345 Quantitative classification and radiomics of [18F]FDG-PET/CT 5 Radiomic analysis All visually [18F]FDG-positive nodules, defined as index nodules with focal [18F]FDG-uptake that was visually higher than the background [18F]FDG-uptake in the surrounding normal thyroid tissue, were included in the radiomic analysis. Volume of interest definition Volumes of interest (VOI) were delineated semi-automatically around visually [18F]FDG-positive nodules using 3DSlicer (version 4.11; slicer.org) and in-house built software implemented in Python (version 3.6.10; Python Software Foundation, Wilmington, Delaware) [512]. VOIs were delineated on the [18F]FDG-PET scans using an isocontour that applies a threshold of 50% of the SUV peak, corrected for local background activity (Figure 2) [511]. Boxing was applied to exclude [18F]FDG-positive tissue surrounding the index nodule and ldCT images were used as a visual reference. VOIs delineated on the PET images were resampled with a nearest neighbour algorithm to derive the ldCT VOIs. Potential mismatch was evaluated visually: no corrections were required. Image processing and radiomic feature extraction Radiomic features were extracted from the VOIs on both the interpolated PET (4×4×4 mm³) and the ldCT (2×2×2 mm³) images using PyRadiomics (version 2.1.2 in Python version 3.6.10; pyradiomics. readthedocs.io) [513]. From both PET and CT images, 107 standardized features were extracted: 14 shape features, 18 intensity features and 75 texture features (24 grey level co-occurrence matrix (GLCM), 16 grey level run length matrix, 16 grey level size zone matrix, 14 grey level dependence matrix, five neighbouring grey tone difference matrix). For PET, the total lesion glycolysis (TLG, defined as the product of the SUVmean and the metabolic tumour volume) was also added. A fixed bin size of 0.5 g/mL for PET and 25 HU for ldCT was used (Supplementary data, Table 2) [514]. Reference standard During participation in the EfFECTS trial, patients were advised to refrain from the scheduled diagnostic surgery when they were allocated to the [18F]FDG-PET/CT-driven group and the index nodule was visually [18F]FDG-negative. These patients remained under active surveillance and had at least a follow-up ultrasound examination after 12 months. All other patients were advised to proceed to the scheduled diagnostic surgery and were treated according to current guidelines [467, 501]. This resulted in the following reference standard for the current study: benign nodules were defined either as benign on final histopathology (i.e., hyperplastic nodules, follicular adenoma or Hürthle cell adenoma) or as index nodules that remained unchanged in size and appearance on ultrasound follow-up, in accordance with definitions from the EfFECTS trial. Malignancies and
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