<p>In this work, I examine the problem of rapid imaging of stroke and present ultrasound-based approaches for addressing it. Specifically, this dissertation discusses aberration and attenuation due to the skull as sources of image degradation and presents a prototype system for simultaneous 3D bilateral imaging via both temporal acoustic windows. This system uses custom sparse array transducers built on flexible multilayer circuits that can be positioned for simultaneous imaging via both temporal acoustic windows, allowing for registration and fusion of multiple real-time 3D scans of cerebral vasculature. I examine hardware considerations for new matrix arrays--transducer design and interconnects--in this application. Specifically, it is proposed that signal-to-noise ratio (SNR) may be increased by reducing the length of probe cables. This claim is evaluated as part of the presented system through simulation, experimental data, and in vivo imaging. Ultimately, gains in SNR of 7 dB are realized by replacing a standard probe cable with a much shorter flex interconnect; higher gains may be possible using ribbon-based probe cables. In vivo images are presented depicting cerebral arteries with and without the use of microbubble contrast agent that have been registered and fused using a search algorithm which maximizes normalized cross-correlation. </p><p>The scanning geometry of a brain helmet-type system is also utilized to allow each matrix array to serve as a correction source for the opposing array. Aberration is estimated using cross-correlation of RF channel signals followed by least mean squares solution of the resulting overdetermined system. Delay maps are updated and real-time 3D scanning resumes. A first attempt is made at using multiple arrival time maps to correct multiple unique aberrators within a single transcranial imaging volume, i.e. several isoplanatic patches. This adaptive imaging technique, which uses steered unfocused waves transmitted by the opposing or "beacon" array, updates the transmit and receive delays of 5 isoplanatic patches within a 64°×64° volume. In phantom experiments, color flow voxels above a common threshold have increased by an average of 92% while color flow variance decreased by an average of 10%. This approach has been applied to both temporal acoustic windows of two human subjects, yielding increases in echo brightness in 5 isoplanatic patches with a mean value of 24.3 ± 9.1%, suggesting such a technique may be beneficial in the future for improving image quality in non-invasive 3D color flow imaging of cerebrovascular disease including stroke.</p><p>Acoustic window failure and the possibility of overcoming it using a low frequency, large aperture array are also examined. In performing transcranial ultrasound examinations, 8-29% of patients in a general population may present with window failure, in which it is not possible to acquire clinically useful sonographic information through the temporal acoustic window. The incidence of window failure is higher in the elderly and in populations of African descent, making window failure an important concern for stroke imaging through the intact skull. To this end, I describe the technical considerations, design, and fabrication of low-frequency (1.2 MHz), large aperture (25.3 mm) sparse matrix array transducers for 3D imaging in the event of window failure. These transducers are integrated into the existing system for real-time 3D bilateral transcranial imaging and color flow imaging capabilities at 1.2 MHz are directly compared with arrays operating at 1.8 MHz in a flow phantom with approximately 47 dB/cm0.8/MHz0.8 attenuators. In vivo contrast-enhanced imaging allowed visualization of the arteries of the Circle of Willis in 5 of 5 subjects and 8 of 10 sides of the head despite probe placement outside of the acoustic window. Results suggest that the decrease from approximately 2 to 1 MHz for 3D transcranial ultrasound may be sufficient to allow acquisition of useful images either in individuals with poor windows or outside of the temporal acoustic window by untrained operators in the field.</p> / Dissertation

<p>Ultrasound can be used for a variety of therapeutic purposes. High-intensity focused ultrasound (HIFU) has progressed over the past decade to become a viable therapeutic method and is valuable as a non-invasive alternative to many surgical procedures. Ultrasonic thermal therapies can also be used to release thermally sensitive liposomes encapsulating chemotherapeutic drugs. In the brain, the permeability of the blood-brain barrier to drugs, antibodies, and gene transfer can be increased with a mechanical mechanism using ultrasound and contrast agent.</p><p>The work presented in this dissertation tests the hypothesis that a diagnostic system can be used for combined imaging and therapeutic applications. In order to evaluate the effectiveness of a diagnostic system for use in therapeutic applications, a set of non-destructive tests is developed that can predict the potential for high acoustic output. A rigorous, nondestructive testing regimen for standard, diagnostic transducers to evaluate their potential for therapeutic use is formulated. Based on this work, transducer heating is identified as the largest challenge. The design and evaluation of several custom diagnostic transducers with various modifications to reduce internal heating are described. These transducers are compared with diagnostic controls using image contrast, face heating, hydrophone, and ARFI displacement measurements. From these results, we conclude that the most promising design is a passively and actively cooled, PZT-4 multilayer composite transducer, while the acoustically lossless lens and capactive micro-machined transducers evaluated herein are determined to be ineffective.</p><p>Three therapeutic applications are evaluated for the combined system. Image-guided spot ablations, such as in the treatment of early stage liver cancers, could not be successfully performed; however, the additional acoustic output requirements are determined to be on the order of 2.4 times those that can be currently produced without transducer damage in a clinically relevant amount of time (10-20 seconds per spot). The potential of a diagnostic system for a hyperthermia application is shown by producing temperatures for the duration necessary to release chemotherapeutic agents from thermally-activated liposomes without damage to the transducer. Finally, a mechanically-based therapeutic method for opening the BBB with ultrasonic contrast agent and specialized sonication regimes under ultrasonic B-mode guidance is demonstrated.</p><p>These studies indicate that a diagnostic system is capable of both moderate thermal and mechanical therapeutic applications under co-registered image-guidance.</p> / Dissertation

Current technology used to diagnose hearing disorders is limited. This is mostly due to the fact that the auditory structures are very small and not easily accessible with existing imaging technologies. The objective of this dissertation was to investigate the potential of high-frequency ultrasound as a tool for exploring the anatomy of the auditory system. Three studies were conducted in order to demonstrate the feasibility of high-frequency ultrasound as a diagnostic technology for hearing disorders. In the first study, an in-house developed 50 MHz annular array-based ultrasound system was used to provide ex-vivo images of auditory structures in cadaveric temporal bones. It was shown that the spatial resolution was sufficient to visualize a high level of detail of the ossicular bones of the middle ear as well as intra-cochlear structures of the inner ear. In the second study, a 50 MHz 1.26? pitch phased array ultrasound transducer was designed for imaging intra-cochlear structures through the round window membrane. As this element pitch results in large grating lobe artifacts, novel transmit beamforming techniques were developed to suppress grating lobes resulting from this large-pitch array. Theoretical techniques using the impulse-response simulation method and experimental verification using high-frequency linear array ultrasound system (Vevo 2100, VisualSonics, Canada) showed that these techniques were able to suppress grating lobe levels up to 40 dB. In the third study, a needle mounted 45 MHz single-element ultrasound probe was fabricated in order to measure the vibrations of intra-cochlear structures on human cadavers. Basilar membrane velocimetry measurements were successfully performed using pulsed-wave Doppler ultrasound in the frequency range between 100 Hz-2 KHz. The measured velocity of the basilar membrane and the round window membrane showed that the middle ear resonance frequency near 1 KHz was present over multiple temporal bones. This is the first work that has explored the human auditory system with high resolution ultrasonic visualization and Doppler velocimetry.

Nonlinear ultrasonic waves have demonstrated high sensitivities to various microstructural changes in metal including coherent precipitates; these precipitates introduce a strain field in the lattice structure. The thermal aging of certain alloy steels leads to the formation of coherent precipitates, which pin dislocations and contribute to the generation of a higher harmonics in an initially monochromatic wave. The objective of this research is to develop a robust technique to perform nonlinear Rayleigh wave measurements in metals using a non-contact receiving transducer. In addition a discussion about the data processing based on the two-dimensional diffraction and attenuation model is provided in order to calculate the relative nonlinearity parameter. A precipitate hardenable material, 17-4 PH stainless steel, is used to obtain different precipitation stages by thermal treatment and the influence of precipitates on the ultrasonic nonlinearity is assessed. Conclusions about the microstrucutural changes in the material are drawn based on the nonlinear Rayleigh surface wave measurement and complementary measurements of thermo-electric power, mircohardness and ultrasonic velocity. The results show that the nonlinearity parameter is sensitive to coherent precipitates in the material and moreover that precipitation characteristics can be characterized based on the obtained experimental data.

A caracterização de tecido ósseo por ultra-som para o diagnóstico de osteoporose tem sido investigada como uma alternativa a densitometria óssea baseada em radiação ionizante. A interação do ultra-som com o tecido ósseo é fundamentalmente diferente da que ocorre com a energia ionizante. O potencial da técnica ultra-sônica baseia-se nos efeitos sobre a propagação do campo acústico causados pela estrutura, composição e massa do tecido que está sendo investigado. Quatro estudos in-vitro e um estudo clínico estão descritos neste trabalho. O primeiro estudo in-vitro compara a correlação entre medidas ultra-sônicas e de densidade mineral óssea (em g/cm3) em tecido trabecular humano e bovino. A velocidade e atenuação ultra-sônicas em amostras ósseas foram determinadas pela técnica de inserção convencional (modo de transmissão) e a medida de densidade mineral óssea foi realizada por absortometria de um fóton (SPA). O mecanismo de interação do ultra-som com osso trabecular é pouco conhecido. O segundo estudo in-vitro investigou como a presença da medula óssea afeta as medidas de velocidade e atenuação. As correlações entre medidas ultrasônicas e de densidade mineral óssea (em g/cm3) por SPA, com e sem a presença da medula óssea, são também determinadas. A medida ultra-sônica de inserção convencional é comparada a medida de inserção por contato. O terceiro estudo in-vitro investigou em amostras de calcâneo as correlações entre medidas ultra-sônicas e de densidade mineral óssea (em g/cm3 e em g/cm2) por SPA. A determinação da densidade mineral Óssea em g/cm2 (BMD) a partir de medidas ultra-sônicas nas amostras foi pela primeira vez investigada, utilizando-se uma técnica de regressão linear univariável e multivariável e uma técnica multivariável não-linear baseada em redes neurais. Um novo parâmetro, baseado na média da frequência instantânea (MIF) do sinal da amostra e de referência, foi proposto para caracterizar o tecido ósseo devido a sua alta correlação com a atenuação. O efeito das corticais ósseas do calcâneo nas medidas ultra-sônicas é pouco conhecido. O quarto estudo in-vitro determinou a correlação entre medidas ultrasônicas e de densidade mineral óssea (em g/cm3) por SPA, com e sem a presença das corticais ósseas. Finalmente, no estudo clínico foram determinadas as correlações entre medidas ultra-sônicas no calcanhar e de densidade mineral óssea por DEXA (em g/cm2) no cólo femoral. A determinação da densidade óssea a partir de medidas ultra-sônicas no calcanhar foi pela primeira vez investigada, utilizando-se uma técnica de regressão linear univariável e multivariável e uma técnica multivariável não-linear baseada em redes neurais. / Ultrasonic assessment of bone for managing osteoporosis has been investigated as an alternative to radition-based bone densitometry technology. In contrast with the ionizing electromagnetic radiation of such clinical bone densitometric technique, ultrasound is a mechanical wave and thus interacts with bone in a fundamentally distinct manner. Ultrasound is viewed as having great potential for assessing bone since its propagation is affected by the structure, composition, and mass of the bone tissue being interrogated. Four in-vitro and one clinical study are reported in this work. In the first in-vitro study a comparison is reported on the ultrasonic assessment of human trabecular and bovine trabecular bone samples. Both ultrasonic velocity and attenuation were evaluated through a standard transmission insertion technique and correlated with bone mineral density (in g/cm3 ) as determined with single photon absorptiometry (SPA). There is a relatively limited understanding of how ultrasound interacts with cancellous bone. One potentially model leads analytically to the demonstration that ultrasound propagation through bone is dependent on several factors, including the properties of the fluid, which saturates the pores of the cancellous bone tissue. The second in-vitro study was carried out to assess how the presence of marrow affects the velocity and attenuation measurements. The correlation between ultrasonic and densitometric measurements (in g/cm3) by SPA, with and without the bone marrow, are also determined. A second part of this study compared the measurements of ultrasonic attenuation and velocity on bovine cancellous bone samples using a standard insertion technique with those obtained using a contac method. The thrid in-vitro study with the calcis trabecular samples investigated the correlations between ultrasonic measurements and bone mineral density (in g/cm3 e em g/cm2) as measured by SPA. A nonlinear multivariate estimation technique based on neural network was the first time investigated to determine the ability of ultrasonic measurements to estimate bone mineral density in g/cm2 (BMD). A linear univariate and multivariate estimation of BMD was compared with the neural network approach. A new parameter to characterize the trabecular bone is been proposed, which is based on the mean instantaneous frequency (MIF) of the sample and reference signals after transmission through the os calcis. It was founded a high correlation between MIF and the attenuation (BUA). Little is known about the effect of the os calcis cortical shell on ultrasonic measurements. The fourth in-vitro study with os calcis samples determined the correlation between ultrasonic and densitometric measurements (in g/cm3) by SPA with and without the cortical shell. Finally, a nonlinear multivariate estimation technique based on neural network was the first time investigated to determine the ability of clinical ultrasonic measurements in the heel to estimate bone mineral density (BMD) in the femoral neck. A linear univariate and multivariate estimation to predict BMD in patients is also compared with the neural network approach.

Pneumoni är globalt sett den största orsaken till sjukdom och mortalitet bland barn under fem år, med 920 000 dödsfall under 2015. I Sverige är pneumoni den största orsaken till sjukdom bland barn, med ett hastigt insjuknande med allmänpåverkan, feber, frossa och andningsproblem. I dagsläget ställs diagnos med hjälp av kliniska symtom och lungröntgen, vilket utsätter barnen för joniserande strålning. Med ultraljud är det möjligt att undersöka lungorna på ett sätt som är harmlöst mot kroppens vävnader. Syftet med denna studie var att ta reda på om ultraljud kan ersätta konventionell lungröntgen för att diagnostisera barn med misstänkt pneumoni. Studien genomfördes som en allmän litteraturöversikt där 13 kvantitativa vetenskapliga artiklar granskades. Ultraljud är en tillförlitlig metod som har högre sensitivitet och specificitet när det gäller att detektera pneumoni än vad lungröntgen har. Ultraljud är även bättre på att detektera små förändringar i lungorna och pleurautgjutningar jämfört med lungröntgen. Ultraljud kan användas för att diagnostisera barn med pneumoni. Att införa den som en alternativ undersökningsmetod till lungröntgen när det kommer till att diagnostisera pneumoni skulle leda till minskade stråldoser för de barn som söker vård med misstänkt pneumoni. / Pneumonia is globally the largest cause of disease and mortality among children under the age of five years, with 920,000 deaths in 2015. In Sweden, pneumonia is the major cause of childhood disease, with a rapid onset of malaise, fever, chills and respiratory problems. It’s currently diagnosed with the help of clinical signs and chest x-ray, which exposes the children to ionizing radiation. With ultrasound it is possible to examine the lungs in a way that’s not harmful to the body tissues. The purpose of this study was to determine whether ultrasound can replace conventional chest x-ray to diagnose children with suspected pneumonia. The study was conducted as a general literature review where 13 quantitative scientific articles were examined. Ultrasound is a reliable method that has higher sensitivity and specificity when it comes to detecting pneumonia compared to chest x-ray. Ultrasound is also better at detecting small consolidations in the lungs and the presence of pleural effusion compared to chest x-ray. Ultrasound can be used to diagnose children with suspected pneumonia. Introducing it as an alternative method of examination to chest x-ray when it comes to diagnosing pneumonia would lead to reduced radiation doses for those seeking pediatric care with suspected pneumonia.

Afin d'accélérer et automatiser l'analyse par ultrasons quantitatifs de ganglions lymphatiques de patients atteints d'un cancer, plusieurs segmentations automatiques des trois milieux rencontrés (le parenchyme du ganglion, la graisse périnodale et le sérum physiologique) sont étudiées. Une analyse statistique du signal d'enveloppe a permis d'identifier la distribution gamma comme le meilleur compromis en termes de qualité de la modélisation, simplicité du modèle et rapidité de l'estimation des paramètres. Deux nouvelles méthodes de segmentation basées sur l'approche par ensemble de niveaux et la distribution gamma sont décrites. Des statistiques locales du signal d'enveloppe permettent de tenir compte des inhomogénéités du signal dues à l'atténuation et la focalisation des ultrasons. La méthode appelée LRGDF modélise les statistiques du speckle dans des régions dont la taille est contrôlable par une fonction lisse à support compact. La seconde, appelée STS-LS, considère des coupes transverses, perpendiculaires au faisceau, pour gagner en efficacité. Une troisième méthode basée sur la classification par forêt aléatoire a été conçue pour initialiser et accélérer les deux précédentes. Ces méthodes automatiques sont comparées à une segmentation manuelle effectuée par un expert. Elles fournissent des résultats satisfaisants aussi bien sur des données simulées que sur des données acquises sur des ganglions lymphatiques de patients atteints d'un cancer colorectal ou du sein. Les paramètres ultrasonores quantitatifs estimés après segmentation automatique ou après segmentation manuelle par un expert sont comparables. / This work investigates approaches to obtain automatic segmentation of three media (i.e., lymph node parenchyma, perinodal fat and normal saline) in lymph node (LN) envelope data to expedite quantitative ultrasound (QUS) in dissected LNs from cancer patients. A statistical modeling study identified a two-parameter gamma distribution as the best model for data from the three media based on its high fitting accuracy, its analytically less-complex probability density function (PDF), and closed-form expressions for its parameter estimation. Two novel level-set segmentation methods that made use of localized statistics of envelope data to handle data inhomogeneities caused by attenuation and focusing effects were developed. The first, local region-based gamma distribution fitting (LRGDF), employed the gamma PDFs to model speckle statistics of envelope data in local regions at a controllable scale using a smooth function with a compact support. The second, statistical transverse-slice-based level-set (STS-LS), used gamma PDFs to locally model speckle statistics in consecutive transverse slices. A novel method was then designed and evaluated to automatically initialize the LRGDF and STS-LS methods using random forest classification with new proposed features. Methods developed in this research provided accurate, automatic and efficient segmentation results on simulated envelope data and data acquired for LNs from colorectal- and breast-cancer patients as compared with manual expert segmentation. Results also demonstrated that accurate QUS estimates are maintained when automatic segmentation is applied to evaluate excised LN data.

This thesis deals with electronic focusing of ultrasonic probes. There is theoretically described, what is the electronic focusing. Further, there are calculations that are used to achieve focusing. These calculations are then implemented into the algorithm that was developed in Matlab. The paper also contains the simulation conducted using the proposed algorithm and the GUI. These simulations are then compared with characteristics measured on a real ultrasound probe.

This diploma thesis aims to implement an active contour method for ultrasound image segmentation. Properties of ultrasound images, basic segmentation approaches and a~principle of choosen active contour methods are described within theoretical part. Two different groups of active contour methods exists, methods with use of gradient and without use of gradient as image feature. For comparision, one method of each group is implemented in practical part and subsequently, segmentation efficiency and properties of methods are compared in evaluation part.

This work deals with the 2D and 3D visualization of simulation outputs from the k-Wave toolbox. This toolbox, designed to accurately model the propagation of ultrasound waves in the human body, usually generates immense amounts of output data (up to hundreds of GB). That is why new methods for both the visualization and the effective data representation are necessary to be developed to help users to easily understand the simulation results. This thesis elaborates on the data format, simulation outputs are stored in, with the use of the HDF5 library and looking for the best way to quickly read the simulation data. Finally, the thesis presents the design and the implementation of the console-based application for big simulation data pre-processing and the GUI-based application for interactive visualization of the pre-processed data. The most significant features of these applications are downsampling data, changing the format of storing, viewing 2D sections, planar and volumetric visualization and animation of the simulation process. The proposed implementation allows parts of the simulation domain to be visualised within tens of milliseconds even if the simulation domain comprises GBs of data - This significantly streamlines the work of scientists and clinicians in the field of HIFU.