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.

Analysis and developments of uncertainty processors for real time flood forecasting

The hydrologic risk (and the hydro-geologic one, closely related to it) is, and has always been, a very relevant issue, due to the severe consequences that may be provoked by a flooding or by waters in general in terms of human and economic losses. Floods are natural phenomena, often catastrophic, and cannot be avoided, but their damages can be reduced if they are predicted sufficiently in advance. For this reason, the flood forecasting plays an essential role in the hydro-geological and hydrological risk prevention. Thanks to the development of sophisticated meteorological, hydrologic and hydraulic models, in recent decades the flood forecasting has made a significant progress, nonetheless, models are imperfect, which means that we are still left with a residual uncertainty on what will actually happen. In this thesis, this type of uncertainty is what will be discussed and analyzed. In operational problems, it is possible to affirm that the ultimate aim of forecasting systems is not to reproduce the river behavior, but this is only a means through which reducing the uncertainty associated to what will happen as a consequence of a precipitation event. In other words, the main objective is to assess whether or not preventive interventions should be adopted and which operational strategy may represent the best option. The main problem for a decision maker is to interpret model results and translate them into an effective intervention strategy. To make this possible, it is necessary to clearly define what is meant by uncertainty, since in the literature confusion is often made on this issue. Therefore, the first objective of this thesis is to clarify this concept, starting with a key question: should be the choice of the intervention strategy to adopt based on the evaluation of the model prediction based on its ability to represent the reality or on the evaluation of what actually will happen on the basis of the information given by the model forecast? Once the previous idea is made unambiguous, the other main concern of this work is to develope a tool that can provide an effective decision support, making possible doing objective and realistic risk evaluations. In particular, such tool should be able to provide an uncertainty assessment as accurate as possible. This means primarily three things: it must be able to correctly combine all the available deterministic forecasts, it must assess the probability distribution of the predicted quantity and it must quantify the flooding probability. Furthermore, given that the time to implement prevention strategies is often limited, the flooding probability will have to be linked to the time of occurrence. For this reason, it is necessary to quantify the flooding probability within a horizon time related to that required to implement the intervention strategy and it is also necessary to assess the probability of the flooding time.

Statistical methods for analysis and processing of medical ultrasound: applications to segmentation and restoration

In this thesis two major topics inherent with medical ultrasound images are addressed: deconvolution and segmentation. In the first case a deconvolution algorithm is described allowing statistically consistent maximum a posteriori estimates of the tissue reflectivity to be restored. These estimates are proven to provide a reliable source of information for achieving an accurate characterization of biological tissues through the ultrasound echo. The second topic involves the definition of a semi automatic algorithm for myocardium segmentation in 2D echocardiographic images. The results show that the proposed method can reduce inter- and intra observer variability in myocardial contours delineation and is feasible and accurate even on clinical data.

Chemical analysis and reactivity of biomass pyrolysis products. Application to the development of carbon-neutral biofuels and chemicals

In this dissertation the pyrolytic conversion of biomass into chemicals and fuels was investigated from the analytical point of view. The study was focused on the liquid (bio-oil) and solid (char) fractions obtainable from biomass pyrolysis. The drawbacks of Py-GC-MS described so far were partially solved by coupling different analytical configurations (Py-GC-MS, Py-GC-MIP-AED and off-line Py-SPE and Py-SPME-GC-MS with derivatization procedures). The application of different techniques allowed a satisfactory comparative analysis of pyrolysis products of different biomass and a high throughput screening on effect of 33 catalysts on biomass pyrolysis. As the results of the screening showed, the most interesting catalysts were those containing copper (able to reduce the high molecular weight fraction of bio-oil without large yield decrease) and H-ZSM-5 (able to entirely convert the bio-oil into “gasoline like” aromatic products). In order to establish the noxious compounds content of the liquid product, a clean-up step was included in the Py-SPE procedure. This allowed to investigate pollutants (PAHs) generation from pyrolysis and catalytic pyrolysis of biomass. In fact, bio-oil from non-catalytic pyrolysis of biomass showed a moderate PAHs content, while the use of H-ZSM-5 catalyst for bio-oil up-grading determined an astonishing high production of PAHs (if compared to what observed in alkanes cracking), indicating an important concern in the substitution fossil fuel with bio-oil derived from biomass. Moreover, the analytical procedures developed in this thesis were directly applied for the detailed study of the most useful process scheme and up-grading route to chemical intermediates (anhydrosugars), transportation fuels or commodity chemicals (aromatic hydrocarbons). In the applied study, poplar and microalgae biomass were investigated and overall GHGs balance of pyrolysis of agricultural residues in Ravenna province was performed. A special attention was put on the comparison of the effect of bio-char different use (fuel or as soil conditioner) on the soil health and GHGs emissions.

Statistical analysis and simulation techniques in wall-bounded turbulence

The present work is devoted to the assessment of the energy fluxes physics in the space of scales and physical space of wall-turbulent flows. The generalized Kolmogorov equation will be applied to DNS data of a turbulent channel flow in order to describe the energy fluxes paths from production to dissipation in the augmented space of wall-turbulent flows. This multidimensional description will be shown to be crucial to understand the formation and sustainment of the turbulent fluctuations fed by the energy fluxes coming from the near-wall production region. An unexpected behavior of the energy fluxes comes out from this analysis consisting of spiral-like paths in the combined physical/scale space where the controversial reverse energy cascade plays a central role. The observed behavior conflicts with the classical notion of the Richardson/Kolmogorov energy cascade and may have strong repercussions on both theoretical and modeling approaches to wall-turbulence. To this aim a new relation stating the leading physical processes governing the energy transfer in wall-turbulence is suggested and shown able to capture most of the rich dynamics of the shear dominated region of the flow. Two dynamical processes are identified as driving mechanisms for the fluxes, one in the near wall region and a second one further away from the wall. The former, stronger one is related to the dynamics involved in the near-wall turbulence regeneration cycle. The second suggests an outer self-sustaining mechanism which is asymptotically expected to take place in the log-layer and could explain the debated mixed inner/outer scaling of the near-wall statistics. The same approach is applied for the first time to a filtered velocity field. A generalized Kolmogorov equation specialized for filtered velocity field is derived and discussed. The results will show what effects the subgrid scales have on the resolved motion in both physical and scale space, singling out the prominent role of the filter length compared to the cross-over scale between production dominated scales and inertial range, lc, and the reverse energy cascade region lb. The systematic characterization of the resolved and subgrid physics as function of the filter scale and of the wall-distance will be shown instrumental for a correct use of LES models in the simulation of wall turbulent flows. Taking inspiration from the new relation for the energy transfer in wall turbulence, a new class of LES models will be also proposed. Finally, the generalized Kolmogorov equation specialized for filtered velocity fields will be shown to be an helpful statistical tool for the assessment of LES models and for the development of new ones. As example, some classical purely dissipative eddy viscosity models are analyzed via an a priori procedure.

Analysis and Implementation of Multiphase-Multilevel Inverter for Open-Winding Loads

Research work carried out in focusing a novel multiphase-multilevel ac motor drive system much suitable for low-voltage high-current power applications. In specific, six-phase asymmetrical induction motor with open-end stator winding configuration, fed from four standard two-level three-phase voltage source inverters (VSIs). Proposed synchronous reference frame control algorithm shares the total dc source power among the 4 VSIs in each switching cycle with three degree of freedom. Precisely, first degree of freedom concerns with the current sharing between two three-phase stator windings. Based on modified multilevel space vector pulse width modulation shares the voltage between each single VSIs of two three-phase stator windings with second and third degree of freedom, having proper multilevel output waveforms. Complete model of whole ac motor drive based on three-phase space vector decomposition approach was developed in PLECS - numerical simulation software working in MATLAB environment. Proposed synchronous reference control algorithm was framed in MATLAB with modified multilevel space vector pulse width modulator. The effectiveness of the entire ac motor drives system was tested. Simulation results are given in detail to show symmetrical and asymmetrical, power sharing conditions. Furthermore, the three degree of freedom are exploited to investigate fault tolerant capabilities in post-fault conditions. Complete set of simulation results are provided when one, two and three VSIs are faulty. Hardware prototype model of quad-inverter was implemented with two passive three-phase open-winding loads using two TMS320F2812 DSP controllers. Developed McBSP (multi-channel buffered serial port) communication algorithm able to control the four VSIs for PWM communication and synchronization. Open-loop control scheme based on inverse three-phase decomposition approach was developed to control entire quad-inverter configuration and tested with balanced and unbalanced operating conditions with simplified PWM techniques. Both simulation and experimental results are always in good agreement with theoretical developments.

Performance Analysis and Improvements for the Future Aeronautical Mobile Airport Communications System (AeroMACS)

This thesis deals with the development of the upcoming aeronautical mobile airport communications system (AeroMACS) system. We analyzed the performance of AeroMACS and we investigated potential solutions for enhancing its performance. Since the most critical results correspond to the channel scenario having less diversity1, we tackled this problem investigating potential solutions for increasing the diversity of the system and therefore improving its performance. We accounted different forms of diversity as space diversity and time diversity. More specifically, space (antenna and cooperative) diversity and time diversity are analyzed as countermeasures for the harsh fading conditions that are typical of airport environments. Among the analyzed techniques, two novel concepts are introduced, namely unequal diversity coding and flexible packet level codes. The proposed techniques have been analyzed on a novel airport channel model, derived from a measurement campaign at the airport of Munich (Germany). The introduced techniques largely improve the performance of the conventional AeroMACS link; representing thus appealing solutions for the long term evolution of the system.

Trascriptome analysis and functional genomics of Neisseria meningitidis in human blood

Neisseria meningitidis (Nm) is the major cause of septicemia and meningococcal meningitis. During the course of infection, it must adapt to different host environments as a crucial factor for survival. Despite the severity of meningococcal sepsis, little is known about how Nm adapts to permit survival and growth in human blood. A previous time-course transcriptome analysis, using an ex vivo model of human whole blood infection, showed that Nm alters the expression of nearly 30% of ORFs of the genome: major dynamic changes were observed in the expression of transcriptional regulators, transport and binding proteins, energy metabolism, and surface-exposed virulence factors. Starting from these data, mutagenesis studies of a subset of up-regulated genes were performed and the mutants were tested for the ability to survive in human whole blood; Nm mutant strains lacking the genes encoding NMB1483, NalP, Mip, NspA, Fur, TbpB, and LctP were sensitive to killing by human blood. Then, the analysis was extended to the whole Nm transcriptome in human blood, using a customized 60-mer oligonucleotide tiling microarray. The application of specifically developed software combined with this new tiling array allowed the identification of different types of regulated transcripts: small intergenic RNAs, antisense RNAs, 5’ and 3’ untranslated regions and operons. The expression of these RNA molecules was confirmed by 5’-3’RACE protocol and specific RT-PCR. Here we describe the complete transcriptome of Nm during incubation in human blood; we were able to identify new proteins important for survival in human blood and also to identify additional roles of previously known virulence factors in aiding survival in blood. In addition the tiling array analysis demonstrated that Nm expresses a set of new transcripts, not previously identified, and suggests the presence of a circuit of regulatory RNA elements used by Nm to adapt to proliferate in human blood.

Experimental analysis and FE Modeling of Aluminium alloys Microstructural Evolution in Extrusion

Extrusion is a process used to form long products of constant cross section, from simple billets, with a high variety of shapes. Aluminum alloys are the materials most processed in the extrusion industry due to their deformability and the wide field of applications that range from buildings to aerospace and from design to automotive industries. The diverse applications imply different requirements that can be fulfilled by the wide range of alloys and treatments, that is from critical structural application to high quality surface and aesthetical aspect. Whether one or the other is the critical aspect, they both depend directly from microstructure. The extrusion process is moreover marked by high deformations and complex strain gradients making difficult the control of microstructure evolution that is at present not yet fully achieved. Nevertheless the evolution of Finite Element modeling has reached a maturity and can therefore start to be used as a tool for investigation and prediction of microstructure evolution. This thesis will analyze and model the evolution of microstructure throughout the entire extrusion process for 6XXX series aluminum alloys. Core phase of the work was the development of specific tests to investigate the microstructure evolution and validate the model implemented in a commercial FE code. Along with it two essential activities were carried out for a correct calibration of the model beyond the simple research of contour parameters, thus leading to the understanding and control of both code and process. In this direction activities were also conducted on building critical knowhow on the interpretation of microstructure and extrusion phenomena. It is believed, in fact, that the sole analysis of the microstructure evolution regardless of its relevance in the technological aspects of the process would be of little use for the industry as well as ineffective for the interpretation of the results.

Integrated analysis and design of optimization and up-scaling of inductively coupled plasma synthesis of nanoparticles

This study is focused on radio-frequency inductively coupled thermal plasma (ICP) synthesis of nanoparticles, combining experimental and modelling approaches towards process optimization and industrial scale-up, in the framework of the FP7-NMP SIMBA European project (Scaling-up of ICP technology for continuous production of Metallic nanopowders for Battery Applications). First the state of the art of nanoparticle production through conventional and plasma routes is summarized, then results for the characterization of the plasma source and on the investigation of the nanoparticle synthesis phenomenon, aiming at highlighting fundamental process parameters while adopting a design oriented modelling approach, are presented. In particular, an energy balance of the torch and of the reaction chamber, employing a calorimetric method, is presented, while results for three- and two-dimensional modelling of an ICP system are compared with calorimetric and enthalpy probe measurements to validate the temperature field predicted by the model and used to characterize the ICP system under powder-free conditions. Moreover, results from the modeling of critical phases of ICP synthesis process, such as precursor evaporation, vapour conversion in nanoparticles and nanoparticle growth, are presented, with the aim of providing useful insights both for the design and optimization of the process and on the underlying physical phenomena. Indeed, precursor evaporation, one of the phases holding the highest impact on industrial feasibility of the process, is discussed; by employing models to describe particle trajectories and thermal histories, adapted from the ones originally developed for other plasma technologies or applications, such as DC non-transferred arc torches and powder spherodization, the evaporation of micro-sized Si solid precursor in a laboratory scale ICP system is investigated. Finally, a discussion on the role of thermo-fluid dynamic fields on nano-particle formation is presented, as well as a study on the effect of the reaction chamber geometry on produced nanoparticle characteristics and process yield.

Analysis and development of ecologically based approaches to coastal defense

Climate-change related impacts, notably coastal erosion, inundation and flooding from sea level rise and storms, will increase in the coming decades enhancing the risks for coastal populations. Further recourse to coastal armoring and other engineered defenses to address risk reduction will exacerbate threats to coastal ecosystems. Alternatively, protection services provided by healthy ecosystems is emerging as a key element in climate adaptation and disaster risk management. I examined two distinct approaches to coastal defense on the base of their ecological and ecosystem conservation values. First, I analyzed the role of coastal ecosystems in providing services for hazard risk reduction. The value in wave attenuation of coral reefs was quantitatively demonstrated using a meta-analysis approach. Results indicate that coral reefs can provide wave attenuation comparable to hard engineering artificial defenses and at lower costs. Conservation and restoration of existing coral reefs are cost-effective management options for disaster risk reduction. Second, I evaluated the possibility to enhance the ecological value of artificial coastal defense structures (CDS) as habitats for marine communities. I documented the suitability of CDS to support native, ecologically relevant, habitat-forming canopy algae exploring the feasibility of enhancing CDS ecological value by promoting the growth of desired species. Juveniles of Cystoseira barbata can be successfully transplanted at both natural and artificial habitats and not affected by lack of surrounding adult algal individuals nor by substratum orientation. Transplantation success was limited by biotic disturbance from macrograzers on CDS compared to natural habitats. Future work should explore the reasons behind the different ecological functioning of artificial and natural habitats unraveling the factors and mechanisms that cause it. The comprehension of the functioning of systems associated with artificial habitats is the key to allow environmental managers to identify proper mitigation options and to forecast the impact of alternative coastal development plans.

Molecular strategies for genetic diversity analysis and development of markers linked to resistance traits in apple

The goal of many plant scientists’ research is to explain natural phenotypic variation in term of simple changes in DNA sequence. DNA-based molecular markers are extensively used for the construction of genome-wide molecular maps and to perform genetic analysis for simple and complex traits. The PhD thesis was divided into two main research lines according to the different approaches adopted. The first research line is to analyze the genetic diversity in an Italian apple germplasm collection for the identification of markers tightly linked to targeted genes by an association genetic method. This made it possible to identify synomym and homonym accessions and triploids. The fruit red skin color trait has been used to test the reliability of the genetic approaches in this species. The second line is related to the development of molecular markers closely linked to the Rvi13 and Rvi5 scab resistance genes, previously mapped on apple’s chromosome 10 and 17 respectively by using the traditional linkage mapping method. Both region have been fine-mapped with various type of markers that could be used for marker-assisted selection in future breeding programs and to isolate the two resistance genes.

Non-Linear Analysis and Design of Synchronous Bearingless Multiphase Permanent Magnet Machines and Drives

A two-dimensional model to analyze the distribution of magnetic fields in the airgap of a PM electrical machines is studied. A numerical algorithm for non-linear magnetic analysis of multiphase surface-mounted PM machines with semi-closed slots is developed, based on the equivalent magnetic circuit method. By using a modular structure geometry, whose the basic element can be duplicated, it allows to design whatever typology of windings distribution. In comparison to a FEA, permits a reduction in computing time and to directly changing the values of the parameters in a user interface, without re-designing the model. Output torque and radial forces acting on the moving part of the machine can be calculated. In addition, an analytical model for radial forces calculation in multiphase bearingless Surface-Mounted Permanent Magnet Synchronous Motors (SPMSM) is presented. It allows to predict amplitude and direction of the force, depending on the values of torque current, of levitation current and of rotor position. It is based on the space vectors method, letting the analysis of the machine also during transients. The calculations are conducted by developing the analytical functions in Fourier series, taking all the possible interactions between stator and rotor mmf harmonic components into account and allowing to analyze the effects of electrical and geometrical quantities of the machine, being parametrized. The model is implemented in the design of a control system for bearingless machines, as an accurate electromagnetic model integrated in a three-dimensional mechanical model, where one end of the motor shaft is constrained to simulate the presence of a mechanical bearing, while the other is free, only supported by the radial forces developed in the interactions between magnetic fields, to realize a bearingless system with three degrees of freedom. The complete model represents the design of the experimental system to be realized in the laboratory.