Method and system for determining hemodynamic parameters

Abstract

A method that can be performed by a system including a processor that communicates with an extravascular imaging device and an intravascular pressure measuring device. The method includes the steps of: acquiring contrast-enhanced angiography images of blood vessels in which contrast agent is present; generating reconstructed geometric objects of blood vessels and estimating blood flow within the blood vessels based on the contrast-enhanced angiography images; determining output parameters based on blood pressure values ​​and blood flow by implementing a physical model of blood distribution using the reconstructed geometric objects; and generating hemodynamic parameters adjusted based on the output parameters. The adjusted hemodynamic parameters are adjusted based on measurements made in various vascular conditions.

Description

[Technical Field]

[0001] This disclosure relates to a method and system for evaluating hemodynamic function. More specifically, it relates to a method and system for determining hemodynamic parameters by combining an intravascular pressure measuring device and a medical imaging diagnostic device. [Background technology]

[0002] Coronary artery disease can be diagnosed by evaluating 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 coronary arteries, which are the blood vessels that supply blood to the heart. Coronary artery stenosis can occur in both thickened and narrowed coronary arteries and can cause angina pectoris, which manifests as chest pain in patients.

[0003] Various hemodynamic parameters (sometimes called "hemodynamic volumes") may be used to determine and characterize coronary artery stenosis. For example, the ratio of coronary flow reserve (FFR) determines the ratio of the maximum blood flow passing through an occluded (stenotic) portion of a coronary artery to the theoretical maximum blood flow in the same coronary artery if there is no occlusion. Another hemodynamic parameter that is useful for assessing the state of the coronary arteries is the coronary flow reserve (CFR). The CFR value provides an estimate of the blood flow throughout the epicardial vessels and microvessels.

[0004] The microvascular resistance index (IMR) is a hemodynamic parameter that reflects the microvascular function of the coronary arteries, which are associated with the smallest blood vessels. Estimating the IMR can reveal the characteristics of blood flow in the microvessels. Currently known methods for measuring IMR yield inaccurate or ambiguous results. [Overview of the Initiative]

[0005] According to one aspect of the disclosed technology, a method is provided that can be performed by a system including a processor that communicates with an intravascular pressure measuring device and an extravascular imaging device. The method includes the steps of: obtaining a first set of contrast-enhanced angiography images of a blood vessel in which a contrast agent is present, using the extravascular imaging device; generating a reconstructed geometric object of the blood vessel based on the first set of contrast-enhanced angiography images; estimating a first blood flow within the blood vessel based on the first set of contrast-enhanced angiography images; obtaining a first set of blood pressure values, using the intravascular pressure measuring device; determining a first set of output parameters based on the first set of blood pressure values ​​and the first blood flow, using the reconstructed geometric object, using the processor; and generating adjusted hemodynamic parameters based on the first set of output parameters.

[0006] A first set of contrast-enhanced angiography images and a first set of blood pressure values ​​may be acquired while the blood vessel is hyperemic and the hyperemetic agent is present within the vessel. In at least one embodiment, the first set of blood pressure values ​​may be acquired as a function of the position within the vessel. The first set of blood pressure values ​​may be a function of the position within the vessel. The method may further include acquiring a first set of pressure-measuring angiography images of the vessel by an extravascular imaging device. The first set of blood pressure values ​​may be aligned with the first set of pressure-measuring angiography images. The method may further include the step of a processor determining a first set of output parameters based on the first set of blood pressure values ​​aligned with the first set of pressure-measuring angiography images. The method may include, when an engorgement agent is present in the blood vessel, the steps of: acquiring a second set of contrast-enhanced angiographic images of the blood vessel containing the contrast agent and the engorgement agent using an extravascular imaging device; estimating a second blood flow in the blood vessel based on the second set of contrast-enhanced angiographic images; acquiring a second set of blood pressure values ​​in the blood vessel containing the engorgement agent using an intravascular pressure measuring device; and determining a second set of output parameters based on the second set of blood pressure values ​​and the second blood flow by implementing a second physical model of the blood distribution in the blood vessel using a reconstructed geometric object using a processor, further comprising the step of generating adjusted hemodynamic parameters, which adjusts the adjusted 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 position in the blood vessel. The method may further include the steps of acquiring a second set of pressure-measuring angiographic images of the blood vessel using an extravascular imaging device and aligning the second set of blood pressure values ​​with the second set of pressure-measuring angiographic images. This method may further include the step of determining a second set of output parameters based on a second set of blood pressure values ​​aligned with a second set of pressure-measuring angiographic images by a processor.

[0007] The method may further include the steps of: obtaining a second set of blood pressure values ​​as a function of the location within the vessel where the engorgement agent is present, using an intravascular pressure measuring device when an engorgement agent is present within the vessel; obtaining a second set of pressure-measuring angiography images of the vessel using an extravascular imaging device; obtaining a second set of contrast-enhanced angiography images of the vessel where the contrast agent and engorgement agent are present, using an extravascular imaging device; estimating a second blood flow within the vessel based on the second set of contrast-enhanced angiography images; determining a second set of output parameters based on a second set of blood pressure values ​​that can be aligned with the second set of pressure-measuring angiography images by implementing a second physical model of the blood distribution within the vessel using reconstructed geometric objects using a processor; and generating adjusted hemodynamic parameters. The adjusted hemodynamic parameters are adjusted based on the first set of output parameters and the second set of output parameters.

[0008] The method may further include the steps of: acquiring a third set of contrast-enhanced angiographic images of the vessel containing the stent and contrast agent using an extravascular imaging device after a stent has been placed in the vessel or after another percutaneous coronary intervention; 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 ​​in the vessel using an intravascular pressure measuring device; and determining a third set of output parameters based on the third blood flow and the third set of blood pressure values ​​by implementing a third physical model of the blood distribution in the vessel using reconstructed geometric objects using a processor, wherein the steps of adjusting the adjusted hemodynamic parameters are performed based on the third set of output parameters. The third set of blood pressure values ​​may be a function of position in the vessel and / or may be measured as a function of position. The method may further include acquiring a third set of pressure-measuring angiographic images of the vessel using an extravascular imaging device and aligning the third set of blood pressure values ​​with the third set of pressure-measuring angiographic images. The method may further include the step of determining a third set of output parameters based on a third set of pressure-measuring angiography images and a third set of blood pressure values ​​aligned by a processor. The third set of contrast-enhanced angiography images, the third set of blood pressure values, and the third set of pressure-measuring angiography images may be acquired while the blood vessels are engorged and the engorgement agent is present in the blood vessels. At least a third period may elapse after the acquisition of the third set of contrast-enhanced angiography images and before the acquisition of the third set of pressure-measuring angiography images and the third set of blood pressure values.

[0009] The method further includes the steps of: acquiring a fourth set of contrast-enhanced angiography images of the vessel containing the stent and contrast agent using an extravascular imaging device; estimating a fourth intravascular blood flow based on the fourth set of contrast-enhanced angiography images; acquiring a fourth set of intravascular blood pressure values ​​using an intravascular pressure measuring device; and determining a fourth set of output parameters based on the fourth set of blood pressure values ​​and the fourth blood flow by implementing a fourth physical model of intravascular blood distribution using reconstructed geometric objects using a processor, wherein the steps of adjusting the adjusted hemodynamic parameters are further performed based on the fourth set of output parameters. The fourth set of blood pressure values ​​may be a function of intravascular location and / or can be measured as a function of intravascular location. The method may further include the steps of: acquiring a fourth set of pressure-measuring angiography images of the vessel using an extravascular imaging device and aligning the fourth set of blood pressure values ​​with the fourth set of pressure-measuring angiography images. This method may further include the step of determining a fourth set of output parameters based on a fourth set of blood pressure values ​​aligned with a fourth set of pressure-measuring angiographic images by a processor.

[0010] In some embodiments, the step of acquiring a fourth blood pressure value set and a fourth pressure measurement angiography image set is performed at least a fourth period after acquiring the fourth contrast agent angiography image set.

[0011] The step of acquiring a first set of blood pressure values ​​may be performed simultaneously with the step of acquiring a first set of pressure-measuring angiographic images of the blood vessels. In at least one embodiment, the step of acquiring a second set of blood pressure values ​​may be performed simultaneously with the step of acquiring a second set of pressure-measuring angiographic images of the blood vessels. The step of acquiring a third set of blood pressure values ​​may be performed simultaneously with the step of acquiring a third set of pressure-measuring angiographic images of the blood vessels. In at least one embodiment, the step of acquiring a fourth set of blood pressure values ​​may be performed simultaneously with the step of acquiring a fourth set of pressure-measuring angiographic images of the blood vessels.

[0012] The method further includes the step of a processor determining a second set of output parameters based on a second set of blood pressure values ​​in which a vasoconstrictor is present but a contrast agent is absent (in other words, a set of blood pressure values ​​obtained after a second period has elapsed since the acquisition of the first set of contrast-enhanced angiography images) and a second blood flow determined from a second set of contrast-enhanced angiography images obtained when the contrast agent and vasoconstrictor are present in the blood vessels, and the step of generating adjusted hemodynamic parameters further includes the step of adjusting the adjusted hemodynamic parameters based on the first set of output parameters and the second set of output parameters. The method may further include the step of acquiring a second set of pressure-measuring angiography images of the blood vessels and the step of aligning a second set of blood pressure values ​​with the second set of pressure-measuring angiography images of the blood vessels.

[0013] The method further includes the step of a processor acquiring a third pressure measurement angiography image set at least a third period after a second contrast angiography image set has been acquired after the stent has been placed in the blood vessel, and determining a third output parameter set based on the acquired third blood pressure value set and a third blood flow determined from the third contrast angiography image set acquired while the contrast agent was present in the blood vessel, wherein the step of adjusting the adjusted hemodynamic parameters is further performed based on the third output parameter set.

[0014] The method may further include the processor determining a fourth set of output parameters based on a fourth blood flow determined from a fourth set of contrast-enhanced angiography images acquired when contrast and hypothermia are present in the blood vessels, and a fourth set of blood pressure values ​​that can be recorded in a fourth set of pressure-measuring angiography images acquired when hypothermia is present in the blood vessels but contrast is absent (at least a fourth period has elapsed since the acquisition of the fourth set of contrast-enhanced angiography images), wherein the step of adjusting the adjusted hemodynamic parameters is further based on the fourth set of output parameters.

[0015] The first set of output parameters may include pressure estimates along the centerline of the blood vessels. The first physical model may be a 3D, 2D, 1D, or 0D physical model. The first, second, third, and / or fourth physical models may be 3D, 2D, 1D, or 0D 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 the step of generating a tuned pressure field as a function of position within a blood vessel. The method may further include the step of generating and displaying a composite output image containing tuned pressure values ​​that represent the tuned pressure field, which are determined based on a first output parameter and superimposed on a reconstructed geometric image. The method may further include the step of generating and displaying a composite output image containing a visual representation of the tuned pressure values ​​that represents the tuned pressure field, which are superimposed on a reconstructed geometric object. The step of estimating a first blood flow within a blood vessel may further be based on the reconstructed geometric object of the blood vessel. The step of adjusting the tuned hemodynamic parameters may further be based on the first blood flow. The step of adjusting the tuned hemodynamic parameters may further be based on at least one of the first, second, third, and fourth blood flows. In at least one embodiment, the first set of blood pressure values ​​includes proximal and distal blood pressure values. The method may further include the step of displaying the tuned hemodynamic parameters on a display.

[0017] The tuned pressure field can be generated as a function of intravascular position based on a first set of output parameters, a second set of output parameters, a third set of output parameters, and / or a fourth set of output parameters. The method may further include the step of generating a tuned pressure field as a function of intravascular position based on a fourth set of output parameters. The method may further include the step of generating a tuned pressure field as a function of intravascular position based on at least one of the first set of output parameters, a second set of output parameters, a third set of output parameters, and a fourth set of output parameters.

[0018] The adjusted hemodynamic parameters may be at least one of the following: microvascular resistance index, flow reserve ratio, 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 angiography images of a blood vessel in which a contrast agent is present; an intravascular pressure measuring device configured to measure blood pressure values ​​that can be measured as a function of position within a blood vessel and generate intravascular pressure data; and a processor, wherein the processor is configured to generate a reconstructed geometric object of a blood vessel based on a set of first contrast-enhanced angiography images, estimate a first blood flow within a blood vessel based on the first set of contrast-enhanced angiography images, and implement a first physical model of blood distribution within a blood vessel using the reconstructed geometric object, thereby determining a first set of output parameters based on a first set of blood flow and a first set of blood pressure values ​​that can be aligned with a first set of pressure-measuring angiography images, and generating hemodynamic parameters adjusted based on the first set of output parameters.

[0020] In at least one embodiment, the system further comprises an adjusted hemodynamic parameter and a display configured to display an image representing the adjusted pressure field. The processor further estimates a second blood flow within the blood vessel based on a second set of contrast agent angiography images acquired when a contrast agent and a vasodilator are present in the blood vessel, and implements a second physical model of blood distribution within the blood vessel using the reconstructed geometric object, thereby obtaining a second set of blood pressure values acquired by an intravascular pressure measuring device, i.e., a second set of output parameters based on a second set of blood pressure values that can be aligned with a second set of pressure measurement angiography images acquired by an extravascular imaging device, and may be configured to adjust the adjusted hemodynamic parameter based on the first set of output parameters and the second set of output parameters.

[0021] The processor further estimates a third blood flow within the blood vessel based on a third set of contrast agent angiography images acquired when a contrast agent is present in the blood vessel, and implements a third physical model of blood distribution within the blood vessel using the reconstructed geometric object, thereby obtaining a third set of blood pressure values acquired by an intravascular pressure measuring device, i.e., a third set of output parameters based on a third set of blood pressure values that can be aligned with a third set of pressure measurement angiography images acquired by an extravascular imaging device, and may be configured to adjust the adjusted hemodynamic parameter based on the third set of output parameters.

[0022] The processor further estimates a fourth blood flow within the blood vessel based on a fourth set of contrast agent angiography images acquired when a contrast agent is present in the blood vessel, and implements a fourth physical model of blood distribution within the blood vessel using the reconstructed geometric object, thereby obtaining a fourth set of blood pressure values acquired by an intravascular pressure measuring device, i.e., a fourth set of output parameters based on a fourth set of blood pressure values that can be aligned with a fourth set of pressure measurement angiography images acquired by an extravascular imaging device, and may be configured to adjust the adjusted hemodynamic parameter based on the fourth set of output parameters.

[0023] According to a further aspect of the disclosed technology, a processor is provided that communicates with an extracorporeal imaging device and an intravascular data acquisition device. The extracorporeal imaging device is configured to acquire at least one angiographic image of a blood vessel, the intravascular data acquisition device is configured to acquire a blood pressure value within the blood vessel, and the processor receives, from the extracorporeal imaging device, a first set of contrast agent angiographic images within the blood vessel where the contrast agent is present, receives, from the intravascular data acquisition device, a first set of blood pressure values that may be a function of the positions within the blood vessel, receives, from the extracorporeal imaging device, a first set of pressure measurement angiographic images within the blood vessel where no contrast agent is present, generates a reconstructed geometric object of the blood vessel and a first blood flow based on the contrast agent angiographic images, and implements a first physical model of the blood distribution within the blood vessel using the reconstructed geometric object to determine a first set of output parameters based on the first set of blood pressure values and the first blood flow that can be aligned with the first set of pressure measurement angiographic images, and generates adjusted hemodynamic parameters based on the first set of output parameters.

[0024] The processor is further configured to determine a second set of output parameters based on a second set of contrast agent angiographic images and a second set of blood pressure values that can be aligned with a second set of pressure measurement angiographic images acquired when a vasodilator is present within the blood vessel, and the generation of the adjusted hemodynamic parameters by the processor is further based on the second set of output parameters. The processor is further configured to determine a third set of output parameters based on a third set of contrast agent angiographic images and a third set of blood pressure values that can be aligned with a third set of pressure measurement angiographic images acquired when a stent is present within the blood vessel, and the generation of the adjusted hemodynamic parameters by the processor is further based on the third set of output parameters.

[0025] The processor is further configured to determine a fourth set of output parameters based on a fourth set of contrast-enhanced angiography images and a fourth set of pressure-measuring angiography images acquired when a stent and hypnotic agent were present in the blood vessel, and the generation of adjusted hemodynamic parameters by the processor is further based on the fourth set of output parameters.

[0026] A further aspect of the disclosed technology provides a method that can be performed by a system having a processor that communicates with an extravascular imaging device and an intravascular pressure measuring device, the method comprising the steps of: acquiring a contrast-enhanced angiographic image when a contrast agent is present in the vessel; separately for the same vessel, acquiring a pressure-measuring angiographic image without a contrast agent (or at a significantly low concentration of a contrast agent) and acquiring intravascular pressure values ​​(which may be measured by measuring proximal and distal blood pressure values ​​and which may be measured as a function of position); reconstructing the geometry of the vessel and applying a physical model to the reconstructed geometric object that can be aligned with intravascular pressure values; generating adjusted hemodynamic parameters and adjusting the adjusted hemodynamic parameters based on contrast-enhanced angiographic images, pressure-measuring angiographic images and intravascular pressure values ​​acquired when the vessel is in at least two of the following vascular states: resting before percutaneous coronary intervention (PCI), hyperemia before PCI, hyperemia after PCI, and resting after PCI.

[0027] According to one aspect of the disclosed technology, the method described herein includes the steps of: acquiring a contrast-enhanced angiographic image of a blood vessel in which a contrast agent is present; acquiring a pressure-measuring angiographic image while measuring blood pressure values; generating a reconstructed geometric object of the blood vessel and estimating blood flow within the blood vessel based on the contrast-enhanced angiographic image; determining output parameters based on blood pressure values ​​and blood flow that can be aligned with the pressure-measuring angiographic image by implementing a physical model of blood distribution using the reconstructed geometric object; and generating hemodynamic parameters adjusted based on the output parameters. The adjusted hemodynamic parameters are adjusted based on measurements made in various vascular conditions. [Brief explanation of the drawing]

[0028] Further features and advantages of this disclosure will become apparent from the following detailed description in conjunction with the attached drawings. [Figure 1A] Figure 1A shows a portion of a blood vessel, such as a coronary artery, into which a guidewire has been inserted, according to at least one embodiment of the present disclosure. [Figure 1B] Figure 1B shows a portion of the coronary artery tree, including two coronary arteries. [Figure 1C] Figure 1C shows the coronary artery of Figure 1A with a stenotic section. [Figure 1D] Figure 1D shows the coronary artery in Figure 1A with a stent. [Figure 2] Figure 2 schematically illustrates a system for determining and displaying a patient's condition according to at least one embodiment of the present disclosure. [Figure 3] Figure 3 schematically shows an intravascular data acquisition device that can be used with the system of Figure 2 according to at least one embodiment of the present disclosure. [Figure 4A] Figure 4A shows a contrast-enhanced angiography image obtained according to at least one embodiment of the present disclosure. [Figure 4B] Figure 4B shows a mask of the angiographic image of Figure 4A generated in the segmentation step according to at least one embodiment of the present disclosure. [Figure 5A] Figure 5A schematically illustrates a method for determining signs of a patient's condition according to at least one embodiment of the present disclosure. [Figure 5B] Figure 5B illustrates another step of the method of Figure 5A according to at least one embodiment of the present disclosure. [Figure 6A] Figure 6A schematically shows a time chart of an implementation of a method for determining hemodynamic parameters according to at least one embodiment of the present disclosure. [Figure 6B] Figure 6B schematically shows a time chart of another embodiment of a method for determining hemodynamic parameters according to at least one embodiment of the present disclosure. [Figure 7] Figure 7 is a flowchart of a method for determining hemodynamic parameters according to at least one embodiment of the present disclosure.

[0029] Please note that similar features are indicated by the same reference numbers throughout the attached drawings. [Modes for carrying out the invention]

[0030] 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 adjusted hemodynamic parameters and images showing the patient's condition, based on blood flow calculations, invasive pressure measurements, and angiographic images. The methods described herein use intravascular pressure measurements, angiographic images, and physical models to generate adjusted hemodynamic parameters and adjusted pressure fields within blood vessels.

[0031] Referring to the drawings, Figures 1A and 1B show a portion of the vessel 110, particularly a portion of the coronary artery having a lumen 112. Figure 1B shows a portion of the coronary artery containing multiple vessels. Figure 1C shows a portion of the coronary artery with a stenosis. Figure 1D shows the coronary artery of Figure 1A with a stent 120. Figures 1A through 1D show the microvascular resistance RM. The microvascular resistance index (IMR) characterizes the microvascular resistance of the vessel 110 and is related to the microvascular resistance RM as is known in the art. In simplified terms, assuming that coronary blood flow and myocardial blood flow are equal and the contribution of collateral flow is negligible, the IMR can be estimated as distal coronary pressure divided by mean coronary transit time.

[0032] Currently known methods for measuring coronary artery resistance (IMR) include invasive and non-invasive methods. In invasive methods, a fluid cooler than the patient's body temperature is injected into the blood vessels (110) to measure the temperature and pressure within the coronary arteries. Non-invasive methods include using angiography to assess microvascular dysfunction in the coronary arteries and theoretically calculating IMR. However, such methods have low reliability because they require the use of many hypotheses and inaccurate assumptions. For example, calculating IMR based solely on angiographic images requires assuming that the effect of hypertensive agents on microvascular resistance is equal to the population mean, or that distal pressure can be accurately estimated from non-invasively obtained fractional flow reserve (FFR) values.

[0033] The methods and systems described herein enable the construction of a blood flow model within a patient's blood vessel 110 using both invasive and non-invasive steps, and the adjustment of that model based on measurements taken within the blood vessel 110. In some embodiments, such adjustment of the model may be performed in real time based on real-time measurements taken within the blood vessel 110. The methods and systems described herein may help improve the accuracy of the obtained IMR values.

[0034] It should be noted that coronary arteries are just one example of blood vessels, and the methods described herein may be used for any other blood vessels. For example, the methods described herein may be used to assess microvascular diseases of blood vessels located in other parts of the body, such as the legs. Pulmonary circulation may also be assessed using the methods and systems described herein. Thus, in this specification, “blood vessels” may refer to, but are not limited to, the blood vessels of the coronary arteries, peripheral arteries, and pulmonary circulation, for example.

[0035] Figure 2 schematically shows a system 200 according to at least one embodiment of the present disclosure. The system 200 comprises a processor 210 that communicates with an extravascular imaging device 215. The extravascular 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 extravascular imaging device 215 may be configured to acquire a video including a sequence of angiographic images. In some embodiments, the coordinate system xyz may be non-standard.

[0036] The system 200 also includes an intravascular data acquisition device 300 (also referred to herein as the “intravascular pressure measuring device”) configured to move through the blood vessel 110 to acquire intravascular pressure measurements 225 of the blood vessel 110 (in other words, blood pressure values ​​225 at various locations in the blood vessel 110). The intravascular data acquisition device 300 is connected to the processor 210 and transmits the pressure measurements 225 to the processor 210. Based on the contrast angiography image 220 and the pressure measurements received from the intravascular data acquisition device 300, the processor 210 determines one or more adjusted hemodynamic parameters and displays the adjusted hemodynamic parameters on the display 240. The display 240 may be a touchscreen display, and / or the system 200 may have additional input devices. Referring to Figure 2, the system 200 also includes a memory 212 for storing computer executable instructions, configured to store computer executable instructions that can be executed by the processor 210. The memory 212 may be implemented as a computer-readable storage medium such as read-only memory, a hard disk drive (HDD), a solid-state drive (SSD), or a flash memory card. The database 230 may be used optionally, as described later. The processor 210 also has communication ports for performing logical operations on signals.

[0037] Figure 3 shows a non-limiting example of an intravascular data acquisition device 300 (a so-called pressure guidewire) that may be used to acquire pressure measurements in system 200. The intravascular data acquisition device 300 comprises a distal pressure sensor 310 positioned on the distal end 315 of a pressure guidewire 305 or catheter and reaching a blood vessel 110 through the cardiovascular system of the patient 302. See also Figures 1A-1C, the 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 the distal pressure sensor 310 with respect to the geometry of the blood vessel, including but not limited to the length of the blood vessel. Thus, the distal pressure sensor 310 of the intravascular data acquisition device 300 is configured to measure blood pressure values ​​225 as a function of position within the blood vessel 110. Position may be measured as coordinates (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 within the blood vessel 110, such as the point where the distal pressure sensor 310 enters the blood vessel 110. In at least two embodiments, the blood pressure value 225 is measured as a function of time (t) and time-stamped.

[0038] The catheter 307 has a proximal pressure sensor 312, which may be positioned at the entrance of the blood vessel 110 while measuring the distal pressure within the blood vessel 110. Measurement of the 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 positioned at approximately the same height.

[0039] Thus, the catheter 307, equipped with a guidewire 305 positioned within the catheter 306, measures proximal pressure Pa and distal pressure Pd together. Proximal and distal pressures can be measured simultaneously (synchronously). In at least one embodiment, the signals 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 of the two measurements of distal pressure 527 and proximal pressure 529 are synchronized and sampled at a predetermined frequency. For example, such a predetermined frequency is in the range of 50 Hz to 1100 Hz, but is not limited thereto.

[0040] In at least one embodiment, the intravascular data acquisition device 300 is introduced into the blood vessel 110 from its proximal end, and its distal end 315 reaches the distal point of the blood vessel 110 being examined, after which the intravascular data acquisition device 300 is withdrawn toward the proximal end of the blood vessel 110. Intravascular pressure measurements 225 can be acquired during such withdrawal of the intravascular data acquisition device 300. As shown in Figure 2, the intravascular data acquisition device 300 is connected to a processor 210 in the in vivo regime that sequentially receives intravascular pressure measurements 225 from the intravascular data acquisition device 300.

[0041] Figures 5A and 5B schematically illustrate the steps of a method 500 for determining hemodynamic parameters according to at least one embodiment of the present disclosure. Method 500 acquires blood pressure values ​​225 using an intravascular data acquisition device 300, and uses angiography images 220 and 222 obtained using an extravascular imaging device 215 under two conditions: when contrast agent is present in the blood vessel 110 and when it is not. The contrast agent angiography image 220 is acquired when contrast agent is present in the blood vessel 110. The pressure measurement angiography image 222 (also called the “guidewire position angiography image”) is acquired when contrast agent is not present in the blood vessel 110, and the blood pressure value 225 is measured using the intravascular data acquisition device 300.

[0042] In this specification, "contrast-enhanced angiography image 220 acquired using a contrast agent" means that the contrast-enhanced angiography image 220 is acquired while the contrast agent is being introduced into the blood vessel 110 or immediately before it is introduced. If a contrast agent is present in the blood vessel 110, the contrast agent is visible to the user (physician) on the contrast-enhanced angiography image 220, or the blood vessel to which the contrast agent is attached is segmented by the processor 210 and separated (distinguished) from the background.

[0043] Figure 4A shows a contrast-enhanced angiographic image 220 acquired according to at least one embodiment of the present disclosure. The contrast agent helps to distinguish the vessels 110 from the background in the angiographic image, indicating the vessels 110 "with contrast agent". The contrast agent may be added, for example, by direct injection into the vessels 110 or by bolus injection of the contrast agent through a diagnostic catheter into the coronary sinus orifice. The contrast agent may be, for example, an iodine-containing iodine contrast agent.

[0044] The contrast agent is added to the blood vessel 110 (the lumen of the blood vessel), and a set of contrast-enhanced angiographic images 220 can be obtained. The contrast-enhanced angiographic images 220 can be obtained when the intravascular concentration of the contrast agent (also referred to herein as the "first concentration of the contrast agent") is sufficiently high to allow identification of the blood vessel in the contrast-enhanced angiographic images 220.

[0045] In at least one embodiment, the extravascular imaging device 215 captures a contrast-enhanced angiography image 220 while the contrast agent is flowing into the vessel 110 during the contrast-enhanced period. The contrast-enhanced period (which may be counted from the injection of the contrast agent or a bolus of the contrast agent) is long enough to acquire (and record) images of the contrast agent filling and propagating through the coronary artery trees before it diffuses. While the contrast agent is flowing into the vessel 110, the concentration of the contrast agent within the vessel 110 is sufficient to provide a discernible contrast between the vascular image and the image surrounding the vessel 110 in the acquired contrast-enhanced angiography image 220. The contrast-enhanced period may be, for example, 3 to 5 seconds, or, for example, less than 10 seconds. The contrast agent duration may be set in advance, or the operator (healthcare worker) may stop introducing the contrast agent into the blood vessel 110 when the contrast-enhanced angiography image 220 displayed on the display 240 has sufficient contrast (in other words, when it has reached a contrast level that allows the blood vessel 110 to be clearly identified from its surroundings).

[0046] The pressure-measuring angiography image 222 is acquired under the "no contrast agent" condition. This means that the pressure-measuring angiography image 222 is acquired when there is no contrast agent in the blood vessel 110 because the contrast agent is not physically present, or when the contrast agent is no longer present in the blood vessel 110 because the contrast agent concentration has decreased due to the time elapsed since the contrast agent was introduced into the blood vessel 110.

[0047] Pressure-measuring angiography image 222 is acquired when the contrast agent concentration in the vessel 110 decreases and reaches a second contrast agent concentration. This can occur after the contrast agent injection period, within a few seconds after the contrast agent injection or after the bolus containing the contrast agent is injected into the vessel 110. In other words, pressure-measuring angiography image 222 is acquired when the contrast agent concentration in the vessel is significantly lower than the first contrast agent concentration, for example, zero or near zero, at the second contrast agent concentration. Since contrast agent injection into the catheter disrupts the aortic pressure signal (Pa), pressure measurement should be performed before contrast agent injection or after sufficient time has elapsed since injection and aortic pressure measurement has recovered. If pressure measurement is performed before contrast agent injection, retrospective pressure signal preservation can be initiated using the contrast agent. For example, the average Pa and Pd of the last 1-10 recorded heartbeats can be preserved.

[0048] Referring again to Figure 2, extravascular measurements (contrast-enhanced angiography image 220 and pressure measurement angiography image 222) and intravascular pressure measurements, distal pressure 527 and proximal pressure 529 can be obtained 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 at rest or congestive, and whether vessel 110 has already undergone percutaneous coronary intervention.

[0049] To induce congestion, an engorgement agent (also called a "congestive inducer") may be introduced into the blood vessel 110. While contrast agents can induce congestion on their own, it is preferable to introduce an engorgement agent into the blood vessel 110 to induce a vascular congestion state. However, in some embodiments, the engorgement agent may be a contrast agent. The engorgement agent can be introduced, for example, by continuous intravenous infusion of adenosine. Transient congestion can also be induced by intracoronary (IC) bolus administration of adenosine or other agents.

[0050] If it is necessary to acquire contrast-enhanced angiography images 220 while blood vessel 110 is hyperemic, the duration of IC-induced hyperemia is very short, so the user (operator) needs to synchronize the injection of the hyperemetic agent with the injection of the contrast agent. Alternatively, the contrast agent may be introduced using a contrast bolus, while the hyperemetic agent may be introduced by continuous intravenous infusion of adenosine.

[0051] 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 subjected to stress induced by the hemophilic agent, and measurements can be taken without introducing (applying) the hemophilic agent.

[0052] In the second state, blood vessel 110 is under stress, i.e., in a state of complete congestion. As previously mentioned, congestion in blood vessel 110 (also called "congestive condition") can be induced by an engorgement agent. Measurements such as angiographic images 220, 222 and intravascular pressure measurements 225 are performed after (and as a result of) the injection of an engorgement agent into blood vessel 110, while the engorgement agent is present in blood vessel 110. In other words, in the second state, a concentration of the engorgement agent is present in blood vessel 110, which can induce stress in blood vessel 110.

[0053] The concentration and amount of the hypertensive agent in the blood vessel 110 decrease over time, and therefore the effect of the hypertensive agent also decreases over time. If no further hypertensive agent is injected after a certain period of time, such as a few seconds, the blood vessel 110 becomes stagnant again. The concentration of the hypertensive agent in the blood in the second state (congestive state) is higher than the concentration of the hypertensive agent in the first state (resting state), and in a preferred embodiment, the concentration of the hypertensive agent in the blood vessel 110 in the resting state is zero or close to zero, because the hypertensive agent has not been recently induced or the effect of the hypertensive agent has worn off.

[0054] As shown in Figure 1D, as is well known in the art, a stent 120 may be placed to open a blood vessel 110 in the heart that has narrowed due to plaque buildup caused by a condition known as atherosclerosis. Such an intervention is sometimes called percutaneous coronary intervention (PCI). Instead of placing a stent 120, angioplasty may be used as PCI. In angioplasty, a balloon may be briefly inflated to push the plaque back into the coronary artery wall and improve blood flow. For example, a drug-coated balloon (DSG) may be used during PCI.

[0055] In the method described herein 500, the first and second states of the blood vessel 110 can be induced prior to PCI. Thus, the first state is also referred to herein as the “pre-PCI resting state” and the second state as the “pre-PCI hyperemia state.”

[0056] The third and fourth states of vessel 110 can be performed after PCI. In the third state, vessel 110 is at rest after PCI. The third state is also referred to herein as “post-PCI rest state,” and the measurements here are obtained after the vessel 110 is unstressed (i.e., not congested) and after the placement of a structure such as a stent. In the third state, angiographic images are taken and blood pressure is measured after the placement of stent 120 (or other structure associated with PCI). In the fourth state (referred to herein as “post-PCI congested state”), vessel 110 is under stress after PCI (i.e., fully congested).

[0057] Referring to Figures 5A and 5B, Method 500 and the preliminary routine 505 of Method 500 may be performed for one or more conditions of the blood vessel 110. In the context of this specification, the term “routine” refers to a subset of computer executable program instructions of Method 500, which are executed by the processor 210 and perform the functions described below in relation to the various routines.

[0058] In at least one embodiment, each preliminary routine 505a, 505b (also referred to as “preliminary routine 505”) is performed for one state of the blood vessel 110 and includes the acquisition of data in steps 510, 512, 515 (also referred to herein as “acquisition data steps”), which is then sent to the processor 210. For example, one or more acquisition data steps may be performed for each additional state. In some embodiments, in a subsequent state performed after the first state, only two measurement steps may be performed, for example, step 510 (acquiring an angiographic image of a blood vessel with contrast agent) and step 512 (acquiring intravascular blood pressure), or step 512 and step 515 (acquiring an angiographic image of a blood vessel without contrast agent). In the preliminary routine, the flow rate is estimated in step 525, pressure and geometry data 535 is generated in step 540, and the pressure measurements are aligned in step 530.

[0059] In contrast agent image acquisition step 510, while the contrast agent is being injected into the blood vessel 110, one or more sets of contrast agent angiography images 220 (e.g., X-ray images) of the blood vessel 110 are acquired. The contrast agent angiography images 220 are two-dimensional images taken from at least two different angles (in other words, different planes) relative to the blood vessel 110. For example, the first contrast agent angiography image 220 is taken in a geometric plane that is approximately parallel to the blood vessel 110, and the second contrast agent angiography image 220 is taken in a second plane that is perpendicular to the plane of the first contrast agent angiography image 220, or at an angle between 60 and 130 degrees, for example. The second plane is also approximately parallel to the blood vessel 110. Images of the same blood vessel 110 taken in different planes are also called "views". Each view corresponds to an image taken in one geometric plane. The contrast-enhanced angiography image 220 can be stored in the storage device 260.

[0060] Each contrast-enhanced angiography image 220a in the set of contrast-enhanced angiography images 220a may be acquired from a video containing angiography images recorded by an extravascular imaging device 215 while the contrast agent is inside the blood vessel 110. Each video, and therefore each contrast-enhanced angiography image 220a, may correspond to one view (a specific angle) of the blood vessel 110.

[0061] As described above, the contrast agent introduced into the blood vessel 110 during angiography in contrast agent image acquisition step 510 helps to distinguish the blood vessel from the background. In other words, the contrast agent angiography image 220, taken with the contrast agent injected into the blood vessel, makes it possible to clearly distinguish the blood vessel, allowing the user to visualize the blood vessel 110 when viewing the contrast agent angiography image 220 and to identify the location and geometry of the blood vessel.

[0062] After at least a first time has elapsed since the introduction of the contrast agent (and acquisition of a set of contrast agent angiography images 220) and the contrast agent is no longer present in the blood vessel 110, a pressure-measuring angiography image 222 (e.g., an X-ray image) is acquired (step 515), and a set of blood pressure values ​​225 is acquired by the intravascular data acquisition device 300 within the blood vessel 110 (step 512). In at least one embodiment, the pressure-measuring angiography image 222 and the set of blood pressure values ​​225 are acquired simultaneously (synchronously). In at least one preferred embodiment, the blood pressure values ​​are acquired simultaneously with the acquisition of a second pressure-measuring angiography image of the blood vessel into which the vasoconstrictor was injected.

[0063] In other words, the intravascular data acquisition device 300 measures the proximal pressure Pa and distal pressure Pd (shown in Figure 1C) as a function of the position within the lumen of the blood vessel 110 (e.g., the distance of the intravascular data acquisition device 300 from the entry point into the blood vessel 110) (step 512 in Figure 5A). In some embodiments, the pressure measurements (proximal pressure Pa and distal pressure Pd) may be measured as a function of time. In some embodiments, the position is described as coordinates, and the proximal and distal pressures may be measured as a function of the coordinates. The acquired set of blood pressure values ​​225 includes the position within the blood vessel 110, and, in some embodiments, the values ​​of distal pressure 527 and proximal pressure 529 measured as a function of time. Referring to Figure 5A, while measuring the distal pressure 527 and proximal pressure 529 values ​​within the blood vessel 110 using the intravascular data acquisition device 300, the system 200 acquires a pressure measurement angiography image 222 of the same blood vessel 110 (step 515 in Figure 5A). Measurement values ​​may be given a timestamp.

[0064] In step 515, the pressure-measuring angiography images 222, measured without contrast agent, do not clearly distinguish the vessels, and when the pressure-measuring angiography images 222 are displayed, the user (e.g., a clinician) cannot see the vessels 110. However, each pressure-measuring angiography image 222 shows the tip of the intravascular data acquisition device 300 and its spatial position, so the user can confirm where the pressure was measured by the intravascular data acquisition device 300 (where within the vessel 110).

[0065] The pressure-measuring angiography image 222 is a two-dimensional image taken from one or more different angles of the blood vessel 110, and the pressure measurement by the intravascular data acquisition device 300 is performed inside the blood vessel 110. The pressure-measuring angiography image 222 may correspond to one or more views and may be acquired from video recorded by the extravascular imaging device 215. The correspondence between the pressure-measuring angiography image 222 and the pressure measurement values ​​225 (distal pressure 527 and proximal pressure 529) may be provided, for example, by a timestamp.

[0066] To determine the pressure field within the blood vessel 110, the method 500 and system 200 described herein merge (in other words, superimpose or overlay) the data obtained during pressure measurement, distal pressure 527, proximal pressure 529, and pressure measurement angiography image 222 with the geometric data of the blood vessel 110 obtained from the contrast angiography image 220 in step 540.

[0067] The geometry of the vessel 110 may be clearly detectable by the segmentation step 520, in which the segmentation of the contrast-enhanced angiography image 220 previously acquired in the contrast-enhanced image acquisition step 510 is performed by the processor 210 (Figures 2 and 5A). In the segmentation step 520, at least one contrast-enhanced angiography image 220 per view is processed and a corresponding mask 420 is generated. 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 vessel 110. Figure 4B shows the mask of the angiography image of Figure 4A generated in the segmentation step 520 according to at least one embodiment of the present disclosure. In Figure 4B, the vessel 110 is a coronary artery. In at least one embodiment, the processor 210 may segment only one image per view (sequence) to perform 3D geometry reconstruction of the blood vessel 110, and may segment two images per view sequence for flow estimation.

[0068] For example, the mask 420 has the same size and shape as the contrast angiography image 220, the background 430 is displayed in black (represented as "0" or "(0,0,0)" in RGB), and blood vessels 110, such as arteries, are displayed in white (corresponding to "1" or "255" depending on the bit depth). In Figure 4B, the blood vessels in the mask are displayed in white, and the background 430 surrounding the blood vessels 110 is black.

[0069] In step 540, the geometric vascular coordinates (also referred to herein as “geometry”) of the vessel 110 are reconstructed based on the output of the segmentation step 520 obtained from the contrast-enhanced angiography image 220. In at least one embodiment, in step 540, the reconstruction routine generates a reconstructed geometry object 545 as an output, which provides the geometric vascular coordinates of the vessel 110.

[0070] The geometric vascular coordinates are three-dimensional (3D) and can be represented as V(x,y,z). In at least one embodiment, the 3D geometry of a vessel 110 can be reconstructed based on a contrast-enhanced angiography image 220 of the vessel 110. Various methods can be used to reconstruct the 3D geometry. Some methods are described in Cimen, 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, model-based methods include forward projection, backward projection, 4D, multi-view, and vascular lumen reconstruction. 3D reconstruction using tomography methods, such as the so-called "gate" method and motion compensation method, is also employed.

[0071] Depending on the number of sets (views) of contrast-enhanced angiography images 220 acquired, a two-dimensional (2D) or three-dimensional (3D) reconstructed geometry of the vessel 110 can be generated, as described below. 3D reconstruction can be performed based on two or more angiography images segmented in step 520. In the case of two dimensions, the system can generate a two-dimensional geometry of the vessel 110 using one or more angiography images acquired in step 510 and subsequently segmented in the segmentation step 520. For example, two or more sets of contrast-enhanced angiography images 220 may be useful for generating a 2D or 3D reconstructed geometry of the vessel 110.

[0072] In at least one embodiment, an initial 3D model of the blood vessel 110 may be obtained by determining a two-dimensional (2D) projection of the blood vessel image and determining the 3D model using elastic registration. Elastic registration provides local stretching of the image to compensate for local nonlinear deformation. In at least one embodiment, the systems and methods described herein may use generative neural networks such as generative adversarial networks (GANs).

[0073] 3D parameters of blood vessels can also be obtained using computed tomography angiography (CTA). CTA is a type of medical examination that combines a computed tomography scan with the injection of a contrast agent to create images of blood vessels and tissues in a part of the patient's body. The contrast agent is injected through an intravenous (IV) line initiated in the arm or hand. 3D models of arteries can also be obtained using other methods, such as iterative model reconstruction.

[0074] 3D reconstruction can be used to estimate volume for calculating flow rate. It can also be used as input data for computational fluid dynamics (CFD) models, as described later. For example, the diameter along the vessel can be used to estimate resistance. Reconstructed 3D geometric data of vessels obtained from a sequence of angiographic images can also be useful in determining blood flow rate (Q). By estimating the volume filled with contrast agent as a function of time, the relationship between volume change and time change (dV / dt) can be obtained. This, by definition, is the blood flow rate (Q) measured in cubic meters multiplied by the time (m). 3 This is the value obtained by dividing by ( / s).

[0075] In at least one embodiment, in step 540, a low-dimensional reconstruction using a low-dimensional embedding may be used instead of a 3D reconstruction of the geometric vascular coordinates of the blood vessel 110. For example, a two-dimensional (2D) reconstruction may be performed in step 540, and the reconstructed geometric object 545 may be obtained by a 2D model, such as a 2D embedding and a model projected onto a plane (but not limited to these). A one-dimensional (1D) reconstruction may be performed by calculating values ​​along nodes and a single line. Alternatively, a zero-dimensional (0D) model in which values ​​are calculated at nodes may be used.

[0076] In at least one embodiment, the contrast-enhanced angiography image 220 received by the processor 210 from the extravascular 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 instrument settings used to capture the image. The metadata can be used to reconstruct the vascular geometry and generate the reconstructed geometry object 545.

[0077] When performing method 500, the geometry of the vessel 110 may be generated for the initial state of the vessel 110. For example, if the execution of method 500 starts from the state of “rest, pre-PCI”, the reconstructed geometry object 545 is generated in step 540. If the preliminary routine 505 is performed for a subsequent state of the vessel 110 (e.g., “congestive, pre-PCI”), the reconstructed geometry object 545 generated for the initial state of the vessel 110 (“rest, pre-PCI”) may be reused in step 530 for alignment with the blood pressure value 225 and the pressure measurement angiography image 222.

[0078] Based on the contrast-enhanced angiography image 220, blood flow (Q) can be estimated. As shown in Figure 5A, after the segmentation step 520, the processor 210 estimates the blood flow in step 525. The blood flow can be estimated based on at least one view. In at least one embodiment, the blood flow can be estimated for the entire coronary tree. Alternatively, the processor 210 can estimate the blood flow field spatially distributed within the coronary tree. In some embodiments, the blood flow (Q) can be estimated using the method described in U.S. Patent No. 11,369,277.

[0079] In at least one embodiment, the flow routine 525 estimates the flow using the reconstructed geometry object 545. The reconstructed geometry object 545 may be computed during reconstruction (e.g., 3D reconstruction) in the reconstruction geometry routine performed in step 540 of method 500. Alternatively, the flow may be estimated by assuming a 2D axisymmetric geometry of the vessel 110. In other words, to estimate the flow, an angiographic image may be used with an axisymmetric model of the vessel, assuming that the vessel lies on a planar (flat) surface.

[0080] The blood flow values ​​generated based on the contrast-enhanced angiography image 220 or the reconstructed geometry object 545 can be used in the physical model routine 550 and the optimization routine 570 of method 500.

[0081] In at least one embodiment, in step 530, data obtained from the contrast angiography image 220 on the one hand and data obtained from the pressure measurement angiography image 222 and the simultaneously measured pressure values ​​527, 529 on the other hand are integrated.

[0082] Based on the pressure-measuring angiography image 222, the processor 210 may, in step 530, determine and store the position of the distal end 315 of the pressure guidewire 305 within the vessel 110 and obtain a sequence of positions of the intravascular 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 given time is represented by coordinates (x,y). The measured pressure values ​​527, 529 may be averaged or dynamically calculated. At each time step, the pressure-measuring angiography image 222 includes one or more angiography images taken (acquired) in one or more geometric planes and thus provide one or more different views of the pressure guidewire 305 positioned within the vessel 110. Thus, the pressure-measuring angiography image 222 may be used to obtain aligned pressure and geometry data 535.

[0083] In at least one embodiment, the measured proximal pressure 529 and distal pressure 527, or only the distal pressure 527, may be superimposed (mapped) onto the reconstructed geometric object 545 of the vessel 110. For example, the reconstructed geometric object 545 may be acquired at the end of diastole and used for superimposition. Thus, in step 530, the processor 210 may superimpose the pressure measurements onto the previously determined (acquired) geometry of the vessel 110. Alternatively, the processor 210 may map the measured pressure values ​​527, 529 relative to the position of the distal pressure sensor 310 on the pressure measurement angiography image 222. Such a step is also called “aligning” or “co-aligning” the pressure measurements to the coordinates of the vessel 110. As used herein, alignment or co-alignment refers to transforming different datasets into a single coordinate system.

[0084] In yet another embodiment, instead of, or in addition to, mapping to the reconstructed geometry object 545, the pressure values ​​527, 529 received as pressure signals from the intravascular data acquisition device 300 may be superimposed (mapped) onto the contrast angiography image 220 (acquired in contrast image acquisition step 510). To this end, in at least one embodiment, the processor 210 calculates the median blood pressure at end diastole and uses the pressure measurement angiography image 222 acquired at end diastole (corresponding to the relaxation phase of the heart cycle). In at least one embodiment, the processor 210 may average the pressure values ​​527, 529 measured over time.

[0085] In at least one embodiment, the measured proximal pressure Pa and distal pressure Pd (or distal pressure 527 only), as well as the measured pressure values ​​527, 529 (or proximal pressure 529 only) and the pressure measurement angiography image 222 acquired simultaneously, can be mapped together onto a reconfigured geometry object 545 of the vessel 110 previously acquired in step 540. Here, the geometry of the vessel 110 is determined based on contrast angiography images 220 acquired in different planes (views) with contrast agent present in the vessel 110.

[0086] In at least one embodiment, in step 530, to “align” the pressure measurements, the measured pressure values ​​527, 529 (or distal pressure 527 only) are first superimposed on the pressure-measuring angiography image 222 to obtain pressure-alignment data that includes one or more images showing displacement tracking. Pressure data is obtained from the intravascular data acquisition device 300 within the vessel 110. Such aligned pressure data is then superimposed on one of the contrast-enhanced angiography images 220, or preferably a reconstructed geometric object 545, to obtain aligned pressure and geometric data 535. The superimposed image obtained in step 530 is displayed on the display 240. The distal pressure 527 may be aligned to the pressure-measuring angiography image 222, and then the pressure-measuring angiography image 222 may be aligned to the reconstructed geometric object 545.

[0087] Referring again to Figure 5A, the flow rate data (such as flow rate), aligned pressure and geometry data 535, and, in some embodiments, the reconstructed geometry object 545 determined in step 540 are sent to the physical model routine 550.

[0088] The physical model routine 550 (also referred to herein as “step 550”) implements (applies) a physical model of the blood distribution (flow) within the blood vessel 110. The physical model routine 550 uses flow data (estimated in step 525), reconstructed geometry objects 545 (in other words, reconstructed 3D (or 2D) parameters of the blood vessel 110 obtained from the contrast angiography image 220), and the intravascular (in other words, along the blood vessel 110) blood pressure distribution obtained by pressure measurement 512.

[0089] The physical model can be implemented using CFD analysis. The physical model routine 550 solves the Navier-Stokes equations, which are partial differential equations describing the movement of blood within the blood vessels 110. When implemented in zero dimensions, the physical model routine 550 may solve the differential equations. In some embodiments, the physical model routine 550 may be run in a steady state (time-independent) using algebraic equations. The physical model may be data-driven, like a low-dimensional model.

[0090] The physical model is based on the geometry of the blood vessel 110 (e.g., reconstructed geometry object 545), boundary conditions (inflow boundary conditions, e.g., flow rate), and invasive (intravascular) pressure and flow measurements. The physical model may solve the Navier-Stokes equations in three dimensions (3D), two dimensions (2D), one dimension (1D), or zero dimensions (0D). Yet another alternative physical model may be based on machine learning. In at least one embodiment, the physical model routine 550 uses a low-dimensional model or machine learning to solve the Navier-Stokes equations. The calculations of the CFD, low-dimensional model, and / or machine learning may use a database 230 that can store initial values ​​for the implementation of the physical model.

[0091] The output of the physical model, i.e., the output of step 550 of method 500, is a set of output parameters 555 that include pressure estimates for coordinates (also called “predicted values,” “corrected blood pressure values,” or “solution of the model”) and flow rates as a function of coordinates. Optimization performed by the optimization routine 570 helps to determine microvascular resistance. In some embodiments, the output parameters 555 of the physical model may include, for example, pressure estimates along the centerline of the blood vessel 110. In other words, the output of the physical model may be the coordinates of a virtual line passing through the geometric center of the blood vessel 110 and pressure estimates along that virtual line determined by the physical model. Thus, the output of the physical model in step 550 is the blood pressure distribution determined with respect to spatial coordinates and, by extension, the blood vessel.

[0092] The physical model in step 550 uses the pressure and geometry data 535 received from the alignment step 530 to generate a set of output parameters, including the calculated (determined) pressure values ​​within the volume of the blood vessel 110. After solving the Navier-Stokes equations, the physical model routine 550 provides the set of output parameters 555 to the optimization routine 570. The pressure values ​​calculated in step 550 are used in the objective function of the optimization routine 570, as described later.

[0093] In at least one embodiment of Method 500, pressure measurement within the blood vessel 110 is performed by the proximal pressure sensor 312 of the guidewire 305 and catheter 307, as described above for step 510, and simultaneously, a determined (predicted) pressure (set of output parameters 555) is obtained based on a hydrodynamic model with boundary conditions. The boundary conditions may be, for example, blood pressure values ​​measured using the pressure sensor 312 at two locations in a portion (segment) of the blood vessel 110. Next, the data obtained from the measurements in steps 512 and 515 (proximal pressure 529 and distal pressure 527) are integrated in step 550 with the contrast-enhanced angiography image 220 obtained in step 510, and the Navier-Stokes equations are solved. In at least one alternative embodiment, in step 530, the processor 210 may integrate the reconstructed geometry object 545 (acquired based on the contrast angiography image 220) with the data obtained in steps 512 (measured pressure values ​​527, 529) and 515 (pressure measurement angiography image 222).

[0094] The physical model 550 generates a set of output parameters 555 as output for a specific state, representing both a pressure prediction based on the contrast-enhanced angiography image 220 and an angiography image 222 and blood pressure value 225 for a reconfigured geometry object 545 (2D or 3D geometry) of the blood vessel 110. The output of the physical model 550, which is the set of output parameters 555, is used by the optimization routine 570.

[0095] Referring again to Figures 2, 5A, and 5B, preliminary routine 505a performs measurements, data acquisition, transmission to processor 210, and calculation of a physical model for the first state of the vessel 110. Similar measurements and similar preliminary routines 505b, 505c, and 505d can be performed for other states of the vessel 110, namely pre-PCI rest, pre-PCI hyperemia, post-PCI rest, and post-PCI hyperemia, as described above.

[0096] After the physical model routine 550 solves the differential equation, the optimization routine 570 for the physical model of the blood vessel 110 is executed. The optimization routine 570 uses a set of output parameters 555 generated by the physical model 550 based on measurements obtained in one or more states to adjust the pressure values, which have been adjusted based on multiple iterations in different states of the blood vessel 110.

[0097] Referring to Figure 5B, for each of the four states described above, the steps of the preliminary routine 505 shown in Figure 5A and various routines are executed to determine the flow rate data and output parameters 555 for each corresponding state (e.g., the first set of output parameters 555a). Each of the preliminary routines 505a, 505b, 505c, and 505d may provide pressure and geometry data 535, reconstructed geometry objects 545, and estimated flow rates to the corresponding physical model routines 550a, 550b, 550c, and 550d. Each of the physical model routines 550a, 550b, 550c, and 550d (hereinafter collectively referred to as "physical model routines 550") corresponding to any of the states may use the database 230 for the initial 3D model.

[0098] A first physical model routine 550a is configured to run a first physical model, a second physical model routine 550b is configured to run a second physical model, a third physical model routine 550c is configured to run a third physical model, and a fourth physical model routine 550d is configured to run a fourth physical model. One or more of the first, second, third, and / or fourth physical models may be a three-dimensional (3D), two-dimensional (2D), one-dimensional (1D), or zero-dimensional (0D) physical model. One or more of the first, second, third, and / or fourth physical models may be a combination of physical models (also referred to herein as a hybrid physical model). One of the first, second, third, or fourth physical models may be a machine learning model.

[0099] A hybrid physical model may combine, for example, a 3D physical model of a critical part of the coronary artery tree, such as a lesion or bifurcation, with an 0D physical model of healthy coronary arteries or microcirculation. Pressure and flow rates may be exchanged at the interface between the two models (3D and 0D models), which may be done by converting flow rates to velocity profiles based on Womersley's solution or other assumed velocity profiles. Alternatively, a hybrid physical model may combine machine learning with 0D modeling techniques. In such a model, machine learning can be used to approximate the behavior of elements such as lesions or bifurcations in a model solved using an 0D solver.

[0100] Next, the physical model routines 550a, 550b, 550c, and 550d provide the optimization routine 570 with one or more sets of output parameters 555 (a first set of output parameters 555a, a second set of output parameters 555b, a third set of output parameters 555c, and a fourth set of output parameters 555d, respectively). In at least one embodiment, the optimization routine 570 receives aligned pressure measurements on a reconstructed 2D or 3D geometry (reconstructed geometry object 545) from each of the physical model routines 550a, 550b, 550c, and 550d.

[0101] After multiple iterations, the optimization routine 570 generates a tuned pressure value (also referred to herein as the "tuned pressure field") as a function of coordinates.

[0102] In at least one embodiment, the optimization routine 570 generates and / or adjusts one or more hemodynamic parameters, such as absolute microvascular resistance, to minimize the difference between a pressure value predicted by the model based on flow rate and contrast angiography image 220 on one side and a measured blood pressure value 225 without contrast on the other side.

[0103] The optimization routine 570 may implement a data assimilation routine. In at least one embodiment, the data assimilation routine includes minimizing an objective function by weighting data corrections with uncertainty-based weights. The weights are predetermined and may correspond to predetermined accuracies of the predicted (calculated) pressure and the measured pressure. The objective function is, for example, the difference between the predicted pressure and / or flow rate and the measured pressure and / or flow rate, and the data assimilation routine may minimize such a difference. For example, data assimilation may include minimizing multiple objective functions. In some embodiments, the weights are uniform (e.g., equal to 1), and data assimilation may include minimizing the error between the predicted pressure and the measured pressure.

[0104] When the input data is dynamic, that is, when the input data to the algorithm is pressure P(t) and flow rate Q(t), assimilation can be performed by filtering. For example, optimization routine 570, which performs data assimilation, may use an ensemble Kalman filter.

[0105] The optimization steps may depend on time, subsequent measurements in a given state, and / or the state of the blood vessel 110. In the subsequent optimization steps, the 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, geometry values, and / or boundary conditions. In at least one embodiment, the processor 210 first adjusts boundary conditions such as microvascular resistance RM or IMR. Alternatively, steady-state optimization may be performed after all measurements have been taken. Implementing the model with dynamic adjustments is more complex than implementing the model in a steady state. In some embodiments, fewer assumptions are used when performing dynamic adjustments, and information is expressed using signal dynamics. In at least one embodiment, the processor 210 performs optimization over time, or instead using average pressure values.

[0106] When the patient is placed on the examination table, one or more of the above-described vascular conditions may be induced. For example, after the first and second conditions of the blood vessel 110 (corresponding to the resting and congestive states) have been implemented, the stent 120 may be placed. Thus, after executing the preliminary routine 505a for the first condition and the physical model routine 550a for each time step, the regulated pressure is a value obtained based on a combination of data obtained by measurement and data obtained based on modeling (simulation). The initial value of the regulated pressure can be either the measured pressure or the model pressure. Alternatively, the initial value of the regulated pressure may be predefined (this may be called a predefined initial regulated pressure). The output of the physical model routine 550a allows for adjustment of the value of the regulated pressure at each optimization step.

[0107] In the operation of method 500, the system 200 acquires a first set of contrast-enhanced angiography images 220, and then, after the contrast agent administration period, acquires a first set of contrast-enhanced angiography images 220 and a first set of blood pressure values. Measurements are taken for a first state of the blood vessel 110, i.e., resting, pre-PCI state. A prompt to start retracting the intravascular data acquisition device 300 may be displayed on the display 240. The steps of the first preliminary routine 505a and the first physical model routine 550a described above may be implemented to generate a first output parameter 555a. In some embodiments, optimization may be performed over multiple time steps. In some embodiments, optimization may be performed, for example, by retracting the intravascular data acquisition device 300 multiple times.

[0108] To improve the accuracy of the adjustment pressure by the optimization routine 570, measurements may be taken in a second state (pre-PCI hyperemia) of the blood vessel 110. Subsequently, a prompt on the display 240 requests the operator to induce the hyperemia of the blood vessel 110 and / or to confirm that the second state has been induced (e.g., by pressing a button or pressing a predetermined part of the display 240). In some embodiments, hyperemia may be detected from the pressure signal. To acquire a second set of contrast angiography images 220 in the second state of the blood vessel 110, the introduction of the contrast agent and the introduction of the hyperemetic agent are preferably in close proximity in time, as described above, to introduce the contrast agent simultaneously with the hyperemia. Measurement of the second set of contrast angiography images 220, followed by acquisition of two sets of pressure measurement angiography images 222 and a second set of blood pressure values ​​225 at load, is initiated and continues, for example, until the results converge. In some embodiments, the operator may be required to induce the second state first. Therefore, measurement data is collected, and the optimization routine 570 is first executed for the second state (pre-PCI hyperemia state). After the optimization routine 570 has been executed for either state, the optimized data may be displayed on the display 240.

[0109] Next, the optimization routine 570 may request the user (operator of the system 200 or clinician) to induce another of the four states. For example, after stent placement, it may check whether the third or fourth state has been induced. Thus, the optimization routine considers the data obtained during the previous optimization period and adjusts the output of the optimization routine based on the previous optimization for the same vessel 110 and the new measurement performed using the stent 120 (presence or absence of hyperemia, i.e., the third or fourth state). The stent 120 may be placed while the guidewire 305 is positioned within the vessel 110. After the stent 120 is placed, optimization in the third or fourth state may be performed during the optimization period for the third or fourth state, respectively. Figure 6A schematically shows a time chart 600 of the implementation of method 500 according to at least one embodiment of the present disclosure. As shown in Figure 6A, method 500 preferably begins with the measurement of a contrast-enhanced angiographic image 220. In each of the four states, the measurement order of the contrast angiography image 220, based on the pressure measurement angiography image 222 and blood pressure value 225, changes and can be selected by the user. For example, the user may provide information (input) about which measurements have been performed or are scheduled to be performed. When the contrast angiography image 220 is measured first, it is preferable that the user waits, for example, a few seconds after performing the contrast angiography image 220 but before acquiring the pressure measurement angiography image 222 and blood pressure value 225, until the blood pressure stabilizes after contrast agent introduction. In other words, there is a preferred delay between the introduction of the contrast agent (and thus the acquisition of the contrast angiography image 220) and the acquisition of the pressure measurement angiography image 222 and blood pressure value 225.

[0110] Referring to Figures 5A and 6A, if measurement data is acquired for multiple states of the vessel 110 (as shown in Figure 6A), the reconstructed geometry object 545 may be generated once for a first state of the vessel 110 (e.g., resting, pre-PCI state). Thereafter, when executing the preliminary routine 505 of method 500, the processor may use (reuse) the reconstructed geometry object 545 previously generated for the first state of the vessel 110, based on the measurements of the contrast-enhanced angiography image 220 performed for the first state of the vessel 110.

[0111] Figure 6B schematically shows another time step 610 of the implementation of method 500 for determining hemodynamic parameters according to at least one embodiment of the present disclosure. As shown in Figure 6B, contrast angiography image 220 is measured after the contrast agent is introduced into the vessel 110 while the vessel 110 is at rest, and can then be used to generate the vessel geometry (step 540 in Figure 5A) and estimate blood flow. Following the measurement of contrast angiography image 220, a hyperemetic agent may be introduced and pressure measurement angiography image 222 and blood pressure value 225 may be measured when the vessel 110 is in a hyperemic state. Subsequent measurements of contrast angiography image 220 may be used to re-estimate blood flow in the hyperemic state and to adjust the pressure adjusted in step 580 (Figure 5B).

[0112] In at least one embodiment, if the measurement is performed and aligned during a hyperemic state (second or fourth state), the equation system may be improved by additional equations that take into account a state in which the geometry of the vessel 110 has not changed but the myocardial resistance has changed. Furthermore, the system 200 may determine the IMR value in the hyperemic state. The system 200 may determine the microvascular resistance RM in the resting state and / or the hyperemic state of the vessel 110. In at least one embodiment, additional equations may be generated using multiple states of hyperemia. For example, the measurement may be performed and aligned between a resting state, an intermediate hyperemic state induced by a contrast agent, and a fully hyperemic state induced by a hyperemetic agent such as adenosine.

[0113] In at least one embodiment, for measurements and registered data (such as corresponding angiographic images and pressure measurement data) performed in the hyperemic state (fourth state) of the blood vessel 110 after PCI, additional equations may be added to the equation system of the optimization routine 570. These additional equations take into account, for example, the state where the lesion model has changed due to PCI but the myocardial resistance has not changed. In other words, the presence of the stent 120 changes the geometry of the coronary artery but does not change the microvascular resistance. By considering the hyperemic state after PCI, the accuracy of the adjusted pressure generated by the optimization routine 570 can be improved.

[0114] In at least one embodiment, the optimization routine 570 takes into account that the blood vessel 110 may have two types of resistance, namely the resistance caused by the lesion and the microvascular resistance. Thus, in the first state of the blood vessel 110, the first blood flow Q1 (e.g., determined in step 525) is the resting resistance R1 of the lesion (stenosis 1 in FIG. 1C) and the resting microvascular resistance R M-r corresponding to (both of which are obtained in the first state and can be determined based on the first set of output parameters 555a received from the corresponding first physical model 505a). The first set of output parameters 555a (P a1 ) obtained in the first state is proportional to Q1(R1 + R M ): P a1 [ ~Q1(R1 + R M-r )

[0115] In the pre-PCI hyperemic state (second state), the second output parameter P a2 is proportional to the sum of the second blood flow Q2, the hyperemic resistance R2 of the lesion, and the hyperemic microvascular resistance R M-h : P a2 ~Q2(R2 + R M-h )

[0116] The hyperemia resistance R2 and the resting resistance R1 are correlated through the geometry of the blood vessel 110 and are provided by a reconstructed geometry object 545 in each state. In at least one embodiment, the optimization routine 570 uses the reconstructed geometry object 545 of the blood vessel 110, which is generated separately for the resting and hyperemia states (first and second states), and the first output parameter 555a and the second output parameter 555b generated by the physical model 550 for the first and second states. Using the above formula, the optimization routine 570 adjusts the regulated pressure.

[0117] In the third state of vessel 110 (resting state after PCI), the third output parameter 555c set is the third blood flow Q3 and the resting microvascular resistance R M-r It is a function of (or proportional to) P a3 ~Q3(R M-r ) is expressed as follows. In the fourth state (congestive state after PCI), the fourth output parameter 555d set is the fourth blood flow Q4 and the resting microvascular resistance R M-h It is a function of (or proportional to) P a4 ~Q4(R M-h ) is expressed as. The formula presented herein assumes that resistance after PCI is negligible. In at least one embodiment, the model may include such resistance. The optimization routine 570 may take into account the above formula and the available third set of output parameters 555c and / or fourth set of output parameters 555d to determine the adjusted pressure value along the vessel 110. The same formula can be determined if there are multiple lesions (stenotic areas) in the vessel 110, and the optimization routine 570 may take into account that one lesion has a stent 120 and other lesions do not. For example, the formula used by the optimization routine 570 after the introduction of stent 120 may include R M In addition, resistance from other lesions within the same vessel 110 may be included.

[0118] To determine the regulated pressure value, the optimization routine 570 considers the set of available output parameters 555 for each state of the blood vessel 110 and their relationship to blood flow in those corresponding states. The optimization routine 570 also considers the reconstructed geometry object 545 determined in the corresponding state. By adjusting the regulated pressure using the optimization routine 570, the regulated pressure value can become more accurate at each optimization step. The optimization routine 570, executed by the processor 210, considers the regulated pressure distribution within the blood vessel (in other words, the coordinate P recThe processor generates a pressure field (with respect to x,y,z,t), flow rate, and adjusted microvascular resistance. Based on this output, the processor 210 generates adjusted hemodynamic parameters in step 580 and may display the adjusted hemodynamic parameters 270 on the display 240 in step 585. The adjusted hemodynamic parameters 270 are, for example, IMR, FFR, coronary flow reserve (CFR), diastolic blood pressure ratio (dPR), absolute flow rate, absolute resistance of one or more coronary branches, and / or absolute resistance ratio at rest and / or hyperemia. In one embodiment, pressure values ​​527 and 529 obtained during pullback or point measurement are localized using the position of the tip of the guidewire 305 in the angiographic image (pressure measurement angiographic image 222) corresponding to the measured pressure and registered (step 530) on the 2D geometry of the vessel (reconstructed geometry object 545) or on the region of interest of the vessel obtained from a single angiographic image with contrast (step 510). The angiographic image may be, for example, a single image taken at the end of diastole. The model may be an 0D cardiovascular model of the artery of interest. The model may use measured pressure or flow rate as boundary conditions. Pressure measurements may be assimilated to model predictions, for example, using a weighted average, based on a single state (505a, 505b, 505c, or 505d) or multiple states. The weights may be calculated based on the confidence associated with the measured and predicted values. Adjusted hemodynamic parameters, such as dPR, FFR, or adjusted pressure, may be displayed on a reference image, such as the vascular geometry (reconstructed geometry object 545) or a reference angiography (e.g., one of the contrast angiography images 220), using a symbol overlay representing the adjusted pressure drop (e.g., the difference between adjusted pressure values ​​at two points along the vessel) or its gradient, a color overlay showing the adjusted pressure value along the vessel of interest, and / or a value overlay displaying the value of the adjusted hemodynamic parameter on the vessel. The adjusted hemodynamic parameter values ​​can be used to determine features on the reference image displayed in the derived view.For example, based on the determination of such features, the display 240 may present the user with a graph showing the values ​​of the adjusted hemodynamic parameters as a function of the vascular geometry or reference angiographic position. Based on this displayed graph, the user may determine (select) the length of the stent to be placed in the blood vessel.

[0119] In at least one embodiment, the optimization routine 570 modifies one or more parameters (also referred to herein as “common parameters”) that are common to two or more physical models 550 corresponding to a state and used for optimization by the optimization routine 570. If the optimization uses measurements from multiple states and therefore outputs from multiple physical models 550 are used in the optimization in step 570, the common parameters may be shared between the optimization routine 570 and at least two physical models 550a, 550b, 550c, 550d, each corresponding to one state. The common parameters may be, for example, boundary conditions and / or geometry of the vessel 110. The optimization routine 570 may have one objective function for the outputs of all physical models corresponding to the states of the vessel 110 used for optimization. For example, if any of the common parameters are changed, that parameter may be shared among two or all physical models. Then, considering all the outputs of all the physical models 550 involved, the error in the objective function may be minimized by using the shared common parameters in the execution of the physical models 550. In at least one embodiment, method 500 may include sharing at least one common parameter among at least two physical models when running physical models for two or more states of a blood vessel. The first physical model 550a, the second physical model 550b, the third physical model 550c, and the fourth physical model 550d may be part of (or form) a single combined (common) physical model having one common system of equations.

[0120] For example, CFR can be calculated based on adjusted pressure obtained for at least two conditions (congestive and resting, pre-PCI). IMR can be calculated based on the calculated blood flow. In at least one embodiment, in step 580, absolute resistance is calculated based on adjusted pressure. The diastolic pressure ratio (dPR) is the mean distal pressure (P) in diastolic pressure at rest. d ) and mean aortic pressure (P a It is defined as the ratio of distal pressure (P) during hyperemia. FFR is defined as the ratio of distal pressure (P) during hyperemia. d ) and proximal pressure (P a It is determined as a ratio to ). The absolute flow rate is determined as the inflow rate into the coronary artery or any of its branches and is expressed in ml / s. The absolute resistance is determined as the pressure drop caused by the segment of the blood vessel 110 for a given absolute flow rate and is expressed in mmHg / ml / s.

[0121] In at least one embodiment, a tuned pressure field is also generated in step 580. The tuned pressure field includes tuned pressure values ​​determined by the optimization routine 570, taking into account the outputs of one or more physical models 550a, 550b, 550c, 550d shown in Figure 5B. To display the tuned pressure field, the processor 210 may generate a composite output image 275 (also referred to herein as the “tuned pressure field image”). The composite output image 275 may be generated by overlaying the tuned pressure values ​​determined by the optimization routine 570 onto either of the measured angiography images 220, 222, or a reconstructed geometric object 545 (e.g., a 3D model image) of the vessels 110. The composite output image 275 has the same size / shape as the contrast angiography image 220, with the background 431 displayed in black (sometimes referred to as “0” or “(0,0,0)” in RGB) and the vessels 110 displayed in black. The blood vessels 110 are displayed in white (which may correspond to "1" or "255" depending on the bit depth) and in various colors representing the adjusted pressure values ​​along the blood vessels. Thus, the various colors and / or color gradients and / or color codes can visually indicate (visualize) the adjusted pressure values ​​and adjusted pressure field values ​​for the vessel geometry and the reconstructed geometry object 545. Thus, the colors and color codes may help the user to visually and quickly identify pressure drops within the blood vessels 110. When the system 200 displays the composite output image 275, it may visually highlight the locations of pressure drops within the blood vessels 110 on the composite output image 275.

[0122] Figure 5B shows an example of a composite output image 275 according to at least one embodiment. In the composite output image 275, the background 431 is dark (e.g., black), and the blood vessels 110 are shown in a light color, indicating a change or gradient of color within the blood vessels and signaling (illustrating) the blood pressure values ​​along the blood vessels. Another example of a composite output image, an inverted composite output image 276, is also shown in Figure 5B, in which the colors of the composite output image 275 are inverted, with the blood vessels shown in a dark color and the background in white. In at least one embodiment, the composite output image 275 is generated, and the system may display a visual representation of the adjusted pressure values ​​superimposed on a reconstructed geometric object, representing an adjusted pressure field.

[0123] Next, the processor 210 provides one or more adjusted hemodynamic parameters and / or a composite output image 275 to the display 240 for the user (operator, clinician) to make a decision. Based on the adjusted hemodynamic parameters and / or the composite output image 275, the clinician can assess the condition of the vessel 110 and determine whether PCI and / or treatment is necessary. For example, the clinician may determine whether PCI is necessary only if measurements were taken before the PCI. Alternatively, they may determine whether the PCI was successful and whether additional intervention or other treatment is unnecessary.

[0124] The adjusted hemodynamic parameter 270 values ​​may help generate indicators of the patient's condition, such as microvascular occlusion (MVO), which characterizes damage and dysfunction of myocardial microvessels. For example, the processor 210 may determine the severity of MVO based on the calculated IMR value and display an indicator of the rate of MVO, or an indicator that the patient has MVO, along with the calculated IMR. The adjusted pressure distribution field determined by the processor 210 may help select and suggest stent positions and lengths that can improve CFR and FFR values. For this purpose, the processor 210 may perform calculations for a suggested set of positions and lengths for the stent 120 using the adjusted pressure distribution.

[0125] Referring again to Figure 5B, the optimization routine 570 may generate output data such as adjusted pressure, flow rate, 3D geometry of the vessel (reconstructed geometry object 545), and boundary conditions, and send them to the display routine 585. The inflow boundary condition is, for example, the flow rate determined at the position of the proximal pressure sensor 312, and may be adjusted during the execution of the optimization routine 570. The outflow boundary condition is, for example, microvascular resistance, which may also be adjusted by the optimization routine 570. While the display routine 585 is running, the display 240 may present (display) the values ​​of the adjusted hemodynamic parameters.

[0126] The method described herein makes it possible to obtain a representation of the pressure field within a blood vessel 110, thereby making it possible to determine the location of the pressure drop within the blood vessel 110. Currently known blood pressure measurement methods cannot determine the exact location within the blood vessel 110 with acceptable accuracy, making it difficult to determine the location of the pressure drop.

[0127] Figure 7 shows a method 700 for determining hemodynamic parameters according to at least one embodiment of the present disclosure. Referring also to Figures 1D, 2, 5A, 5B, and 6A, the method 700 shown in Figure 7 is executable by a system 200 including a processor 210 that communicates with an intravascular data acquisition device 300 and an extravascular imaging device 215. In step 710, the extravascular imaging device 215 acquires a first contrast angiography image 220a of a vessel 110 in which contrast agent is present. In step 712, a reconfigured geometry object 545 of the vessel 110 is generated based on the first contrast angiography image 220a. In step 714, the processor 210 estimates a first blood flow within the vessel 110 based on the first contrast angiography image 220a. In step 716, the intravascular data acquisition device 300 acquires a first set of blood pressure values ​​225a as a function of position within the vessel 110. The extravascular imaging device 215 acquires a first pressure-measuring angiography image set 222a of the blood vessel 110.

[0128] In step 718, the 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 aligned with a first set of pressure-measuring angiographic images 222a. The processor 210 implements a first physical model 550a of the blood distribution within the blood vessel 110 using the reconstructed geometry object 545a. In step 720, adjusted hemodynamic parameters are generated based on the first set of output parameters 555a.

[0129] The first set of contrast-enhanced angiography images 220a, the first set of blood pressure values ​​225a, and the first set of pressure measurement angiography images 222a may be obtained when the blood vessel 110 is in a congested state. The blood vessel 110 contains a congestive agent.

[0130] If a hypertensive agent is present in the blood vessel 110, the extravascular imaging device 215 may acquire a second set of contrast-enhanced angiographic images 220b of the blood vessel 100 containing the contrast agent and hypertensive agent. Based on the second contrast-enhanced angiographic images 220b, the processor 210 may estimate the second blood flow in the blood vessel 110. The intravascular data acquisition device 300 may acquire a second blood pressure value 225b as a function of the location within the blood vessel 110 where the hypertensive agent was injected, and the second pressure-measuring angiographic image 222b of the blood vessel 110 may be acquired using the extravascular imaging device 215. The second output parameter 550b is determined by the processor 210 based on the second blood flow and the second blood pressure value 225b, the second blood pressure value 225b can be aligned with the second pressure measurement angiography image 222b by implementing the second physical model 550b of the blood distribution within the blood vessel 110 and using the reconstructed geometry object 545. The processor 210 uses the second set of output parameters 555b when adjusting the adjusted hemodynamic parameters. The adjusted hemodynamic parameters can be adjusted based on the first set of output parameters 555a and the second set of output parameters 555b.

[0131] After the stent 120 is placed, or after another PCI is performed within the vessel 110, a third set of contrast-enhanced angiographic images 220c of the vessel 110 into which contrast agent has been injected is obtained, and the system may 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 using the contrast agent within the vessel 110. In some embodiments, the third set of blood pressure values ​​225c may be aligned with a third set of pressure-measuring angiographic images 222c. The processor 210 may implement a third physical model 550c of the blood distribution within the vessel 110 using a reconstructed geometry object 545. The adjusted hemodynamic parameters may be further adjusted based on the third set of output parameters 555c, in addition to the previously determined first set of output parameters 555a and second set of output parameters 555b.

[0132] The fourth state of blood vessel 110 is post-PCI hyperemia, for example, as shown in Figure 6A. Using the fourth physical model routine of processor 210, a fourth set of output parameters 555d can be determined based on a fourth set of blood pressure values ​​225d aligned to a fourth set of pressure-measuring angiography images 222d, and a fourth blood flow estimated from a fourth set of contrast-enhanced angiography images 220 measured by an extravascular imaging device 215 using a contrast agent. Using the geometry data 535 determined for the fourth state, a fourth physical model of the blood distribution within blood vessel 110 can be implemented using the reconstructed geometry object 545 and the fourth blood flow. The adjusted hemodynamic parameters can be further adjusted based on the fourth set of output parameters 555d.

[0133] Preferred embodiments have been described above and shown in the accompanying drawings, but it will be apparent to those skilled in the art that modifications are possible without departing from this disclosure. Such modifications are considered variations that may fall within the scope of the disclosure. [Explanation of symbols]

[0134] 1 Stenosis 110 Blood vessels 112 Lumen 120 stents 200 Systems 210 processors 212 memory 215 Extravascular Imaging Device 220 Angiography images 222 Angiography image 225 Blood pressure value 230 databases 240 displays 260 Storage device 270 Hemodynamic Parameters 275 Composite output image 276 Inverted composite output image 300 Intravascular data acquisition device 305 Guidewire 307 Catheter 310 Pressure Sensor 312 Pressure Sensor 315 Distal end 420 masks 430 Background 431 Background 500 ways 505 Reserve routine 505a Reserve routine 505b Reserve routine 505c Reserve routine 505d Reserve routine 520 Segmentation Steps 527 Distal pressure (distal blood pressure value) 529 Proximal pressure (proximal blood pressure value) 535 Pressure and Geometry Data 545 Geometry Objects 550 Physical Models 555 Output Parameters 570 Optimization Routines 700 methods

Claims

1. A method that can be performed by a system including a processor that communicates with an intravascular pressure measuring device and an extravascular imaging device, The aforementioned method, The steps include: obtaining a first set of contrast-enhanced angiography images of the blood vessel containing the contrast agent using the extravascular imaging device; The steps include generating a reconfigured geometric object of the blood vessel based on the first set of contrast-enhanced angiography images, A step of estimating the first blood flow within the blood vessel based on the first set of contrast-enhanced angiography images, The steps include obtaining a first blood pressure value set using the intravascular pressure measuring device, The processor implements a first physical model of the blood distribution within the blood vessels using the reconstructed geometry objects, thereby determining a first set of output parameters based on a first set of blood pressure values ​​and a first set of blood flow. The steps include generating adjusted hemodynamic parameters based on the first set of output parameters. Methods that include...

2. The first contrast-enhanced angiography image set and the first blood pressure value set are acquired while the blood vessel is in a congested state, and the congestive agent is present in the blood vessel. The method according to claim 1.

3. The first set of blood pressure values ​​is a function of the position within the blood vessel, The method according to claim 1 or 2.

4. The extravascular imaging device acquires a first pressure-measuring angiography image set of the blood vessel, and aligns the first blood pressure value set with the first pressure-measuring angiography image set. Further including, The method according to any one of claims 1 to 3.

5. The process involves the processor determining a first set of output parameters based on a first set of blood pressure values ​​aligned with a first set of pressure-measuring angiography images, Further including, The method according to any one of claims 1 to 4.

6. When a congestive agent is present in the aforementioned blood vessel, The steps include: obtaining a second set of contrast-enhanced angiographic images of the blood vessel containing the contrast agent and the hyperemia agent using the extravascular imaging device; A step of estimating the second blood flow within the blood vessel based on the second set of contrast-enhanced angiography images, The steps include obtaining a second set of blood pressure values ​​in the blood vessel where the vasoconstrictor is present using the intravascular pressure measuring device, The processor implements a second physical model of the blood distribution within the blood vessels using the reconstructed geometry objects, thereby determining a second set of output parameters based on a second set of blood pressure values ​​and a second set of blood flow. It further includes, The step of generating the adjusted hemodynamic parameters includes the step of adjusting the adjusted hemodynamic parameters based on the first output parameter set and the second output parameter set, Further including, The method according to any one of claims 1 to 5.

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

8. The extravascular imaging device acquires a second pressure-measuring angiography image set of the blood vessel, and aligns the second blood pressure value set with the second pressure-measuring angiography image set. Further including, The method according to claim 6 or 7.

9. The steps include determining a second output parameter set based on a second blood pressure value set aligned with a second pressure measurement angiography image set by the processor, Further including, The method according to any one of claims 6 to 8.

10. The steps include obtaining a third set of contrast-enhanced angiographic images of the blood vessel containing the stent and the contrast agent using the extravascular imaging device, A step of estimating the third blood flow within the blood vessel based on the third set of contrast-enhanced angiography images, The steps include obtaining a third set of blood pressure values ​​within the blood vessel using the intravascular pressure measuring device, The processor implements a third physical model of the blood distribution within the blood vessels using the reconstructed geometry objects, thereby determining a third set of output parameters based on a third set of blood pressure values ​​and a third set of blood flow. It further includes, The step of adjusting the adjusted hemodynamic parameters is further based on the third set of output parameters, The method according to any one of claims 6 to 9.

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

12. The extravascular imaging device acquires a third pressure-measuring angiography image set of the blood vessel, and aligns the third blood pressure value set with the third pressure-measuring angiography image set. Further including, The method according to claim 10 or 11.

13. The aforementioned processor, The steps include determining a third set of output parameters based on a third set of pressure measurement angiography images and a third set of blood pressure values ​​aligned with that set, Further including, The method according to any one of claims 10 to 12.

14. The third contrast agent angiography image set, the third blood pressure value set, and the third pressure measurement angiography image set are acquired during the vascular congestion state, and the inflammatory agent is present in the vascular space. The method according to any one of claims 10 to 13.

15. After obtaining the third contrast-enhanced angiography image set, and before obtaining the third pressure measurement angiography image set and the third blood pressure value set, at least the third period elapses. The method according to any one of claims 10 to 14.

16. The steps include obtaining a fourth set of contrast-enhanced angiography images of the blood vessel containing the stent and the contrast agent using the extravascular imaging device, A step of estimating the fourth blood flow within the blood vessel based on the fourth set of contrast-enhanced angiography images, The steps include obtaining a fourth set of blood pressure values ​​within the blood vessel using the intravascular pressure measuring device, The steps include: determining a fourth set of output parameters based on a fourth set of blood pressure values ​​and a fourth set of blood flow by implementing a fourth physical model of the blood distribution within the blood vessel using the reconstructed geometry object with the processor; It further includes, The step of adjusting the adjusted hemodynamic parameters is further based on the fourth set of output parameters, The method according to any one of claims 10 to 15.

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

18. The extravascular imaging device acquires a fourth pressure-measuring angiography image set of the blood vessel, and aligns the fourth blood pressure value set with the fourth pressure-measuring angiography image set. Further including, The method according to claim 16 or 17.

19. The steps include determining the fourth output parameter set based on the fourth blood pressure value set aligned with the fourth pressure measurement angiography image set by the processor, Further including, The method according to any one of claims 16 to 18.

20. The step of acquiring the first blood pressure value set is performed simultaneously with the step of acquiring the first pressure measurement angiography image set. The method according to any one of claims 1 to 16.

21. The processor determines a second set of output parameters based on a second set of blood pressure values ​​in which the vasoconstrictor is present and the contrast agent is absent, and a second set of contrast angiography images obtained when the contrast agent and the vasoconstrictor are present in the blood vessel, and a second set of blood flow determined from these values. The step of generating the adjusted hemodynamic parameters is: A step of adjusting the adjusted hemodynamic parameters based on the first output parameter set and the second output parameter set, It also includes. The method according to claim 1.

22. The steps include acquiring a second pressure-measuring angiography image set of the blood vessel, and aligning the second blood pressure value set with the second pressure-measuring angiography image set of the blood vessel, Further including, The method according to claim 21.

23. After the stent is placed in the blood vessel by the aforementioned processor, After at least a third period has elapsed since obtaining the second set of contrast-enhanced angiography images, a third set of pressure-measuring angiography images is obtained, and the obtained third set of blood pressure values ​​is used. The third blood flow determined from the third set of contrast-enhanced angiography images acquired when the contrast agent is present in the blood vessel, Based on this, the steps include determining a third set of output parameters, It further includes, The step of adjusting the adjusted hemodynamic parameters is further based on the third set of output parameters, The method according to claim 21 or 22.

24. The aforementioned processor, The fourth blood flow determined from the fourth set of contrast angiographic images acquired when the contrast agent and the hyperemic agent are present in the blood vessel, A fourth blood pressure value set when the vasoconstrictor is present in the blood vessel and the contrast agent is not present in the blood vessel, Based on this, the steps include determining a fourth set of output parameters, It further includes, The step of adjusting the adjusted hemodynamic parameters is further based on the fourth set of output parameters, The method according to claim 23.

25. The first output parameter set includes pressure estimates along the centerline of the blood vessel, The method according to any one of claims 1 to 24.

26. The first physical model described above is a three-dimensional physical model. The method according to any one of claims 1 to 25.

27. The first physical model described above is a two-dimensional model. The method according to any one of claims 1 to 25.

28. The first physical model described above is a machine learning model. The method according to any one of claims 1 to 25.

29. The first physical model described above is a one-dimensional model. The method according to any one of claims 1 to 25.

30. The first physical model described above is a zero-dimensional model. The method according to any one of claims 1 to 25.

31. The first physical model described above is a hybrid physical model. The method according to any one of claims 1 to 25.

32. The steps include generating a pressure field adjusted as a function of the position within the blood vessel, Further including, The method according to any one of claims 1 to 31.

33. The steps include generating and displaying a composite output image that includes adjusted pressure values ​​representing an adjusted pressure field, which are determined based on a first output parameter, superimposed on a reconstructed geometry image, and which are then displayed. Further including, The method according to any one of claims 1 to 32.

34. The steps include: overlaying a visual representation of the adjusted pressure values ​​onto a reconfigured geometric object to generate and display a composite output image representing the adjusted pressure field; Further including, The method according to any one of claims 1 to 33.

35. The step of estimating the first blood flow within the blood vessel is further based on the reconstructed geometric object of the blood vessel, The method according to any one of claims 1 to 34.

36. The step of adjusting the adjusted hemodynamic parameters is further based on the first blood flow, The method according to any one of claims 1 to 35.

37. The step of adjusting the adjusted hemodynamic parameters is further based on at least one of the first blood flow, the second blood flow, the third blood flow, and the fourth blood flow. The method according to claim 16 or 24.

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

39. The steps include displaying the adjusted hemodynamic parameters on a display, Further including, The method according to any one of claims 1 to 38.

40. A step of generating a pressure field adjusted as a function of the position within the blood vessel based on the first set of output parameters, Further including, The method according to any one of claims 1 to 39.

41. A step of generating a pressure field adjusted as a function of the position within the blood vessel based on at least one of the second output parameter set, the third output parameter set, and the fourth output parameter set, Further including, The method according to claim 40.

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

43. An extravascular imaging device configured to generate a first set of contrast-enhanced angiographic images within a blood vessel containing a contrast agent, An intravascular pressure measuring device configured to measure blood pressure values ​​and generate intravascular pressure data, Processor and Equipped with, The aforementioned processor, Based on the first set of contrast-enhanced angiography images, a reconfigured geometric object of the blood vessel is generated. Based on the first set of contrast-enhanced angiography images, the first blood flow within the blood vessel is estimated. By implementing a first physical model of the blood distribution within the blood vessel using the reconstructed geometry object, a first set of output parameters is determined based on the first blood flow and first set of blood pressure values. Based on the first set of output parameters, the adjusted hemodynamic parameters are generated. It is configured in such a way. system.

44. A display configured to display images representing the adjusted hemodynamic parameters and the adjusted pressure field, Furthermore, The system according to claim 43.

45. The first blood pressure value set is aligned with the first pressure measurement angiography image set. The system according to claim 43 or 44.

46. The aforementioned processor further, Based on a second set of contrast-enhanced angiographic images obtained when the contrast agent and hyperemia agent were present in the blood vessel, the second blood flow in the blood vessel is estimated. By implementing a second physical model of the blood distribution within the blood vessel using the reconstructed geometric object, a second set of output parameters is determined based on a second set of blood pressure values ​​acquired by the intravascular pressure measuring device. Based on the first output parameter set and the second output parameter set, the adjusted hemodynamic parameters are adjusted. It is configured in such a way. The system according to any one of claims 43 to 45.

47. The second blood pressure value set is aligned with the second pressure measurement angiography image set acquired by the extravascular imaging device. The system according to claim 46.

48. The aforementioned processor further, Based on a third set of contrast-enhanced angiography images obtained when the contrast agent was present in the blood vessel, the third blood flow in the blood vessel is estimated. By implementing a third physical model of the blood distribution within the blood vessel using the reconstructed geometric object, a third set of output parameters is determined based on a third set of blood pressure values ​​acquired by the intravascular pressure measuring device. Based on the third set of output parameters, the adjusted hemodynamic parameters are adjusted. It is configured in such a way. The system according to claim 46 or 47.

49. The aforementioned processor further, Based on the fourth set of contrast-enhanced angiography images obtained when the contrast agent was present in the blood vessel, the fourth blood flow in the blood vessel is estimated. By implementing a fourth physical model of the blood distribution within the blood vessel using the reconstructed geometric object, a fourth set of output parameters is determined based on a fourth set of blood pressure values ​​acquired by the intravascular pressure measuring device. Based on the fourth set of output parameters, the adjusted hemodynamic parameters are adjusted. It is configured in such a way. The system according to claim 48.

50. A processor that communicates with an extravascular imaging device and an intravascular data acquisition device, The extravascular imaging device is configured to acquire an angiographic image of at least one blood vessel, and the intravascular data acquisition device is configured to acquire blood pressure values ​​within the blood vessel. The aforementioned processor, The extravascular imaging device receives a first set of contrast-enhanced angiography images of the blood vessel containing the contrast agent. The intravascular data acquisition device receives a first blood pressure value set, and the extravascular imaging device receives a first pressure measurement angiography image set of the intravascular vessel where the contrast agent is absent. Based on the contrast-enhanced angiography image, a reconfigured geometric object of the blood vessel and the first blood flow is generated. By implementing a first physical model of the blood distribution within the blood vessel using the reconstructed geometry object, a first set of output parameters is determined based on the first set of blood pressure values ​​and the first blood flow. Based on the first set of output parameters, the adjusted hemodynamic parameters are generated. Processor.

51. The aforementioned processor further, Based on the second set of contrast-enhanced angiography images and the second set of blood pressure values ​​obtained when the vasoconstrictor was present in the blood vessel, a second set of output parameters is determined. The generation of the adjusted hemodynamic parameters by the processor is further based on the second set of output parameters. The processor according to claim 50.

52. The aforementioned processor further, A third set of output parameters is determined based on a third set of contrast-enhanced angiography images and a third set of blood pressure values ​​obtained when a stent is present in the blood vessel. The generation of the adjusted hemodynamic parameters by the processor is further based on the third output parameter set, The processor according to claim 51.

53. The aforementioned processor further, Based on the fourth set of contrast-enhanced angiography images and the fourth set of blood pressure values ​​obtained when the stent and engorgement agent are present in the blood vessel, a fourth set of output parameters is determined. The generation of the adjusted hemodynamic parameters by the processor is further based on the fourth set of output parameters. The processor according to claim 52.

54. A method that can be implemented by a system having a processor that communicates with an extravascular imaging device and an intravascular pressure measuring device, The aforementioned method, The steps include: acquiring a contrast-mediated angiography image when a contrast agent is present in the blood vessel, The steps include separately acquiring pressure-measuring angiographic images of the same blood vessel without the presence of the contrast agent, and obtaining intravascular pressure values, The steps include: reconstructing the geometry of the blood vessels and applying a physical model to the reconstructed geometric object; The steps include generating the adjusted hemodynamic parameters and adjusting the adjusted hemodynamic parameters based on the contrast-enhanced angiography images, the pressure-measuring angiography images, and the intravascular pressure values ​​obtained when the vascular state is at least two of the following conditions: rest before percutaneous coronary intervention (PCI), hyperemia before PCI, hyperemia after PCI, and rest after PCI. Methods that include...

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