Objectives The purpose of this study was to determine the significance of inter-scanner variability in CT image radiomics studies. Materials and Methods We compared the radiomics features calculated for non-small cell lung cancer (NSCLC) tumors from 20 patients with those calculated for 17 scans of a specially designed radiomics phantom. The phantom comprised 10 cartridges, each filled with different materials to produce a wide range of radiomics feature values. The scans were acquired using General Electric, Philips, Siemens, and Toshiba scanners from four medical centers using their routine thoracic imaging protocol. The radiomics feature studied included the mean and standard deviations of the CT numbers as well as textures derived from the neighborhood gray-tone difference matrix. To quantify the significance of the inter-scanner variability, we introduced the metric feature noise. To look for patterns in the scans, we performed hierarchical clustering for each cartridge. Results The mean CT numbers for the 17 CT scans of the phantom cartridges spanned from -864 to 652 Hounsfield units compared with a span of -186 to 35 Hounsfield units for the CT scans of the NSCLC tumors, showing that the phantom’s dynamic range includes that of the tumors. The inter-scanner variability of the feature values depended on both the cartridge material and the feature, and the variability was large relative to the inter-patient variability in the NSCLC tumors for some features. The feature inter-scanner noise was greatest for busyness and least for texture strength. Hierarchical clustering produced different clusters of the phantom scans for each cartridge, although there was some consistent clustering by scanner manufacturer. Conclusions The variability in the values of radiomics features calculated on CT images from different CT scanners can be comparable to the variability in these features found in CT images of NSCLC tumors. These inter-scanner differences should be considered, and their effects should be minimized in future radiomics studies.

Radiomics is the use of quantitative imaging features extracted from medical images to characterize tumor pathology or heterogeneity. Features measured at pretreatment have successfully predicted patient outcomes in numerous cancer sites. This project was designed to determine whether radiomics features measured from non–small cell lung cancer (NSCLC) change during therapy and whether those features (delta-radiomics features) can improve prognostic models. Features were calculated from pretreatment and weekly intra-treatment computed tomography images for 107 patients with stage III NSCLC. Pretreatment images were used to determine feature-specific image preprocessing. Linear mixed-effects models were used to identify features that changed significantly with dose-fraction. Multivariate models were built for overall survival, distant metastases, and local recurrence using only clinical factors, clinical factors and pretreatment radiomics features, and clinical factors, pretreatment radiomics features, and delta-radiomics features. All of the radiomics features changed significantly during radiation therapy. For overall survival and distant metastases, pretreatment compactness improved the c-index. For local recurrence, pretreatment imaging features were not prognostic, while texture-strength measured at the end of treatment significantly stratified high- and low-risk patients. These results suggest radiomics features change due to radiation therapy and their values at the end of treatment may be indicators of tumor response.

Purpose: Increasing evidence suggests radiomics features extracted from computed tomography (CT) images may be useful in prognostic models for patients with nonsmall cell lung cancer (NSCLC). This study was designed to determine whether such features can be reproducibly obtained from cone-beam CT (CBCT) images taken using medical Linac onboard-imaging systems in order to track them through treatment. Methods: Test-retest CBCT images of ten patients previously enrolled in a clinical trial were retrospectively obtained and used to determine the concordance correlation coefficient (CCC) for 68 different texture features. The volume dependence of each feature was also measured using the Spearman rank correlation coefficient. Features with a high reproducibility (CCC > 0.9) that were not due to volume dependence in the patient test-retest set were further examined for their sensitivity to differences in imaging protocol, level of scatter, and amount of motion by using two phantoms. The first phantom was a texture phantom composed of rectangular cartridges to represent different textures. Features were measured from two cartridges, shredded rubber and dense cork, in this study. The texture phantom was scanned with 19 different CBCT imagers to establish the features' interscanner variability. The effect of scatter on these features was studied by surrounding the same texture phantom with scattering material (rice and solid water). The effect of respiratory motion on these features was studied using a dynamic-motion thoracic phantom and a specially designed tumor texture insert of the shredded rubber material. The differences between scans acquired with different Linacs and protocols, varying amounts of scatter, and with different levels of motion were compared to the mean intrapatient difference from the test-retest image set. Results: Of the original 68 features, 37 had a CCC >0.9 that was not due to volume dependence. When the Linac manufacturer and imaging protocol were kept consistent, 4-13 of these 37 features passed our criteria for reproducibility more than 50% of the time, depending on the manufacturerprotocol combination. Almost all of the features changed substantially when scatter material was added around the phantom. For the dense cork, 23 features passed in the thoracic scans and 11 features passed in the head scans when the differences between one and two layers of scatter were compared. Using the same test for the shredded rubber, five features passed the thoracic scans and eight features passed the head scans. Motion substantially impacted the reproducibility of the features. With 4 mm of motion, 12 features from the entire volume and 14 features from the center slice measurements were reproducible. With 6-8 mm of motion, three features (Laplacian of Gaussian filtered kurtosis, gray-level nonuniformity, and entropy), from the entire volume and seven features (coarseness, high gray-level run emphasis, gray-level nonuniformity, sum-average, information measure correlation, scaled mean, and entropy) from ...

Consistent pixel sizes are of fundamental importance for assessing texture features that relate intensity and spatial information in radiomics studies. To correct for the effects of variable pixel sizes, we combined image resampling with Butterworth filtering in the frequency domain and tested the correction on computed tomography (CT) scans of lung cancer patients reconstructed 5 times with pixel sizes varying from 0.59 to 0.98 mm. One hundred fifty radiomics features were calculated for each preprocessing and field-of-view combination. Intra-patient agreement and inter-patient agreement were compared using the overall concordance correlation coefficient (OCCC). To further evaluate the corrections, hierarchical clustering was used to identify patient scans before and after correction. To assess the general applicability of the corrections, they were applied to 17 CT scans of a radiomics phantom. The reduction in the inter-scanner variability relative to non–small cell lung cancer patient scans was quantified. The variation in pixel sizes caused the intra-patient variability to be large (OCCC <95%) relative to the inter-patient variability in 79% of the features. However, with the resampling and filtering corrections, the intra-patient variability was relatively large in only 10% of the features. With the filtering correction, 8 of 8 patients were correctly clustered, in contrast to only 2 of 8 without the correction. In the phantom study, resampling and filtering the images of a rubber particle cartridge substantially reduced variability in 61% of the radiomics features and substantially increased variability in only 6% of the features. Surprisingly, resampling without filtering tended to increase the variability. In conclusion, applying a correction based on resampling and Butterworth low-pass filtering in the frequency domain effectively reduced variability in CT radiomics features caused by variations in pixel size. This correction may also reduce the variability introduced by other CT scan acquisition parameters.

Background: Despite advances in bronchoscopy, its diagnostic yield for peripheral lung lesions continues to be suboptimal. Cone beam computed tomography (CBCT) could be utilized to corroborate the accuracy of our bronchoscopic navigation and hopefully increase its diagnostic yield. However, data on radiation exposure and feasibility of CBCT-guided bronchoscopy is scarce. Methods: Prospective pilot study of bronchoscopy for peripheral lung nodules under general anesthesia with thin/ultrathin bronchoscope, radial-probe endobronchial ultrasound (RP-EBUS), and CBCT. Main objective was to estimate radiation dose and secondary objective was the additional value of CBCT in terms of navigational and diagnostic yield. Results: A total of 20 patients were enrolled. Median lesion size was 2.1 (range, 1.1-3) cm and distance from pleura was 2.1 (range, 0-2.8) cm. "Bronchus sign" was present in 12 (60%) of the lesions. Totally, 12 lesions (60%) were invisible on fluoroscopy. CBCT identified atelectasis obscuring the target in 4 cases (20%).Eleven patients (55%) underwent 1 CBCT scan and 9 patients (45%) 2. The mean estimated effective dose (E) to patients resulting from CBCT ranged between 8.6 and 23 mSv, depending on utilized conversion factors. Both pre-CBCT navigation and diagnostic yield were 50%. Additional post-CBCT maneuvers increased navigation yield to 75% (P=0.02) and diagnostic yield to 70% (P=0.04). One patient developed a pneumothorax. Conclusions: CBCT-guided bronchoscopy is associated with an acceptable radiation dose. CBCT may potentially increase both navigation and diagnostic yield of thin/ultrathin bronchoscopy for peripheral lung nodules. The above findings as well as the incidental but relevant finding of intra-procedural atelectasis need to be confirmed in larger prospective studies.Trial registration: This study is registered in ClinicalTrials.gov as number NCT02978170.