Simple and Effective Visual Models for Gene Expression Cancer Diagnostics

In the paper we show that diagnostic classes in cancer gene expression data sets, which most often include thousands of features (genes), may be effectively separated with simple two-dimensional plots such as scatterplot and radviz graph. The principal innovation proposed in the paper is a method called VizRank, which is able to score and identify the best among possibly millions of candidate projections for visualizations. Compared to recently much applied techniques in the field of cancer genomics that include neural networks, support vector machines and various ensemble-based approaches, VizRank is fast and finds visualization models that can be easily examined and interpreted by domain experts. Our experiments on a number of gene expression data sets show that VizRank was always able to find data visualizations with a small number of (two to seven) genes and excellent class separation. In addition to providing grounds for gene expression cancer diagnosis, VizRank and its visualizations also identify small sets of relevant genes, uncover interesting gene interactions and point to outliers and potential misclassifications in cancer data sets

The value of MR textural analysis in prostate cancer

Current diagnosis and treatment stratification of patients with suspected prostate cancer relies on a combination of histological and magnetic resonance imaging (MRI) findings. The aim of this article is to provide a brief overview of prostate pathological grading as well as the relevant aspects of multiparametric (MRI) mpMRI, before indicating the potential that magnetic resonance textural analysis (MRTA) offers within prostate cancer. A review of the evidence base on MRTA in prostate cancer will enable discussion of the utility of this field while also indicating recommendations to future research. Radiomic textural analysis allows the assessment of spatial inter-relationships between pixels within an image by use of mathematical methods. First-order textural analysis is better understood and may have more clinical validity than higher-order textural features. Textural features extracted from apparent diffusion coefficient maps have shown the most potential for clinical utility in MRTA of prostate cancers. Future studies should aim to integrate machine learning techniques to better represent the role of MRTA in prostate cancer clinical practice. Nomenclature should be used to reduce misidentification between first-order and second-order energy and entropy. Automated methods of segmentation should be encouraged in order to reduce problems associated with inclusion of normal tissue within regions of interest. The retrospective and small-scale nature of most published studies, make it difficult to draw meaningful conclusions. Future larger prospective studies are required to validate the textural features indicated to have potential in characterisation and/or diagnosis of prostate cancer before translation into routine clinical practice

Machine Learning Methods for Breast Cancer Diagnostic

This chapter discusses radio-pathological correlation with recent imaging advances such as machine learning (ML) with the use of technical methods such as mammography and histopathology. Although criteria for diagnostic categories for radiology and pathology are well established, manual detection and grading, respectively, are tedious and subjective processes and thus suffer from inter-observer and intra-observer variations. Two most popular techniques that use ML, computer aided detection (CADe) and computer aided diagnosis (CADx), are presented. CADe is a rejection model based on SVM algorithm which is used to reduce the False Positive (FP) of the output of the Chan-Vese segmentation algorithm that was initialized by the marker controller watershed (MCWS) algorithm. CADx method applies the ensemble framework, consisting of four-base SVM (RBF) classifiers, where each base classifier is a specialist and is trained to use the selected features of a particular tissue component. In general, both proposed methods offer alternative decision-making ability and are able to assist the medical expert in giving second opinion on more precise nodule detection. Hence, it reduces FP rate that causes over segmentation and improves the performance for detection and diagnosis of the breast cancer and is able to create a platform that integrates diagnostic reporting system

Optimization and Machine Learning Methods for Diagnostic Testing of Prostate Cancer

Technological advances in biomarkers and imaging tests are creating new avenues to advance precision health for early detection of cancer. These advances have resulted in multiple layers of information that can be used to make clinical decisions, but how to best use these multiple sources of information is a challenging engineering problem due to the high cost and imperfect sensitivity and specificity of these tests. Questions that need to be addressed include which diagnostic tests to choose and how to best integrate them, in order to optimally balance the competing goals of early disease detection and minimal cost and harm from unnecessary testing. To study these research questions, we present new optimization-based models and data-driven analytic methods in three parts to improve early detection of prostate cancer (PCa). In the first part, we develop and validate predictive models to assess individual PCa risk using known clinical risk factors. Because not all men with newly-diagnosed PCa received imaging at diagnosis, we use an established method to correct for verification bias to evaluate the accuracy of published imaging guidelines. In addition to the published guidelines, we implement advanced classification modeling techniques to develop accurate classification rules identifying which patients should receive imaging. We propose a new algorithm for a classification model that considers information of patients with unverified disease and the high cost of misclassifying a metastatic patient. We summarize our development and implementation of state-wide, evidence-based imaging criteria that weigh the benefits and harms of radiological imaging for detection of metastatic PCa. In the second part of this thesis, we combine optimization and machine learning approaches into a robust optimization framework to design imaging guidelines that can account for imperfect calibration of predictions. We investigate efficient and effective ways to combine multiple medical diagnostic tests where the result of one test may be used to predict the outcome of another. We analyze the properties of the proposed optimization models from the perspectives of multiple stakeholders, and we present the results of fast approximation methods that we show can be used to solve large-scale models. In the third and final part of this thesis, we investigate the optimal design of composite multi-biomarker tests to achieve early detection of prostate cancer. Biomarker tests vary significantly in cost, and cause false positive and false negative results, leading to serious health implications for patients. Since no single biomarker on its own is considered satisfactory, we utilize simulation and statistical methods to develop the optimal diagnosis procedure for early detection of PCa consisting of a sequence of biomarker tests, balancing the benefits of early detection, such as increased survival, with the harms of testing, such as unnecessary prostate biopsies. In this dissertation, we identify new principles and methods to guide the design of early detection protocols for PCa using new diagnostic technologies. We provide important clinical evidence that can be used to improve health outcomes of patients while reducing wasteful application of diagnostic tests to patients for whom they are not effective. Moreover, some of the findings of this dissertation have been implemented directly into clinical practice in the state of Michigan. The models and methodologies we present in this thesis are not limited to PCa, and can be applied to a broad range of chronic diseases for which diagnostic tests are available.PHDIndustrial & Operations EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/143976/1/smerdan_1.pd

Radiomics in prostate cancer: an up-to-date review

: Prostate cancer (PCa) is the most common worldwide diagnosed malignancy in male population. The diagnosis, the identification of aggressive disease, and the post-treatment follow-up needs a more comprehensive and holistic approach. Radiomics is the extraction and interpretation of images phenotypes in a quantitative manner. Radiomics may give an advantage through advancements in imaging modalities and through the potential power of artificial intelligence techniques by translating those features into clinical outcome prediction. This article gives an overview on the current evidence of methodology and reviews the available literature on radiomics in PCa patients, highlighting its potential for personalized treatment and future applications

Question Classification in the Cancer Domain

We are investigating question classification for restricted domains with the broader goal of supporting mixed-initiative interaction on mobile phones. In this thesis, we present the development of a new domain-specific corpus of cancer-related questions, a new taxonomy of Expected Answer types, and our efforts toward training a classifier. This work is the first of its kind in the cancer domain using a corpus consisting of real user questions gathered from cQA websites, and a taxonomy built from that corpus. Our goal is to create software to engage newly diagnosed prostate cancer patients in question-answering dialogs related to their treatment options. We are focusing our work on the interaction environment afforded by text and multimedia (SMS and MMS) messaging using mobile telephones, because of the prevalence of this technology and the growing popularity of text messaging, especially among underserved populations

Artificial intelligence in histopathology image analysis for cancer precision medicine

In recent years, there have been rapid advancements in the field of computational pathology. This has been enabled through the adoption of digital pathology workflows that generate digital images of histopathological slides, the publication of large data sets of these images and improvements in computing infrastructure. Objectives in computational pathology can be subdivided into two categories, first the automation of routine workflows that would otherwise be performed by pathologists and second the addition of novel capabilities. This thesis focuses on the development, application, and evaluation of methods in this second category, specifically the prediction of gene expression from pathology images and the registration of pathology images among each other. In Study I, we developed a computationally efficient cluster-based technique to perform transcriptome-wide predictions of gene expression in prostate cancer from H&E-stained whole-slide-images (WSIs). The suggested method outperforms several baseline methods and is non-inferior to single-gene CNN predictions, while reducing the computational cost with a factor of approximately 300. We included 15,586 transcripts that encode proteins in the analysis and predicted their expression with different modelling approaches from the WSIs. In a cross-validation, 6,618 of these predictions were significantly associated with the RNA-seq expression estimates with FDR-adjusted p-values <0.001. Upon validation of these 6,618 expression predictions in a held-out test set, the association could be confirmed for 5,419 (81.9%). Furthermore, we demonstrated that it is feasible to predict the prognostic cell-cycle progression score with a Spearman correlation to the RNA-seq score of 0.527 [0.357, 0.665]. The objective of Study II is the investigation of attention layers in the context of multiple-instance-learning for regression tasks, exemplified by a simulation study and gene expression prediction. We find that for gene expression prediction, the compared methods are not distinguishable regarding their performance, which indicates that attention mechanisms may not be superior to weakly supervised learning in this context. Study III describes the results of the ACROBAT 2022 WSI registration challenge, which we organised in conjunction with the MICCAI 2022 conference. Participating teams were ranked on the median 90th percentile of distances between registered and annotated target landmarks. Median 90th percentiles for eight teams that were eligible for ranking in the test set consisting of 303 WSI pairs ranged from 60.1 µm to 15,938.0 µm. The best performing method therefore has a score slightly below the median 90th percentile of distances between first and second annotator of 67.0 µm. Study IV describes the data set that we published to facilitate the ACROBAT challenge. The data set is available publicly through the Swedish National Data Service SND and consists of 4,212 WSIs from 1,153 breast cancer patients. Study V is an example of the application of WSI registration for computational pathology. In this study, we investigate the possibility to register invasive cancer annotations from H&E to KI67 WSIs and then subsequently train cancer detection models. To this end, we compare the performance of models optimised with registered annotations to the performance of models that were optimised with annotations generated for the KI67 WSIs. The data set consists of 272 female breast cancer cases, including an internal test set of 54 cases. We find that in this test set, the performance of both models is not distinguishable regarding performance, while there are small differences in model calibration

Datenbasierte Ansätze für moderne klinische Risikovorhersagen

In this thesis the use of data scientific approaches in the life sciences is illustrated by means of contemporary prostate cancer risk models. Validation techniques are introduced and analytical confidence intervals for selected methods derived. In addition, diverse regression approaches to incorporate heterogeneous cohorts, an update of an online available risk calculator and machine learning methods are analyzed and compared.In der vorliegenden Arbeit wird der Einsatz von datenbasierten Ansätzen in den Lebenswissenschaften anhand von zeitgemäßen Risikomodellen für Prostatakrebs dargestellt. Validierungstechniken werden eingeführt und analytische Konfidenzintervalle für ausgewählte Methoden hergeleitet. Des Weiteren werden verschiedene Regressionsansätze zur Integration von heterogenen Kohorten, eine Aktualisierung eines online verfügbaren Risikorechners und Methoden des maschinellen Lernens analysiert und verglichen

Deep learning applications in the prostate cancer diagnostic pathway

Prostate cancer (PCa) is the second most frequently diagnosed cancer in men worldwide and the fifth leading cause of cancer death in men, with an estimated 1.4 million new cases in 2020 and 375,000 deaths. The risk factors most strongly associated to PCa are advancing age, family history, race, and mutations of the BRCA genes. Since the aforementioned risk factors are not preventable, early and accurate diagnoses are a key objective of the PCa diagnostic pathway. In the UK, clinical guidelines recommend multiparametric magnetic resonance imaging (mpMRI) of the prostate for use by radiologists to detect, score, and stage lesions that may correspond to clinically significant PCa (CSPCa), prior to confirmatory biopsy and histopathological grading. Computer-aided diagnosis (CAD) of PCa using artificial intelligence algorithms holds a currently unrealized potential to improve upon the diagnostic accuracy achievable by radiologist assessment of mpMRI, improve the reporting consistency between radiologists, and reduce reporting time. In this thesis, we build and evaluate deep learning-based CAD systems for the PCa diagnostic pathway, which address gaps identified in the literature. First, we introduce a novel patient-level classification framework, PCF, which uses a stacked ensemble of convolutional neural networks (CNNs) and support vector machines (SVMs) to assign a probability of having CSPCa to patients, using mpMRI and clinical features. Second, we introduce AutoProstate, a deep-learning powered framework for automated PCa assessment and reporting; AutoProstate utilizes biparametric MRI and clinical data to populate an automatic diagnostic report containing segmentations of the whole prostate, prostatic zones, and candidate CSPCa lesions, as well as several derived characteristics that are clinically valuable. Finally, as automatic segmentation algorithms have not yet reached the desired robustness for clinical use, we introduce interactive click-based segmentation applications for the whole prostate and prostatic lesions, with potential uses in diagnosis, active surveillance progression monitoring, and treatment planning