Patients
The current retrospective trial assessed consecutive individuals with thyroid nodules firstly identified by US from January 2018 to March 2019. Based on the American College of Radiology Thyroid Imaging, Reporting, and Data System[31], tumor grades were TR3-TR5.
All patients were examined by multiparametric MRI and subsequently administered thyroid surgery, subtotal or total thyroidectomy, within 1 week following MRI. PTC was pathologically confirmed with surgical specimens. Exclusion criteria were: (1) pathological diagnosis not reflecting PTC; (2) tumor size <5 mm; (3) no association of pathological data of tumor specimens with MR imaging findings; (4) poor MR quality. Finally, 132 cases were assessed. Figure 1 depicts the patient selection process.
The study had approval from our local institutional ethics committee. Signed informed consent was obtained from each participant.
MRI acquisition
All patients were scanned on an EXCITE HD 1.5 T scanner (GE Healthcare, USA) comprising an 8-channel special neck surface coil, using the same scanning protocol. The applied parameters were as follows: axial T2-weighted (T2WI) fast recovery fast spin-echo with fat suppression with an echo time (TE) of 85 ms, a repetition time (TR) of 1280 ms, a slice thickness of 4−5 mm, a matrix of 288×192, spacing of 1 mm, a field of view (FOV) of 18 cm, and a number of excitations (NEX) of 4; DWI with a single-shot echo planar imaging (EPI) sequence, with minimal TE, a TR of 6550 ms, a slice thickness of 4−5 mm, a matrix of 128×128, spacing of 0.5 mm, a FOV of 14 cm, and a NEX of 4 (b value, 800 s/mm2); contrast-enhanced axial T1WI (CE-T1) with multiphase utilizing a fast-spoiled gradient recalled echo sequence (TE =1.7 ms, TR=5.7 ms, matrix=192×256, FOV=14 cm, and NEX=1). The Magnevist contrast agent (Bayer Healthcare, USA) was administered by intravenous injection at 3 ml/s (0.2 ml/kg), followed by flushing with 20 ml of normal saline. Scanning was performed at 30, 60, 120, 180, 240 and 300 s after contrast administration, respectively, and images of the six phases were obtained, including breath-holds. Spatial saturation bands were employed for removing signals generated by overlying fat and surrounding tissues.
Histopathologic analysis
Surgical tumor samples were evaluated and analyzed by an experienced pathologist (>10 years of related experience). Paraffin-embedding of tumor samples was followed by sectioning and hematoxylin and eosin (H&E) staining. Then, established criteria were utilized by the pathologist for evaluating the extrathyroidal extension (ETE) feature[15]. The patients were then assigned to the non-ETE and ETE groups.
MRI radiomics
Tumor segmentation
ITK-SNAP (http://www.itk-snap.org) was applied for the segmentation of thyroid tumors. Regions of interest (ROIs) were manually drawn on MR images by 2 radiologists (9 and 12 years of related experience, respectively). In case of disagreement, they reached a consensus through additional reading sessions. The ROIs were delineated slice-by-slice to represent the 3D volume of the whole tumor. The largest tumor was selected in each patient and delineated on MR images, which could reduce potential bias of multiple tumors in the same individual and improve the applicability of findings.
Radiomics feature extraction
To facilitate imaging analysis, all T2WI, ADC and CE-T1 images were resliced at 4 mm. Radiomic features were automatically extracted with the AK software version 3.2.2 (GE healthcare). A total of 402 features were extracted, including shape, histogram, gray-level run-length matrix (GLRLM), gray-level cooccurrence matrix (GLCM), and gray-level size zone matrix (GLSZM) indexes.
Feature selection and model construction
Participants were randomized to the training and test cohorts (ratio, 7:3). To assess interobserver agreement, 30 patients were randomly selected and intraclass correlation coefficients (ICCs) for various features were calculated. According to the 95% confidence intervals (CIs), values below 0.4, from 0.41 to 0.60, from 0.61 to 0.80, and above 0.80 were classified as poor, medium, good, and excellent reliability, respectively. Various features were utilized for further extraction, with ICCs reaching 0.80[32].
Radiomic feature selection
Firstly, the mRMR (maximum correlation minimum redundancy) algorithm was applied in the training group to eliminate redundant and irrelevant features, and 30 features with high correlation with labels, and without redundancy were retained. Then, the least absolute shrinkage and selection operator (LASSO) with ten-fold cross-validation was applied, and the feature subsets was further selected through regularization by optimizing the hyperparameter λ. The coefficients of some candidate features were compressed to zero at the optimal λ, and features with non-zero coefficients were retained for constructing a radiomics signature via a linear combination. Finally, the radiomics score (rad-score) was calculated.
Model building and validation
The performance of the model in distinguishing the ETE feature of PTC was evaluated and validated by receiver operating characteristic (ROC) curve analysis in the training and test cohorts, respectively. The area under the curve (AUC), sensitivity, specificity, accuracy, and negative and positive predictive values were calculated. In addition, 100 times leave-group-out cross-validation (LGOCV) was carried out to verify the model’s reliability, indicating the results given in the model were not contingent.