Study population
From November 2015 to May 2018, a total of 588 patients who visited the thyroid clinic of Soonchunhyang University Hospital for the evaluation of thyroid nodules and who underwent SWE before US guided FNA or core-needle biopsy were retrospectively reviewed in this study.
Among these subjects, 44 had thyroid cancer on surgical pathology. Patients with poor results in SWE including, thyroid nodules with poor shear wave mapping (n=7) or with macrocalcifications (n=3) and presence of nodules at the isthmic/paraisthmic areas due to the interference produced by the tracheal cartilage (n=5) were excluded. Ultimately, the data from 29 thyroid cancers in 28 patients were included in this study. There were 24 cases of conventional type of PTC, 2 cases of follicular variant PTC, 2 cases of follicular thyroid carcinoma and 1 case of medullary thyroid carcinoma.
Gray-scale ultrasound and shear wave elastography examinations
The patients were positioned for US with their necks extended. Each patient underwent gray-scale US and SWE using the Aixplorer US system (SuperSonic Imagine, Aix-en-Provence, France) and a linear probe with a frequency range of 15-4 MHz. During gray-scale US examination, thyroid nodules were evaluated for size (width, depth and length), volume, composition, orientation, echogenicity, shape, margin, and presence or absence of calcification.
After the gray-scale US, SWE was performed by the same operator who had performed the gray-scale US using the same probe. To avoid compression artifacts, generous amount of gel was used. The probe was held static in transverse plane at the center of the nodule until the image had stabilized and after two or three cine-loop images were acquired, one representative elastogram was selected with fewest artifacts in each cine-loop image.
Total nodular ROI was determined by drawing the margin of the nodule guided by the overlaid B-mode anatomic scan with the mode of the machine setting using the Q-Box Trace program. We draw the margin of ROI avoiding the areas of macrocalcification and cystic portion. The EI of the total nodular ROI was calculated and displayed by the machine. The mean (EMean), minimum (EMin), maximum (EMax), and standard deviation (ESD) of SWE EI values in the ROI were calculated as kPa, and 2D-SWE was color coded from dark blue (less than 36 kPa), light blue (36-72 kPa), green, yellow, to red (greater than 180 kPa). For the focal nodular ROI, the EI in 2-3 ROI using 3-mm circular area containing the stiffest area was measured. Moreover, the high EI area of the nodule where the color-coded EI showed higher EI than light blue (which is greater than 36 kPa) was traced by the manual drawing, and the area was calculated and displayed by the machine. The percentage of high EI area was calculated as follows: high EI area divided by the total nodular area. For the evaluation of interrater agreement, the second physician performed the same examination just after the first physician.
Pathological analysis
Surgical specimen was cut in coronal section in the largest diameter corresponding to the center of the nodule on 2D-SWE. Surgical histopathology was stained with hematoxylin and eosin staining and was diagnosed according to the World Health Organization classification [34]. Collagen fibers on histological slides were stained with Masson’s trichrome stain. Under low-power microscopy (x12 or x40), the image of the area showing the thyroid carcinoma was taken. The area of fibrosis and the total area of the thyroid carcinoma under the low-power microscopy images were taken, and the areas were measured using Q-Box Trace program calculating the area with the irregular margin, and the percentage of fibrotic area was calculated by dividing the fibrotic area by the total area of the tumor.
Statistical analysis
The tumor size and elasticity values of all the lesions were expressed as medians (25th, 75th percentile). The differences between the thyroid carcinoma groups were compared using the Mann-Whitney U-test.
To assess reproducibility of elasticity measurement, intra- and interrater agreements were evaluated using the intraclass correlation coefficient (ICC; two-way random, absolute agreement). Agreement for interrater measurements was also analyzed using Bland-Altman plots [35-37].
The coefficient of variation (CV) was calculated by the ratio of the standard deviation and mean value. A linear regression model was analyzed examining the correlation between EI and the percent of high EI area on SWE with the degree of fibrosis on histopathology. All statistical analyses were performed using the SPSS Statistics 25.0 software package (Chicago, IL, USA). P values less than 0.05 were considered statistically significant.