Carotid body measurement by computed tomography angiography: a cross-sectional population-based study

Abstract

Background

Carotid bodies (CBs) are chemoreceptors located at the bifurcation of the common carotid arteries, playing an essential role in maintaining blood gas homeostasis and regulating cardiovascular function. CBs are increasingly affected in various systemic pathologies, particularly those involving sympathetic overactivation, including hypertension and heart failure. Despite CB hypertrophy in these conditions has been well-studied, normative data on dimensions remain scarce. This study aimed to establish reference ranges for CB size in a large Iranian population using computed tomography angiography (CTA).

Methods

A cross-sectional study of 650 patients who underwent neck CTA (April 2023–April 2025) was conducted. After excluding 36 patients with carotid body tumors and further removing cases with missing, unmeasurable, or outlier measurements, 521 patients were included for final analysis. CB dimensions were measured in both the transverse (R1) and anteroposterior (R2) planes. Reference ranges were calculated and stratified by age, sex, and comorbidity status. In addition, subgroup analysis was performed to examine the influence of chronic diseases including hypertension, diabetes mellitus, hyperlipidemia, cardiovascular disease, chronic obstructive pulmonary diseases, cerebrovascular accident/transient ischemic attack (CVA/TIA), and thyroid disease.

Results

In this study, the mean R1 of the CB was 2.66 ± 0.5 mm, and the mean R2 was 3.25 ± 0.61 mm. Notable size variations were observed across age groups, with the 60–70 years group showing a marginally significant larger R1 of 2.96 ± 0.45 mm and R2 of 3.54 ± 0.51 mm (p-value = 0.070). No statistically significant differences were observed across sex categories. Also, participants with chronic diseases exhibited slightly larger CBs compared to those without (R1 = 2.71 ± 1.20 vs. 2.57 ± 0.52, p-value = 0.128 and R2 = 3.30 ± 1.34 vs. 3.17 ± 0.63, p-value = 0.204, respectively).

Conclusions

This study provides a comprehensive reference ranges for CB dimensions in a general population, with specific subranges based on age, sex, and comorbidities. These findings can enhance diagnostic accuracy and help distinguish between normal CB enlargement and pathological conditions.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12880-026-02529-3.

Introduction

The carotid bodies (CBs) are paired chemoreceptors located bilaterally in the neck at the bifurcation of the common carotid arteries, adjacent to the internal and external carotid branches [1, 2]. These small neurovascular structures are responsible for sensing changes in arterial oxygen tension, carbon dioxide, pH and glucose levels [3]. Activation of CBs regulates respiratory rate and sympathetic tone via afferent input to the brainstem [4]. Also, CBs have been increasingly implicated in systemic cardiovascular pathophysiology. Hyperactivity or enlargement of the CBs has been reported in chronic conditions such as systemic hypertension, heart failure, chronic obstructive pulmonary disease (COPD), asthma, sleep apnea and cirrhosis, all of which involve increased sympathetic activation [5–12]. Histological studies from human autopsies have demonstrated CB hypertrophy in these disease states, with reported size increases ranging from 20% to 130% compared to healthy controls [6, 12].

Visualization of the CB has become feasible with modern imaging, particularly computed tomography angiography (CTA), which depicts the CB as an enhancing structure anteromedial to the carotid bifurcation [13, 14]. Nguyen et al. suggested that a well-enhancing ovoid structure located inferomedially between the internal and external carotid arteries with a size ≤ 6 mm should be considered a normal CB [15]. Carotid body tumors (CBTs) are rare, typically benign paragangliomas arising from the CB. They are usually slow-growing lesions and may present as painless lateral neck masses, although larger tumors can cause compressive symptoms or cranial nerve involvement. Previous studies have reported an estimated annual incidence of approximately 0.3 cases per 100,000 individuals [16, 17].

CTA offers high spatial resolution and contrast differentiation that makes it superior for detailed vascular and soft-tissue assessment in the carotid space [18]. In recent studies, CBs were visualized in up to 80% of adult patients undergoing neck CTA, confirming the modality’s sensitivity for detecting these structures [14]. Several studies have examined correlations between CB size on CTA and chronic disease status. A study from Cramer et al. demonstrated that CBs are significantly larger in patients with hypertension (HTN), diabetes mellitus (DM) or heart failure, even after adjusting for age and sex [14]. Similar findings were reported by Tan et al. using carotid ultrasound, where hypertensive patients had significantly increased CB volume [5].

In contrast, some studies suggest that certain hypoxemic states like obstructive sleep apnea may not lead to CB enlargement, indicating that the etiology of CB hypertrophy is multifactorial [11]. Moreover, recent interest in CB modulation via surgical denervation or ablation as a potential treatment for sympathetic-driven disorders has revived clinical interest in CB imaging [19, 20]. In this regard, CB measurement by CTA may serve not only as a diagnostic tool but also as a screening method for patient selection in interventional trials targeting the CB.

Despite these advances, normative data regarding CB size in the general population remain scarce. Most prior studies were based on small sample sizes or focused on disease-specific populations [21]. Anatomical dissections report varying measurements for CB, with one study noting a height of 5–7 mm and a width of 2.5–4 mm, while another study reports a height ranging from 1 to 5 mm and a width ranging from 2 mm to 5 mm [22, 23]. However, population-based radiologic studies quantifying CB dimensions in healthy or mixed cohorts are lacking. This study presents the transverse and anteroposterior dimensions (R1 and R2) of the CB on CTA in a large Iranian population to establish reference values for clinical and radiological use. Additionally, this study provides data on the variability of the CB dimensions by age, sex, and comorbidities, offering insights into potential influencing factors.

Methods

Study design and patient selection

We conducted a cross-sectional study of patients who underwent routine neck CTA between April 2023 and April 2025 at Alzahra Hospital, a tertiary referral center in Isfahan. Imaging data were retrieved from the hospital archive and electronic medical records. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013) and was approved by the local ethics committee of Isfahan University of Medical Sciences and the national research ethics board (protocol code: IR.MUI.MED.REC.1402.324). Patient data were collected as part of routine clinical practice, accompanied by informed consent forms which had been obtained at the time of hospital admission according to institutional policy. Patients were assured that their information would be used anonymously and in an aggregated manner for research purposes, and that the results would be reported without any identifying details. In addition, all patients were contacted by telephone, and verbal informed consent was obtained after a complete explanation of the study before collecting supplementary clinical information, including smoking status, comorbidities, height, and weight. Informed consent was also obtained from the legal guardians or parents of study participants under the age of 16. Furthermore, written consent for the publication of potentially identifiable information was obtained from all patients, including legal guardians or parents of participants younger than 16.

Inclusion criteria were the availability of a diagnostic-quality carotid CTA scan covering the carotid bifurcation region. Exclusion criteria included scans with poor image quality, including severe motion or streak artifacts that obscured the carotid bifurcation, or those where the CB could not be anatomically identified by our two radiologists, or where the CB size was smaller than what could be visually detected, were excluded [21]. In this 2-year period, the CBs of a total of 650 patients’ the CBs of a total of 650 CBs were evaluated and measurements were recorded. Additionally, 36 patients with CBT (5.8%) were not included in the analysis [21].

During the 2-year study period, a total of 650 patients underwent neck CTA and were initially evaluated for possible inclusion. Among these, 36 patients (5.8%) had carotid body tumors (CBT) and were excluded from further analysis because the aim was to establish reference ranges in tumor-free individuals. This left 614 tumor-free patients in whom both right and left CBs were sought.

For these 614 patients, each scan was evaluated for the presence of a visible CB on both sides. When visible, the CB was measured using electronic calipers on axial images. We measured two orthogonal dimensions in the axial plane: the maximum mediolateral (transverse, indicated as R1) diameter and the maximum anteroposterior (indicated as R2) diameter. The mean of the right and left measurements was used for analysis.

However, not all 614 patients contributed to the final reference range analysis. We additionally excluded patients if: (1) one or both CBs were not visible or could not be reliably measured (e.g., due to motion artefact, poor image quality, or anatomical variation); (2) the measured R1 or R2 values were statistical outliers (determined by boxplot and extreme studentized deviate methods); (3) there was incomplete paired data (right and left measurements not both available). After applying these rigorous quality control steps, the final analysis was performed on 521 patients with complete, reliable, and artefact-free measurements for both R1 and R2 diameters.

Basic demographic data (age, sex) and comorbidity status (including hypertension, DM, history of cardiovascular, cerebrovascular disease and smoking) were extracted for subgroup analyses from patients’ electronic medical records using a standardized data collection form. Indications for CTA in the study sample were diverse, encompassing the evaluation of carotid atherosclerosis or stenosis related to transient ischemic attack (TIA), stroke, or suspected neck trauma.

CTA protocol

All neck CTA examinations were performed by one multi-detector GE LIGHT SPEED VCT 64 detector row 128 slices CT scanner machine (General Electric, Fairfield, Connecticut, USA) using a standardized protocol; The slices were obtained from the aortic arch to the frontal sinus in the helical mode with 1.25 mm slice thickness. The contrast agent, Visipaque (Iodixanol 320; GE Healthcare, Oslo, Norway), was administered intravenously at a flow rate of 5–6 ml/s, followed by 30–50 ml of saline at the same injection rate. During the arterial phase, bolus tracking was employed with a region of interest (ROI) placed inside the carotid artery, and a trigger threshold set at 100 Hounsfield Units (HU), using an individualized delay time. The scan range extended from the thoracic inlet to the vertex of the skull. The venous phase acquisition occurred 60 s after the arterial phase. Scan parameters were as follows: collimation 40 mm, pitch 1.38, effective slice thickness 0.625 mm, reconstruction interval 0.625 mm, tube voltage 120 kV, tube current 200–440 mAs, rotation time 0.5 s, and scan time 4 s. Three-dimensional volume reconstructions of the neck vessels, including Volume Rendering (VR), Maximum Intensity Projection (MIP), and Multiplanar Reformation (MPR) imaging, were performed.

Axial source images were reconstructed at 1 mm slice thickness with a soft-tissue convolution kernel (e.g., B20). Additionally, multi-planar reconstructions in the coronal and sagittal planes were generated at 2 mm thickness (2 mm increments) to facilitate anatomical localization. All CT images were reviewed on the hospital’s picture archiving and communication system (PACS) workstation with standard soft-tissue window settings.

Carotid body identification and measurement

On each CTA, the CB was identified as a small enhancing structure at the carotid bifurcation, distinct from the vessel lumen. In practice, it appears as a well-defined oval focus of contrast enhancement, typically located in the crotch between the internal and external carotid arteries (anteromedial to the external carotid), at the level of the carotid sinus [13, 15]. We carefully distinguished the CB from adjacent vascular structures – linear or tubular enhancing structures continuous with an artery were ignored, as they represent arterial or venous channels rather than globular CB tissue. Each scan was evaluated for the presence of a visible CB on both the right and left sides. When visible, the CB was measured using electronic calipers on axial images.

We measured two orthogonal dimensions of the CB in the axial plane: the maximum mediolateral (transverse, indicated as R1) diameter and the maximum anteroposterior (indicated as R2) diameter. Measurements were performed at 200% magnification to improve accuracy, and in a standard soft-tissue window to optimize the visibility of the mildly hyperdense CB against surrounding fat (Fig. 1). For each participant, the dimensions of the carotid body on both the right and left sides were measured and recorded and the R1 and R2 dimensions were obtained for each side, and the mean values were used for the final analysis. To minimize interobserver variability, all measurements were performed jointly by two readers, including an experienced head and neck radiologist and a senior radiology resident trained in CBT assessment. During each session, both reviewers simultaneously evaluated the CTA images on the PACS workstation, jointly placed the digital calipers on each carotid body, and reached a consensus on the final measurements before documentation. Both readers were blinded to the patients’ clinical data.

Fig. 1.

How to Detect and Measure Diameters of Carotid Body in Axial Images of Cervical Computed Tomography Angiography from Various Cases, There is an Enhancing Circular or Triangular Entity in each Carotid Artery Bifurcation Indicative of the Carotid Body (Red Arrows and Outlines): A and B - a 50-Year-old Male Without Chronic Condition; C- A 57-Year-old Female With a Chronic Condition (Hypertension); D- A 71-Year-old Male With Chronic Conditions (Hypertension and Diabetes Mellitus)

Statistical analysis

Descriptive statistics were presented as mean ± standard deviation (SD) for continuous variables, frequency and percentage were used to summarize categorical variables. Normality of data distribution was assessed using the Shapiro-Wilk test. Reference ranges for CB dimensions were established using percentiles. The 95% reference intervals were defined by the 2.5th and 97.5th percentiles, with additional percentiles (5th, 10th, 90th, 95th) calculated to provide comprehensive distribution profiles. Before calculating percentiles, statistical outliers were identified using boxplot and extreme studentized deviate methods and were excluded from the reference range analysis. These ranges were calculated for the overall tumor-free population and stratified by age groups and sex. For the child subgroup (age ≤ 20 years, n = 23 total; female n = 17, male n = 6), the 97.5th percentile could not be reliably estimated because the sample size was too small; in such cases, the value shown in the tables is the observed maximum in that subgroup, and these estimates are descriptive only and not statistically robust. Subgroup analyses were conducted to examine the influence of comorbidities, including chronic disease status, on CB dimensions. Participants were stratified by the presence or absence of chronic diseases, and reference ranges were calculated within these subgroups, with further stratification by sex and age groups. Participants were stratified by the presence or absence of chronic diseases, and reference ranges were calculated within these subgroups, with further stratification by sex and age groups.

Between-group comparisons (chronic disease vs. no chronic disease) were made using independent samples t-tests for continuous variables. Associations between carotid dimensions and demographic/clinical variables (including sex, age categories, BMI groups, and various medical conditions) were assessed using independent samples t-tests or one-way ANOVA, as appropriate. A p-value of less than 0.05 was considered as statistically significant. Data visualization was performed using ggplot2 package in R, including distribution plots with reference intervals. All other statistical analyses were performed using IBM SPSS Statistics for Windows, Version 20.0 (Released 2011; IBM Corp., Armonk, New York, USA).

Results

Patient characteristics

Initially, 650 patients who underwent neck CTA were identified for potential inclusion in this cross-sectional study. Following the exclusion of 36 patients with carotid body tumors (CBT) to ensure the analysis reflected healthy anatomy, 614 tumor-free patients remained. However, to establish robust reference ranges, we applied strict quality control criteria to the imaging data. Cases were excluded if the carotid bodies were not visible or could not be reliably measured on either side, or if the measured dimensions (transverse R1 and anteroposterior R2) were statistical outliers. After these exclusions, the final analysis was performed on a cohort of 521 patients with complete and reliable measurements.

Demographic data were available for the majority of the final sample. Age information was missing for a small number of patients (< 2%) due to limitations in the hospital records; therefore, the sum of patients across age groups in Table 1 does not exactly equal 521. The baseline characteristics of the 521 patients included in the final analysis are presented in Table 1. Males comprised 63.7% of participants and 36.3% of participants were female. The mean age was 54.44 years (SD = 18.63, range: 9–98 years), with 60.7% of cases being over 50 years old. Mean height and weight were 168.00 cm (SD = 8.66) and 75.46 kg (SD = 12.93), respectively. The mean Body Mass Index (BMI) was 26.73 kg/m² (SD = 4.44), with 34.3% of participants classified as normal weight, 46.1% as overweight, and 19.6% as obese. Both CBs could be identified and measured in 88.4% of cases, and tumors were identified in 5.8%. Chronic underlying diseases were reported in 61.8% of participants. Hypertension was the most frequently reported underlying medical condition (41.7%), followed by diabetes (28.2%), hyperlipidemia (25.2%), and cerebrovascular accidents (29.4%). 17.7% of study participants had previous history of head and/or neck trauma, while 16.5% reported current or previous smoking. Less common underlying comorbidities were cardiovascular disease (10.4%), COPD (7.4%), and thyroid diseases (7.2%). Data completeness was generally high, with missing values ranging from 0% to 9.8% across variables. In this study, CB dimensions were assessed using CTA. Two indices were defined: the transverse dimension in axial projection (R1) and the anteroposterior (AP) dimension in axial projection (R2), representing the mean measurements of the right and left sides.

Table 1.

Reference ranges of carotid body transverse and anteroposterior dimensions in axial projection in total sample and across age groups (tumor-free participants)

Statistical Measure	Overall (n = 521)		Age ≤ 20 (n = 23)		Age 20–30 (n = 44)		Age 30–40 (n = 66)		Age 40–50 (n = 62)		Age 50–60 (n = 96)		Age 60–70 (n = 106)		Age > 70 (n = 97)
	R1	R2	R1	R2	R1	R2	R1	R2	R1	R2	R1	R2	R1	R2	R1	R2
Mean	2.66 ± 0.5	3.25 ± 0.61	2.48 ± 0.40	3.03 ± 0.59	2.49 ± 0.48	3.04 ± 0.60	2.55 ± 0.42	3.13 ± 0.50	2.66 ± 0.48	3.30 ± 0.62	2.64 ± 0.63	3.23 ± 0.77	2.96 ± 0.45	3.54 ± 0.51	2.63 ± 0.47	3.20 ± 0.58
Median	2.60	3.20	2.50	3.05	2.50	3.03	2.50	3.10	2.60	3.35	2.65	3.18	2.70	3.35	2.65	3.20
Minimum	1.00	1.00	1.70	2.00	1.00	1.15	1.16	1.33	1.00	1.60	1.00	1.00	1.33	1.52	1.26	1.49
Maximum	6.80	7.70	3.45	4.05	3.70	4.40	3.95	4.40	3.75	5.55	6.80	7.70	4.40	5.60	4.05	4.85
2.5th Percentile	1.48	2.00	1.70	2.00	1.03	1.23	1.69	2.02	1.28	1.88	1.40	1.58	1.94	2.15	1.34	1.78
5th Percentile	1.95	2.25	1.73	2.00	1.32	1.86	2.00	2.39	1.85	2.27	1.80	2.00	2.10	2.45	1.89	2.34
10th Percentile	2.05	2.50	1.91	2.02	2.01	2.29	2.04	2.50	2.12	2.62	2.00	2.45	2.24	2.54	2.09	2.50
90th Percentile	3.15	3.85	3.06	3.81	3.10	3.75	3.07	3.77	3.29	3.85	3.13	3.93	3.30	3.90	3.06	3.95
95th Percentile	3.35	4.10	3.40	4.01	3.15	3.91	3.22	3.95	3.49	4.38	3.42	4.40	3.70	4.16	3.29	4.31
97.5th Percentile	3.70	4.40	3.40	4.01	3.63	4.34	3.55	4.33	3.64	5.29	3.68	4.48	6.24	7.66	3.96	4.58

*R1 represents the transverse diameter of the carotid body in axial projection, measured as the average of right and left sides. R2 represents the anteroposterior diameter in axial projection, also averaged across both sides. All measurements are reported in millimeters (mm) and obtained via CTA. Subgroup totals may not sum to the overall sample size due to missing data for some variables (e.g., age or chronic disease status)

*Abbreviations: mm, millimeters; CTA, Computed Tomography Angiography

Reference ranges for carotid body dimensions in total tumor-free individuals and stratified by age and sex

In the tumor-free sample, the transverse and anteroposterior carotid dimensions averaged 2.66 ± 0.5 mm and 3.25 ± 0.61 mm, respectively, with 95% reference intervals ranging from 1.48 to 3.70 mm and 2.00 to 4.40 mm. Age-stratified analysis revealed modest variation in CB measurements across decades, with slightly higher values and broader ranges observed in older age groups, particularly those aged 60–70 years, showing the largest transverse diameter (2.96 ± 0.45 mm) and anteroposterior diameter (3.54 ± 0.51 mm). Full percentile distributions are presented in Table 1.

Sex-specific comparisons showed similar mean values between males and females. Among males, the transverse and anteroposterior diameters averaged 2.67 ± 0.62 mm and 3.25 ± 0.75 mm, respectively, with medians of 2.65 and 3.25 mm, and minimum–maximum ranges of 1.00–10.05 mm and 1.00–11.95 mm. In females, corresponding values were 2.64 ± 1.52 mm and 3.25 ± 1.66 mm, with medians of 2.50 and 3.15 mm, and ranges of 1.00–6.80 mm and 1.55–23.05 mm. No statistically significant difference was found between males and females in terms of transverse diameter (P-value 0.732) or anteroposterior diameter (P-value 0.995). Reference intervals by sex are illustrated in Figs. 2 and 3, and 4.

Fig. 2.

Carotid body dimensions in total sample – reference distribution

Fig. 3.

Carotid body dimensions in females – reference distribution

Fig. 4.

Carotid body dimensions in males – reference distribution

Figures 2 and 3, and 4- visually present the distribution of carotid body dimensions in axial projection, offering intuitive reference for both transverse and anteroposterior measurements. Figure 2 displays the full sample, while Figs. 3 and 4 represent sex-specific distributions for males and females, respectively. In each plot, the mean is marked with a dashed blue line, and shaded regions indicate the 90% and 95% reference intervals using percentile boundaries (2.5%, 16%, 84%, and 97.5%). These visualizations allow for rapid comparison of anatomical variability across sex groups and support clinical interpretation by highlighting normative thresholds and population dispersion.

Subgroup-specific reference ranges for carotid dimensions: a stratified approach by comorbidity in total sample and in gender and age groups

To further refine the reference ranges and explore the influence of chronic disease status more precisely, a subgroup analysis was conducted by separating individuals with and without chronic conditions, while maintaining the exclusion of tumor cases. This stratified approach allowed for a clearer understanding of how comorbidities may affect CB morphology across sex and age categories.

Among our study participants, 327 patients had underlying comorbidities and showed modestly higher carotid dimensions and broader reference intervals compared to those without chronic conditions (n = 194). The mean± standard deviation(SD) for transverse diameter was reported 2.57 ± 0.52 mm in patients without any chronic diseases, whereas this value was higher among patients with chronic diseases (2.71 ± 1.20 mm). Likewise, the anteroposterior diameter in patients without underlying diseases was lower at 3.17 ± 0.63 mm compared to their counterpart group, at 3.30 ± 1.34 mm. In addition, greater anatomical variability in transverse diameter was found in patients with chronic diseases (R1 95% range 1.49–3.87 vs. 1.40–3.51in non-diseased individuals), whereas larger variability was observed among participants without chronic diseases (R2 95% range 1.80–4.40) compared with patients with comorbidities (R2 95% range 2.00–4.49). These findings suggest that chronic disease may contribute to subtle arterial enlargement and dispersion, warranting stratified reference definitions.

Among participants without chronic diseases, males exhibited mean transverse and anteroposterior diameters of 2.58 ± 0.41 mm and 3.17 ± 0.54 mm, respectively. The corresponding 90% reference intervals ranged from 2.01 to 3.05 mm for transverse and 2.50 to 3.75 mm for anteroposterior diameters, while the 95% intervals extended from 1.57 to 3.47 mm in transverse and 1.91 to 4.05 mm in anteroposterior diameter. Females in this subgroup showed similar mean values (2.55 ± 0.74 mm for transverse diameter and 3.17 ± 0.84 mm for anteroposterior diameter), though with wider dispersion, reflected in 95% reference limits of 1.08–5.64 mm(transverse) and 1.58–6.46 mm(anteroposterior). Table 2 In contrast, individuals with chronic disease demonstrated slightly higher mean diameters and broader variability. The transverse diameter among males with chronic diseases was measured 2.73 ± 0.71 mm, with anteroposterior diameter of 3.31 ± 0.86 mm. 95% reference intervals for transverse and anteroposterior diameter was 1.33–3.95 mm and 1.69–4.61 mm, respectively. Meanwhile, females showed greater dispersion (2.68 ± 1.77 mm for transverse and 3.29 ± 1.93 mm for anteroposterior diameters), with upper reference limits reaching 3.37 mm and 4.40 mm, respectively Table 2.

Table 2.

Reference ranges for carotid body diameters by sex, age, and chronic disease status

Group	N	R1 Mean ± SD	R190%Range (5th–95th)	R195%Range (2.5th–97.5th)	R2 Mean ± SD	R2 90% Range (5th–95th)	R2 95% Range (2.5th–97.5th)
No Chronic Disease (Total)	194	2.57 ± 0.52	2.01–3.05	1.40–3.51	3.17 ± 0.63	2.50–3.75	1.80–4.40
With Chronic Disease (Total)	327	2.71 ± 1.20	2.09–3.20	1.49–3.87	3.30 ± 1.34	2.50–3.90	2.00–4.49
Male, No Chronic Disease	140	2.58 ± 0.41	2.01–3.05	1.57–3.47	3.17 ± 0.54	2.50–3.75	1.91–4.05
Female, No Chronic Disease	54	2.55 ± 0.74	2.00–3.08	1.08–5.64	3.17 ± 0.84	2.48–3.78	1.58–6.46
Male, With Chronic Disease	211	2.73 ± 0.71	2.20–3.29	1.33–3.95	3.31 ± 0.86	2.55–3.95	1.69–4.61
Female, With Chronic Disease	116	2.68 ± 1.77	2.00–3.05	1.73–3.37	3.29 ± 1.93	2.35–3.85	2.00–4.40
With Chronic Disease – by age
Age ≤ 20	4	2.29 ± 0.28	2.15–2.70	2.15–2.70	2.75 ± 0.49	2.35–3.45	2.35–3.45
Age 20–30	7	2.61 ± 0.55	1.65–3.15	1.65–3.15	3.47 ± 0.32	2.90–3.80	2.90–3.80
Age 30–40	30	2.58 ± 0.49	2.05–3.14	1.16–3.95	3.19 ± 0.59	2.56–3.99	1.33–4.40
Age 40–50	32	2.72 ± 0.49	2.11–3.42	1.48–3.75	3.35 ± 0.62	2.53–4.13	2.08–5.10
Age 50–60	76	2.57 ± 0.48	2.00–3.10	1.28–3.65	3.12 ± 0.65	2.27–3.90	1.28–4.50
Age 60–70	89	2.99 ± 2.14	2.15–3.35	1.87–8.64	3.57 ± 2.35	2.50–3.90	2.15–10.36
Age > 70	89	2.63 ± 0.49	2.05–3.10	1.34–3.98	3.21 ± 0.60	2.50–3.95	1.68–4.61
No Chronic Disease – by age
Age ≤ 20	19	2.52 ± 0.42	1.70–3.40	1.70–3.45	3.09 ± 0.61	2.00–4.01	2.00–4.05
Age 20–30	37	2.47 ± 0.47	1.19–3.21	1.00–3.21	2.96 ± 0.61	1.75–4.00	1.15–4.00
Age 30–40	36	2.52 ± 0.35	1.99–3.27	1.95–3.27	3.09 ± 0.41	2.44–3.81	2.35–3.81
Age 40–50	30	2.61 ± 0.47	1.55–3.39	1.00–3.39	3.26 ± 0.63	1.96–4.67	1.60–4.67
Age 50–60	20	2.93 ± 0.98	2.06–6.65	2.05–6.65	3.64 ± 1.06	2.81–7.54	2.80–7.54
Age 60–70	17	2.79 ± 0.30	2.30–3.25	2.30–3.25	3.38 ± 0.25	3.00–3.80	3.00–3.80
Age > 70	8	2.62 ± 0.21	2.25–2.90	2.25–2.90	3.10 ± 0.16	2.80–3.25	2.80–3.25

*R1 represents the transverse diameter of the CB in axial projection, measured as the average of right and left sides. R2 represents the anteroposterior diameter in axial projection, also averaged across both sides. All measurements are reported in millimeters (mm) and obtained via Computed Tomography angiography

Subgroup counts may not add to total N (or subtotal) due to missing values. (e.g., age or chronic disease status)

Age-stratified results within each subgroup revealed overall increases in carotid body dimensions with advancing age, particularly among those with chronic disease. For example, in the 30–40 year group without chronic disease, transverse (R1) and anteroposterior (R2) diameters averaged 2.52 ± 0.35 mm and 3.09 ± 0.41 mm, while in the same age group with chronic disease, values were slightly higher (2.58 ± 0.49 mm and 3.19 ± 0.59 mm). In older age categories (≥ 60 years), the presence of chronic disease was associated with markedly wider distributions and higher upper percentiles, suggesting potential vascular remodeling or dilatation. For instance, in the 60–70 year group with chronic disease, the 95% reference range for R1 extended up to 8.64 mm (2.5th–95th: 1.87–8.64 mm), whereas in the same age group without chronic disease the upper bound was much lower (2.30–3.25 mm). Similarly, in the > 70 year group, those with chronic disease showed a wider 95% range for R2 (1.68–4.61 mm) compared to those without chronic disease (2.80–3.25 mm).

Among younger age groups (≤ 20 years and 20–30 years), sample sizes were very small, especially in the chronic disease category (n = 4 and n = 7, respectively). Consequently, the reference ranges for these subgroups should be interpreted with caution and are provided primarily for descriptive purposes. For individuals without chronic disease, the youngest age group (≤ 20 years, n = 19) had R1 and R2 95% ranges of 1.70–3.45 mm and 2.00–4.05 mm, respectively, which were comparable to those of the 20–30 year group without chronic disease (R1: 1.00–3.21 mm, R2: 1.15–4.00 mm).

These subgroup findings underscore the importance of accounting for chronic disease status when interpreting carotid body dimensions. While overall reference ranges provide a general framework, stratified values offer more nuanced benchmarks for clinical and research applications. Full percentile distributions and subgroup comparisons are detailed in Table 2.

Validation of reference ranges: no significant associations with demographic or clinical factors

To assess the potential influence of demographic and clinical variables on CB dimensions, comparative analyses were conducted across sex, age groups, BMI categories, and a range of clinical conditions. No statistically significant differences were observed in either transverse or anteroposterior diameters across these subgroups, including chronic disease status, cardiovascular and metabolic conditions, or smoking history. Although a non-significant trend toward increased diameter was noted in older age groups, particularly between 60 and 70 years, however p-values remained above the significance threshold.

These findings suggest that the reference ranges established for tumor-free individuals are broadly applicable and not substantially influenced by the examined variables. As such, they may reflect normative carotid dimensions within the general population from which the sample was drawn. Detailed statistical comparisons are provided in Supplementary Table 1 (supplement).

Sensitivity analysis

To evaluate whether the inclusion of pediatric participants (age ≤ 20 years) influenced the reference ranges, we repeated the percentile analysis after excluding all individuals aged ≤ 20 years. The adult-only sample (age > 20 years) comprised 471 valid measurements for both R1 and R2 (male n = 316, female n = 155). The resulting reference percentiles for the adult-only sample were nearly identical to those derived from the full sample that included children, indicating that the small child subgroup did not meaningfully affect the overall reference intervals.

For the child subgroup (age ≤ 20 years, n = 23 valid measurements; male n = 17, female n = 6), the sample size was too small to generate statistically reliable 90% or 95% reference ranges. The percentiles presented in the table for this subgroup are provided for descriptive purposes only and should be interpreted with caution. Notably, the upper bounds (95th and 97.5th percentiles) for children were similar to or slightly lower than those for adults, but the lack of statistical precision precludes firm conclusions (Table 3).

Table 3.

Reference percentiles (2.5th, 5th, 95th, 97.5th) for carotid body dimensions by age subgroup and gender

Subgroup	Gender	Diameter	2.5th	5th	95th	97.5th
Adult (> 20 years)	Total	R1 (mm)	1.52	2.00	3.35	3.66
		R2 (mm)	2.00	2.31	4.15	4.40
	Female	R1 (mm)	1.34	2.00	3.41	3.75
		R2 (mm)	2.05	2.44	4.21	4.46
	Male	R1 (mm)	1.72	1.88	3.21	3.38
		R2 (mm)	1.99	2.13	4.06	4.40
Child (≤ 20 years)	Total	R1 (mm)	1.70	1.73	3.40	3.45*
		R2 (mm)	2.00	2.00	4.01	4.05*
	Female	R1 (mm)	1.70	1.70	3.25	3.45*
		R2 (mm)	2.00	2.00	3.89	4.05*
	Male	R1 (mm)	1.85	1.85	2.64	2.70*
		R2 (mm)	2.00	2.00	3.26	3.30*

*For the child subgroup (n = 23 total, female n = 17, male n = 6), the 97.5th percentile could not be reliably estimated because the sample size is too small; the value shown is the observed maximum in that subgroup. These estimates are descriptive only and not statistically robust

These findings support the robustness of the primary reference ranges derived from the full sample, while acknowledging that pediatric-specific reference ranges require larger dedicated studies.

Discussion

In this cross-sectional study, we established reference ranges for CB size in transverse and AP diameters using CTA. We evaluated patients without CBTs and proposed cut-off values for the transverse and AP diameters across different age and sex groups, and the presence of certain underlying medical conditions (such as hyperlipidemia, diabetes mellitus, cardiovascular diseases, previous cerebrovascular accidents or transient ischemic attack, thyroid diseases, smoking, and head and neck trauma). We also established subgroup-specific reference values for CB dimension stratified by age groups, gender, and comorbidities status. Several studies were conducted to evaluate the size of CB, particularly in patients with cardio-metabolic diseases and CBTs [5, 14, 24]. Nevertheless, to the best of our knowledge, information regarding a valid reference range for CB dimension across different demographic and clinical categories remains limited. Considering the proposed functional relationship between the CB and development of diverse diseases, including sympathetically-mediated diseases [5], measuring CB dimensions could be utilized as a promising screening tool for earlier, more accurate detection of carotid pathologies.

The CB is a highly vascular structure positioned at the infero-medial aspect of carotid bifurcation [15]. The CB is the prototypical acute oxygen-sensing organ in mammals, playing an essential role in maintaining blood gas components through initiating cardiorespiratory reflexes. Derived from neural crest cells, chemoreceptor glomus cells play an integral role in regulating CB’s autonomic and chemoreceptor functions [25, 26]. Due to its high vascularity, carotid bodies could be visualized in 88% of cases examined using routine CTA [27].Other imaging modalities to detect CBs include magnetic resonance angiography (MRA) and color Doppler ultrasonography (CDU) using high-frequency probes [28].Various studies have demonstrated hyperplastic changes in CB manifesting as CB enlargement in response to chronic hypoxemic states, such as chronic obstructive lung disease [14, 27], COVID-19 pneumonia [27], as well as in diseases associated with sympathetic system over-activation, including heart failure, hypertension, and obstructive sleep apnea [6, 24]. Other cardio-metabolic diseases were also reported to be associated with dysfunctional CB, including diabetes mellitus and internal carotid artery stenosis [14, 24, 25, 29]. Measuring CB size has been proposed as a promising imaging marker to predict the presence and progression of comorbidities, particularly those affecting sympathetic nervous system [24]. In addition, it appears that the extent of CB enlargement due to tumors(paragangliomas) differs from non-cancerous causes of CB hypertrophy [29].

Small lesions located at the carotid bifurcation were widely known to be a diagnostic dilemma to the clinicians. In other words, a prominently-enhancing normal CB should be distinguished from a small CBT, such as paraganglioma or nerve sheath tumor [27]. Normal prominent CBs might be misdiagnosed as a small CB paraganglioma, leading to unnecessary interventions [14]. Hence, understanding the normal accepted values for CB size has become crucial while interpreting the results of CTA. Nevertheless, no imaging-based reference values for CB dimensions have been comprehensively proposed in the literature for routine application in the general population and across diverse age, gender, and chronic diseases groups.

RP Nguyen et al. [15] conducted a study to assess the imaging appearance of CB, depicting normal-sized CB as 1.1 to 3.9 mm ± 2 SDs. According to their study, transverse diameter of the CB was 2.4 ± 0.8 mm at right and 2.2 ± 0.7 mm at left, while AP diameter averaged at 2.0 ± 0.6 mm at right and 2.1 ± 0.5 mm on left. Subsequently, they concluded that values greater than 6 mm should be suspected to be a paraganglioma, necessitating further evaluation [15]. In a study of Tan et al. [5] assessing CB volume in 1226 individuals using carotid ultrasonography, normal CB volume was reported to be 2.63 µl, whereas CB volume was significantly higher among individuals with hypertension(3.11 µl, P < 0.001), heart failure(3.27 µl, P = 0.004), and smoking (3.47 µl, P < 0.001) [5]. In a study of Yılmazer Zorlu et al. [29] aimed at investigating imaging features of CB and CBT, the median long and short diameters in the axial plane and vertical diameter in the coronal plane of normal CBs were 2.7, 1.9, and 3 mm, respectively, while these values were reported 27, 22.1, and 30.9 mm in their counterpart group. Moreover, Cramer et al. [14] reported mean CB diameter in individuals without underlying comorbidities 2.3 mm. In contrast to previous studies [14, 15, 29], the average transverse diameter in the general population was higher, at 2.66 ± 0.5 mm(mean ± SD), with AP diameter average of 3.25 ± 0.61 mm. Sex-specific reference values also revealed higher cut-off ranges for CB diameters. This discrepancy could be explained by higher visualization rate in this study in contrast to 82% to 86% in similar previous studies [14, 15] and larger sample size of current study. While CB size was shown to not being affected by gender in previous study [14], current study lies with more recent literature [29] depicting slightlly greater sizes for CB in males versus females.

Ageing was shown to be associated with changes in CBs, including decreased chemoreceptor sensitivity, increased CB connective tissue composition, and larger transverse diameters and length, which are significantly greater in the three consecutive age groups (10–20 years; 21–40 years and 41–70 years) [30]. In line with previous histopathological examinations of CB across different age groups [30], our study showed wider variability and slightly higher references in advanced age groups, particularly in those aged 60–70 years. On the contrary, Nguyen et al. [15] did not show any statistically significance change in CB size across different age groups. This discrepancy could be explained in part by the fact that the authors in the latter utilized analysis of covariance test to explore the association between gender and CB dimension, which might have limited to detect effects and power.

To further refine reference values, current study performed sub-group analysis across different categories. Stratified analysis based on chronic disease status revealed slightly greater transverse (2.71 ± 1.20 mm) and anteroposterior diameter (3.30 ± 1.34 mm) compared to disease-free individuals (2.57 ± 0.52 mm and 3.17 ± 1.20 mm, respectively). In a study of Nguyen et al. [15] measuring CB size in 154 patients with diabetes mellitus, hypertension, or heart failure, CB size was found to be 20–25% larger relative to control group(P-value < 0.01), ranging from 2.7 mm to 2.8 mm. Likewise, Csizmadia et al. [13] demonstrated the average CB size at right side 2.31 ± 0.82 mm² and at left side 2.34 ± 0.66 mm^{2 ,} with values higher in patients with hypertension, as 3.07 ± 0.81 mm² and 2.91 ± 0.74 mm² for the right side and left side, respectively. Evaluating the size of CB in patients with hypertension and heart failure, Sreejit Nair et al. [6] found similar results, with mean cross-sectional area of right CB 2.79 mm² in the former group compared to 1.40 mm² in disease-free individuals(P-value = 0.02) and mean cross-sectional area of 3.13 mm² in HF and HTN patients vs. 1.53 mm² in controls (p = 0.03). The largest average CB size reported in literature was demonstrated by Goksu et al. [27], showing total CB area in patients with COVID-19 pneumonia 4.9 ± 3.7 mm², whereas this value was averaged at 3.7 ± 2.4 mm² in control individuals (P-value < 0.05). In line with other studies, Tan et al. [5] found greater CB volume in the presence of comorbidities, ranging from 3.11 µl (micro liter) to 4.05 µl relative to the control group(2.63 µl)(P-value < 0.001). Compared to previous studies, current study demonstrated larger reference ranges for CB dimension in the presence of chronic diseases.

To get a better understanding of combined impacts of sex and chronic disease status on CB size, we further stratified our participants based on their gender and chronic disease state. To the best of our knowledge, this work represents the first study exploring CB size stratified by sex in the presence or absence of comorbidities. The mean ± SD values for anteroposterior and transverse diameters were slightly larger among males without chronic diseases in comparison to females, although females displayed wider variability in CB dimension. A similar pattern was observed among males and females with chronic diseases. These differences in CB sizes across genders might be partly explained by distinct histomorphological differences in CB structure between males and females, as shown by smaller carotid artery diameter in females than males and Sex differences in carotid bifurcation anatomy [31–33]. Sex-driven differences in tunica and intima layers of the common carotid and internal carotid arteries and their significance to the pathogenesis of several cardio-metabolic diseases have been widely studied [31, 34]. More recent study showed adventitial layer contribution to atheroma formation in carotid arteries [35]. Derived from the tunica adventitia, the authors of this study speculate that adventitia layer and thus CBs might also be influenced by sex-specific hormonal changes and body composition.

To further underpin the importance of chronic disease status, we performed age-stratified analysis among individuals with underlying comorbidities. A similar pattern was observed: Modestly increased transverse and AP diameter of CB with advancing age, with wider dispersion and variability observed among older individuals (≥ 60 years of age), ranging from 1.34 to 4.61 mm. Likewise, the presence of chronic disease was associated with larger diameters as compared to their disease-free counterpart. Comprehensive literature review in published papers in English did not reveal similar papers comparing CB dimension across different age groups in individuals with chronic diseases, setting our study apart from prior research. In a retrospective analysis on patients with CBTs, made by Yılmazer Zorlu et al. [29] found that age was not an independent predictor of imaging characteristics suggestive of CBT, including larger CB dimension. We speculate that aging could potentially accentuate the impacts of chronic diseases states on CB size, leading to progression of underlying comorbidities. Further studies are needed to investigate the relationship between aging and chronic diseases with CB morphology and function.

Using comparative analyses, we explored the potential impact of various comorbidities- including hypertension, hyperlipidemia, diabetes, thyroid diseases, cardiovascular diseases, chronic obstructive pulmonary diseases, CVA or TIA- as well as smoking status, head and neck trauma, as well as age groups, different BMI categories (healthy, overweight, obese), and gender. This analysis revealed no statistically significant differences in CB dimensions across different subgroups (P-value > 0.05), although a statistically significant difference in CB diameters was observed between CVA versus non-CVA group(P-value < 0.05), the effect size was very small (Eta Squared 0.010 to 0.012), implying limited clinical or practical importance. A few studies reported the development of CVA as a presenting manifestation of CB diseases, particularly paraganglioma [36, 37]. Considering the well-established association between stroke development and carotid artery degenerative changes [38] and the proposed relationship between CB function and cardio-metabolic diseases [24], one could speculate that CB sizes might be different in patients with previous stroke. However, the observed effects were small, which could be partly explained by the fact that CBs react to different initiating and propagating disturbances commonly observed in pathogenesis of stroke, such as hypoxia and reduced cerebral perfusion [39], leading to alterations in CB structure and morphology. Another possible explanation for such observation would be our study’s relatively large sample size compared to similar studies [15, 24], which translates into statistically significant associations even in the presence of small changes in the CB diameters. Overall, our proposed reference values for CB diameters could be employed in diverse clinical states with a limited potential to be influenced by variables. Thorough literature search did not reveal similar studies, making comparison with previous research improbable.

Study strengths and limitations

Strengths

The current study represents the first to explore CB size across to offer a comprehensive reference range across different demographic and clinical comorbidities groups. Despite previous research evaluating CBs, information regarding CB cut-off values remains scarce in the literature. Considering the association between CBs and the pathogenesis of various cardiometabolic diseases, distinguishing hyperplastic CBs from CBTs remains of clinical significance. Our study could serve as a potential clinical framework for radiologists to distinguish CBTs from non-neoplastic enlargement, which could mitigate the need for unnecessary investigations. Compared to the current literature, the population size in our study was large, which remains of significant importance in reference range studies. Moreover, we performed subgroup-specific cut- off values for CB dimension stratified by age groups, gender, and co-morbidity status. Collectively, the recommended cut-off values could serve as a promising diagnostic tool in clinical settings.

Limitations

This study has some limitations. First of all, we did not assess other CB imaging features, such as shape characteristics and enhancement features. Previous studies have shown distinct morphological alterations in CBs observed in hyperplastic forms [29, 40] and different density ratio in CTA of CBTs versus normal individuals [29]. Incorporating CB shape and enhancement features into future studies might provide more comprehensive framework for CB reference dimensions. Secondly, we did not incorporate volumetric measurement in our study. We believed that a volumetric measurement would be of questionable accuracy due to the following reasons: Firstly, we initially presumed to measure the CB volume in our study. However, due to ongoing software limitations and reconstruction techniques in our hospital PACS workstation, tracing and delineate identification of CBs were not feasible. Secondly, significant anatomical variations in CBs have been reported in the literature [33], which makes discrete identification difficult. Furthermore, most of the CBs have variable oval-to-round shape in the axial plane, and are not symmetric. Due to the small size and close proximity of CBs to adjacent structures, discriminating CBs from nearby structures was difficult, and therefore; volumetric measurement of CBs was infeasible using CTA. Collectively, we decided to measure the AP and transverse diameters, which has shown to be compatible with CB size data obtained from anatomical examinations [27], further supporting our study design.

Although assessments were conducted by two evaluators (radiologists), inter-rater agreement was not formally quantified using classic statistical measures such as the intraclass correlation coefficient (ICC), which could have further strengthened the reliability of the results. Another limitation may be the lack of histopathological confirmation in our study participants, particularly among those with larger than previously reported values on CB diameters, however, tissue sampling in tumor-free individuals would only be feasible in cadaveric studies. In contrast to previous study [15] using the Pearson Correlation Coefficient to assess the reliability of right and left CB sizes, we averaged the right and left side measurements to obtain a single measurement per subject. Using Paired T-test, the observed difference in measurements among right and left sides was found to be insignificant (P-value > 0.05), indicating that mean difference was negligible among both sides. Several other methodological limitations should be considered when interpreting our findings. First, the sample size of certain subgroups was too small to generate statistically reliable reference ranges. Specifically, the number of participants aged ≤ 20 years (n = 23) was insufficient for robust pediatric-specific reference intervals, and the very small subgroups with chronic disease (e.g., age ≤ 20 with chronic disease, n = 4; age 20–30 with chronic disease, n = 7) precluded any meaningful subgroup analysis. Therefore, the reference ranges for these groups are presented only descriptively and must be interpreted with caution. Second, the study is cross-sectional and single-center, which may introduce selection bias and limit generalizability to other populations or imaging protocols. Third, despite rigorous quality control, we excluded cases where carotid bodies were not clearly visible or measurable (e.g., due to motion artefact, poor image quality, or anatomical variation), which could have introduced some degree of selection bias. Fourth, a small number of patients (< 2% of the final sample) had missing age data, resulting in minor discrepancies between the total sample size and the sum of age-group frequencies in Table 1. Fifth, we used the mean of right and left carotid body measurements for analysis; although this reduces measurement error, it does not account for potential side-specific differences. Finally, because our primary aim was to establish reference ranges for tumor-free individuals, we excluded all patients with carotid body tumors (n = 36). While this was necessary for the reference range calculation, it limits the applicability of our findings to pathological populations. Future prospective, multicenter studies with larger pediatrics and chronic-disease cohorts are needed to validate and extend our results.

Conclusions

In conclusion, our study represents the first to explore reference ranges for carotid bodies based on CTA. We evaluated CB diameters across various comorbidities and age and sex categories, and proposed reference ranges for AP and transverse diameters in each group. Overall, transverse diameter of CB was reported 2.66 ± 0.5 mm, while AP diameter was averaged at 3.25 ± 0.61 mm. Overall, chronic diseases and advanced age were associated with larger diameters. Incorporating the proposed size reference values could provide a valuable insight for clinicians to distinguish patients requiring further investigation from individuals with subtle CB enlargements due to underlying comorbidities or advanced aging, leading to improved diagnostic accuracy and reduced unnecessary interventions. However, future studies are required to investigate other imaging characteristics of CBs-including enhancement and morphological features-and correlate them with size measurements, to validate our findings for generalized clinical application.

Supplementary Information

Below is the link to the electronic supplementary material.

Abbreviations

CB

Carotid body

CBT

Carotid body tumor

CTA

Computed tomography angiography

COPD

Chronic obstructive pulmonary disease

BMI

Body mass index

CVA

Cerebrovascular accidents

TIA

Transient ischemic attack

MRA

Magnetic resonance angiography

CDU

Color doppler ultrasonography

CVD

Cardiovascular diseases

SD

Standard deviation

VR

Volume rendering

MIP

Maximum intensity projection

MPR

Multiplanar reformation

mm

millimeters

PACS

Picture archiving and communication system

HU

Hounsfield units

ROI

Region of interest

Author contributions

Somayeh Hajiahmadi , Conceptualization, Data collection, image interpretation, Methodology, Supervision, Formal data analysis, Writing – review & editing ; Negin Faghih Dolatabadi , Conceptualization, Methodology, Data collection, image interpretation, Formal data analysis, Writing – review & editing ; Paria Bolourinejad , Conceptualization , Methodology, Formal data analysis, Supervision, Writing- initial, Writing – review & editing ; Fatemeh Dashti, Conceptualization , Methodology, Formal data analysis, Supervision, Writing- initial, Writing – review & editing.

Funding

None.

Data availability

The authors of this manuscript declare that the datasets used in this study are deposited in machine-readable format and are available to any scientists aiming to use them for non-commercial purposes provided that patient confidentiality is maintained.

Declarations

Ethics approval and consent to participate

Informed consent was obtained from all subjects involved in the study. Informed consent was also obtained from the legal guardians or parents of study participants under the age of 16. The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013), and approved by the Institutional Ethics Committee of Isfahan University of Medical Sciences (protocol code IR.MUI.MED.REC.1402.324).

Consent for publication

Written consent for the publication of potentially identifiable information was obtained from all patients, including legal guardians or parents of study participants below the age of 16.

Competing interests

The authors declare no competing interests.