Introduction
The thyroid gland is an important endocrine gland in the body, and the incidence of thyroid cancer has increased over the last few years in many countries.1 The incidence of incidental thyroid nodules is also increasing, especially in middle-aged women.2 Relevant surveys have shown that the proportion of malignant thyroid nodules is about 5% to 15%.3 The increasing detection of thyroid cancer has raised concerns regarding overdiagnosis, overtreatment, and the associated healthcare burden.4 Based on epidemiological data, the increasing incidence of thyroid cancer may reflect both a true increase in disease occurrence and the increased detection of occult thyroid cancers resulting from advances in diagnostic testing.5
Most differentiated thyroid cancers grow slowly and generally exhibit indolent biological behavior. With appropriate and standardized treatment, their prognosis is generally favorable.6 Thyroid cancer may be accompanied by cervical lymph node metastasis, particularly central lymph node metastasis, which can complicate surgical management. In addition, treatment and long-term follow-up may impose psychological burdens and adversely affect patients’ quality of life.7 Therefore, the most critical issue is the diagnosis and evaluation of malignant thyroid nodules and early standardized treatment of thyroid diseases. Accurate and effective diagnostic methods for detecting malignant thyroid nodules are essential for early standardized diagnosis and treatment.8
This narrative review aims to comprehensively summarize the imaging principles, clinical indications, diagnostic performance, advantages, and limitations of the aforementioned imaging techniques and to propose a stratified selection strategy based on clinical scenarios to guide precision imaging diagnosis of thyroid nodules and thyroid cancer.
Commonly used imaging techniques for thyroid disease
The imaging modalities discussed in this review include ultrasound, computed tomography (CT), positron emission tomography-computed tomography (PET-CT), spectral CT, and magnetic resonance imaging (MRI) (Table 1). In traditional clinical practice, radiologists visually interpret images and characterize lesions based on their size, morphology, margins, density, echogenicity, and signal characteristics. Among advanced ultrasound techniques, ultrasound elastography has been investigated as an adjunctive method for evaluating tissue stiffness in thyroid nodules.9 In recent years, with the advancement of science and technology, radiomics has gradually become an important area of medical research. It mainly includes four steps: image acquisition, region of interest segmentation, texture feature extraction, and further data analysis. Through texture analysis, computer-aided diagnosis, traditional machine-learning models, and deep learning, radiomics can extract and analyze large amounts of quantitative information from medical images to assist clinical assessment.
Table 1Comparison of commonly used imaging techniques for thyroid nodules
| Imaging technique | Imaging principle | Primary clinical indications | Key advantages | Main limitations | Radiation exposure | Cost level |
|---|
| Ultrasound | High-frequency sound wave reflection | Initial nodule screening, TI-RADS classification, FNA biopsy guidance, follow-up monitoring | Noninvasive, no radiation, real-time, low cost, high resolution | Operator-dependent, limited visualization in retrosternal/obese patients | None | Low |
| CT | X-ray computed tomography | Evaluating retrosternal extension, lymph node metastasis, tumor invasion extent, postoperative assessment | High spatial resolution, clear anatomical delineation, fast scanning | Ionizing radiation; potential adverse effects of iodinated contrast agents; limited role in primary nodule risk stratification | Yes | Medium |
| PET-CT | Metabolic (FDG) and anatomical fusion imaging | Evaluation of suspected recurrent or metastatic high-risk disease; selected radioiodine scan-negative cases; adjunctive assessment of cytologically indeterminate nodules | Whole-body imaging; functional and metabolic assessment | Expensive, high radiation dose, false positives possible (e.g., thyroiditis) | Yes | High |
| Spectral CT | Dual-energy/Multi-energy X-ray imaging | Adjunctive nodule characterization; iodine quantification in selected cases | Multiparametric quantification; iodine mapping; virtual monoenergetic imaging; potential aid in lesion characterization | Equipment not widely available, protocols need standardization, complex post-processing | Yes; protocol- and platform-dependent | Medium-High |
| MRI | Magnetic fields and radiofrequency pulses | Evaluation of soft-tissue invasion and neurovascular relationships; postoperative residual disease or recurrence; alternative when iodinated contrast-enhanced CT is unsuitable | No radiation, excellent soft-tissue contrast, multi-planar imaging | Long scan time; high cost; limited sensitivity to calcifications; restrictions with some non-MRI-compatible implants or severe claustrophobia | None | High |
Diagnostic ultrasound
At present, in the clinical application of examination methods for the diagnosis of thyroid diseases, it is recommended that all patients with suspicious thyroid gland nodules should initially undergo ultrasound examination.10 Ultrasound technology is highly dependent on the operator’s level of expertise, and accurate diagnosis needs to be performed by physicians during image acquisition. The ultrasound diagnosis of thyroid nodules is often based on morphology (the shape, aspect ratio, and size), nodule margins, echo characteristics, and the presence or absence of calcifications on ultrasound images as the basis for malignant diagnosis.11 Predominantly cystic or spongiform composition and well-defined margins are generally associated with a lower risk of malignancy. Suspicious ultrasound features include irregular margins, a taller-than-wide shape, and punctate echogenic foci. In clinical practice, the Thyroid Imaging Reporting and Data System (TI-RADS) is usually used to score and quantify thyroid nodules based on ultrasound image characteristics and then refine the classification to determine the likelihood of malignancy.12 In addition to traditional ultrasound diagnostic technology, the relatively new ultrasound superb microvascular imaging (SMI) technique has gradually entered clinical practice. SMI can improve the visualization of low-velocity microvascular flow and may provide adjunctive information for differentiating benign and malignant thyroid nodules based on vascular distribution and morphology, although standardized diagnostic criteria are still needed.13 Two-dimensional shear-wave elastography can quantitatively evaluate malignant thyroid nodules through real-time transverse wave propagation based on rapid sequence recording. Ultrasound shear-wave elastography (SWE) can provide qualitative and quantitative information about nodule stiffness. These advanced ultrasound techniques may provide adjunctive information for thyroid nodule characterization.
While conventional ultrasound provides excellent morphological characterization, advanced ultrasound techniques offer functional and hemodynamic information that can further refine diagnostic accuracy, particularly for indeterminate nodules or those with overlapping features. SMI is an advanced Doppler technique that uses a unique algorithm to separate low-velocity microvascular flow from tissue motion artifacts without the need for contrast agents. SMI provides superior visualization of intranodular microvascular architecture compared with conventional color or power Doppler. SMI has demonstrated improved sensitivity for detecting microvessels in small nodules and can aid in distinguishing benign from malignant lesions, especially when conventional Doppler is inconclusive. SWE is a real-time quantitative technique that measures tissue stiffness by tracking the propagation velocity of shear waves induced by acoustic radiation force. SWE has been investigated as an adjunctive method for thyroid nodule characterization, particularly in indeterminate nodules, although its incremental diagnostic value varies across clinical settings.9 Contrast-enhanced ultrasound (CEUS) involves intravenous administration of microbubble contrast agents to evaluate macro- and microvascular perfusion in real time. CEUS enables dynamic assessment of enhancement patterns, including the degree, homogeneity, and wash-in/wash-out kinetics. CEUS may provide ancillary information on nodule perfusion and enhancement patterns, although its routine clinical role and diagnostic criteria remain insufficiently standardized.
Ultrasound is currently the preferred noninvasive screening tool for thyroid nodules, offering significant advantages such as real-time imaging, absence of radiation, relatively low cost, and the ability to guide biopsy procedures. Its high-frequency probes provide excellent resolution for superficial structures, clearly depicting internal microcalcifications, margin morphology, and blood flow distribution within nodules. When combined with the TI-RADS classification system, it substantially enhances diagnostic standardization. However, ultrasound diagnosis is highly operator-dependent, has limited visualization of retrosternal thyroid tissue or thyroid tissue in obese patients, and the interpretation of subtle malignant features remains somewhat subjective.
CT
Compared with ultrasound, conventional CT provides high spatial and density resolution and can clearly demonstrate cervical lymph nodes, retrosternal lesions, and coarse or deeply located calcifications. CT assessment of thyroid nodules may include lesion location, size, number, morphology, margins, calcification, hemorrhage, cystic change, necrosis, enhancement pattern, regional lymph node metastasis, and distant metastasis (Fig. 1). Malignant thyroid nodules may present as lobulated lesions with irregular soft-tissue density. Poorly defined margins, absence of a capsule, or capsular discontinuity may raise suspicion for malignancy. Infiltrative tumors may also be accompanied by cervical lymph node metastasis or vascular invasion. Microcalcifications may suggest malignancy, particularly in papillary thyroid carcinoma. CT can provide important anatomical information for surgical planning, particularly in patients with retrosternal extension or suspected invasion of adjacent structures. In addition, CT-based computer-aided diagnostic systems have been investigated for assessing the malignancy risk of thyroid lesions.14
CT offers excellent spatial and density resolution, enabling clear visualization of the anatomical relationships between the thyroid and surrounding cervical structures (such as the trachea, esophagus, blood vessels, and lymph nodes). It is particularly valuable for assessing retrosternal thyroid lesions, lymph node metastasis, and the extent of tumor invasion, providing crucial information for surgical planning. However, CT involves exposure to ionizing radiation, and iodine-based contrast agents may trigger allergic reactions or interfere with thyroid function. Furthermore, its sensitivity for detecting microcalcifications is lower than that of high-frequency ultrasound.
PET-CT
PET-CT has been investigated as an adjunctive tool for selected patients with cytologically indeterminate thyroid nodules, although it is not routinely recommended for initial nodule evaluation.15 Generally, the standardized uptake value is an important quantitative index, and increased uptake of fluorodeoxyglucose (FDG) usually represents a higher risk of malignancy. In selected patients with high-risk differentiated thyroid cancer, FDG PET-CT may be used to evaluate suspected recurrent or metastatic disease, provide prognostic information, and assess treatment response, particularly when serum thyroglobulin is elevated but radioiodine imaging is negative.16 PET-CT can also be used to further identify sonographically suspicious and scintigraphically hypofunctional thyroid nodules.17 However, the high cost of PET-CT also affects its application in the diagnosis of thyroid nodules.
PET-CT, by reflecting tissue glucose metabolic activity (e.g., FDG uptake), holds unique value in staging thyroid cancer, monitoring recurrence, and evaluating distant metastasis. This is especially true for postoperative patients with elevated thyroglobulin levels but negative iodine scans. Its whole-body imaging capability aids in detecting unsuspected distant metastases. Nonetheless, PET-CT is expensive, delivers a high radiation dose, and can yield false-positive results because some benign conditions (e.g., thyroiditis) may also exhibit high FDG uptake. Therefore, it is not recommended as a routine initial screening tool for thyroid nodules.
Spectral CT
Spectral CT acquires energy-resolved data using dual-energy or multi-energy techniques and can generate iodine maps, virtual monoenergetic images, and spectral curves. Depending on the platform, spectral data may be acquired using dual-source, rapid kilovoltage-switching, dual-layer detector, or photon-counting approaches.18 The advantages of this technology include the potential to reduce radiation dose, reduce the need for additional acquisitions, decrease artifacts, and improve lesion conspicuity.19 Virtual monoenergetic imaging, material decomposition, and spectral curves are commonly used for spectral CT analysis of thyroid nodules. Virtual monoenergetic imaging reconstructs images at selected energy levels from dual-energy or multi-energy datasets and may improve lesion conspicuity at an optimized energy level.20 Material decomposition provides quantitative information on iodine and other constituent materials that may assist in thyroid nodule characterization. Because thyroid tissue is rich in iodine, when thyroid follicular epithelial cells are damaged, the iodine content decreases correspondingly, and the iodine content in the lesion area is reduced compared with adjacent normal tissue.21 Similarly, iodine-based images of thyroid scans in the arterial phase have been found to be the most helpful for diagnosing the nature of thyroid nodules.
Spectral CT, based on dual-energy or multi-energy imaging, provides quantitative parameters such as iodine concentration maps, virtual non-contrast images, and spectral curves that may aid in distinguishing benign from malignant nodules. However, its diagnostic performance, radiation dose, and contrast requirements depend on the imaging platform and protocol. The equipment is not yet widely available, scanning protocols and diagnostic criteria require further standardization, and the technique involves greater operational and post-processing complexity.
MRI
MRI is also a commonly used examination method for evaluating thyroid diseases. It can not only provide better soft tissue information but also display anatomical details in multiple directions and planes.22 Generally, the signal characteristics of most malignant thyroid nodules on MRI are similar to or lower than those of normal thyroid tissue on T1-weighted images, whereas the signal characteristics on T2-weighted images are mostly high.
MRI offers superior soft tissue contrast and multi-planar imaging capabilities without ionizing radiation. It can clearly display the anatomical relationships between the thyroid and surrounding nerves and blood vessels, holding significant value in assessing tumor invasion, postoperative residual disease, or recurrence. Functional sequences such as dynamic contrast-enhanced and diffusion-weighted imaging can provide additional tissue characterization information. However, MRI involves longer scan times, higher costs, is insensitive to calcifications, and is not suitable for patients with certain metallic implants or claustrophobia.
Optimal clinical scenarios
Ultrasound is best suited for initial screening of thyroid nodules, TI-RADS-based risk stratification, real-time guidance for FNA biopsy, and longitudinal follow-up of benign nodules. It is ideal for outpatients, pregnant women, and repeated examinations due to its lack of radiation, low cost, and wide availability. CT is indicated for preoperative assessment of patients with confirmed or suspected malignant nodules, particularly when retrosternal goiter, extensive cervical lymph node metastasis, or invasion of the trachea, esophagus, or major vessels is clinically suspected. It is also valuable for postoperative evaluation when deep-seated recurrence is not well visualized by ultrasound. PET-CT is recommended for staging and restaging of high-risk thyroid cancer patients, especially those with elevated thyroglobulin levels but negative iodine scans. It is also useful for detecting distant metastases and monitoring treatment response. PET-CT is not indicated for routine screening of thyroid nodules. Spectral CT may provide adjunctive quantitative information, including iodine concentration and spectral attenuation parameters, for selected thyroid nodules incidentally evaluated by CT. However, its role in routine nodule characterization remains investigational and requires further validation.20,21 MRI may be considered when iodinated contrast-enhanced CT is unsuitable, particularly for assessing soft-tissue invasion or postoperative residual or recurrent disease. The use of gadolinium-based contrast agents should be individualized according to renal function and other patient-specific factors.
Comparison and selection strategies of thyroid imaging techniques
Initial screening and risk assessment: Ultrasound should be used as the preferred examination method for thyroid nodules, combined with TI-RADS classification for risk stratification and guidance regarding the need for needle biopsy.
Preoperative assessment and staging: For patients with high-risk ultrasound findings or confirmed malignant nodules, especially those with clinical suspicion of retrosternal extension, lymph node metastasis, or local invasion, contrast-enhanced CT is recommended to clarify the anatomical extent and assist in surgical planning. MRI can be used as an alternative or supplement to CT, especially for assessing soft tissue invasion or when patients have contraindications to iodinated contrast agents.
Recurrence and metastasis monitoring: FDG PET-CT may be useful after thyroid cancer surgery when serum thyroglobulin levels are elevated but radioiodine imaging is negative, or when distant metastases are clinically suspected.
Technological complementarity and multimodal integration: In difficult cases, quantitative iodine maps from spectral CT or MRI functional sequences (e.g., diffusion-weighted imaging, dynamic enhancement) can be combined to provide auxiliary information. The integration of radiomics and artificial intelligence technology is expected to further improve differential diagnosis and prognosis prediction.
Individualized and evidence-based selection: The final imaging strategy should be individualized based on the patient’s specific condition, nodule characteristics, medical resource availability, economic factors, and evidence-based guidelines.