A Rapid Segmentation-Insensitive "Digital Biopsy" Method for Radiomic Feature Extraction: Method and Pilot Study Using CT Images of Non-Small Cell Lung Cancer.

Quantitative imaging approaches compute features within images' regions of interest. Segmentation is rarely completely automatic, requiring time-consuming editing by experts. We propose a new paradigm, called "digital biopsy," that allows for the collection of intensity- and texture-based features from these regions at least 1 order of magnitude faster than the current manual or semiautomated methods. A radiologist reviewed automated segmentations of lung nodules from 100 preoperative volume computed tomography scans of patients with non-small cell lung cancer, and manually adjusted the nodule boundaries in each section, to be used as a reference standard, requiring up to 45 minutes per nodule. We also asked a different expert to generate a digital biopsy for each patient using a paintbrush tool to paint a contiguous region of each tumor over multiple cross-sections, a procedure that required an average of <3 minutes per nodule. We simulated additional digital biopsies using morphological procedures. Finally, we compared the features extracted from these digital biopsies with our reference standard using intraclass correlation coefficient (ICC) to characterize robustness. Comparing the reference standard segmentations to our digital biopsies, we found that 84/94 features had an ICC >0.7; comparing erosions and dilations, using a sphere of 1.5-mm radius, of our digital biopsies to the reference standard segmentations resulted in 41/94 and 53/94 features, respectively, with ICCs >0.7. We conclude that many intensity- and texture-based features remain consistent between the reference standard and our method while substantially reducing the amount of operator time required

Towards automatic pulmonary nodule management in lung cancer screening with deep learning

The introduction of lung cancer screening programs will produce an unprecedented amount of chest CT scans in the near future, which radiologists will have to read in order to decide on a patient follow-up strategy. According to the current guidelines, the workup of screen-detected nodules strongly relies on nodule size and nodule type. In this paper, we present a deep learning system based on multi-stream multi-scale convolutional networks, which automatically classifies all nodule types relevant for nodule workup. The system processes raw CT data containing a nodule without the need for any additional information such as nodule segmentation or nodule size and learns a representation of 3D data by analyzing an arbitrary number of 2D views of a given nodule. The deep learning system was trained with data from the Italian MILD screening trial and validated on an independent set of data from the Danish DLCST screening trial. We analyze the advantage of processing nodules at multiple scales with a multi-stream convolutional network architecture, and we show that the proposed deep learning system achieves performance at classifying nodule type that surpasses the one of classical machine learning approaches and is within the inter-observer variability among four experienced human observers.Comment: Published on Scientific Report

Histogram-based models on non-thin section chest CT predict invasiveness of primary lung adenocarcinoma subsolid nodules.

109 pathologically proven subsolid nodules (SSN) were segmented by 2 readers on non-thin section chest CT with a lung nodule analysis software followed by extraction of CT attenuation histogram and geometric features. Functional data analysis of histograms provided data driven features (FPC1,2,3) used in further model building. Nodules were classified as pre-invasive (P1, atypical adenomatous hyperplasia and adenocarcinoma in situ), minimally invasive (P2) and invasive adenocarcinomas (P3). P1 and P2 were grouped together (T1) versus P3 (T2). Various combinations of features were compared in predictive models for binary nodule classification (T1/T2), using multiple logistic regression and non-linear classifiers. Area under ROC curve (AUC) was used as diagnostic performance criteria. Inter-reader variability was assessed using Cohen's Kappa and intra-class coefficient (ICC). Three models predicting invasiveness of SSN were selected based on AUC. First model included 87.5 percentile of CT lesion attenuation (Q.875), interquartile range (IQR), volume and maximum/minimum diameter ratio (AUC:0.89, 95%CI:[0.75 1]). Second model included FPC1, volume and diameter ratio (AUC:0.91, 95%CI:[0.77 1]). Third model included FPC1, FPC2 and volume (AUC:0.89, 95%CI:[0.73 1]). Inter-reader variability was excellent (Kappa:0.95, ICC:0.98). Parsimonious models using histogram and geometric features differentiated invasive from minimally invasive/pre-invasive SSN with good predictive performance in non-thin section CT

Unlocking biomarker discovery: Large scale application of aptamer proteomic technology for early detection of lung cancer

Lung cancer is the leading cause of cancer deaths, because ~84% of cases are diagnosed at an advanced stage. Worldwide in 2008, ~1.5 million people were diagnosed and ~1.3 million died – a survival rate unchanged since 1960. However, patients diagnosed at an early stage and have surgery experience an 86% overall 5-year survival. New diagnostics are therefore needed to identify lung cancer at this stage. Here we present the first large scale clinical use of aptamers to discover blood protein biomarkers in disease with our breakthrough proteomic technology. This multi-center case-control study was conducted in archived samples from 1,326 subjects from four independent studies of non-small cell lung cancer (NSCLC) in long-term tobacco-exposed populations. We measured >800 proteins in 15uL of serum, identified 44 candidate biomarkers, and developed a 12-protein panel that distinguished NSCLC from controls with 91% sensitivity and 84% specificity in a training set and 89% sensitivity and 83% specificity in a blinded, independent verification set. Performance was similar for early and late stage NSCLC. This is a significant advance in proteomics in an area of high clinical need

Anomaly Detection for imbalanced datasets with Deep Generative Models

Many important data analysis applications present with severely imbalanced datasets with respect to the target variable. A typical example is medical image analysis, where positive samples are scarce, while performance is commonly estimated against the correct detection of these positive examples. We approach this challenge by formulating the problem as anomaly detection with generative models. We train a generative model without supervision on the `negative' (common) datapoints and use this model to estimate the likelihood of unseen data. A successful model allows us to detect the `positive' case as low likelihood datapoints. In this position paper, we present the use of state-of-the-art deep generative models (GAN and VAE) for the estimation of a likelihood of the data. Our results show that on the one hand both GANs and VAEs are able to separate the `positive' and `negative' samples in the MNIST case. On the other hand, for the NLST case, neither GANs nor VAEs were able to capture the complexity of the data and discriminate anomalies at the level that this task requires. These results show that even though there are a number of successes presented in the literature for using generative models in similar applications, there remain further challenges for broad successful implementation.Comment: 15 pages, 13 figures, accepted by Benelearn 2018 conferenc