1. Patients Selection
This single-center retrospective study was approved by the institutional review board of the First Affiliated Hospital of Chongqing Medical University. The requirement for written informed consent was waived.
Search the electronic medical record system for patients who underwent surgical resection in thoracic surgery due to pulmonary ground glass opacities between January 2019 and May 2023. A total of 715 patients were reviewed. Two radiologists (with >5 years of post-training experience) manually reviewed the patients at the picture archiving and communication system (Carestream Vue PACS) workstation. The patients who met the following inclusion criteria were included: (1) lesions appearing as GGNs (diameter ≤ 3 cm) on CT images; (2) patients with complete clinical, CT, and pathological data; (3) the GGNs were confirmed as neoplastic lesions; (4) all the examinations were performed by the same brand of CT scanners; and (5) no needle biopsy or treatment was performed for lesions prior to CT examination. Patients with the following conditions were excluded: (1) the interval between chest CT examination and surgery was >1 month (n = 16); (2) absence of thin-section CT images (≤ 1.0 mm) (n = 11); (3) patients had severe and diffuse lung diseases (emphysema, interstitial lung disease, etc.) (n = 25); and (4) their CT images had artifacts or poor image quality, which affected evaluation (n = 9). Finally, a total of 687 nodules in 654 patients were further analyzed in this study.
2. CT Examinations
The CT examinations were performed by the following scanners, including Somatom Definition Flash (Siemens Healthineers, Erlangen, Germany), Somatom Perspective (Siemens Healthineers, Erlangen, Germany), and Somatom Force (Siemens Healthineers, Erlangen, Germany). All patients were examined in a supine position with raised upper limbs, followed by performing a breath-holding exercise before image acquisition. CT examination was performed from the thoracic inlet to the costophrenic angle at the end of inspiration during a single breath-hold. The scanning parameters were as follows: tube voltage, 120 kVp; tube current, 50–130 mAs (using automatic current modulation technology); scanning slice thickness 5 mm; rotation time, 0.5 second; pitch, 1.0–1.1; collimation, 0.60 mm; and matrix, 512 × 512. Images were reconstructed at a slice thickness and slice interval of 1.00 mm using iterative reconstruction with medium-sharpness algorithm. Both mediastinal window (width, 350–400 HU; level, 20–40 HU) and lung window (width, 1200–1600 HU; level, −500 to −700 HU) were obtained.
3. Image Interpretation
AI software (InferRead CT Lung, InferVision Medical Health, China) was used to automatically segmented the GGNs from CT images and obtain their density histograms first, and then the proportions of the components with higher density in lesions at density reference values (≥ −800HU, ≥ −750HU, ≥ −700HU, ≥ −650HU, ≥ −600HU, ≥ −550HU, ≥ −500HU, ≥ −450HU, ≥ −400HU, ≥ −350HU, ≥ −300HU, ≥ −250HU, ≥ −200HU) were acquired by manually adjusting the bar (Figure 1). At the same time, the CT images and clinical information of the lesions were reviewed independently by two additional thoracic radiologists (with more than 10 years of post-training experience) who were blinded to the pathological results. The following indicators were evaluated: size (the average of the maximum diameter of the nodule and the diameter perpendicular to the maximum diameter), distribution in lobes (right upper, middle and lower lobe; and left upper and lower lobe), shape (irregular vs. regular [round or oval]), boundary (well-defined vs. ill-defined), air bronchogram sign (present vs. absent), vacuole sign (present vs. absent), vascular changes (present vs. absent), lobulation sign (present vs. absent), spiculation sign (present vs. absent), and pleural indentation sign (present vs. absent). Air bronchogram sign was defined as visible air-filled bronchi detected in the nodule [20]. Vacuole sign was defined as a round or oval air density within a nodule [21], whereas spiculation sign was defined as linear strands extending beyond the lesion [22]. Lobulation sign was defined as a wavy or scalloped configuration of a portion of the nodule’s surface [23], while pleural indentation sign was defined as a linear strand radiating from the nodule and extending distal to the pleural surface [24]. In addition, vascular changes included dilation and distortion of involved vessels. Vascular dilation was observed when the diameter of the vascular segment within lesions was larger than the proximal segment (before entering lesions) or other vessels at the same branch level, whereas vascular distortion was observed when the vessel deviated from its normal route [25]. Consensus was reached through consultation and discussion just in case there were differences in opinion between the two radiologists.
4. Statistical Methods
All data were processed by SPSS 25 software (IBM Corp, NY, USA). Clinical data and various CT features were statistically analyzed for each patient. Continuous variables were represented by mean ± SD. Kruskal–Wallis Test was used for age and size, whereas Pearson’s Chi-squared test was used for sex, shape, location, boundary, lobulation, spiculation, vacuole sign, vascular change, air bronchogram, and pleural indentation. Then, the optimal density thresholds and the corresponding cutoff values for the proportions of the components in lesions with density higher than the thresholds for determining ILs and IACs were determined via receiver operating characteristic (ROC) curve analysis and comparing the area under the curves (AUCs) and Youden indexes. The Delong test was performed to assess the statistical difference between the traditional morphological features model and the combined model of the optimal density indicators and traditional morphological features in determining ILs and IACs. For morphological features selection, all factors were entered into the multivariate logistic regression models to identify independent factors associated with the invasiveness of ILs and IACs, respectively. P-value less than 0.05 was considered statistically significant.