Ingegneria industriale e dell'informazione

ABSTRACT The student started his work towards the PhD. in 2005, joining the Bioengineering and ICT group of the University of Trieste, whose core research was in the e-health area. The personal research project conducted by the PhD student was inserted in the O3 Consortium research project, which had the aim to propose a complete solution for the adoption of open technology in the healthcare environment. The solution should become a whole new model for e-health application and include new products integrated with a development, support and business model. The PhD student contributed to the project in thinking and designing all the aspects of the complete solution presented in this thesis, in the development and business models, as well as in developing the products and in writing and publishing the results of the steps of this work. He personally contributed proposing the original idea of the support model and designing and implementing a product to test the proposed model. The student had an intermediate step in his personal project: he built a state of the art server for the management of DICOM data and of imaging objects (PACS – Picture and Archiving Communication System), with the aim to ease the adoption of e-health technology and to develop a product on which the model would have been tested. The research was conducted in the following way: first, based on the analysis of real world needs, literature and past experience, the definition of the O3 Consortium project software design guidelines (called “requirements” in the thesis) was performed. Then the product was designed and a new release of the PACS system was developed, implementing original solutions to best achieve all those “requirements”. The technological choices and the original aspects against the state of the art have been discussed and underlined throughout the entire thesis, such as the compliance to all the requirements and the choices for portability, project organization, standard implementation and performance. The idea of O3-DPACS being an integrated project, system plus support model has been also presented and discussed in the thesis.. It should be remarked again that the O3 Consortium means not only software development but also new procedures in both technology and service delivering. Moreover, the PhD student performed the validation of the software and the model, which needed to verify the assumption and to obtain the first results in the O3 Consortium research on e-health adoption. Should be noted the originality of the O3 Consortium project proposal of a whole complete application model to the healthcare real world based on open source software. No other solution for open source software application makes a complete proposal for all the topics of development, design, software architecture, support and business opportunity. Thus, a real research interest exists in testing and validating the model.

L'elaborazione dei segnali biomedici è fondamentale per l'interpretazione oggettiva dei sistemi fisiologici, infatti, permette di estrarre e quantificare le informazioni contenute nei segnali che sono generati dai sistemi oggetto di studio. Per analizzare i segnali biomedici, sono stati introdotti un gran numero di algoritmi inizialmente nati in ambiti di ricerca differenti. Negli ultimi decenni, il classico approccio lineare, basato principalmente sull'analisi spettrale, è stato affiancato con successo da metodi e tecniche derivanti dalla teoria della dinamica nonlineare e, in particolare, da quella del caos deterministico. L'obiettivo di questa tesi è quello di valutare i risultati dell'applicazione di diversi metodi di elaborazione, lineari e non lineari, a specifici studi clinici basati sul segnale di variabilità cardiaca (Heart Rate Variability, HRV) e sul segnale elettroencefalografico (EEG). Questi segnali, infatti, mostrano comportamenti attribuibili a sistemi la cui natura può essere alternativamente di tipo lineare o non, a seconda delle condizioni nelle quali i sistemi vengono analizzati. Nella prima parte della tesi, sono presentati i due segnali oggetto di studio (HRV ed EEG) e le tecniche di analisi utilizzate. Nel capitolo 1 vengono descritti il significato fisiologico, i requisiti necessari per l'acquisizione dei dati e i metodi di pre-elaborazione dei segnali. Nel capitolo 2 sono presentati i metodi e gli algoritmi utilizzati in questa tesi per la caratterizzazione delle diverse condizioni sperimentali in cui HRV e EEG sono stati studiati, prestando particolare attenzione alle tecniche di analisi non lineare. Nei capitoli seguenti (capitoli 3-7), sono presentate le cinque applicazioni dell'analisi dei segnali HRV ed EEG esaminate durante il dottorato. Più precisamente, le prime tre riguardano la variabilità cardiaca, le altre due il segnale EEG. Per quanto riguarda il segnale HRV, il primo studio analizza le variazioni delle proprietà spettrali e frattali in soggetti sani di diversa età; il secondo è focalizzatosull'importanza dell'approccio nonlineare nell'analisi del segnale HRV ricavato da registrazioni polisonnografiche di pazienti affetti da gravi apnee notturne; il terzo presenta le differenze nelle caratteristiche spettrali e nonlineari della variabilità cardiaca in pazienti con scompenso cardiaco determinato da diverse eziologie. Invece, per il segnale EEG, il primo studio analizza le alterazioni negli indici spettrali e nonlineari in pazienti con deficit cognitivi soggettivi e lievi, mentre il secondo valuta l'efficacia di un nuovo protocollo per la riabilitazione della malattia di Parkinson, attraverso la quantificazione dei parametri spettrali dell'EEG.

Therapy delivery in modern cardiac electrotherapy systems is based almost exclusively on the information about cardiac electrical depolarization. This kind of detection lacks any data about the myocardial contraction. An optimal heart rhythm control should integrate the assessment of the mechanical cardiac activity and related hemodynamic parameters to the already existing electrical signal analysis. A hemodynamic sensor integrated in pacing systems would be a valuable instrument for many applications. Only few hemodynamic sensors integrated in cardiac electrotherapy systems are currently available on the market. In order to fill the gap, I have explored the possibility of building a hemodynamic sensor for myocardial contraction detection that could be easily integrated in the existing cardiac pacing and defibrillator leads. In this thesis I propose two sensors. One is based on tribolectricity and the other one requires the measurement of high frequency lead parameters. The triboelectric sensor system measures the charge generated due to the triboelectric effect between one of the lead conductors and the inserted stylet as a result of the lead bending. The measurement system consists in sterile charge amplifiers for use in sterile operation field and a non-sterile enclosure containing isolation amplifiers and power supply. Atrial and right ventricular tensiometric signals were recorded during numerous ovine and human experiments and have shown good results under different measurement conditions. The main downside is the necessity of the additional hardware in terms of chronic stylet insertion in the pacing lead lumen. The sensor based on the measurement of high frequency (HF) pacing lead parameters has its origin in previous extensive in vitro experiments on the HF characteristics of the lead. These experiments have supported the idea of considering any bipolar lead to be a HF transmission line with its characteristic impedance and attenuation. An original study revaluing lead HF parameters after being soaked for more than a decade in the saline solution is presented. A parallel study on dry new leads was also carried out. The hemodynamic HF sensor is based on the variation of the pacing lead HF impedance and reflection coefficient due to its movement during cardiac contractions. The quality of the signal was proven in a series of ovine and human experiments and during dobutamine test in sheep. Both sensors would be feasible hemodynamic sensors for various applications: capture management, rate responsiveness, heart failure monitoring, CRT optimization, tachycardia hemodynamic stability assessment, AF therapy titration and vasovagal syncope prediction. These two sensors are unique for their simplicity and universality for all existing endovenous bipolar cardiac leads.

Tomographic imaging is both the science and the tool to explore the internal structure of objects. The mission is to use images to characterize the static and/or dynamic properties of the imaged object in order to further integrate these properties into principles, laws or theories. Among the recent trends in tomographic imaging, three- dimensional (3D) methods are gaining preference and there is the quest for overcoming the bare qualitative observation towards the extraction of quantitative parameters directly from the acquired images. To this aim, Computed Tomography (CT) and Magnetic Resonance Imaging (MRI), as well as the related micro-scale techniques (μ-CT and μ-MRI), are promising tools for all the fields of science in which non-destructive tests are required. In order to support the interpretation of the images produced by these techniques, there is a growing demand of reliable image analysis methods for the specific 3D domain. The aim of this thesis is to present approaches for effective and efficient three-dimensional image analysis with special emphasis on porous media analysis. State-of-the art as well as innovative tools are included in a special software and hardware solution named Pore3D, developed in a collaboration with the Italian 3rd generation synchrotron laboratory Elettra (Basovizza - Trieste, Italy). Algorithms and methods for the characterization of different kinds of porous media are described. The key steps of image segmentation and skeletonization of the segmented pore space are also discussed in depth. Three different clinical and biomedical applications of quantitative analysis of tomographic images are presented. The reported applications have in common the characterization of the micro-architecture of trabecular bone. The trabecular (or cancellous) bone is a 3D mesh- work of bony trabeculae and void spaces containing the bone marrow. It can then be thought of as a porous medium with an interconnected porous space. To be more specific, the first application aims at characterizing a structure (a tissue engineering scaffold) that has to mimic the architecture of trabecular bone. The relevant features of porosity, pore- and throat-size distributions, connectivity and structural anisotropy indexes are automatically extracted from μ-CT images. The second application is based on ex vivo experiments carried out on femurs and lumbar spines of mice affected by microgravity conditions. Wild type and transgenic mice were hosted in the International Space Station (ISS) for 3 months and the observed bone loss due to the near-zero gravity was quantified by means of synchrotron radiation μ-CT image analysis. Finally, the results of an in vivo study on the risk of fracture in osteoporotic subjects is reported. The study is based on texture analysis of high resolution clinical magnetic resonance (MR) images.

Most of the knowledge about physiological systems has been learned using linear system theory. The randomness of many biomedical signals has been traditionally ascribed to a noise-like behavior. An alternative explanation for the irregular behavior observed in systems which do not seem to be inherently stochastic is provided by one of the most striking mathematical developments of the past few decades, i.e., chaos theory. Chaos theory suggests that random-like behavior can arise in some deterministic nonlinear systems with just a few degrees of freedom. One of the most evocative aspects of deterministic chaos is the concept of fractal geometry. Fractal structure, characterized by self-similarity and noninteger dimension, is displayed in chaotic systems by a subset of the phase space known as strange attractor. However, fractal properties are observed also in the unpredictable time evolution and in the 1/f^β power-law of many biomedical signals. The research activities carried out by the Author during the PhD program are concerned with the analysis of the fractal-like behavior of the EEG. The focus was set on those methods which evaluate the fractal geometry of the EEG in the time domain, in the hope of providing physicians and researchers with new valuable tools of low computational cost for the EEG analysis. The performances of three widely used techniques for the direct estimation of the fractal dimension of the EEG were compared and the accuracy of the fBm scaling relationship, often used to obtain indirect estimates from the slope of the spectral density, was assessed. Direct estimation with Higuchi's algorithm turned out to be the most suitable methodology, producing correct estimates of the fractal dimension of the electroencephalogram also on short traces, provided that minimum sampling rate required to avoid aliasing is used. Based on this result, Higuchi's fractal dimension was used to address three clinical issues which could involve abnormal complexity of neuronal brain activity: 1) the monitoring of carotid endarterectomy for the prevention of intraoperative stroke, 2) the assessment of the depth of anesthesia to monitor unconsciousness during surgery and 3) the analysis of the macro-structural organization of the EEG in autism with respect to mental retardation. The results of the clinical studies suggest that, although linear spectral analysis still represents a valuable tool for the investigation of the EEG, time domain fractal analysis provides additional information on brain functioning which traditional analysis cannot achieve, making use of techniques of low computational cost.

The scope of this study was to examine ICT telemedicine innovations and potentialities in web-portals, intranet services and tele-radiology topics respectively, in order to design, develop and, possibly, realize apposite telemedicine systems and solutions for healthcare and in particular for the hospitals. ICT techniques and technologies are nowadays applied in every area of our common living from work places to our homes, our free-time, schools, universities and so on. The healthcare services offered by hospitals are heavily supported by technologies and, behind them, by a wide research both in ICT and biomedical sciences. Thanks to these advances telemedicine is now becoming a fundamental part of services offered by hospitals and healthcare structures. The healthcare management, the doctors and the common people are now experimenting how telemedicine is an added value to all the services offered in terms of the quality of care, the patient follow up, the early diagnose and treatment of pathologies and diseases. In this research is presented an all-inclusive approach to telemedicine problems and challenges in particular studying, developing and proposing ICT methods and technologies in the above mentioned three areas of interest: •innovative healthcare and telemedicine-ready hospital website or portal design and development; •analysis and study of models for the realization of intranet healthcare services to enhance both quality of care and the management of healthcare personnel evaluation; •tele-radiology and some of its actual new perspectives as the study and the evaluation of the “mobile” tele-radiology approach using commercial tablets (and what it could mean).For the first topic the results may be summarized in the development of a more interactive and “social” hospital web-portal offering original solutions and services to all the categories of users (audience, professionals, researchers), allowing them – through the use of advanced tools - to configure and select their own pages and interests. The originality of this approach consists in a good cost/effective result in the respect of the last and worldwide accepted Internet regulations and policies too. A similar approach regarded the intranet services and the design of web interfaces for the clinical practice and the executive evaluation. These kind of innovative systems regard a limited and selected number of more skilled users, typically belonging to a corporation or to specific offices. As above the approach is important: interactive services, innovative tools and affordable instruments are the keywords of the systems designed or proposed to solve specific problems or needs. The last research topic concerned the proposal of a protocol for the assessment of medical images on commercial displays, interesting the stakeholders and the groups involved in medical images treatment, visualization and communication. The potentialities of the mobile tablet devices improve day after day and new devices are marketed every week and the innovation is round the corner. These potentialities must encounter the medical diagnostics world and meet the standards and the regulations the international community established. It will be difficult for a commercial tablet to obtain the medical device CE mark not only for commercial reasons, but the technical limits may be reached and even surpassed adopting objective measures and evaluations. This study demonstrates that commercial tablets may be used in clinical practice for the correct visualization and diagnose of medical images. The measures of some display characteristics may be considered acceptable for mobile interpretation (even report?) of medical images, but if and only if the ambient lighting conditions are under objective control and integrated automated systems in tablets warns physicians about bad or borderline technical and ambient restrictions or bonds.

The thesis describes the study on the characterization of the percussive ventilator; the activities have been carried out in cooperation with the “D.A.I. di Medicina Perioperatoria, Terapia Intensiva ed Emergenza - UCO di Anestesia, Rianimazione e Terapia Antalgica dell'Azienda Mista Universitaria - Ospedaliera di Trieste”. The first chapter describes the physiology of the respiratory system and the classical models presented in literature, the second chapter illustrates the main modes of mechanical ventilation, particularly in the percussive ventilation. The third chapter describes the classical laboratory equipment for the measurement of breathing. The fourth chapter examines the state of the art of methods and instruments for the analysis of respiratory parameters. The fifth chapter discusses the instruments for measuring respiratory parameters, developed in the biomedical laboratory of the DEEI of University of Trieste. The sixth chapter contains a detailed study on the characterization of the percussive ventilator: the model, the method for estimating parameters, the system tests and the results. Particularly, the ability to monitor respiratory parameters by using the instrument developed avoids the volutrauma (alveolar-capillary permeability increase owing to excessive distension of the lung) during controlled ventilation. The instrument also allows to accurately estimate the lung elastance, determining factor of the volume distribution in the used model. At the conclusion of the work, the seventh chapter summarizes the results from the study of the volumes distribution in the two-compartment model of the lung conditioned to percussive ventilation.

High Frequency Percussive Ventilation (HFPV) is a non-conventional ventilatory modality which has proven highly effective in patients with severe gas exchange impairment. However, at the present time, HFPV ventilator provides only airway pressure measurement. The airway pressure measurements and gas exchange analysis are currently the only parameters that guide the physician during the HFPV ventilator setup and treatment monitoring. The evaluation of respiratory system resistance and compliance parameters in patients undergoing mechanical ventilation is used for lung dysfunctions detection, ventilation setup and treatment effect evaluation. Furthermore, the pressure measured by ventilator represents the sum of the endotracheal tube pressure drop and the tracheal pressure. From the clinical point of view, it is very important to take into account the real amount of pressure dissipated by endotracheal tube to avoid lung injury. HFPV is pressure controlled logic ventilation, thus hypoventilation and hyperventilation cases are possible because of tidal volume variations in function of pulmonary and endotracheal tube impedance. This thesis offers a new approach for HFPV ventilator setup in accordance with protective ventilatory strategy and optimization of alveolar recruitment using estimation of the respiratory mechanics parameters and endotracheal pressure drop. Respiratory system resistance and compliance parameters were estimated, firstly in vitro and successively in patients undergoing HFPV, applying least squares regression on Dorkin high frequency model starting from measured respiratory signals. The Blasius model was identified as the most adequate to estimate pressure drop across the endotracheal tube during HFPV. Beside measurement device was developed in order to measure respiratory parameters in patients undergoing HFPV. The possibility to tailor HFPV ventilator setup, using respiratory signals measurement and estimation of respiratory system resistance, compliance and endotracheal tube pressure drop, provided by this thesis, opens a new prospective to this particular ventilatory strategy, improving its beneficial effects and minimizing ventilator-induced lung damage.

Le funzioni fine-motorie sono la base per il rapido conseguimento della piena autonomia strumentale, in particolare il disegno e la scrittura a mano, sono fondamentali per le prestazioni scolastiche e lo sviluppo umano generale. Una varietà di condizioni neurologiche e psichiatriche dell'infanzia e dell'adolescenza potrebbe compromettere il normale sviluppo delle abilità motorie. La ricerca nel settore, soprattutto nel nostro Paese, manca di un sistema di riferimento per la determinazione precoce dei disturbi dell’apprendimento, necessario, inoltre, per una valutazione opportuna del trattamento riabilitativo. A tale scopo, le attività di ricerca svolte dall’Autore nel corso del dottorato hanno inizialmente riguardato lo studio dell’apprendimento in un campione di soggetti a sviluppo tipico, madrelingua italiana e destrimani. Per raggiungere quest’obiettivo sono stati sviluppati algoritmi di elaborazione che permettessero l’analisi delle caratteristiche dinamiche del movimento, da acquisizioni di prove di scrittura eseguite su tavoletta grafica digitale. Una volta definiti i test e i parametri cinematici più informativi per l’analisi dello sviluppo, quali velocità, grado di automazione, arrangiamento spaziale e tempi di pianificazione motoria, sono stati determinati i relativi valori di riferimento per ogni fascia d’età. A questo punto, creato tale sistema di riferimento, è stato possibile fare ulteriori studi su campioni con caratteristiche diverse. Si è avuta l’occasione di analizzare le prestazioni di un gruppo di studenti in cui è stato sperimentato, durante gli anni delle scuole primarie, un metodo di insegnamento ideato nella prima metà del Novecento da Ida Terzi, insegnante elementare all’istituto per ciechi di Reggio Emilia. Il metodo è utilizzato per migliorare la percezione e l’integrazione dello schema corporeo, per organizzare l’orientamento e la rappresentazione mentale dello spazio, facilitando la coerenza percettiva e il passaggio da un utilizzo inconscio a un uso consapevole del corpo in movimento. Confrontando le performance cinematiche di tale campione con un gruppo di controllo, sono state osservate diverse strategie nell’esecuzione delle prove di scrittura proposte, inoltre, grazie allo sviluppo di strumenti per l'analisi della qualità del prodotto scritto, è stato possibile distinguere una migliore accuratezza nel gruppo in cui è stato adottato il Metodo Terzi.

The use of High Frequency Percussive Ventilation (HFPV) is still debated although this type of non-conventional ventilation has proven effective and safe in patients with acute respiratory failure. In the clinical practice, HFPV is not an intuitive ventilatory modality and the absence of real-time delivered volume monitoring produces disaffection among the physicians. Avoiding the "volutrauma" is the cornerstone of the "protective ventilation strategy", which assumes a constant monitoring of inspiratory volume delivered to the patient. Currently the system capable of delivering HFPV is the VDR-4® (Volumetric Diffusive Respirator), which provides only analog airway pressure waveform and digital output of peak and the mean airway pressure. The latter is involved in the determination of oxygenation and hemodynamics, irrespective of the mode of ventilation. At the present time, the mean airway pressure, together with gas exchange analysis, are the only parameters that indirectly guide the physician in assessing the clinical effectiveness of HFPV. Till now, flow, volume and pressure curves generated by HFPV have never been studied in relation to the specific patients respiratory mechanics. The real-time examination of these parameters could allow the physicians to analyze and understand elements of respiratory system mechanics as compliance (Crs), resistance (Rrs), inertance (Irs) and of patient-ventilator interaction. The mechanical effects are complex and result from interactions between ventilator settings and patient’s respiratory system impedance. The aim of this doctoral thesis was to acquire and study volume and respiratory parameters during HFPV in order to explain this complex patients-machine interaction and transfer the results in clinical practice.

Le principali attività di ricerca svolte durante il dottorato hanno riguardano la validazione e caratterizzazione dell’applicabilità di un protocollo per l’analisi della cinematica di spalla in ambito clinico (ISEO - INAIL Shoulder and Elbow Outpatient protocol). Lo scopo principale era quello di creare uno strumento che fornisse al personale sanitario informazioni sulla performance motoria dei pazienti, supportando, con informazioni di tipo quantitativo, la valutazione ambulatoriale delle patologie della spalla. E’ possibile suddividere l’attività di ricerca in tre temi principali: caratterizzazione e validazione di ISEO; applicazione di ISEO per valutazioni di tipo clinico; applicazione di ISEO per valutazione di performance motoria in ambito sportivo. Grazie ai processi di validazione e caratterizzazione svolti e alle applicazioni di ISEO, ad oggi il protocollo può essere utilizzato in studi clinici e sportivi riguardanti la cinematica di spalla (coordinazione scapolo-omerale), per i quali la sensibilità dello strumento può essere considerata adatta alle esigenze valutative.