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Quantitative analysis of computed tomography (CT) images traditionally utilizes real patient data that can pose challenges with replicability, efficiency, and radiation exposure. Instead, virtual imaging trials (VITs) can overcome these hurdles through computer simulations of models of patients and imaging systems. DukeSim is a scanner-specific CT imaging simulator that has previously been validated with simple cylindrical phantoms, but not with anthropomorphic conditions and clinically relevant measurements.To validate a scanner-specific CT simulator (DukeSim) for the assessment of lung imaging biomarkers under clinically relevant conditions across multiple scanners using an anthropomorphic chest phantom, and to demonstrate the utility of virtual trials by studying the effects or radiation dose and reconstruction kernels on the lung imaging quantifications.An anthropomorphic chest phantom with customized tube inserts was imaged with two commercial scanners (Siemens Force and Siemens Flash) at 28 dose and reconstruction conditions. A computational version of the chest phantom was used with a scanner-specific CT simulator (DukeSim) to simulate virtual images corresponding to the settings of the real acquisitions. Lung imaging biomarkers were computed from both real and simulated CT images and quantitatively compared across all imaging conditions. The VIT framework was further utilized to investigate the effects of radiation dose (20-300 mAs) and reconstruction settings (Qr32f, Qr40f, and Qr69f reconstruction kernels using ADMIRE strength 3) on the accuracy of lung imaging biomarkers, compared against the ground-truth values modeled in the computational chest phantom.The simulated CT images matched closely the real images for both scanners and all imaging conditions qualitatively and quantitatively, with the average biomarker percent error of 3.51% (range 0.002%-18.91%). The VIT study showed that sharper reconstruction kernels had lower accuracy with errors in mean lung HU of 84-94 HU, lung volume of 797-3785 cmWe comprehensively evaluated the realism of DukeSim in an anthropomorphic setup across a diverse range of imaging conditions. This study paves the way toward utilizing VITs more reliably for conducting medical imaging experiments that are not practical using actual patient images.

CT imaging provides physicians valuable insights when diagnosing disease in a clinical setting. In order to provide an accurate diagnosis, is it important to have a high accuracy with controlled variability across CT scans from different scanners and imaging parameters. The purpose of this study was to analyze variability of lung imaging biomarkers across various scanners and parameters using a customized version of a commercially available anthropomorphic chest Phantom (Kyoto Kagaku) with several experimental sample inserts. The phantom was across 10 different CT scanners with a total of 209 imaging conditions. An algorithm was developed to compute different imaging biomarkers. Variability across images from the same scanner and from different scanners was analyzed by computing coefficients of variation (CV) and standard deviations of HU values. LAA −950 and LAA −856 biomarkers had the highest levels of variability, while the majority of other biomarkers had variability less than 10 HU or 10% CV in both inter and intra-scan measurements. There was no clear trend present between the biomarker measurements and CTDIvol. The results of this study demonstrates the existing variability in CT quantifications for lung imaging, which prompt further studies on how to reduce such variation.

Traditional methods of quantitative analysis of CT images typically involve working with patient data, which is often expensive and limited in terms of ground truth. To counter these restrictions, quantitative assessments can instead be made through Virtual Imaging Trials (VITs) which simulate the CT imaging process. This study sought to validate DukeSim (a scanner-specific CT simulator) utilizing clinically relevant biomarkers for a customized anthropomorphic chest phantom. The physical phantom was imaged utilizing two commercial CT scanners (Siemens Somatom Force and Definition Flash) with varying imaging parameters. A computational version of the phantom was simulated utilizing DukeSim for each corresponding real acquisition. Biomarkers were computed and compared between the real and virtually acquired CT images to assess the validity of DukeSim. The simulated images closely matched the real images both qualitatively and quantitatively, with the average biomarker percent difference of 3.84% (range 0.19% to 18.27%). Results showed that DukeSim is reasonably well validated across various patient imaging conditions and scanners, which indicates the utility of DukeSim for further VIT studies where real patient data may not be feasible.

Asthma is a heterogeneous disease, with multiple underlying inflammatory pathways and structural airway abnormalities that impact disease persistence and severity. Recent progress has been made in developing targeted asthma therapeutics, especially for subjects with eosinophilic asthma. However, there is an unmet need for new approaches to treat patients with severe and exacerbation-prone asthma, who contribute disproportionately to disease burden. Extensive deep phenotyping has revealed the heterogeneous nature of severe asthma and identified distinct disease subtypes. Acurrent challenge in the field is to translate new and emerging knowledge about different pathobiologic mechanisms in asthma into patient-specific therapies, with the ultimate goal of modifying the natural history of disease. Here, we describe the Precision Interventions for Severe and/or Exacerbation-Prone Asthma (PrecISE) Network, a groundbreaking collaborative effort of asthma researchers and biostatisticians from around the United States. The PrecISE Network was designed to conduct phase II/proof-of-concept clinical trials of precision interventions in the population with severe asthma, and is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health. Using an innovative adaptive platform trial design, the PrecISE Network will evaluate up to 6 interventions simultaneously in biomarker-defined subgroups of subjects. We review the development and organizational structure of the PrecISE Network, and choice of interventions being studied. We hope that the PrecISE Network will enhance our understanding of asthma subtypes and accelerate the development of therapeutics for severe asthma.