at least one embodiment of the present disclosure is illustrated schematically;

[0038] Figure 5B At least one embodiment according to the present disclosure is shown. Figure 5A Other steps of the method;

[0039] Figure 6A A timing diagram schematically illustrates an implementation of a method for determining hemodynamic parameters according to at least one embodiment of the present disclosure;

[0040] Figure 6B A timing diagram schematically illustrates another embodiment of a method for determining hemodynamic parameters according to at least one embodiment of the present disclosure; and

[0041] Figure 7 This is a flowchart of a method for determining hemodynamic parameters according to at least one embodiment of the present disclosure.

[0042] It should be noted that throughout the accompanying drawings, the same reference numerals identify the same or similar features. Detailed Implementation

[0043] Various aspects of this disclosure generally address one or more problems in determining hemodynamic parameters. The methods and systems described herein are configured to generate harmonic hemodynamic parameters and images that provide an indication of patient condition, obtained based on blood flow calculations, invasive pressure measurements, and angiographic images. The methods described herein utilize intravascular pressure measurements, angiographic images, and physical models to generate harmonic hemodynamic parameters and harmonic pressure fields within the blood vessel.

[0044] Now refer to the attached diagram, Figure 1A-1B A portion of the vessel 110 is shown, particularly the portion of the coronary artery with a lumen 112. Figure 1B This shows a portion of the coronary tree, which includes multiple blood vessels. Figure 1C This shows a portion of the coronary artery with a narrowed area. Figure 1D A bracket 120 is shown. Figure 1A The coronary arteries in the heart. Figure 1A-1D It shows the microvascular resistance R M The microvascular resistance index (IMR) characterizes the microvascular resistance of vessel 110 and is compared with the known microvascular resistance R in the art. M Related. In the simplified form, assuming that coronary artery flow and myocardial flow are equal and the contribution of collateral blood flow is negligible, then IMR can be estimated as distal coronary artery pressure divided by the mean transit time of coronary artery flow.

[0045] Currently known methods for determining IMR are either invasive or non-invasive. IMR can be invasively determined by simultaneously measuring temperature and pressure in the coronary arteries while injecting fluid cooler than the patient's body temperature into the vessel 110. Alternative non-invasive methods may include using angiography to assess coronary microvascular dysfunction and theoretically calculating IMR. However, these methods provide unreliable results due to the need to use numerous or inaccurate assumptions. For example, to calculate IMR solely from angiographic images, it is necessary to assume that the effect of the emery on microvascular resistance is equal to the overall mean, or that distal pressure can be accurately estimated using non-invasively obtained fractional flow reserve (FFR) values.

[0046] The methods and systems described herein employ both invasive and non-invasive procedures, allowing for the creation of a blood flow model within a patient's vessel 110 and the adjustment of that model based on measurements performed within the vessel 110. In some embodiments, this adjustment of the model can be performed in real time based on real-time measurements performed within the vessel 110. The methods and systems described herein can help improve the accuracy of the obtained IMR values.

[0047] It should be noted that the coronary arteries are one example of a blood vessel, and the methods described herein can be used for any other blood vessel. For example, the methods described herein can be used to assess microvascular disease in blood vessels located in other parts of the body, such as the legs. The pulmonary circulation can also be assessed using the methods and systems described herein. Therefore, when referred to herein, "blood vessel" can be, for example, but not limited to, coronary arteries, peripheral arteries, and pulmonary circulation vessels.

[0048] Figure 2 A system 200 according to at least one embodiment of the present disclosure is schematically illustrated. System 200 includes a processor 210 in communication with an extracavitary imaging device 215. The extracavitary imaging device 215 is a non-invasive instrument configured to acquire one or more two-dimensional angiographic images 220, 222 (e.g., X-ray images) of a blood vessel 110. In at least one embodiment, the extracavitary imaging device 215 may be configured to acquire video with a sequence of angiographic images. In some embodiments, the coordinate system xyz may be non-standard.

[0049] System 200 also includes an intravascular data acquisition device 300 (also referred to herein as "intravascular pressure measurement device 300") configured to move through blood vessel 110 to obtain intravascular pressure measurements 225 of blood vessel 110 (in other words, blood pressure values ​​225 at various locations within blood vessel 110). The intravascular data acquisition device 300 is connected to processor 210 and transmits the pressure measurements 225 to processor 210. Processor 210 determines one or more harmonic hemodynamic parameters based on contrast-enhanced angiography image 220 and the pressure measurements received from the intravascular data acquisition device 300, and displays the harmonic hemodynamic parameters on display 240. Display 240 may be a touchscreen display and / or system 200 may have additional input devices. Still refer to Figure 2 System 200 also includes memory 212, which provides a location for storing computer-executable instructions and is configured to store computer-executable instructions that can be executed by processor 210. Memory 212 can be implemented as a computer-readable storage medium, such as a read-only memory, hard disk drive (HDD), solid-state drive (SSD), and flash memory card. Database 230 can be optionally used as described below. Processor 210 also has a communication port for performing logical operations on signals.

[0050] Figure 3 A non-limiting example of an endovascular data acquisition device 300 is shown, which can be used in system 200 to acquire pressure measurements, i.e., a so-called pressure guidewire. The endovascular data acquisition device 300 includes a distal pressure sensor 310 located at the distal end 315 of the pressure guidewire 305 or catheter and moved through the cardiovascular system of patient 302 to reach blood vessel 110. See also... Figure 1A-1CThe intravascular data acquisition device 300 measures pressure at different locations within the blood vessel 110. The intravascular data acquisition device 300 acquires the position of a distal pressure sensor 310 relative to the geometry of the blood vessel (including, but not limited to, the length of the blood vessel). Therefore, the distal pressure sensor 310 of the intravascular data acquisition device 300 is configured to measure a blood pressure value 225 as a function of its position within the blood vessel 110. This position can be measured as a coordinate (x, y) and / or longitudinal position (l) along the blood vessel 110. In some embodiments, the blood pressure value 225 is measured as a function of the distance (e.g., within the blood vessel 110) from a reference point in the blood vessel 110 (e.g., the entry point where the distal pressure sensor 310 enters the blood vessel 110). In at least one embodiment, the blood pressure value 225 is measured as a function of time (t) and is timestamped.

[0051] The catheter 307 has a proximal pressure sensor 312, which can be located at the inlet of the vessel 110 during the measurement of distal pressure within the vessel 110. The measurement of distal pressure 527 and proximal pressure 529 (collectively referred to as blood pressure value 225) is performed when the distal pressure sensor 310 and the proximal pressure sensor 312 are at approximately the same height.

[0052] Therefore, catheter 307, together with guidewire 305 located within catheter 307, measures proximal pressure P. a and remote pressure P d The proximal and distal pressures can be measured simultaneously (synchronously). In at least one embodiment, signals associated with and representing the values ​​of distal pressure 527 and proximal pressure 529 are measured synchronously and sampled at a predetermined frequency. In other words, the two signals from the two measurements of distal pressure 527 and proximal pressure 529 are synchronized and sampled at a predetermined frequency. For example, but not limited to, such a predetermined frequency can be between 50 and 1100 Hz.

[0053] In at least one embodiment, the intravascular data acquisition device 300 can be introduced into the blood vessel 110 through its proximal end until its distal end 315 reaches the distal end of the blood vessel 110 under study, and then the intravascular data acquisition device 300 can be pulled back to the proximal end of the blood vessel 110. Intravascular pressure data 225 can be obtained during this pull-back process of the intravascular data acquisition device 300. Figure 2 As shown, the intracavitary data acquisition device 300 is connected to the processor 210, and the processor 210 sequentially receives intracavitary pressure data 225 from the intracavitary data acquisition device 300 while in vivo.

[0054] Figure 5A and 5BThe steps of a method 500 for determining hemodynamic parameters according to at least one embodiment of the present disclosure are illustrated schematically. In addition to obtaining a blood pressure value 225 using an intravascular data acquisition device 300, the method 500 further includes acquiring and using obtained angiographic images 220, 222 under two conditions using an extravascular imaging device 215: with and without contrast agent in the vessel 110. When contrast agent is present in the vessel 110, a contrast-treated angiographic image 220 is acquired. A pressure-measuring angiographic image 222 (also referred to as a “guidewire position angiographic image”) is acquired when there is no contrast agent in the vessel 110, while the blood pressure value 225 is measured using the intravascular data acquisition device 300.

[0055] When referred to herein, "contrast-enhanced angiography image 220 obtained / acquired with contrast agent" means that the contrast-enhanced image 220 is acquired immediately before or simultaneously with the introduction of contrast agent into vessel 110. When vessel 110 contains contrast agent, the contrast agent is visible to the user (clinician) on the contrast-enhanced angiography image 220, and / or the processor 210 can segment and separate (distinguish) the contrast-enhanced vessel from the background.

[0056] Figure 4A A contrast-enhanced angiography image 220, taken according to at least one embodiment of the present disclosure, is shown. The contrast agent helps to distinguish the vessel 110 from the background in the angiography image and displays the vessel 110 with "contrast". Contrast agent can be added, for example, by injecting the contrast agent directly into the vessel 110 or by injecting a contrast agent bolus through a diagnostic catheter at the coronary sinus ostium. The contrast agent can be, for example, an iodine-containing iodide contrast agent.

[0057] A contrast agent can be added to blood vessel 110 (the lumen of the blood vessel) to obtain a set of contrast agent angiography images 220. Contrast agent angiography images 220 can be acquired when the concentration of contrast agent in the blood vessel (also referred to here as the "first concentration" of contrast agent) is high enough to allow the blood vessel to be distinguishable in the contrast agent angiography images 220.

[0058] In at least one embodiment, extravascular imaging device 215 captures contrast-enhanced angiography image 220 while the contrast agent flows within the contrast agent duration in vessel 110. The contrast agent duration (which can be calculated from the start of contrast agent injection or contrast agent bolus) is long enough to acquire (and record) an image with contrast agent filling and propagation through the coronary tree before all contrast agent diffusion. While the contrast agent flows within vessel 110, the concentration of contrast agent in vessel 110 is sufficient to provide distinguishable contrast between the vessel image and the surrounding environment in the acquired contrast-enhanced angiography image 220. The contrast agent duration can be, for example, 3 to 5 seconds, or, for example, less than 10 seconds. The contrast agent duration can be predetermined, or alternatively, the operator (medical practitioner) can stop introducing contrast agent into vessel 110 when the contrast-enhanced angiography image 220 displayed on monitor 240 has sufficient contrast (in other words, has reached a contrast level that allows clear distinction between vessel 110 and its environment).

[0059] The pressure measurement angiography image 222 was obtained / acquired in the absence of contrast agent, which means that the pressure measurement angiography image 222 was acquired when there was no contrast agent in the vessel 110, either because the contrast agent was physically absent in the vessel 110 or because the contrast agent time period since the contrast agent was introduced into the vessel 110 had passed and the contrast agent concentration had decreased.

[0060] Pressure measurement angiography image 222 is acquired when the contrast agent concentration in vessel 110 decreases and reaches a second contrast agent concentration. This may occur after the contrast agent time period, and as soon as a few seconds after the injection of contrast agent or a clump containing contrast agent into vessel 110. In other words, pressure measurement angiography image 222 is obtained when the contrast agent concentration in the vessel is a second contrast agent concentration (e.g., zero or near zero) that is significantly lower than the first contrast agent concentration. Because injecting contrast agent into the catheter disrupts the aortic pressure signal (P... a Therefore, pressure measurements must be performed before or after contrast agent injection (during the recovery of aortic pressure measurement). In cases where pressure measurements are performed before contrast agent injection, the contrast agent can be used to trigger the preservation of retrospective pressure signals, for example, by preserving the average P value of the last 1 to 10 recorded heartbeats. a and P d .

[0061] Refer again Figure 2Extraluminal measurements (contrast-enhanced angiography image 220 and pressure measurement angiography image 222) and intraluminal pressure measurements 527 and 529 can be acquired in one, two, three, or four of the four states of the patient's vessel 110. These states of vessel 110 depend on whether vessel 110 is in a resting or congested state, and whether vessel 110 has undergone percutaneous coronary intervention.

[0062] To induce congestion, a congestion-inducing agent (also referred to as a "congestion inducer") may be introduced into blood vessel 110. While contrast agents themselves may cause congestion, it is preferable to introduce a congestion-inducing agent into blood vessel 110 to induce a congested state of the vessel. However, in some embodiments, the congestion-inducing agent may be a contrast agent. The congestion-inducing agent may be introduced, for example, by continuous intravenous injection of adenosine. Intracoronary (IC) bolus injection of adenosine or other drugs may also induce transient congestion.

[0063] When it is necessary to capture contrast-enhanced angiographic images 220 during the congested state of vessel 110, the user (operator) must synchronize the injection of the congestion-inducing drug with the injection of the contrast agent, because the duration of IC-induced congestion is very short. Alternatively, the contrast agent can be introduced using a contrast agent clump, while the congestion-inducing agent can be introduced by continuous intravenous injection of adenosine.

[0064] In the first state of blood vessel 110, measurements can be obtained when blood vessel 110 is at rest (in other words, "in a resting state"). In the resting state, blood vessel 110 is not under stress caused by a vasodilator, and measurements are taken without introducing (applying) a vasodilator.

[0065] In the second state, blood vessel 110 is in a state of stress, i.e., in a state of complete congestion. As mentioned above, the congestion state of blood vessel 110 (also referred to as "congestion condition") may be caused by a congesting agent. After the congesting agent is introduced into blood vessel 110 (and because) blood vessel 110 contains a congesting agent, measurements such as angiographic images 220, 222 and intravascular pressure measurements 225 can be performed. In other words, in the second state, blood vessel 110 may contain a certain concentration of congesting agent that would cause stress within blood vessel 110.

[0066] The concentration and amount of the engorgement agent in blood vessel 110 decrease over time, thus reducing the effect of the engorgement agent. After a period of time, such as a few seconds, blood vessel 110 returns to a resting state without the introduction of additional engorgement agent. The concentration of engorgement agent in the blood in the second state (engorged state) is higher than that in the first state (resting state). In a preferred embodiment, the concentration of engorgement agent in blood vessel 110 in the resting state is zero or close to zero because no engorgement agent has been introduced recently or the effect of the engorgement agent has subsided.

[0067] As is known in the art, such as Figure 1D As shown, a stent 120 can be implanted to open a blood vessel 110 in the heart that has narrowed due to plaque buildup caused by atherosclerosis. This intervention can be called percutaneous coronary intervention (PCI). As an alternative to implanting the stent 120, angioplasty can be used as PCI. In angioplasty, a balloon can be inflated briefly to push the plaque back onto the coronary artery wall, improving blood flow. For example, a drug-coated balloon (DSG) can be used during PCI.

[0068] In the method 500 described herein, first and second states of the vessel 110 can be induced prior to any PCI. Thus, the first state may also be referred to herein as the “resting state before PCI”, and the second state is also referred to herein as the “congested state before PCI”.

[0069] The third and fourth states of vessel 110 can be achieved after PCI. In the third state, vessel 110 is in a resting state and after PCI. The third state may also be referred to herein as the "post-PCI resting state," where measurements are taken after vessel 110 is without stress (i.e., without congestion) and after the stent or other structures have been placed. In the third state, angiographic images are taken, and blood pressure is measured after the placement of stent 120 (or another structure associated with PCI). In the fourth state, referred to herein as the "post-PCI congestion state," vessel 110 is in a stressed state (i.e., fully congested) and after PCI.

[0070] Now for reference Figure 5A and 5B Method 500 and its initial routine 505 can be implemented for one or more states of blood vessel 110. In the context of this specification, the term "routine" refers to a subset of computer-executable program instructions of method 500 that can be executed by processor 210 to perform the functions explained below in association with various routines.

[0071] In at least one embodiment, each preliminary routine 505a, 505b (also referred to as "preliminary routine 505") is performed for a state of vessel 110 and includes acquiring data in steps 510, 512, 515 (also referred to herein as "data acquisition steps") for subsequent transmission to processor 210. For example, one or more data acquisition steps may be performed for each additional state. In some embodiments, in subsequent states performed after the first state, only two measurement steps may be performed, such as: step 510 (acquiring an angiographic view of the vessel with contrast agent) and step 512 (acquiring blood pressure within the vessel), or steps 512 and 515 (acquiring an angiographic view of the vessel without contrast agent). Still in the preliminary routine, flow rate is estimated in step 525, pressure and geometry data 535 is generated in step 540, and pressure and geometry data 535 is generated in step 530.

[0072] In contrast agent image acquisition step 510, when the blood vessel 110 contains contrast agent, one or more sets of contrast agent angiography images 220 (such as X-ray images) of the blood vessel 110 are obtained. The contrast agent angiography images 220 are two-dimensional images taken from at least two different angles (in other words, in different planes) relative to the blood vessel 110. For example, a first contrast agent angiography image 220 may be taken in a geometric plane substantially parallel to the blood vessel 110, and a second contrast agent angiography image 220 may be taken in a second plane, which may, for example, be perpendicular to the plane of the first contrast agent angiography image 220, or, for example, at an angle between 60 and 130 degrees to the plane of the first contrast agent angiography image 220. The second plane may also be substantially parallel to the blood vessel 110. Images of the same blood vessel 110 taken in different planes may also be referred to as "views". Each view corresponds to multiple images taken in one geometric plane. The contrast agent angiography images 220 may be stored in memory 260.

[0073] Each contrast-enhanced angiography image 220a in the set of contrast-enhanced angiography images 220 can be obtained from a video of angiography images acquired and recorded by an extravascular imaging device 215 when the contrast agent is in the vessel 110. Each video and the contrast-enhanced angiography image 220a obtained therefrom can correspond to a view of the vessel 110 (at a specific angle).

[0074] As described above, the contrast agent introduced into the blood vessel 110 during the angiography imaging in the contrast agent image acquisition step 510 helps to distinguish the blood vessel from the background. In other words, the contrast agent-enhanced angiography image 220 containing the contrast agent allows for clear differentiation of the blood vessel, enabling the user to see the blood vessel 110 when displaying the contrast agent-enhanced angiography image 220, and allowing for determination of the location and geometry of the blood vessel.

[0075] After at least a first time period has elapsed following the introduction of the contrast agent (and the acquisition of a set of contrast-induced angiographic images 220), and after the contrast agent has been removed from vessel 110, pressure-measuring angiographic images 222 (e.g., X-ray images) are acquired (step 515), and a set of blood pressure values ​​225 are acquired in vessel 110 via an intravascular pressure measuring device 300 (step 512). In at least one embodiment, pressure-measuring angiographic images 222 and a set of blood pressure values ​​225 are acquired simultaneously (synchronously). In at least one preferred embodiment, blood pressure values ​​are acquired simultaneously with the acquisition of a second set of pressure-measuring angiographic images of the vessel containing the engorgement agent.

[0076] In other words, the intracavitary data acquisition device 300 measures the proximal pressure P. a and remote pressure P d (like Figure 1C As shown), these pressures are a function of the intraluminal position of blood vessel 110 (e.g., the distance from the entry point of the intraluminal data acquisition device 300 into blood vessel 110 to blood vessel 110). Figure 5A Step 512). In some embodiments, the pressure measurement value—proximal pressure P a and remote pressure P d —It can be measured as a function of time. In some embodiments, location (or orientation) can be described as coordinates, and proximal and distal pressures can be measured as functions of coordinates. A set of blood pressure values ​​225 acquired includes distal blood pressure value 527 and proximal blood pressure value 529, which are measured as a function of location within the vessel 110, and in some embodiments, also as a function of time. Still referring to Figure 5A While using the intravascular data acquisition device 300 to measure the distal blood pressure value 527 and the proximal blood pressure value 529 within the blood vessel 110, the system 200 simultaneously acquires a pressure measurement angiography image 222 of the same blood vessel 110. Figure 5A (Step 515 in the text). Measurements can be timestamped.

[0077] Step 515 involves measurement without contrast agent. The pressure measurement angiography image 222 does not allow for clear differentiation of blood vessels. If the pressure measurement angiography image 222 is displayed, the user (e.g., a clinician) cannot see the blood vessel 110. However, each pressure measurement angiography image 222 shows the tip of the endovascular data acquisition device 300 and its spatial location, so the user can see where (where within the blood vessel 110) the endovascular data acquisition device 300 measured the pressure.

[0078] The pressure measurement angiography image 222 is a two-dimensional image taken from one or more different angles relative to the blood vessel 110, while the pressure measurement by the endovascular data acquisition device 300 is performed within the blood vessel 110. The pressure measurement angiography image 222 may correspond to one or more views and may also be obtained from video recorded by the extravascular imaging device 215. The correspondence between the pressure measurement angiography image 222 and the blood pressure measurement value 225 (distal pressure value 527 and pressure measurement value 529) may be provided, for example, through timestamps.

[0079] To determine the pressure field within the vessel 110, the method 500 and system 200 described herein combine (in other words, overlay or superimpose) the data obtained during pressure measurements 527, 529, 222 with the geometric data of the vessel 110 obtained from the contrast-enhanced angiography image 220 in step 540.

[0080] Due to segmentation step 520, the geometry of blood vessel 110 may become clearly detectable. In this step, processor 210 segments the contrast-enhanced angiography image 220 acquired earlier in contrast-enhanced image acquisition step 510. Figure 2 and 5A During segmentation step 520, at least one contrast-enhanced angiography image 220 of each view is processed to generate a corresponding mask 420. The mask 420 identifies the portion of the contrast-enhanced angiography image 220 corresponding to the background 430 and the portion of the contrast-enhanced angiography image 220 corresponding to the blood vessel 110. Figure 4B The diagram illustrates the generation in segmentation step 520 according to at least one embodiment of the present disclosure. Figure 4A Mask of angiographic images. Figure 4B In this context, vessel 110 is a coronary artery. In at least one embodiment, processor 210 may segment only one image for each view (sequence) to perform 3D geometric reconstruction of vessel 110, and segment two images for each view sequence to estimate flow.

[0081] For example, mask 420 can have the same size / shape as contrast-enhanced angiography image 220, where background 430 is displayed as black (which can be referred to as "0" or "(0,0,0)" in RGB) and blood vessels 110 (e.g., arteries) are displayed as white (which can correspond to "1" or "255", depending on the number of bits). Figure 4B In the mask, blood vessels are shown as white, and the background 430 around the blood vessels 110 is black.

[0082] In step 540, based on the output of segmentation step 520 obtained from contrast-enhanced angiography image 220, the geometrical vascular coordinates (also referred to herein as "geometry") of vessel 110 are reconstructed. In at least one embodiment, in step 540, the reconstruction routine generates a reconstructed geometry object 545 as output, which provides the geometrical vascular coordinates of vessel 110.

[0083] The geometric coordinates of a blood vessel can be three-dimensional (3D) and can be represented as V(x, y, z). In at least one embodiment, the 3D geometry of blood vessel 110 can be reconstructed based on contrast-enhanced angiography image 220 of blood vessel 110. Various methods for reconstructing the 3D geometry can be used. Some of these methods are published in public publications. S., Gooya, A., Grass, M., & Frangi, AF (2016) Reconstruction of coronary arteries from X-ray angiography: A review: Medical Image Analysis, Vol. 32, pp. 46-68 ( This is described in S., Gooya, A., Grass, M., & Frangi, AF (2016). Reconstruction of coronary arteries from X-ray angiography: A review. Medical Image Analysis, 32, 46–68. For example, there are model-based methods, such as orthographic projection, back-projection, four-dimensional, multi-view, or vascular cavity reconstruction. Tomographic methods, such as so-called “gated” and motion-compensated 3D reconstruction methods, can also be used.

[0084] Depending on the number of sets (views) of the acquired contrast-enhanced angiography images 220, a two-dimensional (2D) or three-dimensional (3D) reconstructed geometry of the vessel 110 can be generated, as described below. 3D reconstruction can be based on two or more angiography views 510 that have been segmented in step 520. In two dimensions, the system can use one or more angiography views acquired in step 510, then segment them in step 520, and then generate a two-dimensional geometry of the vessel 110. For example, two or more sets of contrast-enhanced angiography images 220 can help generate a 2D or 3D reconstructed geometry of the vessel 110.

[0085] In at least one embodiment, an initial 3D model of the blood vessel 110 can be obtained by determining a two-dimensional (2D) projection of the blood vessel image and using elastic registration to determine the 3D model. Elastic registration provides local stretching of the image to correct for local nonlinear deformations. In at least one embodiment, the systems and methods described herein can use generative neural networks, such as generative adversarial networks (GANs).

[0086] 3D parameters of blood vessels can also be obtained using computed tomography angiography (CTA). CTA is a medical test that combines a computed tomographic scan with the injection of dye to produce images of blood vessels and tissues in a patient's body. The dye is injected via a vein (IV) line starting in the arm or hand. Other methods, such as iterative model reconstruction, can be used to obtain 3D models of arteries.

[0087] 3D reconstruction can be used to estimate volume to calculate flow rate. It can also be used as input data for computational fluid dynamics (CFD) models, as described below. For example, the diameter along the vessel can be used to estimate resistance. Reconstructed 3D geometric data of the vessel obtained from angiographic image sequences also helps determine blood flow (Q). By estimating the volume of contrast agent filling as a function of time, the relationship between volume change and time change (dV / dt) can be obtained, which, by definition, is the blood flow (Q) measured in cubic meters divided by seconds (m²). 3 / s).

[0088] In at least one embodiment, in step 540, low-dimensional reconstruction and low-dimensional embedding can be used instead of 3D reconstruction of the geometric vessel coordinates of vessel 110. For example, a two-dimensional (2D) reconstruction can be performed in step 540 to obtain the reconstructed geometry 545 through a 2D model (e.g., but not limited to 2D embedding or a model projected onto a plane). One-dimensional (1D) reconstruction can be performed by calculating values ​​at nodes and along a line. Alternatively, a zero-dimensional (0D) model can be used, where values ​​are calculated at nodes.

[0089] In at least one embodiment, the contrast-enhanced angiography image 220 received by the processor 210 from the extracavitary imaging device 215 may include metadata. The metadata of the contrast-enhanced angiography image 220 may be, for example, DICOM metadata, and may include additional information about the image data, such as size, dimensions, bit depth, modality used to create the data, and device settings used to capture the image. The metadata can be used for reconstructing the vessel geometry and generating the reconstructed geometric object 545.

[0090] When method 500 is executed, the geometry of blood vessel 110 can be generated for a first state of blood vessel 110. For example, if the execution of method 500 begins from a “PCI preoperative rest” state, a reconstructed geometry object 545 is generated in step 540. When the preliminary routine 505 is executed for a subsequent state of blood vessel 110 (e.g., “PCI preoperative hyperemia”), the reconstructed geometry object 545 generated for the first state of blood vessel 110 (“PCI preoperative rest”) can be reused for subsequent registration with blood pressure value 225 and pressure measurement angiography image 222 in step 530.

[0091] Based on contrast-enhanced angiography images 220, blood flow (Q) can be estimated. For example... Figure 5A As shown, after segmentation step 520, processor 210 estimates blood flow in step 525. Blood flow can be estimated based on at least one view. In at least one embodiment, blood flow across the entire coronary tree can be estimated. Alternatively, processor 210 can estimate the spatially distributed blood flow field within the coronary tree. In some embodiments, the method described in U.S. Patent No. US11369277 can be used to estimate blood flow (Q).

[0092] In at least one embodiment, the flow rate routine 525 uses a reconstructed geometry 545 to estimate the flow rate. In the geometry reconstruction routine performed at step 540 of method 500, the reconstructed geometry 545 can be computed during reconstruction (e.g., 3D reconstruction). Alternatively, the flow rate can be estimated by assuming a 2D axisymmetric geometry of the vessel 110. In other words, to estimate the flow rate, an angiographic image can be used in an axisymmetric model of the vessel, assuming the vessel lies on a planar (flat) surface.

[0093] Blood flow values ​​generated from contrast-enhanced angiography images 220 or reconstructed geometry 545 can be used in the physical model routine 550 and optimization routine 570 of method 500.

[0094] In at least one embodiment, in step 530, data obtained from contrast angiography image 220 on the one hand, and data obtained from pressure measurement angiography image 222 and simultaneous pressure measurements 527, 529 on the other hand, can be combined.

[0095] Based on the pressure measurement angiography image 222, the processor 210 can determine and store the position of the distal tip 315 of the pressure guidewire 305 within the vessel 110 in step 530, and obtain a sequence of positions of the endovascular data acquisition device 300 as a function of time and two coordinates (x, y). For example, the position of the distal pressure sensor 310 at a specific time can be represented by coordinates (x, y). Pressure measurements 527, 529 can be averaged or dynamic. At each time step, the pressure measurement angiography image 222 can include one or more angiography images captured (acquired) on one or more geometric planes, thereby providing one or more different views of the pressure guidewire 305 located within the vessel 110. Therefore, the pressure measurement angiography image 222 can be used to obtain registered pressure and geometric data 535.

[0096] In at least one embodiment, the measured proximal pressure 529 and distal pressure 527, or distal pressure 527 alone, can be superimposed (mapped onto) with a reconstructed geometry 545 of the vessel 110. For example, the reconstructed geometry 545 can be obtained at the end of the diastolic phase and used for superposition. Thus, in step 530, the processor 210 can superimpose the pressure measurements with the previously determined (obtained) geometry of the vessel 110. Alternatively, the processor 210 can map the pressure measurements 527, 529 relative to the position of the distal pressure sensor 310 on the pressure measurement angiography image 222. These steps may also be referred to as “registration” or “co-registration” of the pressure measurements with the coordinates of the vessel 110. As used herein, registration or co-registration refers to transforming different datasets into a single coordinate system.

[0097] However, in another embodiment, as an alternative or supplement to mapping onto the reconstructed geometry 545, the pressure values ​​527, 529 received as pressure signals from the intracavitary data acquisition device 300 can be superimposed (mapped onto) with the contrast-enhanced angiography image 220 (acquired in the contrast-enhanced image acquisition step 510). For this purpose, in at least one embodiment, the processor 210 can calculate the median pressure at the end of the diastolic phase and use the pressure measurement angiography image 222 captured (acquired) at the end of the diastolic phase (corresponding to the relaxation phase of the cardiac cycle). In at least one embodiment, the processor 210 can average the blood pressure values ​​527, 529 measured over time.

[0098] In at least one embodiment, the measured proximal pressure P a and remote pressure P d (Or distal pressure 527 alone) and the pressure measurement angiography image 222 obtained simultaneously with pressure measurements 527, 529 (or distal pressure 529 alone) can be mapped together onto the reconstructed geometry object 545 of the vessel 110 previously obtained in step 540, wherein the geometry of the vessel 110 is determined based on the contrast-enhanced angiography image 220 obtained from different planes (views) in the presence of contrast agent in the vessel 110.

[0099] In at least one embodiment, in order to “register” pressure measurements in step 530, pressure measurements 527, 529 (or distal pressure 527 alone) may first be superimposed on pressure measurement angiography image 222 to obtain pressure registration data, which includes one or more images illustrating displacement tracking of the intraluminal data acquisition device 300 within the vessel 110. This pressure registration data may then be superimposed on one of the contrast-enhanced angiography images 220, or preferably on a reconstructed geometry object 545, to obtain registered pressure and geometry data 535. The resulting superimposed image obtained in step 530 may be displayed on display 240. Distal pressure 527 may be registered with pressure measurement angiography image 222, and then pressure measurement angiography image 222 may be registered with reconstructed geometry object 545.

[0100] Refer again Figure 5A The flow data (e.g., flow rate) determined in step 525, the registered pressure and geometric data 535, and the reconstructed geometric objects 545 determined in step 540 in some embodiments are then transferred to the physical model routine 550.

[0101] Physical modeling routine 550 (also referred to herein as "step 550") implements (applies) a physical model of the blood distribution (flow) in blood vessel 110. Physical modeling routine 550 uses flow data (estimated in step 525), reconstructed geometry 545 (in other words, reconstructed 3D (or 2D) parameters of blood vessel 110 obtained from contrast-enhanced angiography image 220), and intravascular (in other words, along blood vessel 110) blood pressure distribution obtained by pressure measurement 512.

[0102] The physical model can be implemented using CFD analysis. Physical model routine 550 solves the Navier-Stokes equations, which are partial differential equations describing blood flow within vessel 110. When implemented in OD, physical model routine 550 can solve differential equations. In some embodiments, physical model routine 550 can be executed in steady state (independent of time) using algebraic equations. The physical model can be data-driven, such as a reduced-order model.

[0103] The physical model is based on the geometry of the blood vessel 110 (e.g., reconstructed geometry 545), boundary conditions (inflow boundary conditions, such as flow rate), and invasive (intravascular) measurements of pressure and flow. The physical model can solve the Navier-Stokes equations in three dimensions (3D), two dimensions (2D), one dimension (1D), or zero dimension (0D). An alternative physical model can be based on machine learning. In at least one embodiment, the physical model routine 550 uses a reduced-order model or machine learning to solve the Navier-Stokes equations. CFD, reduced-order model, and / or machine learning computations can be performed using a database 230, which can store initial values ​​used to implement the physical model.

[0104] The output of the physical model, and the output of step 550 of method 500, is a set of output parameters 555, which includes a pressure estimate (also referred to as a “prediction”, “blood pressure correction”, or “solution to the model”) relative to coordinates and flow rate as a function of coordinates. The optimization implemented by optimization routine 570 helps to find microvascular resistance. In some embodiments, the output parameters 555 of the physical model may include, for example, a pressure estimate along the centerline of blood vessel 110. In other words, the output of the physical model may be the coordinates of an imaginary line passing through the geometric center of blood vessel 110, and a pressure estimate along that imaginary line determined by the physical model. Therefore, the output of the physical model in step 550 is a defined distribution of blood pressure relative to spatial coordinates and thus relative to the blood vessel.

[0105] The physical model in step 550 uses the pressure and geometry data 535 received from registration step 530 to generate a set of output parameters, which includes the calculated (determined) pressure values ​​in the volume of vessel 110. After solving the Navier-Stokes equations, the physical model routine 550 provides a set of output parameters 555 to the optimization routine 570. The pressure values ​​calculated in step 550 are then used in the objective function in the optimization routine 570, described below.

[0106] In at least one embodiment of method 500, pressure measurements in blood vessel 110 are performed by proximal pressure sensors 312 of guidewire 305 and catheter 307 as described in step 510 above, while a determined (predicted) pressure (a set of output parameters 555) can be obtained based on a fluid dynamics model with boundary conditions. The boundary conditions may be, for example, blood pressure values ​​measured by pressure sensors 312 at two locations within a portion (segment) of blood vessel 110. Then, in step 550, the data obtained from the measurements in steps 512 and 515 (proximal pressure 529 and distal pressure 527) can be merged with the contrast-enhanced angiography image 220 obtained in step 510, and the Navier-Stokes equations can be solved. In at least one alternative embodiment, in step 530, processor 210 can merge the reconstructed geometry 545 (obtained based on contrast-enhanced angiography image 220) with the data obtained in steps 512 (pressure measurements 527, 529) and 515 (pressure measurement angiography image 222).

[0107] The physical model 550 generates a set of output parameters 555 as output for a specific state. These output parameters 555 represent pressure predictions based on the contrast-enhanced angiography image 220 and pressure measurements 222, 225 relative to the reconstructed geometric object 545 (2D or 3D geometry) of the blood vessel 110. The output of the physical model 550, i.e., the set of output parameters 555, can then be used by the optimization routine 570.

[0108] Refer to the diagram again Figure 2 , 5A As shown in 5B, in preliminary routine 505a, measurements, data acquisition, transmission to processor 210, and calculation of the physical model are performed for the first state of vessel 110. Similar measurements can be performed for other states of vessel 110 as described above (pre-PCI rest, pre-PCI hyperemia, post-PCI rest, and post-PCI hyperemia), as shown in similar preliminary routines 505b, 505c, and 505d.

[0109] After solving the differential equations in the physical model routine 550, an optimization routine 570 for the physical model of blood vessel 110 will be implemented. The optimization routine 570 uses a set of output parameters 555 generated by the physical model 550 based on measurements obtained during one or more states, and adjusts the harmonic pressure value based on multiple iterations of blood vessel 110 under different states.

[0110] refer to Figure 5B For each of the four states mentioned above, implement Figure 5AThe steps of the preliminary routine 505 and various routines shown are used to determine the flow data and output parameters 555 (e.g., the first set of output parameters 555a) for each corresponding state. Each of the preliminary routines 505a, 505b, 505c, and 505d can provide pressure and geometry data 535, reconstruct geometry 545, and estimated flow to the corresponding physical model routines 550a, 550b, 550c, and 550d. Each of the physical model routines 550a, 550b, 550c, and 550d corresponding to one of the multiple states (also collectively referred to herein as "physical model routine 550") can use database 230 for the initial 3D model.

[0111] The first physics model routine 550a is configured to execute the first physics model, the second physics model routine 550b is configured to execute the second physics model, the third physics model routine 550c is configured to execute the third physics model, and the fourth physics model routine 550d is configured to execute the fourth physics model. Any one or more of the first, second, third, and / or fourth physics models can be a three-dimensional (3D) physics model, a two-dimensional (2D) physics model, a one-dimensional (1D) physics model, or a zero-dimensional (0D) physics model. Any one or more of the first, second, third, and / or fourth physics models can be a combination of physics models, also referred to herein as a hybrid physics model. Any one of the first, second, third, or fourth physics models can be a machine learning model.

[0112] For example, a hybrid physics model could be a combination of a 3D physical model of key parts of the coronary tree (such as lesions or bifurcations) and an 0D physical model of healthy coronary arteries or microcirculation. Pressure and flow can be exchanged at the interface between the two models (3D and 0D models), possibly by converting flow to velocity profiles based on Womersley's solutions or another hypothetical velocity profile. Alternatively, a hybrid physics model could be a combination of machine learning and 0D modeling methods. Machine learning can be used in such models to approximate the behavior of elements such as lesions or bifurcations in a model solved using an 0D solver.

[0113] Then, physical model routines 550a, 550b, 550c, and 550d provide one or more sets of output parameters 555 (the first, second, third, and fourth sets of output parameters 555a, 555b, 555c, and 555d, respectively) to optimization routine 570. In at least one embodiment, optimization routine 570 receives registration pressure measurements regarding the reconstructed 2D or 3D geometry (reconstructed geometry object 545) from each of the physical model routines 550a, 550b, 550c, and 550d.

[0114] After multiple iterations, optimization routine 570 generates harmonic pressure values ​​(also referred to as "harmonic pressure field" in this paper) as a function of coordinates.

[0115] In at least one embodiment, optimization routine 570 generates and / or adjusts one or more hemodynamic parameters (e.g., absolute microvascular resistance) and minimizes the difference between the pressure value predicted by the model based on the flow and contrast-enhanced angiography image 220 on one side and the blood pressure 225 measured on the other side without contrast agent.

[0116] The optimization routine 570 can implement a data assimilation routine. In at least one embodiment, the data assimilation routine includes minimizing an objective function by weighting the data correction with uncertainty-based weights. The weights can be predetermined and correspond to a predetermined accuracy of the predicted (calculated) pressure and the measured pressure values. For example, the objective function could be the difference between the predicted and measured pressure and / or flow rate, so the data assimilation routine can minimize this difference. For example, data assimilation may include minimizing several objectives. In some embodiments, the weights can be uniform (e.g., equal to 1), and data assimilation can include minimizing the error between the predicted pressure and the measured pressure.

[0117] When the input data is dynamic, i.e., when the algorithm's input data is pressure P(t) and flow rate Q(t), assimilation can be achieved through filtering. For example, optimization routine 570, which implements data assimilation, can use an integrated Kalman filter.

[0118] The optimization steps may depend on time, subsequent measurements in a given state, and / or the state of the blood vessel 110. In subsequent optimization steps, each current set of output parameters 555 received from the physical model is compared with a previously received set of output parameters 555, and the processor 210 adjusts the pressure values, geometric values, and / or boundary conditions. In at least one embodiment, the processor 210 first adjusts the boundary conditions, such as the microvascular resistance R. M Or IMR. Alternatively, steady-state optimization can be performed after all measurements have been taken. Implementing a dynamically adjusted model is more complex than implementing a steady-state model. In some embodiments, when implementing dynamic adjustment, fewer assumptions are used, and signal dynamics are used to represent information. In at least one embodiment, processor 210 performs optimization over time or alternatively using average pressure values.

[0119] While the patient is on the examination table, one or more of the aforementioned vascular states can be induced. For example, stent 120 can be implanted after both the first state (corresponding to the resting state) and the second state (corresponding to the congested state) of vessel 110 have been implemented. Therefore, after implementing the initial routine 505a for the first state and the physical model routine 550a for each time step, the harmonic pressure is a value obtained based on a combination of data obtained from measurements and data obtained based on modeling (simulation). The initial value of the harmonic pressure can be either the measured pressure or the modeled pressure. Alternatively, the initial value of the harmonic pressure can be predefined (which may be referred to as the predefined initial harmonic pressure). The output of the physical model routine 550a allows adjustment of the value of the harmonic pressure in each optimization step.

[0120] In the operation of method 500, system 200 acquires a first set of contrast-enhanced angiography images 220, and then, after the contrast-enhanced time period, acquires a first set of pressure-measured angiography images 222 and a first set of blood pressure values. These measurements are taken for a first state of vessel 110 (PCI resting state). A prompt to begin retracting the intravascular data acquisition device 300 can be displayed on display 240. The steps of the first preliminary routine 505a and the first physical model routine 550a described above can be implemented to generate a first set of output parameters 555a. In some embodiments, several time steps can be optimized. In some embodiments, optimization can be performed, for example, by performing multiple retractions of the intravascular data acquisition device 300.

[0121] To improve the accuracy of the harmonized pressure in the optimized routine 570, measurements can be taken in a second state of vessel 110 (pre-PCI congestion state). A prompt on display 240 may then prompt the operator to induce the congestion state of vessel 110 and / or confirm (e.g., by pressing a button or a predetermined portion of display 240) that the second state has been induced. In some embodiments, congestion can be detected from a pressure signal. To obtain a second set of contrast-enhanced angiographic images 220 in the second state of vessel 110, as described above, the introduction of the contrast agent and the congestion agent are preferably time-proximity so that the contrast agent is introduced simultaneously in the congestion state. Measurements of the second set of contrast-enhanced angiographic images 220 can begin, followed by the acquisition of a second set of pressure-measured angiographic images 222 and a second set of blood pressure values ​​225 with stress, and can continue, for example, until the results converge. In some embodiments, the induction of the second state can be requested first. Therefore, measurement data are collected, and the optimized routine 570 can be implemented first for the second state (pre-PCI congestion state). After implementing optimization routine 570 for one of the states, the optimization data can be displayed on display 240.

[0122] Then, optimization routine 570 can request the user (operator or clinician of system 200) to induce another of the four states, for example, stent placement, and then confirm whether a third or fourth state was induced. Therefore, the optimization program considers data obtained during previous optimization periods and adjusts its output based on previous optimizations for the same vessel 110 and new measurements taken using stent 120 (with or without congestion, i.e., the third and fourth states). It should be noted that stent 120 can be placed while guidewire 305 is inside vessel 110. After stent 120 placement, optimizations for the third and fourth states can be performed separately during the third and fourth optimization periods. Figure 6A A timing diagram 600 schematically illustrates an implementation of a method 500 according to at least one embodiment of the present disclosure. Figure 6A As shown, preferably, method 500 begins with the measurement of contrast-enhanced angiography image 220. For each of the four states, the measurement order of contrast-enhanced angiography image 220 relative to pressure measurement angiography image 222 and blood pressure 225 can vary and can be selected by the user. For example, the user can provide information (input) about which measurements have been or will be performed. If contrast-enhanced angiography image 220 is measured first, the user may preferably need to wait (e.g., a few seconds) after performing contrast-enhanced angiography image 220 and before acquiring pressure measurement angiography image 222 and blood pressure 225 to allow the blood pressure to stabilize after the contrast agent is introduced. In other words, there is a preferred delay between the introduction of the contrast agent (and thus the acquisition of contrast-enhanced angiography image 220) and the acquisition of pressure measurement angiography image 222 and blood pressure 225.

[0123] refer to Figure 5A and 6A When measuring and collecting data on multiple states of blood vessel 110 (e.g.) Figure 6A As shown, a reconstructed geometry 545 can be generated for the first state of vessel 110 (e.g., for the pre-PCI resting state). When the initial routine 505 of method 500 is subsequently executed, the processor can use (reuse) the reconstructed geometry 545 previously generated for the first state of vessel 110 based on measurements of the contrast-enhanced angiography image 220 of the first state of vessel 110.

[0124] Figure 6B A timing diagram 610 schematically illustrates another embodiment of a method 500 for determining hemodynamic parameters according to at least one embodiment of the present disclosure. Figure 6B As shown, when blood vessel 110 is in a resting state, contrast-enhanced angiography image 220 can be measured after the contrast agent is introduced into blood vessel 110, and can subsequently be used to generate the geometry of the blood vessel. Figure 5AIn step 540), flow rate is estimated. After the measurement of contrast agent angiography image 220, a vasodilator can be introduced, and pressure is measured when vessel 110 is congested, measuring angiography image 222 and blood pressure 225. In step 580 ( Figure 5B Subsequent measurements of contrast-enhanced angiography images 220 can be used to re-estimate flow in the congested state and adjust the harmonizing pressure.

[0125] In at least one embodiment, if measurements have been performed and registered during congestion (second or fourth state), the equation system can be improved by adding equations that consider a state where the geometry of vessel 110 remains unchanged while myocardial resistance has changed. Furthermore, system 200 can determine the IMR value during congestion. System 200 can determine the microvascular resistance R during the resting state and / or congestion of vessel 110. M In at least one embodiment, several congestion states can be used to generate additional equations. For example, measurements can be performed and registered during a resting state, an intermediate congestion state induced by a contrast agent, and a full congestion state induced by a congesting agent (such as adenosine).

[0126] In at least one embodiment, the equation system at optimization routine 570 may include additional equations for measurements and registration data (such as corresponding angiographic images and pressure measurements) performed in the post-PCI hyperemia state (fourth state) of vessel 110. These additional equations take into account states where the lesion model changes, for example, due to PCI, but myocardial resistance remains unchanged. In other words, the presence of stent 120 alters the geometry of the coronary artery but does not change microvascular resistance. Considering the post-PCI hyperemia state may help improve the accuracy of the harmonic pressure generated by optimization routine 570.

[0127] In at least one embodiment, the optimization routine 570 takes into account the fact that the blood vessel 110 may have two types of resistance: resistance caused by lesions and microvascular resistance. Therefore, for the first state of the blood vessel 110, the first blood flow Q1 (e.g., determined in step 525) corresponds to the lesion ( Figure 1C The resting resistance R1 and resting microvascular resistance R in the stenosis 1) M-r (Both can be determined based on the first set of output parameters 555a obtained in the first state, which are received from the corresponding first physical model 505a). The first set of output parameters 550a-P obtained for the first state. a1 With Q1(R1+R) M Proportional: P a1 ~Q1(R1+R M-r ).

[0128] For the hyperemia (second) state during PCI, the second set of output parameters Pa2 The second blood flow Q2, as well as the congestion resistance R2 and congestion microvascular resistance R of the lesion. m-h The sum is proportional: P a2 ~Q2(R2+R M-h ).

[0129] The congestion resistance R2 and resting resistance R1 are correlated with each other by the geometry of the vessel 110 and are provided by the reconstructed geometry object 545 in each state. In at least one embodiment, the optimization routine 570 uses the reconstructed geometry object 545 of the vessel 110 generated at rest and in congestion (first and second states), respectively, and a first set and a second set of output parameters 555a, 555b generated by the physical model 550 for the first and second states. By using the above equations, the optimization routine 570 adjusts the harmonizing pressure.

[0130] In the third state of vessel 110—the resting state after PCI—the third set of output parameters 555c consists of the third blood flow Q3 and the resting microvascular resistance R. M-r A function (or related function) can be represented as: P a3 ~Q3(R) M-r In the fourth state—post-PCI congestion state—the fourth set of output parameters 555d are the fourth blood flow Q4 and resting microvascular resistance R. M-h A function of (or proportional to): P a4 ~Q4(R) M-h The equations provided herein assume that resistance after PCI is negligible. In at least one embodiment, the model may include such resistance. Optimization routine 570 may consider available third and / or fourth sets of output parameters 555c, 555d and the above equations to determine the harmonic pressure value along vessel 110. When multiple lesions (stenotic areas) are present in vessel 110, similar equations may be determined, and optimization routine 570 may consider one lesion with stent 120 while other lesions do not have stent 120. For example, after the introduction of stent 120, the equations used by optimization routine 570, in addition to R... M In addition, it may include resistance from other lesions in the same blood vessel 110.

[0131] To determine the value of the harmonic pressure, optimization routine 570 therefore considers the available set of output parameters 555 for each state of blood vessel 110 and their relationship to blood flow in the corresponding state. Optimization routine 570 also considers the reconstructed geometry 545 determined in the corresponding state. By adjusting the harmonic pressure using optimization routine 570, the harmonic pressure value can become more accurate in each optimization step. Optimization routine 570, implemented by processor 210, generates the harmonic pressure distribution within the blood vessel (in other words, the distribution with respect to coordinate P). rec(x, y, z, t) pressure field), flow rate, and harmonized microvascular resistance. Based on this output, processor 210 can then generate harmonized hemodynamic parameters in step 580 and display harmonized hemodynamic parameters 270 on display 240 in step 585. Harmonized hemodynamic parameters 270 can be, for example, IMR, FFR, coronary flow reserve (CFR), diastolic pressure ratio (dPR), absolute flow rate, absolute resistance of one or more coronary artery branches, and / or absolute resistance ratio during rest and / or congestion. In one embodiment, pressure measurements 527 and 529 obtained during pullback or point measurement can be located using the tip of guidewire 305 at the position in an angiographic image (pressure measurement angiographic image 222) corresponding to the measured pressure, and registered on the 2D geometry of the vessel (reconstructed geometry object 545) or on a region of interest of the vessel derived from a single angiographic view with contrast agent (step 510) (step 530). An angiographic view can be, for example, a single image taken at the end of the diastolic phase. The model can be a 0D cardiovascular model of the artery of interest. The model can use measured pressure or flow rate as boundary conditions. Based on a single state (505a, 505b, 505c, or 505d) or multiple states, pressure measurements can be assimilated to model predictions using, for example, a weighted average. The weights can be based on confidence levels associated with the measurements and predictions. Harmonic hemodynamic parameters, such as dPR, FFR, or harmonic pressure, can be displayed on a reference image, such as vessel geometry (reconstructed geometry object 545) or a reference angiography (e.g., one of contrast-enhanced angiography images 220), using, for example, symbol overlay to represent the harmonic pressure drop (e.g., the difference between harmonic pressure values ​​at two points along the vessel) or its gradient, using color overlay to display the values ​​of harmonic pressure along the vessel of interest, and / or using value overlay to display the values ​​of harmonic hemodynamic parameters on the vessel. The values ​​of the harmonic hemodynamic parameters can be used to determine features on the reference image to be displayed in the derived view. For example, based on this determination of features, the display 240 can present a graph to the user showing the values ​​of harmonic hemodynamic parameters as a function of the vessel geometry or the location on a reference angiography (i.e., the relationship between the values ​​of the harmonic hemodynamic parameters and changes in the vessel geometry or the location on the reference angiography). Based on this displayed graph, the user can determine (select) the length of the stent to be deployed in the vessel.

[0132] In at least one embodiment, optimization routine 570 modifies one or more parameters (also referred to herein as "common parameters") shared by two or more physical models 550 corresponding to a state, which are used by optimization routine 570 for optimization. When measurements from multiple states are used for optimization, and therefore outputs from multiple physical models 550 are used during optimization in step 570, the common parameters can be shared between optimization routine 570 and at least two physical models 550a, 550b, 550c, 550d, each physical model corresponding to a state. Common parameters can be, for example, the boundary conditions and / or geometry of blood vessel 110. Optimization routine 570 can set an objective function for all physical model outputs corresponding to the state of blood vessel 110 used for optimization. For example, it may be shared between two or all physical models when any common parameter changes. The objective function then minimizes the error of the objective function by taking into account all outputs 555 of all physical models 550 involved, and the shared common parameters used when executing physical models 550. In at least one embodiment, method 500 may include sharing at least one common parameter between at least two physical models when executing physical models of two or more states of a blood vessel. The first, second, third, and fourth physical models 550a, 550b, 550c, and 550d may be part of a coupled (common) physical model having a common system of equations (the first, second, third, and fourth physical models 550a, 550b, 550c, and 550d may form a coupled (common) physical model having a common system of equations).

[0133] For example, CFR can be calculated based on harmonic pressures obtained under at least two conditions (pre-PCI congestion and rest). IMR can be calculated based on calculated blood flow. In at least one embodiment, absolute resistance can be calculated based on harmonic pressures in step 580. Diastolic pressure ratio (dPR) can be defined as the mean distal pressure P during resting diastole. d With mean aortic pressure P a The ratio of FFR to distal pressure during congestion (P0.05). d ) and proximal pressure (P a The ratio of absolute flow rate to absolute resistance. Absolute flow rate can be determined as the inflow rate into the coronary artery or any branch, expressed in ml / s. Absolute resistance can be determined as the pressure drop across a segment of vessel 110 for a given absolute flow rate, expressed in mmHg / ml / s.

[0134] In at least one embodiment, a harmonic pressure field is also generated in step 580. The harmonic pressure field includes harmonic pressure values ​​determined by optimization procedure 570, which takes into account... Figure 5BThe results are the outputs of one or more physical models 550a, 550b, 550c, 550d shown. To display the harmonic pressure field, processor 210 can generate a combined output image 275 (also referred to herein as "harmonic pressure field image 275"). The combined output image 275 can be generated by overlaying the harmonic pressure values ​​(determined by optimization routine 570) with one of the measured angiographic images 220, 222 or a reconstructed geometry 545 of vessel 110 (e.g., a 3D modeled image). The combined output image 275 can have the same size / shape as the contrast-enhanced angiographic image 220, and has a background 431 and vessel 110, where the background 431 is displayed as black (which may be referred to as "0" or "(0,0,0)" in RGB). Vessel 110 can be displayed as white (which may correspond to "1" or "255", depending on the number of bits) and various colors representing the harmonic pressure values ​​along the vessel. Therefore, various colors and / or color gradients and / or color codes can visually represent (visualize) the values ​​of harmonic pressure and harmonic pressure field relative to the geometry of the blood vessel and the reconstructed geometry 545. Thus, colors and color codes can help users quickly visually identify the pressure drop in blood vessel 110. When displaying the combined output image 275, system 200 can also visually highlight the location of the pressure drop in blood vessel 110 on the combined output image 275.

[0135] Figure 5B An example of a combined output image 275 according to at least one embodiment is shown. The background 431 of the combined output image 275 may be dark (e.g., black), while the blood vessels 110 may be represented by a brighter color, thereby representing a change or gradient of color in the blood vessels, which in turn represents the blood pressure value along the blood vessels in signal form (shown). Figure 5B Another example of a combined output image is also shown—an inverted combined output image 276, in which the colors of combined output image 275 are inverted, with darker colors representing blood vessels and white representing the background. In at least one embodiment, combined output image 275 can be generated, and the system can display a visual representation of the harmonic stress values, which are superimposed on the reconstructed geometry and represent the harmonic stress field.

[0136] The processor 210 then renders one or more harmonic hemodynamic parameters and / or combined output images 275 onto the display 240 and displays them to the user (operator, clinician) for decision-making. Based on the harmonic hemodynamic parameters and / or combined output images 275, the clinician can assess the condition of the vessel 110 and determine whether any PCI and / or treatment is needed. For example, if the measurements are only completed before any PCI, the clinician can decide whether any PCI is needed, or the clinician can determine whether the PCI was successful and no additional intervention or other treatment is required.

[0137] The values ​​of harmonized hemodynamic parameters 270 can help generate indications of a patient's condition, such as microvascular occlusion (MVO) characterizing myocardial microvascular injury and dysfunction. For example, processor 210 can determine the severity of MVO based on calculated IMR values ​​and display an indication of the MVO rate or that the patient has MVO, along with the calculated IMR. The harmonized pressure distribution field determined by processor 210 can help select and recommend stent location and length to improve CFR and FFR values. To this end, processor 210 can perform calculations using the harmonized pressure distribution and a set of recommended locations and lengths for stent 120.

[0138] Refer again Figure 5B The optimization routine 570 can generate output data such as harmonized pressure, flow rate, 3D geometry of the blood vessels (reconstructed geometry object 545), and boundary conditions, and transmit them to the display routine 585. The inflow boundary condition can be, for example, the flow rate determined at the location of the proximal pressure sensor 312, and can be adjusted during the execution of the optimization routine 570. The outflow boundary condition can be, for example, microvascular resistance, and can also be adjusted via the optimization routine 570. When the display routine 585 is executed, the display 240 can present (show) the values ​​of the harmonized hemodynamic parameters.

[0139] The method described herein allows for the acquisition of a representation of the pressure field within blood vessel 110, which allows for the determination of the location of the pressure drop within blood vessel 110. It is difficult to determine the location of the pressure drop using currently known blood pressure measurement methods because they do not allow for the accurate measurement of blood pressure within blood vessel 110 with acceptable precision.

[0140] Figure 7 A method 700 for determining hemodynamic parameters according to at least one embodiment of the present disclosure is shown. (Refer again) Figure 1D , 2 As shown in 5A, 5B and 6A, Figure 7 Method 700 can be executed by system 200, which includes processor 210 communicating with intravascular pressure measurement device 300 and extravascular imaging device 215. In step 710, extravascular imaging device 215 acquires a first set of contrast-enhanced angiographic images 220a of a blood vessel 110 containing contrast agent. In step 712, a reconstructed geometric object 545 of blood vessel 110 is generated based on the first set of contrast-enhanced angiographic images 220a. In step 715, processor 210 estimates a first blood flow in blood vessel 110 based on the first set of contrast-enhanced angiographic images 220a. In step 716, intravascular pressure measurement device 300 acquires a first set of blood pressure values ​​225a as a function of position within blood vessel 110. Extravascular imaging device 215 acquires a first set of pressure-measuring angiographic images 222a of blood vessel 110.

[0141] In step 718, processor 210 determines a first set of output parameters 555a based on a first set of blood pressure values ​​225a and a first set of blood flow. In at least one embodiment, the first set of blood pressure values ​​225a is registered with a first set of pressure measurement angiographic images 222a. Processor 210 uses reconstructed geometry objects 545a to implement a first physical model 550a of blood distribution in blood vessel 110. In step 720, harmonic hemodynamic parameters are generated based on the first set of output parameters 555a.

[0142] The first set of contrast agent angiography images 220a, the first set of blood pressure values ​​225a, and the first set of pressure measurement angiography images 222a can be obtained during the congestion state of the blood vessel 110, which contains a congesting agent.

[0143] When a vasculature 110 contains a vasculature agent, the extravascular imaging device 215 can acquire a second set of contrast-enhanced angiographic images 220b of the vasculature 110 containing both the contrast agent and the vasculature agent. Based on the second set of contrast-enhanced angiographic images 220b, the processor 210 can estimate a second blood flow in the vasculature 110. The intravascular pressure measurement device 300 can acquire a second set of blood pressure values ​​225b as a function of the position within the vasculature 110 containing the vasculature agent, and can acquire a second set of pressure-measured angiographic images 222b of the vasculature 110 using the extravascular imaging device 215. The processor 210 can determine a second set of output parameters 550b based on the second blood flow and the second set of blood pressure values ​​225b by implementing a second physical model 550b of the blood distribution in the vasculature 110 and using a reconstructed geometry object 545. The second set of blood pressure values ​​225b can be registered with the second set of pressure-measured angiographic images 222b. The processor 210 can use the second set of output parameters 555b when adjusting the harmonic hemodynamic parameters. The harmonized hemodynamic parameters can be adjusted based on the first set of output parameters 555a and the second set of output parameters 505b.

[0144] After stent 120 is implanted in vessel 110 or after another PCI, a third set of contrast-enhanced angiographic images 220c of vessel 110 containing contrast agent is obtained. The system can determine a third set of output parameters 555c based on a third set of blood pressure values ​​225c and a third blood flow determined based on the third set of contrast-enhanced angiographic images 220c acquired when contrast agent is present in vessel 110. In some embodiments, the third set of blood pressure values ​​225c can be registered with a third set of pressure measurement angiographic images 222c. Processor 210 can use reconstructed geometry object 545 to implement a third physical model 550c of blood distribution in vessel 110. In addition to the previously determined first and second sets of output parameters 555a, 555b, the harmonized hemodynamic parameters can be further adjusted based on the third set of output parameters 555c.

[0145] like Figure 6A As shown, the fourth state of vessel 110 can be post-PCI congestion. Using the fourth physical model routine of processor 210, the fourth set of output parameters 555d can be determined based on the fourth set of blood pressure values ​​225d and the fourth blood flow. The fourth set of blood pressure values ​​225d can be registered with the fourth set of pressure measurement angiography images 222d, and the fourth blood flow is estimated based on the fourth set of contrast-enhanced angiography images 220 with contrast agent measured by extravascular imaging device 215. Using the geometric data 535 determined for the fourth state, a fourth physical model of blood distribution in vessel 110 can be implemented using reconstructed geometry 545 and the fourth blood flow. The harmonized hemodynamic parameters can be further adjusted based on the fourth set of output parameters 555d.

[0146] While preferred embodiments have been described above and illustrated in the accompanying drawings, those skilled in the art will understand that various modifications can be made without departing from the scope of this disclosure. Such modifications are considered possible variations within the scope of this disclosure.

Claims

1. A method executable by a system including a processor communicating with an intravascular pressure measurement device and an extravascular imaging device, characterized in that, The method includes: The extracavitary imaging device is used to acquire a first set of contrast-induced vascular angiography images of the blood vessels containing the contrast agent. The reconstructed geometric object of the blood vessel is generated based on the first set of contrast agent angiography images; Based on the first set of contrast-enhanced angiography images, the first blood flow in the blood vessel is estimated; The first set of blood pressure values ​​was collected using the intravascular pressure measuring device. A first physical model of blood distribution in the blood vessel is realized by using the reconstructed geometric object, and a first set of output parameters is determined by the processor based on the first set of blood pressure values ​​and the first blood flow rate; and Harmonized hemodynamic parameters are generated based on the first set of output parameters.

2. The method according to claim 1, characterized in that, During the congestion of the blood vessel, the first set of contrast agent angiography images and the first set of blood pressure values ​​are acquired, the blood vessel containing the congestant.

3. The method according to any one of claims 1 or 2, characterized in that, The first set of blood pressure values ​​is a function of the location within the blood vessel.

4. The method according to any one of claims 1 to 3, characterized in that, It also includes acquiring a first set of pressure measurement angiography images of the blood vessel through the extracavitary imaging device, and registering the first set of blood pressure values ​​with the first set of pressure measurement angiography images.

5. The method according to any one of claims 1 to 5, characterized in that, It also includes determining the first set of output parameters by the processor based on a first set of blood pressure values ​​registered with the first set of pressure measurement angiography images.

6. The method according to any one of claims 1 to 5, characterized in that, The method further includes, when the blood vessel contains a vasodilator: A second set of contrast agent angiography images of blood vessels containing the contrast agent and the vasodilator are acquired using the extracavitary imaging device; Based on the second set of contrast-enhanced angiography images, the second blood flow in the blood vessel is estimated; A second set of blood pressure values ​​is collected from the blood vessels containing the engorgement agent using the intravascular pressure measuring device; and By implementing a second physical model of blood distribution in the blood vessels and using the reconstructed geometry, the processor determines a second set of output parameters based on the second set of blood pressure values ​​and the second blood flow rate. The generation of the harmonized hemodynamic parameters also includes: The harmonized hemodynamic parameters are adjusted based on the first set of output parameters and the second set of output parameters.

7. The method according to claim 6, characterized in that, The second set of blood pressure values ​​is a function of the location within the blood vessel.

8. The method according to any one of claims 6 or 7, characterized in that, It also includes acquiring a second set of pressure measurement angiography images of the blood vessel through the extracavitary imaging device, and registering the second set of blood pressure values ​​with the second set of pressure measurement angiography images.

9. The method according to any one of claims 6 to 8, characterized in that, It also includes determining the second set of output parameters by the processor based on a second set of blood pressure values ​​registered with the second set of pressure measurement angiography images.

10. The method according to any one of claims 6 to 9, characterized in that, The method further includes: A third set of contrast-induced vascular angiography images were acquired using the extracavitary imaging device, which contained a stent and the contrast agent. Based on the third set of contrast agent angiography images, the third blood flow in the blood vessel is estimated; The third set of blood pressure values ​​within the blood vessel is collected using the intravascular pressure measuring device; and A third physical model of the blood distribution in the blood vessel is realized by using the reconstructed geometric object, and the processor determines a third set of output parameters based on the third set of blood pressure values ​​and the third set of blood flow. The adjustment of the harmonized hemodynamic parameters is also based on the third set of output parameters.

11. The method according to claim 10, characterized in that, The third set of blood pressure values ​​is a function of the location within the blood vessel.

12. The method according to any one of claims 10 or 11, characterized in that, It also includes acquiring a third set of pressure measurement angiography images of the blood vessel through the extracavitary imaging device, and registering the third set of blood pressure values ​​with the third set of pressure measurement angiography images.

13. The method according to any one of claims 10 to 12, characterized in that, It also includes determining the third set of output parameters by the processor based on the third set of blood pressure values ​​registered with the third set of pressure measurement angiography images.

14. The method according to any one of claims 10 to 13, characterized in that, The third set of contrast agent angiography images, the third set of blood pressure values, and the third set of pressure measurement angiography images were obtained in the congested state of the blood vessels, which contain the congesting agent.

15. The method according to any one of claims 10 to 14, characterized in that, After acquiring the third set of contrast agent angiography images, and before acquiring the third set of pressure measurement angiography images and the third set of blood pressure values, at least a third time period has elapsed.

16. The method according to any one of claims 10 to 15, characterized in that, The method further includes: A fourth set of contrast-induced vascular angiography images of the blood vessels containing the stent and the contrast agent are acquired using the extracavitary imaging device. Based on the fourth set of contrast agent angiography images, estimate the fourth blood flow in the blood vessel; The fourth set of blood pressure values ​​within the blood vessel was collected using the intravascular pressure measuring device; and The processor implements a fourth physical model of blood distribution in the blood vessels by using the reconstructed geometry object, and determines a fourth set of output parameters based on the fourth set of blood pressure values ​​and the fourth set of blood flow. The adjustment of the harmonized hemodynamic parameters is also based on the fourth set of output parameters.

17. The method according to claim 16, characterized in that, The fourth set of blood pressure values ​​is a function of the location within the blood vessel.

18. The method according to any one of claims 16 or 17, characterized in that, It also includes acquiring a fourth set of pressure measurement angiography images of the blood vessel through the extracavitary imaging device, and registering the fourth set of blood pressure values ​​with the fourth set of pressure measurement angiography images.

19. The method according to any one of claims 16 to 18, characterized in that, It also includes determining the fourth set of output parameters by the processor based on the fourth set of blood pressure values ​​registered with the fourth set of pressure measurement angiography images.

20. The method according to any one of claims 1 to 16, characterized in that, The acquisition of the first set of blood pressure values ​​and the acquisition of the first set of pressure measurement angiography images of the blood vessels are performed simultaneously.

21. The method according to claim 1, characterized in that, The method further includes: The processor determines a second set of output parameters based on a second set of blood pressure values ​​containing the engorgement agent but without the contrast agent, and a second set of contrast-induced angiography images acquired when the blood vessel contains both the contrast agent and the engorgement agent. The generation of the harmonized hemodynamic parameters also includes adjusting the harmonized hemodynamic parameters based on the first set of output parameters and the second set of output parameters.

22. The method according to claim 21, characterized in that, It also includes acquiring a second set of pressure measurement angiography images of the blood vessel and registering the second set of blood pressure values ​​with the second set of pressure measurement angiography images of the blood vessel.

23. The method according to any one of claims 21 or 22, characterized in that, This also includes, after a stent is implanted in the blood vessel, the processor determines a third set of output parameters based on the following: After acquiring the second set of contrast-enhanced angiography images, at least a third time period later, the third set of blood pressure values ​​were acquired simultaneously with the acquisition of the third set of pressure-measured angiography images, and The third blood flow rate was determined based on a third set of contrast-enhanced angiography images acquired when the blood vessel contained the contrast agent; and The adjustment of the harmonized hemodynamic parameters is also based on the third set of output parameters.

24. The method according to claim 23, characterized in that, It also includes determining a fourth set of output parameters by the processor based on the following: The fourth blood flow rate was determined based on a fourth set of contrast-enhanced angiography images acquired when the blood vessel contained the contrast agent and the engorgement agent. The fourth group of blood pressure values ​​when the blood vessel contains the engorgement agent but not the contrast agent; and The adjustment of the harmonized hemodynamic parameters is also based on the fourth set of output parameters.

25. The method according to any one of claims 1 to 24, characterized in that, The first set of output parameters includes a pressure estimate along the centerline of the blood vessel.

26. The method according to any one of claims 1 to 25, characterized in that, The first physical model is a three-dimensional physical model.

27. The method according to any one of claims 1 to 25, characterized in that, The first physical model is a two-dimensional model.

28. The method according to any one of claims 1 to 25, characterized in that, The first physical model is a machine learning model.

29. The method according to any one of claims 1 to 25, characterized in that, The first physical model is a one-dimensional model.

30. The method according to any one of claims 1 to 25, characterized in that, The first physical model is a zero-dimensional model.

31. The method according to any one of claims 1 to 25, characterized in that, The first physical model is a hybrid physical model.

32. The method according to any one of claims 1 to 31, characterized in that, It also includes generating a harmonic pressure field that is a function of the location within the blood vessel.

33. The method according to any one of claims 1 to 32, characterized in that, It also includes generating and displaying a combined output image, the combined output image including a harmonic pressure value determined based on the first set of output parameters, the harmonic pressure value being superimposed on the reconstructed geometry and representing a harmonic pressure field.

34. The method according to any one of claims 1 to 33, characterized in that, It also includes generating and displaying a combined output image, which includes a visual representation of harmonic stress values ​​superimposed on the reconstructed geometry to represent a harmonic stress field.

35. The method according to any one of claims 1 to 34, characterized in that, The initial blood flow in the blood vessel is also estimated based on the reconstructed geometry of the blood vessel.

36. The method according to any one of claims 1 to 35, characterized in that, The adjustment of the harmonized hemodynamic parameters is also based on the first blood flow rate.

37. The method according to any one of claims 16 or 24, characterized in that, The adjustment of the harmonized hemodynamic parameters is also based on at least one of the first blood flow rate, the second blood flow rate, the third blood flow rate, and the fourth blood flow rate.

38. The method according to any one of claims 1 to 37, characterized in that, The first set of blood pressure values ​​includes proximal blood pressure values ​​and distal blood pressure values.

39. The method according to any one of claims 1 to 38, characterized in that, It also includes displaying the harmonized hemodynamic parameters on a monitor.

40. The method according to any one of claims 1 to 39, characterized in that, It also includes generating a harmonic pressure field as a function of the position within the blood vessel based on the first set of output parameters.

41. The method according to claim 40, characterized in that, It also includes generating a harmonic pressure field as a function of the position within the blood vessel, based on at least one of the second set of output parameters, the third set of output parameters, and the fourth set of output parameters.

42. The method according to any one of claims 1 to 41, characterized in that, The harmonized hemodynamic parameters are at least one of the following: microvascular resistance index, fractional flow reserve, coronary flow reserve, diastolic pressure ratio, absolute flow rate, absolute resistance, and absolute resistance ratio.

43. A system, characterized in that, include: An extracavitary imaging device, the extracavitary imaging device being configured to generate a first set of contrast-induced angiographic images of blood vessels containing contrast agents; An intravascular pressure measuring device, wherein the intravascular pressure measuring device is configured to measure blood pressure values ​​and generate intravascular pressure data; and The processor is configured as follows: The reconstructed geometric object of the blood vessel is generated based on the first set of contrast agent angiography images; Based on the first set of contrast-enhanced angiography images, the first blood flow in the blood vessel is estimated; A first physical model of blood distribution in the blood vessel is realized by using the reconstructed geometric object, and a first set of output parameters is determined by the processor based on the first set of blood pressure values ​​and the first blood flow. and Harmonized hemodynamic parameters are generated based on the first set of output parameters.

44. The system according to claim 43, characterized in that, It also includes a display configured to show the harmonized hemodynamic parameters and an image representing the harmonized pressure field.

45. The system according to any one of claims 43 or 44, characterized in that, The first set of blood pressure values ​​were registered with the first set of pressure measurement angiography images.

46. ​​The system according to any one of claims 43 to 45, characterized in that, The processor is also configured to: The second blood flow in the blood vessel is estimated based on a second set of contrast-enhanced angiography images acquired when the blood vessel contains the contrast agent and the vasodilator. By implementing a second physical model of blood distribution in the blood vessel and using the reconstructed geometry, a second set of output parameters is determined based on a second set of blood pressure values ​​acquired by the intravascular pressure measurement device; and The harmonized hemodynamic parameters are adjusted based on the first set of output parameters and the second set of output parameters.

47. The system according to claim 46, characterized in that, The second set of blood pressure values ​​is registered with the second set of pressure measurement angiography images acquired by the extracavitary imaging device.

48. The system according to any one of claims 46 or 47, characterized in that, The processor is also configured to: The third blood flow in the blood vessel is estimated based on a third set of contrast-enhanced angiography images acquired when the blood vessel contains the contrast agent and the vasodilator. By implementing a third physical model of blood distribution within the blood vessel and using the reconstructed geometry, a third set of output parameters is determined based on a third set of blood pressure values ​​acquired by the intravascular pressure measurement device; and The harmonized hemodynamic parameters are further adjusted based on the third set of output parameters.

49. The system according to claim 48, characterized in that, The processor is also configured to: Based on the fourth set of contrast-enhanced angiography images acquired when the blood vessel contains contrast agent, the fourth blood flow in the blood vessel is estimated; By implementing a fourth physical model of blood distribution in the blood vessels and using the reconstructed geometry, a fourth set of output parameters is determined based on a fourth set of blood pressure values ​​acquired by the intravascular pressure measurement device; and The harmonized hemodynamic parameters are further adjusted based on the fourth set of output parameters.

50. A processor communicating with an extracavitary imaging device and an intracavitary data acquisition device, the extracavitary imaging device being configured to acquire at least one angiographic image of a blood vessel, and the intracavitary data acquisition device being configured to acquire a blood pressure value within the blood vessel, characterized in that, The processor is configured to: Receive a first set of contrast-enhanced angiographic images of blood vessels containing contrast agent from the extracavitary imaging device; The device receives a first set of blood pressure values ​​from the intracavitary data acquisition device and receives a first set of pressure measurement angiography images of the blood vessels without contrast agent from the extracavitary imaging device. Based on the contrast-enhanced angiography image, a reconstructed geometric object of the blood vessel and a first blood flow are generated; A first physical model of blood distribution in the blood vessel is realized by using the reconstructed geometric object, and a first set of output parameters is determined based on the first set of blood pressure values ​​and the first blood flow. and Harmonized hemodynamic parameters are generated based on the first set of output parameters.

51. The processor according to claim 50, characterized in that, The processor is also configured to: Based on the second set of contrast-enhanced angiography images and the second set of blood pressure values, a second set of output parameters is determined. The second set of contrast-enhanced angiography images and the second set of blood pressure values ​​were acquired when there was a vasodilator in the blood vessels. and The harmonized hemodynamic parameters generated by the processor are also based on the second set of output parameters.

52. The processor according to claim 51, characterized in that, The processor is also configured to: Based on the third set of contrast-enhanced angiography images and the third set of blood pressure values, the third set of output parameters are determined. The third set of contrast-enhanced angiography images and the third set of blood pressure values ​​are acquired when there is a stent in the blood vessel. and The harmonized hemodynamic parameters generated by the processor are also based on the third set of output parameters.

53. The processor according to claim 52, characterized in that, The processor is also configured to: Based on the third set of contrast-enhanced angiography images and the fourth set of blood pressure values, a fourth set of output parameters is determined. The third set of contrast-enhanced angiography images and the fourth set of blood pressure values ​​were acquired when the blood vessel contained a stent and a vasodilator. The harmonized hemodynamic parameters generated by the processor are also based on the fourth set of output parameters.

54. A method executable by a system including a processor communicating with an extravascular imaging device and an intravascular pressure measurement device, characterized in that, The method includes: When blood vessels contain contrast agent, images of the contrast-containing blood vessels are acquired. Pressure measurement angiography images were acquired separately and for the same blood vessel without contrast agent, and intravascular pressure values ​​were collected. Reconstruct the geometry of the blood vessels and apply the physical model to the reconstructed geometric objects; and Harmonized hemodynamic parameters are generated and adjusted based on contrast-enhanced angiography images, pressure-measured angiography images, and intravascular pressure values ​​acquired when the vessel is in at least two of the following vascular states: pre-percutaneous coronary intervention (PCI) rest, pre-PCI hyperemia, post-PCI hyperemia, and post-PCI rest.

Images