<p>This dissertation aims to demonstrate the feasibility of direct infarct visualization using 3D medical ultrasound. The dissertation proceeds by providing the first ever demonstration of fully-sampled 3D ultrasonic speckle tracking using raw B-Mode data of the heart. The initial demonstration uses a Cramer-Rao lower bound limited displacement estimator. The dissertation then proceeds to develop an implementable method for biased time-delay estimation. Biased time-delay estimation is shown to surpass the traditional limits described by the Cramer-Rao lower bound in a mean square error sense. Additional characterization of this new class of estimator is performed to demonstrate that with easily obtainable levels of prior information it is possible to estimate displacements that do surpass the Cramer-Rao lower bound. Finally, using 2D and 3D realizations of biased displacement estimation (Bayesian speckle tracking) the passive strain induced in the ventricle walls during atrial systole is shown to be sufficient to distinguish healthy and chronically infarcted myocardium.</p> / Dissertation

Η διπλωματική εργασία περιγράφει 2 τεχνικές οι οποίες αξιοποιούν το φαινόμενο του πυρηνικού μαγνητικού συντονισμού προκειμένου να αναλύσουν τη χημική σύσταση του μαλακού ιστού και να απεικονίσουν τις ελαστικές ιδιότητές του. Οι τεχνικές αυτές ονομάζονται Φασματοσκοπία και Ελαστογραφία Μαγνητικού Συντονισμού αντίστοιχα και η εφαρμογή τους σε κλινικό επίπεδο προβλέπεται να πραγματοποιηθεί στα επόμενα δέκα χρόνια. Η εφαρμογή ενός πειράματος MR Φασματοσκοπίας επηρεάζεται από πολλούς παράγοντες τόσο σε υπολογιστικό όσο και σε μηχανικό επίπεδο. Τα λάθη υπεισέρχεται από μια σειρά πηγές και αλλοιώνουν τα τελικά φάσματα, καθιστούν απαραίτητο τον ορισμό ενός πρωτοκόλλου μέσα από το οποίο θα ελέγχονται όλες οι παράμετροι που αξιολογούν την απόδοση της MR Φασματοσκοπίας. Στην εργασία παραθέτουμε ένα συγκεκριμένο πρωτόκολο ποιοτικού ελέγχου και ορίζουμε μια σειρά παραμέτρων η βελτιστοποίηση των οπίων αυξάνει την απόδοση των πειραμάτων in vivo φασματοσκοπίας πρωτονίου του ανθρώπινου εγκεφάλου. ΠΡος αυτό το σκοπό κατασκευάσαμε ένα ιατρικό ομοίωμα, στα πρότυπα άλλων ερευνητικών ομοιωμάτων το οποίο προσομοιώνει τις ανατομικές δομές της ανθρώπινης κεφαλής, αποτελούμενο από 3 ανεξάρτητα μέρη για την καλύτερη προσέγγιση των περιοχών του εγκεφαλονωτιαίου υγρού, του κρανίου και της ασθενούς περιοχής. Το ομοίωμα αυτό τοποθετήθηκε σε ένα σύστημα MRI 1.5T και τα αποτελέσματα των διαφόρων πειραμάτων επεξεργάστηκαν και αξιολογήθηκαν βάσει των παραμέτρων ποιοτικού ελέγχου για την εξαγωγή σημαντικών συμπερασμάτων. Στην εργασία επίσης αναλύουμε μαθηματικά ένα απλό μοντέλο MR Ελαστογραφίας. Συγκεκριμένα, σε ένα σύστημα μαγνητικού τομογράφου Bo Tesla τοποθετούμε ένα ελλειπτικό 3Δ σώμα στο κέντρο των αξόνων, η μάζα του οποίου ακολουθεί κανονική κατανομή σε κάθε άξονα. Πραγματοποιώντας του μετασχηματισμούς Fourier κάτω από την επίδραση της ακουστικής ταλάντωσης συχνότητας Ω στον άξονα z μπορούμε να υπολογίσουμε τη σχέση που περιγράφει την τάση εξόδου και τη συνολική μαγνήτιση. Στη συνέχεια, πραγματοποιούμε την υπολογιστική απεικόνιση των μαθηματικών σχέσεων και εξάγουμε σημαντικά συμπεράσματα, τα οποία μας δείχνουν τον τρόπο με τον οποίο επηρεάζονται τα εξαγόμενα αποτελέσματα υπό την παρουσία του ακουστικού κύματος. / The diploma thesis is divided in two sections. In the first part, we construct a medical phantom for the quality assessment of proton single-volume MR Spectroscopy and MR Spectroscopic Imaging of the human brain. The experiments were analyzed and lead to some important results on the localization issues of the spectroscopic procedure. Inb the second part of the thesis, we create a mathematical model of MR Elastography and we calculate the output of the experiment. More specifically, we apply an acoustic wave on a body inserted in a homogenous magnetic field and see the reaction that take place in the final images.

Posterior tibial tendon dysfunction (PTTD) is a common degenerative condition leading to a severe impairment of gait. There is currently no effective method to determine whether a patient with advanced PTTD would benefit from several months of bracing and physical therapy or ultimately require surgery. Tendon degeneration is closely associated with irreversible degradation of its collagen structure, leading to changes to its mechanical properties. If these properties could be monitored in vivo, it could be used to quantify the severity of tendonosis and help determine the appropriate treatment. Ultrasound elasticity imaging (UEI) is a real-time, noninvasive technique to objectively measure mechanical properties in soft tissue. It consists of acquiring a sequence of ultrasound frames and applying speckle tracking to estimate displacement and strain at each pixel. The goals of my dissertation were to 1) use acoustic simulations to investigate the performance of UEI during tendon deformation with different geometries; 2) develop and validate UEI as a potentially noninvasive technique for quantifying tendon mechanical properties in human cadaver experiments; 3) design a platform for UEI to measure mechanical properties of the PTT in vivo and determine whether there are detectable and quantifiable differences between healthy and diseased tendons. First, ultrasound simulations of tendon deformation were performed using an acoustic modeling program. The effects of different tendon geometries (cylinder and curved cylinder) on the performance of UEI were investigated. Modeling results indicated that UEI accurately estimated the strain in the cylinder geometry, but underestimated in the curved cylinder. The simulation also predicted that the out-of-the-plane motion of the PTT would cause a non-uniform strain pattern within incompressible homogeneous isotropic material. However, to average within a small region of interest determined by principal component analysis (PCA) would improve the estimation. Next, UEI was performed on five human cadaver feet mounted in a materials testing system (MTS) while the PTT was attached to a force actuator. A portable ultrasound scanner collected 2D data during loading cycles. Young's modulus was calculated from the strain, loading force and cross sectional area of the PTT. Average Young's modulus for the five tendons was (0.45±0.16GPa) using UEI. This was consistent with simultaneous measurements made by the MTS across the whole tendon (0.52±0.18GPa). We also calculated the scaling factor (0.12±0.01) between the load on the PTT and the inversion force at the forefoot, a measurable quantity in vivo. This study suggests that UEI could be a reliable in vivo technique for estimating the mechanical properties of the human PTT. Finally, we built a custom ankle inversion platform for in vivo imaging of human subjects (eight healthy volunteers and nine advanced PTTD patients). We found non-linear elastic properties of the PTTD, which could be quantified by the slope between the elastic modulus (E) and the inversion force (F). This slope (ΔE/ΔF), or Non-linear Elasticity Parameter (NEP), was significantly different for the two groups: 0.16±0.20 MPa/N for healthy tendons and 0.45±0.43 MPa/N for PTTD tendons. A receiver operating characteristic (ROC) curve revealed an area under the curve (AUC) of 0.83±0.07, which indicated that the classifier system is valid. In summary, the acoustic modeling, cadaveric studies, and in vivo experiments together demonstrated that UEI accurately quantifies tendon mechanical properties. As a valuable clinical tool, UEI also has the potential to help guide treatment decisions for advanced PTTD and other tendinopathies.

In der vorliegenden medizinischen Promotionsschrift werden verschiedene nicht-invasive Untersuchungsverfahren bei erwachsenen Patienten mit Zystischer Fibrose (CF) zur Detektion einer Leberbeteiligung (CFLD) evaluiert. Das diagnostische Standard-verfahren bei vielen Hepatopathien, die Leberbiopsie, ist auf Grund der fokalen Manifestation der CFLD und der häufigen pulmonalen Begleiterkrankung bei CF nicht Bestandteil der Routinediagnostik. CF- Patienten werden daher im Rahmen der vorliegenden Studie mittels konventionellen Ultraschalls, Acoustic Radiation Force Impulse (ARFI) - Imagings, Transienter Elastographie (TE) und verschiedener Fibrosescores untersucht. Ferner wird die Eignung der elastographischen Methoden als Verlaufsparameter bei einem Teil der Studienkohorte evaluiert. Ziel ist die Bewertung des diagnostischen Nutzens der angewandten Untersuchungsmethoden bezüglich der Differenzierung zwischen CF-Patienten ohne Leberbeteiligung, CFLD und CFLD-induzierter Zirrhose. Lebergesunde Probanden und Patienten mit ethyltoxischer Leberzirrhose dienen als Kontrollgruppen. Die Ergebnisse dieser wissenschaftlichen Arbeit zeigen, dass die elastographische Untersuchung der Leber bei erwachsenen CF- Patienten, als nicht-invasives Verfahren im Rahmen der Routinediagnostik zur Detektion einer CFLD-induzierten Zirrhose, ergänzend genutzt werden kann. Für die Beurteilung des klinischen Nutzens als Verlaufsparameter sind weitere Studien notwendig.

Interest in elastographic techniques for soft tissue imaging has grown as relevant research continues to indicate a correlation between tissue histology and mechanical stiffness. Digital Image Elasto-Tomography (DIET) presents a novel method for identifying cancerous lesions via a three-dimensional image of elastic properties. Stiffness reconstruction with DIET takes steady-state motion captured with a digital camera array as the input to an elastic property reconstruction algorithm, where finite element methods allow simulation of phantom motion at a range of internal stiffness distributions. The low cost and high image contrast achievable with a DIET system may be particularly suited to breast cancer screening, where traditional modalities such as mammography have issues with limited sensitivity and patient discomfort. Proof of concept studies performed on simulated data sets confirmed the potential of the DIET technique, leading to the development of an experimental apparatus for surface motion capture from a range of soft tissue approximating phantoms. Error studies performed on experimental data from these phantoms using a limited number of shape and modulus parameters indicated that accurate measurements of surface motion provide sufficient information to identify a stiffness distribution in both homogeneous and heterogeneous cases. The elastic reconstruction performed on simulated and experimental data considered both deterministic and stochastic algorithms, with a combination of the two approaches found to give the most accurate results, for a realistic increase in computational cost. The reconstruction algorithm developed has the ability to successfully resolve a hard spherical inclusion within a soft phantom, and in addition demonstrated promise in reconstructing the correct stiffness distribution when no inclusion is present.

The work present in this thesis report introduces a novel non-destructive technique for experimentally measuring through thickness hygro-thermal strain of Nafion membranes though digital image correlation. An Optical Coherence Tomography (OCT) system was used to acquire images of a Nafion-TiO2 (titanium dioxide powder) composite membranes in a fuel cell like device. The proposed technique, commonly known as optical coherence elastography (OCE) makes use of the normalized correlation algorithm to calculate strain between two successive scans of different relative humidity step values. Different normalized correlation parameters were compared to measured results of PDMS-TiO2 phantoms in order to analyze accuracy. The effect of TiO2 on Nafion membranbes mechanical properties was further analysed by comparing the swelling behaviour of membranes with different concentrations. It has been found that Nafion undergoes approximately 25 – 30% more strain on the land section than on the channel section, regardless gas diffusion electrode (GDE) layer presence. Furthermore, it was shown that the overall strain on the material decrease by approximately 10% when GDE layers are present. Overall this work demonstrated how OCE is a viable technique for measuring through thickness strain distribution in Nafion composite membranes and has the potential to be implemented for non-destructive in situ measurements. / Graduate / 0548 / kellerv@uvic.ca

Die vorliegende medizinische Dissertation beschäftigt sich mit der Evaluation nicht-invasiver Diagnostikverfahren zur Detektion einer Leberfibrose bei Patienten mit Morbus Wilson. Untersucht wurden die Transiente Elastographie (TE), die Acoustic Radiation Force Impulse (ARFI)-Elastographie sowie verschiedene laborbasierte Fibrose-Indices bezüglich der Anwendbarkeit und ihres diagnostischen Nutzens. Der Morbus Wilson ist eine seltene hereditäre Kupferspeicherkrankheit, die über Kupferakkumulation im Leberparenchym zur Ausbildung einer Zirrhose führen kann. Die Kenntnis des Leberfibrosegrades ist unabdingbar für therapeutische Entscheidungen und prognostische Einschätzungen. Dafür sind regelmäßige Kontrollen der Leber im Krankheitsverlauf notwendig, wobei die Leberbiopsie den diagnostischen Goldstandard darstellt. Die Invasivität sowie das Komplikationspotential limitieren jedoch deren wiederholte Anwendbarkeit. TE sowie ARFI bieten hierzu eine moderne Alternative, deren Nutzen anhand großer Studien bei Patienten mit verschiedenen chronischen Lebererkrankungen bereits aufgezeigt werden konnte. Die Verfahren beurteilen die Parenchymsteifigkeit als Surrogatparameter der Leberfibrose, wobei mit steigendem Fibrosegrad die Gewebesteifigkeit zunimmt. Die Grenzwerte zur Definition des Fibrosegrades sowie die Anwendbarkeit beider Verfahren variieren in Abhängigkeit von der Grunderkrankung. Ziel dieser Studie war es, Grenzwerte und diagnostischen Nutzen der Elastographieverfahren bei M. Wilson zu definieren. Beide Verfahren können eine Leberbeteiligung des M. Wilson nachweisen und das Vorliegen einer Leberzirrhose detektieren. Die potentiell bessere diagnostische Treffsicherheit der TE wird durch Einschränkungen in der Anwendbarkeit limitiert.

A primary purpose of elasticity imaging, commonly known as elastography, is to extract the viscoelastic properties of a medium (including soft tissue) from the displacement caused by a stress field. Dynamic elastography methods that use the acoustic radiation force of ultrasound have several advantages, such as, non-invasiveness, low cost, and ability to produce a highly localized force field. A method for remotely generating localized low frequency shear waves in soft tissue is investigated, by using the modulated radiation force resulting from two intersecting quasi-CW confocal ultrasound beams of slightly different frequencies. In contrast to most radiation force-based methods previously presented, such shear waves are narrowband rather than broadband. As they propagate within a viscoelastic medium, different frequency-dependent effects will not significantly affect their spectrum, thereby providing a means for measuring the shear attenuation and speed as a function of frequency. Furthermore, to improve the detection signal-to-noise-ratio (SNR), increased acoustic pressure conditions may be needed, causing higher harmonics to be generated due to nonlinear propagation effects. Shear-wave propagation at harmonic modulation frequencies does not appear to have been previously discussed in the elastography literature. The properties of the narrowband shear wave propagation in soft tissue are studied by using the Voigt viscoelastic model and Green’s functions. In particular, the manner in which the characteristics of the viscoelastic medium affect their evolution under both low-amplitude (linear) and high-amplitude (nonlinear) source excitation and conditions that conform to human safety standards. It is shown that an exact solution of the viscoelastic Green’s function is needed to properly represent the propagation in higher-viscosity media, such as soft tissue, at frequencies much beyond a few hundred hertz. Methods for estimating the shear modulus and viscosity in viscoelastic media are developed based on both the fundamental and harmonic shear components.

We consider the design of finite element methods for inverse problems with full-field data governed by elliptic forward operators. Such problems arise in applications in inverse heat conduction, in mechanical property characterization, and in medical imaging. For this class of problems, novel finite element methods have been proposed (Barbone et al., 2010) that give good performance, provided the solutions are in the H^1(Ω) function space. The material property distributions being estimated can be discontinuous, however, and therefore it is desirable to have formulations that can accommodate discontinuities in both data and solution. Toward this end, we present a mixed variational formulation for this class of problems that handles discontinuities well. We motivate the mixed formulation by examining the possibility of discretizing using a discontinuous discretization in an irreducible finite element method, and discuss the limitations of that approach. We then derive a new mixed formulation based on a least-square error in the constitutive equation. We prove that the continuous variational formulations are well-posed for applications in both inverse heat conduction and plane stress elasticity. We derive a priori error bounds for discretization error, valid in the limit of mesh refinement. We demonstrate convergence of the method with mesh refinement in cases with both continuous and discontinuous solutions. Finally we apply the formulation to measured data to estimate the elastic shear modulus distributions in both tissue mimicking phantoms and in breast masses from data collected in vivo.

Orientador: Maria Jaqueline Mamprim / Resumo: A literatura veterinária possui escasso conteúdo a respeito do uso da ultrassonografia e elastossonografia para caracterização de lesões em linfonodos de cães. O objetivo do primeiro estudo foi comparar as características ultrassonográficas e elastossonográficas entre 50 linfonodos neoplásicos (LN) e 69 linfonodos não neoplásicos (LNN), em cães, com base no diagnóstico microscópico. A hipótese desse estudo é que seja possível distinguir lesões neoplásicas e não neoplásicas com tais técnicas de imagem. Variáveis quantitativas foram comparadas entre os grupos com teste t de student não pareado e, as variáveis categóricas, com teste U de Mann-Whitney. Linfonodos neoplásicos apresentaram dimensões significativamente maiores, relação entre eixo curto e eixo longo (RECEL) superior, maior frequência na perda da arquitetura interna, distribuição vascular predominante mista, índices de resistividade (IR) e de pulsatilidade (IP) superiores e maior rigidez à distribuição do escore elastográfico, em comparação com LNN. O objetivo do segundo estudo foi descrever as características ultrassonográficas e elastossonográficas de 25 linfonodos caninos parasitados por Leishmania spp. A hipótese desse estudo é que seja possível padronizar linfonodos contendo formas amastigotas de Leishmania spp por meio da ultrassonografia e elastografia. Houve aumento nas dimensões dos linfonodos, com RECEL próximo da normalidade. Observou-se alta prevalência de contornos irregulares, bordas nítidas e ausência d... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Applicability of ultrasonography and sonoelastography for characterization of lymph node lesions has not been established. The aim of the first study was to compare sonographic and sonoelastographic features between 50 neoplastic and 69 non-neoplastic lymph nodes of dogs, categorized according to microscopy. We hypothesize that sonography and sonoelastography allow the differentiation between neoplastic and non-neoplastic lymph node lesions. Quantitative variables were compared using Student’s unpaired t test and categoric variables were assessed using non-parametric Mann-Whitney U test. Neoplastic nodes had larger size, and short-to-long axis, predominantly mixed vascular flow distribution (hilar and peripheral) on Color Doppler and on Power Doppler, higher resistivity and pulsatility indices, and higher stiffness (score predominantly 4) on elastographic chromatic scale in comparison with non-neoplastic lymph nodes. The aim of the second study was to describe sonographic and elastosonographic features of 25 canine lymph nodes parasitized with Leishmania spp. We hypothesize that sonography and sonoelastography allow standardization of lymph nodes with Leishmania spp. There was enlargement of the lymph nodes associated with maintenance of the shape. Most of the nodes had irregular contour, well-defined borders and absent hilar tissue definition. A minority of the nodes had heterogeneous uniformity due to focal hypoechoic areas or peripheric hypoechoic areas. Vascular flow dist... (Complete abstract click electronic access below) / Doutor