Evaluation of the Prevalence of Atherosclerosis Within the Course of Internal Carotid Artery in Cone Beam Computed Tomography Images

Abstract

The aim of the present study was to retrospectively evaluate the gender-related and age-related prevalence and severity of calcifications within the segments of the internal carotid artery in cone beam computed tomography (CBCT). By using a documented visual scale, out of 400 CBCT examinations a total of 304 CBCT scans of adult patients over 40 years old were evaluated as to the prevalence and severity of intracranial calcifications within the segments of the internal carotid artery. Calcifications were found in 117 CBCT scans. These calcifications were detected along the extracranial (C1: 53%), petrous (C2: 22.2%), Lacerum (C3:27%), cavernous (C4: 94%), and ophthalmic-clinoid (C5/C6: 65%) segments. The Friedman test showed significant differences in the severity of calcifications among the internal carotid artery segments. The McNemar test showed no significant differences between calcifications on the right or left side segments. The Chi square test showed no significant differences in the prevalence of calcifications between men and women; it also showed that the prevalence of calcifications increased with increase in age (P < 0.05). In this study, the frequency and severity of calcifications decreased throughout the C4, C5/C6, and C1 segments in a descending order; moreover, an increased incidence of calcifications by increase in age was documented irrespective of gender.

Introduction

During recent years, atherosclerosis is well recognized as a disease which is strongly related to human aging and lifestyle [1, 2]. Data have shown that atherosclerosis is an inherent component of human aging because of its presence in pre-modern human beings [2]. According to WHO statistics, cardiovascular heart diseases like ischemic heart disease and stroke continued to be the main cause of morbidity and mortality worldwide in the last 15 years [3]. Millions of people have at least one manifestation of atherosclerosis which is an important mysterious harbinger of serious cardiovascular events that affects many people all around the world [4]. The presence of calcifications on any arterial wall will increase the risk of cardiovascular events [5]. Furthermore, there is a great association of stroke with presence of calcification in the internal carotid artery, independent of cardiovascular risk factors [6]. In the study of Babiarz et al. [7], it is also indicated that ‘‘the extent of cavernous carotid artery calcification reflects the total atherosclerotic burden.’’ It has been shown that there is a difference in the presence of calcification according to ethnicity independent of atherosclerotic risk factors [8–10]. Electron beam tomography indicated a substantially higher prevalence and severity of coronary artery calcification in Caucasians compared with Asians and African Americans [8]. Moreover, the northern Manhattan stroke study showed that, after controlling sociodemographic variables and atherosclerotic risk factors, Hispanics had significantly less carotid atherosclerosis than blacks and whites [11]. In the late 1980s, dental panoramic radiographs were used to evaluate the early signs of atherosclerosis [12]. As a result of identification of calcified carotid artery atheroma in panoramic radiographs, the American Dental Association’s Council on Scientific Affairs recommended in 2006 that dentists should review the radiographs of their patients for such signs and refer them for a medical assessment [13]. It is well known that CBCT is a relatively common modality which provides accurate and reliable linear measurements for imaging of the maxillofacial structures and it is widely used in maxillofacial imaging for various purposes in dentistry [14–16]. Therefore, in the present study, the observers have used CBCT to evaluate the internal carotid artery calcifications.

As the result of the high frequency of CBCT examination in the dental field and the great number of dental patients, any additional information acquired by CBCT, like identifying intracranial carotid calcification, is substantial and physician referral is recommended for assessment of the risk factors of stroke [17]. Yet, few studies have described and evaluated the ability of CBCT to depict the presence of calcifications within the segments of the internal carotid artery. Although that racial, ethnic, gender, and socioeconomic status are independently associated with the risk of stroke, there are few studies to assess the prevalence of calcifications in the course of ICA in different populations. In this retrospective study, we aimed to evaluate the prevalence of calcifications in the segments of the internal carotid artery and the assessment of their severity using CBCT scans. Also, we aimed to compare the severity of calcifications with respect to age and gender based on an evidence-based predefined visual scale that estimates the severity of atherosclerosis.

Materials and Methods

Patients

The CBCT examinations in this study were obtained from the databases of a private dental imaging clinic. Patients were referred by maxillofacial surgeons and dentists for various purposes, for instance radiographic evaluation for implant placements and impacted teeth, before orthognathic surgery and before teeth extractions for complex cases in the either maxilla or mandible. CBCT examinations were carried out between January 2016 and December 2017. Out of 400 examinations initially submitted in our study, 304 from both genders were finally used in our study. The CBCT examinations were selected as follows: (a) patients should be 40 years of age or older, (b) CBCT examinations were taken with the maxillofacial protocol mode (full volume or large FOV), and (c). There were no movement or strip artifacts. Both age and gender of patients were recorded and then CBCT scans were codified for anonymity.

CBCT Imaging

All CBCT examinations were scanned by the same clinician by a NewTom VGi CBCT machine (QR-SRL, Verona, Italy) with the exposure factor set at 110 KVP, 2.04 mA, exposure time of 3.6 S, and a field of view of 15 × 15 cm.

CBCT images of a total of 304 patients (168 males and 136 females) with a mean age of 54 years (ranging from 40 to 89) who were referred to a private oral and maxillofacial radiology center for various reasons were evaluated. The patients with the history of trauma and/or surgical intervention in the TMJ and/or craniofacial abnormalities were not included in the study. Patients’ age and gender were recorded.

Image Evaluation

All CBCT images were examined concomitantly by two oral and maxillofacial radiologists who were blind to the patients’ age and gender and had more than 10 years of experience in interpretation of CBCT images. The observers were blinded about the patients’ dental and medical history. All multiplanar reconstructions (axial, coronal, and sagittal) of each volume were performed and each CBCT data was evaluated until agreement was achieved. The viewing procedure was standardized and done by assessing the multiplanar reconstructions of the volume under investigation; calcifications were characterized if they were present in a series of at least 3 sequential slices (axial or/and coronal or/and sagittal) to avoid false positive findings as a result of imaging artifacts, noise or movement.

The presence of calcifications in the segments of ICA was described as absent, mild (thin, discontinuous), moderate (thin continuous), and severe (thick, continuous) [18] (Fig. 1). Six segments of ICA were evaluated (Figs. 2, 3, 4). Identification of certain anatomic landmarks enabled us to detect the calcifications along the course of the segments of the internal carotid artery, including the extracranial segment (C1), intracranial petrous (C2), lacerum (C3), cavernous (C4), clinoid (C5), and ophthalmic (C6) segments. We recorded the radiopacities displayed along the course of ICA from the cervical portion (C1) to the petrous segment (C2) in the posterior edge of the foramen lacerum. According to the diagnostic cerebral angiography book [19], the lacerum segment (C3) turns upward, ascending toward the cavernous sinus. In addition, the ICA’s cavernous segment (C4) area was diagnosed as the one that begins at the end of the carotid canal near the posterolateral margin of the foramen lacerum. It bends twice to form the anterior loop and reverses its course by 180°, after exiting from the cavernous sinus. C4 segment is surrounded by the anterior clinoid process. At last, the clinoid segment (C5) and the ophthalmic segment (C6) were detected on CBCT with the presence of calcifications as indicated by the corresponding anatomic landmarks. Through the sphenoid sinus and the anterior clinoid processes, in the coronal sections within the C4–C6 segments of ICA, the shape of radiopacities was seen as single or multiple ‘rice grains’ characteristic oblique ring-like or figure eight shaped. In the axial sections, these findings could be seen as tubular or curvilinear oblique structures, continued from the anterior to posterior clinoid process (C4), located in the lateral part of the hypophysial fossa (C6). Also in the sagittal projections, calcifications were seen as linear or curvilinear structures along the petrous portion of the carotid canal in the temporal bone to the lacerum segment: (C2, C3), along the adjacent cavernous portion and on the medial side of the anterior clinoid process (C4). The last two segments, the clinoid and ophthalmic, were assessed together, as a result of the limited dimensions of the ophthalmic segment. The CBCT images were evaluated again by the observers with a two-week interval to assess the intra-observer reliability. Intra-observer reliability was assessed using the kappa values.

Fig. 1.

Severity of calcification patterns within the ICA, a mild, b moderate, c severe

Fig. 2.

CBCT images of calcifications within the C3 segment of the ICA, (arrows) in (a), sagittal (b), Coronal (c), axial

Fig. 3.

CBCT images of calcifications within the C4 segment of the ICA, (arrows) in (a), coronal (b), sagittal (c), axial

Fig. 4.

CBCT images of calcifications within the C5 segment of the ICA, (arrows) in (a), sagittal (b), Coronal (c), axial

Statistical Analysis

The frequencies of either the presence or absence of calcifications were noted. The data were analyzed using SPSS software, version 21 (SPSS Inc., Chicago, IL USA). The degree of the severity of the calcifications recorded along the segments of ICA was evaluated, and descriptive statistics, the Friedman test, the McNemar test, and the Wilcoxon signed-rank test were used to analyze the results. These were applied to our study’s cohort that was subdivided into 5 decade-based age-groups: 40–49, 50–59, 60–69, 70–79, and 80–89 years of age, for both genders, together with distribution and severity of calcification in each segment of the ICA. The Wilcoxon signed rank test was used to analyze the correlation between the extra-cranial and the intra-cranial severity in the segments of ICA. The McNemar test was used to analyze the differences on the prevalence between the right and left-sided calcifications. The severity and distribution of the calcifications between the genders were analyzed by the Chi square. P value of less than 0.05 was considered as statistically significant. Kappa coefficients were calculated to assess the intra-observer agreements of CBCT images assessment, according to the following interpretation of the values: 0.10, no agreement; 0.10–0.40, poor agreement; 0.41–0.60, significant agreement; 0.61–0.80, strong agreement; 0.81–1.00, excellent agreement.

Results

In total, 304 patients’ CBCT data sets were evaluated (136 female and 168 male patients). The patients’ age ranged from 40 to 89 years (mean age = 54 years ± 11). The intra-observer agreement in the CBCT images was excellent (0.853). Out of these, the presence of calcification within the course of the internal carotid artery was documented in 117 CBCT scans (38.4%) of the patients (female = 54, male = 63). The frequency of calcification in the course of ICA within age groups of the studied population is shown in Table 1.

Table 1.

The gender and age related distribution of calcifications along the course of internal carotid artery

	No. of scans	Presence of calcification	C1			C2			C3
			Mild	Moderate	Severe	Mild	Moderate	Severe	Mild	Moderate	Severe
Female
40–49	55	16 (29%)	3 (5.45%)	0	0	0	0	0	0	0	0
50–59	44	16 (36.3%)	4 (9%)	3 (6.8%)	0	0	0	1 (2.2%)	4 (9%)	1 (2%)	0
60–69	26	14 (53.84%)	4 (15.3%)	3 (11%)	3 (11%)	2 (14.2%)	4 (15.3%)	0	2 (14.2%)	2 (14.2%)	0
70–79	7	4 (57.2%)	0	3 (42%)	1 (14%)	2 (28%)	0	0	1 (14%)	0	1 (14%)
80–89	4	4 (100%)	1 (25%)	1 (25%)	1 (25%)	0	0	0	0	0	1 (25%)
Male
40–49	60	9 (15%)	1 (1%)	1 (1%)	0	0	0	0	1 (1%)	0	0
50–59	49	20 (40%)	7 (14.2%)	1 (2%)	0	1 (2%)	0	0	0	0	0
60–69	37	18 (48%)	4 (10.8%)	6 (16.2%)	2 (5.4%)	4 (10.8%)	1 (2.7%)	0	4 (10.8%)	1 (2.7%)	0
70–79	14	8 (50%)	0	3 (21.4%)	4 (28.5%)	4 (28.5%)	1 (7.1%)	0	3 (21.4%)	3 (21.4%)	0
80–89	8	8 (100%)	1 (12.5%)	0	7 (87.5%)	1 (12.5%)	4 (50%)	2 (25%)	0	5 (62.5%)	3 (37.5%)

	No. of scans	Presence of calcification	C4			C5/C6
			Mild	Moderate	Severe	Mild	Moderate	Severe
Female
40–49	55	16 (29%)	13 (23.6%)	0	0	3 (5.45%)	1 (1.8%)	0
50–59	44	16 (36.3%)	8 (18.18%)	7 (16%)	1 (2.2%)	7 (16%)	2 (4%)	1 (2.2%)
60–69	26	14 (53.84%)	0	9 (34%)	5 (19.2%)	2 (14.2%)	8 (30%)	2 (14.2%)
70–79	7	4 (57.2%)	0	2 (28%)	2 (28%)	1 (14%)	2 (28%)	1 (14%)
80–89	4	4 (100%)	3 (75%)	0	1 (25%)	0	0	0
Male
40–49	60	9 (15%)	4 (6%)	3 (5%)	0	4	0	0
50–59	49	20 (40%)	6 (12.2%)	10 (20%)	0	9 (18.3%)	6 (12.2%)	0
60–69	37	18 (48%)	2 (5.4%)	10 (27%)	7 (19%)	6 (16.2%)	6 (16.2%)	0
70–79	14	8 (50%)	0	3 (21.4%)	4 (28.5%)	2 (14.2%)	5 (35.7%)	1 (7.1%)
80–89	8	8 (100%)	0	1 (12.5%)	8 (100%)	0	1 (12.5%)	6 (75%)

The percentages listed after the numbers of scans for each age group refers to the number of findings per number of scans in that age-group

With regard to the degree of severity of the calcifications, the Friedman test showed that the C4 segment presented the highest degree of severity (33.3, 42.7, 17.9 of these segments showed mild, moderate and severe calcifications, respectively) followed by C5/C6 and C1 segments in a decreasing order. (Table 2, Fig. 5). These results showed that the degree of severity of calcifications differs among the segments of ICA. The McNemar test showed no significant difference in the presence of the calcifications in the right and left sides (Table 3.) It showed that the presence of calcifications increased with aging significantly. Furthermore, the result of the Chi squared test showed significant differences in the severity of the calcifications between different age groups. Also, the Chi square test showed no significant differences in the severity of calcifications in each segment between the genders.

Table 2.

The Friedman test results for comparison between segments of the internal carotid artery in respect to severity

	Mean rank
Extracranial severity	3.05
Petrous severity	1.98
Lacerum severity	2
Cavernous severity	4
Ophthalmic-clinoid severity	3.32
N	304
Chi- squared	226.046
df	4
Asymptotic significance	.000

Fig. 5.

Percentage of prevalence of calcification in each segment of internal carotid artery

Table 3.

the Wilcoxon signed rank test results for the comparison of calcifications between the right and left sides in each internal carotid artery segment

	Extracranial Left-extracranial right	Petrous Left-petrous right	Lacerum Left- Lacerum right	Cavernous Left- cavernous right	Ophthalmic-clinoid left- ophthalmic-clinoid right
Asymptotic significance (2-sided)	.985	.916	.951	.285	.448

Discussion

The significance of the presence of carotid artery calcifications was recently noticed by a consortium of OMFRs and medical radiologists [20]; these calcifications represent the ‘‘ tip of the iceberg’’ and a later manifestation of a mature atheroma has been associated with a high risk of cerebral emboli [20–22]. Hence, it is recommended to refer these patients for further medical evaluation that can decrease the morbidity and potential adverse effects on the quality of life. As a result of the severity and importance of the presence of calcifications in the course of ICA, it would be better to evaluate CBCT examinations in their entirety instead of just the requested diagnostic region. Therefore, in this study, we aimed to assess the distribution and presence of calcifications along the course of the internal carotid artery and also evaluate the significance of the gender and age related prevalence of calcifications in CBCT examinations in adult patients over 40 years. As there are limited data on the presence of arterial calcifications in different populations as depicted in panoramic radiographs or CBCTs in the dental literature, in this study we compared our CBCT based results not only with a few studies reported in the dental literature, but also with those results reported in medical literature and based on other imaging methods.

Several imaging modalities have been proposed to evaluate the carotid artery calcifications including modified posteroanterior radiographs of the neck mode in which calcifications within the carotid arteries appear lateral to the spine [20], CT as the most sensitive means of detecting intracranial calcifications [23], panoramic radiographs [24] MR angiography(MRA), Doppler ultrasound [25], and CBCT [26]. Unlike Doppler ultrasound or MRA Cone-beam, CT provides high-resolution 3-D images of calcification [27] and CBCT has lower cost and lower exposure than CT [28]. Furthermore, CBCT scans frequently consist of the anatomic area where segments of the extracranial and intracranial courses of ICA are located [29], so CBCT has been used in this article according to these rationales.

The result of our study showed the prevalence of calcifications mainly in the C4, C5/C6, C1 segments of ICA in decreasing order; this observation is similar to the result of both literature using other imaging techniques [30, 31] and those similar to our study [21, 29] (Table 4). An evidence-based predefined visual scale scheme was introduced by Fisher et al. [32] to define the severity of the signs of atherosclerotic lesions. Like some other studies, we used this scheme to evaluate the severity of calcifications in the course of ICA. The highest degree of severity was seen in the C4 segment. Our findings strongly correlated with those reported by Damaskos et al. [29]. Then, the C5/C6 and C1 showed a high degree of severity in descending order. As the results of the McNemar’s test showed no statistical difference in the presence of calcifications between the right and left sides of these segments. This implicates that the presence of calcification in the course of ICA in our study is a rather symmetrical findings that is similar to the findings of numerous studies [21, 29, 33, 34].

Table 4.

Overview on the prevalence of calcifications in C4 segment in different studies

	n	Modality	Prevalence(percent)
Present study	304	CBCT	94 (of patients with calcif.)
Damaskos et al. [29]	161	CBCT	92.5 (of patients with calcif.)
Woodcock et al. [30]	128	CT	51 (of all patients)
Taoka et al. [31]	72	CT	61.8 (of all detected calcium score)

Our results showed that prevalence and severity of calcifications increased with increasing ages; this is similar to the result of other reports [6, 17, 22, 29, 35–38]. Increase in the prevalence of calcifications can be the result of increase in calcium deposition within the arterial wall by increasing age [22, 39–41]. No significant gender differences in the presence of calcifications were found. Our findings are aligned with some other studies that did not reveal different patterns in calcifications between men and women [6, 36, 38, 42, 43] (Table 5). On the other hand, Weert et al. [33] in their study indicated that the frequency and severity of calcifications along the course of intra-cranial internal carotid artery was more in women; this difference can be attributed to different population that were studied and the limited number of participants enrolled in our study.

Table 5.

Overview on the prevalence of calcifications according to gender in different studies

	N	Modality	Gender
Present study	304	CBCT	Men = women
Bos et al. [6]	885	MRI, CT	Men = women
Hong et al. [36]	445	MRI, CT	Men = women
Bayram et al. [42]	4106	OPG	Men = women
Chen et al. [43]	175	CT	Men = women
Damaskos et al. [29]	161	CBCT	Men = women
Weert et al. [33]	406	CT	Men > women

As the result of the study of Heiland et al. [44] that showed no significant differences between CT and CBCT in visualization of the atherosclerosis, it can be supposed that our results showed the ability of CBCT to identify the patients at the risk of intracranial stenosis due to their pattern of calcification.

In this study, we used multiplanar evaluation of the CBCT volume in 0.3 mm slice thickness, like Damaskos et al.’s study [29] rather than the larger slice thickness in axial planes only in other studies [7, 35, 45], that minimized the uncertainty of the degree of severity of calcifications.

This study had several limitations. First, in this retrospective study our investigators were blinded to the subjects’ potentially existing medical and dental history information; it is well known that the prevalence of carotid artery calcifications increases when a predisposing factor (like hypertension, diabetes mellitus, smoking, menopause, history of cardiovascular disease and neck radiotherapy is present. Therefore, it is suggested that the association between calcifications in ICA and different predisposing factors should be evaluated in future studies. Furthermore, it seems that the CBCT’s sensitivity and specificity in the diagnosis of atherosclerosis need to be further investigated in future studies.

Conclusions

The frequency and severity of calcifications decreases throughout the C4, C5/C6, C1 segments in a descending order. Furthermore, our results reveal that the prevalence of calcifications increases with increasing age irrespective of gender.

Compliance with Ethical Standards

Ethics

The research plan of the present study was approved by the institutional ethics committee.