Evaluation of linear classifiers on articles containing pharmacokinetic evidence of drug-drug interactions

Background. Drug-drug interaction (DDI) is a major cause of morbidity and mortality. [...] Biomedical literature mining can aid DDI research by extracting relevant DDI signals from either the published literature or large clinical databases. However, though drug interaction is an ideal area for translational research, the inclusion of literature mining methodologies in DDI workflows is still very preliminary. One area that can benefit from literature mining is the automatic identification of a large number of potential DDIs, whose pharmacological mechanisms and clinical significance can then be studied via in vitro pharmacology and in populo pharmaco-epidemiology. Experiments. We implemented a set of classifiers for identifying published articles relevant to experimental pharmacokinetic DDI evidence. These documents are important for identifying causal mechanisms behind putative drug-drug interactions, an important step in the extraction of large numbers of potential DDIs. We evaluate performance of several linear classifiers on PubMed abstracts, under different feature transformation and dimensionality reduction methods. In addition, we investigate the performance benefits of including various publicly-available named entity recognition features, as well as a set of internally-developed pharmacokinetic dictionaries. Results. We found that several classifiers performed well in distinguishing relevant and irrelevant abstracts. We found that the combination of unigram and bigram textual features gave better performance than unigram features alone, and also that normalization transforms that adjusted for feature frequency and document length improved classification. For some classifiers, such as linear discriminant analysis (LDA), proper dimensionality reduction had a large impact on performance. Finally, the inclusion of NER features and dictionaries was found not to help classification.Comment: Pacific Symposium on Biocomputing, 201

3D Shape Reconstruction from Sketches via Multi-view Convolutional Networks

We propose a method for reconstructing 3D shapes from 2D sketches in the form of line drawings. Our method takes as input a single sketch, or multiple sketches, and outputs a dense point cloud representing a 3D reconstruction of the input sketch(es). The point cloud is then converted into a polygon mesh. At the heart of our method lies a deep, encoder-decoder network. The encoder converts the sketch into a compact representation encoding shape information. The decoder converts this representation into depth and normal maps capturing the underlying surface from several output viewpoints. The multi-view maps are then consolidated into a 3D point cloud by solving an optimization problem that fuses depth and normals across all viewpoints. Based on our experiments, compared to other methods, such as volumetric networks, our architecture offers several advantages, including more faithful reconstruction, higher output surface resolution, better preservation of topology and shape structure.Comment: 3DV 2017 (oral

Computerized Analysis of Magnetic Resonance Images to Study Cerebral Anatomy in Developing Neonates

The study of cerebral anatomy in developing neonates is of great importance for the understanding of brain development during the early period of life. This dissertation therefore focuses on three challenges in the modelling of cerebral anatomy in neonates during brain development. The methods that have been developed all use Magnetic Resonance Images (MRI) as source data. To facilitate study of vascular development in the neonatal period, a set of image analysis algorithms are developed to automatically extract and model cerebral vessel trees. The whole process consists of cerebral vessel tracking from automatically placed seed points, vessel tree generation, and vasculature registration and matching. These algorithms have been tested on clinical Time-of- Flight (TOF) MR angiographic datasets. To facilitate study of the neonatal cortex a complete cerebral cortex segmentation and reconstruction pipeline has been developed. Segmentation of the neonatal cortex is not effectively done by existing algorithms designed for the adult brain because the contrast between grey and white matter is reversed. This causes pixels containing tissue mixtures to be incorrectly labelled by conventional methods. The neonatal cortical segmentation method that has been developed is based on a novel expectation-maximization (EM) method with explicit correction for mislabelled partial volume voxels. Based on the resulting cortical segmentation, an implicit surface evolution technique is adopted for the reconstruction of the cortex in neonates. The performance of the method is investigated by performing a detailed landmark study. To facilitate study of cortical development, a cortical surface registration algorithm for aligning the cortical surface is developed. The method first inflates extracted cortical surfaces and then performs a non-rigid surface registration using free-form deformations (FFDs) to remove residual alignment. Validation experiments using data labelled by an expert observer demonstrate that the method can capture local changes and follow the growth of specific sulcus

Multi-Material Mesh Representation of Anatomical Structures for Deep Brain Stimulation Planning

The Dual Contouring algorithm (DC) is a grid-based process used to generate surface meshes from volumetric data. However, DC is unable to guarantee 2-manifold and watertight meshes due to the fact that it produces only one vertex for each grid cube. We present a modified Dual Contouring algorithm that is capable of overcoming this limitation. The proposed method decomposes an ambiguous grid cube into a set of tetrahedral cells and uses novel polygon generation rules that produce 2-manifold and watertight surface meshes with good-quality triangles. These meshes, being watertight and 2-manifold, are geometrically correct, and therefore can be used to initialize tetrahedral meshes. The 2-manifold DC method has been extended into the multi-material domain. Due to its multi-material nature, multi-material surface meshes will contain non-manifold elements along material interfaces or shared boundaries. The proposed multi-material DC algorithm can (1) generate multi-material surface meshes where each material sub-mesh is a 2-manifold and watertight mesh, (2) preserve the non-manifold elements along the material interfaces, and (3) ensure that the material interface or shared boundary between materials is consistent. The proposed method is used to generate multi-material surface meshes of deep brain anatomical structures from a digital atlas of the basal ganglia and thalamus. Although deep brain anatomical structures can be labeled as functionally separate, they are in fact continuous tracts of soft tissue in close proximity to each other. The multi-material meshes generated by the proposed DC algorithm can accurately represent the closely-packed deep brain structures as a single mesh consisting of multiple material sub-meshes. Each sub-mesh represents a distinct functional structure of the brain. Printed and/or digital atlases are important tools for medical research and surgical intervention. While these atlases can provide guidance in identifying anatomical structures, they do not take into account the wide variations in the shape and size of anatomical structures that occur from patient to patient. Accurate, patient-specific representations are especially important for surgical interventions like deep brain stimulation, where even small inaccuracies can result in dangerous complications. The last part of this research effort extends the discrete deformable 2-simplex mesh into the multi-material domain where geometry-based internal forces and image-based external forces are used in the deformation process. This multi-material deformable framework is used to segment anatomical structures of the deep brain region from Magnetic Resonance (MR) data

Generating semantically enriched diagnostics for radiological images using machine learning

Development of Computer Aided Diagnostic (CAD) tools to aid radiologists in pathology detection and decision making relies considerably on manually annotated images. With the advancement of deep learning techniques for CAD development, these expert annotations no longer need to be hand-crafted, however, deep learning algorithms require large amounts of data in order to generalise well. One way in which to access large volumes of expert-annotated data is through radiological exams consisting of images and reports. Using past radiological exams obtained from hospital archiving systems has many advantages: they are expert annotations available in large quantities, covering a population-representative variety of pathologies, and they provide additional context to pathology diagnoses, such as anatomical location and severity. Learning to auto-generate such reports from images presents many challenges such as the difficulty in representing and generating long, unstructured textual information, accounting for spelling errors and repetition or redundancy, and the inconsistency across different annotators. In this thesis, the problem of learning to automate disease detection from radiological exams is approached from three directions. Firstly, a report generation model is developed such that it is conditioned on radiological image features. Secondly, a number of approaches are explored aimed at extracting diagnostic information from free-text reports. Finally, an alternative approach to image latent space learning from current state-of-the-art is developed that can be applied to accelerated image acquisition.Open Acces

Attention Gated Networks: Learning to Leverage Salient Regions in Medical Images

We propose a novel attention gate (AG) model for medical image analysis that automatically learns to focus on target structures of varying shapes and sizes. Models trained with AGs implicitly learn to suppress irrelevant regions in an input image while highlighting salient features useful for a specific task. This enables us to eliminate the necessity of using explicit external tissue/organ localisation modules when using convolutional neural networks (CNNs). AGs can be easily integrated into standard CNN models such as VGG or U-Net architectures with minimal computational overhead while increasing the model sensitivity and prediction accuracy. The proposed AG models are evaluated on a variety of tasks, including medical image classification and segmentation. For classification, we demonstrate the use case of AGs in scan plane detection for fetal ultrasound screening. We show that the proposed attention mechanism can provide efficient object localisation while improving the overall prediction performance by reducing false positives. For segmentation, the proposed architecture is evaluated on two large 3D CT abdominal datasets with manual annotations for multiple organs. Experimental results show that AG models consistently improve the prediction performance of the base architectures across different datasets and training sizes while preserving computational efficiency. Moreover, AGs guide the model activations to be focused around salient regions, which provides better insights into how model predictions are made. The source code for the proposed AG models is publicly available.Comment: Accepted for Medical Image Analysis (Special Issue on Medical Imaging with Deep Learning). arXiv admin note: substantial text overlap with arXiv:1804.03999, arXiv:1804.0533