Thyroglobulin measurement is the most powerful outcome predictor in differentiated thyroid cancer: a decision tree analysis in a European multicenter series.

OBJECTIVES: An accurate prognostic assessment is pivotal to adequately inform and individualize follow-up and management of patients with differentiated thyroid cancer (DTC). We aimed to develop a predictive model for recurrent disease in DTC patients treated by surgery and 131I by adopting a decision tree model. METHODS: Age, sex, histology, T stage, N stage, risk classes, remnant estimation, thyroid-stimulating hormone (TSH), thyroglobulin (Tg), administered 131I activities and post-therapy whole body scintigraphy (PT-WBS) were identified as potential predictors and put into regression algorithm (conditional inference tree, c-tree) to develop a risk stratification model for predicting persistent/recurrent disease over time. RESULTS: The PT-WBS pattern identified a partition of the population into two subgroups (PT-WBS positive or negative for distant metastases). Patients with distant metastases exhibited lower disease-free survival (either structural, DFS-SD, and biochemical, DFS-BD, disease) compared to those without metastases. Meanwhile, the latter were further stratified into three risk subgroups based on their Tg values. Notably, Tg values >63.1 ng/mL predicted a shorter survival time, with increased DFS-SD for Tg values <63.1 and <8.9 ng/mL, respectively. A comparable model was generated for biochemical disease (BD), albeit different DFS were predicted by slightly different Tg cutoff values (41.2 and 8.8 ng/mL) compared to DFS-SD. CONCLUSIONS: We developed a simple, accurate and reproducible decision tree model able to provide reliable information on the probability of structurally and/or biochemically persistent/relapsed DTC after a TTA. In turn, the provided information is highly relevant to refine the initial risk stratification, identify patients at higher risk of reduced structural and biochemical DFS, and modulate additional therapies and the relative follow-up.

Thyroid Imaging Reporting and Data Systems: Applicability of the "Taller than Wide" Criterium in Primary/Secondary Care Units and the Role of Thyroid Scintigraphy.

BACKGROUND: To examine the applicability of the "taller than wide" (ttw) criterium for risk assessment of thyroid nodules (TNs) in primary/secondary care units and the role of thyroid scintigraphy therein. METHODS: German bicenter study performed in a setting of primary/secondary care. Patient recruitment and analysis in center A was conducted in a prospective manner. In center B, patient data were retrieved from a database that was originally generated by prospective data collection. TNs were assessed by ultrasound and thyroid scans, mostly fine needle biopsy and occasionally surgery and others. In center A, only patients who presented for the first time were included. The inclusion criterion was any TN ≥ 10 mm that had at least the following two sonographic risk features: solidity and a ttw shape. In center B, consecutive patients who had at least ttw and hypofunctioning nodules ≥ 10 mm were retrieved from the above-mentioned database. The risk of malignancy was determined according to a mixed reference standard and compared with literature data. RESULTS: In center A, 223 patients with 259 TNs were included into the study. For further analysis, 200 nodules with a reference standard were available. The overall malignancy rate was 2.5% (upper limit of the 95% CI: 5.1%). After the exclusion of scintigraphically hyperfunctioning nodules, the malignancy rate increased slightly to 2.8% (upper limit of the 95% CI: 5.7%). Malignant nodules exhibited sonographic risk features additional to solidity and ttw shape more often than benign ones. In addition to the exclusion of hyperfunctioning nodules, when considering only nodules without additional US risk features, i.e., exclusively solid and ttw-nodules, the malignancy rate decreased to 0.9% (upper limit 95% CI: 3.7%). In center B, from 58 patients, 58 ttw and hypofunctioning TNs on thyroid scans with a reference standard were available. Malignant nodules from center B were always solid and hypoechoic. The overall malignancy rate of hypofunctioning and ttw nodules was 21%, with the lower limit of the 95% CI (one-sided) being 12%. CONCLUSIONS: In primary/secondary care units, the lowest TIRADS categories for indicating FNB, e.g., applying one out of five sonographic risk features, may not be appropriate owing to the much lower a priori malignancy risk in TNs compared to tertiary/quaternary care units. Even the combination of two sonographic risk features, "solidity" and "ttw", may only be appropriate in a limited fashion. In contrast, the preselection of TNs according to hypofunctioning findings on thyroid scans clearly warranted FNB, even when applying only one sonographic risk criterion ("ttw"). For this reason, thyroid scans in TNs may not only be indicated to rule out hyperfunctioning nodules from FNB but also to rule in hypofunctioning ones.

Correct and Incorrect Recommendations for or against Fine Needle Biopsies of Hypofunctioning Thyroid Nodules: Performance of Different Ultrasound-based Risk Stratification Systems.

PURPOSE: To evaluate the recommendations for or against fine needle biopsy (FNB) of hypofunctioning thyroid nodules (TNs) using of five different Ultrasound (US) -based risk stratification systems (RSSs). METHODS: German multicenter study with 563 TNs (≥ 10 mm) in 534 patients who underwent thyroid US and surgery. All TNs were evaluated with ACR TI-RADS, EU-TIRADS, ATA, K-TIRADS 2016 and modified K-TIRADS 2021. A correct recommendation was defined as: malignant TN with recommendation for FNB (appropriate) or benign TN without recommendation for FNB (avoided). An incorrect recommendation was defined as: malignant TN without recommendation for FNB (missed) or benign TN with recommendation for FNB (unnecessary). RESULTS: ACR TI-RADS demonstrated the highest rate of correct (42.3 %) and lowest rate of incorrect recommendations (57.7 %). The other RRSs showed similar results for correct (26.5 %-35.7 %) and incorrect (64.3 %-73.5 %) recommendations. ACR TI-RADS demonstrated the lowest rate of unnecessary (73.4 %) and the highest rate of appropriate (26.6 %) FNB recommendation. For other RSSs, the rates of unnecessary and appropriate FNB were between 75.2 %-77.1 % and 22.9 %-24.8 %. The lowest rate of missed FNB (14.7 %) and the highest rate of avoided FNB (85.3 %) was found for ACR TI-RADS. For the other RSSs, the rates of missed and avoided FNB were between 17.8 %-26.9 % and 73.1 %-82.2 %. When the size cutoff was disregarded, an increase of correct recommendations and a decrease of incorrect recommendations was observed for all RSSs. CONCLUSION: The RSSs vary in their ability to correctly recommend for or against FNB. An understanding of the impact of nodule size cutoffs seems necessary for the future of TIRADS.

[Elastography in thyroid nodules]. / Elastografie von Schilddrüsenknoten.

BACKGROUND: Elastography is an imaging method to examine the elasticity of tissue. In the meantime, various elastography methods have been developed, which are subdivided according to the type of stimulus applied. In principle, a distinction should be made between strain elastography (SE) and shear wave elastography (SWE). Both methods provide another means of assessing thyroid disease in addition to conventional B-mode sonography. OBJECTIVE: The aim is to provide an overview of elastography techniques including physical basics and their importance in the clarification algorithm of thyroid nodules. MATERIALS AND METHODS: International guidelines and recent publications on elastography were selectively assessed. RESULTS: Elastography provides additional information compared to conventional B-mode sonography. The change in shear stiffness is the essential physical mechanism for tissue contrast in all elastograms. In addition to the qualitative assessment of elasticity in SE, quantification is possible with SWE. In the international literature, elastography was analyzed as a single method or in comparison or combination with conventional B-mode sonography and especially with standardization using a risk stratification system (RSS, TIRADS). The results are quite controversial. In nodules with unclear findings on fine-needle biopsy (Bethesda III/IV), the combination of morphologic criteria and elastography improved diagnostic accuracy. In particular, the high negative predictive value of soft nodules represents a relevant added value. This strength of the method can play an important role in the clarification of nodules with intermediate malignancy risk or of unclear FNB results. Elastography has previously only been incorporated into French-TIRADS. Although the procedure is mentioned in the EU-TIRADS as a complementary method, integration has not been described. Limitations of the method are idealized basic assumptions, dependence of manufacturer and examiner, and artifacts. CONCLUSION: Elastography can be a useful adjunct to standard diagnostic procedures in the evaluation of thyroid nodules, especially in nodules with intermediate risk of malignancy and unclear results on fine needle aspiration.

Thyroid Nodule Detection and Region Estimation in Ultrasound Images: A Comparison between Physicians and an Automated Decision Support System Approach.

BACKGROUND: Thyroid nodules are very common. In most cases, they are benign, but they can be malignant in a low percentage of cases. The accurate assessment of these nodules is critical to choosing the next diagnostic steps and potential treatment. Ultrasound (US) imaging, the primary modality for assessing these nodules, can lack objectivity due to varying expertise among physicians. This leads to observer variability, potentially affecting patient outcomes. PURPOSE: This study aims to assess the potential of a Decision Support System (DSS) in reducing these variabilities for thyroid nodule detection and region estimation using US images, particularly in lesser experienced physicians. METHODS: Three physicians with varying levels of experience evaluated thyroid nodules on US images, focusing on nodule detection and estimating cystic and solid regions. The outcomes were compared to those obtained from a DSS for comparison. Metrics such as classification match percentage and variance percentage were used to quantify differences. RESULTS: Notable disparities exist between physician evaluations and the DSS assessments: the overall classification match percentage was just 19.2%. Individually, Physicians 1, 2, and 3 had match percentages of 57.6%, 42.3%, and 46.1% with the DSS, respectively. Variances in assessments highlight the subjectivity and observer variability based on physician experience levels. CONCLUSIONS: The evident variability among physician evaluations underscores the need for supplementary decision-making tools. Given its consistency, the CAD offers potential as a reliable "second opinion" tool, minimizing human-induced variabilities in the critical diagnostic process of thyroid nodules using US images. Future integration of such systems could bolster diagnostic precision and improve patient outcomes.

Postoperative thyroglobulin as a yard-stick for radioiodine therapy: decision tree analysis in a European multicenter series of 1317 patients with differentiated thyroid cancer.

PURPOSE: An accurate postoperative assessment is pivotal to inform postoperative 131I treatment in patients with differentiated thyroid cancer (DTC). We developed a predictive model for post-treatment whole-body scintigraphy (PT-WBS) results (as a proxy for persistent disease) by adopting a decision tree model. METHODS: Age, sex, histology, T stage, N stage, risk classes, remnant estimation, TSH, and Tg were identified as potential predictors and were put into regression algorithm (conditional inference tree, ctree) to develop a risk stratification model for predicting the presence of metastases in PT-WBS. RESULTS: The lymph node (N) stage identified a partition of the population into two subgroups (N-positive vs N-negative). Among N-positive patients, a Tg value > 23.3 ng/mL conferred a 83% probability to have metastatic disease compared to those with lower Tg values. Additionally, N-negative patients were further substratified in three subgroups with different risk rates according to their Tg values. The model remained stable and reproducible in the iterative process of cross validation. CONCLUSIONS: We developed a simple and robust decision tree model able to provide reliable informations on the probability of persistent/metastatic DTC after surgery. These information may guide post-surgery 131I administration and select patients requiring curative rather than adjuvant 131I therapy schedules.

Distribution of Functional Status of Thyroid Nodules and Malignancy Rates of Hyperfunctioning and Hypofunctioning Thyroid Nodules in Germany.

AIM: Thyroid scintigraphy enables the depiction of the functional status of thyroid nodules (TNs) with both, 99mTc-pertechnetate and 123Iodine. The functional status is relevant for diagnostic procedures for the differentiation of benign and malignant TNs. The aim of this study was to examine the current frequencies of hyper-, hypo- and isofunctioning TNs in Germany and to estimate the risk of malignancy with regard to functional status. METHODS: In 11 study centers, a minimum of 100 nodules per center were consecutively enrolled between July 2019 and April 2020. Inclusion criteria were: newly diagnosed nodule, nodule' size of 10 mm or more, thyroid scintigraphy. Exclusion criteria were: completely cystic TNs, patients with prior radioiodine therapy or thyroid surgery. The risk of malignancy was estimated for hyper- and hypofunctioning TNs. RESULTS: Overall, 849 patients (72 % women) with 1262 TNs were included. Patients' age ranged from 18 to 90 years. Most TNs were hypofunctioning (n=535, 42%) followed by isofunctioning TNs (n=488, 39%) and hyperfunctioning TNs (n=239, 19%). When only TNs with a maximum size of 2 cm or more were considered the rate of hyperfunctioning and hypofunctioning TNs increased (to 27% and 49%) while isofunctioning TNs decreased. Only one of all hyperfunctioning TNs was malignant. In hypofunctioning nodules, the malignancy rate was estimated at 10%. CONCLUSION: In Germany, the proportion of hyperfunctioning TNs is approximately 20% and increases in larger TNs to up to 27%. Due to the low risk of malignancy in hyperfunctioning TNs, no further procedures to rule out malignancy are necessary. The risk of malignancy of hypofunctioning TNs is significantly higher. Thus, a thyroid scintigraphy is a useful diagnostic tool in Germany.

Diagnostic Performance of 99mTc-Methoxy-Isobuty-Isonitrile (MIBI) for Risk Stratification of Hypofunctioning Thyroid Nodules: A European Multicenter Study.

99mTc-MIBI (MIBI) imaging is able to exclude malignancy of hypofunctioning thyroid nodules (TNs) with high probability but false positive results are frequent due to low specificity. Therefore, pre-test selection of appropriate TNs is crucial. For image evaluation visual and semiquantitative methods (Washout index, WOInd) are used. Aim of this study was to evaluate the diagnostic performance of MIBI imaging in hypofunctioning TNs with indeterminate fine-needle aspiration cytology results in a multicentric European setting. Patients with hypofunctioning TNs, EU-TIRADS 4 or 5, Bethesda III/IV and MIBI imaging were included. For visual evaluation the intensity of MIBI uptake in the TN was compared to normal thyroid tissue. 358 patients with 365 TNs (n = 68 malignant) were included. Planar imaging (SPECT) showed a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 96% (94%), 21% (22%), 22% (15%), 96% (96%), and 35% (32%). The WOInd (38.9% of all cases, optimal cutoff: -19%) showed a sens 100% (spec 89%, PPV 82%, NPV 100%, ACC 93%). For hypofunctioning TNs at intermediate or high risk with indeterminate cytology, a MIBI negative result on visual evaluation is an effective tool to rule-out thyroid malignancy. The semi-quantitative method could considerably improve overall diagnostic performance of MIBI imaging.

Introducing a Pole Concept for Nodule Growth in the Thyroid Gland: Taller-than-Wide Shape, Frequency, Location and Risk of Malignancy of Thyroid Nodules in an Area with Iodine Deficiency.

Purpose: (i) To examine the criterion taller-than-wide (TTW) for the sonographic assessment of thyroid nodules in areas of iodine deficiency in terms of frequency, anatomical distribution within the thyroid gland and risk of malignancy. (ii) To develop a model for nodule growth in the thyroid gland. Methods: German multicenter study consisting of two parts. In the prospective part, thyroid nodules were sonographically measured in all three dimensions, location within the thyroid gland and contact to a protrusion-like formation (horn) in the dorsal position of thyroid gland was noted. In addition, further sonographic features such as the composition, echogenity, margins and calcifications were investigated. All nodules from the prospective part were assessed for malignancy as part of clinical routine at the decision of the treating physician adhering to institutionally based algorithms. In the retrospective part, only nodules with fine needle aspiration and/or histology were included. The risk of malignancy in TTW nodules was determined by correlating them with cyotological and histological results. Results: Prospective part: out of 441 consecutively evaluated thyroid nodules, 6 were found to be malignant (1.4%, 95% CI 0.6-2.7%). Among the 74 TTW nodules (17%), 1 was malignant (1%, 95% CI 0-4%). TTW nodules were more often located in the dorsal half of the thyroid than non-TTW nodules (factor 2.3, p = 0.01, 95% CI 2.1-2.5) and more often located in close proximity to a horn than non-TTW nodules (factor 3.0, p = 0.01, 95% CI 2.4-3.8). Retrospective part: out of 1315 histologically and/or cytologically confirmed thyroid nodules, 163 TTW nodules were retrieved and retrospectively analyzed. A TTW nodule was 1.7 times more often benign when it was dorsal (95% CI 1.1-2.5) and 2.5 times more often benign when it was associated with a horn (95% CI 1.2-5.3). The overall probability of malignancy for TTW nodules was 38% (95% CI 30-46%) in this highly preselected patient group. Conclusion: TTW nodules are common in iodine deficient areas. They are often located in the dorsal half of the thyroid gland and are frequently associated with a dorsal protrusion-like formation (horn) of the thyroid. Obviously, the shape of benign nodules follows distinct anatomical preconditions within the thyroid gland. The frequency of TTW nodules and their predominant benignity can be explained by a pole concept of goiter growth. The difference between the low malignancy risk of TTW nodules found on a prospective basis and the high risk found retrospectively may be the result of a positive preselection in the latter.

Shear Wave Elastography and Thyroid Imaging Reporting and Data System (TIRADS) for the Risk Stratification of Thyroid Nodules-Results of a Prospective Study.

PURPOSE: To compare the diagnostic performance of thyroid imaging reporting and data system (TIRADS) in combination with shear wave elastography (SWE) for the assessment of thyroid nodules. METHODS: A prospective study was conducted with the following inclusion criteria: preoperative B-mode ultrasound (US) including TIRADS classification (Kwak-TIRADS, EU-TIRADS), quantitative SWE and available histological results. RESULTS: Out of 43 patients, 61 thyroid nodules were detected; 10 nodules were found to be thyroid cancer (7 PTC, 1 FTC, 2 HüCC) and 51 were benign. According to Kwak-TIRADS the majority of benign nodules (47 out of 51, 92.2%) were classified in the low-risk- and intermediate-risk class, four nodules were classified as high-risk (7.8%). When using EU-TIRADS, the benign nodules were distributed almost equally across all risk classes, 21 (41.2%) nodules were classified in the low-risk class, 16 (31.4%) in the intermediate-risk class and 14 (27.4%) in the high-risk class. In contrast, most of the malignant nodules (eight out of ten) were classified as high-risk on EU-TIRADS. One carcinoma was classified as low-risk and one as intermediate-risk nodule. For SWE, ROC analysis showed an optimal cutoff of 18.5 kPa to distinguish malignant and benign nodules (sensitivity 80.0%, specificity 49.0%, PPV 23.5% and NPV 92.6%). The addition of elastography resulted in an increase of accuracy from 65.6% to 82.0% when using Kwak-TIRADS and from 49.2% to 72.1% when using EU-TIRADS. CONCLUSION: Our data demonstrate that the combination of TIRADS and SWE seems to be superior for the risk stratification of thyroid nodules than each method by itself. However, verification of these results in a larger patient population is mandatory.

Diagnostic Performance of Kwak, EU, ACR, and Korean TIRADS as Well as ATA Guidelines for the Ultrasound Risk Stratification of Non-Autonomously Functioning Thyroid Nodules in a Region with Long History of Iodine Deficiency: A German Multicenter Trial.

Germany has a long history of insufficient iodine supply and thyroid nodules occur in over 30% of the adult population, the vast majority of which are benign. Non-invasive diagnostics remain challenging, and ultrasound-based risk stratification systems are essential for selecting lesions requiring further clarification. However, no recommendation can yet be made about which system performs the best for iodine deficiency areas. In a German multicenter approach, 1211 thyroid nodules from 849 consecutive patients with cytological or histopathological results were enrolled. Scintigraphically hyperfunctioning lesions were excluded. Ultrasound features were prospectively recorded, and the resulting classifications according to five risk stratification systems were retrospectively determined. Observations determined 1022 benign and 189 malignant lesions. The diagnostic accuracies were 0.79, 0.78, 0.70, 0.82, and 0.79 for Kwak Thyroid Imaging Reporting and Data System (Kwak-TIRADS), American College of Radiology (ACR) TI-RADS, European Thyroid Association (EU)-TIRADS, Korean-TIRADS, and American Thyroid Association (ATA) Guidelines, respectively. Receiver Operating Curves revealed Areas under the Curve of 0.803, 0.795, 0.800, 0.805, and 0.801, respectively. According to the ATA Guidelines, 135 thyroid nodules (11.1%) could not be classified. Kwak-TIRADS, ACR TI-RADS, and Korean-TIRADS outperformed EU-TIRADS and ATA Guidelines and therefore can be primarily recommended for non-autonomously functioning lesions in areas with a history of iodine deficiency.

Quantitative imaging of bone remodeling in patients with a unicompartmental joint unloading knee implant (ATLAS Knee System)-effect of metal artifacts on a SPECT-CT-based quantification.

BACKGROUND: SPECT-CT using radiolabeled phosphonates is considered a standard for assessing bone metabolism (e.g., in patients with osteoarthritis of knee joints). However, SPECT can be influenced by metal artifacts in CT caused by endoprostheses affecting attenuation correction. The current study examined the effects of metal artifacts in CT of a specific endoprosthesis design on quantitative hybrid SPECT-CT imaging. The implant was positioned inside a phantom homogenously filled with activity (955 MBq 99mTc). CT imaging was performed for different X-ray tube currents (I = 10, 40, 125 mA) and table pitches (p = 0.562 and 1.375). X-ray tube voltage (U = 120 kVp) and primary collimation (16 × 0.625 mm) were kept constant for all scans. The CT reconstruction was performed with five different reconstruction kernels (slice thickness, 1.25 mm and 3.75 mm, each 512 × 512 matrix). Effects from metal artifacts were analyzed for different CT scans and reconstruction protocols. ROI analysis of CT and SPECT data was performed for two slice positions/volumes representing the typical locations for target structures relative to the prosthesis (e.g., femur and tibia). A reference region (homogenous activity concentration without influence from metal artifacts) was analyzed for comparison. RESULTS: Significant effects caused by CT metal artifacts on attenuation-corrected SPECT were observed for the different slice positions, reconstructed slice thicknesses of CT data, and pitch and CT-reconstruction kernels used (all, p < 0.0001). Based on the optimization, a set of three protocols was identified minimizing the effect of CT metal artifacts on SPECT data. Regarding the reference region, the activity concentration in the anatomically correlated volume was underestimated by 8.9-10.1%. A slight inhomogeneity of the reconstructed activity concentration was detected inside the regions with a median up to 0.81% (p < 0.0001). Using an X-ray tube current of 40 mA showed the best result, balancing quantification and CT exposure. CONCLUSION: The results of this study demonstrate the need for the evaluation of SPECT-CT protocols in prosthesis imaging. Phantom experiments demonstrated the possibility for quantitative SPECT-CT of bone turnover in a specific prosthesis design. Meanwhile, a systematic bias caused by metal implants on quantitative SPECT data has to be considered.

Update on diagnosis and treatment of hyperthyroidism: ultrasonography and functional imaging.

Ultrasonography and radionuclide imaging using [99mTc]Pertechnetate or radioactive iodine isotopes are essential tools used during the diagnostic workup of hyperthyroidism with or without structural alterations of the thyroid. Color duplex sonography and ultrasound elastography may add important information to find the cause of the hormone excess. During the last few years, hybrid imaging using SPECT/-(CT) or PET-based methods, such as [124]Iodine-PET/CT or [124]Iodine-PET/ultrasound have been increasingly used, playing a role in the context of localizing ectopic thyroid tissue or in multinodular goiter. Recently, promising data has been published on the use of [99mTc]MIBI imaging in amiodarone induced hyperthyroidism.

Characteristics of different histological subtypes of thyroid nodules classified with 99mTc-methoxy-isobutyl-isonitrile imaging and Thyroid Imaging Reporting And Data System.

INTRODUCTION: Thyroid Imaging Reporting And Data System (TIRADS) is helpful for risk stratification of thyroid nodules. However, there is a lack of data for TIRADS classification of different histological subtypes [classical papillary thyroid cancer (PTC), follicular variant of papillary thyroid cancer (FVPTC), and follicular thyroid cancer (FTC)], and benign thyroid nodules (follicular adenoma, oncocytic adenoma, and multinodular goiter (MNG)]. Methoxy-isobutyl-isonitrile (MIBI) imaging has a high negative predictive value for the exclusion of thyroid malignancy in hypofunctioning thyroid nodules. The aim of this analysis was to compare malignant and benign subtypes of thyroid nodule using three TIRADS and MIBI imaging. METHODS: Retrospective analysis of MIBI imaging studies. Hypofunctioning thyroid nodules were classified with Kwak-TIRADS, EU-TIRADS, and K-TIRADS. MIBI imaging was visually categorized. RESULTS: We included 242 thyroid nodules (32 malignant, 19 PTC, 7 FVPTC, and 6 FTC). When using Kwak-TIRADS 4C and 5 as a marker for high-risk nodules, we found 85.5% of the follicular adenoma, 80.8% of the MNG, 100% of the oncocytic adenoma, 100% of the FTC, 57.1% of the FVPTC, and 42.2% of the PTC to be below this cutoff. All PTC and FVPTC were MIBI-positive, 83% of the FTC, 78% of the follicular adenoma, 75% of the oncocytic adenoma, and 60% of the MNG were MIBI-positive. CONCLUSION: TIRADS is useful to detect PTC, but FVPTC and FTC may be missed. MIBI imaging seems to be more suitable to detect FVPTC and FTC. However, neither TIRADS nor MIBI imaging are able to differentiate between follicular adenoma and FTC or FVPTC.

Ultrasound Assessment of Autonomous Thyroid Nodules before and after Radioiodine Therapy Using Thyroid Imaging Reporting and Data System (TIRADS).

The Thyroid Imaging and Reporting System (TIRADS) allows a sonographic assessment of the malignancy risk of thyroid nodules (TNs). To date, there is a lack of systematic data about the change in ultrasound (US) features after therapeutic interventions. The aim of this study was to characterize the changes in autonomously functioning thyroid nodules (AFTNs) after radioiodine therapy (RIT) by using TIRADS. We retrospectively assessed data from 68 patients with AFTNs treated with RIT between 2016 and 2018 who had available first and second follow-up US imaging. Before RIT, 69.1% of the AFTNs were classified as low-risk TNs when applying Kwak TIRADS (EU-TIRADS 52.9%), 22.1% were intermediate-risk TNs (EU-TIRADS 19.1%), and 8.8% were high-risk TNs (EU-TIRADS 27.9%). Twelve months after RIT, 22.1% of the AFTNs showed features of high-risk TNs according to Kwak TIRADS (EU-TIRADS 45.6%). The proportion of intermediate TNs also increased to 36.8% (EU-TIRADS 29.4%), and 41.2% were low-risk TNs (EU-TIRADS 25%). A significant percentage of AFTNs presented with features suspicious for malignancy according to TIRADS before RIT, and this number increased significantly after therapy. Therefore, before thyroid US, thorough anamnesis regarding prior radioiodine treatment is necessary to prevent unneeded diagnostic procedures.

Thyroid Nodule Classification for Physician Decision Support Using Machine Learning-Evaluated Geometric and Morphological Features.

The classification of thyroid nodules using ultrasound (US) imaging is done using the Thyroid Imaging Reporting and Data System (TIRADS) guidelines that classify nodules based on visual and textural characteristics. These are composition, shape, size, echogenicity, calcifications, margins, and vascularity. This work aims to reduce subjectivity in the current diagnostic process by using geometric and morphological (G-M) features that represent the visual characteristics of thyroid nodules to provide physicians with decision support. A total of 27 G-M features were extracted from images obtained from an open-access US thyroid nodule image database. 11 significant features in accordance with TIRADS were selected from this global feature set. Each feature was labeled (0 = benign and 1 = malignant) and the performance of the selected features was evaluated using machine learning (ML). G-M features together with ML resulted in the classification of thyroid nodules with a high accuracy, sensitivity and specificity. The results obtained here were compared against state-of the-art methods and perform significantly well in comparison. Furthermore, this method can act as a computer aided diagnostic (CAD) system for physicians by providing them with a validation of the TIRADS visual characteristics used for the classification of thyroid nodules in US images.

Analysis of Bone Scans in Various Tumor Entities Using a Deep-Learning-Based Artificial Neural Network Algorithm-Evaluation of Diagnostic Performance.

The bone scan index (BSI), initially introduced for metastatic prostate cancer, quantifies the osseous tumor load from planar bone scans. Following the basic idea of radiomics, this method incorporates specific deep-learning techniques (artificial neural network) in its development to provide automatic calculation, feature extraction, and diagnostic support. As its performance in tumor entities, not including prostate cancer, remains unclear, our aim was to obtain more data about this aspect. The results of BSI evaluation of bone scans from 951 consecutive patients with different tumors were retrospectively compared to clinical reports (bone metastases, yes/no). Statistical analysis included entity-specific receiver operating characteristics to determine optimized BSI cut-off values. In addition to prostate cancer (cut-off = 0.27%, sensitivity (SN) = 87%, specificity (SP) = 99%), the algorithm used provided comparable results for breast cancer (cut-off 0.18%, SN = 83%, SP = 87%) and colorectal cancer (cut-off = 0.10%, SN = 100%, SP = 90%). Worse performance was observed for lung cancer (cut-off = 0.06%, SN = 63%, SP = 70%) and renal cell carcinoma (cut-off = 0.30%, SN = 75%, SP = 84%). The algorithm did not perform satisfactorily in melanoma (SN = 60%). For most entities, a high negative predictive value (NPV ≥ 87.5%, melanoma 80%) was determined, whereas positive predictive value (PPV) was clinically not applicable. Automatically determined BSI showed good sensitivity and specificity in prostate cancer and various other entities. Particularly, the high NPV encourages applying BSI as a tool for computer-aided diagnostic in various tumor entities.

Fusion iENA Scholar Study: Sensor-Navigated I-124-PET/US Fusion Imaging versus Conventional Diagnostics for Retrospective Functional Assessment of Thyroid Nodules by Medical Students.

In conventional thyroid diagnostics, the topographical correlation between thyroid nodules (TN) depicted on ultrasound (US) in axial or sagittal orientation and coronally displayed scintigraphy images can be challenging. Sensor-navigated I-124-PET/US fusion imaging has been introduced as a problem-solving tool for ambiguous cases. The purpose of this study was to investigate the results of multiple unexperienced medical students (MS) versus multiple nuclear medicine physicians (MD) regarding the overvalue of I-124-PET/US in comparison to conventional diagnostics (CD) for the functional assessment of TN. METHODS: Out of clinical routine, cases with ambiguous findings on CD were selected for I-124-PET/US fusion imaging. Sixty-eight digital patient case files (PCF) of 34 patients (CDonly and CD+PET/US PCF) comprising 66 TN were provided to be retrospectively evaluated by 70 MD and 70 MS, respectively. A total of 2174 ratings (32.9 per TN) were carried out: 555 ratings (8.4 per TN) for CDonly and 532 ratings (8.1 per TN) for CD+PET/US by each MD and MS. RESULTS: Functional assessment revealed 8.5%/11.7% (n.s.) (16.4%/25.8% (p = 0.0002)), 41.8%/28.5% (p < 0.0001) (23.9%/17.9% (p = 0.0193)), 36.0%/30.5% (n.s.) (57.3%/53.9% (n.s.)), and 13.7%/29.4% (p < 0.0001) (2.4%/2.4% (n.s.)) hyperfunctioning, indifferent, hypofunctioning, and not rateable TNs for CDonly (CD+PET/US) and MD/MS, respectively. The respective rating confidence was indicated as absolute certain, quite certain, equivocal, uncertain, and not rateable in 11.7/3.4% (p < 0.0001) (44.9%/38.9% (p = 0.0541), 51.9%/26.7% (p < 0.0001) (46.2%/41.5% (n.s.)), 21.6%/29.0% (p = 0.0051) (6.2%/14.8% (p < 0.0001)), 1.1%/11.5% (p < 0.0001) (0.2%/2.3% (p = 0.0032)), and 13.7%/29.4% (p < 0.0001) (2.4%/2.4% (n.s.)) by MD/MS, respectively. There was a significant difference in the diversity of the observers' functional assessment of TN (MD 0.84 vs. MS 1.02, p = 0.0006) and the respective confidence in functional assessment (MD 0.93 vs. MS 1.16, p < 0.0001) between MD and MS on CDonly, whereas CD+PET/US revealed weaker differences for both groups (MD 0.48 vs. MS 0.47, p = 0.57; and MD 0.66 vs. MS 0.83, p = 0.0437). With the additional application of I-124-PET/US, the rating diversity of both MD and MS markedly tends towards more consistency (p < 0.0001 in each case). CONCLUSION: The additional application of sensor-navigated I-124-PET/US fusion imaging significantly influenced the functional assessment of TN positively, especially for unexperienced observers.

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).

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.

Interobserver agreement and efficacy of consensus reading in Kwak-, EU-, and ACR-thyroid imaging recording and data systems and ATA guidelines for the ultrasound risk stratification of thyroid nodules.

PURPOSE: To investigate the interobserver agreement (IA) and the impact of consensus reading using four risk stratification systems for thyroid nodules (TN). METHODS: Four experienced specialists independently rated US images of 80 TN according to the Kwak-TIRADS, EU-TIRADS, ACR TI-RADS, and ATA Guidelines. The cases were randomly extracted from a prospectively acquired database (n > 1500 TN). The observers were blinded to clinical data. This study was divided into two sessions (S1 and S2) with 40 image sets each. After every session, a consensus reading was carried out (C1, C2). Subsequently, the effect of C1 was tested in S2 with 40 new cases followed by C2. Fleiss' kappa (κ) was calculated for S1 and S2 to estimate the IA and learning curves. The results of C1 and C2 were used as reference for diagnostic accuracy calculations. RESULTS: IA significantly increased (p < 0.01) after C1 with κ values of 0.375 (0.615), 0.411 (0.596), 0.321 (0.569), and 0.410 (0.583) for the Kwak-TIRADS, EU-TIRADS, ACR TI-RADS, and ATA Guidelines in S1 (S2), respectively. ROC analysis (C1 + C2) revealed similar areas under the curve (AUC) for the Kwak-TIRADS, EU-TIRADS, ACR TI-RADS, and ATA Guidelines (0.635, 0.675, 0.694, and 0.654, respectively, n.s.). AUC did not increase from C1 (0.677 ± 0.010) to C2 (0.632 ± 0.052, n.s.). ATA Guidelines were not applicable in five cases. CONCLUSIONS: IA and diagnostic accuracy were very similar for the four investigated risk stratification systems. Consensus reading sessions significantly improved the IA but did not affect the diagnostic accuracy.