TWI740600B - Method for estimating degree of arterial occlusion - Google Patents

Abstract

Disclosed herein is a method for estimating a degree of arterial occlusion in a subject. The method comprises: (a) providing a plurality of image frames of an artery of the subject taken in sequence; (b) selecting a plurality of cross-sections of the artery based on the plurality of image frames of the step (a), and determining a maximum diameter and a minimum diameter of each of the plurality of cross-sections of the artery among the plurality of image frames; (c) calculating an average vasodilation ratio of the artery base on the maximum diameter and the minimum diameter of each the plurality of cross-sections of the artery determined in the step (b); and (d) determining the degree of arterial occlusion of the artery based on the average vasodilation ratio calculated in the step (c).

Description

Methods used to assess the degree of arterial blockage

This disclosure is about methods used to assess the degree of arterial blockage. In particular, it relates to a method that can determine the average vasodilation ratio based on the difference in the diameter of an artery to assess the degree of vascular occlusion.

Arterial stenosis is a stenosis at the exit of the left ventricle of the heart (start of the aorta), and has been the main cause of heart failure worldwide. Conventional methods for assessing heart stenosis involve visual or quantitative coronary angiography (Quantitative Coronary Angiography, QCA) to assess the target blood vessel, however, neither method can be used to assess the blood flow of the lesion in the blood vessel. The affected arterial function. On the other hand, it is generally accepted that fractional flow reserve (FFR) is a reliable indicator for determining the degree of occlusion/blockage of arteries (for example, coronary arteries). This is because it is more invasive than invasive. Conventional angiography, FFR can more effectively identify the lesions caused by ischemia. In practice, it has been proven that measuring FFR by inserting a pressure wire into a narrow blood vessel is a better choice for medical practitioners to guide decisions related to revascularization.

However, pressure line-based FFR measurement involves risks associated with the intervention required to insert the pressure line into a blood vessel, and for very narrow blood vessel stenosis, the pressure line may cause an additional pressure drop. Therefore, some mechanical models have been proposed to reduce the risk caused by invasive processes. These mechanical models use mathematical equations to simulate the blood flow physics in the three-dimensional anatomical model of the patient's coronary blood vessels extracted from medical images. Such a method relies on physical-based mathematical equations to simulate the physiological state of rest and hyperemia, thereby allowing relevant persons to solve the equations on a computer and digitally determine the blood flow and pressure drop of individual patients.

However, this type of mechanical model is based on the model pre-work and numerical solution of physical equations, and has the disadvantages of high computational cost and high computational complexity. In addition, such mechanical models usually only contain anatomical and some physiological measurements but ignore other meaningful values. Even if machine learning can be applied to the calculation of one or more hemodynamic indexes, there are still a lot of calculation costs, so it is not suitable for clinical diagnosis where every second counts.

In view of this, the related field urgently needs an improved method for evaluating the degree of arterial blockage in an individual.

In order to provide readers with a basic understanding, the following provides a brief summary of the present disclosure. This summary of the invention is not an extensive overview of the disclosure, and is not used to identify the key/essential elements of the invention or outline the scope of the invention. Its sole purpose is to present some concepts of this disclosure in a simplified conceptual form as a prelude to the more detailed description presented later.

As implemented and broadly described herein, the present disclosure aims to provide a method for assessing the degree of obstruction of a body artery mainly through non-invasive operations and based on the difference in blood vessel diameters. In particular, it specifically provides features that do not include direct measurement of blood vessels. Evaluation method of internal blood flow steps.

In one aspect of the present disclosure, it relates to a method for assessing the degree of clogged arteries in a body. The method includes: a method for assessing the degree of obstruction of an artery in a body, including: (a) continuously photographing the artery to obtain a plurality of image frames of the artery; (b) based on the plurality of images obtained in step (a) Select multiple cross sections of the artery, and determine a maximum diameter and a minimum diameter of each of the multiple cross sections of the artery in the multiple image frames; (c) according to each of the plurality of steps (b) Calculating an average vasodilation ratio of the artery for the maximum diameter and the minimum diameter of each cross section; and (d) judging the degree of blockage of the artery according to the average vasodilation ratio of step (c).

According to the embodiments of the present disclosure, the aforementioned method is characterized in that it does not include the step of measuring the arterial blood flow of the individual; the aforementioned method is also characterized in that it is operated non-invasively and does not use catheters, sheaths, or guide wires. Or any combination thereof.

According to some embodiments of the present disclosure, step (b) is to determine the maximum diameter and the minimum diameter in the following steps: (i) aligning the plurality of image frames with each other to determine a boundary and a center of the artery Axis; (ii) according to the normal vector of the central axis of step (i), select the plurality of cross-sections of the artery; and (iii) based on the boundary of step (i), among the plurality of image frames, determine the step (ii) The maximum diameter and the minimum diameter of each of the plurality of cross-sections selected.

Preferably, in step (i), the central axis of the artery is determined by performing polynomial regression on the aligned plural image frames.

(1)，

(2)， 其中， i是該動脈之該複數個截面的任一截面； n是該複數個截面的總數； D _max,i 是在該截面 i上，該動脈的該最大直徑； D _min,i 是在該截面 i上，該動脈的該最小直徑； V _i 是對應該截面 i的一血管舒張比；且 V _avg 表示該動脈的該平均血管舒張比。 According to the embodiment of the present disclosure, in step (c), the average vasodilation ratio is calculated by the following equations (1) and (2):

(1),

(2), where i is any cross section of the plurality of cross sections of the artery; n is the total number of the plurality of cross sections; D _max,i is the maximum diameter of the artery on the cross section i ; D _{min, i} is the smallest diameter of the artery on the section i ; V _i is a vasodilation ratio corresponding to the section i _{; and Vavg} represents the average vasodilation ratio of the artery.

In some embodiments, in step (a), the plurality of image frames are captured at a frame rate of about 30 to 60 frames per second.

In some embodiments, in step (a), the plurality of image frames are captured in a period of about 5 seconds to 8 seconds.

Through the foregoing steps, the method of the present disclosure can accurately and quickly assess the degree of clogging of individual arteries.

After referring to the following embodiments, those skilled in the art to which the present invention pertains can easily understand the basic spirit and other objectives of the present invention, as well as the technical means and implementation aspects of the present invention.

In order to make the description of the present disclosure more detailed and complete, the following provides an illustrative description for the implementation aspects and specific embodiments of the present invention; this is not the only way to implement or use the specific embodiments of the present invention. The implementation manners cover the characteristics of a number of specific embodiments and the method steps and sequences used to construct and operate these specific embodiments. However, other specific embodiments can also be used to achieve the same or equal functions and sequence of steps.

I. Definition

For ease of description, the specific terms described in the specification, the embodiments and the appended patent scope are collectively described here. Unless otherwise defined in this specification, the scientific and technical terms used herein have the same meaning as understood and used by those with ordinary knowledge in the technical field of the present invention. In addition, without conflict with the context, the singular nouns used in this specification cover the plural nouns; and the plural nouns used also cover the singular nouns. Specifically, unless the context clearly indicates otherwise, the singular form "one" (a and an) used in the scope of the patent application herein and appended includes plural forms. In addition, in this specification and the scope of the patent application, expressions such as "at least one" and "one or more" have the same meaning, and both of them mean that they include one, two, and three. Or more.

Although the numerical ranges and parameters used to define the broader scope of the present invention are approximate numerical values, the relevant numerical values in the specific embodiments are presented here as accurately as possible. However, any value inevitably contains standard deviations due to individual test methods. Here, "about" usually means that the actual value is within plus or minus 10%, 5%, 1%, or 0.5% of a specific value or range. Or, the word "about" means that the actual value falls within the acceptable standard error of the average value, depending on the consideration of a person with ordinary knowledge in the technical field of the present invention. In addition to the experimental examples, or unless otherwise clearly stated, all ranges, quantities, values and percentages used herein (for example, used to describe the amount of material, length of time, temperature, operating conditions, quantity ratios and other similar Those) have been modified by "about". Therefore, unless otherwise stated, the numerical parameters disclosed in this specification and the accompanying patent scope are approximate values and can be changed according to requirements. At least these numerical parameters should be understood as the indicated effective number of digits and the value obtained by applying the general carry method.

The term "image frame(s)" (image frame(s) or frame(s)) refers to one or more still images captured by a photo capture device and/or software, which can form a complete moving picture. Generally speaking, multiple single images can be recorded on a photo film strip or as a digital file with inter-sequence, and these multiple single images can be aggregated to present a continuous movement. Any medical imaging device (such as X-ray imaging, magnetic resonance imaging, medical ultrasound scanning, endoscopy, elastography, tactile imaging, thermal imaging, positron emission tomography, PET) And single-photon emission computed tomography (single-photon emission computed tomography) to capture the image frames of the present disclosure. The term "sequential image frame", "sequential image frame" or "sequence of image frames" is used in A continuous image taken within a given period of time, and the frequency at which each frame is taken is called "frame rate" or "frame rate" (frame rate or frame frequency), usually expressed in hertz.

The term "vasodilation" refers to the widening of blood vessels caused by the relaxation of smooth muscle cells in the vascular wall. The so-called vascular wall usually refers to the blood vessels of the arteries, such as the aorta, coronary arteries and aorta. "Vasodilation ratio" (vasodilation ratio) is used to express the degree of widening of blood vessels that are usually affected by vascular occlusion or obstruction. In the present disclosure, the "vasodilation ratio" is determined by the difference between the maximum diameter and the minimum diameter of a given cross-section or cross-section in a section of blood vessel, not by measuring the blood vessel To determine the blood flow.

The term "image registration" or "image alignment" refers to the conversion of different data groups or information groups in an image (for example, multiple photos/images, field of view, or time) into a common coordinate system the process of. In the present disclosure, "image alignment" or "image alignment" is applied to multiple medical images. Specifically, the specific concept of the algorithm used to perform "image alignment" or "image alignment" is to designate one of the images as the target image, and the others as the source image or moving image. (moving image), and "image alignment" or "image alignment" involves spatially transforming the source image or moving the image to align with the target image.

In this article, "subject" refers to mammals (including humans) capable of applying the method of the present disclosure. Unless otherwise specified, "individuals" generally include males and females.

II. Specific implementation

The present disclosure relates to a method for evaluating the degree of obstruction of a blood vessel in a body based on calculating the difference in diameter of a given blood vessel.

Accordingly, the aspect of the present disclosure relates to a method for assessing the degree of arterial blockage in a body. Please refer to FIG. 1, which shows a flowchart of the steps of the method 100 of the present disclosure. The method 100 of the present disclosure includes at least the following steps, which are denoted by symbols 102 to 108 in FIG. 1 respectively: (a) Continuously photograph the artery to obtain multiple image frames of the artery; (b) Based on the plurality of image frames obtained in step (a), select a plurality of cross sections of the artery, and determine a maximum diameter and a minimum diameter of each of the plurality of cross sections of the artery in the plurality of image frames; (c) calculating an average vasodilation ratio of the artery according to the maximum diameter and the minimum diameter of each of the plurality of cross-sections in step (b); and (d) Judging the degree of blockage of the artery according to the average vasodilation ratio of step (c).

Before proceeding to the method 100 of the present disclosure, first select a section of a human artery (usually a section with more severe blockage) for imaging. In some embodiments, it is preferable to select the left anterior descending branch of the coronary artery. Then, X-ray contrast is performed to capture images of the selected section of the artery, wherein the X-ray contrast agent has been injected into the artery before the X-ray contrast. The choice of the type of X-ray developer and the injection dose can vary according to the needs of each individual, as long as a person with ordinary knowledge in the field can interpret the generated image.

Alternatively or not, an angiographic contrast agent can also be given to the individual before the medical image is taken, so as to temporarily clear the blockage in the selected blood vessel and immediately increase the blood flow in the blood vessel. Commonly used angiography agents include, but are not limited to: adenosine, dipyridamole, isosorbide dinitrate, and combinations thereof.

In step (a), medical images of a given section of the artery are taken continuously for a period of time. In one embodiment, it is continuously performed at about 30 to 60 frames per second (for example, 30, 32, 35, 37, 40, 42, 45, 47, 50, 52, 55 , 56, 57, 58, 59 or 60 frames) to take X-ray images of a specific blood vessel segment. In a preferred embodiment, multiple image frames are captured at a frame rate of 45 Hertz (Hz) within six seconds.

Next, in step (b), among the plurality of image frames obtained in step (a), a maximum diameter and a minimum diameter of the artery in a specific section are determined. Preferably, a plurality of cross sections of the artery can be selected among the plurality of image frames obtained in step (a), and then the maximum diameter and minimum diameter of the artery in each cross section can be determined. Specifically, in step (b), image alignment is performed on the plurality of image frames obtained in step (a), that is, the plurality of image frames are aligned with each other, and the frames are analyzed to determine the arteries in each image frame The boundary and its central axis. Specifically, the frame arrangement calibration can be performed by executing a conventional algorithm, for example, by using a feature value algorithm to determine the area and range of the arterial segment to be interpreted. In this embodiment, the Kanade-Lucas-Tomasi (KLT) algorithm is executed, and the aligned and calibrated images are fixed by the algorithm, and then the tracking algorithm is executed. To track multiple feature points on each frame image and zoom and/or rotate the frame image, so that each frame of a plurality of image frames can be superimposed on each other according to a common feature point. In some cases, the last image frame of the image frame sequence can be used as a target image with a fixed relative position, thereby speeding up the alignment and calibration of the remaining image frames. After aligning and superimposing all image frames, binarization is performed on a plurality of image frames to simplify the target object and minimize background information, thereby determining the boundaries of arteries and blood vessels. Then perform polynomial regression analysis to determine the central axis based on the determined boundary.

The same is the step (b). Once the boundary and central axis of the selected artery in the picture are determined, the diameter of the artery can be determined. The specific method is to first specify at least one sampling point on the central axis. According to this, in the image, through the normal vector of each sampling point of the central axis, at least one cross section in the selected artery segment can be obtained. In other words, by using the normal vector of any sampling point, a cross section passing through the sampling point and perpendicular to the artery can be obtained. Specifically, each sampling point on the central axis can correspond to a cross-section of the artery. After the cross-section is obtained, the diameter of the artery on the same cross-section of each image frame can be obtained according to the two boundaries of the artery. It should be understood that the number of sampling points or sections can be changed according to actual needs. In the specific embodiment of the present invention, a plurality of sampling points are selected in the alignment image frame. For example, the number of sampling points is preferably 20 to 500, such as 20, 30, 40, 50, 100, 200, 300 , 400 or 500. In some embodiments, the sampling points are more preferably 200. Due to pulse and blood flow, the diameter of any selected cross-section of the artery will change over time, and a plurality of image frames continuously taken during this time period will reflect such changes. Therefore, for each sampling point, the maximum diameter and minimum diameter of a sampling point can be determined by sorting the collected image frames.

(1)，

(2)。 Then in step (c), based on the maximum diameter and minimum diameter determined in step (b), the average vasodilation ratio of the artery can be calculated. Preferably, the average vasodilation ratio is calculated by the following equations (1) and (2):

(1),

(2).

In equations (1) and (2), i represents any section of the plurality of sections of the artery, n represents the total number of the plurality of sections (that is, the total number of corresponding sampling points), and D _max,i is in On the section i, the maximum diameter of the artery, D _min,i is the minimum diameter of the artery on the section i, V _i is a vasodilation ratio corresponding to the section i, and _Vavg represents the artery’s The average vasodilation ratio.

(3)。 In some embodiments, _Vavg exhibits a negative correlation with a hemodynamic parameter. Hemodynamic parameters can be used as indicators of blood flow, such as coronary flow reserve (CFR) and blood flow reserve (hereinafter referred to as FFR). In some embodiments, the hemodynamic parameter is FFR, which is defined as the ratio of the maximum blood flow in a stenotic vessel to the maximum blood flow in a normal vessel, and can be used as an indicator of the severity of the stenosis. In a preferred embodiment, the average vasodilation ratio of the present disclosure has a negative correlation with FFR. Preferably, the correlation coefficient between the average vasodilation ratio and FFR of the present disclosure is about -0.9 to -0.95. In a preferred embodiment, the average vasodilation ratio and FFR satisfy the following equation (3):

(3).

According to the present disclosure, since FFR is a well-known indicator of vascular occlusion, the average vasodilation ratio correlated with FFR can naturally also be used as an indicator of vascular occlusion. Therefore, in a specific embodiment, according to the equation (3), the degree of vascular occlusion can be obtained by calculating the average vasodilation ratio reflecting the degree of vascular occlusion.

It should be understood that in the method 100 of the present disclosure, the step of estimating the degree of vascular occlusion does not involve the step of directly measuring the blood flow in the artery. More specifically, the present disclosure only uses the difference in blood vessel diameter as an index to determine the degree of arterial blockage. By determining the change of blood vessel diameter within a limited period of time, appropriate follow-up treatments can then be given to the individual or patient.

In addition, the steps (a)-(c) used to estimate the degree of vascular obstruction in the present disclosure are performed in a non-invasive manner, specifically, catheters and sheaths that are conventionally useful for detection are not used. , Guide wire or any combination thereof.

Then in step (d), the degree of blockage of the target artery can be judged according to the average vasodilation ratio obtained in steps (a)-(c). According to an embodiment of the present disclosure, when the value of the average vasodilation ratio is larger, the degree of vascular occlusion is greater; conversely, when the value of the average vasodilation ratio is smaller, the degree of vascular occlusion is smaller. In a preferred embodiment, the present disclosure uses an average vasodilation ratio of 0.2 as a reference threshold. If the average vasodilation ratio is greater than 0.2, the arterial occlusion is more severe.

In non-essential implementations, the individual may also be subjected to subsequent processing according to the reference threshold. The aforementioned subsequent treatment may include various clinically or medically well-known treatments to those skilled in the relevant field, and may also include behaviors and treatments that the individual adopts in response to his own physiological needs. Specifically, after comprehensively judging the individual's remaining physiological conditions, drugs or medical auxiliary materials that can improve arterial obstruction can be administered to the individual. For example, the drug may include vasodilators, such as nitroglycerin, alprostadil, riociguat, hydralazine, and minoxidil. ), nesiritide and nitroprusside, etc. Medical auxiliary materials include stents that can increase arterial blood flow, or even coronary artery bypass surgery for more severe arterial blockages.

A number of embodiments are presented below to illustrate certain aspects of the present invention, so as to facilitate those skilled in the art to which the present invention belongs to implement the present invention. These experimental examples should not be regarded as limiting the scope of the present invention. Without further explanation, it is believed that those with ordinary knowledge in the technical field can use the present invention to the fullest extent based on the description herein. All publications cited herein are incorporated herein by reference in their entirety.

Example

1. Establish an average vasodilation ratio model

25 individuals who were diagnosed with arterial stenosis were randomly selected from the medical database of Mackay Memorial Hospital (Taiwan), and the clinically measured FFR values of these individuals are stored in the database.

A section of the left anterior descending artery of each individual was selected, and 1 mg of isosorbide dinitrate was injected into the blood vessel, and then continuous X-ray medical images were taken immediately after 8 seconds. The frame rate is 45 Hz (that is, there are 45 image frames per second), and the last image frame is designated as the standard template frame. After the region of interest (ROI) is selected on the image, it is processed by the Kanade-Lucas-Tomasi (KLT) method, tracking algorithm and image processing procedures (such as zooming and selecting the image) Frame) to process each image frame so that the common feature point of all image frames is fixed at a fixed point, and all image frames are aligned with each other through the fixed feature point. Then binarization processing and polynomial regression analysis are performed on the aligned image frames, and the boundary of the artery and its central axis are determined through the aforementioned analysis.

Along the central axis of the arterial vessel, take 200 sampling points on it, and calculate the diameter of the corresponding sampling point according to the normal vector of each sampling point.

(1)，

(2)， 其中 i是表示動脈200個截面的任一截面； n表示複數個截面的總數(也就是對應的取樣點的總數200)； D _max,i 是在該截面 i上，該動脈的該最大直徑； D _min,i 是在該截面 i上，該動脈的該最小直徑； V _i 是對應該截面i的一血管舒張比；且 V _avg 表示該動脈的該平均血管舒張比。 The average vasodilation ratio of each individual is obtained by the following equation:

(1),

(2), where i represents any of the 200 cross-sections of the artery; n represents the total number of multiple cross-sections (that is, the total number of corresponding sampling points 200); D _{max, i} is on the cross-section i , the artery The maximum diameter; D _min,i is the minimum diameter of the artery on the section i ; V _i is a vasodilation ratio corresponding to the section i; and _Vavg represents the average vasodilation ratio of the artery.

2. The correlation between the average vasodilation ratio model and FFR

The average statistical results of the average vasodilation ratio of 25 patients are shown in Figure 2. For each patient, the average vasodilation ratio and FFR value satisfy the following equation: V _avg =-1.13 FFR+1.1954, and The correlation coefficient is about -0.92.

3. Judge the degree of arterial obstruction through the average vasodilation ratio model of Example 1

Clinically, when the average vasodilation ratio of the test patient is less than 0.2, it means that the occurrence of severe and acute arterial obstruction is less likely. Therefore, a more suitable vasodilator for the other clinical conditions of the test patient can be used. drug. Conversely, when the average vasodilator pen of the test patient is equal to or greater than 0.2, the patient is considered to be given an invasive heart stent for assistance.

It should be understood that the foregoing description of the embodiments is only given in the form of examples, and various modifications can be made by those with ordinary knowledge in the technical field of the art. The above specification, examples and experimental results provide a complete description of the structure and use of the exemplary embodiments of the present invention. Although various specific embodiments of the present invention are disclosed in the above embodiments, they are not intended to limit the present invention. Those with ordinary knowledge in the technical field to which the present invention belongs, without departing from the principle and spirit of the present invention, Various changes and modifications can be made to it, so the protection scope of the present invention shall be subject to the scope of the accompanying patent application.

100: method

102, 104, 106, 108: steps

In order to make the above and other objects, features, advantages and embodiments of the present invention more comprehensible, the description of the accompanying drawings is as follows:

FIG. 1 is a flowchart of a method 100 for evaluating the degree of arterial occlusion according to an embodiment of the present disclosure; and

Figure 2 presents the regression line of the average vasodilation ratio versus FFR drawn according to an embodiment of the present disclosure.

According to the usual operation method, the various elements and features in the figure are not drawn to scale, and the drawing method is to present the specific features and elements related to the present invention in the best way. In addition, between different drawings, the same or similar element symbols are used to refer to similar elements/components.

100: method

102, 104, 106, 108: steps

Claims (6)

A method for evaluating the degree of obstruction of an artery in a body, comprising: (a) continuously photographing the artery to obtain a plurality of image frames of the artery; (b) combining each of the plurality of image frames obtained in step (a) Align with each other to determine a boundary and a central axis of the artery, wherein polynomial regression is performed on the aligned image frames to determine the central axis of the artery; (c) according to step (b) The normal vector of the central axis selects a plurality of cross-sections of the artery; (d) based on the boundary of step (b), determines the artery in the plurality of image frames, a maximum diameter and a minimum of each of the plurality of cross-sections Diameter; (e) calculating an average vasodilation ratio of the artery according to the maximum diameter and the minimum diameter of each of the plurality of cross-sections in step (d); and (f) according to the average vasodilation ratio of step (e) , To determine the degree of blockage of the artery. The method according to claim 1, wherein in step (e), the average vasodilation ratio is calculated by the following equations (1) and (2): V _i = ( D _max,i - D _{min, i} )/ D _min,i (1),

Wherein, i is any cross section of the plurality of cross sections of the artery; n is the total number of the plurality of cross sections; D _max,i is on the cross section i , the maximum diameter of the artery; D _min,i is on the cross section i, the minimum diameter of the artery; V _i should be on a cross-sectional ratio i of vasodilation; and V _avg represents the average diastolic blood vessels than the arterial. The method according to claim 1, wherein in step (a), the plurality of image frames are captured at a frame rate of about 30 to 60 frames per second. The method according to claim 1, wherein in step (a), the plurality of image frames are captured in a period of about 5 seconds to 8 seconds. The method according to claim 1, wherein the method is characterized in that it does not include the step of measuring the arterial blood flow of the individual. The method according to claim 1, wherein the method is characterized by being operated non-invasively and without using any one of a catheter, a sheath, a guide wire, or a combination thereof.

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