The Image Biomarker Standardization Initiative: Standardized Quantitative Radiomics for High-Throughput Image-based Phenotyping.

Background Radiomic features may quantify characteristics present in medical imaging. However, the lack of standardized definitions and validated reference values have hampered clinical use. Purpose To standardize a set of 174 radiomic features. Materials and Methods Radiomic features were assessed in three phases. In phase I, 487 features were derived from the basic set of 174 features. Twenty-five research teams with unique radiomics software implementations computed feature values directly from a digital phantom, without any additional image processing. In phase II, 15 teams computed values for 1347 derived features using a CT image of a patient with lung cancer and predefined image processing configurations. In both phases, consensus among the teams on the validity of tentative reference values was measured through the frequency of the modal value and classified as follows: less than three matches, weak; three to five matches, moderate; six to nine matches, strong; 10 or more matches, very strong. In the final phase (phase III), a public data set of multimodality images (CT, fluorine 18 fluorodeoxyglucose PET, and T1-weighted MRI) from 51 patients with soft-tissue sarcoma was used to prospectively assess reproducibility of standardized features. Results Consensus on reference values was initially weak for 232 of 302 features (76.8%) at phase I and 703 of 1075 features (65.4%) at phase II. At the final iteration, weak consensus remained for only two of 487 features (0.4%) at phase I and 19 of 1347 features (1.4%) at phase II. Strong or better consensus was achieved for 463 of 487 features (95.1%) at phase I and 1220 of 1347 features (90.6%) at phase II. Overall, 169 of 174 features were standardized in the first two phases. In the final validation phase (phase III), most of the 169 standardized features could be excellently reproduced (166 with CT; 164 with PET; and 164 with MRI). Conclusion A set of 169 radiomics features was standardized, which enabled verification and calibration of different radiomics software. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Kuhl and Truhn in this issue.

Revisiting the identification of tumor sub-volumes predictive of residual uptake after (chemo)radiotherapy: influence of segmentation methods on 18F-FDG PET/CT images.

Our aim was to evaluate the impact of the accuracy of image segmentation techniques on establishing an overlap between pre-treatment and post-treatment functional tumour volumes in 18FDG-PET/CT imaging. Simulated images and a clinical cohort were considered. Three different configurations (large, small or non-existent overlap) of a single simulated example was used to elucidate the behaviour of each approach. Fifty-four oesophageal and head and neck (H&N) cancer patients treated with radiochemotherapy with both pre- and post-treatment PET/CT scans were retrospectively analysed. Images were registered and volumes were determined using combinations of thresholds and the fuzzy locally adaptive Bayesian (FLAB) algorithm. Four overlap metrics were calculated. The simulations showed that thresholds lead to biased overlap estimation and that accurate metrics are obtained despite spatially inaccurate volumes. In the clinical dataset, only 17 patients exhibited residual uptake smaller than the pre-treatment volume. Overlaps obtained with FLAB were consistently moderate for esophageal and low for H&N cases across all metrics. Overlaps obtained using threshold combinations varied greatly depending on thresholds and metrics. In both cases overlaps were variable across patients. Our findings do not support optimisation of radiotherapy planning based on pre-treatment 18FDG-PET/CT image definition of high-uptake sub-volumes. Combinations of thresholds may have led to overestimation of overlaps in previous studies.

Sexual and ethnic polymorphism render prosthetic overhang and under-coverage inevitable using off-the shelf TKA implants.

PURPOSE: Unexplained pain and stiffness after total knee arthroplasty (TKA) often result from mismatch between implant geometry and knee morphology, which depends on patient size, sex, and ethnicity. This study aimed to determine whether size, sex, or ethnicity are independently associated with distal femoral morphology in healthy Caucasian and Asian knees, and to compare anatomic ratios to those of commercially available TKA implants. METHODS: Two series of computed tomography (CT) angiograms from France (264 knees) and China (259 knees) were used to digitize osteometric landmarks at the level of the femoral epicondyles, to measure anteroposterior (AP) and mediolateral (ML) dimensions at the anterior, posterior, medial, and lateral zones. The aspect (ML/AP), trapezoidicity (MLp/MLa), and asymmetry (APl/APm) ratios, as well as the sulcus angle were calculated and compared to those of 9 TKA models. Multivariable analyses were performed to determine whether anatomic ratios were independently associated with sex, origin, or size. RESULTS: Multivariable analyses revealed that, independently from size, female knees were narrower (ß = - 0.03; p < 0.001) and more asymmetric (ß = 0.02; p < 0.001), while Chinese knees were more trapezoidal (ß = 0.04; p = 0.002) and asymmetric (ß = 0.02; p < 0.001) with shallower trochleae (ß = 6.4°; p < 0.001). Compared to native knees, most implants were too wide, and many of the recent models too 'trapezoidal'. Most prosthetic trochleae were too shallow compared to French knees, but within the third quartile of Chinese knees. CONCLUSIONS: The morphology of the distal femur depends on sex and ethnicity independently from size. The wide spectrum of morphotypes observed cannot be covered by 'off-the-shelf' TKA models, and until customized implants become more accessible, prosthetic overhang, and under-coverage remain inevitable. LEVEL OF EVIDENCE: III, Retrospective comparative study.

Potential Complementary Value of Noncontrast and Contrast Enhanced CT Radiomics in Colorectal Cancers.

RATIONALE AND OBJECTIVES: The aim of our study was to assess the relationships between textural features extracted from contrast enhanced (CE) and noncontrast enhanced (NCE) computed tomography (CT) images of primary colorectal cancer, in order to identify radiomics features more likely to provide potential complementary information regarding outcome. MATERIALS AND METHODS: Sixty-one patients with primary colorectal cancer underwent both CE-CT and NCE-CT scans within the same acquisition. First-order and textural features (with three different methods for grey-level discretization) were extracted from the tumor volume in both modalities and their correlation was assessed with Spearman's rank correlation (rs). Significance was assessed at p < 0.05 with correction for multiple comparisons. Kaplan-Meier estimation and log-rank tests were used to identify features associated with long term patient survival. RESULTS: Moderate positive correlations were observed between CE-CT and NCE-CT histogram-derived entropy (EntropyHist) and area under the curve (CHAUC) (rs = 0.49, p < 0.001 and rs= 0.45, p < 0.001, respectively). Some second and third order textural features were found highly correlated between CE-CT and NCE-CT, such as small zone-size emphasis SZSE (rs = 0.729, p < 0.001) and zone-size percentage (rs = 0.770, p < 0.001). Grey-levels discretization methods influenced these correlations. A few of the third order NCE-CT and CE-CT features were significantly associated with survival. CONCLUSION: Some radiomics features with moderate correlations between nonenhanced and enhanced CT images were found to be associated with survival, thus suggesting that complementary prognostic value may be extracted from both modalities when available.

External validation of a combined PET and MRI radiomics model for prediction of recurrence in cervical cancer patients treated with chemoradiotherapy.

PURPOSE: The aim of this study was to validate previously developed radiomics models relying on just two radiomics features from 18F-fluorodeoxyglucose positron emission tomography (PET) and magnetic resonance imaging (MRI) images for prediction of disease free survival (DFS) and locoregional control (LRC) in locally advanced cervical cancer (LACC). METHODS: Patients with LACC receiving chemoradiotherapy were enrolled in two French and one Canadian center. Pre-treatment imaging was performed for each patient. Multicentric harmonization of the two radiomics features was performed with the ComBat method. The models for DFS (using the feature from apparent diffusion coefficient (ADC) MRI) and LRC (adding one PET feature to the DFS model) were tuned using one of the French cohorts (n = 112) and applied to the other French (n = 50) and the Canadian (n = 28) external validation cohorts. RESULTS: The DFS model reached an accuracy of 90% (95% CI [79-98%]) (sensitivity 92-93%, specificity 87-89%) in both the French and the Canadian cohorts. The LRC model reached an accuracy of 98% (95% CI [90-99%]) (sensitivity 86%, specificity 100%) in the French cohort and 96% (95% CI [80-99%]) (sensitivity 83%, specificity 100%) in the Canadian cohort. Accuracy was significantly lower without ComBat harmonization (82-85% and 71-86% for DFS and LRC, respectively). The best prediction using standard clinical variables was 56-60% only. CONCLUSIONS: The previously developed PET/MRI radiomics predictive models were successfully validated in two independent external cohorts. A proposed flowchart for improved management of patients based on these models should now be confirmed in future larger prospective studies.

Prediction of outcome using pretreatment 18F-FDG PET/CT and MRI radiomics in locally advanced cervical cancer treated with chemoradiotherapy.

PURPOSE: The aim of this study is to determine if radiomics features from 18fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) images could contribute to prognoses in cervical cancer. METHODS: One hundred and two patients (69 for training and 33 for testing) with locally advanced cervical cancer (LACC) receiving chemoradiotherapy (CRT) from 08/2010 to 12/2016 were enrolled in this study. 18F-FDG PET/CT and MRI examination [T1, T2, T1C, diffusion-weighted imaging (DWI)] were performed for each patient before CRT. Primary tumor volumes were delineated with the fuzzy locally adaptive Bayesian algorithm in the PET images and with 3D Slicer™ in the MRI images. Radiomics features (intensity, shape, and texture) were extracted and their prognostic value was compared with clinical parameters for recurrence-free and locoregional control. RESULTS: In the training cohort, median follow-up was 3.0 years (range, 0.43-6.56 years) and relapse occurred in 36% of patients. In univariate analysis, FIGO stage (I-II vs. III-IV) and metabolic response (complete vs. non-complete) were probably associated with outcome without reaching statistical significance, contrary to several radiomics features from both PET and MRI sequences. Multivariate analysis in training test identified Grey Level Non UniformityGLRLM in PET and EntropyGLCM in ADC maps from DWI MRI as independent prognostic factors. These had significantly higher prognostic power than clinical parameters, as evaluated in the testing cohort with accuracy of 94% for predicting recurrence and 100% for predicting lack of loco-regional control (versus ~50-60% for clinical parameters). CONCLUSIONS: In LACC treated with CRT, radiomics features such as EntropyGLCM and GLNUGLRLM from functional imaging DWI-MRI and PET, respectively, are independent predictors of recurrence and loco-regional control with significantly higher prognostic power than usual clinical parameters. Further research is warranted for their validation, which may justify more aggressive treatment in patients identified with high probability of recurrence.

Reliability of PET/CT Shape and Heterogeneity Features in Functional and Morphologic Components of Non-Small Cell Lung Cancer Tumors: A Repeatability Analysis in a Prospective Multicenter Cohort.

The main purpose of this study was to assess the reliability of shape and heterogeneity features in both the PET and the low-dose CT components of PET/CT. A secondary objective was to investigate the impact of image quantization. Methods: A Health Insurance Portability and Accountability Act-compliant secondary analysis of deidentified prospectively acquired PET/CT test-retest datasets of 74 patients from multicenter Merck and American College of Radiology Imaging Network trials was performed. Metabolically active volumes were automatically delineated on PET with a fuzzy locally adaptive bayesian algorithm. Software was used to semiautomatically delineate the anatomic volumes on the low-dose CT component. Two quantization methods were considered: a quantization into a set number of bins (quantization B) and an alternative quantization with bins of fixed width (quantization W). Four shape descriptors, 10 first-order metrics, and 26 textural features were evaluated. Bland-Altman analysis was used to quantify repeatability. Features were subsequently categorized as very reliable, reliable, moderately reliable, or poorly reliable with respect to the corresponding volume variability. Results: Repeatability was highly variable among features. Numerous metrics were identified as poorly or moderately reliable. Others were reliable or very reliable in both modalities and in all categories (shape and first-, second-, and third-order metrics). Image quantization played a major role in feature repeatability. Features were more reliable in PET with quantization B, whereas quantization W showed better results in CT. Conclusion: The test-retest repeatability of shape and heterogeneity features in PET and low-dose CT varied greatly among metrics. The level of repeatability also depended strongly on the quantization step, with different optimal choices for each modality. The repeatability of PET and low-dose CT features should be carefully considered when selecting metrics to build multiparametric models.

Development of a nomogram combining clinical staging with (18)F-FDG PET/CT image features in non-small-cell lung cancer stage I-III.

PURPOSE: Our goal was to develop a nomogram by exploiting intratumour heterogeneity on CT and PET images from routine (18)F-FDG PET/CT acquisitions to identify patients with the poorest prognosis. METHODS: This retrospective study included 116 patients with NSCLC stage I, II or III and with staging (18)F-FDG PET/CT imaging. Primary tumour volumes were delineated using the FLAB algorithm and 3D Slicer™ on PET and CT images, respectively. PET and CT heterogeneities were quantified using texture analysis. The reproducibility of the CT features was assessed on a separate test-retest dataset. The stratification power of the PET/CT features was evaluated using the Kaplan-Meier method and the log-rank test. The best standard metric (functional volume) was combined with the least redundant and most prognostic PET/CT heterogeneity features to build the nomogram. RESULTS: PET entropy and CT zone percentage had the highest complementary values with clinical stage and functional volume. The nomogram improved stratification amongst patients with stage II and III disease, allowing identification of patients with the poorest prognosis (clinical stage III, large tumour volume, high PET heterogeneity and low CT heterogeneity). CONCLUSION: Intratumour heterogeneity quantified using textural features on both CT and PET images from routine staging (18)F-FDG PET/CT acquisitions can be used to create a nomogram with higher stratification power than staging alone.