Efficient ultrasonic signal processing techniques for aided medical diagnostics

Ultrasound imaging is widely used in medical diagnostics as it is the fastest, least invasive, and least expensive imaging modality. However, ultrasound images are intrinsically difficult to be interpreted. In this scenario, Computer Aided Detection (CAD) systems can be used to support physicians during diagnosis providing them a second opinion. This thesis discusses efficient ultrasound processing techniques for computer aided medical diagnostics, focusing on two major topics: (i) Ultrasound Tissue Characterization (UTC), aimed at characterizing and differentiating between healthy and diseased tissue; (ii) Ultrasound Image Segmentation (UIS), aimed at detecting the boundaries of anatomical structures to automatically measure organ dimensions and compute clinically relevant functional indices. Research on UTC produced a CAD tool for Prostate Cancer detection to improve the biopsy protocol. In particular, this thesis contributes with: (i) the development of a robust classification system; (ii) the exploitation of parallel computing on GPU for real-time performance; (iii) the introduction of both an innovative Semi-Supervised Learning algorithm and a novel supervised/semi-supervised learning scheme for CAD system training that improve system performance reducing data collection effort and avoiding collected data wasting. The tool provides physicians a risk map highlighting suspect tissue areas, allowing them to perform a lesion-directed biopsy. Clinical validation demonstrated the system validity as a diagnostic support tool and its effectiveness at reducing the number of biopsy cores requested for an accurate diagnosis. For UIS the research developed a heart disease diagnostic tool based on Real-Time 3D Echocardiography. Thesis contributions to this application are: (i) the development of an automated GPU based level-set segmentation framework for 3D images; (ii) the application of this framework to the myocardium segmentation. Experimental results showed the high efficiency and flexibility of the proposed framework. Its effectiveness as a tool for quantitative analysis of 3D cardiac morphology and function was demonstrated through clinical validation.

Learning Methods and Algorithms for Semantic Text Classification across Multiple Domains

Information is nowadays a key resource: machine learning and data mining techniques have been developed to extract high-level information from great amounts of data. As most data comes in form of unstructured text in natural languages, research on text mining is currently very active and dealing with practical problems. Among these, text categorization deals with the automatic organization of large quantities of documents in priorly defined taxonomies of topic categories, possibly arranged in large hierarchies. In commonly proposed machine learning approaches, classifiers are automatically trained from pre-labeled documents: they can perform very accurate classification, but often require a consistent training set and notable computational effort. Methods for cross-domain text categorization have been proposed, allowing to leverage a set of labeled documents of one domain to classify those of another one. Most methods use advanced statistical techniques, usually involving tuning of parameters. A first contribution presented here is a method based on nearest centroid classification, where profiles of categories are generated from the known domain and then iteratively adapted to the unknown one. Despite being conceptually simple and having easily tuned parameters, this method achieves state-of-the-art accuracy in most benchmark datasets with fast running times. A second, deeper contribution involves the design of a domain-independent model to distinguish the degree and type of relatedness between arbitrary documents and topics, inferred from the different types of semantic relationships between respective representative words, identified by specific search algorithms. The application of this model is tested on both flat and hierarchical text categorization, where it potentially allows the efficient addition of new categories during classification. Results show that classification accuracy still requires improvements, but models generated from one domain are shown to be effectively able to be reused in a different one.

Adaptive and Maladaptive Implications of Reinforcement Learning Processes: Fronto-Striatal Loops and Behavioural Correlates

That humans and animals learn from interaction with the environment is a foundational idea underlying nearly all theories of learning and intelligence. Learning that certain outcomes are associated with specific actions or stimuli (both internal and external), is at the very core of the capacity to adapt behaviour to environmental changes. In the present work, appetitive and aversive reinforcement learning paradigms have been used to investigate the fronto-striatal loops and behavioural correlates of adaptive and maladaptive reinforcement learning processes, aiming to a deeper understanding of how cortical and subcortical substrates interacts between them and with other brain systems to support learning. By combining a large variety of neuroscientific approaches, including behavioral and psychophysiological methods, EEG and neuroimaging techniques, these studies aim at clarifying and advancing the knowledge of the neural bases and computational mechanisms of reinforcement learning, both in normal and neurologically impaired population.

Applications of metrological techniques for clinical implementation of dosimetry and radiobiology in molecular radiotherapy

Molecular radiotherapy (MRT) is a fast developing and promising treatment for metastasised neuroendocrine tumours. Efficacy of MRT is based on the capability to selectively "deliver" radiation to tumour cells, minimizing administered dose to normal tissues. Outcome of MRT depends on the individual patient characteristics. For that reason, personalized treatment planning is important to improve outcomes of therapy. Dosimetry plays a key role in this setting, as it is the main physical quantity related to radiation effects on cells. Dosimetry in MRT consists in a complex series of procedures ranging from imaging quantification to dose calculation. This doctoral thesis focused on several aspects concerning the clinical implementation of absorbed dose calculations in MRT. Accuracy of SPECT/CT quantification was assessed in order to determine the optimal reconstruction parameters. A model of PVE correction was developed in order to improve the activity quantification in small volume, such us lesions in clinical patterns. Advanced dosimetric methods were compared with the aim of defining the most accurate modality, applicable in clinical routine. Also, for the first time on a large number of clinical cases, the overall uncertainty of tumour dose calculation was assessed. As part of the MRTDosimetry project, protocols for calibration of SPECT/CT systems and implementation of dosimetry were drawn up in order to provide standard guidelines to the clinics offering MRT. To estimate the risk of experiencing radio-toxicity side effects and the chance of inducing damage on neoplastic cells is crucial for patient selection and treatment planning. In this thesis, the NTCP and TCP models were derived based on clinical data as help to clinicians to decide the pharmaceutical dosage in relation to the therapy control and the limitation of damage to healthy tissues. Moreover, a model for tumour response prediction based on Machine Learning analysis was developed.

Development of advanced methods for the simulation of the reacting mixture formation in internal combustion engines with the use of machine learning algorithms

Besides increasing the share of electric and hybrid vehicles, in order to comply with more stringent environmental protection limitations, in the mid-term the auto industry must improve the efficiency of the internal combustion engine and the well to wheel efficiency of the employed fuel. To achieve this target, a deeper knowledge of the phenomena that influence the mixture formation and the chemical reactions involving new synthetic fuel components is mandatory, but complex and time intensive to perform purely by experimentation. Therefore, numerical simulations play an important role in this development process, but their use can be effective only if they can be considered accurate enough to capture these variations. The most relevant models necessary for the simulation of the reacting mixture formation and successive chemical reactions have been investigated in the present work, with a critical approach, in order to provide instruments to define the most suitable approaches also in the industrial context, which is limited by time constraints and budget evaluations. To overcome these limitations, new methodologies have been developed to conjugate detailed and simplified modelling techniques for the phenomena involving chemical reactions and mixture formation in non-traditional conditions (e.g. water injection, biofuels etc.). Thanks to the large use of machine learning and deep learning algorithms, several applications have been revised or implemented, with the target of reducing the computing time of some traditional tasks by orders of magnitude. Finally, a complete workflow leveraging these new models has been defined and used for evaluating the effects of different surrogate formulations of the same experimental fuel on a proof-of-concept GDI engine model.

Digital Forensics AI: on Practicality, Optimality, and Interpretability of Digital Evidence Mining Techniques

Digital forensics as a field has progressed alongside technological advancements over the years, just as digital devices have gotten more robust and sophisticated. However, criminals and attackers have devised means for exploiting the vulnerabilities or sophistication of these devices to carry out malicious activities in unprecedented ways. Their belief is that electronic crimes can be committed without identities being revealed or trails being established. Several applications of artificial intelligence (AI) have demonstrated interesting and promising solutions to seemingly intractable societal challenges. This thesis aims to advance the concept of applying AI techniques in digital forensic investigation. Our approach involves experimenting with a complex case scenario in which suspects corresponded by e-mail and deleted, suspiciously, certain communications, presumably to conceal evidence. The purpose is to demonstrate the efficacy of Artificial Neural Networks (ANN) in learning and detecting communication patterns over time, and then predicting the possibility of missing communication(s) along with potential topics of discussion. To do this, we developed a novel approach and included other existing models. The accuracy of our results is evaluated, and their performance on previously unseen data is measured. Second, we proposed conceptualizing the term “Digital Forensics AI” (DFAI) to formalize the application of AI in digital forensics. The objective is to highlight the instruments that facilitate the best evidential outcomes and presentation mechanisms that are adaptable to the probabilistic output of AI models. Finally, we enhanced our notion in support of the application of AI in digital forensics by recommending methodologies and approaches for bridging trust gaps through the development of interpretable models that facilitate the admissibility of digital evidence in legal proceedings.

Machine learning as a service for high energy physics (MLaaS4HEP): a service for ML-based data analyses

With the CERN LHC program underway, there has been an acceleration of data growth in the High Energy Physics (HEP) field and the usage of Machine Learning (ML) in HEP will be critical during the HL-LHC program when the data that will be produced will reach the exascale. ML techniques have been successfully used in many areas of HEP nevertheless, the development of a ML project and its implementation for production use is a highly time-consuming task and requires specific skills. Complicating this scenario is the fact that HEP data is stored in ROOT data format, which is mostly unknown outside of the HEP community. The work presented in this thesis is focused on the development of a ML as a Service (MLaaS) solution for HEP, aiming to provide a cloud service that allows HEP users to run ML pipelines via HTTP calls. These pipelines are executed by using the MLaaS4HEP framework, which allows reading data, processing data, and training ML models directly using ROOT files of arbitrary size from local or distributed data sources. Such a solution provides HEP users non-expert in ML with a tool that allows them to apply ML techniques in their analyses in a streamlined manner. Over the years the MLaaS4HEP framework has been developed, validated, and tested and new features have been added. A first MLaaS solution has been developed by automatizing the deployment of a platform equipped with the MLaaS4HEP framework. Then, a service with APIs has been developed, so that a user after being authenticated and authorized can submit MLaaS4HEP workflows producing trained ML models ready for the inference phase. A working prototype of this service is currently running on a virtual machine of INFN-Cloud and is compliant to be added to the INFN Cloud portfolio of services.

Big Data approaches as a support for precision livestock farming techniques

With the advent of new technologies it is increasingly easier to find data of different nature from even more accurate sensors that measure the most disparate physical quantities and with different methodologies. The collection of data thus becomes progressively important and takes the form of archiving, cataloging and online and offline consultation of information. Over time, the amount of data collected can become so relevant that it contains information that cannot be easily explored manually or with basic statistical techniques. The use of Big Data therefore becomes the object of more advanced investigation techniques, such as Machine Learning and Deep Learning. In this work some applications in the world of precision zootechnics and heat stress accused by dairy cows are described. Experimental Italian and German stables were involved for the training and testing of the Random Forest algorithm, obtaining a prediction of milk production depending on the microclimatic conditions of the previous days with satisfactory accuracy. Furthermore, in order to identify an objective method for identifying production drops, compared to the Wood model, typically used as an analytical model of the lactation curve, a Robust Statistics technique was used. Its application on some sample lactations and the results obtained allow us to be confident about the use of this method in the future.

Computational creativity: an interdisciplinary approach to sequential learning and creative generations

Creativity seems mysterious; when we experience a creative spark, it is difficult to explain how we got that idea, and we often recall notions like ``inspiration" and ``intuition" when we try to explain the phenomenon. The fact that we are clueless about how a creative idea manifests itself does not necessarily imply that a scientific explanation cannot exist. We are unaware of how we perform certain tasks, such as biking or language understanding, but we have more and more computational techniques that can replicate and hopefully explain such activities. We should understand that every creative act is a fruit of experience, society, and culture. Nothing comes from nothing. Novel ideas are never utterly new; they stem from representations that are already in mind. Creativity involves establishing new relations between pieces of information we had already: then, the greater the knowledge, the greater the possibility of finding uncommon connections, and the more the potential to be creative. In this vein, a beneficial approach to a better understanding of creativity must include computational or mechanistic accounts of such inner procedures and the formation of the knowledge that enables such connections. That is the aim of Computational Creativity: to develop computational systems for emulating and studying creativity. Hence, this dissertation focuses on these two related research areas: discussing computational mechanisms to generate creative artifacts and describing some implicit cognitive processes that can form the basis for creative thoughts.

Learning representations for graph-structured socio-technical systems

The recent widespread use of social media platforms and web services has led to a vast amount of behavioral data that can be used to model socio-technical systems. A significant part of this data can be represented as graphs or networks, which have become the prevalent mathematical framework for studying the structure and the dynamics of complex interacting systems. However, analyzing and understanding these data presents new challenges due to their increasing complexity and diversity. For instance, the characterization of real-world networks includes the need of accounting for their temporal dimension, together with incorporating higher-order interactions beyond the traditional pairwise formalism. The ongoing growth of AI has led to the integration of traditional graph mining techniques with representation learning and low-dimensional embeddings of networks to address current challenges. These methods capture the underlying similarities and geometry of graph-shaped data, generating latent representations that enable the resolution of various tasks, such as link prediction, node classification, and graph clustering. As these techniques gain popularity, there is even a growing concern about their responsible use. In particular, there has been an increased emphasis on addressing the limitations of interpretability in graph representation learning. This thesis contributes to the advancement of knowledge in the field of graph representation learning and has potential applications in a wide range of complex systems domains. We initially focus on forecasting problems related to face-to-face contact networks with time-varying graph embeddings. Then, we study hyperedge prediction and reconstruction with simplicial complex embeddings. Finally, we analyze the problem of interpreting latent dimensions in node embeddings for graphs. The proposed models are extensively evaluated in multiple experimental settings and the results demonstrate their effectiveness and reliability, achieving state-of-the-art performances and providing valuable insights into the properties of the learned representations.

Real-time anomaly detection of gamma-ray bursts for the Cherenkov Telescope Array using deep learning

The Cherenkov Telescope Array (CTA) will be the next-generation ground-based observatory to study the universe in the very-high-energy domain. The observatory will rely on a Science Alert Generation (SAG) system to analyze the real-time data from the telescopes and generate science alerts. The SAG system will play a crucial role in the search and follow-up of transients from external alerts, enabling multi-wavelength and multi-messenger collaborations. It will maximize the potential for the detection of the rarest phenomena, such as gamma-ray bursts (GRBs), which are the science case for this study. This study presents an anomaly detection method based on deep learning for detecting gamma-ray burst events in real-time. The performance of the proposed method is evaluated and compared against the Li&Ma standard technique in two use cases of serendipitous discoveries and follow-up observations, using short exposure times. The method shows promising results in detecting GRBs and is flexible enough to allow real-time search for transient events on multiple time scales. The method does not assume background nor source models and doe not require a minimum number of photon counts to perform analysis, making it well-suited for real-time analysis. Future improvements involve further tests, relaxing some of the assumptions made in this study as well as post-trials correction of the detection significance. Moreover, the ability to detect other transient classes in different scenarios must be investigated for completeness. The system can be integrated within the SAG system of CTA and deployed on the onsite computing clusters. This would provide valuable insights into the method's performance in a real-world setting and be another valuable tool for discovering new transient events in real-time. Overall, this study makes a significant contribution to the field of astrophysics by demonstrating the effectiveness of deep learning-based anomaly detection techniques for real-time source detection in gamma-ray astronomy.

Meaningful insights: explainability techniques for black-box models on tabular data

Artificial Intelligence (AI) and Machine Learning (ML) are novel data analysis techniques providing very accurate prediction results. They are widely adopted in a variety of industries to improve efficiency and decision-making, but they are also being used to develop intelligent systems. Their success grounds upon complex mathematical models, whose decisions and rationale are usually difficult to comprehend for human users to the point of being dubbed as black-boxes. This is particularly relevant in sensitive and highly regulated domains. To mitigate and possibly solve this issue, the Explainable AI (XAI) field became prominent in recent years. XAI consists of models and techniques to enable understanding of the intricated patterns discovered by black-box models. In this thesis, we consider model-agnostic XAI techniques, which can be applied to Tabular data, with a particular focus on the Credit Scoring domain. Special attention is dedicated to the LIME framework, for which we propose several modifications to the vanilla algorithm, in particular: a pair of complementary Stability Indices that accurately measure LIME stability, and the OptiLIME policy which helps the practitioner finding the proper balance among explanations' stability and reliability. We subsequently put forward GLEAMS a model-agnostic surrogate interpretable model which requires to be trained only once, while providing both Local and Global explanations of the black-box model. GLEAMS produces feature attributions and what-if scenarios, from both dataset and model perspective. Eventually, we argue that synthetic data are an emerging trend in AI, being more and more used to train complex models instead of original data. To be able to explain the outcomes of such models, we must guarantee that synthetic data are reliable enough to be able to translate their explanations to real-world individuals. To this end we propose DAISYnt, a suite of tests to measure synthetic tabular data quality and privacy.

Advancing digital healthcare research and machine learning-aided knowledge extraction amidst the COVID-19 pandemic

The rapid progression of biomedical research coupled with the explosion of scientific literature has generated an exigent need for efficient and reliable systems of knowledge extraction. This dissertation contends with this challenge through a concentrated investigation of digital health, Artificial Intelligence, and specifically Machine Learning and Natural Language Processing's (NLP) potential to expedite systematic literature reviews and refine the knowledge extraction process. The surge of COVID-19 complicated the efforts of scientists, policymakers, and medical professionals in identifying pertinent articles and assessing their scientific validity. This thesis presents a substantial solution in the form of the COKE Project, an initiative that interlaces machine reading with the rigorous protocols of Evidence-Based Medicine to streamline knowledge extraction. In the framework of the COKE (“COVID-19 Knowledge Extraction framework for next-generation discovery science”) Project, this thesis aims to underscore the capacity of machine reading to create knowledge graphs from scientific texts. The project is remarkable for its innovative use of NLP techniques such as a BERT + bi-LSTM language model. This combination is employed to detect and categorize elements within medical abstracts, thereby enhancing the systematic literature review process. The COKE project's outcomes show that NLP, when used in a judiciously structured manner, can significantly reduce the time and effort required to produce medical guidelines. These findings are particularly salient during times of medical emergency, like the COVID-19 pandemic, when quick and accurate research results are critical.

Network analysis and machine learning assist drug repurposing and safety assessment in neurological diseases

In recent decades, two prominent trends have influenced the data modeling field, namely network analysis and machine learning. This thesis explores the practical applications of these techniques within the domain of drug research, unveiling their multifaceted potential for advancing our comprehension of complex biological systems. The research undertaken during this PhD program is situated at the intersection of network theory, computational methods, and drug research. Across six projects presented herein, there is a gradual increase in model complexity. These projects traverse a diverse range of topics, with a specific emphasis on drug repurposing and safety in the context of neurological diseases. The aim of these projects is to leverage existing biomedical knowledge to develop innovative approaches that bolster drug research. The investigations have produced practical solutions, not only providing insights into the intricacies of biological systems, but also allowing the creation of valuable tools for their analysis. In short, the achievements are: • A novel computational algorithm to identify adverse events specific to fixed-dose drug combinations. • A web application that tracks the clinical drug research response to SARS-CoV-2. • A Python package for differential gene expression analysis and the identification of key regulatory "switch genes". • The identification of pivotal events causing drug-induced impulse control disorders linked to specific medications. • An automated pipeline for discovering potential drug repurposing opportunities. • The creation of a comprehensive knowledge graph and development of a graph machine learning model for predictions. Collectively, these projects illustrate diverse applications of data science and network-based methodologies, highlighting the profound impact they can have in supporting drug research activities.