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Imaging and Imaging-Based Management of Thyroid Nodules

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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) | Viewed by 37352

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Prof. Dr. Luca Giovanella

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1. Clinic for Nuclear Medicine and Molecular Imaging, Imaging Institute of Southern Switzerland, Ente Ospedaliero Cantonale, 6500 Bellinzona, Switzerland
2. Clinic for Nuclear Medicine and Intedisciplinary Thyroid Centre, University Hospital of Zurich, 8091 Zurich, Switzerland
Interests: nuclear medicine; molecular imaging; theranostics; thyroid diseases; endocrine tumors; radiomics; predictive imaging; molecular biomarkers; integrated diagnostics
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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

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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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9 pages, 805 KiB

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

by Simone Schiaffino, Francesca Serpi, Duccio Rossi, Valerio Ferrara, Ciriaco Buonomenna, Marco Alì, Lorenzo Monfardini, Luca Maria Sconfienza and Giovanni Mauri

J. Clin. Med. 2020, 9(5), 1504; https://doi.org/10.3390/jcm9051504 - 16 May 2020

Cited by 17 | Viewed by 2392

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, 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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11 pages, 3813 KiB

Open AccessArticle

Intraoperative Autofluorescence and Indocyanine Green Angiography for the Detection and Preservation of Parathyroid Glands

by Marco Stefano Demarchi, Wolfram Karenovics, Benoît Bédat and Frédéric Triponez

J. Clin. Med. 2020, 9(3), 830; https://doi.org/10.3390/jcm9030830 - 18 Mar 2020

Cited by 46 | Viewed by 3915

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 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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18 pages, 2830 KiB

Open AccessArticle

Proteomic Analysis of Iodinated Contrast Agent-Induced Perturbation of Thyroid Iodide Uptake

by Maha Hichri, Georges Vassaux, Jean-Marie Guigonis, Thierry Juhel, Fanny Graslin, Julien Guglielmi, Thierry Pourcher and Béatrice Cambien

J. Clin. Med. 2020, 9(2), 329; https://doi.org/10.3390/jcm9020329 - 23 Jan 2020

Cited by 3 | Viewed by 3559

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 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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8 pages, 363 KiB

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)

by Simone Schenke, Rigobert Klett, Philipp Seifert, Michael C. Kreissl, Rainer Görges and Michael Zimny

J. Clin. Med. 2020, 9(1), 236; https://doi.org/10.3390/jcm9010236 - 16 Jan 2020

Cited by 29 | Viewed by 3984

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 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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13 pages, 264 KiB

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

by María Molina-Vega, Carlos Antonio Rodríguez-Pérez, Ana Isabel Álvarez-Mancha, Gloria Baena-Nieto, María Riestra, Victoria Alcázar, Ana Reyes Romero-Lluch, Juan C. Galofré and José C. Fernández-García

J. Clin. Med. 2019, 8(12), 2172; https://doi.org/10.3390/jcm8122172 - 9 Dec 2019

Cited by 4 | Viewed by 2938

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 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)

24 pages, 6554 KiB

Open AccessArticle

Artificial Intelligence-Based Thyroid Nodule Classification Using Information from Spatial and Frequency Domains

by Dat Tien Nguyen, Tuyen Danh Pham, Ganbayar Batchuluun, Hyo Sik Yoon and Kang Ryoung Park

J. Clin. Med. 2019, 8(11), 1976; https://doi.org/10.3390/jcm8111976 - 14 Nov 2019

Cited by 65 | Viewed by 6326

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 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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16 pages, 2282 KiB

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

by Katarzyna Dobruch-Sobczak, Zbigniew Adamczewski, Ewelina Szczepanek-Parulska, Bartosz Migda, Kosma Woliński, Agnieszka Krauze, Piotr Prostko, Marek Ruchała, Andrzej Lewiński, Wiesław Jakubowski and Marek Dedecjus

J. Clin. Med. 2019, 8(11), 1781; https://doi.org/10.3390/jcm8111781 - 25 Oct 2019

Cited by 18 | Viewed by 3130

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 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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16 pages, 281 KiB

Open AccessReview

Imaging and Imaging-Based Management of Pediatric Thyroid Nodules

by Ioannis Iakovou, Evanthia Giannoula and Christos Sachpekidis

J. Clin. Med. 2020, 9(2), 384; https://doi.org/10.3390/jcm9020384 - 1 Feb 2020

Cited by 15 | Viewed by 2922

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 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)

15 pages, 2831 KiB

Open AccessReview

Correlations between Molecular Landscape and Sonographic Image of Different Variants of Papillary Thyroid Carcinoma

by Andrzej Lewiński, Zbigniew Adamczewski, Arkadiusz Zygmunt, Leszek Markuszewski, Małgorzata Karbownik-Lewińska and Magdalena Stasiak

J. Clin. Med. 2019, 8(11), 1916; https://doi.org/10.3390/jcm8111916 - 8 Nov 2019

Cited by 16 | Viewed by 3840

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 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 BRAF^V600E 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 BRAF^V600E 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 BRAF^K601E, 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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12 pages, 1276 KiB

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

by Marco Castellana, Pierpaolo Trimboli, Arnoldo Piccardo, Luca Giovanella and Giorgio Treglia

J. Clin. Med. 2019, 8(9), 1333; https://doi.org/10.3390/jcm8091333 - 28 Aug 2019

Cited by 25 | Viewed by 3627

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 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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