The combination of virtual touch tissue imaging quantification (VTIQ) and American College of Radiology’s Thyroid Imaging Reporting and Data System (ACR TI-RADS) improves the diagnostic efficiency for thyroid nodules with Hashimoto’s thyroiditis: a retrospective study
Introduction
Hashimoto’s thyroiditis (HT) is a common autoimmune thyroid disease characterized by a large number of lymphocytes infiltrating the thyroid interstitium, leading to fibrous tissue hyperplasia and thyroid follicle atrophy (1). HT is defined on the basis of the presence of thyroid peroxidase antibodies and/or thyroglobulin antibodies. The relationship between HT and malignant thyroid tumors is not clear, but studies have shown that HT is significantly related to papillary thyroid carcinoma (2-5). However, conventional ultrasound examination has certain limitations for distinguishing benign and malignant thyroid nodules (TNs) (6). There is a certain overlap of ultrasound images, especially morphology, margins, internal blood flow, and echoes of benign and malignant TNs with concurrent HT (7,8). This underscores the need for more reliable and sensitive diagnostic modalities to enhance clinical decision-making and improve patient prognosis.
To improve the standardization of the diagnosis and treatment of TNs, the American College of Radiology’s Thyroid Imaging Reporting and Data System (ACR TI-RADS) was released in May 2017 (9). However, according to the ACR guidelines, the proportion of highly suspicious malignant TI-RADS 5 nodules is more than 20%. Therefore, to avoid unnecessary fine-needle aspiration (FNA) cytology, some studies have suggested combination evaluation with ultrasound elastography to further confirm the diagnosis (10,11). Virtual touch tissue imaging quantification (VTIQ) is a new shear wave-based ultrasound elastography technology that can obtain quantitative characteristics of tissue elasticity (12,13). Researchers have postulated that VTIQ technology is a useful and reproducible tool for predicting thyroid malignancy (14,15). Previous studies have established the efficacy of the ACR TI-RADS in stratifying TNs, and the integration of VTIQ technology into this framework could increase diagnostic accuracy (16,17).
However, there are few reports on the identification of benign and malignant TNs in the context of HT (18-20). This study aimed to assess the diagnostic value of VTIQ combined with ACR TI-RADS in benign and malignant TNs with HT and to facilitate clinical diagnosis, treatment, and risk management. We present this article in accordance with the STARD reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1-2705/rc).
Methods
Study population
Patients who had undergone thyroid ultrasound examination at The Fourth Affiliated Hospital of Nanjing Medical University from January 2018 to April 2025 were consecutively selected. All patients had complete clinical data. The patients with HT tested positive for thyroglobulin antibodies (TgAb) and/or thyroid peroxidase antibodies (TPOAb) in serum. The exclusion criteria were as follows: spongy or cystic nodules (solid parts <25%); no VTIQ technical examination; maximum diameter of the nodules <5 mm; previous history of head and neck radiotherapy or TN thermal ablation; no postoperative pathologically confirmed benign or malignant nodules in the context of an HT background; and pregnancy. Surgical treatment was performed based on cytologically confirmed malignancy (the Bethesda category VI) by FNA, or for clinically significant compressive symptoms (such as dysphagia, dyspnea, and/or hoarseness). The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Institutional Review Board (IRB) of The Fourth Affiliated Hospital of Nanjing Medical University (No. 20240226-K012). Considering that this study was retrospective and posed no risk to patients, the IRB waived the requirement for informed consent. A total of 146 patients with HT (235 nodules) were ultimately included in this study (Figure 1).
Instruments and methods
Conventional ultrasound and VTIQ imaging: a German Siemens Acuson S3000 colour Doppler ultrasound diagnostic instrument (Siemens, Erlangen, Germany) was used. The instrument was equipped with VTIQ imaging software, and 9L4 (4–9 MHz) and 18L6 (6–18 MHz) linear array probes were used, of which 9L4 probes were used for VTIQ technical examination, and 18L6 probes were used for routine ultrasound examination. In accordance with the ACR TI-RADS assessment standard, five aspects, including the nodule composition, echogenicity, shape, margins, and echogenic foci, were recorded in detail. The score of each nodule was recorded. After switching to acoustic radiation force impulse (ARFI) mode, the largest section of the TNs was selected, and the patient was instructed to hold their breath when the image was clearest. Then, VTIQ mode was used to display the VTIQ quality mode diagram and speed mode diagram, and image acquisition was performed. A total of 100 thyroid nodes from the first 75 patients enrolled in the study were examined by two skilled attending physicians who had been proficient in VTIQ examination for more than six months to assess the consistency between VTIQ examiners. The VTIQ results from the remaining TNs were independently evaluated by two ultrasound physicians. To ensure the uniformity and stability of the measurement results, shear wave velocity (SWV) data measurements (≥5) were performed at multiple sites within the nodules, and the maximum, minimum, and average values of the SWV were collected and recorded in m/s (21).
Image interpretation: the investigators assessed the characteristics of the TNs, including their composition, echogenicity, shape, margins, and presence of echogenic foci, following the ACR TI-RADS classification system. Each nodule was assigned a score on the basis of these features. The ultrasound malignant risk classification was determined by calculating the ACR TI-RADS (TR) score, which categorized patients into four groups: the highly suspicious malignant group (TR5: ≥7 points), the moderately suspicious malignant group (TR4: 4–6 points), the low suspicious malignant group (TR3: 3 points), and the slightly suspicious malignant group (TR2: 2 points). The mildly suspicious malignant group (TR2) and low suspicious malignant group (TR3) were judged as benign nodules, and the moderately suspicious malignant group (TR4) and highly suspicious malignant group (TR5) were classified as malignant nodules. Two investigators, each with over five years of experience in thyroid ultrasound, independently analyzed and recorded the ACR TI-RADS categories without knowledge of the patients’ identities. They were also unaware of the image acquisition process, VTIQ assessments, and cytologic or pathologic results. In cases of disagreement between the two investigators, a third investigator with 20 years of experience in thyroid ultrasound reviewed the images and made the final decision.
Pathological examination: pathology results were acquired by two pathologists with more than five years of experience in thyroid pathology. Nodules were classified as benign or malignant on the basis of the postoperative pathological findings.
Statistical methods
Statistical analysis of the data was performed via the software SPSS 16.0 (IBM Corp., Armonk, NY, USA) and R 4.3.1 (R Foundation for Statistical Computing, Vienna, Austria). Normally distributed data were represented as mean ± standard deviation, and the independent samples t-test was used for comparisons between two groups. The χ2 test was used for the comparison of count data. The consistency of the measurements between different examiners was analyzed via intraclass correlation coefficient (ICC) analysis. A receiver operating characteristic (ROC) curve was drawn to determine the best cut-off value for each SWV to calculate the sensitivity, specificity, and accuracy of VTIQ technology for identifying benign and malignant TNs with concurrent HT. A restricted cubic spline (RCS) was used to explore the dose-response relationship between the average SWV and malignant TNs. P<0.05 was considered statistically significant.
Results
Pathological results
A total of 146 patients, including 56 males and 90 females aged 16–79 years, with HT (235 nodules) who had undergone thyroid ultrasound examination from January 2018 to April 2025 were included. The average age was 37.5±15.6 years. The nodule size, based on longitudinal and transverse diameters measured on ultrasound, ranged from 0.7 cm × 0.5 cm to 5.8 cm × 2.3 cm. The largest diameter ranged from 0.7 to 5.8 cm, and the average diameter was 1.45±0.56 cm. According to the results of the postoperative pathological examination, 146 HT patients had a total of 235 TNs, including 133 benign nodules (56 adenomas, 35 nodular goiters, and 42 nodular HTs) and 102 malignant nodules (98 papillary thyroid carcinomas, 3 follicular carcinomas, and 1 medullary carcinoma).
Comparison of ultrasound sonographic features of benign and malignant TNs with concurrent HT
On the basis of the results of postoperative pathological examination, the sizes of benign and malignant TNs with concurrent HT were not significantly different (P>0.05); however, the composition, echogenicity, shape, margins, and echogenic foci were significantly different between the two groups (P<0.05) (Table 1).
Table 1
| US features | Benign | Malignant | P value |
|---|---|---|---|
| Size (cm) | 2.26±1.41 | 1.91±1.33 | 0.0545 |
| Composition | 0.0002 | ||
| Solid or almost solid | 73 | 80 | |
| Mixed | 60 | 22 | |
| Echogenicity | <0.0001 | ||
| Isoechoic or hyperechoic | 60 | 18 | |
| Hypoechoic | 51 | 61 | |
| Very hypoechoic | 22 | 23 | |
| Shape | <0.0001 | ||
| Taller than wider | 14 | 31 | |
| Wider than taller | 119 | 71 | |
| Margin | <0.0001 | ||
| Smooth or ill defined | 99 | 43 | |
| Lobulated or irregular | 34 | 56 | |
| Extrathyroidal extension | 0 | 3 | |
| Echogenic foci | <0.0001 | ||
| Punctate echogenic foci | 35 | 54 | |
| Macrocalcifications or peripheral (rim) calcifications | 22 | 15 | |
| No echogenic foci | 76 | 33 |
Data are presented as mean ± standard deviation or number. US, ultrasound.
Value of the ACR TI-RADS classification for distinguishing benign and malignant TNs with concurrent HT
The ACR TI-RADS classification identified benign and malignant nodules with concurrent HT, as shown in Table 2. The mildly suspicious malignant group (TR2) and low suspicious malignant group (TR3) were judged as benign nodules, and the moderately suspicious malignant group (TR4) and highly suspicious malignant group (TR5) were classified as malignant nodules. The sensitivity, specificity, and accuracy of the diagnosis of benign and malignant TNs were 84.3%, 85.0%, and 84.7%, respectively.
Table 2
| ACR TR-RADS | Benign nodules | Malignant nodules |
|---|---|---|
| TR2 | 82 | 6 |
| TR3 | 31 | 10 |
| TR4 | 12 | 17 |
| TR5 | 8 | 69 |
| TR2 + TR3 | 113 | 16 |
| TR4 + TR5 | 20 | 86 |
Data are presented as number. ACR TI-RADS, American College of Radiology’s Thyroid Imaging Reporting and Data System; TR, TI-RADS.
Value of the VTIQ technique for distinguishing benign and malignant TNs with concurrent HT
When VTIQ technology was used to distinguish between benign and malignant TNs with concurrent HT, the maximum, minimum, and average SWVs of the benign nodules were significantly lower than those of the malignant nodules, and the difference was statistically significant (P<0.05) (Table 3, Figures 2,3). The ROC curve revealed that the optimal threshold of the SWV maximum for the differential diagnosis of benign and malignant TNs with concurrent HT by VTIQ technology was 3.37 m/s, and the corresponding sensitivity, specificity, and accuracy for diagnosing malignant TNs with concurrent HT were 80.4% (82/102), 71.4% (95/133), and 75.4% (177/235), respectively. The optimal threshold of the SWV minimum was 2.65 m/s, and the corresponding sensitivity, specificity, and accuracy for diagnosing malignant TNs with concurrent HT were 79.4% (81/102), 82.0% (109/133), and 80.9% (190/235), respectively. The optimal threshold of the average SWV was 3.02 m/s, and the corresponding sensitivity, specificity, and accuracy for diagnosing malignant TNs with concurrent HT were 86.3% (88/102), 85.7% (114/133), and 85.9% (202/235), respectively. Among them, the average SWV and ROC curve had the greatest AUC, and the average SWV presented the highest sensitivity, specificity, and accuracy. The RCS analysis revealed a linear correlation between the average SWV and the risk of malignant TNs (P for overall <0.01, P for nonlinearity >0.05) (Figure 4).
Table 3
| Category | SWVmax | SWVmin | SWVavg |
|---|---|---|---|
| Benign nodules | 3.24±0.98 | 2.22±0.56 | 2.68±0.82 |
| Malignant nodules | 4.77±1.72 | 3.27±1.01 | 4.01±1.11 |
| P value | <0.0001 | <0.0001 | <0.0001 |
Data are presented as mean ± standard deviation. SWV, shear wave velocity (m/s); SWVavg, average SWV; SWVmax, maximum SWV; SWVmin, minimum SWV.
Comparison of VTIQ and ACR TI-RADS classification in the diagnosis of benign and malignant TNs with concurrent HT and pathological results
The sensitivity, specificity, and accuracy of the ACR TI-RADS classification for the diagnosis of benign and malignant TNs with concurrent HT were 84.3%, 85.0%, and 84.7%, respectively. According to the diagnostic results of the three SWVs measured by VTIQ, the average SWV had high sensitivity, specificity, and accuracy in diagnosing benign and malignant TNs with concurrent HT, corresponding to 86.3%, 85.7%, and 85.9%, respectively. For VTIQ combined with the ACR TI-RADS classification of 128 benign TNs and 107 malignant nodules with concurrent HT, the corresponding sensitivity, specificity, and accuracy were 88.0%, 89.2%, and 88.5%, respectively (Table 4, Figure 5).
Table 4
| Diagnostic method | Pathological results | Total | AUC (95% CI) | Sensitivity (%) | Specificity (%) | Accuracy (%) | |
|---|---|---|---|---|---|---|---|
| Benign | Malignant | ||||||
| ACR TI-RADS | 0.846 (0.793–0.900) | 84.3 | 85.0 | 84.7 | |||
| Malignant | 20 | 86 | 106 | ||||
| Benign | 113 | 16 | 129 | ||||
| VTIQ | 0.865 (0.814–0.916) | 86.3 | 85.7 | 85.9 | |||
| Malignant | 19 | 89 | 108 | ||||
| Benign | 114 | 13 | 127 | ||||
| ACR TI-RADS + VTIQ | 0.886 (0.839–0.933) | 88.0 | 89.2 | 88.5 | |||
| Malignant | 16 | 91 | 107 | ||||
| Benign | 117 | 11 | 128 | ||||
| Total | 133 | 102 | 235 | ||||
ACR TI-RADS, American College of Radiology’s Thyroid Imaging Reporting and Data System; AUC, area under the curve; CI, confidence interval; VTIQ, virtual touch tissue imaging quantification.
Inter-examiner consistency of VTIQ quantification
VTIQ examination of 100 TNs was independently performed by two different examiners. The results obtained by the two examiners were analyzed via the ICC and were found to be consistent. There was no significant difference in the maximum SWV (SWVmax), minimum SWV (SWVmin), or average SWV (SWVavg) calculated by the two examiners, and the ICC values were 0.79, 0.78, and 0.80, respectively.
Discussion
This study aimed to address the diagnostic challenges associated with evaluating TNs in patients with HT by integrating ACR TI-RADS with VTIQ technology. The main findings of this study are as follows: First, the VTIQ technique is a valuable tool for distinguishing malignant from benign TNs in patients with HT. Second, the combination of VTIQ and ACR TI-RADS can help to improve the diagnostic efficiency in distinguishing between benign and malignant TNs with HT. Third, there is a linear dose-response relationship between the average SWV and malignant TNs. This highlights the potential of a synergistic approach in refining the diagnostic process for TNs with HT, ultimately aiming to facilitate early identification of malignant lesions and improve patient management outcomes.
By applying ACR TI-RADS for classification, our study investigated the acoustic characteristics provided by both conventional ultrasound and VTIQ to increase the accuracy of malignancy differentiation. These findings suggest that although both ACR TI-RADS and VTIQ individually demonstrate high sensitivity and specificity, their combined application significantly improves diagnostic performance, with a sensitivity reaching 88.0% and a specificity of 89.2%. According to the results presented, 43.4% (102 nodules) of the nodules were malignant. Hu et al. (22) reported that compared with non-HT patients, the risk of HT patients with thyroid cancer increased by 0.49 times [relative risk (RR) =1.49, 95% confidence interval (CI): 1.42–1.57, I2=45.3%, P=0.067]. Given this high prevalence of malignancy, the application of VTIQ combined with ACR TI-RADS is necessary in patients with HT.
In this study, TR2 and TR3 patients were diagnosed with benign nodules, and TR4 and TR5 patients were diagnosed with malignant nodules. The sensitivity, specificity, and accuracy of this combination for the diagnosis of benign and malignant TNs were 84.3%, 85.0%, and 84.7%, respectively. Compared with the results of Li et al. (17) reported that the diagnostic sensitivity decreased, whereas the specificity and accuracy significantly increased. The reason for the decrease in sensitivity may be the pathological evidence in this group of data. The main reason is that there were benign nodules, but there were fewer malignant nodules. The increased diagnostic accuracy may be related to the following factors. First, TR2 and TR3 were classified as benign in this study, and TR4 and TR5 were classified as malignant. Second, all the TNs in this study were concurrent with HT. Papillary thyroid carcinoma is prone to occur in a background of HT. Therefore, many patients with suspected malignancies have undergone biopsy or surgical resection, and the disease is ultimately confirmed to be a malignant nodule through pathological diagnosis (23).
In our study, we used VTIQ technology to identify benign and malignant TNs with concurrent HT to reduce the dependence and repeatability of the examination (15). This group of data revealed that the maximum, average, and minimum SWVs of malignant nodules with concurrent HT were significantly greater than those of benign nodules (P<0.01); namely, malignant nodules with concurrent HT are harder than benign nodules are. The ROC curves of the diagnostic results of the three SWV values measured by VTIQ technology revealed that the average SWV has high sensitivity, specificity, and accuracy in diagnosing benign and malignant TNs with concurrent HT. Compared with the results of Zhang et al. (24), the diagnostic sensitivity and specificity were improved, which may be related to the VTIQ technology applied in this study. Hao et al. (25) demonstrated that ACR TI-RADS combined with three-dimensional shear wave elastography has higher diagnostic efficiency than conventional ACR TI-RADS. The sensitivity and accuracy of combined ACR TI-RADS showed significant improvements. Our findings collectively demonstrate that combining ACR TI-RADS with elastography can further improve the diagnostic efficiency in evaluating TNs.
The RCS analysis revealed a linear correlation between the average SWV and the risk of malignant TNs (P for overall <0.01, P for nonlinearity >0.05), suggesting that as the average SWV increased, the risk of malignant TNs increased. In clinical practice, the average SWV can be considered for inclusion in the risk assessment process for TNs with HT. Our study provides additional information on the value of ultrasonic elastography for detecting TNs in patients with different thyroid diseases.
The clinical implications of our study are profound. The enhanced diagnostic accuracy in diagnosing benign and malignant TNs with HT achieved through the combination of ACR TI-RADS and VTIQ has the potential to significantly influence treatment decisions. Accurate differentiation between benign and malignant TNs with HT can lead to reduced unnecessary surgical interventions, thereby minimizing the associated risks and costs for patients. Furthermore, our findings could inform clinical guidelines and policies regarding the management of TNs in patients with autoimmune thyroid disease. In clinical practice, ultrasonic elastography can be considered for inclusion in the risk assessment process for TNs with HT.
This study has several limitations. First, the patients included in the current study were surgical patients. We excluded participants without VTIQ technical examination and those who did not undergo surgery. For these reasons, the results may be inaccurate due to selection bias, suggesting that a prospective group control study is essential. Second, the TNs in this study were classified according to the ACR TI-RADS, but further treatment methods, such as puncture or follow-up standards, were not completely consistent with the guidelines. Third, this study was a retrospective analysis; the results of this study still need to be validated by prospective, multicenter, large-scale studies. In addition, the study had a small sample size, which needs to be further expanded in future studies.
Conclusions
The ACR TI-RADS classification has high clinical value in the qualitative diagnosis of TNs in the context of HT. VTIQ technology also has good application prospects for the differential diagnosis of benign and malignant TNs in the context of HT. The technique is simple and easy to perform, the measurement results are highly repeatable, and the diagnostic accuracy is high. The combined application of these two methods is helpful for improving the accuracy of diagnosis.
Acknowledgments
None.
Footnote
Reporting Checklist: The authors have completed the STARD reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1-2705/rc
Data Sharing Statement: Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1-2705/dss
Funding: This work was supported by
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1-2705/coif). The authors have no conflicts of interest to declare.
Ethical Statement: 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 and its subsequent amendments. The study was approved by the Institutional Review Board (IRB) of The Fourth Affiliated Hospital of Nanjing Medical University (No. 20240226-K012). As this was a retrospective study with no risk to patients, the requirement for written informed consent was waived.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
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