Orientadores: Eduardo Tavares Costa, Rosana Almada Bassani / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia Elétrica e de Computação / Made available in DSpace on 2018-08-19T01:08:15Z (GMT). No. of bitstreams: 1 Buiochi_ElaineBelassiano_D.pdf: 9610613 bytes, checksum: 5fefa9e6cf5eaf8478c002d7ab57dc23 (MD5) Previous issue date: 2011 / Resumo: No ultrassom diagnóstico faz-se uso de ondas acústicas de baixa intensidade para investigar os tecidos biológicos, sendo uma técnica não invasiva. Ondas ultrassônicas de maior intensidade podem alterar as características do tecido, e isto é de interesse para aplicações terapêuticas, nas quais a ocorrência de efeitos biológicos é, até certo ponto, desejável. Com relação à cardiologia, o uso do ultrassom diagnóstico é bem estabelecido, enquanto há um potencial inexplorado para aplicações terapêuticas. Soma-se a isso o fato de que os tratamentos disponíveis para as arritmias com estimulação elétrica são limitados por sérias complicações, incluindo infecção sistêmica, choques desnecessários, potencial para pró-arritmia, falha em estimular e, até mesmo, morte. O ultrassom pode se mostrar uma alternativa atraente à estimulação elétrica, porém há poucos estudos sobre a possibilidade de aplicação do ultrassom para o tratamento de arritmias. O objetivo deste estudo foi desenvolver transdutores ultrassônicos de potência e usá-los para investigar conjuntos de parâmetros acústicos capazes de interferir na atividade cardíaca, sem provocar danos teciduais, buscando possíveis aplicações terapêuticas do ultrassom em cardiologia. Os parâmetros acústicos variados foram frequência de ressonância, modo de operação, frequência de repetição de pulso, e pressão de saída. Dois dos sete transdutores construídos se mostraram mais eficientes e, portanto, foram calibrados e usados nos experimentos biológicos. Em experimentos preliminares realizados em corações isolados de ratos Wistar, foi observada geração esporádica de arritmia usando-se o transdutor de 65 kHz, e aumento da frequência espontânea, acompanhada por redução da força de contração do miocárdio, usando-se o transdutor de 1MHz em exposição contínua prolongada. Em estudos in vivo, dez ratos Sprague-Dawley foram anestesiados com isoflurano e expostos a uma seqüência terapêutica de ultrassom, e outros cinco ratos foram usados como grupo controle. A estimulação ultrassônica consistiu de bursts de 1MHz, ciclo de trabalho de 1%, pico de pressão negativa de 3MPa (ISPTA=3W/cm2), e freqüência de repetição de pulso variável e decrescente. O ultrassom transtorácico exerceu efeito cronotrópico negativo, uma vez que foi capaz de reduzir a freqüência cardíaca em 19% logo ao final do período de estimulação. Os efeitos duraram, no mínimo, 15 minutos, sem aparente prejuízo hemodinâmico, que foi monitorado principalmente por meio da medição da fração de ejeção. Trata-se de um fenômeno promissor para o tratamento de taquiarritmias. O regime de exposição utilizado excluiu efeitos térmicos, de forma que o efeito observado foi provavelmente resultante de mecanismos não-térmicos, possivelmente da força da radiação. A variação na frequência de repetição de pulso parece ter sido a chave para a indução do efeito em questão, uma vez que experimentos realizados com frequências de repetição constantes não resultaram em tal efeito / Abstract: Diagnostic ultrasound consists of application of low intensity acoustic waves to noninvasively investigate biological tissues. Higher ultrasound intensities may alter tissue characteristics, and this is of interest for therapeutic applications, when the occurrence of bioeffects is - to a certain extent - desirable. The use of diagnostic ultrasound in Cardiology is well established, although there is an unexplored potential for therapeutic applications. The currently available treatments of arrhythmias by electrical stimulation are limited by serious complications, including systemic infection, inappropriate shock delivery, proarrhythmia, failure to pace and to defibrillate, and even death. Ultrasound can be an interesting alternative for electrical stimulation, but there are only a few studies that investigate the possibility of applying ultrasound for treating arrhythmias. The objective of this study was to develop power ultrasonic transducers to be applied to the investigation of sets of acoustical parameters able to interfere with the cardiac activity without causing tissue damage, thus aiming at potential therapeutic applications of ultrasound in cardiology. The acoustical parameters investigated were resonance frequency, operation mode, pulse repetition frequency, and output pressure. The two most efficient out of the seven transducers built were calibrated and used in biological experiments. In preliminary experiments conducted on isolated hearts from Wistar rats, arrhythmia was esporadically observed at the onset of ultrasound application using the 65kHz transducer, whereas an increase in spontanous beating rate accompanied by a reduction in the force developed by the myocardium occurred during continuous, prolonged exposure using the 1MHz transducer. In in vivo studies, ten Sprague-Dawley rats were anesthetized with isoflurane and exposed to a sequence of therapeutic ultrasound, and other five rats were used as a control group. The ultrasonic stimulation consisted of 1-MHz bursts of 1% duty cycle, 3 MPa peak negative pressure (ISPTA=3W/cm2), and decreasingly variable pulse repetition frequencies. Transthoracic ultrasound application was able to promote a negative chronotropic effect, decreasing the heart rate by 19% just after stimulation ceased. The effect lasted at least 15 minutes, without apparent alteration of pumping function, which was monitored mainly by evaluation of the ejection fraction. This phenomenon is promising for treating tachyarrhythmias. The insonification scheme used in this study excluded thermal effects, so the observed effect seems to have resulted from nonthermal mechanisms, possibly from radiation force. The variation in the pulse repetition frequency seems to be the key element for induction of the described effect, because the latter was not observed for constant repetition rates / Doutorado / Engenharia Biomedica / Doutor em Engenharia Elétrica

[pt] Ensaios não-destrutivos são técnicas utilizadas na inspeção de materiais e equipamentos sem danificá-los, sendo executados nas etapas de fabricação, construção, montagem e manutenção. Constituem uma das principais ferramentas do controle e garantia da qualidade de materiais e produtos, sendo largamente utilizados nos setores petróleo/petroquímico, químico, aeronáutico, aeroespacial, siderúrgico, naval, eletromecânico, papel e celulose, entre outros. Representam métodos capazes de proporcionar informações sobre defeitos, características tecnológicas do material, ou ainda, monitoração da degradação em serviço de componentes, equipamentos e estruturas, o que permite o uso de ações de extensão de suas vidas úteis. O objetivo desta pesquisa foi comparar a adequação de diferentes técnicas não destrutivas na detecção e estimativa da dimensão de trincas de fadiga, nucleadas e propagadas intencionalmente, em material estrutural. Para tal, corpos de provas cilíndricos do aço 42CrMo4 com um entalhe em V sofreram carregamentos cíclicos até diferentes números de ciclos, o que proporcionou diferentes tamanhos de trinca. O comprimento das trincas passantes foi monitorado por meio de lupa posicionada na lateral do corpo de prova. Após a etapa de nucleação e propagação das trincas de fadiga, todos os corpos de prova foram inspecionados com emprego das técnicas de Ultrassom Convencional, Ultrassom Phased Array e Radiografia Digital, para permitir a indicação das trincas de fadiga e o estabelecimento de suas dimensões. Terminada as inspeções, os corpos de prova foram resfriados em nitrogênio líquido e fraturados com aplicação de uma carga de flexão, o que permitiu a visualização das superfícies das trincas. Em seguida, as trincas foram medidas visualmente com o auxílio de uma lupa, o que permitiu comparar as indicações (virtual) de defeitos nos corpos de prova com a existência (real) dos mesmos e, ainda correlacionar as dimensões indicadas nas inspeções com aquelas medidas nas superfícies das trincas. Neste contexto, todas as técnicas se mostraram adequadas para a indicação de defeitos. Além disso, para trincas curtas, o Ultrassom Phased Array foi a técnica que apresentou a melhor suscetibilidade para o dimensionamento de descontinuidades, enquanto que a Radiografia Digital se mostrou mais eficiente para trincas mais longas. / [en] Non-destructive tests are techniques used in material and equipment inspection without permanent damage, applied in the stages of manufacture, construction, assembly and maintenance. They are one of the main tools to control and insure the quality of materials and products, with widely applications in oil / petrochemical, chemical, aeronautical, aerospace, steel industry, naval, electromechanical industries. They represent with capacity of providing information about defects, technological characteristics of the material, or monitoring the degradation in service of components, equipment and structures, which allows the use of useful live extensions in service. The objective of this research was to compare the application of different non-destructive techniques in the detection and size estimation of fatigue cracks, nucleated and propagated intentionally, in structural material. For this purpose, cylindrical specimens of 42CrMo4 steel with a V-notch were subjected to cyclic loading with different cycle numbers, which provided different crack sizes. The length of the cracks was monitored by a magnifying glass positioned on the specimen surface. After the crack nucleation and propagation, all specimens were subjected to non-destructive tests making use of Conventional Ultrasound, Phased Array Ultrasound and Digital Radiography, in order to provide crack indications and crack dimensions. After the inspections, the specimens were cooled down in nitrogen and fractured in three point bending to promote opened crack surfaces. In the sequence, the cracks were measured using a magnifying glass, which allowed a comparison between the indicated and measured defects. In this context, all techniques were adequate for crack indications. On the other hands, for short cracks, the Phased Array Ultrasound was the technique that presented the best susceptibility for estimate the discontinuity dimensions, while Digital Radiography proved to be more efficient for longer cracks.

Ce travail de thèse a pour objectif de développer et de valider expérimentalement un modèle de diffusion adapté au sang agrégeant, prenant en compte une forte fraction volumique de globules rouges (hématocrite de 40%) et des structures d’agrégats polydisperses. Un modèle développé récemment pour l’estimation de la microstructure du sang est la théorie de milieu effectif combinée à un modèle de facteur de structure monodisperse. Pour augmenter le domaine de validité de ce modèle en hautes fréquences, nous proposons une théorie de milieu effectif prenant en compte la composante incohérente de la diffusion par des agrégats de globules rouges. A l’aide de simulation numériques tridimensionnelles, nous montrons que la nouvelle modélisation permet de prédire les coefficients de rétrodiffusion de façon satisfaisante pour un produit $kR<2$ ($k$ étant le nombre d’ondes et $R$ le rayon d’un agrégat). Par ailleurs, nous proposons une théorie de milieu effectif combinée à un facteur de structure polydisperse afin d’estimer, à partir de la mesure expérimentale du coefficient de rétrodiffusion, des paramètres de structure des agrégats : le rayon moyen de la distribution de tailles, son étalement, et la compacité des agrégats. Des expériences réalisées sur du sang de porc cisaillé dans un dispositif de Couette couplé à une sonde ultrasonore montrent que le modèle polydisperse permet d’obtenir de meilleures courbes d’ajustement des coefficients de rétrodiffusion en comparaison des modèles monodisperses classiques. Les tailles d’agrégats estimées par ultrasons sont corrélées de façon satisfaisante (r$^2$ $\approx$ 0.92) avec les tailles estimées par ailleurs dans un dispositif optique. / This thesis aims to develop and evaluate a scattering model for aggregating blood, taking into account the high volume fraction of red blood cells in blood (40%) and the polydispersity in terms of aggregate size. The effective medium theory combined with the monodisperse structure factor model was recently developed to estimate blood microstructure. In order to improve the modeling at high frequency range, we proposed an effective medium theory that takes into account the incoherent component of the scattering by aggregates of RBCs. Three dimensional simulations were performed and showed that the consideration of the incoherent component allows to approximate the simulation satisfactorily for a product of the wavenumber times the aggregates radius $kR$ up to 2. Besides, we proposed an effective medium theory combined with a polydisperse structure factor. From the measured BSC, this model allows to estimate three structural parameters: the mean radius of the aggregate size distribution, the width of the distribution, and the compactness of the aggregates. Experiments were performed on pig blood shared in a Couette device coupled with an ultrasonic probe, and showed that the polydisperse modeling provides better fitting to the experimental BSC data, when compared to the classical monodisperse models. Satisfactory correlation is obtained (r$^2$ $\approx$ 0.92) between the aggregate sizes estimated with ultrasound and the aggregate sizes estimated on the same sample in an optical device.

Extensions to k-Wave toolbox used for ultrasound modelling are described. Aim of extensions is to reduce time and space complexity by presenting alternative representations of tissues and transducers in simulation. This project clarifies basic principles and features of k-Wave, describes design of new representations and finally describes implementation of the suggested extensions.

The work deals with design and implementation of 2D ultrasound simulation. Applications of the ultrasound simulation can be found in medicine, biophysic or image reconstruction. As an example of using the ultrasound simulation we can mention High Intensity Focused Ultrasound that is used for diagnosing and treating cancer. The program is part of the k-Wave toolbox designed for supercomputer systems, specifically for machines with shared memory architecture. The program is implemented in the C++ language and using OpenMP acceleration.  Using the designed solution, it is possible to solve large-scale simulations in 2D space. The work also deals with merging and unification of the 2D and 3D simulation using modern C++. A realistic example of use is ultrasound simulation in transcranial neuromodulation and neurostimulation in large domains, which have more than 16384x16384 grid points. Simulation of such size may take several days if we use the original MATLAB 2D k-Wave. Speedup of the new implementation is up to 8 on the Anselm and Salomon supercomputers.

Thirty-four patients with acute hemispheric ischemic strokes underwent both CT angiography and contrast-enhanced transcranial color-coded duplexsonography (TCCD) to study the effectiveness of the combined noninvasive techniques for evaluation of the circle of Willis. In 3/34 patients, CT angiography and contrast-enhanced TCCD demonstrated middle cerebral artery (MCA) occlusion, in 5 others MCA stenosis. A severe posterior cerebral artery stenosis was missed by CT angiography. In 8 patients, contrast-enhanced TCCD failed because of poor bone windows. In these patients, CT angiography was normal. CT angiography and contrast-enhanced TCCD are complementary noninvasive diagnostic tools. Disagreements between the diagnostic findings of these methods still need further evaluation by digital subtraction angiography. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Mit dieser Arbeit wurde erstmalig eine qualitative und quantitative Analyse zum Status quo der studentischen US-Ausbildung im deutschsprachigen Raum durchgeführt. Eingeschlossen wurden alle medizinischen Fakultäten (n=44) Deutschlands, Österreichs und der deutschsprachigen Schweiz, die im Dezember 2015 auf den Webseiten des MFT und Thieme.de verzeichnet waren [3, 70]. Ein standardisierter Fragebogen mit insgesamt 32 Fragen beleuchtete folgende Aspekte der studentischen US-Ausbildung: 1. Allgemeine Angaben 2. Organisation 3. Ressourcen 4. Überprüfung des Lernerfolgs 5. Evaluation Der Fragebogen wurde an alle LeiterInnen der jeweiligen fakultätseigenen Skillslabs verschickt mit der Bitte nach Beantwortung bzw. Weiterleitung an die US-Verantwortlichen der Fakultät. Die Befragung begann im Dezember 2015 und endete im Mai 2016. Die finale Rücklaufquote betrug 64% (28/44). Die statistische Auswertung erfolgte mit SPSS® 20, IBM Chicago. Die Mehrzahl der medizinischen Fakultäten im deutschsprachigen Raum bieten US-Kurse an. Allerdings ist die studentische US-Ausbildung vielerorts heterogen organisiert mit eher zu kurzer praktischer Übungszeit und zu hohem Studierenden-Lehrenden-Verhältnis. Damit US als bereicherndes Lehrmittel sinnvoll in das bereits überfüllte Curriculum des Humanmedizinstudiums integriert werden kann, sind minimale Standards notwendig. Basierend auf den Ergebnissen dieser Studie und einer Literaturrecherche schlagen der Autor und die Koautoren ein mögliches Rahmenwerk und Meilensteine auf dem Weg zu einem longitudinalen US-Curriculum im Humanmedizinstudium vor.:A Abkürzungsverzeichnis 3 B Einführung 4 1 Ultraschall als Grundkompetenz zukünftiger ÄrztInnen 4 2 Ultraschall als integraler Bestandteil des Humanmedizinstudiums 7 2.1 Ultraschall als Lehrmethode in der Makroanatomie und Physiologie 7 2.2 Ultraschall als Erweiterung der körperlichen Untersuchung 7 2.3 Wesentliche Inhalte publizierter Ultraschall-Curricula 8 2.4 Peer-Teaching und Studierendeninitiativen 10 2.5 Rahmencurriculum für die studentische Ultraschallausbildung 11 3 Ableitung der Rationale für die publizierte Studie 13 C Originalpublikation 14 1 Allgemeine Angaben 14 2 Skizzierung der publizierten Studie 15 3 Formatierte Originalpublikation 16 D Zusammenfassung 28 1 Hintergrund und Durchführung 28 2 Ergebnisse und Auswertung 29 E Literaturverzeichnis 33 F Anlagen 41 1 Anschreiben 41 2 Fragebogen 42 G Darstellung des eigenen Beitrags 52 H Verzeichnis über die wissenschaftlichen Veröffentlichungen und Vorträge 53 I Lebenslauf 54 J Erklärung über die eigenständige Abfassung der Arbeit 56 K Danksagung 57

An 53 Hündinnen aus dem Patientengut der Klinik für Kleintiere der Universität Leipzig, die mit Umfangsvermehrungen der Mamma vorgestellt und anschließend in der Klinik für Kleintiere operiert wurden, wurde präoperativ eine sonographische Untersuchung der Mamma durchgeführt. Darüber hinaus wurden die Mammarkomplexe von acht tragenden und einer laktierenden Hündin mit dieser Technik untersucht. Ziel war es, Kriterien zur Einschätzung der Dignität der Tumoren mit Hilfe dieser nichtinvasiven Methode zu erarbeiten. Es sollten die Fragen geklärt werden, ob mit Hilfe der hochauflösenden Sonographie eine Aussage über Gut- oder Bösartigkeit eines Herdes möglich ist und ob dabei dieselben Kriterien entscheidend sind, die in der Humanmedizin eine zuverlässige Differenzierung erlauben. Außerdem sollte überprüft werden, welchen Beitrag die farbkodierte Duplexsonographie oder Resistance- und Pulsatilitätsindex zur Charakterisierung von Mammatumoren der Hündin leisten. Die Gesamtzahl der in die Studie eingehenden Komplexe beträgt 114. Die sonographischen Untersuchungen erfolgten mit einem 14 MHz Matrix-Linearschallkopf. Bei 70 der 114 untersuchten Lokalisationen erfolgte zusätzlich zur B-Mode-Untersuchung eine Untersuchung mit der farbkodierten Duplexsonographie. Konnten mit Hilfe dieser Methode Gefäße in der Umfangsvermehrung nachgewiesen werden, wurde in 47 von 70 Fäl-len zusätzlich der PW-Doppler eingesetzt, um Flussspektren aus den dargestellten Gefäßen abzuleiten. Aus diesen wurden Resistance-Index und Pulsatilitätsindex bestimmt. Bei der retrospektiven Auswertung der Grauwertbilder aus der B-Mode-Untersuchung wurde für jeden Komplex die Ausprägung von 12 Parametern beurteilt. Die Bilder aus der farbkodierten Duplexsonographie lieferten zusätzlich Informationen zu Gefäßzahl, Gefäßdurchmesser und Gefäßverteilung innerhalb eines Tumors. Die Exstirpate wurden pathohistologisch untersucht. Die aus der Gewebetypisierung entsprechend der WHO-Klassifikation resultierenden Gruppen sind so klein, dass nur eine deskriptive statistische Auswertung möglich war. Es erfolgte die Zusammenfassung unterschiedlicher Gewebetypen zu den Gruppen der „malignen“ bzw. „benignen“ Tumoren. Für Malignität sprechen eine unregelmäßige Randkontur (32 von 61 malignen, 4 von 48 benignen Lokalisationen), eine Schallverstärkung (36/61 malignen, 9/48 benignen Lokalisationen) oder –auslöschung (8/61 malignen, 0 /48 benignen Lokalisationen) hinter dem Tumor, Verkalkungen (20/61 malignen, 6/48 benignen Lokalisationen) sowie ein unregelmäßiger Durchmesser der Tumorgefäße (25/61 malignen, 12/48 benignen Lokalisationen). Meist gutartig sind Umfangsvermehrungen der Mamma, denen sonographisch eine klare Abgrenzung zum umgebenden Gewebe fehlt (15/61 malignen, 36/48 benignen Lokalisationen). Außerdem solche mit indifferentem retroläsionalem Schallverhalten (17/61 malignen, 39/48 benignen Lokalisationen). Kombiniert man mehrere der Parameter miteinander, ist die resultierende Teilmenge der betreffenden Läsionen kleiner, die Aussagekraft höher. Für Bösartigkeit spricht beispielsweise eine Kombination von Verkalkung und unregelmäßiger Randkontur (13 von 61 malignen, 1 von 48 benignen Lokalisationen), Verkalkung und echodichtem Randsaum („deutlich“ oder „fraglich“; 9/61 malignen, 0/48 benignen Lokalisationen) sowie mittlerer Echodichte und retroläsionaler Schallverstärkung (21/61 malignen, 6/48 benignen Lokalisationen). Für Gutartigkeit sprechen mittlere Echodichte des Tumorzentrums in Kombination mit indifferentem Schallverhalten (13/61 malignen, 33/48 benignen Lokalisationen) sowie regelmäßiger Gefäßdurchmesser bei diffuser Gefäßverteilung (3/36 malignen, 14/29 benignen Lokalisationen). Es konnte dargestellt werden, dass sich mit Hilfe der hochauflösenden B-Mode-Sonographie Kriterien aufzeigen lassen, die tendenziell für Gut- oder Bösartigkeit eines Mammatumors sprechen. Dabei ist es zweckmäßig, mehrere Parameter in die Beurteilung einfließen zu lassen. Auch die farbkodierte Duplexsonographie kann dabei einen Beitrag leisten. Die Ermittlung von Resistance- und Pulsatilitätsindex hingegen erweist sich als nicht sinnvoll. Ein Parameter, welcher in der Humanmedizin eine entscheidende Rolle zur Unterscheidung bösartiger von gutartigen Tumoren der Mamma spielt ist die Randkontur eines Tumors. Dies ist das einzige Kriterium, das auch bei Mammatumoren der Hündin einen diagnostischen Nutzen aufweist. Anhand einzelner sonographischer Parameter ist es nicht möglich, die Dignität eines Tumors vorherzusagen. Die sonographische Untersuchung kann jedoch in einigen Fällen beim Abschätzen der Prognose helfen. / In 53 bitches that underwent surgery because of tumors of the mammary gland at the Department of small animal medicine of the University of Leipzig we carried out a preoperative ultrasonographic examination of the mammary gland. Furthermore eight pregnant and one lactating bitch were examined the same way. We aimed to find out, whether high-resolution ultrasound helps differentiate benign from malignant tumors. Also we wanted to evaluate criteria established for that purpose in human medicine. Use of colour-coded duplex sonography, resistance index and pulsatility index for this question are reassessed too. The total number of mammary complexes examined for this study is 114. A GE Logiq™ 9 with a 14 MHz linear array transducer was used for all examinations. Seventy of the 114 sites of mammary tissue underwent a colour-coded duplex sonography after the B scan. Blood vessels were detectet in 70 of the tumors. In 47 of these sites the PW-Doppler was used to gain flow patterns to achieve resistance- and pulsatility-index. The images were analysed retrospectively. In B scan images lesions were judged by 12 parameters. Additional information about number, diameter and distribution of vessels within a tumor was taken from the images of colour-coded duplex sonography. The excised complexes were evaluated pathohistologically. Only descriptive statistical analysis was possible because the resulting groups were very small after being sorted according to WHO-classification. Therefore the complexes of mammary glands were subsumpted into two groups – „malignant“ and „benign“ tumours. An irregular contour of the tumor (32 of 61 malignant, 4 of 48 benign tumors), signal enhancement (36/61 malignant, 9/48 benign tumors) or total shadowing (8/61 malignant, 0/48 benign tumors) behind the tumor, calcification (20/61 malignant, 6/48 benign tumors) and irregular vessel diameters (25/61 malignant, 12/48 benign tumors) are signs of malignancy. Tumors that miss a clearly detactable borderline (15/61 malignant, 36/48 benign tumors) and tumors with no signal alteration behind the tumor (17/61 malignant, 39/48 benign tumors) are benign more often. The combination of parameters reduces the number of adequate tumors and rises significance. A tumor showing an irregular contour and calcification (13/61 malignant, 1/48 benign tumors) is more likely to be malignant as well as a tumor of medium echodensity showing signal enhancement (21/61 malignant, 6/48 benign tumors). Tumors of medium echodensity without signal alteration behind the lesion (13/61 malignant, 33/48 benign tumors) and tumors with diffusely distributed vessels of regular diameter (3/36 malignant, 14/29 benign tumors) are more likely to be benign. It could be shown that high-resolution B scan parameters can help differentiate between malignant and benign tumors of the mammary gland, especially if they are used in combination with each other. Parameters from colour-coded duplex sonography can increase predicting value of B scan examinations too but there is no use of analysing resistance index or pulsatility index. One of the criteria established in human medicine ist the contour of a tumor. This parameter is of diagnostic use in mammary tumours of the bitch too. It is not possible to clearly predict the character of a tumor of the mammary gland of a bitch by only a few parameters based on a sonogram but sonographic examination can be helpful for assessing prognosis sometimes.

<p>Miniaturization of technologies to milli-, micro- and nanoscale offers numerous advantages for diagnostic and therapeutic biomedical applications. In comparison to their macro-scale counterparts, these small-scale systems are more portable, less invasive and less costly. They can facilitate rapid, sensitive and high throughput detection of abnormalities, help track disease progression, reduce sample consumption and improve therapeutic efficacy of drug delivery while decreasing systemic toxicity. Thus, there is clearly a need for creating innovative milli-, micro- and nanoscale tools that can uncover new possibilities in detection and treatment of various types of diseases. The overall objective of this dissertation was to develop novel small-scale technologies that could help enhance diagnostic and/or therapeutic outcomes in patients with cancer, opioid addiction and inflammatory bowel disease. First, we developed an echogenically stable nanodroplet ultrasound contrast agent with potential applications in extravascular molecular imaging of tumors and targeted cancer therapies. Then, we created a polymer blend microsphere system that could be integrated in prescription opioid tablets to develop an abuse-deterrent formulation against smoking. Finally, we designed a release system for localized delivery of aminosalicylates from magnetically actuated millirobots in the colon to improve therapeutic outcomes in patients suffering from inflammatory bowel disease. Overall, the technologies we developed could serve as a basis for designing diagnostic and therapeutic tools that are superior to currently existing platforms.</p>

No description available.