Advancements and Breakthroughs in Ultrasound Imaging

Ultrasonic imaging is a powerful diagnostic tool available to medical practitioners, engineers and researchers today. Due to the relative safety, and the non-invasive nature, ultrasonic imaging has become one of the most rapidly advancing technologies. These rapid advances are directly related to the parallel advancements in electronics, computing, and transducer technology together with sophisticated signal processing techniques. This book focuses on state of the art developments in ultrasonic imaging applications and underlying technologies presented by leading practitioners and researchers from many parts of the world

Machine learning for efficient recognition of anatomical structures and abnormalities in biomedical images

Three studies have been carried out to investigate new approaches to efficient image segmentation and anomaly detection. The first study investigates the use of deep learning in patch based segmentation. Current approaches to patch based segmentation use low level features such as the sum of squared differences between patches. We argue that better segmentation can be achieved by harnessing the power of deep neural networks. Currently these networks make extensive use of convolutional layers. However, we argue that in the context of patch based segmentation, convolutional layers have little advantage over the canonical artificial neural network architecture. This is because a patch is small, and does not need decomposition and thus will not benefit from convolution. Instead, we make use of the canonical architecture in which neurons only compute dot products, but also incorporate modern techniques of deep learning. The resulting classifier is much faster and less memory-hungry than convolution based networks. In a test application to the segmentation of hippocampus in human brain MR images, we significantly outperformed prior art with a median Dice score up to 90.98% at a near real-time speed (<1s). The second study is an investigation into mouse phenotyping, and develops a high-throughput framework to detect morphological abnormality in mouse embryo micro-CT images. Existing work in this line is centred on, either the detection of phenotype-specific features or comparative analytics. The former approach lacks generality and the latter can often fail, for example, when the abnormality is not associated with severe volume variation. Both these approaches often require image segmentation as a pre-requisite, which is very challenging when applied to embryo phenotyping. A new approach to this problem in which non-rigid registration is combined with robust principal component analysis (RPCA), is proposed. The new framework is able to efficiently perform abnormality detection in a batch of images. It is sensitive to both volumetric and non-volumetric variations, and does not require image segmentation. In a validation study, it successfully distinguished the abnormal VSD and polydactyly phenotypes from the normal, respectively, at 85.19% and 88.89% specificities, with 100% sensitivity in both cases. The third study investigates the RPCA technique in more depth. RPCA is an extension of PCA that tolerates certain levels of data distortion during feature extraction, and is able to decompose images into regular and singular components. It has previously been applied to many computer vision problems (e.g. video surveillance), attaining excellent performance. However these applications commonly rest on a critical condition: in the majority of images being processed, there is a background with very little variation. By contrast in biomedical imaging there is significant natural variation across different images, resulting from inter-subject variability and physiological movements. Non-rigid registration can go some way towards reducing this variance, but cannot eliminate it entirely. To address this problem we propose a modified framework (RPCA-P) that is able to incorporate natural variation priors and adjust outlier tolerance locally, so that voxels associated with structures of higher variability are compensated with a higher tolerance in regularity estimation. An experimental study was applied to the same mouse embryo micro-CT data, and notably improved the detection specificity to 94.12% for the VSD and 90.97% for the polydactyly, while maintaining the sensitivity at 100%.Open Acces

Online Super-Resolution For Fibre-Bundle-Based Confocal Laser Endomicroscopy

Probe-based Confocal Laser Endomicroscopy (pCLE) produces microscopic images enabling real-time in vivo optical biopsy. However, the miniaturisation of the optical hardware, specifically the reliance on an optical fibre bundle as an imaging guide, fundamentally limits image quality by producing artefacts, noise, and relatively low contrast and resolution. The reconstruction approaches in clinical pCLE products do not fully alleviate these problems. Consequently, image quality remains a barrier that curbs the full potential of pCLE. Enhancing the image quality of pCLE in real-time remains a challenge. The research in this thesis is a response to this need. I have developed dedicated online super-resolution methods that account for the physics of the image acquisition process. These methods have the potential to replace existing reconstruction algorithms without interfering with the fibre design or the hardware of the device. In this thesis, novel processing pipelines are proposed for enhancing the image quality of pCLE. First, I explored a learning-based super-resolution method that relies on mapping from the low to the high-resolution space. Due to the lack of high-resolution pCLE, I proposed to simulate high-resolution data and use it as a ground truth model that is based on the pCLE acquisition physics. However, pCLE images are reconstructed from irregularly distributed fibre signals, and grid-based Convolutional Neural Networks are not designed to take irregular data as input. To alleviate this problem, I designed a new trainable layer that embeds Nadaraya- Watson regression. Finally, I proposed a novel blind super-resolution approach by deploying unsupervised zero-shot learning accompanied by a down-sampling kernel crafted for pCLE. I evaluated these new methods in two ways: a robust image quality assessment and a perceptual quality test assessed by clinical experts. The results demonstrate that the proposed super-resolution pipelines are superior to the current reconstruction algorithm in terms of image quality and clinician preference

Real-time Ultrasound Signals Processing: Denoising and Super-resolution

Ultrasound acquisition is widespread in the biomedical field, due to its properties of low cost, portability, and non-invasiveness for the patient. The processing and analysis of US signals, such as images, 2D videos, and volumetric images, allows the physician to monitor the evolution of the patient's disease, and support diagnosis, and treatments (e.g., surgery). US images are affected by speckle noise, generated by the overlap of US waves. Furthermore, low-resolution images are acquired when a high acquisition frequency is applied to accurately characterise the behaviour of anatomical features that quickly change over time. Denoising and super-resolution of US signals are relevant to improve the visual evaluation of the physician and the performance and accuracy of processing methods, such as segmentation and classification. The main requirements for the processing and analysis of US signals are real-time execution, preservation of anatomical features, and reduction of artefacts. In this context, we present a novel framework for the real-time denoising of US 2D images based on deep learning and high-performance computing, which reduces noise while preserving anatomical features in real-time execution. We extend our framework to the denoise of arbitrary US signals, such as 2D videos and 3D images, and we apply denoising algorithms that account for spatio-temporal signal properties into an image-to-image deep learning model. As a building block of this framework, we propose a novel denoising method belonging to the class of low-rank approximations, which learns and predicts the optimal thresholds of the Singular Value Decomposition. While previous denoise work compromises the computational cost and effectiveness of the method, the proposed framework achieves the results of the best denoising algorithms in terms of noise removal, anatomical feature preservation, and geometric and texture properties conservation, in a real-time execution that respects industrial constraints. The framework reduces the artefacts (e.g., blurring) and preserves the spatio-temporal consistency among frames/slices; also, it is general to the denoising algorithm, anatomical district, and noise intensity. Then, we introduce a novel framework for the real-time reconstruction of the non-acquired scan lines through an interpolating method; a deep learning model improves the results of the interpolation to match the target image (i.e., the high-resolution image). We improve the accuracy of the prediction of the reconstructed lines through the design of the network architecture and the loss function. %The design of the deep learning architecture and the loss function allow the network to improve the accuracy of the prediction of the reconstructed lines. In the context of signal approximation, we introduce our kernel-based sampling method for the reconstruction of 2D and 3D signals defined on regular and irregular grids, with an application to US 2D and 3D images. Our method improves previous work in terms of sampling quality, approximation accuracy, and geometry reconstruction with a slightly higher computational cost. For both denoising and super-resolution, we evaluate the compliance with the real-time requirement of US applications in the medical domain and provide a quantitative evaluation of denoising and super-resolution methods on US and synthetic images. Finally, we discuss the role of denoising and super-resolution as pre-processing steps for segmentation and predictive analysis of breast pathologies

Wavelets and sparse methods for image reconstruction and classification in neuroimaging

This dissertation contributes to neuroimaging literature in the fields of compressed sensing magnetic resonance imaging (CS-MRI) and image-based detection of Alzheimer’s disease (AD). It consists of three main contributions, based on wavelets and sparse methods. The first contribution is a method for wavelet packet basis optimisation for sparse approximation and compressed sensing reconstruction of magnetic resonance (MR) images of the brain. The proposed method is based on the basis search algorithm developed by Coifman and Wickerhauser, with a cost function designed specifically for compressed sensing. It is tested on MR images available from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The second contribution consists of evaluating and comparing several sparse classification methods in an application to detection of AD based on positron emission tomography (PET) images of the brain. This comparison includes univariate feature selection, feature clustering and classifiers that automatically select a small subset of features due to their mathematical or algorithmic construction. The evaluation is based on PET images available from ADNI. The third contribution is proposing an extension of wavelet-based scattering networks (originally proposed by Mallat and Bruna) to three-dimensional tomographic images. The proposed extension is evaluated as a feature representation in an application to detection of AD based on MR images available from ADNI. There are several possible extensions of the work presented in this dissertation. The wavelet packet basis search method proposed in the first contribution can be improved to take into account the coherence between the sparse approximation basis and the sensing basis. The evaluation presented in the second contribution can be extended with additional algorithms to make it more comprehensive. The three-dimensional scattering networks that are the core part of the third contribution can be combined with other machine learning methods, such as manifold learning or deep convolutional neural networks. As a whole, the methods proposed in this dissertation contribute to the work towards efficient screening for Alzheimer’s disease, by making MRI scans of the brain faster and helping to automate image analysis for AD detection. The first contribution is a method for wavelet packet basis optimisation for sparse approximation and compressed sensing reconstruction of magnetic resonance (MR) images of the brain. The proposed method is based on the basis search algorithm developed by Coifman and Wickerhauser, with a cost function designed specifically for compressed sensing. It is tested on MR images available from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The second contribution consists of evaluating and comparing several sparse classification methods in an application to detection of AD based on positron emission tomography (PET) images of the brain. This comparison includes univariate feature selection, feature clustering and classifiers that automatically select a small subset of features due to their mathematical or algorithmic construction. The evaluation is based on PET images available from ADNI. The third contribution is proposing an extension of wavelet-based scattering networks (originally proposed by Mallat and Bruna) to three-dimensional tomographic images. The proposed extension is evaluated as a feature representation in an application to detection of AD based on MR images available from ADNI. There are several possible extensions of the work presented in this dissertation. The wavelet packet basis search method proposed in the first contribution can be improved to take into account the coherence between the sparse approximation basis and the sensing basis. The evaluation presented in the second contribution can be extended with additional algorithms to make it more comprehensive. The three-dimensional scattering networks that are the core part of the third contribution can be combined with other machine learning methods, such as manifold learning or deep convolutional neural networks. This dissertation contributes to neuroimaging literature in the fields of compressed sensing magnetic resonance imaging (CS-MRI) and image-based detection of Alzheimer’s disease (AD). It consists of three main contributions, based on wavelets and sparse methods. The first contribution is a method for wavelet packet basis optimisation for sparse approximation and compressed sensing reconstruction of magnetic resonance (MR) images of the brain. The proposed method is based on the basis search algorithm developed by Coifman and Wickerhauser, with a cost function designed specifically for compressed sensing. It is tested on MR images available from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The second contribution consists of evaluating and comparing several sparse classification methods in an application to detection of AD based on positron emission tomography (PET) images of the brain. This comparison includes univariate feature selection, feature clustering and classifiers that automatically select a small subset of features due to their mathematical or algorithmic construction. The evaluation is based on PET images available from ADNI. The third contribution is proposing an extension of wavelet-based scattering networks (originally proposed by Mallat and Bruna) to three-dimensional tomographic images. The proposed extension is evaluated as a feature representation in an application to detection of AD based on MR images available from ADNI. There are several possible extensions of the work presented in this dissertation. The wavelet packet basis search method proposed in the first contribution can be improved to take into account the coherence between the sparse approximation basis and the sensing basis. The evaluation presented in the second contribution can be extended with additional algorithms to make it more comprehensive. The three-dimensional scattering networks that are the core part of the third contribution can be combined with other machine learning methods, such as manifold learning or deep convolutional neural networks. As a whole, the methods proposed in this dissertation contribute to the work towards efficient screening for Alzheimer’s disease, by making MRI scans of the brain faster and helping to automate image analysis for AD detection.Open Acces

Echocardiography

The book "Echocardiography - New Techniques" brings worldwide contributions from highly acclaimed clinical and imaging science investigators, and representatives from academic medical centers. Each chapter is designed and written to be accessible to those with a basic knowledge of echocardiography. Additionally, the chapters are meant to be stimulating and educational to the experts and investigators in the field of echocardiography. This book is aimed primarily at cardiology fellows on their basic echocardiography rotation, fellows in general internal medicine, radiology and emergency medicine, and experts in the arena of echocardiography. Over the last few decades, the rate of technological advancements has developed dramatically, resulting in new techniques and improved echocardiographic imaging. The authors of this book focused on presenting the most advanced techniques useful in today's research and in daily clinical practice. These advanced techniques are utilized in the detection of different cardiac pathologies in patients, in contributing to their clinical decision, as well as follow-up and outcome predictions. In addition to the advanced techniques covered, this book expounds upon several special pathologies with respect to the functions of echocardiography

Landmark Localization, Feature Matching and Biomarker Discovery from Magnetic Resonance Images

The work presented in this thesis proposes several methods that can be roughly divided into three different categories: I) landmark localization in medical images, II) feature matching for image registration, and III) biomarker discovery in neuroimaging. The first part deals with the identification of anatomical landmarks. The motivation stems from the fact that the manual identification and labeling of these landmarks is very time consuming and prone to observer errors, especially when large datasets must be analyzed. In this thesis we present three methods to tackle this challenge: A landmark descriptor based on local self-similarities (SS), a subspace building framework based on manifold learning and a sparse coding landmark descriptor based on data-specific learned dictionary basis. The second part of this thesis deals with finding matching features between a pair of images. These matches can be used to perform a registration between them. Registration is a powerful tool that allows mapping images in a common space in order to aid in their analysis. Accurate registration can be challenging to achieve using intensity based registration algorithms. Here, a framework is proposed for learning correspondences in pairs of images by matching SS features and random sample and consensus (RANSAC) is employed as a robust model estimator to learn a deformation model based on feature matches. Finally, the third part of the thesis deals with biomarker discovery using machine learning. In this section a framework for feature extraction from learned low-dimensional subspaces that represent inter-subject variability is proposed. The manifold subspace is built using data-driven regions of interest (ROI). These regions are learned via sparse regression, with stability selection. Also, probabilistic distribution models for different stages in the disease trajectory are estimated for different class populations in the low-dimensional manifold and used to construct a probabilistic scoring function.Open Acces

New Statistical Algorithms for the Analysis of Mass Spectrometry Time-Of-Flight Mass Data with Applications in Clinical Diagnostics

Mass spectrometry (MS) based techniques have emerged as a standard forlarge-scale protein analysis. The ongoing progress in terms of more sensitive machines and improved data analysis algorithms led to a constant expansion of its fields of applications. Recently, MS was introduced into clinical proteomics with the prospect of early disease detection using proteomic pattern matching. Analyzing biological samples (e.g. blood) by mass spectrometry generates mass spectra that represent the components (molecules) contained in a sample as masses and their respective relative concentrations. In this work, we are interested in those components that are constant within a group of individuals but differ much between individuals of two distinct groups. These distinguishing components that dependent on a particular medical condition are generally called biomarkers. Since not all biomarkers found by the algorithms are of equal (discriminating) quality we are only interested in a small biomarker subset that - as a combination - can be used as a fingerprint for a disease. Once a fingerprint for a particular disease (or medical condition) is identified, it can be used in clinical diagnostics to classify unknown spectra. In this thesis we have developed new algorithms for automatic extraction of disease specific fingerprints from mass spectrometry data. Special emphasis has been put on designing highly sensitive methods with respect to signal detection. Thanks to our statistically based approach our methods are able to detect signals even below the noise level inherent in data acquired by common MS machines, such as hormones. To provide access to these new classes of algorithms to collaborating groups we have created a web-based analysis platform that provides all necessary interfaces for data transfer, data analysis and result inspection. To prove the platform's practical relevance it has been utilized in several clinical studies two of which are presented in this thesis. In these studies it could be shown that our platform is superior to commercial systems with respect to fingerprint identification. As an outcome of these studies several fingerprints for different cancer types (bladder, kidney, testicle, pancreas, colon and thyroid) have been detected and validated. The clinical partners in fact emphasize that these results would be impossible with a less sensitive analysis tool (such as the currently available systems). In addition to the issue of reliably finding and handling signals in noise we faced the problem to handle very large amounts of data, since an average dataset of an individual is about 2.5 Gigabytes in size and we have data of hundreds to thousands of persons. To cope with these large datasets, we developed a new framework for a heterogeneous (quasi) ad-hoc Grid - an infrastructure that allows to integrate thousands of computing resources (e.g. Desktop Computers, Computing Clusters or specialized hardware, such as IBM's Cell Processor in a Playstation 3)