Special Issue "Imaging and Imaging-Based Management of Thyroid Nodules"

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Nuclear Medicine & Radiology".

Deadline for manuscript submissions: closed (31 December 2019).

Special Issue Editor

Prof. Dr. med. Luca Giovanella
Website
Guest Editor
Clinic for Nuclear Medicine and Competence Centre for Thyroid Diseases; Ente Ospedaliero Cantonale, Bellinzona 6500 Switzerland
Interests: thyroid diseases; thyroid imaging; ultrasound-assisted mini-invasive therapies; endocrine biomarkers; molecular imaging; nuclear imaging
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

The term thyroid nodule refers to an abnormal growth of thyroid cells that forms a lump within the thyroid gland. Although the vast majority of thyroid nodules are benign (noncancerous), a small proportion of thyroid nodules do contain thyroid cancer. In order to diagnose and treat thyroid cancer at the earliest stage, most thyroid nodules need some type of evaluation. Tools that allows us to preoperatively exclude a cancer might help to reduce the number of inappropriate diagnostic fine-needle aspirations and diagnostic surgical interventions. A proper, evidence-based, use of different imaging modalities would allow us to properly select suspicious nodules for more aggressive diagnostic procedures and, if needed, treatments.

The focus of this Special Issue is to review current diagiostic imaging options, as well as imaging-assisted therapies and potential novel advances in the care of thyroid nodules.

Prof. Dr. med. Luca Giovanella
Guest Editor

Manuscript Submission Information

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Keywords

  • thyroid nodule
  • thyroid cancer
  • ultrasound
  • scintigraphy
  • molecular imaging
  • thermal ablation
  • fine-needle aspiration

Published Papers (10 papers)

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Research

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Open AccessArticle
Reproducibility of Ablated Volume Measurement Is Higher with Contrast-Enhanced Ultrasound than with B-Mode Ultrasound after Benign Thyroid Nodule Radiofrequency Ablation—A Preliminary Study
J. Clin. Med. 2020, 9(5), 1504; https://doi.org/10.3390/jcm9051504 - 16 May 2020
Cited by 6
Abstract
The reproducibility of contrast-enhanced ultrasound (CEUS) and standard B-mode ultrasound in the assessment of radiofrequency-ablated volume of benign thyroid nodules was compared. A preliminary study was conducted on consecutive patients who underwent radiofrequency ablation (RFA) of benign thyroid nodules between 2014 and 2016, [...] Read more.
The reproducibility of contrast-enhanced ultrasound (CEUS) and standard B-mode ultrasound in the assessment of radiofrequency-ablated volume of benign thyroid nodules was compared. A preliminary study was conducted on consecutive patients who underwent radiofrequency ablation (RFA) of benign thyroid nodules between 2014 and 2016, with available CEUS and B-mode post-ablation checks. CEUS and B-mode images were retrospectively evaluated by two radiologists to assess inter- and intra-observer agreement in the assessment of ablated volume (Bland–Altman test). For CEUS, the mean inter-observer difference (95% limits of agreement) was 0.219 mL (-0.372–0.809 mL); for B-mode, the mean difference was 0.880 mL (-1.655–3.414 mL). Reproducibility was significantly higher for CEUS (85%) than for B-mode (27%). Mean intra-observer differences (95% limits of agreement) were 0.013 mL (0.803–4.097 mL) for Reader 1 and 0.031 mL (0.763–3.931 mL) for Reader 2 using CEUS, while they were 0.567 mL (-2.180–4.317 mL, Reader 1) and 0.759 mL (-2.584–4.290 mL, Reader 2) for B-mode. Intra-observer reproducibility was significantly higher for CEUS (96% and 95%, for the two readers) than for B-mode (21% and 23%). In conclusion, CEUS had higher reproducibility and inter- and intra-observer agreement compared to conventional B-mode in the assessment of radiofrequency-ablated volume of benign thyroid nodules. Full article
(This article belongs to the Special Issue Imaging and Imaging-Based Management of Thyroid Nodules)
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Open AccessArticle
Intraoperative Autofluorescence and Indocyanine Green Angiography for the Detection and Preservation of Parathyroid Glands
J. Clin. Med. 2020, 9(3), 830; https://doi.org/10.3390/jcm9030830 - 18 Mar 2020
Cited by 6
Abstract
Fluorescence imaging is a well-known method for both the in vivo and in vitro identification of specific cells or tissues. This imaging tool is gaining importance in the intraoperative detection and preservation of parathyroid glands during endocrine surgery owing to the intrinsic properties [...] Read more.
Fluorescence imaging is a well-known method for both the in vivo and in vitro identification of specific cells or tissues. This imaging tool is gaining importance in the intraoperative detection and preservation of parathyroid glands during endocrine surgery owing to the intrinsic properties of parathyroid tissue. The aim of this paper is to provide an overview of the basics of the technology, its history, and the recent surgical intraoperative applications of near-infrared imaging methods. Moreover, a literature review of the utilization of fluorescence devices in thyroid surgery suggests that the use of near-infrared imaging seems to be beneficial in reducing postoperative hypoparathyroidism, which is one of the most frequent complications of thyroid surgery. Full article
(This article belongs to the Special Issue Imaging and Imaging-Based Management of Thyroid Nodules)
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Open AccessArticle
Proteomic Analysis of Iodinated Contrast Agent-Induced Perturbation of Thyroid Iodide Uptake
J. Clin. Med. 2020, 9(2), 329; https://doi.org/10.3390/jcm9020329 - 23 Jan 2020
Cited by 1
Abstract
(1) Background: We recently showed that iodinated contrast media (ICM) reduced thyroid uptake of iodide independently of free iodide through a mechanism different from that of NaI and involving a dramatic and long-lasting decrease in Na/I symporter expression. The present study aimed at [...] Read more.
(1) Background: We recently showed that iodinated contrast media (ICM) reduced thyroid uptake of iodide independently of free iodide through a mechanism different from that of NaI and involving a dramatic and long-lasting decrease in Na/I symporter expression. The present study aimed at comparing the response of the thyroid to ICM and NaI using a quantitative proteomic approach. (2) Methods: Scintiscans were performed on ICM-treated patients. Micro Single-Photon Emission Computed Tomography (microSPECT/CT) imaging was used to assess thyroid uptakes in ICM- or NaI-treated mice and their response to recombinant human thyroid-stimulating hormone. Total thyroid iodide content and proteome was determined in control, NaI-, or ICM-treated animals. (3) Results: The inhibitory effect of ICM in patients was selectively observed on thyroids but not on salivary glands for up to two months after a systemic administration. An elevated level of iodide was observed in thyroids from NaI-treated mice but not in those from ICM animals. Exposure of the thyroid to NaI modulates 15 cellular pathways, most of which are also affected by ICM treatment (including the elF4 and P706SK cell signaling pathway and INSR identified as an upstream activator in both treatments). In addition, ICM modulates 16 distinct pathways and failed to affect thyroid iodide content. Finally, administration of ICM reduces thyroid-stimulating hormone (TSH) receptor expression which results in a loss of TSH-induced iodide uptake by the thyroid. (4) Conclusions: Common intracellular mechanisms are involved in the ICM- and NaI-induced reduction of iodide uptake. However, ICM fails to affect thyroid iodide content which suggests that the modulation of these common pathways is triggered by separate effectors. ICM also modulates numerous distinct pathways which may account for its long-lasting effect on thyroid uptake. These observations may have implications in the management of patients affected by differentiated thyroid carcinomas who have been exposed to ICM. They also provide the basis for the utilization of ICM-based compounds in radioprotection of the thyroid. Full article
(This article belongs to the Special Issue Imaging and Imaging-Based Management of Thyroid Nodules)
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Open AccessArticle
Diagnostic Performance of Different Thyroid Imaging Reporting and Data Systems (Kwak-TIRADS, EU-TIRADS and ACR TI-RADS) for Risk Stratification of Small Thyroid Nodules (≤10 mm)
J. Clin. Med. 2020, 9(1), 236; https://doi.org/10.3390/jcm9010236 - 16 Jan 2020
Cited by 3
Abstract
Due to the widespread use of ultrasound, small thyroid nodules (TNs) ≤ 10 mm are common findings. Standardized approaches for the risk stratification of TNs with Thyroid Imaging Reporting and Data Systems (TIRADS) were evaluated for the clinical routine. With TIRADS, the risk [...] Read more.
Due to the widespread use of ultrasound, small thyroid nodules (TNs) ≤ 10 mm are common findings. Standardized approaches for the risk stratification of TNs with Thyroid Imaging Reporting and Data Systems (TIRADS) were evaluated for the clinical routine. With TIRADS, the risk of malignancy in TNs is calculated by scoring the number or combination of suspicious ultrasound features, leading to recommendations for further diagnostic steps. However, there are only scarce data on the performance of TIRADS for small TNs. The aim was to compare three different TIRADS for risk stratification of small TNs in routine clinical practice. We conducted a retrospective cohort analysis of TNs ≤ 10 mm and their available histology. Nodules were classified according to three different TIRADS. In the study, 140 patients (n = 113 female) with 145 thyroid nodules (n = 76 malignant) were included. Most of the malignant nodules were papillary carcinoma (97%), and the remaining 3% were medullary carcinoma. For all tested TIRADS, the prevalence of malignancy rose with increasing category levels. The highest negative predictive value was found for ACR TI-RADS and the highest positive predictive value for Kwak-TIRADS. All tested variants of TIRADS showed comparable diagnostic performance for the risk stratification of small TNs. TIRADS seems to be a promising tool to reliably assess the risk of malignancy of small TNs. Full article
(This article belongs to the Special Issue Imaging and Imaging-Based Management of Thyroid Nodules)
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Open AccessArticle
Clinical and Ultrasound Thyroid Nodule Characteristics and Their Association with Cytological and Histopathological Outcomes: A Retrospective Multicenter Study in High-Resolution Thyroid Nodule Clinics
J. Clin. Med. 2019, 8(12), 2172; https://doi.org/10.3390/jcm8122172 - 09 Dec 2019
Abstract
Introduction: Thyroid nodules are a common finding. A high-resolution thyroid nodule clinic (HR-TNC) condenses all tests required for the evaluation of thyroid nodules into a single appointment. We aimed to evaluate the clinical outcomes at HR-TNCs. Design and Methods: A retrospective cross-sectional multicenter [...] Read more.
Introduction: Thyroid nodules are a common finding. A high-resolution thyroid nodule clinic (HR-TNC) condenses all tests required for the evaluation of thyroid nodules into a single appointment. We aimed to evaluate the clinical outcomes at HR-TNCs. Design and Methods: A retrospective cross-sectional multicenter study including data from four HR-TNCs in Spain. We evaluated fine-needle aspiration (FNA) indications and the association between clinical and ultrasound characteristics with cytological and histopathological outcomes. Results: A total of 2809 thyroid nodules were included; FNA was performed in 82.1%. Thyroid nodules that underwent FNA were more likely larger, isoechoic, with microcalcifications, and in younger subjects. The rate of nondiagnostic FNA was 4.3%. A solid component, irregular margins or microcalcifications, significantly increased the odds of Bethesda IV-V-VI (vs. Bethesda II). Irregular margins and a solid component were independently associated with increased odds of malignancy. Thyroid nodules <20 mm and ≥20–<40 mm had a 6.5-fold and 3.3-fold increased risk for malignancy respectively in comparison with those ≥40 mm. Conclusion: In this large multicenter study, we found that the presence of a solid component and irregular margins are factors independently related to malignancy in thyroid nodules. Since nodule size ≥40 mm was associated with the lowest odds of malignancy, this cut-off should not be a factor leading to indicate thyroid surgery. HR-TNCs were associated with a low rate of nondiagnostic FNA. Full article
(This article belongs to the Special Issue Imaging and Imaging-Based Management of Thyroid Nodules)
Open AccessArticle
Artificial Intelligence-Based Thyroid Nodule Classification Using Information from Spatial and Frequency Domains
J. Clin. Med. 2019, 8(11), 1976; https://doi.org/10.3390/jcm8111976 - 14 Nov 2019
Cited by 9
Abstract
Image-based computer-aided diagnosis (CAD) systems have been developed to assist doctors in the diagnosis of thyroid cancer using ultrasound thyroid images. However, the performance of these systems is strongly dependent on the selection of detection and classification methods. Although there are previous researches [...] Read more.
Image-based computer-aided diagnosis (CAD) systems have been developed to assist doctors in the diagnosis of thyroid cancer using ultrasound thyroid images. However, the performance of these systems is strongly dependent on the selection of detection and classification methods. Although there are previous researches on this topic, there is still room for enhancement of the classification accuracy of the existing methods. To address this issue, we propose an artificial intelligence-based method for enhancing the performance of the thyroid nodule classification system. Thus, we extract image features from ultrasound thyroid images in two domains: spatial domain based on deep learning, and frequency domain based on Fast Fourier transform (FFT). Using the extracted features, we perform a cascade classifier scheme for classifying the input thyroid images into either benign (negative) or malign (positive) cases. Through expensive experiments using a public dataset, the thyroid digital image database (TDID) dataset, we show that our proposed method outperforms the state-of-the-art methods and produces up-to-date classification results for the thyroid nodule classification problem. Full article
(This article belongs to the Special Issue Imaging and Imaging-Based Management of Thyroid Nodules)
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Open AccessArticle
Histopathological Verification of the Diagnostic Performance of the EU-TIRADS Classification of Thyroid Nodules—Results of a Multicenter Study Performed in a Previously Iodine-Deficient Region
J. Clin. Med. 2019, 8(11), 1781; https://doi.org/10.3390/jcm8111781 - 25 Oct 2019
Cited by 7
Abstract
Background: To validate the European Thyroid Imaging and Reporting Data System EU-TIRADS classification in a multi-institutional database of thyroid nodules by analyzing the obtained scores and histopathology results. Methods: A total of 842 thyroid lesions (613 benign, 229 malignant) were identified in 428 [...] Read more.
Background: To validate the European Thyroid Imaging and Reporting Data System EU-TIRADS classification in a multi-institutional database of thyroid nodules by analyzing the obtained scores and histopathology results. Methods: A total of 842 thyroid lesions (613 benign, 229 malignant) were identified in 428 patients (mean age 62.7 years) and scored according to EU-TIRADS, using ultrasound examination. In all tumors, histopathological verification was performed. Results: In EU-TIRADS 2 (154 nodules) all nodules were benign; in EU-TIRADS 3, only 3/93 malignancies were identified. In EU-TIRADS 4, 12/103 were malignant, and in EU-TIRADS 5 (278 benign vs. 214 malignant). The malignant nodules that would not have qualified for biopsy were: EU-TIRADS 3, 2/3 (67%) malignancies were <20 mm, in EU-TIRADS 4, 7/12 (58%) were <15 mm. In EU-TIRADS 5, 72/214 (34%) were <10 mm; in total, 81/229 (36%) malignant lesions would have been missed. The cutoff between EU-TIRADS 3/4 had sensitivity of 100%, specificity of 25.1%. Using cutoff for EU-TIRADS 5, 93.4%, 54.6%, respectively. Conclusion: The application of EU-TIRADS guidelines allowed us to achieve moderate specificity. The vast majority of malignancies in EU-TIRADS 3, 4, and 5 would not have been recommended for biopsy because having a smaller size than that proposed classification. Full article
(This article belongs to the Special Issue Imaging and Imaging-Based Management of Thyroid Nodules)
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Review

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Open AccessReview
Imaging and Imaging-Based Management of Pediatric Thyroid Nodules
J. Clin. Med. 2020, 9(2), 384; https://doi.org/10.3390/jcm9020384 - 01 Feb 2020
Abstract
Thyroid nodules are less frequent in children than adults. Childhood thyroid nodules carry specific features, including a higher risk of malignancy than nodules in adults, rendering them unique in terms of management. Subsequently, they should be considered a distinct clinical entity with specific [...] Read more.
Thyroid nodules are less frequent in children than adults. Childhood thyroid nodules carry specific features, including a higher risk of malignancy than nodules in adults, rendering them unique in terms of management. Subsequently, they should be considered a distinct clinical entity with specific imaging recommendations. Initial evaluation requires a thorough workup, including clinical examination, and a detailed personal and familial history to determine the presence of possible risk factors. Laboratory and radiologic evaluation play an integral part in the diagnostic algorithm, with ultrasonography (US) being the first diagnostic test in all patients. US elastography has been recently introduced as an incremental method, reducing the subjectivity of the clinical diagnosis of nodule firmness associated with increased malignancy risk. However, fine-needle aspiration biopsy (FNAB) remains the mainstay in the diagnostic work-up of thyroid nodules and is documented to be best method for differentiating benign from malignant thyroid nodules. In addition, thyroid scintigraphy provides functional imaging information, which has a role both in the diagnostic management of thyroid nodules and during follow up in malignancies. Finally, despite providing additional information in certain clinical scenarios, 18F-fludeoxyglucose Positron Emission Tomography (18F-FDG-PET), computed tomography (CT), and magnetic resonance imaging (MRI) imaging are not routinely recommended for the evaluation of patients with newly detected thyroid nodules or in all cases of thyroid cancer. The objective of this review is to summarize the concepts in imaging and imaging-based management of nodular thyroid disease in the pediatric population, acknowledging the unique features that this patient group carries and the specific approach it requires. Full article
(This article belongs to the Special Issue Imaging and Imaging-Based Management of Thyroid Nodules)
Open AccessReview
Correlations between Molecular Landscape and Sonographic Image of Different Variants of Papillary Thyroid Carcinoma
J. Clin. Med. 2019, 8(11), 1916; https://doi.org/10.3390/jcm8111916 - 08 Nov 2019
Cited by 4
Abstract
Papillary thyroid carcinoma (PTC), the most common thyroid cancer, is predominantly driven by mutations in BRAF (primarily p. V600E) and RAS oncogenes. Ultrasound (US) examination provides significant diagnostic data in the management of thyroid nodules, as many sonographic features of thyroid lesions [...] Read more.
Papillary thyroid carcinoma (PTC), the most common thyroid cancer, is predominantly driven by mutations in BRAF (primarily p. V600E) and RAS oncogenes. Ultrasound (US) examination provides significant diagnostic data in the management of thyroid nodules, as many sonographic features of thyroid lesions are correlated with the potential risk of thyroid carcinoma. The aim of the study was to analyze the current literature in regard to the potential associations between genetic landscape and sonographic features of PTC. Based on the current literature, sonographic features of PTCs correlate with their molecular drivers, particularly between tumors harboring BRAFV600E versus activating RAS mutations, although many of these findings appear to be dependent on the tumor variant. Suspicious US findings, such as hypoechogenicity, spiculated/microlobulated margins, non-parallel orientation/taller-than-wide shape, and the presence of microcalcifications, are typical for PTC positive for BRAFV600E mutations. On the contrary, tumors with RAS mutations are most frequently hypo- or isoechoic and ovoid-to-round in shape, with smooth margins and without calcifications. There are also some US features typical for PTCs harboring other mutations, including BRAFK601E, RET/PTC rearrangements, PAX8-PPARγ, CTNNB1, and APC. However, further research is necessary, as some rare PTC variants still cannot be reliably analyzed due to the scarce published data. Full article
(This article belongs to the Special Issue Imaging and Imaging-Based Management of Thyroid Nodules)
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Open AccessReview
Performance of 18F-FDG PET/CT in Selecting Thyroid Nodules with Indeterminate Fine-Needle Aspiration Cytology for Surgery. A Systematic Review and a Meta-Analysis
J. Clin. Med. 2019, 8(9), 1333; https://doi.org/10.3390/jcm8091333 - 28 Aug 2019
Cited by 4
Abstract
Thyroid nodules with indeterminate fine-needle aspiration cytology (FNA) represent a major challenge in clinical practice. We conducted a systematic review and meta-analysis evaluating the ability of hybrid imaging using fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to appropriately select these nodules [...] Read more.
Thyroid nodules with indeterminate fine-needle aspiration cytology (FNA) represent a major challenge in clinical practice. We conducted a systematic review and meta-analysis evaluating the ability of hybrid imaging using fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to appropriately select these nodules for surgery. PubMed, CENTRAL, Scopus, and Web of Science were searched until July 2019. Original articles reporting data on the performance of 18F-FDG PET/CT in thyroid nodules with indeterminate FNA were included. Summary operating points including 95% confidence interval values (95% CI) were estimated using a random-effects model. Out of 786 retrieved papers, eight studies evaluating 104 malignant and 327 benign thyroid nodules were included. The pooled positive and negative likelihood ratios (LR+ and LR-) and diagnostic odds ratio (DOR) of 18F-FDG PET/CT were 1.7 (95% CI: 1.4–2.0), 0.4 (95% CI: 0.2–0.7), and 3.5 (95% CI: 1.7–7.1), respectively. No heterogeneity was found for LR+ and DOR. In patients with thyroid nodules with indeterminate FNA, 18F-FDG PET/CT has a moderate ability to correctly discriminate malignant from benign lesions and could represent a reliable option to reduce unnecessary diagnostic surgeries. However, further studies using standardized criteria for interpretation are needed to confirm the reproducibility of these findings. Full article
(This article belongs to the Special Issue Imaging and Imaging-Based Management of Thyroid Nodules)
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