Analysis and modeling techniques for ultrasonic tissue characterization

This thesis introduces new processing techniques for computer-aided interpretation of ultrasound images with the purpose of supporting medical diagnostic. In terms of practical application, the goal of this work is the improvement of current prostate biopsy protocols by providing physicians with a visual map overlaid over ultrasound images marking regions potentially affected by disease. As far as analysis techniques are concerned, the main contributions of this work to the state-of-the-art is the introduction of deconvolution as a pre-processing step in the standard ultrasonic tissue characterization procedure to improve the diagnostic significance of ultrasonic features. This thesis also includes some innovations in ultrasound modeling, in particular the employment of a continuous-time autoregressive moving-average (CARMA) model for ultrasound signals, a new maximum-likelihood CARMA estimator based on exponential splines and the definition of CARMA parameters as new ultrasonic features able to capture scatterers concentration. Finally, concerning the clinical usefulness of the developed techniques, the main contribution of this research is showing, through a study based on medical ground truth, that a reduction in the number of sampled cores in standard prostate biopsy is possible, preserving the same diagnostic power of the current clinical protocol.

Congenital Nystagmus eye movements analysis and oculomotor system models evaluation

The term Congenital Nystagmus (Early Onset Nystagmus or Infantile Nystagmus Syndrome) refers to a pathology characterised by an involuntary movement of the eyes, which often seriously reduces a subject’s vision. Congenital Nystagmus (CN) is a specific kind of nystagmus within the wider classification of infantile nystagmus, which can be best recognized and classified by means of a combination of clinical investigations and motility analysis; in some cases, eye movement recording and analysis are indispensable for diagnosis. However, interpretation of eye movement recordings still lacks of complete reliability; hence new analysis techniques and precise identification of concise parameters directly related to visual acuity are necessary to further support physicians’ decisions. To this aim, an index computed from eye movement recordings and related to the visual acuity of a subject is proposed in this thesis. This estimator is based on two parameters: the time spent by a subject effectively viewing a target (foveation time - Tf) and the standard deviation of eye position (SDp). Moreover, since previous studies have shown that visual acuity largely depends on SDp, a data collection pilot study was also conducted with the purpose of specifically identifying eventual slow rhythmic component in the eye position and to characterise in more detail the SDp. The results are presented in this thesis. In addition, some oculomotor system models are reviewed and a new approach to those models, i.e. the recovery of periodic orbits of the oculomotor system in patients with CN, is tested on real patients data. In conclusion, the results obtained within this research consent to completely and reliably characterise the slow rhythmic component sometimes present in eye position recordings of CN subjects and to better classify the different kinds of CN waveforms. Those findings can successfully support the clinicians in therapy planning and treatment outcome evaluation.

Foetal heart rate recording: analysis and comparison of different methodologies

Monitoring foetal health is a very important task in clinical practice to appropriately plan pregnancy management and delivery. In the third trimester of pregnancy, ultrasound cardiotocography is the most employed diagnostic technique: foetal heart rate and uterine contractions signals are simultaneously recorded and analysed in order to ascertain foetal health. Because ultrasound cardiotocography interpretation still lacks of complete reliability, new parameters and methods of interpretation, or alternative methodologies, are necessary to further support physicians’ decisions. To this aim, in this thesis, foetal phonocardiography and electrocardiography are considered as different techniques. Further, variability of foetal heart rate is thoroughly studied. Frequency components and their modifications can be analysed by applying a time-frequency approach, for a distinct understanding of the spectral components and their change over time related to foetal reactions to internal and external stimuli (such as uterine contractions). Such modifications of the power spectrum can be a sign of autonomic nervous system reactions and therefore represent additional, objective information about foetal reactivity and health. However, some limits of ultrasonic cardiotocography still remain, such as in long-term foetal surveillance, which is often recommendable mainly in risky pregnancies. In these cases, the fully non-invasive acoustic recording, foetal phonocardiography, through maternal abdomen, represents a valuable alternative to the ultrasonic cardiotocography. Unfortunately, the so recorded foetal heart sound signal is heavily loaded by noise, thus the determination of the foetal heart rate raises serious signal processing issues. A new algorithm for foetal heart rate estimation from foetal phonocardiographic recordings is presented in this thesis. Different filtering and enhancement techniques, to enhance the first foetal heart sounds, were applied, so that different signal processing techniques were implemented, evaluated and compared, by identifying the strategy characterized on average by the best results. In particular, phonocardiographic signals were recorded simultaneously to ultrasonic cardiotocographic signals in order to compare the two foetal heart rate series (the one estimated by the developed algorithm and the other provided by cardiotocographic device). The algorithm performances were tested on phonocardiographic signals recorded on pregnant women, showing reliable foetal heart rate signals, very close to the ultrasound cardiotocographic recordings, considered as reference. The algorithm was also tested by using a foetal phonocardiographic recording simulator developed and presented in this research thesis. The target was to provide a software for simulating recordings relative to different foetal conditions and recordings situations and to use it as a test tool for comparing and assessing different foetal heart rate extraction algorithms. Since there are few studies about foetal heart sounds time characteristics and frequency content and the available literature is poor and not rigorous in this area, a data collection pilot study was also conducted with the purpose of specifically characterising both foetal and maternal heart sounds. Finally, in this thesis, the use of foetal phonocardiographic and electrocardiographic methodology and their combination, are presented in order to detect foetal heart rate and other functioning anomalies. The developed methodologies, suitable for longer-term assessment, were able to detect heart beat events correctly, such as first and second heart sounds and QRS waves. The detection of such events provides reliable measures of foetal heart rate, potentially information about measurement of the systolic time intervals and foetus circulatory impedance.

Streaming audio e video nei sistemi Peer-To-Peer TV: il caso Sopcast P2PTV

La tesi si propone di affrontare il tema del Live Streaming in sistemi P2P con particolare riferimento a Sopcast, un applicativo di P2PTV. Viene fatto un ricorso storico riguardo alla nascita dello streaming e al suo sviluppo, vengono descritte le caratteristiche, il protocollo di comunicazione e i modelli più diffusi per il live streaming P2P. Inoltre si tratterà come viene garantita la qualità del servizio e valutate le performance di un servizio P2PTV.

Numerical simulation of ion transport through ion channels and solid-state nanopores

Ion channels are pore-forming proteins that regulate the flow of ions across biological cell membranes. Ion channels are fundamental in generating and regulating the electrical activity of cells in the nervous system and the contraction of muscolar cells. Solid-state nanopores are nanometer-scale pores located in electrically insulating membranes. They can be adopted as detectors of specific molecules in electrolytic solutions. Permeation of ions from one electrolytic solution to another, through a protein channel or a synthetic pore is a process of considerable importance and realistic analysis of the main dependencies of ion current on the geometrical and compositional characteristics of these structures are highly required. The project described by this thesis is an effort to improve the understanding of ion channels by devising methods for computer simulation that can predict channel conductance from channel structure. This project describes theory, algorithms and implementation techniques used to develop a novel 3-D numerical simulator of ion channels and synthetic nanopores based on the Brownian Dynamics technique. This numerical simulator could represent a valid tool for the study of protein ion channel and synthetic nanopores, allowing to investigate at the atomic-level the complex electrostatic interactions that determine channel conductance and ion selectivity. Moreover it will provide insights on how parameters like temperature, applied voltage, and pore shape could influence ion translocation dynamics. Furthermore it will help making predictions of conductance of given channel structures and it will add information like electrostatic potential or ionic concentrations throughout the simulation domain helping the understanding of ion flow through membrane pores.

Multi-level models and infrastructures for simulating biological system development

The hierarchical organisation of biological systems plays a crucial role in the pattern formation of gene expression resulting from the morphogenetic processes, where autonomous internal dynamics of cells, as well as cell-to-cell interactions through membranes, are responsible for the emergent peculiar structures of the individual phenotype. Being able to reproduce the systems dynamics at different levels of such a hierarchy might be very useful for studying such a complex phenomenon of self-organisation. The idea is to model the phenomenon in terms of a large and dynamic network of compartments, where the interplay between inter-compartment and intra-compartment events determines the emergent behaviour resulting in the formation of spatial patterns. According to these premises the thesis proposes a review of the different approaches already developed in modelling developmental biology problems, as well as the main models and infrastructures available in literature for modelling biological systems, analysing their capabilities in tackling multi-compartment / multi-level models. The thesis then introduces a practical framework, MS-BioNET, for modelling and simulating these scenarios exploiting the potential of multi-level dynamics. This is based on (i) a computational model featuring networks of compartments and an enhanced model of chemical reaction addressing molecule transfer, (ii) a logic-oriented language to flexibly specify complex simulation scenarios, and (iii) a simulation engine based on the many-species/many-channels optimised version of Gillespie’s direct method. The thesis finally proposes the adoption of the agent-based model as an approach capable of capture multi-level dynamics. To overcome the problem of parameter tuning in the model, the simulators are supplied with a module for parameter optimisation. The task is defined as an optimisation problem over the parameter space in which the objective function to be minimised is the distance between the output of the simulator and a target one. The problem is tackled with a metaheuristic algorithm. As an example of application of the MS-BioNET framework and of the agent-based model, a model of the first stages of Drosophila Melanogaster development is realised. The model goal is to generate the early spatial pattern of gap gene expression. The correctness of the models is shown comparing the simulation results with real data of gene expression with spatial and temporal resolution, acquired in free on-line sources.

Innovazione e governance delle reti di assistenza integrate: il caso delle cure palliative

In ambito oncologico il dolore affligge la maggior parte dei pazienti (incidenza riportata dal 53 al 90%), in tutte le fasi della malattia: nonostante l’esistenza di Linee Guida (OMS), l’attuale “undertreatment” del sintomo dolore oncologico, legato a un inappropriato uso degli oppioidi, in Italia raggiunge stime fino al 40% dei casi. Segnalazioni recenti sul consumo degli oppioidi in Italia riportano un aumento imputabile a un solo farmaco (fentanil TTS), il che suggerisce un comportamento prescrittivo inappropriato. Letteratura in merito alle valutazioni di efficacia delle terapie di controllo del dolore sia in fase iniziale – quando la terapia medica oncologica è attiva- sia in fase avanzata di malattia – quando il controllo del dolore si configura come una delle principali terapie di supporto- è ormai disponibile , con un buon livello di affidabilità. Quello che è necessario è aumentare la capacità del Servizio Sanitario di trasferire nella pratica clinica e assistenziale i risultati della ricerca sulla efficacia delle cure. Questi i quesiti ai quali la ricerca ha inteso rispondere: a. Le competenze globalmente espresse dal servizio sanitario dell’Emilia Romagna sono adeguate per consentire un tempestivo, globale, appropriato ed efficace controllo del dolore oncologico, in tutte le fasi della malattia e lungo tutto il percorso di assistenza si a domiciliare che ospedaliero, per tutti i malati che ne hanno bisogno? b. Quali raccomandazioni possiamo fornire, basate sulle evidenze di efficacia, a clinici e gestori per migliorare l’identificazione del bisogno, la scelta del trattamento, il suo monitoraggio, la possibilità di garantirne l’accesso e la disponibilità non solo in ospedale ma anche a domicilio? c. Quale efficacia hanno dimostrato i percorsi di formazione relativi al riconoscimento e al controllo del dolore messi in atto finora? d. Quali percorsi possono essere raccomandati per mettere a disposizione dei cittadini le conoscenze scientifiche sul controllo del dolore oncologico?

Video transmission over wireless channel

This work has been realized by the author in his PhD course in Electrical, Computer Science and Telecommunication at the University of Bologna, Faculty of Engineering, Italy. All the documentation here reported is a summary of years of work, under the supervision of Prof. Oreste Andrisano, coordinator of Wireless Communication Laboratory - WiLab, in Bologna. The subject of this thesis is the transmission of video in a context of heterogeneous network, and in particular, using a wireless channel. All the instrumentation that has been used for the characterization of the telecommunication systems belongs to CNR (National Research Council), CNIT (Italian Inter- University Center), and DEIS (Dept. of Electrical, Computer Science, and Systems). From November 2009 to July 2010, the author spent his time abroad, working in collaboration with DLR - German Aerospace Center in Munich, Germany, on channel coding area, developing a general purpose decoder machine to decode a huge family of iterative codes. A patent concerning Doubly Generalized-Low Density Parity Check codes has been produced by the author as well as some important scientic papers, published on IEEE journals and conferences.

Cooperative and reconfigurable telecommunication systems based on FPGA

This work has been realized by the author in his PhD course in Electronics, Computer Science and Telecommunication at the University of Bologna, Faculty of Engineering, Italy. The subject of this thesis regards important channel estimation aspects in wideband wireless communication systems, such as echo cancellation in digital video broadcasting systems and pilot aided channel estimation through an innovative pilot design in Multi-Cell Multi-User MIMO-OFDM network. All the documentation here reported is a summary of years of work, under the supervision of Prof. Oreste Andrisano, coordinator of Wireless Communication Laboratory - WiLab, in Bologna. All the instrumentation that has been used for the characterization of the telecommunication systems belongs to CNR (National Research Council), CNIT (Italian Inter-University Center), and DEIS (Dept. of Electronics, Computer Science, and Systems). From November 2009 to May 2010, the author spent his time abroad, working in collaboration with DOCOMO - Communications Laboratories Europe GmbH (DOCOMO Euro-Labs) in Munich, Germany, in the Wireless Technologies Research Group. Some important scientific papers, submitted and/or published on IEEE journals and conferences have been produced by the author.

Il collegamento contrattuale, buona fede ed equilibrio tra i contratti

Il fenomeno del collegamento contrattuale prevede la presenza di due o più contratti, diversi e distinti, che, pur caratterizzati dagli elementi e dalla disciplina propri di ognuno, risultano coordinati teleologicamente da un nesso di reciproca dipendenza, in modo che le vicende dell’uno si trasmettono all’altro, influenzandone la validità e l’efficacia. Tale nozione è il frutto dell’elaborazione della dottrina e della giurisprudenza, poiché la disciplina positiva difetta di previsioni recanti la definizione di operazioni in cui si ricorra all’impiego di più contratti in vista di uno scopo economico unitario. Fra le molteplici classificazioni realizzate in relazione a tale strumento, la tipologia che è oggetto di analisi nel presente lavoro è espressione dell’autonomia contrattuale dei contraenti che istituiscono fra i negozi un nesso bilaterale, funzionale e volontario. I presupposti del fenomeno de quo sono, allora, rappresentati dalla necessaria intenzione delle parti di attuare il collegamento, del vincolo che viene creato in concreto e, soprattutto, dal fine pratico unitario ed ulteriore, che esse intendono perseguire coordinando i vari atti. Da qui, l’inquadramento di siffatta figura di collegamento nel fenomeno dell’atipicità contrattuale, frutto dell’attività creativa dei privati di autoregolamentazione dei propri interessi. Dottrina e giurisprudenza, in particolare, reputano il collegamento un meccanismo che agisce sul piano degli effetti dei contratti. Infatti, ogni negozio coinvolto, pur conservando una causa autonoma, è finalizzato ad un unico regolamento di interessi, di talché le vicende che investono uno dei negozi possono ripercuotersi sull’altro (che in sé considerato è immune da vizi) e, pertanto, tutti i contratti simul stabunt simul cadent. In definitiva, così opinando, le patologie che riguardano un atto finiscono per condizionare non solo l’esecuzione, ma anche la validità dell’altro. Successivamente, l’indagine si incentra sull’esegesi dei rari interventi normativi, quasi esclusivamente ascrivibili alla legislazione speciale, che trattano del meccanismo de quo e che si pongono nel solco di quanto affermato dagli interpreti. Muovendo, poi, dal presupposto che l’ordinamento riconosce ai contraenti il potere di dar vita ad autodeterminazioni strutturalmente semplici ovvero come in tal caso più articolate, si cerca di dimostrare che in tali fattispecie l’apprezzamento non va condotto sul singolo contratto, bensì sull’operazione economica unitariamente considerata, come risultante dal collegamento fra più contratti. Infatti, una volta accertata l’interdipendenza funzionale delle diverse prestazioni, l’analisi su di esse assume un rilievo diverso se è compiuta per valutare l’assetto complessivo dell’intera operazione giuridico-economica posta in essere dalle parti: solo a fronte di una valutazione globale dei diritti e degli obblighi, anche in termini economici, si può appurare la reale portata giuridico-economica dell’affare. In forza di tali premesse può, quindi, procedersi ad un compiuto approfondimento del possibile ruolo svolto dalle clausole generali di buona fede ed equilibrio, quali strumenti di garanzia della giustizia negli scambi. Ne consegue l’abbandono di una prospettiva atomistica e, tenendo conto dell’unicità degli interessi perseguiti che vanno oltre le cause proprie dei singoli contratti collegati, si tenta di superare l’assunto per il quale il difetto che inficia uno dei contratti comporti l’automatica caducazione dell’altro. In una visione complessiva dell’operazione, la verifica attinente all’equilibrio tra i singoli atti nei quali essa si svolge ed alla sua possibile alterazione a causa di circostanze sopravvenute o originarie potrebbe sovvertire le certezze interpretative sotto il profilo della disciplina del collegamento, degli effetti dello stesso e delle patologie.