Ultrasound grayscale ratio: a reliable parameter for differentiating papillary thyroid microcarcinoma from micronodular goiter

doi:10.21203/rs.2.21897/v1

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Ultrasound grayscale ratio: a reliable parameter for differentiating papillary thyroid microcarcinoma from micronodular goiter

https://doi.org/10.21203/rs.2.21897/v1

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posted 27 Jan, 2020

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Background: To evaluate the reliability and diagnostic efficacy of the ultrasound grayscale ratio (UGSR) for differentiating papillary thyroid microcarcinomas (PTMC) from micronodular goiters (diameter ≤ 1.0cm).

Methods: The ultrasound data of 241 pathologically-confirmed cases of patients with 265 PTMC and 141 patients with 168 micronodular goiters were retrospectively reviewed. All patients underwent outpatient ultrasonic examination and preoperative ultrasonic positioning. The RADinfo radiograph reading system (Zhejiang RAD Information Technology Co., Ltd., China) was used to measure and calculated the UGSR of PTMC, micronodular goiters. Patients were divided into the outpatient examination, preoperative positioning, and mean value groups, and the receiver operating characteristic curves (ROC) were calculated to obtain the optimal UGSR threshold for distinguishing PTMC from micronodular goiters.

Results: The UGSR values of the PTMC and micronodular goiters were 0.56±0.14 and 0.80±0.19 (t=5.84, P<0.01) in the outpatient examination group, 0.55±0.14 and 0.80±0.19 (t=18.74, P<0.01) in the preoperative positioning group, and 0.56±0.12 and 0.80±0.18 (t=16.49, P<0.01) in the mean value group. The areas under the ROC curves in the outpatient examination, preoperative positioning, and mean value groups were 0.860, 0.856, and 0.875, respectively. When the cut-off UGSR values for the outpatient examination, preoperative positioning, and mean value groups were 0.649, 0.646, and 0.657, the sensitivity and specificity for predicting PTMC were 78.9% and 86.9%, 79.2% and 83.9%, 82.6%, and 85.7%, respectively. A reliable UGSR value was obtained between the outpatient examination and preoperative positioning groups (ICC=0.79, P=0.68).

Conclusion: The UGSR is an accurate and feasible tool for differentiating PTMC from micronodular goiters with better diagnostic efficacy.

Nuclear Medicine & Medical Imaging

Ultrasound Grayscale Ratio

Papillary Thyroid Microcarcinoma

Micronodular Goiters

Thyroid lesions are divided into five categories based on the comparison of echogenicity between the cervical strap muscle and thyroid: anechoic, markedly hypoechoic, hypoechoic, isoechoic and hyperechoic[1–3]. Of the five categories, the diagnostic values of the hypoechoic and markedly hypoechoic categories have been widely accepted for thyroid malignant nodules[1, 4–7]. However, distinguishing between hypoechoic and markedly hypoechoic categories is a subjective process and is thus influenced by the observer’s judgement. Thus, their diagnostic values for malignant nodules vary in different studies: the sensitivity and specificity are 79%-93.8% and 21.8%-61% for the hypoechoic category, respectively, and 17.1–41.4% and 90.9–98.8% for the markedly hypoechoic category, respectively[8–12]. Evidently, the specificity of the hypoechoic category and the sensitivity of the markedly hypoechoic category are insufficient for clinical diagnosis. The quantification of the echogenicity of nodules will, to a large extent, eliminate differences due to subjective judgement. In addition, as computer intelligent auxiliary diagnosis progresses, the quantification of grayscale values will contribute to rapid and accurate diagnosis on a large scale.

It is well known that the absolute ultrasound grayscale value is affected by the scanning apparatus, scan gain, dynamic range, frequency, and operators. Thus, it is impossible to assess the echogenicity using the absolute grayscale value. The ultrasound grayscale ratio (UGSR) is the grayscale ratio of pathologic tissues to surrounding normal tissues at the same gain level. Moreover, it is unknown whether UGSR is affected by the aforementioned factors. In this study, we compared the UGSR values in the outpatient examination, preoperative positioning, and mean value groups, and analyzed the association between the UGSR and several factors including the scanning apparatus, gain level, dynamic range, frequency, and operator. In addition, we assessed the diagnostic efficacy of the UGSR in differentiating papillary thyroid microcarcinomas (PTMC) from micronodular goiters.

Subjects

This study was approved by the ethics committee of Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine (No. 2018. 108-01) and written informed consent was obtained from all subjects. A total of 891 pathologically-confirmed cases of patients with 1086 thyroid nodules were recruited from January 2016 to October 2018. All patients were examined by preoperative ultrasonography and ultrasonic positioning. Patients with nodule diameter > 1.0 cm or < 0.3 cm, cystic dominated nodules and nodules with calcification that precluded the measurement of soft tissues, and thyroid nodules with complicating Hashimoto thyroiditis were excluded from the study[13-15]. Finally, this study involved 349 patients with 433 nodules, including 71 men and 292 women, with an average age of 48±11 years (range 23-78 years) (Figure 1).

Methods

Ultrasonic examination of thyroid lesions was performed using one of the following ultrasonic diagnostic scanners: MyLab 70 XVG (Genova, Italy), Esaote MyLab Classic C (Genova, Italy), Esaote Mylab 90 (Genova, Italy), GE Voluson E8 (Tiefenbach15, Austria), GE Voluson E10 (Tiefenbach15, Austria), GE logic E9 (Wauwatosa, USA）, Philips HD 11 XE (Amsterdam, Netherlands), Philips HDI 5000 (Amsterdam, Netherlands), Siemens S2000 (Buffalo Grove, USA), Mindray Resona7 (Shenzhen, China), and so on. Then, 5-13 MHz broadband linear array probes were used for this study, and the central frequency was 7.5 MHz. Patients were placed in a supine position, exposing the anterior cervical region, after which transverse, longitudinal, and oblique scans were performed.

Ultrasonic examination

The ultrasonographic data, selected from the Picture Archiving and Communication Systems database, were analyzed by two radiologists with 14 and 16 years of experience, respectively. The ultrasound grayscale values of the PTMC, micronodular goiters and thyroid tissues at the same gain level were retrospectively reviewed using the RADinfo radiograph reading system (Yilaida, Zhejiang Province), and the corresponding UGSR values were calculated. UGSR was the specific value between the grayscale of PTMC or micronodular goiters and the normal thyroid tissue at the same level. Afterward, patients were divided into the outpatient examination, preoperative positioning, and mean value groups. Outpatient examination group included patients who underwent thyroid ultrasound examination, preoperative positioning group included these outpatients to receive ultrasound again before thyroidectomy, the mean value group included the mean UGSR of the two groups above. The optimal UGSR value for differentiating PTMC from micronodular goiters was determined by analyzing receiver operating characteristic (ROC) curves. The calcification and necrosis regions were avoided during the region of interest (ROI) measurements. For nodules with homogeneous echo, an ROI > 1/2 of the largest areas of nodules was selected; for nodules with heterogeneous echo, an ROI > 1/2 of echo-dominated areas within regions was selected; and for measuring the grayscales of surrounding normal thyroids, ROIs of nodules at the same gain level and size were selected (Figure 2-4).

Statistical analysis

The SPSS for Windows version 17.0 software package (IBM Corporation, Armonk, NY) was used to generate the ROC curves for differentiating PTMC from micronodular goiters. The UGSR threshold was determined by measuring the area under the ROC curve. Differences in the UGSR value between and within groups were compared using either the analysis of variance or Student’s t-test. Reliability analysis of the UGSR was performed in the outpatient examination and preoperative positioning groups. P-values less than 0.05 were considered to be statistically significant.

A total of 349 patients with 433 nodules comprised 241 cases with 265 PTMC and 141 cases with 168 micronodular goiters. Among them, 33 cases presented with both PTMC and micronodular goiters. As shown in Table 1, the UGSR values of PTMC and micronodular goiters were 0.56±0.14 and 0.80±0.19 in the outpatient examination group, 0.55±0.14 and 0.80±0.19 in the preoperative positioning group, and 0.56±0.12 and 0.80±0.18 in the mean value group.

The area under the ROC curve for distinguishing PTMC and micronodular goiters was 0.860 in the outpatient examination group, 0.856 in the preoperative positioning group, and 0.875 in the mean value group. When the UGSR for the outpatient examination, preoperative positioning, and mean value groups were 0.649, 0.646, and 0.657, respectively, each group obtained its largest Youden index (0.658, 0.631, and 0.683). The sensitivity and specificity for diagnosing PTMC for the outpatient examination, preoperative positioning, and mean value groups were 78.9% and 86.9%, 79.2% and 83.9%, and 82.6% and 85.7%, respectively (Figure 5). A reliable UGSR value was obtained between the outpatient examination and preoperative positioning groups (ICC=0.79, P =0.68).

Table 1. Comparisons of UGSR for distinguishing PTMC from MNG in different groups

Nodule size	Number		UGSR		t	P
Nodule size	PTMC	micronodular goiters	PTMC	micronodular goiters	t	P
Outpatient examination	265	168	0.56 ± 0.14	0.80 ± 0.19	5.84	P<0.01
Preoperative positioning	265	168	0.55 ± 0.14	0.80 ± 0.19	18.74	P<0.01
Mean value	265	168	0.56 ± 0.12	0.80 ± 0.18	16.49	P<0.01

The absolute ultrasound grayscale value is affected by the apparatus, scan gain, dynamic range, frequency, and operator. Thus, unlike CT scans, the absolute ultrasound grayscale is not suitable for the diagnosis of thyroid lesions. The UGSR is defined as the ratio of the pathologic tissue to the surrounding normal tissue at the same gain level. If the grayscale ratios of pathologic lesions and normal surrounding tissues would be relatively stable regardless of the operator or the apparatus, gain level, dynamic range, and frequency used, especially based on the standardized scanning examination. It would be an objective method for quantifying the echo levels.

In 2013, Erol et al.[16] proposed the concept of Lesion Echogenicity Ratios (LER), i.e., the ratio between echogenicity values of the neighboring fat lobule to the echogenicity values of lesions. In this study, the LER was considered to be significantly higher in malignant lesions than in benign lesions. Although this study quantified the echogenicity of mammary glands, the following three points were not elaborated: 1) effects of physiological factors such as menstrual cycle and age on LER; 2) the neighboring fat lobules were scattered and measured data were different in various regions; and 3) the LER may be affected by various apparatus, gain levels, dynamic ranges, frequencies, and operators. Evidently, the UGSR is not influenced by physiological factors and scattered fat lobules. Regarding the third point, we compared the UGSR of 265 PTMC and 168 micronodular goiters in the outpatient examination and preoperative positioning groups. The results showed no statistical differences among the outpatient examination, preoperative positioning, and mean value groups. The areas under the ROC and the optimal threshold were 0.860 and 0.649, 0.856 and 0.646, and 0.875 and 0.657, in the outpatient examination, preoperative positioning, and mean value groups, respectively. The sensitivity and specificity for diagnosing PTMC in the outpatient examination, preoperative positioning, and mean value groups were 78.9% and 86.9%, 79.2% and 83.9%, and 82.6% and 85.7%, respectively. As the UGSR decreased, the sensitivity and specificity for predicting PTMC decreased and increased, respectively. The area under the ROC curve, optimal threshold, sensitivity, and specificity in the three groups were highly identical with an optimal diagnostic efficacy in the mean value group. Compared to our previous study[17], the sensitivity decreased, the specificity increased, and the area under the ROC curves were identical. The diagnostic efficacy for the three groups was better than that for some previously reported data[18–20]. Moreover, a reliable UGSR value was obtained for the outpatient examination and preoperative positioning groups (ICC = 0.79, P = 0.68), suggesting that the UGSR was a reliable parameter for predicting PTMC and micronodular goiters.

There are two limitations to this study. First, for nodules with heterogeneous echo and normal thyroid tissues with heterogeneous echo, a variation in the ROI selection and measurement may exist due to technical issues. Cooperation between two or more experienced radiologists could reduce this variation. Second, selection bias inevitably existed in this retrospective study. A multiple-center and prospective study may reduce this bias.

UGSR

Ultrasound Grayscale Ratio; PTMC = Papillary Thyroid Microcarcinoma; MNG = Micronodular Goiters; ROC = Receiver Operating Characteristic; ICC = Intraclass Correlation Cofficient

Acknowledgments

Not applicable.

Authors’ contributions

All authors have made substantial contributions to the entire image analysis procedures including data acquisition, image analysis, and classification. XCK and YLF were major contributors in writing and revising the manuscript. LMK participated in collecting data and performed the statistical analysis. FJH and LDC interpreted the patients’ data. HZJ supervised the entire procedures and helped to draft the manuscript. All authors read and approved the final manuscript.

Funding

This stduy was supported by Key Project of Scientific and Technological Innovation in Hangzhou (20131813A08), and Science Research Program of Hangzhou (20180533B39).

Availability of data and materials

The data used in this study are available from the corresponding author on reasonable request.

Ethics approval and consent to participate

Not applicable

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Ultrasound grayscale ratio: a reliable parameter for differentiating papillary thyroid microcarcinoma from micronodular goiter

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Abstract

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Introduction

Materials And Methods

Results

Discussion

Abbreviations

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References

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