Radiogenomic Associations Clear Cell Renal Cell Carcinoma: An Exploratory Study.

INTRODUCTION: This study investigates how quantitative texture analysis can be used to non-invasively identify novel radiogenomic correlations with clear cell renal cell carcinoma (ccRCC) biomarkers. METHODS: The Cancer Genome Atlas-Kidney Renal Clear Cell Carcinoma open-source database was used to identify 190 sets of patient genomic data that had corresponding multiphase contrast-enhanced CT images in The Cancer Imaging Archive. 2,824 radiomic features spanning fifteen texture families were extracted from CT images using a custom-built MATLAB software package. Robust radiomic features with strong inter-scanner reproducibility were selected. Random forest, AdaBoost, and elastic net machine learning (ML) algorithms evaluated the ability of the selected radiomic features to predict the presence of 12 clinically relevant molecular biomarkers identified from the literature. ML analysis was repeated with cases stratified by stage (I/II vs. III/IV) and grade (1/2 vs. 3/4). 10-fold cross validation was used to evaluate model performance. RESULTS: Before stratification by tumor grade and stage, radiomics predicted the presence of several biomarkers with weak discrimination (AUC 0.60-0.68). Once stratified, radiomics predicted KDM5C, SETD2, PBRM1, and mTOR mutation status with acceptable to excellent predictive discrimination (AUC ranges from 0.70 to 0.86). CONCLUSIONS: Radiomic texture analysis can potentially identify a variety of clinically relevant biomarkers in patients with ccRCC and may have a prognostic implication.

Predicting Soft Tissue Sarcoma Response to Neoadjuvant Chemotherapy Using an MRI-Based Delta-Radiomics Approach.

OBJECTIVES: To evaluate the performance of machine learning-augmented MRI-based radiomics models for predicting response to neoadjuvant chemotherapy (NAC) in soft tissue sarcomas. METHODS: Forty-four subjects were identified retrospectively from patients who received NAC at our institution for pathologically proven soft tissue sarcomas. Only subjects who had both a baseline MRI prior to initiating chemotherapy and a post-treatment scan at least 2 months after initiating chemotherapy and prior to surgical resection were included. 3D ROIs were used to delineate whole-tumor volumes on pre- and post-treatment scans, from which 1708 radiomics features were extracted. Delta-radiomics features were calculated by subtraction of baseline from post-treatment values and used to distinguish treatment response through univariate analyses as well as machine learning-augmented radiomics analyses. RESULTS: Though only 4.74% of variables overall reached significance at p ≤ 0.05 in univariate analyses, Laws Texture Energy (LTE)-derived metrics represented 46.04% of all such features reaching statistical significance. ROC analyses similarly failed to predict NAC response, with AUCs of 0.40 (95% CI 0.22-0.58) and 0.44 (95% CI 0.26-0.62) for RF and AdaBoost, respectively. CONCLUSION: Overall, while our result was not able to separate NAC responders from non-responders, our analyses did identify a subset of LTE-derived metrics that show promise for further investigations. Future studies will likely benefit from larger sample size constructions so as to avoid the need for data filtering and feature selection techniques, which have the potential to significantly bias the machine learning procedures.

CT-based radiomics stratification of tumor grade and TNM stage of clear cell renal cell carcinoma.

OBJECTIVES: To evaluate the utility of CT-based radiomics signatures in discriminating low-grade (grades 1-2) clear cell renal cell carcinomas (ccRCC) from high-grade (grades 3-4) and low TNM stage (stages I-II) ccRCC from high TNM stage (stages III-IV). METHODS: A total of 587 subjects (mean age 60.2 years ± 12.2; range 22-88.7 years) with ccRCC were included. A total of 255 tumors were high grade and 153 were high stage. For each subject, one dominant tumor was delineated as the region of interest (ROI). Our institutional radiomics pipeline was then used to extract 2824 radiomics features across 12 texture families from the manually segmented volumes of interest. Separate iterations of the machine learning models using all extracted features (full model) as well as only a subset of previously identified robust metrics (robust model) were developed. Variable of importance (VOI) analysis was performed using the out-of-bag Gini index to identify the top 10 radiomics metrics driving each classifier. Model performance was reported using area under the receiver operating curve (AUC). RESULTS: The highest AUC to distinguish between low- and high-grade ccRCC was 0.70 (95% CI 0.62-0.78) and the highest AUC to distinguish between low- and high-stage ccRCC was 0.80 (95% CI 0.74-0.86). Comparable AUCs of 0.73 (95% CI 0.65-0.8) and 0.77 (95% CI 0.7-0.84) were reported using the robust model for grade and stage classification, respectively. VOI analysis revealed the importance of neighborhood operation-based methods, including GLCM, GLDM, and GLRLM, in driving the performance of the robust models for both grade and stage classification. CONCLUSION: Post-validation, CT-based radiomics signatures may prove to be useful tools to assess ccRCC grade and stage and could potentially add to current prognostic models. Multiphase CT-based radiomics signatures have potential to serve as a non-invasive stratification schema for distinguishing between low- and high-grade as well as low- and high-stage ccRCC. KEY POINTS: • Radiomics signatures derived from clinical multiphase CT images were able to stratify low- from high-grade ccRCC, with an AUC of 0.70 (95% CI 0.62-0.78). • Radiomics signatures derived from multiphase CT images yielded discriminative power to stratify low from high TNM stage in ccRCC, with an AUC of 0.80 (95% CI 0.74-0.86). • Models created using only robust radiomics features achieved comparable AUCs of 0.73 (95% CI 0.65-0.80) and 0.77 (95% CI 0.70-0.84) to the model with all radiomics features in classifying ccRCC grade and stage, respectively.

Whole-tumor 3D volumetric MRI-based radiomics approach for distinguishing between benign and malignant soft tissue tumors.

OBJECTIVES: Our purpose was to differentiate between malignant from benign soft tissue neoplasms using a combination of MRI-based radiomics metrics and machine learning. METHODS: Our retrospective study identified 128 histologically diagnosed benign (n = 36) and malignant (n = 92) soft tissue lesions. 3D ROIs were manually drawn on 1 sequence of interest and co-registered to other sequences obtained during the same study. One thousand seven hundred eight radiomics features were extracted from each ROI. Univariate analyses with supportive ROC analyses were conducted to evaluate the discriminative power of predictive models constructed using Real Adaptive Boosting (Adaboost) and Random Forest (RF) machine learning approaches. RESULTS: Univariate analyses demonstrated that 36.89% of individual radiomics varied significantly between benign and malignant lesions at the p ≤ 0.05 level. Adaboost and RF performed similarly well, with AUCs of 0.77 (95% CI 0.68-0.85) and 0.72 (95% CI 0.63-0.81), respectively, after 10-fold cross-validation. Restricting the machine learning models to only sequences extracted from T2FS and STIR sequences maintained comparable performance, with AUCs of 0.73 (95% CI 0.64-0.82) and 0.75 (95% CI 0.65-0.84), respectively. CONCLUSION: Machine learning decision classifiers constructed from MRI-based radiomics features show promising ability to preoperatively discriminate between benign and malignant soft tissue masses. Our approach maintains applicability even when the dataset is restricted to T2FS and STIR fluid-sensitive sequences, which may bolster practicality in clinical application scenarios by eliminating the need for complex co-registrations for multisequence analysis. KEY POINTS: • Predictive models constructed from MRI-based radiomics data and machine learning-augmented approaches yielded good discriminative power to correctly classify benign and malignant lesions on preoperative scans, with AUCs of 0.77 (95% CI 0.68-0.85) and 0.72 (95% CI 0.63-0.81) for Real Adaptive Boosting (Adaboost) and Random Forest (RF), respectively. • Restricting the models to only use metrics extracted from T2 fat-saturated (T2FS) and Short-Tau Inversion Recovery (STIR) sequences yielded similar performance, with AUCs of 0.73 (95% CI 0.64-0.82) and 0.75 (95% CI 0.65-0.84) for Adaboost and RF, respectively. • Radiomics-based machine learning decision classifiers constructed from multicentric data more closely mimic the real-world practice environment and warrant additional validation ahead of prospective implementation into clinical workflows.

Imaging of COVID-19: CT, MRI, and PET.

Soon after reports of a novel coronavirus capable of causing severe pneumonia surfaced in late 2019, expeditious global spread of the Severe Acute Respiratory Distress Syndrome Coronavirus 2 (SARS-CoV-2) forced the World Health Organization to declare an international state of emergency. Although best known for causing symptoms of upper respiratory tract infection in mild cases and fulminant pneumonia in severe disease, Coronavirus Disease 2019 (COVID-19) has also been associated with gastrointestinal, neurologic, cardiac, and hematologic presentations. Despite concerns over poor specificity and undue radiation exposure, chest imaging nonetheless remains central to the initial diagnosis and monitoring of COVID-19 progression, as well as to the evaluation of complications. Classic features on chest CT include ground-glass and reticular opacities with or without superimposed consolidations, frequently presenting in a bilateral, peripheral, and posterior distribution. More recently, studies conducted with MRI have shown excellent concordance with chest CT in visualizing typical features of COVID-19 pneumonia. For patients in whom exposure to ionizing radiation should be avoided, particularly pregnant patients and children, pulmonary MRI may represent a suitable alternative to chest CT. Although PET imaging is not typically considered among first-line investigative modalities for the diagnosis of lower respiratory tract infections, numerous reports have noted incidental localization of radiotracer in parenchymal regions of COVID-19-associated pulmonary lesions. These findings are consistent with data from Middle East Respiratory Syndrome-CoV cohorts which suggested an ability for 18F-FDG PET to detect subclinical infection and lymphadenitis in subjects without overt clinical signs of infection. Though highly sensitive, use of PET/CT for primary detection of COVID-19 is constrained by poor specificity, as well as considerations of cost, radiation burden, and prolonged exposure times for imaging staff. Even still, decontamination of scanner bays is a time-consuming process, and proper ventilation of scanner suites may additionally require up to an hour of downtime to allow for sufficient air exchange. Yet, in patients who require nuclear medicine investigations for other clinical indications, PET imaging may yield the earliest detection of nascent infection in otherwise asymptomatic individuals. Especially for patients with concomitant malignancies and other states of immunocompromise, prompt recognition of infection and early initiation of supportive care is crucial to maximizing outcomes and improving survivability.

Coronavirus Disease 2019 (COVID-19): A Modeling Study of Factors Driving Variation in Case Fatality Rate by Country.

Background: The novel Severe Acute Respiratory Syndrome Coronavirus-2 has led to a global pandemic in which case fatality rate (CFR) has varied from country to country. This study aims to identify factors that may explain the variation in CFR across countries. Methods: We identified 24 potential risk factors affecting CFR. For all countries with over 5000 reported COVID-19 cases, we used country-specific datasets from the WHO, the OECD, and the United Nations to quantify each of these factors. We examined univariable relationships of each variable with CFR, as well as correlations among predictors and potential interaction terms. Our final multivariable negative binomial model included univariable predictors of significance and all significant interaction terms. Results: Across the 39 countries under consideration, our model shows COVID-19 case fatality rate was best predicted by time to implementation of social distancing measures, hospital beds per 1000 individuals, percent population over 70 years, CT scanners per 1 million individuals, and (in countries with high population density) smoking prevalence. Conclusion: Our model predicted an increased CFR for countries that waited over 14 days to implement social distancing interventions after the 100th reported case. Smoking prevalence and percentage population over the age of 70 years were also associated with higher CFR. Hospital beds per 1000 and CT scanners per million were identified as possible protective factors associated with decreased CFR.

Coronavirus Disease 2019 (COVID-19) diagnostic technologies: A country-based retrospective analysis of screening and containment procedures during the first wave of the pandemic.

Since first report of a novel coronavirus in December of 2019, the Coronavirus Disease 2019 (COVID-19) pandemic has crippled healthcare systems around the world. While many initial screening protocols centered around laboratory detection of the virus, early testing assays were thought to be poorly sensitive in comparison to chest computed tomography, especially in asymptomatic disease. Coupled with shortages of reverse transcription polymerase chain reaction (RT-PCR) testing kits in many parts of the world, these regions instead turned to the use of advanced imaging as a first-line screening modality. However, in contrast to previous Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome coronavirus epidemics, chest X-ray has not demonstrated optimal sensitivity to be of much utility in first-line screening protocols. Though current national and international guidelines recommend for the use of RT-PCR as the primary screening tool for suspected cases of COVID-19, institutional and regional protocols must consider local availability of resources when issuing universal recommendations. Successful containment and social mitigation strategies worldwide have been thus far predicated on unified governmental responses, though the underlying ideologies of these practices may not be widely applicable in many Western nations. As the strain on the radiology workforce continues to mount, early results indicate a promising role for the use of machine-learning algorithms as risk stratification schema in the months to come.