Quantitative assessment of thyroid glands in healthy children with shear wave elastography

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Quantitative Assessment of Thyroid Glands in Healthy

Children With Shear Wave Elastography

Emine Uysal, MD and Mehmet Öztürk, MD

Abstract: The local shear wave speed (in meters per second) and Young modulus (in kilopascals) of normal thyroid glands were defined in healthy children to determine reference values.

This prospective study assessed 107 pediatric cases (age interval, 3–17 years; mean, 9.37 ± 3.68 years), including 52 boys and 55 girls. The study group included children without thyroid gland disease (autoimmune, infectious, or neoplastic). Data about the sex, age, weight, height, and body mass index (BMI) of the subjects were recorded for all subjects. Elasticity values were measured from 3 different sites in both thyroid lobes and averaged.

Median values for elasticity and shear wave velocity measured in bilateral

thyroid lobes were 6.38 ± 1.97 kPa (range, 3.00–12.5 kPa) and

1.45 ± 0.21 m/s (range, 1.03–2.04 m/s) on the right and 8.81 ± 3.00 kPa

(range, 3.80–22.6 kPa) and 1.69 ± 0.26 m/s (range, 1.13–2.68 m/s) on

the left. There was no significant difference between the elasticity values for the right and left thyroid lobes between boys and girls. There was a pos-itive correlation between right thyroid lobe mean elasticity (in kilopascals) and shear wave velocity (in meters per second) values with age, BMI, and right thyroid lobe volume in the whole group. No significant correlation was found between left thyroid lobe mean elasticity (in kilopascals) and shear wave velocity (in meters per second) values with age, BMI, and left thyroid lobe volume in the study population.

This study determined mean elasticity and shear wave velocity values for thyroid gland in healthy children. This information can be used as a baseline for the investigation of thyroid diseases.

Key Words: children, shear wave elastography, thyroid gland, ultrasonography

(Ultrasound Quarterly 2019;35: 297–300)

U

ltrasonography (US) is a valued diagnostic modality for de-tecting focal or diffuse lesions within the thyroid gland.1 Ultrasonography plays a significant role in the assessment of thyroid diseases in pediatric patients. Thyroid gland size and pa-renchyma echogenicity are requisite components in assessment and follow-up of thyroid pathologies.2

In shear wave elastography (SWE), a short duration (0.03–0.4 milliseconds) high-power acoustic repulsive radiation

force is applied to the tissue with US transducer. This force stimulates mechanical waves that propagate transversely in the tissue (1–10 μm). These horizontally spaced displacements are called“shear waves.” The production of the radiation force by the probe rather than the operator means that SWE is more op-erator independent, quantitative, and reproducible.3Shear wave elastography allows measurement of the propagation speed of shear waves within the tissue to locally quantify its stiffness in kilopascals or meters per second.4

Ultrasonography elastography has been researched with respect to differentiating malignant and benign thyroid nod-ules.5There are a few studies evaluating thyroid parenchyma in autoimmune thyroiditis using SWE for the pediatric popula-tion.6There is a single study assessing normal thyroid paren-chyma using acoustic radiation force impulse elastography in the pediatric population.7

In this study, we measured the local shear wave speed (in meters per second) and Young modulus (in kilopascals) of nor-mal thyroid glands in healthy children to determine reference values and to supply information for further studies dealing with thyroid gland diseases. We believe that knowing the normal elas-ticity values of healthy thyroid glands in the pediatric population will help us use SWE for diagnosis of thyroid pathologies.

MATERIALS AND METHODS

This prospective study assessed 107 pediatric cases (age interval, 3–17 years; mean, 9.37 ± 3.68), including 52 boys and 55 girls. Informed consent was acquired from all parents of the children, and approval was secured from our local ethics committee. The subjects were children who were admitted to the outpatient clinic for problems other than the thyroid gland. The study group included children without thyroid gland disease (autoimmune, infectious, or neoplastic). The exclusion criteria were autoimmune, infectious, inflammatory, or neoplastic thy-roid gland disorders and abnormal grayscale US findings of the thyroid gland. Data on the sex, age, weight, and height of the sub-jects were recorded for all subsub-jects. Body mass index (BMI) was calculated using the following formula: BMI = weight (kg)/ height (m)2.

None of the studies were excluded because optimal quality images were obtained in all patients.

US and SWE Technique

Ultrasonography and SWE examinations of the thyroid gland were performed with an Aplio500 US system (Toshiba Medical Systems, Tokyo, Japan) using a linear array transducer (frequency 14 MHz). Measurements were performed by 2

Received for publication November 2, 2018; accepted December 12, 2018. Department of Radiology, Selçuk University Faculty of Medicine, Konya,

Turkey.

The authors declare no conflict of interest.

Address correspondence to: Mehmet Öztürk, MD, Department of Radiology, Selçuk University Faculty of Medicine, 42030 Konya, Turkey (e‐mail: drmehmet2121@gmail.com).

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ESEARCH

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radiologists with 5 and 2 years of SWE experience. Normal thy-roid parenchyma was described as normal size, homogeneous echotexture, comprising no nodular or cystic lesion. After a dedicated US examination, dimensions of each thyroid lobe were measured and volumes of the right and left lobes were cal-culated using the following formula width (cm) length (cm) depth (cm) 0.523.

After this, the SWE software was activated. The subjects were requested not to move or swallow during the examination. While getting the images, pressure was not implemented to the probe, and care was taken that the operator's hand was not moving. In split-screen mode, the 2-dimensional SWE map (left side) and quality mode (right side) were examined (Figs. 1A, B). The quality mode, which is identified as the propagation mode (arrival time contour), is a mode in which dependable data are acquired when the lines are smooth and parallel, and the increase in distance be-tween the lines is parallel to the increase in elasticity. Bilgici et al7 made measurements in the axial plane during their study of acoustic radiation force impulse elastography measurements of the thyroid gland in healthy children. Subsequently, a 2-mm-diameter region of interest was used to take measurements at 3 different points within homogeneous parenchyma that did not contain vascular structures from the center of each lobe in the ax-ial plane. All measurements were recorded both as kilopascals and meters per second. The mean stiffness and velocity values for each lobe were calculated by averaging 3 measurements per lobe. The main carotid artery was kept out from the 2-dimensional SWE map to prevent pulsation artifact. The measurements in both thyroid lobes were made from the center of the lobe as far away as possible to the main carotid artery.

Statistical Analysis

We performed all statistical analyses using SPSS Statistics 22 (IBM, Armonk, NY). Continuous variables are expressed as arithmetic mean ± SD. The Shapiro-Wilk test was used to deter-mine the normality in the distribution of the quantitative data. To

compare 2 independent groups, Student t test was used for nor-mally distributed data. Pearson correlation and regression analy-sis were applied to the continuous variables of the study. A P value less than 0.05 was considered statistically significant.

RESULTS

The descriptive analysis of age, BMI, each thyroid lobe volume, and the elasticity (in kilopascals) and shear wave velocity (in meters per second) values of the right and left thyroid lobes from SWE are given in Table 1. The relationship between sex and age, BMI, bilateral thyroid lobe volume, and elasticity are summarized in Table 2. Regardless of sex, there was a positive cor-relation between each thyroid lobe volume and age, as well as BMI (P < 0.05). The mean volumes of the bilateral thyroid lobes showed a significant difference between boys and girls. Right and left thyroid lobe volume in boys was found to be higher than that in girls (P < 0.05).

Using SWE, the median values for elasticity and shear wave velocity measured in bilateral thyroid lobes were 6.38 ± 1.97 kPa (range, 3.00–12.5 kPa) and 1.45 ± 0.21 m/s (range, 1.03–2.04 m/s) on the right and 8.81 ± 3.00 kPa (range, 3.80–22.6 kPa) and 1.69 ± 0.26 m/s (range, 1.13–2.68 m/s) on the left. There was a positive correlation between right thyroid lobe mean elasticity (in kilopascals) values and age (r = 0.255, P = 0.008), BMI (r = 0.252, P = 0.009), and right thyroid lobe volume (r = 0.283, P = 0.003) in the whole group. Similarly, a positive correlation was found between right thyroid lobe shear

FIGURE 1. A and B, Three measurements in a single transverse plane from 2 different sections were carried out for each thyroid lobe.

TABLE 1. Descriptive Analysis of Age, BMI, Volume, and Elasticity

n = 107 Mean SD Minimum Maximum

Age, y 9.37 3.68 3 17

BMI, kg/m2 18.06 4.56 0.17 30.47

Right thyroid lobe

Volume, cm3 _2.21 _1.34 _0.4 ₉

SWE, kPa 6.38 1.97 3 12.5

SWE, m/s 1.45 0.21 1.03 2.04

Left thyroid lobe

Volume, cm3 _1.49 _0.88 _0.1 _4.6

SWE, kPa 8.81 3 3.8 22.6

SWE, m/s 1.69 0.26 1.13 2.68

TABLE 2. The Relationship between Sex With Age, BMI, Bilateral Thyroid Lobe Volume, and Elasticity

Boys (Mean) Girls (Mean) P

Age, y 10.42 8.38 0.004

BMI, kg/m2 18.35 17.78 0.525

Right thyroid lobe

Volume, cm3 _2.55 _1.89 _0.01

SWE, kPa 6.36 6.4 0.91

SWE, m/s 1.45 1.45 0.98

Left thyroid lobe

Volume, cm3 _1.78 _1.21 _0.001

SWE, kPa 9.04 8.6 0.44

SWE, m/s 1.71 1.67 0.4

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wave velocity (in meters per second) values with age, BMI, and right thyroid lobe volume (Table 3). Elasticity of right thyroid lobe increased as age, BMI, and volume increased. However, no significant correlation was found between left thyroid lobe mean elasticity (in kilopascals) and shear wave velocity (in meters per second) values with age, BMI, and left thyroid lobe volume in the study population (P > 0.05).

For the right thyroid lobe in boys, the median elasticity values were 6.36 kPa and 1.45 m/s, whereas for the left thyroid lobe, the median values were 9.04 kPa and 1.71 m/s. In girls, the median values were 6.4 kPa and 1.45 m/s for the right thyroid lobe and 8.6 kPa and 1.67 m/s for the left thyroid lobe. There was no significant difference between the elasticity values for the right and left thyroid lobes between boys and girls (Figs. 2A, B). There was a positive correlation between right thyroid lobe mean elasticity (in kilopascals) values and age (r = 0.36, P = 0.008) and right thyroid lobe volume (r = 0.32, P = 0.017) in boys. Similarly, a positive correlation was found between right thyroid lobe shear wave velocity (in meters per second) values with age and right thyroid lobe volume (Table 4). However, no correlation was found between left thyroid lobe elasticity values with age and thyroid lobe volume in boys (P > 0.05). In girls, there was a positive correlation between BMI and left thyroid lobe with mean elasticity (in kilopascals) values (r = 0.35, P = 0.007) and shear wave velocity (in meters per second) values (r = 0.32, P = 0.014). There was no correla-tion between BMI, age, right thyroid lobe volume, and right thyroid lobe elasticity values in girls (P > 0.05).

DISCUSSION

Thyroid pathologies including goiter, hyperthyroidism, hypothyroidism, autoimmune thyroiditis, and nodular diseases of the thyroid may affect children.8Although childhood thyroid carcinomas have a low mortality rate, the risk of recurrence is high.9The most common thyroid disorder in the pediatric age group is autoimmune thyroiditis; it is more widespread in genet-ically responsive children, mainly among girls, and its frequency increases with age, peaking during adolescence.10,11

For the diagnosis of thyroid pathologies, clinical exami-nation, laboratory findings, and imaging modalities are used.12

B-mode US is the primary imaging test for thyroid pathologies, but it is operator dependent, and features of thyroid parenchyma are not enough to reach a precise diagnosis.13Besides grayscale US, elastography can provide additional knowledge about tissue stiffness. Elastography using shear waves is less operator de-pendent when compared with strain elastography and ensures quantitative information on tissue elasticity.7 There seems to be an increasing tendency in studies showing added diagnostic value of elastography to the routine US assessments for diffuse or focal thyroid pathologies.6,14,15

Yurttutan et al16found the mean strain index value for the thyroid gland to be 0.54 ± 0.38 in a group of healthy children. In a study using acoustic radiation force impulse elastography by Bilgici et al,7the mean shear wave velocity of the thyroid gland was reported as 1.22 ± 0.20 m/s in 145 healthy children. There have also been some studies that evaluated SWE using Young modulus of elasticity (in kilopascals) in adults.17–19

In this study, we demonstrated that mean volumes of the bilateral thyroid lobes in boys were higher than in girls. The me-dian values for elasticity were measured as 6.38 ± 1.97 kPa (range, 3.00–12.5 kPa) for the right lobe and 8.81 ± 3.00 kPa (range, 3.80–22.6 kPa) for the left in our study. Arda et al17

dis-covered the mean elasticity value for the thyroid gland to be 10.97 ± 3.1 kPa (range, 1–24 kPa) in their study assessing the elastography values of various tissues. In a study by Vlad et al,18

the mean elasticity value for the thyroid gland was 19.5 ± 7.6 kPa in 52 healthy adults. Sebag et al19reported that the mean elastic-ity value of the thyroid gland was 15.9 ± 7.6 (5–35) kPa in 39 controls in their studies evaluating malignant and benign thyroid nodules. The thyroid elasticity values in our study were found to be lower than the adult values revealed in these studies. Similarly,

TABLE 3. Correlations of Right Thyroid Lobe Shear Wave Velocity With Age, BMI and Volume

Parameter Value Age Pearson r 0.26 P 0.006 BMI Pearson r 0.24 P 0.013

Right thyroid lobe volume

Pearson r 0.29

P 0.002

FIGURE 2. A and B, Box plot showing no significant difference between elasticity values for the right (A) and left (B) thyroid lobes between boys and girls. The asterisks indicate extreme outliers. The circles indicate mild outliers.

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Sporea et al20and Friedrich-Rust et al21demonstrated that shear wave velocity values of the healthy thyroid gland in children are lower than healthy adult subjects.

In the present study, we found no difference between the mean elasticity and shear wave velocity values of the bilateral thyroid lobes in girls and boys. Bilgici et al and Yurttutan et al reported no difference between elasticity values of the thyroid gland in girls and boys, too. We identified a positive correlation between right thyroid lobe mean elasticity and shear wave ve-locity values with age, BMI and right thyroid lobe volume in the whole group. Bilgici et al demonstrated no correlation be-tween shear wave velocity of the thyroid gland and age. No cor-relation was found between thyroid gland strain index values and age and BMI in the study by Yurttutan et al. Similarly, there was no significant correlation between left thyroid lobe mean elasticity and shear wave velocity values with age, BMI, and left thyroid lobe volume in our study population. In our study, left thyroid lobe volume values were found to be lower than right thyroid lobe volume values (Table 1). We think that this volume difference may affect elasticity measurements. In the fu-ture, we hope that studies about this topic will be performed with larger populations. There was a positive correlation between right thyroid lobe mean elasticity and shear wave velocity values with age as well as right thyroid lobe volume for boys, as in the whole group. However, there was no correlation between right thyroid lobe mean elasticity and shear wave velocity values with age, BMI, and right thyroid lobe volume in girls. We demon-strated a positive correlation between BMI and left thyroid lobe mean elasticity and shear wave velocity values in girls. As stated in Table 2, the mean age of girls was statistically signifi-cantly lower than that of boys. The mean age of boys was 10.42 years, whereas it was 8.38 years for girls. There seemed to be more boys in the adolescent age group. Most girls were in the preadolescent period. The positive correlation between elasticity values in boys with age and right thyroid lobe volume may be linked to more active working of the thyroid gland in the adolescent period.

Our study has some limitations. The subjects were se-lected among children who applied to the outpatient clinic for reasons other than thyroid diseases. Thyroid function tests were not performed in these children, so we are unaware of possible hormonal abnormality apart from grayscale US findings. Our study population consisted of 107 children. It would be useful to research in larger groups to ensure that reference elasticity and velocity values are correctly determined in children.

CONCLUSIONS

Our study defined the normal elasticity and shear wave velocity values of thyroid glands in healthy children. Such in-formation can be used as a baseline for the investigation of thy-roid diseases. Shear wave elastography has potential use in the evaluation of various thyroid pathologies in children, especially as a complement to US in the diagnosis of diffuse thyroid parenchymal diseases.

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TABLE 4. Correlations of Right Thyroid Lobe Shear Wave Velocity With Age and Volume in Boys

Parameter Value

Age

Pearson r 0.38

P 0.005

Right thyroid lobe volume

Pearson r 0.35

P 0.01

Uysal and Öztürk Ultrasound Quarterly • Volume 35, Number 3, September 2019