Vascular deformation in human atherosclerotic carotid artery evaluated by 2D analysis of ultrasonography

Abstract

Objectives

Common carotid artery (CCA) remodelling in the atherosclerosis process is an inherent necessary element that decreases the progress of significant lumen compromise. The present study used a semi-automated method to assess relationships of intima-media thickness (IMT), lumen diameter (LD) and inter-adventitial diameter (IAD) using ultrasound B-mode images of atherosclerotic carotid artery.

Methods

In the cross-sectional study, 120 male subjects (age range: 40–60 years) were classified into four research groups namely control, mild, moderate, and severe stenosis. The maximum near and far wall IMT, mean of both walls’ IMT and IAD, and also LD of the left CCA were extracted for all participants. Pearson correlation coefficient was utilized to investigate relationships of IMT, LD, and IAD.

Results

Results revealed that the maximum far and near wall IMT, mean of both walls’ IMT and IAD in the CCA were significantly different in stenosis patients and the control group (p< 0.001). However, there were no significant differences among the four studied groups in terms of LD of CCA (p = 0.65). There was a stronger correlation between mean of both walls’ IMT and IAD in comparison with mean far wall IMT and IAD (p < 0.001).

Conclusions

Results indicated that changes of IAD in the left CCA were associated with carotid deformation, and thus it can be considered as a predictor of atherosclerosis process.

Keywords

Atherosclerosis adventitia carotid arteries carotid stenosis ultrasonography

Introduction

Atherosclerosis is considered as a slowly extended disease that may begin in the early life due to the damage to the endothelial function and gradual changes in the arterial wall.¹ Moreover, atherosclerosis is usually followed by lumen narrowing, cardiovascular diseases (CVD), and stroke.² These gradual changes in the endothelium highlight the importance of using some specific tools that can evaluate pre-clinical arterial wall remodelling during the atherosclerosis.

According to previous reports, the arterial evaluation including carotid artery through B-mode images of ultrasound is a simple and quantitative method that can be efficiently used for the early diagnosis of atherosclerosis in the arterial wall.^3,4 Among various non-invasive methods, changes in lumen diameter (LD), inter-adventitial diameter (IAD) and intima-media thickness (IMT) provide the most important data about the vascular remodelling.⁵ Changes in IAD is associated with aging, higher blood pressure, glucose intake, body mass index, lipid, atherosclerotic lesions, CVD, and stroke.⁶ The common carotid artery (CCA) wall is straight and parallel to the skin surface. The proximal internal carotid artery (ICA) walls are regularly deviating curvilinear and the vessel normally descends deeper into the neck as distance increases from the skin’s surface. They lead a less optimal angle of insolation than the CCA, and thus a less sharp image.⁷

Most studies have mainly focused on evaluating arterial properties by manual tracing.⁸ However, manual tracing is not a reliable method since it works based on the subjective operator assessment. Some studies have suggested a preferable automated algorithm for measurement of arterial properties.^8,9 The automated algorithm reduces the length of image processing time and increases the reproducibility of results.^8,9 Meanwhile, the thickness measurement of intimal and medial layers without measuring adventitial layer thickness seems insufficient to estimate magnitude of mechanical changes in an arterial wall.¹⁰

In the present research, a novel semi-automated method was used to evaluate the vascular deformation in the human atherosclerotic left CCA throughout the cardiac cycle and assess relationships of IMT with LD and IAD that might provide a predictor of the atherosclerosis process on B-mode ultrasound images.

Methods

The present study was reviewed and approved by the ethics committee of Kashan University of Medical Sciences (Iran). All subjects gave informed written consent forms prior to the participation in the study according to the World Medical Association Declaration of Helsinki revised in Edinburgh in 2000.

Research population

In the present cross-sectional study, 120 men aged 40–60 were examined from November 2017 to October 2018. Stages of stenosis in the left bulb and internal carotid were evaluated using the Doppler ultrasonography and angiography. Research groups were divided into (1) control group including participants without any history of cardiovascular/cerebrovascular diseases, hypertension, hypercholesterolemia, diabetes mellitus and tobacco consumption, (2) mild stenosis group (<50%), (3) moderate stenosis group (50–69%), and (4) severe stenosis group (≥70% stenosis). The classification was based on the North American symptomatic carotid endarterectomy trial (NASCET) and our previous work.^11,12 Table 1 presents the Doppler’s characterizations and ultrasonography findings for the above four groups.

Table 1.

Doppler’s characterizations and sonography findings in all the studied groups of subjects including; control, mild, moderate, and severe stenosis.

Characteristics of DopplerStenosislevel	PSV of ICA	EDV of ICA	ICA/CCA PSV	Ultrasonography findings
Control	<125 cm/s	<40 cm/s	<2	No evident plaque or intimal thickness
Mild (<50%)	<125 cm/s	<40 cm/s	<2	The plaque or intimal thickening was evident
Moderate (50–69%)	125–230 cm/s	40–100 cm/s	2–4	Plaque was evident
Severe (≥70%)	>230 cm/s	>100 cm/s	>4	Plaque or luminal narrowing was evident at gray scale and Doppler ultrasound

CCA: common carotid artery; EDV: end diastolic velocity; ICA: internal carotid artery; PSV: peak systolic velocity.

In terms of angiography, the stenosis magnitude was measured by comparing residual lumen diameter at narrowing point and diameter of distal ICA at a level relating to non-disease, free calcification and a normal wall thickness. The measurement was not performed when the ICA was normal.¹³

Ultrasound studies and offline analysis

Research participants were in the supine position and their heart rates and blood pressure were recorded using an oscilloscopic method (ALP, Tokyo, Japan) on the left brachial. According to current guidelines, measurements were performed in a room with controlled temperature.¹³ The left CCA in the longitudinal direction (2–3 cm proximate to the bifurcation) was examined using a 5–13 MHz linear array ultrasound system (Sonoline Antares, Siemens, Germany) by a certificated sonographer in our radiology department. Ultrasonography parameters such as gray level range, dynamic range, and depth of focus were set to 0–255, 55 dB, and 3.5 cm, respectively.¹⁴ Video files of the CCA were captured from the hard drive during three cardiac cycles, and they were then transferred to a personal computer (PC) for an offline analysis. An in-house program was written in MATLAB 7.0.1 (Math Software Co., Math Works, USA) to extract sequential images from AVI movies into the bitmap image file format (image size of 547 × 692 pixels). Maximum gradient and dynamic programming algorithms were composed and implemented for the above program. It should be noted that these algorithms are widely introduced and utilized for an ultrasonic image analysis.^11,15,16

In an offline procedure, the proposed computerized analysis algorithm was used for detection of instantaneous changes in carotid IMT, IAD, and LD in consecutive ultrasound images. For measurements, IAD was defined as a distance between near wall adventitia and the far wall adventitia; and LD was considered as a distance between near wall intima and far wall intima (Figures 1 and 2).

Figure 1.

A B-mode ultrasonography image of a typical common carotid artery, showing IMT, IAD and LD. IAD: Inter-adventitial diameter; IMT: intima-media thickness; LD: lumen diameter.

Figure 2.

A sample for demonstrating variations in the diameter and IMT during three cardiac cycles on the common carotid artery B-mode sonographic image. (a) Variations in the lumen diameter. (b) Variations in the inter-adventitial diameter. (c) Variations in the IMT on the far wall. (d) Variations in the IMT on the near wall. IMT: intima-media thickness.

This method was fully introduced and evaluated in the ultrasound imaging of carotid artery giving the best results in our previous studies.^9,11 The suggested method was applied on all generated frames on a sequence of IMT, IAD, and LD throughout cardiac cycles (three cycles). This tracing was used to calculate maximum near and far wall IMT during three cardiac cycles in the CCA, and then average values were recorded. The final IAD and LD measurements were based on average of three baseline diameter measurements. Measurements of diameter and IMT were synchronized with electrocardiogram (ECG) and blood velocity during evaluation of CCA.

Statistical analysis

All statistical analyses were performed using the SPSS (v13.0). Data of normal distribution and equality of variance was tested using the Kolmogorov–Smirnov test and Levene’s test, respectively. All continuous variables were presented as the mean ± standard deviation. Afterwards, an ANOVA was utilized with Bonferroni post hoc test to detect any significant difference of maximum near wall IMT, maximum far wall IMT, and average of both walls’ IMT, IAD, and LD separately in four research groups. Linear regression analysis was used to compute the correlation between continuous variables, and the Pearson correlation coefficient was applied to assess relationships of IMT, LD, and IAD. A p < 0.001 was considered to be statistically significant. The statistical reproducibility was calculated and reported as a coefficient of variance percentage (%COV). Frequency distribution of different grades of carotid artery stenosis was analyzed in patients with a history of myocardial infarction (MI), hyperlipidemia (triglyceride ≥150 mg/dL or total cholesterol level ≥200 mg/dL or HDL cholesterol level ≤50 mg/dL), hypertension (systolic blood pressure ≥140 mmHg and diastolic blood pressure ≥90 mmHg in two separate measurements), diabetes mellitus (fast blood sugar (FBS) ≥126 mg/dL or blood sugar (BS) ≥200 mg/dl or a haemoglobin A1c level ≥6.5% in two separate measurements), and cigarette smoking (smoking frequency ≥10 cigarettes per day) through chi-square test with a p-value < 0.05.

Results

Table 2 summarizes main demographic characteristics in our four research groups. Furthermore, risk factors of the CVD such as hyperlipidaemia, hypertension, diabetes mellitus, cigarette smoking, and MI were 14%, 17%, 14%, 41%, and 24% for mild stenosis group; 37%, 17%, 20%, 60%, and 43% for moderate stenosis group; and 11%, 48%, 21%, 55%, and 59% for severe stenosis group respectively. The data were analyzed using the chi-square test considering p-value = 0.031 for hyperlipidaemia, p-value = 0.008 for hypertension, and p-value = 0.029 for MI. There was a significant relationship between the history of these criteria and severity of stenosis in mild, moderate, and severe groups. Our results indicated that there was not any significant relationship between the history of diabetes mellitus, cigarette smoking (p-value = 0.754, and p-value = 0.334, respectively) and different grades of carotid artery stenosis groups.

Table 2.

Main demographic characteristics of four research groups (control, and mild, moderate, and severe stenosis).

Parameters (mean ± SD)	Control (n = 32)	Mild stenosis (n = 29)	Moderate stenosis (n = 30)	Severe stenosis (n = 29)	p-Value
Age (year)	51 ± 3	52 ± 5	52 ± 2	53 ± 2	0.38
BMI (kg/m²)	25 ± 2	24 ± 2	24 ± 2	25 ± 1	0.06
Ps (mmHg)	127 ± 19	130 ± 13	131 ± 19	135 ± 10	0.18
Pd (mmHg)	80 ± 9	81 ± 6	80 ± 6	82 ± 7	0.64
HR (bpm)	75 ± 7	72 ± 11	73 ± 5	75 ± 6	0.56

BMI: Body mass index; Ps: systolic pressure; Pd: diastolic pressure on the left brachial artery; HR: heart rate; bpm: beat per minute.

Figure 3 presents a significant increase in the maximum far wall IMT, near wall IMT, and average of the both walls’ IMT of the left CCA in the severe group compared to the control group (p-value < 0.001). The COVs were 14.64%, 12.48%, and 12.38%; 16.33%, 14.08%, and 14.77%; 13.60%, 13.60% and 11.88%; 15.85%, 14.60%, and 15.42%, respectively for three extracted parameters of the left CCA in terms of IMT from control group to severe group. The COV% of IAD was 8.80%, 12.96%, 8.93% and 7.34% for control, mild stenosis, moderate stenosis, and severe stenosis groups, respectively. There was no significant correlation between maximum far wall IMT and IAD of the left CCA in the control group (r = 0.35, p-value = 0.07), whereas a significant correlation was seen between these two parameters in mild (r = 0.65, p-value < 0.001), moderate (r = 0.72, p-value < 0.001), and severe (r = 0.82, p-value < 0.001) stenosis groups. Figure 4 shows a weak correlation between IAD and the average near and far walls’ IMT in the control group (r = 0.37, p-value = 0.04) where there is a significant correlation between two indices in the mild (r = 0.68, p-value < 0.001), moderate (r = 0.75, p-value < 0.001), and severe (r = 0.86, p-value < 0.001) groups.

Figure 3.

IMT results (mean and standard deviation) in left common carotid artery in each study group, showing (a) far wall, (b) near wall, and (c) IMT averaged of both walls. IMT: Intima-media thickness.

Figure 4.

IAD in LCCA is plotted versus mean far and near walls IMT in the (a) control, (b) mild stenosis, (c) moderate stenosis, and (d) severe stenosis groups. R is correlation coefficient. IAD: inter-adventitial diameter; IMT: intima-media thickness; LCCA: left common carotid artery; LD: lumen diameter.

According to Table 3, which reports all measured values of IMT, IAD, LD for the left CCA during three cardiac cycles, IMT and LD values in participants’ left CCA, respectively, showed the most and the least significant differences among four studied groups. COVs of LD were 13.35% for the control group and 14.49%, 12.85% and 15.45% for the mild, moderate and severe groups, respectively. Results of the present study did not show any significant correlation between the far wall IMT and LD on the left CCA among participants in the control group (r = 0.17, p-value = 0.38) and mild (r = 0.21, p-value = 0.26), moderate (r = 0.29, p-value = 0.11) and severe (r = 0.32, p-value = 0.08) stenosis groups. No significant correlation was seen between LD and average of both walls’ IMT on the left CCA among participants in the control group (r = 0.21, p-value = 0.25) and three other groups of mild (r = 0.25, p-value = 0.19), moderate (r = 0.30, p-value = 0.18) and severe (r = 0.34, p-value = 0.07) stenosis groups.

Table 3.

Measured values of IMT, IAD, LD for the left CCA during three cardiac cycles.

Parameter (mm)	Maximum	Minimum	Mean	Median	SD
Indices	Maximum	Minimum	Mean	Median	SD
IMT for near wall (Control)	0.82	0.54	0.68	0.66	0.08
IMT for far wall (Control)	0.77	0.40	0.60	0.62	0.09
IMT average between far and near wall (Control)	0.80	0.50	0.64	0.65	0.08
IAD(Control)	7.29	4.99	5.93	5.97	0.52
LD (Control)	6.48	4.01	4.98	4.92	0.67
IMT for near wall (Mild)	0.94	0. 58	0.78	0.79	0.11
IMT for far wall (Mild)	0.88	0.52	0.73	0.71	0.12
IMT average between far and near wall (Mild)	0.91	0.55	0.78	0.75	0.11
IAD (Mild)	8.42	5.37	6.63	6.32	0.86
LD (Mild)	6.72	3.97	5.24	5.17	0.76
IMT for near wall (Moderate)	1.07	0. 63	0.90	0.87	0.11
IMT for far wall (Moderate)	1.08	0.58	0.86	0.87	0.12
IMT average between far and near wall (Moderate)	1.08	0.61	0.88	0.89	0.11
IAD (Moderate)	8.36	6.12	7.21	7.10	0.64
LD (Moderate)	6.97	4.31	5.51	5.52	0.71
IMT for near wall (Severe)	1.35	0.60	1.06	1.08	0.16
IMT for far wall (Severe)	1.21	0.56	0.96	0.93	0.15
IMT average between far and near wall (Severe)	1.25	0.56	0.98	1.00	0.15
IAD (Severe)	8.81	6.39	7.68	7.69	0.56
LD (Severe)	8.89	3.98	5.57	5.20	0.86

CCA: Common carotid artery; COV: coefficient of variance; IAD: inter-adventitial diameter; IMT: intima media thickness; LD: lumen diameter.

Discussion

Various studies have suggested that the measurement of arterial diameter and/or its wall surface area, which are both related to the wall thickness, may produce comprehensive predictive data for conceiving the atherosclerosis process and vascular damage.⁶ Most studies are performed based on manual tracing that is time-consuming and depends on operator evaluation skills.^8,9 Other studies on the atherosclerosis process have been designed based on the active contour, Hough transform, and Nakagami distribution methods.^15,17 These methods were explained to all subjects suffering from a precise differentiation of layers’ intensities. For instance, Hough transform cannot correctly discern intima, media, and adventitia layers because the acquisition devices may vary for adapting in acquisition protocol when the CCA is not completely in the horizontal direction. Other methods, which were planned based on the measurement of diameter and IMT from just one frame, suffer from a deficiency of inter-frame correlation in video ultrasound data and uncertainty due to motion and speckle artifacts. Moreover, the local contrast between proper anatomic parts can be altered from one frame to another.¹⁸

According to the above-mentioned aspects of the current study, two methods namely dynamic programming and maximum gradient were used to measure the arterial diameter and IMT in the CCA during three cardiac cycles. The former had high accuracy and latter offered the lower computation complexity.^9,11 It should be noted that reference points and the cost function were related to dynamic programming and maximum gradient algorithms, respectively. The arterial wall is where a kind of biological balance occurs among functions of endothelium, smooth muscles, ratio of collagen to elastin, and makes vasa vasorum in adventitial layer during atherosclerosis process.¹⁹ Magnoni et al. found a relationship between the magnitude of adventitial vasa vasorum and the IMT of carotid artery.²⁰ This association affected the IAD during prior steps of atherosclerosis; the artery expansion retained the blood flow and shear stress via Glagov event. In this phenomenon, the LD may remain unchanged where IAD considers the enhancement of arterial wall thickness.²⁰

Eigenbrodt et al.²¹ found that carotid arterial IAD was an index of the injuring phenomenon of atherosclerosis and most probably an adaptive event. Another study indicated that both IMT and IAD in the CCA were widely related to the incident stroke.⁵ Polak et al.²² found that IAD in the CCA was independently related to the left ventricular mass and they proposed this relation as an explanation for the ability of IAD to improve prediction of CVD. Other studies indicated that CCA-IMT and IAD values were complementary in identifying atherosclerotic disease and stroke risks.²³ In addition to these aspects, the measured mean IMT on far CCA wall is likely more practical than measured mean IMT on far bifurcation and internal wall carotid artery. Schott et al.²⁴ argued that the measurement of mean far CCA wall IMT and IAD had proper reproducibility. A research indicated that the measurement of near and far CCA walls IMT could provide a more sophisticated assessment of atherosclerosis progression.²⁵ Rodriguez-Hernandez et al.²⁶ reported that there was a significant difference between IMT of the right- and left-side CCA in untreated hypertensive patients. According to this difference, the potential trend for cerebrovascular diseases on the left CCA may be due to the greater intimal hyperplasia or more extensive medial hypertrophy. Both conditions could be shown as a sequel increased hemodynamic stress on the side. Eigenbrodt et al.²³ confirmed the finding of a significantly higher CCA-IMT on the left side, but its results also included some uncertainties about measurement of different blood pressures between two sides, shear stress and vascular anatomy. According to these problems, the present study assessed the maximum near wall IMT, maximum far wall IMT, average of both walls IMT, IAD, and LD of the left CCA in 90 men in order to assess the atherosclerosis process.

Vascular remodelling is a useful method for evaluating sclerotic artery especially when the artery shape alters as a response to the atherosclerosis process. Glagov et al.²⁷ found that compensatory remodelling event preserved or even enlarged diameter during an atherosclerotic process.^2,27 Compensatory enlargement of arteries can be due to withering and thinning of media layer produced by atherosclerosis. This may lead to the extensive passive dilation of artery. In addition, as the second effective factor, structural weakening of layer may result from the interaction of LDL with collagen and elastin expanding the endocytosis by smooth muscle cells and macrophages.²⁸ Some studies have explained that the artery wall is affected by shear stress changes.²⁸ A rise in wall shear stress and a reduction in LD by improved atheroma may lead to the compensated enlargement artery until the equalization of wall shear stress.²⁸ Emphasizing these aspects, the present study indicated a significant increase in the maximum near wall IMT, far wall IMT, average both walls IMT, and IAD (p-value < 0.001) in the control group compared to the severe stenosis group. The findings were consistent with some previous studies.^5,6 Eigebrodt et al.⁶ presented significant increase in IMT and external diameter (IAD) in subjects with carotid sclerotic injuries compared to those without injuries.

Findings of the present research might be due to the following results: first, compensatory enlargement of the carotid artery occurred with a diameter stenosis of 15–85%. As expected, the IAD was sensitive enough to assess the vascular enlargement.²⁹ Second, the CCA wall thickening was strongly related to the larger IAD. Third, there was a salient improvement in media with adventitia growth and intima formation, and the outward remodelling was probably more important for preliminary alternations in the CCA wall rather than changes in the lumen size.³⁰ There was no significant increase from control group to severe stenosis in term of LD in the CCA (p-value = 0.65). It might be a reason for the marginal accompaniment with wall thickening and the enlargement of IAD. Furthermore, the vascular remodelling strongly preserved lumen dimension even at advanced stages of atherosclerosis. Finding also indicated that there was a little higher significant correlation between the average of both walls IMT and IAD. The current study indicated that, first there were significant relationships between risk factors of CVD and the severity of arterial sclerotic stenosis. It could be emphasized on the substantial impression of risk factor of CVD in the creation of stenosis in carotid artery. Second, there was a significant increment in the IMT and IAD of CCA with enhancement in the severity of atherosclerotic–related cardiovascular incident; and finally, there was a significant correlation between IMT and IAD in three stenosis groups. According to the above-mentioned aspects of simultaneous evaluation of the IMT and the IAD, they can be used as clinical markers for detecting risk groups and their convenient therapies, which may decrease risks of cerebrovascular phenomenon and stroke.

Displacement of the CCA, mainly due to the ultrasound probe pressure during scanning, as well as the reduction of artery pulsating movements were the main limitations of study. Moreover, the comprehensive validation of derived findings needs paying attention to some important confounding factors such as genetic evaluation and life style. The investigation of a significant larger multi-centric population may yield more accurate results with higher predictive capability.

Conclusions

According to the present study, changes in inter-adventitial diameter on the left common carotid artery were associated with the carotid deformation and provided a potential predictor for the atherosclerosis process. According to results, there was a stronger correlation between inter-adventitial diameter and averages of both walls intima-media thickness compared to the mean far wall intima-media thickness.

Further studies on the association between common carotid artery remodelling and the atherosclerosis process may contribute to prediction of the incidence of sudden cardiovascular diseases and stroke.

Footnotes

Acknowledgements

We would like to thank Dr Kamran Hami, Yaser Hamedian and the personnel of sonography department of Beheshti cardiovascular medical and research hospital in Kashan, Iran.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

References

Sharma

Kasliwal

Bansal

, et al. Carotid intima-media thickness: current evidence, practices, and Indian experience. Indian J Endocr Metab 2014; 18: 13

Renna

de Las Heras

Miatello

, et al. Pathophysiology of vascular remodeling in hypertension. Int J Hypertens 2013; 2013: 808353

Zavodni

AEH

Wasserman

McClelland

, et al. Carotid artery plaque morphology and composition in relation to incident cardiovascular events: the multi-ethnic study of atherosclerosis (MESA). Radiology 2014; 271: 381–389.

Qin

Luo

, et al. Decision tree analysis of traditional risk factors of carotid atherosclerosis and a cutpoint-based prevention strategy. PLoS One 2014; 9: e111769.

Baldassarre

Hamsten

Veglia

, et al. Measurements of carotid intima-media thickness and of interadventitia common carotid diameter improve prediction of cardiovascular events: results of the IMPROVE (Carotid Intima Media Thickness [IMT] and IMT-Progression as Predictors of Vascular Events). J Am Coll Cardiol 2012; 60: 1489–1499.

Eigenbrodt

Sukhija

Rose

, et al. Common carotid artery wall thickness and external diameter as predictors of prevalent and incident cardiac events in a large population study. Cardiovasc Ultrasound 2007; 5: 11

Sutton-Tyrrell

Wolfson

Thompson

, et al. Measurement variability in duplex scan assessment of carotid atherosclerosis. Stroke 1992; 23: 215–220.

Kumar

Nagarajan

Common carotid artery intima media thickness segmentation survey. World Acad Sci Eng Technol Int J Medical, Heal Biomed Bioeng Pharm Eng 2015; 8: 689–693.

Rafati

Bitarafan-Rajabi

Hami

Performance intima-media thickness of carotid artery and flow mediated dilation of brachial artery for assessing atherosclerosis progression. J Med Imaging Hlth Inform 2014; 4: 724–732.

10.

Yamashita

Shoji

Tsuruda

, et al. Medial and adventitial macrophages are associated with expansive atherosclerotic remodeling in rabbit femoral artery. Histol Histopathol 2008; 23: 127–136.

11.

Rafati

Rafati Rahimzadeh

Raygan

, et al. A New 2D-based method for carotid intima-media thickness quantification from ultrasound sequences. Iran Red Crescent Med J 2015; 17: e24691

12.

Högberg

Dellagrammaticas

Kragsterman

, et al. Simplified ultrasound protocol for the exclusion of clinically significant carotid artery stenosis. Ups J Med Sci 2016; 121: 165–169.

13.

Rafati

Havaee

Moladoust

, et al. Appraisal of different ultrasonography indices in patients with carotid artery atherosclerosis. Excli J 2017; 16: 727–741.

14.

Touboul

P-J

Hennerici

Meairs

, et al. Mannheim carotid intima-media thickness consensus (2004–2006). An update on behalf of the Advisory Board of the 3rd and 4th watching the risk symposium, 13th and 15th European Stroke conferences, Mannheim, Germany, 2004, and Brussels, Belgium, 2006. Cerebrovasc Dis 2007; 23: 75–80.

15.

Molinari

Zeng

Suri

JS.

A state of the art review on intima-media thickness (IMT) measurement and wall segmentation techniques for carotid ultrasound. Comput Methods Programs Biomed 2010; 100: 201–221.

16.

Rocha

Campilho

Silva

, et al. Segmentation of the carotid intima-media region in B-mode ultrasound images. Image Vis Comput 2010; 28: 614–625.

17.

Lisowska

Knapp

Bolińska

, et al. The importance of intima-media thickness (IMT) measurements in monitoring of atherosclerosis progress after myocardial infarction. Adv Med Sci 2012; 57: 112–117.

18.

Ilea

Duffy

Kavanagh

, et al. Fully automated segmentation and tracking of the intima media thickness in ultrasound video sequences of the common carotid artery. IEEE Trans Ultrason Ferroelectr Freq Control 2013; 60: 158–177.

19.

Özcan

Deleskog

Schjerning Olsen

A-M

, et al. Coronary artery disease severity and long-term cardiovascular risk in patients with myocardial infarction: a Danish nationwide register-based cohort study. Eur Hear J – Cardiovasc Pharmacother 2018; 4: 25–35.

20.

Magnoni

Coli

Marrocco-Trischitta

, et al. Contrast-enhanced ultrasound imaging of periadventitial vasa vasorum in human carotid arteries. Eur J Echocardiogr 2008; 10: 260–264.

21.

Eigenbrodt

Bursac

Tracy

, et al. B-mode ultrasound common carotid artery intima-media thickness and external diameter: cross-sectional and longitudinal associations with carotid atherosclerosis in a large population sample. Cardiovasc Ultrasound 2008; 6: 10

22.

Polak

Wong

Johnson

, et al. Associations of cardiovascular risk factors, carotid intima-media thickness and left ventricular mass with inter-adventitial diameters of the common carotid artery: the Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis 2011; 218: 344–349.

23.

Eigenbrodt

Evans

Rose

, et al. Bilateral common carotid artery ultrasound for prediction of incident strokes using intima-media thickness and external diameter: an observational study. Cardiovasc Ultrasound 2013; 11: 22

24.

Schott

Kao

Cunningham

, et al. Do carotid artery diameters manifest early evidence of atherosclerosis in women with rheumatoid arthritis? J Womens Health (Larchmt) 2009; 18: 21–29.

25.

Mitchell

Aeschlimann

Korcarz

CE.

Carotid intima-media thickness testing: technical considerations. J Am Soc Echocardiogr 2004; 17: 690–692.

26.

Rodríguez Hernández

Kroon

van Boxtel

MPJ

, et al. Is there a side predilection for cerebrovascular disease? Hypertens 2003; 42: 56–60.

27.

Glagov

Weisenberg

Zarins

, et al. Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med 1987; 316: 1371–1375.

28.

Eghbalieh

SDD

Chowdhary

Muto

, et al. Age-related neointimal hyperplasia is associated with monocyte infiltration after balloon angioplasty. J Gerontol Ser A Biol Sci Med Sci 2012; 67A: 109–117.

29.

Saito

Oka

Kajiyama

, et al. Factors predicting compensatory vascular remodelling of the carotid artery affected by atherosclerosis. Heart 2002; 87: 136–139.

30.

Korshunov

Berk

BC.

Flow-induced vascular remodeling in the mouse: a model for carotid intima-media thickening. Arterioscler Thromb Vasc Biol 2003; 23: 2185–2191.