Automated Strategies in Multimodal and Multidimensional Ultrasound Image-based Diagnosis

Medical ultrasonography is an effective technique in traditional anatomical and functional diagnosis. However, it requires the visual examination by experienced clinicians, which is a laborious, time consuming and highly subjective procedure. Computer-aided diagnosis (CADx) have been extensively used in clinical practice to support the interpretation of images; nevertheless, current ultrasound CADx still entails a substantial user-dependency and are unable to extract image data for prediction modelling. The aim of this thesis is to propose a set of fully automated strategies to overcome the limitations of ultrasound CADx. These strategies are addressed to multiple modalities (B-Mode, Contrast-Enhanced Ultrasound-CEUS, Power Doppler-PDUS and Acoustic Angiography-AA) and dimensions (2-D and 3-D imaging). The enabling techniques presented in this work are designed, developed and quantitively validated to efficiently improve the overall patients’ diagnosis. This work is subdivided in 2 macro-sections: in the first part, two fully automated algorithms for the reliable quantification of 2-D B-Mode ultrasound skeletal muscle architecture and morphology are proposed. In the second part, two fully automated algorithms for the objective assessment and characterization of tumors’ vasculature in 3-D CEUS and PDUS thyroid tumors and preclinical AA cancer growth are presented. In the first part, the MUSA (Muscle UltraSound Analysis) algorithm is designed to measure the muscle thickness, the fascicles length and the pennation angle; the TRAMA (TRAnsversal Muscle Analysis) algorithm is proposed to extract and analyze the Visible Cross-Sectional Area (VCSA). MUSA and TRAMA algorithms have been validated on two datasets of 200 images; automatic measurements have been compared with expert operators’ manual measurements. A preliminary statistical analysis was performed to prove the ability of texture analysis on automatic VCSA in the distinction between healthy and pathological muscles. In the second part, quantitative assessment on tumor vasculature is proposed in two automated algorithms for the objective characterization of 3-D CEUS/Power Doppler thyroid nodules and the evolution study of fibrosarcoma invasion in preclinical 3-D AA imaging. Vasculature analysis relies on the quantification of architecture and vessels tortuosity. Vascular features obtained from CEUS and PDUS images of 20 thyroid nodules (10 benign, 10 malignant) have been used in a multivariate statistical analysis supported by histopathological results. Vasculature parametric maps of implanted fibrosarcoma are extracted from 8 rats investigated with 3-D AA along four time points (TPs), in control and tumors areas; results have been compared with manual previous findings in a longitudinal tumor growth study. Performance of MUSA and TRAMA algorithms results in 100% segmentation success rate. Absolute difference between manual and automatic measurements is below 2% for the muscle thickness and 4% for the VCSA (values between 5-10% are acceptable in clinical practice), suggesting that automatic and manual measurements can be used interchangeably. The texture features extraction on the automatic VCSAs reveals that texture descriptors can distinguish healthy from pathological muscles with a 100% success rate for all the four muscles. Vascular features extracted of 20 thyroid nodules in 3-D CEUS and PDUS volumes can be used to distinguish benign from malignant tumors with 100% success rate for both ultrasound techniques. Malignant tumors present higher values of architecture and tortuosity descriptors; 3-D CEUS and PDUS imaging present the same accuracy in the differentiation between benign and malignant nodules. Vascular parametric maps extracted from the 8 rats along the 4 TPs in 3-D AA imaging show that parameters extracted from the control area are statistically different compared to the ones within the tumor volume. Tumor angiogenetic vessels present a smaller diameter and higher tortuosity. Tumor evolution is characterized by the significant vascular trees growth and a constant value of vessel diameter along the four TPs, confirming the previous findings. In conclusion, the proposed automated strategies are highly performant in segmentation, features extraction, muscle disease detection and tumor vascular characterization. These techniques can be extended in the investigation of other organs, diseases and embedded in ultrasound CADx, providing a user-independent reliable diagnosis

Deep Learning Models to Characterize Smooth Muscle Fibers in Hematoxylin and Eosin Stained Histopathological Images of the Urinary Bladder

Muscularis propria (MP) and muscularis mucosa (MM), two types of smooth muscle fibers in the urinary bladder, are major benchmarks in staging bladder cancer to distinguish between muscle-invasive (MP invasion) and non-muscle-invasive (MM invasion) diseases. While patients with non-muscle-invasive tumor can be treated conservatively involving transurethral resection (TUR) only, more aggressive treatment options, such as removal of the entire bladder, known as radical cystectomy (RC) which may severely degrade the quality of patient’s life, are often required in those with muscle-invasive tumor. Hence, given two types of image datasets, hematoxylin & eosin-stained histopathological images from RC and TUR specimens, we propose the first deep learning-based method for efficient characterization of MP. The proposed method is intended to aid the pathologists as a decision support system by facilitating accurate staging of bladder cancer. In this work, we aim to semantically segment the TUR images into MP and non-MP regions using two different approaches, patch-to-label and pixel-to-label. We evaluate four different state-of-the-art CNN-based models (VGG16, ResNet18, SqueezeNet, and MobileNetV2) and semantic segmentation-based models (U-Net, MA-Net, DeepLabv3+, and FPN) and compare their performance metrics at the pixel-level. The SqueezeNet model (mean Jaccard Index: 95.44%, mean dice coefficient: 97.66%) in patch-to-label approach and the MA-Net model (mean Jaccard Index: 96.64%, mean dice coefficient: 98.29%) in pixel-to-label approach are the best among tested models. Although pixel-to-label approach is marginally better than the patch-to-label approach based on evaluation metrics, the latter is computationally efficient using least trainable parameters

LeCo: Lightweight Compression via Learning Serial Correlations

Lightweight data compression is a key technique that allows column stores to exhibit superior performance for analytical queries. Despite a comprehensive study on dictionary-based encodings to approach Shannon's entropy, few prior works have systematically exploited the serial correlation in a column for compression. In this paper, we propose LeCo (i.e., Learned Compression), a framework that uses machine learning to remove the serial redundancy in a value sequence automatically to achieve an outstanding compression ratio and decompression performance simultaneously. LeCo presents a general approach to this end, making existing (ad-hoc) algorithms such as Frame-of-Reference (FOR), Delta Encoding, and Run-Length Encoding (RLE) special cases under our framework. Our microbenchmark with three synthetic and six real-world data sets shows that a prototype of LeCo achieves a Pareto improvement on both compression ratio and random access speed over the existing solutions. When integrating LeCo into widely-used applications, we observe up to 3.9x speed up in filter-scanning a Parquet file and a 16% increase in Rocksdb's throughput

Surface EMG and muscle fatigue: multi-channel approaches to the study of myoelectric manifestations of muscle fatigue

In a broad view, fatigue is used to indicate a degree of weariness. On a muscular level, fatigue posits the reduced capacity of muscle fibres to produce force, even in the presence of motor neuron excitation via either spinal mechanisms or electric pulses applied externally. Prior to decreased force, when sustaining physically demanding tasks, alterations in the muscle electrical properties take place. These alterations, termed myoelectric manifestation of fatigue, can be assessed non-invasively with a pair of surface electrodes positioned appropriately on the target muscle; traditional approach. A relatively more recent approach consists of the use of multiple electrodes. This multi-channel approach provides access to a set of physiologically relevant variables on the global muscle level or on the level of single motor units, opening new fronts for the study of muscle fatigue; it allows for: (i) a more precise quantification of the propagation velocity, a physiological variable of marked interest to the study of fatigue; (ii) the assessment of regional, myoelectric manifestations of fatigue; (iii) the analysis of single motor units, with the possibility to obtain information about motor unit control and fibre membrane changes. This review provides a methodological account on the multi-channel approach for the study of myoelectric manifestation of fatigue and on the experimental conditions to which it applies, as well as examples of their current applications

AI MSK clinical applications: spine imaging

Recent investigations have focused on the clinical application of artificial intelligence (AI) for tasks specifically addressing the musculoskeletal imaging routine. Several AI applications have been dedicated to optimizing the radiology value chain in spine imaging, independent from modality or specific application. This review aims to summarize the status quo and future perspective regarding utilization of AI for spine imaging. First, the basics of AI concepts are clarified. Second, the different tasks and use cases for AI applications in spine imaging are discussed and illustrated by examples. Finally, the authors of this review present their personal perception of AI in daily imaging and discuss future chances and challenges that come along with AI-based solutions

Towards Personalized and Human-in-the-Loop Document Summarization

The ubiquitous availability of computing devices and the widespread use of the internet have generated a large amount of data continuously. Therefore, the amount of available information on any given topic is far beyond humans' processing capacity to properly process, causing what is known as information overload. To efficiently cope with large amounts of information and generate content with significant value to users, we require identifying, merging and summarising information. Data summaries can help gather related information and collect it into a shorter format that enables answering complicated questions, gaining new insight and discovering conceptual boundaries. This thesis focuses on three main challenges to alleviate information overload using novel summarisation techniques. It further intends to facilitate the analysis of documents to support personalised information extraction. This thesis separates the research issues into four areas, covering (i) feature engineering in document summarisation, (ii) traditional static and inflexible summaries, (iii) traditional generic summarisation approaches, and (iv) the need for reference summaries. We propose novel approaches to tackle these challenges, by: i)enabling automatic intelligent feature engineering, ii) enabling flexible and interactive summarisation, iii) utilising intelligent and personalised summarisation approaches. The experimental results prove the efficiency of the proposed approaches compared to other state-of-the-art models. We further propose solutions to the information overload problem in different domains through summarisation, covering network traffic data, health data and business process data.Comment: PhD thesi

Autologous Peripheral Nerve Grafts to the Brain for the Treatment of Parkinson\u27s Disease

Parkinson’s disease (PD) is a disorder of the nervous system that causes problems with movement (motor symptoms) as well as other problems such as mood disorders, cognitive changes, sleep disorders, constipation, pain, and other non-motor symptoms. The severity of PD symptoms worsens over time as the disease progresses, and while there are treatments for the motor and some non-motor symptoms there is no known cure for PD. Thus there is a high demand for therapies to slow the progressive neurodegeneration observed in PD. Two clinical trials at the University of Kentucky College of Medicine (NCT02369003, NCT01833364) are currently underway that aim to develop a disease-modifying therapy that slows the progression of PD. These clinical trials are evaluating the safety and feasibility of an autologous peripheral nerve graft to the substantia nigra in combination with Deep Brain Stimulation (DBS) for the treatment of PD. By grafting peripheral nerve tissue to the Substantia Nigra, the researchers aim to introduce peripheral nerve tissue, which is capable of functional regeneration after injury, to the degenerating Substantia Nigra of patients with PD. The central hypothesis of these clinical trials is that the grafted tissue will slow degeneration of the target brain region through neural repair actions of Schwann cells as well as other pro-regenerative features of the peripheral nerve tissue. This dissertation details analysis of the peripheral nerve tissue used in the above clinical trials with respect to tissue composition and gene expression, both of injury-naive human peripheral nerve as well as the post-conditioning injury nerve tissue used in the grafting procedure. RNA-seq analysis of sural nerve tissue pre and post-conditioning show significant changes in gene expression corresponding with transdifferentiation of Schwann cells from a myelinating to a repair phenotype, release of growth factors, activation of macrophages and other immune cells, and an increase in anti-apoptotic and neuroprotective gene transcripts. These results reveal in vivo gene expression changes involved in the human peripheral nerve injury repair process, which has relevance beyond this clinical trial to the fields of Schwann cell biology and peripheral nerve repair. To assess the neurobiology of the graft post-implantation we developed an animal model of the grafting procedure, termed Neuro-Avatars, which feature human graft tissue implanted into athymic nude rats. Survival and infiltration of human graft cells into the host brain were shown using immunohistochemistry of Human Nuclear Antigen. Surgical methods and outcomes from the ongoing development of this animal model are reported. To connect the results of these laboratory studies to the clinical trial we compared the severity of motor symptoms before surgery to one year post-surgery in patients who received the analyzed graft tissue. Motor symptom severity was assessed using the Unified Parkinson’s Disease Rating Scale Part III. Finally, the implications and future directions of this research is discussed. In summary, this dissertation advances the translational science cycle by using clinical trial findings and samples to answer basic science questions that will in turn guide future clinical trial design

Efficient Algorithms to Compute Hierarchical Summaries from Big Data Streams

Many data stream applications have hierarchical data; containing time, geographic locations, product information, clickstreams, server logs, IP addresses. A hierarchical summary of such volumous data offers multiple advantages including compactness, quick understanding, and abstraction. The goal of this thesis is to design algorithmic approaches for summarizing hierarchical data streams. First, this thesis provides a theoretical analysis of the benchmark hierarchical heavy hitters' algorithms and uncovers their shortcomings such as requiring high theoretical memory, updates and coverage problem. To address these shortcomings, this thesis proposes efficient algorithms which offer deterministic estimation accuracy using O(η/ε) worst-case memory and O(η) worst-case time complexity per item, where ε ∈ [0,1] is a user defined parameter and η is a small constant derived from the data. The proposed hierarchical heavy hitters' algorithms are shown to have improved significantly over existing algorithms both theoretically as well as empirically. Next, this thesis introduces a new concept called hierarchically correlated heavy hitters, which is different from existing hierarchical summarization techniques. The thesis provides a formal definition of the proposed concept and compares it with existing hierarchical summarization approaches both at definition level and empirically. It also proposes an efficient hierarchy-aware algorithm for computing hierarchically correlated heavy hitters. The proposed algorithm offers deterministic estimation accuracy using O(η / (ε_p * ε_s )) worst-case memory and O(η) worst-case time complexity per item, where η is as defined previously, and ε_p ∈ [0,1], ε_s ∈ [0,1] are other user defined parameters. Finally, the thesis proposes a special hierarchical data structure and algorithm to summarize spatiotemporal data. It can be used to extract interesting and useful patterns from high-speed spatiotemporal data streams at multiple spatial and temporal granularities. Theoretical and empirical analysis are provided, which show that the proposed data structure is very efficient concerning data storage and response to queries. It updates a single item in O(1) time and responds to a point query in O(1) time. Importantly, the memory requirement of the proposed data structure is independent of the size of the data and only depends on user-supplied parameters ψ ⃗ and φ ⃗. In summary, this thesis provides a general framework consisting of a set of algorithms and data structures to compute hierarchical summaries of the big data streams. All of the proposed algorithms exploit a lattice structure built from the hierarchical attributes of the data to compute different hierarchical summaries, which can be used to address various data analytic issues in many emerging applications