RU2693169C1 - Method of determining structural characteristics of atherosclerotic plaque carotid arteries - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to neurology, cardiology and radiation diagnostics, and can be used to determine structure of atherosclerotic plaque (ASP) of carotid arteries. Ultrasonic examination of an atherosclerotic plaque is carried out at depth of 5.0–10.0 mm in the area of maximum narrowing of carotid artery lumen in longitudinal and transverse projections in B-mode using a linear sensor with radiation frequency of 11 MHz, with average frame frequency and maximum dynamic range of 60 dB. Areas of atherosclerotic plaques measuring up to 10 mm are isolated on the obtained fixed frames. Ultrasonic system software calculates a median of the ultrasonic signal intensity in decibels (dB) reflected from the analyzed sections of the atherosclerotic plaque. And if the intensity of the ultrasonic signal is 1.1–8.0 dB, the atheromatosis lesions are determined in the atherosclerotic plaque, at 9.0–22.0 – foci of atheromatosis with multiple cholesterol crystals, at 23.0–31.0 – fibrosis centers with diffusely located lipophages and/or vessels, at 32.0–39.0 – centers of fibrosis with calcifications, at 40.0–45.0 – calcinosis centers.

EFFECT: method provides higher accuracy of determining structural characteristics of atherosclerotic plaque carotid arteries by standardizing the measurement protocol, which enables to minimize their error, with calculating the median intensity of the ultrasonic signal in dB.

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Description

The invention relates to the field of medicine, in particular to neurology and can be used to determine the structure and morphological features of atherosclerotic plaque (ASB).

In the development of cerebral circulatory disorders (NMC) in the carotid system of the brain, not only the degree of carotid sinus stenosis (CS) is important, but also the structure of ASB: the presence of progressive atheromatosis during the inflammatory process, thinning and destruction of the plaque cap, infiltration of the plaque by macrophages and other cells, destructive changes in the newly formed vessels with the development of hemorrhages in the plaque.

These processes in ASBs increase the risk of increased stenosis of the CS and its thrombosis, as well as emboli of the distal internal carotid artery (ICA) and its branches, which ultimately leads to severe NMC with the development of cerebral infarction. One of the most effective methods of preventing NMC in the ICA system is carotid endarterectomy (CEE) - the operation of removing ASB from the CS. To assess the risk of NMC and address the issue of indications for CEE, ultrasound of the carotid arteries is widely used to determine the degree of stenosis of the CS, as well as the echo structure of ASB, reflecting their morphological composition. In recent years, the need (regardless of the degree of CS stenosis) to perform CEE in the presence of ultrasound signs of an “unstable” plaque structure has been discussed in patients with postponed MMC and in patients with asymptomatic stenosis (Madieke IL, Fiona K., Bonati LH, et al Investigations of the Carotid Stenosis to Identify Vulnerable Atherosclerotic Plaque and Determine Individual Stroke Risk. Circulation (2017; 81: 1246-53).

With the introduction of the technology of quantitative analysis of computer images, new opportunities have emerged for studying the structure of ASB [Tegos T.J., Sohail M., Sabetai MM, et al. Echomorphologic and histopathologic characteristics of unstable carotid plaques. Am. J. Neuroradiol. 2000; 21: 1937-44]. The methodology for comparing the structure and morphological features of the ABS has been developed. Such studies, despite their importance, are still few.

A known quantitative method for determining the homogeneity of the structure of an atherosclerotic plaque using the median of the gray scale or GSM (gray scale median). Images of atherosclerotic plaques obtained using standard ultrasound examination in gray scale, were subjected to subsequent computer processing. A quantitative determination of the intensity (or echogenicity) of an atherosclerotic plaque was carried out. In this case, reference areas, such as vessel lumen (which corresponds to the value of GSM 0-5) and its adventitial layer (GSM 185-195) were selected in the image. Then the image was normalized and the plaque echogenicity was evaluated. The ratio of areas with low (GSM <50) or high (GSM> 50) echogenicity determined the homogeneity of ASBs (MM Sabetai, TJ Tegos, AN Nicolaides, S. Dhanjil, GJ Pare and JM Stevens Reproducibility of Computer-Quantified Carotid Plaque Echogenicity : Can We Overcome the Subjectivity? Stroke. 2000; 31: 2189-2196). The disadvantages of this method is its use only to determine the homogeneity of the CRS.

There is a method for determining the structural characteristics of atherosclerotic plaque of the carotid arteries by ultrasound examination in B-mode, tissue harmonic mode and non-Doppler blood flow visualization mode and comparing these data with histological data (Timina I.Ye., Burtseva E.A., Skuba N.D. . et al. Comparison of the structure of atherosclerotic plaque in the carotid artery according to the data of a complex ultrasound and histological research (Ultrasound and Functional Diagnostics, 2004, No. 3, pp. 81-87). However, the method does not have sufficient accuracy in relation to the structural characteristics of the atherosclerotic plaque of the carotid arteries due to the lack of standardization of the measurement protocol. This source of information is considered as the closest analogue.

The technical result is to improve the accuracy of determining the structural characteristics of the atherosclerotic plaque of the carotid arteries, due to the standardization of the measurement protocol to minimize their error.

The technical result is achieved in that the determination of the structural characteristics of the atherosclerotic plaque of the carotid arteries is carried out by ultrasound, while an ultrasound of the atherosclerotic plaque is performed at a depth of 5.0-10.0 mm in the region of the greatest narrowing of the lumen of the carotid artery in the longitudinal and transverse projections in B - mode using a linear sensor with a radiation frequency of 11 MHz, with an average frame rate and a maximum dynamic range of 60 dB, then on the received fixed frame ah allocate atherosclerotic plaque areas up to 1 cm in size, and using the ultrasound system software, calculate the median ultrasonic signal intensity in decibels (dB) reflected from the atherosclerotic plaque areas studied and determine the intensity of the ultrasonic signal 1.1-8.0 dB atherosclerotic plaque foci of atheromatosis, 9.0-22.0 - foci of atheromatosis with numerous cholesterol crystals, 23.0-31.0 - foci of fibrosis with diffusely located lipophages and / or vessels, 32.0-39.0 - och and fibrosis with calcification 40,0-45,0 - foci of calcification.

The method is as follows.

Ultrasound examination of atherosclerotic plaque is performed on a Phillips iE33 device at a depth of 5.0-10.0 mm in longitudinal and transverse projections. The study is performed in the gray scale mode (B-mode) using a linear sensor with a radiation frequency of 11 MHz, with an average frame rate and a maximum dynamic range (60 dB). Before each study, the standard settings of the ultrasound system (display settings, color effects, power, frequency of radiation) are set. On still frames, they identify (describe) the most informative, in terms of echogenic characteristics, patches of up to 1 cm in size, located in the region of the greatest narrowing of the artery lumen. Next, using the software of the ultrasound system, the median of the intensity (in decibels, dB) of the ultrasonic signal reflected from the ASB areas studied is calculated. All images of sections of ASB in B-mode are converted to JPG format. When the intensity of the ultrasound signal is 1.1-8.0 dB, the atheromatosis foci are determined in atherosclerotic plaque, 9.0-22.0 - foci of atheromatosis with numerous cholesterol crystals, 23.0-31.0 - foci of fibrosis with diffusely located lipophages and / or vessels, 32.0-39.0 - foci of fibrosis with calcifications, 40.0-45.0 - foci of calcification.

This prospective search study included 90 patients (71 men and 19 women, median age 62 (47-79) years) observed in the Department of General Angioneurology of the Scientific Center of Neurology (Moscow) from April 2015 to March 2016. In all patients, an atherosclerotic stenosis of the CS was performed using the ultrasound study of the carotid arteries, as measured by the ECST study algorithm [European Carotid Surgery Trialist's Collaborative Group. Randomized Trial of the Cartod Surgery Trial (ECST). Lancet. 1998; 351: 1379-87], and performed CEE. An ASB ultrasound study was performed on a Phillips iE33 instrument at a depth of 5.0–10.0 mm in the region of greatest narrowing of the lumen of the carotid artery in longitudinal and transverse projections in B-mode using a linear sensor with an emission frequency of 11 MHz, with an average frame rate and maximum 60 dB dynamic range.

Standardization of the measurement protocol allows to minimize the possible measurement error. The results of the ultrasound study of the ASB structure were compared with the results of the morphological study of ASB removed during CEE. To assess the morphological structure of the CRS as a whole and its individual sections, those for which the signal intensity was established prior to surgery, each plaque was cut into blocks 0.3-0.5 cm thick in a plane perpendicular to the longitudinal axis of the artery. From each block embedded in paraffin, serial sections of 5–6 µm thick were obtained, which were stained with hematoxylin and eosin by the method of van Gieson. To identify elastic fibers, compounds of iron, lime and fibrin in plaques, sections were additionally stained using Weigert, Perls, Kossa and Shueninov respectively. Microscopic examination of the structure of each ASB was assessed by 24 components and processes: foci of atheromatosis, fibrosis, calcification, edema and necrosis of fibrous structures, the presence of lipophages, newly formed blood vessels, foci of hemorrhage, thinning and ulceration of the plaque tire, thrombus on its surface and others. the ratio in ASB sections to the area of atheromatosis, fibrosis and calcification foci, as well as the amount (severity) of other components (small, moderate, large). Statistical evaluation of the homogeneity of the compared groups was carried out using the Kruskal-Wallis criterion (with subsequent post-hoc analysis). For calculations, the statistical package SAS 9.4 was used.

Atherosclerotic stenosis of the COP in one group of patients studied was symptomatic (symptomatic patients), in the other - asymptomatic (asymptomatic patients). Asymptomatic patients, we attributed those patients who did not have anamnestic data for the presence of cerebral circulatory disorders in the stenotic ICA system for the last 6 months, as well as for the ipsilateral (in relation to stenosis) side of the brain, there were no clinical symptoms of cerebral or retinal ischemia. Patients who have undergone some form of ischemic NMC (in the vascular basin under consideration) over the past six months were regarded as symptomatic. There were more than 2 times more patients with asymptomatic course (among 90 people studied), compared with patients with symptomatic course: 62 (69%) to 28 (21%). This ratio among the studied patients to a certain extent assesses the corresponding ratio in the population of people with atherosclerotic stenosis of the CS as a whole.

The distribution of patients (n = 90) depending on the structure of ASB, the degree of stenosis of the COP and the clinical manifestations of cerebrovascular insufficiency are presented in table 1.

In order to determine the quantitative ultrasonic intensity values from certain components of the ABS in 37 of them microscopically investigated from 1 to 4 sections (a total of 67 sections of size up to 10 mm).

Analysis of a microscopic study of 67 sites with sizes up to 10 mm of ASB selected for quantitative ultrasound evaluation allowed to establish that 29 of them had foci of atheromatosis, including 17 — centers with partial calcification of fat-protein detritus, 12 - centers with numerous cholesterol crystals among atheromatous masses. Fibrous tissue foci were detected in 34 sites, while 6 sites contained foci with diffusely located lipophages and 5 sites with diffusely located vessels, 13 had large clusters of them, and 10 sites had foci of fibrosis along with individual lipophages and / or vessels small calcifications were determined. The remaining 4 plots were large foci of calcification. The results of the comparison of the quantitative ultrasound assessment of the areas of ASB with their morphological structure are presented in table 3.

As a result of the comparison, statistically significantly different ranges of ultrasonic signal intensity for atheromatosis foci, foci of atheromatosis with numerous cholesterol crystals, foci of fibrosis with diffusely located lipophages and / or newly formed vessels, foci of fibrosis with calcifications and foci of calcification were determined: 1.1-8 , 0 dB, 9.0-22.0 dB, 23.0-31.0 dB, 32.0-39.0 dB and 40.0-45.0 dB, respectively (values from 15 to 85 are given th percentiles).

All variants of ASB on the intensity of the reflected ultrasonic signal differ statistically significantly.

As examples, ultrasound and morphological studies of samples of atherosclerotic plaques of patients with ischemic NMC are presented.

Examples of the method.

Sample 1. Ultrasound and morphological characteristics of the main components of the ABS are shown in Fig. 1a, b:

a - a dedicated area with the intensity of the ultrasonic signal up to 2 dB;

b - atheromatosis focus (indicated by an arrow), corresponding to the area on the ultrasound image (histological section of ASB, stained with hematoxylin and eosin, magnification × 40).

Sample 2. Ultrasonic and morphological characteristics of the main components of the ABS are shown in Fig. 2a, b:

a - a dedicated area with an ultrasonic signal intensity of 10 dB;

b - atheromatosis focus with numerous cholesterol crystals (indicated by an arrow), corresponding to the area on the ultrasound image (histological section of ASB, stained with hematoxylin and eosin, magnification × 40).

Sample 3. Ultrasonic and morphological characteristics of the main components of the ABS are shown in Fig. 3a, b:

a - a dedicated area with an ultrasonic signal intensity of 23 dB;

b - center of fibrosis with diffusely located lipophages (indicated by an arrow), corresponding to the area on the ultrasound image (histological section of ASB, stained with hematoxylin and eosin, magnification × 40).

Sample 4. Ultrasonic and morphological characteristics of the main components of the ABS are shown in Fig. 4a, b:

a - a dedicated area with an ultrasonic signal intensity of 32 dB;

b - center of fibrosis with calcifications (indicated by an arrow), corresponding to the area on the ultrasound image (histological section of ASB, stained with hematoxylin and eosin, magnification × 40).

Sample 5. Ultrasonic and morphological characteristics of the main components of the ABS are shown in Fig. 5a, b:

a - a dedicated area with an ultrasonic signal intensity of 40 dB;

b - center of calcification (indicated by an arrow), corresponding to the area on the ultrasound image (histological section of ASB, stained with hematoxylin and eosin, magnification × 40).

Claims (1)

Method for determining the structure of atherosclerotic plaque of the carotid arteries, including ultrasound examination of atherosclerotic plaque in longitudinal and transverse projections in B-mode using a linear sensor with a medium frame rate and a maximum dynamic range of 60 dB, atherosclerotic plaques are obtained on the fixed frames and by means of software ultrasound systems calculate the median ultrasonic signal intensity in decibels (dB) reflected from Atherosclerotic plaque areas studied, characterized in that ultrasound of atherosclerotic plaque is performed at a depth of 5.0-10.0 mm in the region of the greatest narrowing of the carotid artery lumen using a sensor with an emission frequency of 11 MHz, areas of atherosclerotic plaques up to 10 mm in size and with the intensity of the ultrasound signal 1.1-8.0 dB determine atheromatosis foci in atherosclerotic plaque, at 9.0-22.0 - foci of atheromatosis with numerous cholesterol crystals, at 23.0-31.0 - foci of fibro and arranged to diffusely lipofagami and / or vessels, with 32,0-39,0 - fibrosis with foci of calcification at 40,0-45,0 - calcification foci.

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