13 research outputs found

    Predicting clinical outcomes in Glioblastoma: an application of topological and functional data analysis

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    Glioblastoma multiforme (GBM) is an aggressive form of human brain cancer that is under active study in the field of cancer biology. Its rapid progression and the relative time cost of obtaining molecular data make other readily available forms of data, such as images, an important resource for actionable measures in patients. Our goal is to use information given by medical images taken from GBM patients in statistical settings. To do this, we design a novel statistic—the smooth Euler characteristic transform (SECT)—that quantifies magnetic resonance images of tumors. Due to its well-defined inner product structure, the SECT can be used in a wider range of functional and nonparametric modeling approaches than other previously proposed topological summary statistics. When applied to a cohort of GBM patients, we find that the SECT is a better predictor of clinical outcomes than both existing tumor shape quantifications and common molecular assays. Specifically, we demonstrate that SECT features alone explain more of the variance in GBM patient survival than gene expression, volumetric features, and morphometric features. The main takeaways from our findings are thus 2-fold. First, they suggest that images contain valuable information that can play an important role in clinical prognosis and other medical decisions. Second, they show that the SECT is a viable tool for the broader study of medical imaging informatics. Supplementary materials for this article, including a standardized description of the materials available for reproducing the work, are available as an online supplement

    Histopathological image analysis with connections to genomics

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    The fields of imaging and genomics in cancer research have been mostly studied independently, but recently available datasets have made investigation into the synergy of these two fields possible. This work demonstrates the efficacy of computational histopathological image analysis to extract meaningful quantitative nuclear and cellular features from hematoxylin and eosin stained images that have meaningful connections to genomic data. Additionally, with the advent of whole slide images, significantly more data representing the variation in nuclear characteristics and tumor heterogeneity is available, which can aid in developing new analytical tools, such as the proposed convolutional neural network for nuclear segmentation, which produces state-of-the-art segmentation results on challenging cases seen in normal pathology. This robust segmentation tool is essential for capturing reliable features for computational pathology. Additionally, whole slide images capture rich spatial information about tumors, which presents a challenge, but also an opportunity for the development of new image processing tools to capture this spatial information, which could be considered for future work. Other histopathological image modalities and relevant machine learning tools are also considered for elucidating cellular processes of cancer

    Localization of Diagnostically Relevant Regions of Interest in Whole Slide Images: a Comparative Study

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    Whole slide digital imaging technology enables researchers to study pathologists’ interpretive behavior as they view digital slides and gain new understanding of the diagnostic medical decision-making process. In this study, we propose a simple yet important analysis to extract diagnostically relevant regions of interest (ROIs) from tracking records using only pathologists’ actions as they viewed biopsy specimens in the whole slide digital imaging format (zooming, panning, and fixating). We use these extracted regions in a visual bag-of-words model based on color and texture features to predict diagnostically relevant ROIs on whole slide images. Using a logistic regression classifier in a cross-validation setting on 240 digital breast biopsy slides and viewport tracking logs of three expert pathologists, we produce probability maps that show 74 % overlap with the actual regions at which pathologists looked. We compare different bag-of-words models by changing dictionary size, visual word definition (patches vs. superpixels), and training data (automatically extracted ROIs vs. manually marked ROIs). This study is a first step in understanding the scanning behaviors of pathologists and the underlying reasons for diagnostic errors. © 2016, Society for Imaging Informatics in Medicine

    Image analysis with deep learning to predict breast cancer grade, ER status, histologic subtype, and intrinsic subtype

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    RNA-based, multi-gene molecular assays are available and widely used for patients with ER-positive/HER2-negative breast cancers. However, RNA-based genomic tests can be costly and are not available in many countries. Methods for inferring molecular subtype from histologic images may identify patients most likely to benefit from further genomic testing. To identify patients who could benefit from molecular testing based on H&E stained histologic images, we developed an image analysis approach using deep learning. A training set of 571 breast tumors was used to create image-based classifiers for tumor grade, ER status, PAM50 intrinsic subtype, histologic subtype, and risk of recurrence score (ROR-PT). The resulting classifiers were applied to an independent test set (n = 288), and accuracy, sensitivity, and specificity of each was assessed on the test set. Histologic image analysis with deep learning distinguished low-intermediate vs. high tumor grade (82% accuracy), ER status (84% accuracy), Basal-like vs. non-Basal-like (77% accuracy), Ductal vs. Lobular (94% accuracy), and high vs. low-medium ROR-PT score (75% accuracy). Sampling considerations in the training set minimized bias in the test set. Incorrect classification of ER status was significantly more common for Luminal B tumors. These data provide proof of principle that molecular marker status, including a critical clinical biomarker (i.e., ER status), can be predicted with accuracy >75% based on H&E features. Image-based methods could be promising for identifying patients with a greater need for further genomic testing, or in place of classically scored variables typically accomplished using human-based scoring

    Discriminative Representations for Heterogeneous Images and Multimodal Data

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    Histology images of tumor tissue are an important diagnostic and prognostic tool for pathologists. Recently developed molecular methods group tumors into subtypes to further guide treatment decisions, but they are not routinely performed on all patients. A lower cost and repeatable method to predict tumor subtypes from histology could bring benefits to more cancer patients. Further, combining imaging and genomic data types provides a more complete view of the tumor and may improve prognostication and treatment decisions. While molecular and genomic methods capture the state of a small sample of tumor, histological image analysis provides a spatial view and can identify multiple subtypes in a single tumor. This intra-tumor heterogeneity has yet to be fully understood and its quantification may lead to future insights into tumor progression. In this work, I develop methods to learn appropriate features directly from images using dictionary learning or deep learning. I use multiple instance learning to account for intra-tumor variations in subtype during training, improving subtype predictions and providing insights into tumor heterogeneity. I also integrate image and genomic features to learn a projection to a shared space that is also discriminative. This method can be used for cross-modal classification or to improve predictions from images by also learning from genomic data during training, even if only image data is available at test time.Doctor of Philosoph

    Optimizing the Privacy Risk - Utility Framework in Data Publication

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    Identifying Relevant Evidence for Systematic Reviews and Review Updates

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    Systematic reviews identify, assess and synthesise the evidence available to answer complex research questions. They are essential in healthcare, where the volume of evidence in scientific research publications is vast and cannot feasibly be identified or analysed by individual clinicians or decision makers. However, the process of creating a systematic review is time consuming and expensive. The pace of scientific publication in medicine and related fields also means that evidence bases are continually changing and review conclusions can quickly become out of date. Therefore, developing methods to support the creating and updating of reviews is essential to reduce the workload required and thereby ensure that reviews remain up to date. This research aims to support systematic reviews, thus improving healthcare through natural language processing and information retrieval techniques. More specifically, this thesis aims to support the process of identifying relevant evidence for systematic reviews and review updates to reduce the workload required from researchers. This research proposes methods to improve studies ranking for systematic reviews. In addition, this thesis describes a dataset of systematic review updates in the field of medicine created using 25 Cochrane reviews. Moreover, this thesis develops an algorithm to automatically refine the Boolean query to improve the identification of relevant studies for review updates. The research demonstrates that automating the process of identifying relevant evidence can reduce the workload of conducting and updating systematic reviews
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