The Image Biomarker Standardization Initiative validated consensus-based reference values for 169 radiomics features, thus enabling calibration and verification of radiomics software. Key results: • research teams found agreement for calculation of 169 radiomics features derived from a digital phantom and a human lung cancer on CT scan. • Of these 169 candidate radiomics features, good to excellent reproducibility was achieved for 167 radiomics features using MRI, 18F-FDG PET and CT images obtained in 51 patients with soft-tissue sarcoma.

We explored the clinical and pathological impact of epidermal growth factor receptor (EGFR) extracellular domain missense mutations. Retrospective assessment of 260 de novo glioblastoma patients revealed a significant reduction in overall survival of patients having tumors with EGFR mutations at alanine 289 (EGFR). Quantitative multi-parametric magnetic resonance imaging analyses indicated increased tumor invasion for EGFR mutants, corroborated in mice bearing intracranial tumors expressing EGFR and dependent on ERK-mediated expression of matrix metalloproteinase-1. EGFR tumor growth was attenuated with an antibody against a cryptic epitope, based on in silico simulation. The findings of this study indicate a highly invasive phenotype associated with the EGFR mutation in glioblastoma, postulating EGFR as a molecular marker for responsiveness to therapy with EGFR-targeting antibodies.

No abstract

Brain extraction, or skull-stripping, is an essential pre-processing step in neuro-imaging that has a direct impact on the quality of all subsequent processing and analyses steps. It is also a key requirement in multi-institutional collaborations to comply with privacy-preserving regulations. Existing automated methods, including Deep Learning (DL) based methods that have obtained state-of-the-art results in recent years, have primarily targeted brain extraction without considering pathologically-affected brains. Accordingly, they perform sub-optimally when applied on magnetic resonance imaging (MRI) brain scans with apparent pathologies such as brain tumors. Furthermore, existing methods focus on using only T1-weighted MRI scans, even though multi-parametric MRI (mpMRI) scans are routinely acquired for patients with suspected brain tumors. In this study, we present a comprehensive performance evaluation of recent deep learning architectures for brain extraction, training models on mpMRI scans of pathologically-affected brains, with a particular focus on seeking a practically-applicable, low computational footprint approach, generalizable across multiple institutions, further facilitating collaborations. We identified a large retrospective multi-institutional dataset of n = 3340 mpMRI brain tumor scans, with manually-inspected and approved gold-standard segmentations, acquired during standard clinical practice under varying acquisition protocols, both from private institutional data and public (TCIA) collections. To facilitate optimal utilization of rich mpMRI data, we further introduce and evaluate a novel “modality-agnostic training” technique that can be applied using any available modality, without need for model retraining. Our results indicate that the modality-agnostic approach 1 obtains accurate results, providing a generic and practical tool for brain extraction on scans with brain tumors.

PURPOSE To construct a multi-institutional radiomic model that supports upfront prediction of progression-free survival (PFS) and recurrence pattern (RP) in patients diagnosed with glioblastoma multiforme (GBM) at the time of initial diagnosis. PATIENTS AND METHODS We retrospectively identified data for patients with newly diagnosed GBM from two institutions (institution 1, n = 65; institution 2, n = 15) who underwent gross total resection followed by standard adjuvant chemoradiation therapy, with pathologically confirmed recurrence, sufficient follow-up magnetic resonance imaging (MRI) scans to reliably determine PFS, and available presurgical multiparametric MRI (MP-MRI). The advanced software suite Cancer Imaging Phenomics Toolkit (CaPTk) was leveraged to analyze standard clinical brain MP-MRI scans. A rich set of imaging features was extracted from the MP-MRI scans acquired before the initial resection and was integrated into two distinct imaging signatures for predicting mean shorter or longer PFS and near or distant RP. The predictive signatures for PFS and RP were evaluated on the basis of different classification schemes: single-institutional analysis, multi-institutional analysis with random partitioning of the data into discovery and replication cohorts, and multi-institutional assessment with data from institution 1 as the discovery cohort and data from institution 2 as the replication cohort. RESULTS These predictors achieved cross-validated classification performance (ie, area under the receiver operating characteristic curve) of 0.88 (single-institution analysis) and 0.82 to 0.83 (multi-institution analysis) for prediction of PFS and 0.88 (single-institution analysis) and 0.56 to 0.71 (multi-institution analysis) for prediction of RP. CONCLUSION Imaging signatures of presurgical MP-MRI scans reveal relatively high predictability of time and location of GBM recurrence, subject to the patients receiving standard first-line chemoradiation therapy. Through its graphical user interface, CaPTk offers easy accessibility to advanced computational algorithms for deriving imaging signatures predictive of clinical outcome and could similarly be used for a variety of radiomic and radiogenomic analyses.

No abstract

We utilize a multiscale modeling framework to study the effect of shape, size, and ligand composition on the efficacy of binding of a ligand-coated particle to a substrate functionalized with the target receptors. First, we show how molecular dynamics along with steered molecular dynamics calculations can be used to accurately parameterize the molecular-binding free energy and the effective spring constant for a receptor-ligand pair. We demonstrate this for two ligands that bind to the αβ-domain of integrin. Next, we show how these effective potentials can be used to build computational models at the meso- and continuum-scales. These models incorporate the molecular nature of the receptor-ligand interactions and yet provide an inexpensive route to study the multivalent interaction of receptors and ligands through the construction of Bell potentials customized to the molecular identities. We quantify the binding efficacy of the ligand-coated-particle in terms of its multivalency, binding free-energy landscape, and the losses in the configurational entropies. We show that 1) the binding avidity for particle sizes less than 350 nm is set by the competition between the enthalpic and entropic contributions, whereas that for sizes above 350 nm is dominated by the enthalpy of binding; 2) anisotropic particles display higher levels of multivalent binding compared to those of spherical particles; and 3) variations in ligand composition can alter binding avidity without altering the average multivalency. The methods and results presented here have wide applications in the rational design of functionalized carriers and also in understanding cell adhesion.

No abstract