Longitudinal study of carotid artery bifurcation geometry using magnetic resonance angiography

Abstract

Objectives

Geometry of carotid artery has been known as a risk factor for atherosclerotic carotid disease. Though aging and disease progression can both attribute to geometric changes in the arteries, the exact nature of this phenomenon remains elusive. The aim of our study was to investigate carotid artery geometric changes in a longitudinal study.

Methods

We conducted a retrospective study of 114 subjects who underwent carotid contrast-enhanced magnetic resonance angiography at our clinic at baseline (2005 to 2007) and after 10 years. The right carotid arteries were segmented using semi-automated methods to obtain various measurements of carotid artery geometry. For each patient, these parameters were assessed at both time points, including bifurcation angle, internal carotid artery angle, vessel diameter, and circumference.

Results

The median age for the total patient population (n = 114) at baseline was 59.06 ± 10.40 years. Mean time interval between baseline magnetic resonance angiography and magnetic resonance angiography after 10 years of these patients was 129.18 ± 7.77 months. For the whole group, there was a significant increase in the bifurcation angle (p < 0.05) over a 10-year period. A significant increase was also noted in the diameter and circumference of the common carotid artery (p < 0.05). However, the other vessel diameters and circumferences (bulb carotid, internal carotid) as well as the internal carotid angle did not significantly change (p ≥ 0.05).

Conclusions

The diameter and circumference of the common carotid artery and bifurcation angle significantly increased over a decade of life.

Keywords

Carotid artery geometry longitudinal study magnetic resonance angiography

Introduction

The importance of carotid atherosclerosis has been widely recognized because of its relation to stroke, which is the third leading cause of death in the United States¹ and a major contributor to severe disability. Although every carotid artery has a bulb and associated blood flow disturbances, in many patients, only one of the carotid arteries develops atherosclerotic carotid artery disease. Because the right and left carotid arteries are exposed to the same systemic risk factors in each patient, the presence of unilateral disease implies that certain arteries have special features that produce pathologic conditions that predispose the artery to atherosclerotic disease.^2–5 Instead, it has been suggested, at least as far back as the early 1980s, that aspects of artery geometry might serve as a clinically feasible surrogate of local risk markers for atherosclerosis.^2,6 Increases in diameter and tortuosity occur throughout the arterial tree with aging and disease,⁷ but the precise nature of how certain anatomic change occur with age is much less well understood.

Studies have shown that the diameter as well as inflow and outflow area ratios of the carotid bifurcation exhibit considerable variation among individuals, and the variations in the geometry of the carotid bifurcation increase significantly with age or early atherosclerotic progression.^5,8 However, there are fewer data on a longitudinal study of carotid artery geometry.⁹ These data come from studies comparing carotid geometry in young people with older healthy subjects than directly studying in an individual person.⁵ Consequently, the association of carotid geometry with aging is inferred rather than known. Therefore, the aim of this study was to investigate the changes in the carotid artery geometry over a 10-year period. For each patient, these parameters were assessed at both time points, testing the hypothesis that there is a significant increase in the vessel diameter and the angle of the carotid artery for over a decade of life.

Materials and methods

This study protocol was approved by the institutional review board of our institute. We investigated the geometry of the carotid bifurcation with contrast-enhanced magnetic resonance angiography (MRA) for 114 subjects at baseline (2005 to 2007) and after 10 years.

MR imaging protocol

All patients initially underwent contrast-enhanced MR angiography of the carotid, including MR imaging of the brain, with a 3.0-T scanner (Verio; Siemens, Erlange, Germany). Routine contrast-enhanced MRA was performed in the coronal plane using a T1-weighted spoiled gradient-echo sequence optimized for high spatial resolution and a short acquisition time. The baseline parameters were as follows: ratio of repetition time (TR) to time to echo (TE) = 3.8/1.5 ms; flip angle = 30°; slice thickness = 0.90 mm; matrix size = 384 × 180; field of view = 183 × 300 mm; echo train length = 1; number of average = 1; and acquisition time = 90 s. The parameters after 10 years were as follows: TR/TE = 3.3/1.2 ms; flip angle = 21°; slice thickness = 1.0 mm; gapless, matrix = 448 × 280; field of view = 281 × 360 mm; echo train length = 1; number of average = 1; and acquisition time = 90 s (60 maximum-intensity-projection reformatted images).

Imaging and lumen reconstruction

For all enrolled patients, the carotid angiography was uniformly performed on the right side. The carotid artery was segmented with semi-automated software (MIMICS; Materialise, Leuven, Belgium) using coronal source data for contrast-enhanced MR angiography of the artery.

Measurement of carotid artery geometry

The measurement of carotid anatomy and geometry was suggested by Thomas et al.⁵ The 3-dimensional geometric characteristics of the arterial tree were computed from the skeleton of the carotid artery generated by the segmentation software. Using the software, the central lines were first generated from the common carotid artery (CCA) to the internal carotid artery (ICA) and external carotid artery (ECA) individually. According their definition, each central line hosts the centers of spheres of maximal radius inscribed in the vessel. These central line tracts and their associated sphere radii were then used to identify the origin and nominal plane of the bifurcation and to split the vessel into its three constituent branches.^5,10 The diameter and circumference of the carotid bulb were defined at the points of the largest values in the distal CCA. The diameter and circumference of the ICA and CCA were measured at a distance of 2 cm from the carotid artery bifurcation. The bifurcation angle was then defined simply as the angle between the projections of the ICA and ECA vectors at the carotid bifurcation. The ICA angle was defined as the angle made by the vertical lines of the CCA and ICA vectors in the bifurcation plane. The medial location of the ICA was defined as the point of complete separation between the ICA and ECA and the medial course of the ICA, as defined by the frontal view of the contrast-enhanced MR angiography (Figure 1).

Figure 1.

Segmentation of carotid artery on MIMICS software showing diameter and circumference measurement. (a) The 3-dimensional geometric characteristics of the arterial tree were computed from the skeleton of the carotid artery generated by the MIMICS software. (b) The central lines were generated from the common carotid artery (CCA) to the internal carotid artery (ICA) and external carotid artery (ECA) individually. (c) The bifurcation point (i) is defined automatically on the MIMICS software base on the flow divider; Then, we identified the points on the central lines of the CCA (ii) and the ICA (iii) at a distance of 2 cm based on the bifurcation point. (d) The diameter and circumference of the carotid bulb were defined at the points of the largest values in the distal CCA. The Diameter and circumference of CCA and ICA measured through the two points (ii) and (iii). Artery diameters at each location were computed automatically using the radius of the largest sphere centered on the measurement point that could be inscribed inside the artery segmentation.

Statistical analysis

Statistical analysis was performed using SPSS version 23.0 (IBM Corp., Armonk, NY). Differences between baseline and the 10-year follow-up were assessed by paired-samples T-tests. All levels of significance were set at 0.05.

Results

Three hundred patients who underwent carotid contrast-enhanced magnetic resonance angiography at our clinic from 2005 to 2007 were included in this study. No patient had a history of carotid surgery or intervention. For 21 patients, the baseline MR images were not of sufficient quality, so carotid plaque assessment could not be performed. For 161 patients, the longitudinal coverage of repeated MRI was not sufficient (not over 10 years). For 4 patients, the CCA were occluded; therefore, these cases could not be analyzed. Eventually, 114 patients (51 men, median age = 59.06 ± 10.40) without carotid stenosis with baseline and follow-up MRI scans covering at least 10 years of carotid artery bifurcation geometry were compared. The mean time interval between baseline MRI and MRI after 10 years for these patients was 129.18 ± 7.77 months.

The geometric features of the carotid artery and results of statistical analysis between each generation are summarized in Table 1. For the whole group, the bifurcation angle significantly increased over a 10-year period (p < 0.05; 33.21 ± 15.29° for baseline vs. 34.89 ± 15.92° for 10 years or more). However, the ICA angle did not change significantly (p > 0.05; 19.09 ± 14.66° for baseline vs. 20.33 ± 14.99° for 10 years or more). A significant increase was also noted in the diameter and circumference of the CCA (p < 0.05) over a decade (diameter: 6.47 ± 1.11 mm at baseline vs. 7.12 ± 1.19 mm at 10 years or more; circumference: 20.78 ± 3.44 mm at baseline vs. 22.72 ± 3.81 mm at 10 years or more). The other vessel diameters and circumferences (bulb carotid, internal carotid) did not significantly change (p ≥ 0.05).

Table 1.

Association between the geometric parameters at baseline and after 10 years of follow-up.

Geometric parameter (n =114)	Baseline^a	After^b	p
Bifurcation angle (°)	33.21 ± 15.29	34.89 ± 15.92	0.003
ICA angle (°)	19.09 ± 14.66	20.33 ± 14.99	0.620
ICA diameter (mm)	4.98 ± 1.05	5.06 ± 1.07	0.301
CCA diameter (mm)	6.47 ± 1.11	7.12 ± 1.19	<0.0001
Bulb diameter (mm)	9.30 ± 1.38	9.39 ± 1.51	0.283
ICA circumference (mm)	16.19 ± 3.22	16.21 ± 3.35	0.926
CCA circumference (mm)	20.78 ± 3.44	22.72 ± 3.81	<0.0001
Bulb circumference (mm)	33.06 ± 5.01	32.68 ± 5.44	0.228

ICA: internal carotid artery; CCA: common carotid artery.

^aMRI at baseline (2005 to 2007).

^bMRI after over 10 years (2015 to 2018).

Discussion

The aging process is accompanied by complex structural and functional changes in the arterial system, including changes in microRNA expression patterns, autophagy, smooth muscle cell migration, and proliferation, but also in arterial calcification that progressively increases vessel rigidity and stiffness.¹¹ Normal aging and disease development both can lead to geometric changes in the artery. However, aging appears to be a more important factor.^7,12 For example, a previous study has suggested that aging is associated with increases in vessel volume and diameter of the carotid artery and ICA as well as the bifurcation angle.¹⁰ Our results demonstrated that the diameter and circumference of the CCA as well as the bifurcation angle significantly increased over a decade of life.

The rheology of the carotid bifurcation is complex; this complexity is further compounded by atherosclerotic narrowing. A previous study suggested that the increase in carotid bifurcation angle was likely related to carotid remodeling due to aging. With normal aging, the bifurcation angle progressively widens as arteries dilate and become more tortuous.¹² In our study, there was significant increase in the bifurcation angle (p < 0.05) over a 10-year period. A similar result was obtained by Kamenskiy et al. They found that the carotid bifurcation angle became wider with age, increasing by 10° over every decade of life. Additional work is necessary to better determine if there is a causal relationship between these disease-associated anatomic factors. Artery walls are known to remodel by increasing their diameters to compensate for arterial narrowing in early stages of an occlusive disease. It is also intriguing to consider that the limitation of the angle of the bifurcation could also be a factor in disease progression.¹²

In an earlier ultrasound-based study of normal individuals aged 40–70 years, Sitzer et al. concluded that “angle of ICA origin may be an independent risk factor for early atherosclerotic changes at the ICA bulb”.¹³ Another extended previous work involving healthy elderly individuals (mean age, 63 years: n = 25) showed less variation in ICA angle in older people compare with healthy younger individuals (mean age, 24 years; n = 25), suggesting that such rotation may simply be a consequence rather than a cause of vascular aging.⁵ This is because there is no obvious relationship between rotation of the carotid bifurcation and flow disturbances within the carotid bifurcation. Another previous study found that a greater ICA angle was independently associated with age and a higher degree of ICA stenosis. Unlike these results, our work suggests that there is no significant change in ICA angle over a 10-year period. This result seems to contradict Thomas et al.; however, our study is an overview of subjects who underwent carotid contrast-enhanced magnetic resonance angiography for clinical purposes, not just healthy and asymptomatic patients, like in other studies.^5,13 Furthermore, a study by Gregg noted an opposed result, in which they revealed a negative correlation between ICA angle and plaque volume.¹⁴

The impact of hemodynamic factors on the progression of atherosclerotic disease has been highlighted. Blood vessels are constantly exposed to several mechanical forces exerted on their walls, including the circumference of the vessel.^2,6 The CCA has a dense network of elastin fibers, which are distributed through the media and organized in layers. Pulse pressure-related cyclic stretch can lead to increased mechanical stress, resulting in dilation of large elastic arteries such as the common carotid.¹⁵ Kamenskiy et al. observed a trend toward increasing diameters with increasing age in the CCA and ICA, though their results did not reach statistical significance.¹² Our result with a longitudinal study revealed a significant increase in the diameter and circumference of the CCA after a 10-year period. Previous authors suggested that this could be related to degenerative changes in the longitudinally oriented elastin. Moreover, disruption of the large elastic fibers because of aging or plaque formation may also cause outer wall expansion in the CCA.

Since the 1980s, carotid bifurcation geometry has been implicated as a marker for atherosclerosis,^2,6 but it was not until the last decade that the impact of various geometrical factors was associated with changes in local hemodynamics and the development of atheroma.¹⁶ Additionally, increased vessel diameter in participants with cardiovascular risk factors may be a sign of attenuated vasoregulation, which could be an important factor for the development of atherosclerosis.¹⁷ Kamenskiy et al. suggested that the bulb exhibited a balance between longitudinal and circumferential elastin. The bulb does not contain the relatively thick layers of circumferential elastin seen in the CCA, nor does it have the smooth muscle cell layer of the ICA. This may explain the greater propensity of the bulb for circumferential dilatation with aging.¹² Our study observed a nonsignificant change in diameter and circumference of the bulb carotid after a decade of life. This result seems not to be in accordance with Kamenskiy or Jeon;^10,12 however, our result studied patients who underwent carotid MRI for clinical purposes, where almost all of them had a symptomatic disease and could have a higher risk of carotid atherosclerosis. In a recent study, Watase et al. noted that the lumen area in the bifurcation segment decreased significantly by 9.4 mm² for every millimeter increase of maximum wall thickness, whereas total vessel area did not change. This information showed that patterns of remodeling differ by carotid arterial segment: the CCA demonstrated a pattern consistent with positive remodeling, whereas the bifurcation demonstrated negative remodeling.¹⁸

In a study on the non-stenosis carotid, Jeon demonstrated a significant increase in ICA diameter and circumference with an increase in age.¹⁰ In addition, another study on abnormal intima media thickness of the carotid artery showed that the total vessel area increased significantly by 5.9 mm² for every millimeter increase of maximum wall thickness.¹⁸ Our study, with its randomization of patients and analysis of variance with aging, reports a nonagreement with previous studies that the diameter and circumference of the internal carotid artery are not significantly changed over a decade of life. By contrast, the CCA in our result had a significant increase over a 10-year period, similar to Jeon and Kamenskiy. This differentiation can be explained by the fact that the vessel wall in the ICA segment has a more muscular structure compared with the CCA segment, which may affect the capacity of the vessel segment to compensatorily remodel as a result of an increase in vascular smooth muscle mass that comes with aging and the effects of blood pressure.¹⁹

One limitation of our study is its retrospective nature and the consequent possibility of selection bias. The MRI imagings were performed for clinical purposes. As a result, these subjects were more likely to have higher vascular risks than the general population. In addition, we merely analyzed the carotid geometry; no relationship between cardiovascular risk factors and carotid geometric changes was evaluated. Furthermore, our study was not intended to be an epidemiological study; therefore, our patients do not necessarily represent the characteristics of the general population. Finally, the carotid bifurcation geometric was evaluated on the right side unilaterally.

In conclusion, our study investigating the right carotid bifurcation geometry on the patients with clinical purposes revealed that the diameter and circumference of the CCA as well as the bifurcation angle significantly increased after a decade of life. However, the other vessel diameters and circumferences (bulb carotid, internal carotid) as well as the internal carotid angle did not significantly change over this same period of time. These geometric changes may be related to degradation and fragmentation of intramural elastin,¹² but it is still unclear whether these geometric changes indeed predispose disease development or are just a consequence of remodeling during aging. On the other hand, major interindividual variations that were seen in older vessels suggest a more complex interrelationship between vascular geometry, local hemodynamics, vascular aging, and atherosclerosis, the elucidation of which needs further consideration in future studies.

Footnotes

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) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported by the Dongkook Life Science. Co., Ltd., Republic of Korea.

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