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Article

Comparison between Two Different Scanners for the Evaluation of the Role of 18F-FDG PET/CT Semiquantitative Parameters and Radiomics Features in the Prediction of Final Diagnosis of Thyroid Incidentalomas

1
Nuclear Medicine, Università degli Studi di Brescia and ASST Spedali Civili Brescia, 25123 Brescia, Italy
2
Radiation Oncology Department, ASST Valcamonica Esine and Università degli Studi di Brescia, 25040 Brescia, Italy
3
Dipartimento di Scienze Cliniche e Sperimentali dell’Università degli Studi di Brescia, 25123 Brescia, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
J. Clin. Med. 2022, 11(3), 615; https://doi.org/10.3390/jcm11030615
Submission received: 27 December 2021 / Revised: 19 January 2022 / Accepted: 25 January 2022 / Published: 26 January 2022
(This article belongs to the Special Issue PET/CT Imaging in Oncology: Clinical Updates and Perspectives)

Abstract

:
The aim of this study was to compare two different tomographs for the evaluation of the role of semiquantitative PET/CT parameters and radiomics features (RF) in the prediction of thyroid incidentalomas (TIs) at 18F-FDG imaging. A total of 221 patients with the presence of TIs were retrospectively included. After volumetric segmentation of each TI, semiquantitative parameters and RF were extracted. All of the features were tested for significant differences between the two PET scanners. The performances of all of the features in predicting the nature of TIs were analyzed by testing three classes of final logistic regression predictive models, one for each tomograph and one with both scanners together. Some RF resulted significantly different between the two scanners. PET/CT semiquantitative parameters were not able to predict the final diagnosis of TIs while GLCM-related RF (in particular GLCM entropy_log2 e GLCM entropy_log10) together with some GLRLM-related and GLZLM-related features presented the best predictive performances. In particular, GLCM entropy_log2, GLCM entropy_log10, GLZLM SZHGE, GLRLM HGRE and GLRLM HGZE resulted the RF with best performances. Our study enabled the selection of some RF able to predict the final nature of TIs discovered at 18F-FDG PET/CT imaging. Classic semiquantitative and volumetric PET/CT parameters did not reveal these abilities. Furthermore, a good overlap in the extraction of RF between the two scanners was underlined.

1. Introduction

Differentiated thyroid cancer (DTC) represents about 1% of all malignant tumors; moreover, it is the most frequent form of endocrine carcinoma and is usually characterized by good prognosis [1,2,3,4]. In recent years, its incidence has been growing due to the increasing use of needle aspiration and thyroid ultrasound [5,6,7].
The role of nuclear medicine in the diagnostic and therapeutic work-up of DTC is pivotal. In fact, nowadays, exams performed with 131I are fundamental for the staging, the restaging, and the therapy of this carcinoma [4,8].
In recent years, we have been continuously experiencing an increase in the use of positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose (18F-FDG) for the evaluation of various pathologies, both neoplastic and inflammatory. In this context, even in the diagnostic work-up of DTC this hybrid imaging modality has a central role, in particular in the evaluation of patients with no evidence of 131I avid disease but a persistence of elevated thyroglobulin levels [4,9,10].
With the increasing use of 18F-FDG PET/CT in the clinical practice, we have also been experiencing an increase in the detection of thyroid incidentalomas (TI) [11,12,13]. TIs are defined as thyroid lesions detected at imaging studies performed for non-thyroid pathologies [14,15].
The precise evaluation of TIs is mandatory, given the non-negligible risk of presence of CTD in a high amount of these findings [16,17,18]. In this context, a lot of authors have tried to clarify the role of 18F-FDG PET/CT for the definition of the precise nature of TIs, in terms of malignancy or benignancy [4]. However, the role of some PET/CT semiquantitative parameters, such as standardized uptake value (SUV), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) has not yet been fully clarified and the results in literature are really heterogeneous [4].
Furthermore, in recent years we have been appreciating an increase in the extraction of specific quantitative features from PET images, called radiomics or texture analysis. In this setting, the use of radiomics for the correct evaluation of every type of incidentalomas is waking increasing interest [19,20]. The case of TIs is not an exception and some works about the use of texture analysis for their correct classification have been produced [21,22,23,24]. However, similarly to semiquantitative parameters, the use of radiomics in this setting has given non-clarifying and initial results.
The aim of this retrospective study is to evaluate the role of semiquantitative PET/CT parameters and radiomics features for the correct classification of TIs discovered at 18F-FDG PET/CT scans. Furthermore, the impact of different PET/CT tomographs on texture analysis and on its ability to predict the final outcome is a fundamental part of this work.

2. Materials and Methods

2.1. Patients Selection

We retrospectively analyzed the 18F-FDG PET/CT scans performed in our center between January 2012 and December 2020 in order to find presence of TIs. All of the patients performed PET/CT exams for staging or restaging purpose of various diseases, but no one had a previous history of DTC. Specifically, 82 patients suffered from lymphoma, 19 from carcinomas of the head and neck, 51 from lung cancer, 6 from fever of unknown origin, 12 from vasculitis, 38 from breast cancer, 3 from esophageal cancer, 2 from ovarian cancer, 5 from colorectal cancer and 2 from endocarditis, while 1 patient performed the examination in order to characterize a formation of the right adrenal gland.
Tis were defined as focal uptakes of 18F-FDG inside the thyroid gland with an uptake higher than the background uptakes. Given the fact that diffuse uptakes on thyroid gland are usually expression of benign conditions, they were excluded from the study [4]. Furthermore, other inclusion criteria were the presence of an ultrasound follow-up of at least 1 year for suspected benignant uptakes and the execution of a cytological evaluation and/or histological examination for suspected malignant uptakes. A total of 237 patients were therefore included in the study and data about the lobe of TIs and ultrasound dimension were collected.

2.2. 18F-FDG PET/CT Acquisition and Interpretation

18F-FDG PET/CT scans were acquired after at least 6 h of fasting and with blood glucose levels below 150 mg/dL. An activity of 3.5–4.5 MBq/kg of 18F-FDG was intravenously administrated to the patients 1 hour before images acquisition. Images were acquired from the base of the skull to the mid-thigh. All of the patients were instructed to void before the PET/CT acquisition and no type of oral or intravenous contrast agents were given for the execution of the scan. Similarly, none of the patients had performed any intestinal preparation.
In our study, we made use of 2 different PET/CT tomographs: the first (scanner 1) was a Discovery 690 PET/CT (General Electric Company-Milwaukee, WI, USA) while the second (scanner 2) was a Discovery STE PET/CT (General Electric Company, Milwaukee, WI, USA). On both of them standard acquisition parameters (CT: 80 mA, 120 Kv without contrast; 2.5–4 min per bed- PET-step, axial width 15 cm) and standard reconstruction parameters were used (256 × 256 matrix and 60 cm field of view).
Furthermore, scanner 1 was characterized by the presence of LYSO (cerium-doped lutetium yttrium oxyorthosilicate) scintillator crystals with a decay time of 45 ns, while scanner 2 had BGO (bismuth germanate) scintillator crystals with a decay time of 300 ns. Scanners were not harmonized with a cross-calibration program and all PET/CT scans were acquired at free-breath, instructing the patients to have regular breathing. For both scanners, a low dose CT at free breathing and without contrast agent was acquired in order to perform attenuation correction and for anatomical correlation. In particular, CT acquisition parameters for scanner 1 were: 120 kV, fixed tube current ≈ 60 mAs (40–100 mAs), 64 slices × 3.75 mm and 3.27 mm interval, pitch 0.984:1, tube rotation 0.5 s. CT acquisition parameters for scanner 2 were: 120 kV, fixed tube current ≈ 73 mAs (40–160 mAs), 4 slices × 3.75 mm and 3.27 mm interval, pitch 1.5:1, tube rotation 0.8 s. Furthermore, on scanner 1 time of flight (TOF) and point spread function (PSF) algorithm were used for the reconstruction of images, with filter cut-off 5 mm, 18 subsets and 3 iterations. Again, on scanner 2, an ordered subset expectation maximization (OSEM) algorithm with filter cut-off 5 mm, 21 subsets and 2 iterations were used.
PET images were visually and semiquantitatively analyzed by a nuclear physician with at least 10 years of experience, measuring parameters of TIs: the maximum standardized uptake value corrected for body weight (SUVmax), mean SUV corrected for body weight (SUVmean), maximum standardized uptake value lean body mass (SUVlbm), maximum standardized uptake value body surface area (SUVbsa), MTV and TLG. SUV-related parameters were measured on a Xeleris 3.1 GE workstation. MTV was calculated by drawing a volume of interest (VOI) on TIs on 18F-FDG PET/CT images corrected for attenuation, using a SUV-based automated contouring program (Advantage Workstation 4.6, GE HealthCare) with an isocounter threshold method based on 41% of the SUVmax, as previously recommended by the European Association of Nuclear Medicine (EANM) because of its high inter-observer reproducibility [25]. TLG values were calculated as the product of the MTV of the VOI for its SUVmean.

2.3. Radiomics Features Extraction

Image features were extracted from PET images by using LIFEx 2.20 software (LIFEx, by the French Alternative Energies and Atomic Energy Commission (CEA), Gif-sur-Yvette, France) (http://www.lifexsoft.org, accessed on 10 September 2021) [26] with the same procedure previously described for SUV-related parameters extraction, with similar VOI and after a new segmentation process.
The extraction of radiomics features (RF) was performed without spatial resampling, with an intensity discretization of 64 grey levels and with a distance from neighbors of 1 voxel for the extraction of GLCM parameters.
A total of 42 RF were generated (Table 1), divided in first-order statistics (histogram-related and shape-related) and second-order statistics: grey level co-occurrence matrix (GLCM) related, grey-level run length matrix (GLRLM) related, neighborhood grey level different matrix (NGLDM) related and grey-level zone length matrix (GLZLM) related.

2.4. Statistical Analysis

Statistical analysis was performed using MedCalc Software version 18.1 (8400, Ostend, Belgium) and R (http://www.R-project.org/) software version 4.1.1 (Statistics Department of the University of Auckland, Auckland, New Zealand). In the descriptive analysis, the categorical variables were represented as simple and relative frequencies, while the numeric variables with mean, standard deviation, and range values. For both scanners, the kernel density estimation built on the RF values were qualitatively compared and the presence of significant differences were evaluated with the Mann–Whitney test.
The general statistical analysis line of the study was structured of various steps. First of all, a univariate analysis (with a logistic regressor, in a 10-cross-fold validation) was performed for the group of patients evaluated on scanner 1, 1 for the group of patients of scanner 2 and 1 for the entire group of patients (scanner 1 and scanner 2 considered together). This first analysis had the purpose to evaluate the influence of the two scanners on the ability of RF to correlate with the final clinical outcome.
Furthermore, a bivariate analysis was performed with the purpose of developing 3 predictive models (1 for scanner 1, 1 for scanner 2 and 1 for both scanners considered together), by analyzing all of the possible couples of variables (the cartesian product of semiquantitative parameters, RF and the major clinical features such as age, gender and ultrasound dimension of the Tis). This bivariate analysis was performed with a bivariate logistic regression model was applied in order to classify them on the basis of the area under the curve (AUC) under the receiving operator curve (ROC) after a 10-cross fold validation training/testing test. This bivariate model had the purpose to clearly explore all the space of RF presented in the study. Similarly, for each couple of variables, the accuracy was extrapolated and to obtain a more complete statistic, the p-value were also extracted.
Lastly, a selection of the models with the best bivariate logistic regression was performed for scanner 1, scanner 2 and for both scanners considered together. In this setting an AUC higher than 0.8 was arbitrarily considered optimal to predict the final diagnosis of TIs, while an AUC between 0.6 and 0.8 was considered acceptable. Similarly, a p-value < 0.05 was arbitrarily considered as statistically significant.

3. Results

3.1. Patients Characteristics

A total of 221 patients were included in the study (Table 2), with a mean age of 66 years (range 16–88). The majority of the patients were female (n = 149, 67%) while 72 (33%) were male. No significant difference in terms of sex between the 2 groups of malignant TIs and benignant TIs was underlined (p value = 0.07).
TIs were most frequent findings on the right thyroid lobe with 123 (56%) subjects, while in 87 (39%) the incidental uptake were discovered on the left lobe and only in 11 (5%) cases they were underlined at the isthmus. Again, the site of TIs was not significantly correlated with the final diagnosis (p value = 0.79).
The mean diameter of the TIs, evaluated on subsequent ultrasound evaluation, was of 17 mm (range 5–75).
Overall, the final diagnosis of TIs was malignant for 71 (32%) patients and benignant in 150 (68%) patients. In this setting, for the correct evaluation of their final diagnosis, 97 (44%) subjects were evaluated only with ultrasound exams, with a mean follow-up of 24 months (range 12–168). Five (2%) patients performed a 99mTc thyroid scintigraphy, that revealed the presence of an hyperfunctioning adenoma.
For 118 (53%) patients, a cytological examination for the correct diagnosis of incidental 18F-FDG uptakes was performed, classifying the results according to the Italian Thyroid Cytology Classification System [27]. In particular, in 16 (14%) cases the result of the cytological examination was TIR5, in 13 (11%) it was TIR4, in 54 (45%) it was TIR3 while in 35 (30%) it was TIR2. Furthermore, of the 54 patients with a TIR3 classification, 24 (44%) had a TIR3a result while TIR3b was the final cytological result for 30 (56%) patients. A histological diagnosis of the TIs was performed in 71 (32%) cases and all of them revealed the presence of malignancy. In particular, in 3 (4%) cases the presence of anaplastic carcinoma was revealed, in 7 (10%) the presence of follicular carcinoma was underlined and in 61 (86%) there was a final diagnosis of papillary carcinoma. An evaluation of the predictive abilities of semiquantitative PET/CT parameters and of RF to predict the final cytological or histologic diagnosis was not performed because of the low sample of subjects beneath all the subgroups mentioned before.
A total of 128 (58%) scans were performed on the Discovery 690 tomograph (scanner 1), while 93 (42%) of them were acquired on the Discovery STE tomograph (scanner 2). The mean value of the SUVmax of the TIs was 7.9, it was 4.3 for SUVmean, 5.8 for SUVlbm, 2.0 for SUVbsa, 9.2 for MTV and 35.0 for TLG. (Figure 1).
Analyzing PET/CT acquisition depending on the tomograph used for their execution, in 92 (72%) scans performed on scanner 1 the incidental uptake resulted of benign nature while in 36 (28%) cases the final diagnosis was malignancy (1 anaplastic carcinoma, 4 follicular carcinomas and 31 papillary carcinomas). Regarding scanner 2, in 58 (62%) scans the final diagnosis of incidental uptake was benignancy while in 35 (38%) cases the presence of malignancy was underlined (2 anaplastic carcinomas, 3 follicular carcinomas and 30 papillary carcinomas). No significant difference in terms of final diagnosis was reported between the 2 scanners (p value = 0.1).

3.2. Comparison between the Two Scanners

The major clinical and epidemiological characteristics of the patients (age, sex, ultrasound dimension and final diagnosis of the TIs) were not significantly different between the two scanners.
Regarding semiquantitative parameters of PET/CT, only the values of SUVmax resulted significantly different between the 2 scanners (p value = 0.046), while the remaining parameters were not. In particular, the SUVmax values resulted higher on scanner 1 compared to scanner 2.
Focusing on RF, only 9 of 42 resulted in significant differences between the 2 scanners. In particular, RF with apparent correlation on the type of scanner used for the acquisition were Histo entropy_log10, Histo entropy_log2, Histo Energy, GLRLM LGRE, GLRLM SRLGE, NGLDM busyness, GLZLM SZE, GLZLM SZHGE and GLZLM ZLNU (Table 3). However, cross-correlation maps of RF between the two scanners were quite similar (Figure 2).

3.3. Predictive Accuracy

At univariate analysis (Table 4), for scanner 1 (Discovery 690) all PET/CT semiquantitative parameters and RF obtained an AUC value between 0.6 and 0.8. Regarding scanner 2 (Discovery STE), again all of the semiquantitative PET/CT parameters and RF reached a value of AUC between 0.6 and 0.8; in general, these values were lower than the those reported for scanner 1. Furthermore, the evaluation of p-value allowed the selection of some parameters with the best performances for the prediction of the final diagnosis of Tis, for both scanner 1 and scanner 2.
Considering the combined analysis of both the scanners together (scanner 1 + 2), in general PET/CT semiquantitative parameters revealed a higher AUC compared to RF, with significant p-value. Interestingly, the combined evaluation of both scanners revealed acceptable values of UAC with significant p-value for some RF, even if the same RF did not reach these values at the analysis for single scanner.
After performing a bivariate analysis, for both the single scanners and for both of the scanners considered together, the best combinations between PET/CT semiquantitative parameters and RF are summarized in Table 5. Similarly to univariate analysis, none of the combinations reached an optimal AUC of 0.8 and the couples of parameters generally obtained higher AUC values on scanner 1 than on scanner 2. Furthermore, for this analysis, the p-values were statistically more significant on scanner 1 than on scanner 2. In this setting, even if a comparison between the couples of variables obtained before is complex given the heterogeneity between the two scanners, in general GLCM-related parameters variously combined resulted the ones with best performances. This is true for both scanner 1 and scanner 2 and these findings are confirmed by the good results at univariate analysis previously described. The GLRLM-related and GLZLM-related RF also revealed good performances in this setting. Interestingly, PET/CT semiquantitative parameters were confirmed as good predictors only for scanner 2 (Figure 3).

4. Discussion

The aim of this study was to verify the predictive abilities of semiquantitative PET/CT parameters and of RF to discriminate between benignant and malignant nature of TIs revealed at 18F-FDG imaging.
On the basis of the resulting evidence we identified some remarkable points concerning the effect of different PET scanners on RF extraction and the predictive features and associated models.
In our experimental setting, we had to deal with images coming from different PET/CT tomographs and this fact required a preliminary investigation of the effect of different technologies in producing images and subsequent image features. The results showed that the scanner technology concretely affects some RF, as previously underlined in literature, and in clinical day practice the use of different tomographs in the same department is frequent [20,28,29,30,31,32,33,34]. In particular, the acquisition of the same phantoms on different tomographs with different scintillators and algorithm used for the reconstruction (number of iterations, number of subsets or on the presence of partial volume correction) demonstrated this evidence.
These findings suggest two relevant points: the former indicates that different scanners can potentially have different preferred features in terms of correlations with a clinical outcome; the second point suggests that we must critically consider radiomics models coming from centers adopting different technologies. In other words, on one hand a unique radiomic best model trained on many scanners is probably suboptimal for each of them and on the other hand, any radiomic model coming from different centers should be internally validated before considering its use in the daily practice. In particular, in the literature only one study which evaluated the predictive role of RF in TIs [23] used different scanners for the extraction of RF: this means that the reproducibility of the results (which is one of the biggest challenges in radiomics) still remain uninvestigated in this field. Furthermore, in our evaluation, only a small amount of RF demonstrated to be significantly different between the two scanners, together with SUVmax, but nevertheless the cross-correlation maps resulted quite similar, adding value to our results. In this setting, of the parameters that after bivariate analysis demonstrated the best performances, GLZLM SZHGE was the only one significantly different between the two scanners.
Regarding the predictive role of RF for the correct evaluation of Tis, at univariate and bivariate analysis a good percentage of the aforementioned parameters revealed an acceptable AUC between 0.6 and 0.8. However, none of them demonstrated an AUC above 0.8. Similarly, these AUC were coupled with a significant p-value in a high percentage of the cases. It is worth underlining the fact that at bivariate analysis performed for both the scanner considered together, the AUC values and the p-values were the best in the whole study. This fact underlines a good predictive ability of some RF such as GLCM-related (in particular GLCM entropy_log2 e GLCM entropy_log10), GLRLM-related and GLZLM-related.
Only a small amount of works that investigate the predictive role of radiomics in the evaluation of TIs at 18F-FDG PET/CT are available in literature [21,22,23,24].
Even if not clearly characterized by the presence of a proper texture analysis, the first study to evaluate the distributive heterogeneity of 18F-FDG in TIs was produced by Kim et al. [24]. In this work, the authors revealed that this heterogeneity was a promising parameter which was able to predict the final nature of these TIs.
Subsequently, Sollini et al. [23] were the first to evaluate the predictive abilities of texture analysis in this setting. Data of this study underlined the fact that SUVstd (the standard deviation of the distribution of SUV inside the considered VOI), SUVmax, MTV, TLG, Histo skewness, Histo kurtosis and GLCM correlation were the only parameters that were able to predict the final diagnosis of TIs, with a general positive predictive value of 54% and a general negative predictive value of 85%.
A similar analysis was also performed by Aksu et al. [22], who underlined how the semiquantitative PET/CT parameters and some shape-related, GLCM-related, GLRLM-related and GLZLM-related RF obtained AUC values superior to 0.7. These findings were partially confirmed in our study, where the same parameters confirmed these good results, with the exception of semiquantitative parameters and shape-related RF. Furthermore, the authors of the study developed a machine-learning algorithm using GLRLM RLNU e SUVmax with a good general AUC value (0.731).
Lastly, Ceriani et al. [21] demonstrated the ability to predict the final nature of TIs of some PET/CT semiquantitative parameters (SUVmax, SUVmean, SUVpeak, MTV e TLG) and some RF. In this case, the authors performed texture analysis with a different software from LIFEx and so RF resulted partly different in comparison to the ones used in our study. In general, some shape-related and GLCM-related features demonstrated good performances and multivariate analysis confirmed TLG, SUVmax and Shape sphericity as able to predict the final nature of Tis.
It is interesting to underline that PET/CT semiquantitative parameters resulted good predictors in all of the studies, while in our work only SUVmean obtained a certain predictive role at bivariate analysis. In this setting, we reported that AUC of semiquantitative parameters were quite similar to AUC of RF only at monovariate analysis. Given the fact that the bivariate predictive model did not confirm this evidence, we can assume that these parameters do not perform well when trying to build models with multiple variables as in our case. Furthermore, as previously described, data in literature about the role of these parameters for the assessment of TIs are really heterogeneous and our findings confirm these insights. Moreover, RF describe quality and parameters of images that cannot be visually assessed and this is why we focused our attention on the evaluation of these features, allowing us to better understand the role of 18F-FDG PET/CT in the prediction of Tis nature.
Our study surely presents some limitations. First of all, this is a retrospective study with the use of tomography that are not the actual state. Furthermore, the relatively low sample of patients included in the work, even if higher than similar studies, appears sub-optimal to clearly evaluate the predictive abilities of texture analysis. Furthermore, RF extrapolation with a single software appears another limit of our analysis. Lastly, the aforementioned problem of the reproducibility of radiomics analysis in terms of multicentric evaluation is still an open issue and, in this setting, further research in this field are mandatory.

5. Conclusions

In conclusion, our study enabled the selection of some RF that are able to predict with a certain good accuracy, the final nature of TIs discovered at 18F-FDG PET/CT imaging. Classic semiquantitative and volumetric PET/CT parameters did not reveal this ability. Furthermore, a good overlap in the extraction of RF between the two scanners was underlined.

Author Contributions

Conceptualization, F.D., R.G. (Roberto Gattaand) and D.A.; methodology, R.G. (Raffaele Giubbini) and N.P.; formal analysis, F.D. and R.G. (Roberto Gattaand); writing—original draft preparation, F.D., D.A. and R.G. (Raffaele Giubbini); writing—review and editing, N.P. and F.B. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Ethical review and approval were waived for this study due to the retrospective design of the study according to the local laws.

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

Data are not public, but are present in our institution.

Conflicts of Interest

The authors declare no conflict of interest.

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Figure 1. (A): Axial CT, axial PET and axial fused PET/CT images demonstrating the presence of TI revealed as intense focal uptake of 18F-FDG on the right lobe of thyroid. The lesion had a SUVmax of 44.47, an MTV of 0.7 and a TLG of 18.1 and subsequent cytological exam revealed no malignancy (TIR2). (B): Axial CT, axial PET and axial fused PET/CT images of another scan demonstrating again the presence of TI as a faint uptake on the right lobe of thyroid. The values of SUVmax, MTV and TLG of the lesion were 2.64, 6.9 and 10.3, respectively. Cytological evaluation (TIR5) and subsequent total thyroidectomy revealed the presence of papillary carcinoma.
Figure 1. (A): Axial CT, axial PET and axial fused PET/CT images demonstrating the presence of TI revealed as intense focal uptake of 18F-FDG on the right lobe of thyroid. The lesion had a SUVmax of 44.47, an MTV of 0.7 and a TLG of 18.1 and subsequent cytological exam revealed no malignancy (TIR2). (B): Axial CT, axial PET and axial fused PET/CT images of another scan demonstrating again the presence of TI as a faint uptake on the right lobe of thyroid. The values of SUVmax, MTV and TLG of the lesion were 2.64, 6.9 and 10.3, respectively. Cytological evaluation (TIR5) and subsequent total thyroidectomy revealed the presence of papillary carcinoma.
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Figure 2. Correlation maps for first and second order RF between the two scanners. Scanner 1 (Discovery 690) is presented on the left, while scanner 2 (Discovery STE) is presented on the right. Blue means high positive correlation; red means high negative correlation; white means no correlation.
Figure 2. Correlation maps for first and second order RF between the two scanners. Scanner 1 (Discovery 690) is presented on the left, while scanner 2 (Discovery STE) is presented on the right. Blue means high positive correlation; red means high negative correlation; white means no correlation.
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Figure 3. Visual representations of the three combinations ((A) GLCM Entropy_log10+GLZLM_SZHGE, (B) GLCM Entropy_log2+GLZLM:SZHGE; (C) GLCM Entropy_lo10+GLRLM_HGRE) with best performances at bivariate analysis for both scanners considered together.
Figure 3. Visual representations of the three combinations ((A) GLCM Entropy_log10+GLZLM_SZHGE, (B) GLCM Entropy_log2+GLZLM:SZHGE; (C) GLCM Entropy_lo10+GLRLM_HGRE) with best performances at bivariate analysis for both scanners considered together.
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Table 1. List of semiquantitative parameters and of radiomics features considered in the study.
Table 1. List of semiquantitative parameters and of radiomics features considered in the study.
Semiquantitave Parameters
SUV-related
   SUVmax
   SUVmean
   SUVlbm
   SUVbsa
Volumetric parameters
   MTV
   TLG
Radiomics features
First order features
   Histogram related
     Histo skewness
     Histo kurtosis
     Histo excess kurtosis
     Histo entropy_log10
     Histo entropy_log2
     Histo energy
   Shape related
     Shape volume_mL
     Shape volume_vx
     Shape sphericity
     Shape compacity
Second order features
   Grey level co-occurrence matrix (GLCM) related
     GLCM homogeneity
     GLCM energy
     GLCM contrast
     GLCM correlation
     GLCM entropy_log10
     GLCM entropy_log2
     GLCM dissimilarity
   Grey-level run length matrix (GLRLM) related
     GLRLM SRE
     GLRLM LRE
     GLRLM LGRE
     GLRLM HGRE
     GLRLM SRLGE
     GLRLM SRHGE
     GLRLM LRLGE
     GLRLM LRHGE
     GLRLM GLNU
     GLRLM RLNU
     GLRLM RP
   Neighborhood grey level different matrix (NGLDM) related
     NGLDM coarseness
     NGLDM contrast
     NGLDM busyness
   Grey-level zone length matrix (GLZLM) related
     GLZLM SZE
     GLZLM LZE
     GLZLM LGZE
     GLZLM HGZE
     GLZLM SZLGE
     GLZLM SZHGE
     GLZLM LZLGE
     GLZLM LZHGE
     GLZLM GLNU
     GLZLM ZLNU
     GLZLM ZP
SUVmax: standardized uptake value body weight max; SUVmean: standardized uptake value body weight mean; SUVlbm: standardized uptake value lean body mass, SUVbsa: standardized uptake value body surface area; MTV: metabolic tumor volume; TLG: total lesion glicolysis; SRE: short-run emphasis; LRE: long-run emphasis; LGRE: Low Gray-level Run Emphasis; HGRE: High Gray-level Run Emphasis; SRLGE: Short-Run Low Gray-level Em-phasis; SRHGE: Short-Run High Gray-level Emphasis; LRLGE: Long-Run Low Gray-level Emphasis; LRHGE: Long-Run High Gray-level Emphasis; GLNU: Gray-Level Non-Uniformity; RLNU: Run Length Non-Uniformity; RP: Run Percentage; SZE: Short-zone emphasis; LZE: Long-zone emphasis; LGZE: Low Gray-level Zone Emphasis; HGZE: High Gray-level Zone Emphasis; SZLGE: Short-Zone Low Gray-level Emphasis; SZHGE: Short-Zone High Gray-level Em-phasis; LZLGE: Long-Zone Low Gray-level Emphasis; LZHGE: Long-Zone High Gray-level Emphasis; ZLNU: Zone Length Non-Uniformity.Extraction of RF by LIFEx is only possible for VOI of at least 64 voxels, therefore 16 patients were excluded from the study because the volume of the TIs uptake was below this limit. As a consequence, the final number of patients included in the study was 221.
Table 2. Characteristics of the 221 patients included in the study.
Table 2. Characteristics of the 221 patients included in the study.
CharacteristicN. (%)
Age, mean ± SD (range)66 ± 14 (16–88)
Sex
   Male72 (33%)
   Female149 (67%)
Thyroid Lobe
   Right123 (56%)
   Left87 (39%)
   Isthmus11 (5%)
Ultrasound diameter (mm), mean ± SD (range)17 ± 12 (5–75)
Final Diagnosis
   Benign150 (68%)
   Malign71 (32%)
Cytology (N. = 118)
   TIR235 (30%)
   TIR3a24 (20%)
   TIR3b30 (25%)
   TIR413 (11%)
   TIR516 (14%)
Histology (N. = 71)
   Anaplastic carcinoma3 (4%)
   Follicular carcinoma7 (10%)
   Papillary carcinoma61 (86%)
PET/CT Scanner
   Scanner 1 (Discovery 690)128 (58%)
   Scanner 2 (Discovery STE)93 (42%)
Semiquantitative PET/CT parameters
   SUVmax, mean ± SD (range)7.9 ± 8 (1.3–56.7)
   SUVmean, mean ± SD (range)4.3 ± 4 (1.0–37.1)
   SUVlbm, mean ± SD (range)5.8 ± 6 (1.0–41.3)
   SUVbsa, mean ± SD (range)2.0 ± 2 (0.4–12.6)
   MTV, mean ± SD (range)9.2 ± 18 (0.4–198.0)
   TLG, mean ± SD (range)35.0 ± 75 (1.9–722.4)
N.: number, SD: standard deviation, mm: millimeters, SUVmax: standardized uptake value body weight max, SUVmean: standardized uptake value body mean, SUVlbm: standardized uptake value lean body mass, SUVbsa: standardized uptake value body surface area, MTV: metabolic tumor volume, TLG: total lesion glicolysis.
Table 3. Comparison of clinical parameters, semiquantitative PET/CT parameters and radiomics features between the two scanners.
Table 3. Comparison of clinical parameters, semiquantitative PET/CT parameters and radiomics features between the two scanners.
Parametersp-Value
Clinical
      Age0.787
      Sex0.522
      Diameters at ultrasound0.446
Semiquantitative PET/CT parameters
      SUVmax0.046
      SUVmean0.118
      SUVlbm0.119
      SUVbsa0.076
      MTV0.595
      TLG0.869
Radiomics features
      Histo skewness0.193
      Histo kurtosis0.924
      Histo excess kurtosis0.924
      Histo entropy_log100.023
      Histo entropy_log20.024
      Histo energy0.017
      Shape volume_mL0.211
      Shape volume_vx0.560
      Shape sphericity0.088
      Shape compacity0.518
      GLCM homogeneity0.104
      GLCM energy0.638
      GLCM contrast0.132
      GLCM correlation0.889
      GLCM entropy_log100.319
      GLCM entropy_log20.315
      GLCM dissimilarity0.145
      GLRLM SRE0.123
      GLRLM LRE0.113
      GLRLM LGRE0.026
      GLRLM HGRE0.069
      GLRLM SRLGE0.036
      GLRLM SRHGE0.069
      GLRLM LRLGE0.098
      GLRLM LRHGE0.135
      GLRLM GLNU0.260
      GLRLM RLNU0.962
      GLRLM RP0.126
      NGLDM coarseness0.471
      NGLDM contrast0.476
      NGLDM busyness0.006
      GLZLM SZE0.017
      GLZLM LZE0.168
      GLZLM LGZE0.053
      GLZLM HGZE0.086
      GLZLM SZLGE0.069
      GLZLM SZHGE0.041
      GLZLM LZLGE0.102
      GLZLM LZHGE0.561
      GLZLM GLNU0.366
      GLZLM ZLNU0.026
      GLZLM ZP0.093
Table 4. Univariate analysis for semiquantitative PET/CT parameters and for radiomics features for the single scanner and for both scanners considered together. Only values with AUC > 0.6 and p-value < 0.05 are reported.
Table 4. Univariate analysis for semiquantitative PET/CT parameters and for radiomics features for the single scanner and for both scanners considered together. Only values with AUC > 0.6 and p-value < 0.05 are reported.
Mean AUCMean p-Value
ParametersScanner 1Scanner 2Scanner 1 + 2Scanner 1Scanner 2Scanner 1 + 2
SUVmax0.7620.6790.748<0.010.02<0.01
SUVmean0.7240.6750.748<0.01<0.01<0.01
SUVlbm0.7570.6850.748<0.010.01<0.01
SUVbsa0.7560.6890.742<0.010.01<0.01
Histo entropy_log100.7090.6740.724<0.01<0.01<0.01
Histo entropy_log20.7050.6740.724<0.01<0.01<0.01
GLCM entropy_log100.7130.6640.7020.020.03<0.01
GLCM entropy_log20.7120.6640.7030.020.03<0.01
GLCM dissimilarity0.7190.6820.7270.01<0.01<0.01
GLRLM HGRE0.7310.6930.7410.030.03<0.01
GLRLM SRHGE0.7390.6820.7440.020.02<0.01
GLRLM LRLGE0.7070.6530.7150.010.01<0.01
GLZLM SZE0.7340.6710.693<0.01<0.010.01
GLZLM HGZE0.7400.6680.7400.020.03<0.01
GLZLM SZHGE0.7580.6930.7330.020.03<0.01
GLZLM ZP0.6920.6690.699<0.010.01<0.01
Variables with good performances only at Scanner 1 + 2 analysis
GLCM contrast0.7330.01
GLZLM ZLNU0.7290.04
GLRLM LRLGE0.715<0.01
GLZLM LGZE0.706<0.01
GLRLM LGRE0.703<0.01
GLCM homogeneity0.702<0.01
GLRLM SRLGE0.687<0.01
NGLDM busyness0.6840.01
GLRLM RP0.6600.04
GLZLM SZLGE0.651<0.01
AUC: area under the curve.
Table 5. Bivariate analysis for clinical, semiquantitative PET/CT parameters and radiomics features for the single scanner and for both scanners considered together. For each analysis, only the couples with best performances are reported.
Table 5. Bivariate analysis for clinical, semiquantitative PET/CT parameters and radiomics features for the single scanner and for both scanners considered together. For each analysis, only the couples with best performances are reported.
Covariate 1Covariate 2Mean p-Value 1Mean p-Value 2Mean AUC
Scanner 1
GLZLM GLNUMTV<0.010.010.779
GLRLM RLNUMTV0.020.030.776
GLCM energyGLCM entropy_log20.04<0.010.771
GLCM energyGLCM entropy_log100.04<0.010.771
GLCM entropy_log2GLRLM HGRE0.010.030.763
GLCM entropy_log10GLZLM HGZE0.020.020.762
GLCM entropy_log10GLRLM HGRE0.010.030.761
GLCM entropy_log2GLZLM HGZE0.020.020.760
GLCM entropy_log10GLZLM SZHGE0.010.020.760
GLCM entropy_log2GLZLM SZHGE0.010.020.759
GLRLM RPGLZLM SZHGE0.040.020.751
GLRLM HGREGLRLM RP0.020.030.745
MTVTLG<0.010.010.741
GLRLM SREGLZLM HGZE0.030.010.740
NGLDM coarsenessNGLDM busyness<0.010.010.738
Shape volume_mLGLRLM GLNU0.030.010.736
GLRLM GLNUNGLDM coarseness0.03<0.010.734
GLRLM SREGLZLM SZHGE0.030.020.732
GLRLM SREGLRLM HGRE0.030.020.730
GLRLM LRLGENGLDM coarseness<0.010.040.730
Shape volume_vxGLRLM GLNU0.020.020.723
GLCM entropy_log10GLZLM SZHGE0.04<0.010.713
Shape compacityGLZLM GLNU0.01<0.010.707
Shape volume_mLMTV0.020.020.693
Ultrasound dimensionMTV0.010.020.691
GLCM correlationNGLDM coarseness<0.01<0.010.690
Shape compacityNGLDM coarseness0.030.010.680
Ultrasound dimensionGLRLM GLNU0.010.010.677
Scanner 2
GLRLM SRESUVmean0.040.010.712
GLCM entropy_log10SUVbsa0.050.010.697
GLCM entropy_log2SUVbsa0.050.020.696
GLCM entropy_log2GLZLM SZHGE0.030.020.689
GLCM entropy_log10GLZLM SZHGE0.030.020.689
GLRLM RPSUVmean0.050.020.686
GLCM entropy_log2GLZLM HGZE0.050.020.682
GLCM entropy_log10GLZLM HGZE0.050.020.680
GLCM entropy_log10GLRLM HGRE0.040.020.679
GLCM energyGLRLM LRHGE0.010.020.679
GLCM entropy_log2GLRLM HGRE0.040.020.679
NGLDM coarsenessGLZLM ZP0.03<0.010.677
Histo energyGLRLM HGRE0.040.030.676
GLCM homogeneityNGLDM coarseness<0.010.060.675
GLCM contrastGLCM entropy_log100.040.040.673
GLCM contrastGLCM entropy_log20.040.040.673
Histo energyGLZLM SZHGE0.040.030.669
GLRLM SREGLRLM HGRE0.040.030.669
GLRLM SRENGLDM coarseness0.010.050.668
GLRLM LRESUVmean0.040.010.668
NGLDM coarsenessNGLDM busyness0.020.020.666
GLZLM GLNUMTV0.020.020.663
GLCM energyGLZLM SZHGE0.06<0.010.660
GLCM energyGLRLM HGRE0.06<0.010.659
GLRLM RPNGLDM coarseness0.010.050.657
GLRLM RLNUMTV0.010.010.650
NGLDM coarsenessMTV0.040.030.627
Scanner 1 + 2
GLCM entropy_log2GLZLM SZHGE<0.01<0.010.769
GLCM entropy_log10GLRLM HGRE<0.01<0.010.769
GLCM entropy_log10GLZLM SZHGE<0.01<0.010.769
GLCM entropy_log10GLZLM HGZE<0.01<0.010.769
GLCM entropy_log2GLRLM HGRE<0.01<0.010.768
GLCM entropy_log2GLZLM HGZE<0.01<0.010.768
GLRLM SRESUVmean<0.01<0.010.763
GLRLM GLNUNGLDM Coarseness<0.01<0.010.756
GLCM homogeneityGLRLM HGRE<0.01<0.010.749
GLCM homogeneityGLZLM HGZE<0.01<0.010.749
Histo energyGLRLM HGRE<0.01<0.010.749
Histo energyUniformityGLZLM SZHGE<0.01<0.010.748
GLCM homogeneityGLZLM SZHGE<0.01<0.010.748
NGLDM coarsenessNGLDM busyness<0.01<0.010.746
GLRLM SREGLRLM HGRE<0.01<0.010.742
GLRLM RPGLZLM HGZE<0.01<0.010.742
GLRLM SREGLZLM HGZE<0.01<0.010.742
GLRLM HGREGLRLM RP<0.01<0.010.742
NGLDM coarsenessGLZLM ZP<0.01<0.010.741
GLZLM GLNUMTV<0.01<0.010.738
GLRLM SREGLZLM SZHGE<0.01<0.010.738
GLRLM RPGLZLM SZHGE<0.01<0.010.737
GLRLM LREGLRLM LRHGE<0.01<0.010.737
GLRLM RLNUMTV<0.01<0.010.730
Histo energyGLCM energy<0.01<0.010.717
Shape compacityNGLDM coarseness<0.01<0.010.681
GLCM correlationNGLDM coarseness<0.01<0.010.654
Shape compacityGLZLM GLNU<0.01<0.010.640
AUC: area under the curve.
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Dondi, F.; Pasinetti, N.; Gatta, R.; Albano, D.; Giubbini, R.; Bertagna, F. Comparison between Two Different Scanners for the Evaluation of the Role of 18F-FDG PET/CT Semiquantitative Parameters and Radiomics Features in the Prediction of Final Diagnosis of Thyroid Incidentalomas. J. Clin. Med. 2022, 11, 615. https://doi.org/10.3390/jcm11030615

AMA Style

Dondi F, Pasinetti N, Gatta R, Albano D, Giubbini R, Bertagna F. Comparison between Two Different Scanners for the Evaluation of the Role of 18F-FDG PET/CT Semiquantitative Parameters and Radiomics Features in the Prediction of Final Diagnosis of Thyroid Incidentalomas. Journal of Clinical Medicine. 2022; 11(3):615. https://doi.org/10.3390/jcm11030615

Chicago/Turabian Style

Dondi, Francesco, Nadia Pasinetti, Roberto Gatta, Domenico Albano, Raffaele Giubbini, and Francesco Bertagna. 2022. "Comparison between Two Different Scanners for the Evaluation of the Role of 18F-FDG PET/CT Semiquantitative Parameters and Radiomics Features in the Prediction of Final Diagnosis of Thyroid Incidentalomas" Journal of Clinical Medicine 11, no. 3: 615. https://doi.org/10.3390/jcm11030615

APA Style

Dondi, F., Pasinetti, N., Gatta, R., Albano, D., Giubbini, R., & Bertagna, F. (2022). Comparison between Two Different Scanners for the Evaluation of the Role of 18F-FDG PET/CT Semiquantitative Parameters and Radiomics Features in the Prediction of Final Diagnosis of Thyroid Incidentalomas. Journal of Clinical Medicine, 11(3), 615. https://doi.org/10.3390/jcm11030615

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