The induced rupturing of Poly Vinyl Alcohol (PVA) microbubbles with high mechanical index (MI)ultrasound beam is used in multiple medical application such as drug delivery, image contrastenhancement and perfusion imaging.In this work, Triggered imaging technique with subtraction algorithm is used to enhance themicrobubble’s (MB) contrast over tissue (CTR). The technique is performed by rupturing MBwith one destruction wave sequence followed by 100 B-mode imaging pulse sequences. Theimages obtained are then subtracted by a base image that is selected after the destruction pulse[1].The result of this technique depends mainly on the effectiveness of destruction pulse inrupturing highest number of MB. This has been tested through tissue mimicking phantomwithout replenishing the MB. The evaluation of the methods is done through the CTR and CNRcalculation for each of the 100 frames.The contrast enhancement technique used has also been tested with similar setup but withcontinuous replenishment of MB. The evaluation is done by comparing CNR and CTR results forthe 100 frames obtained by B-mode imaging with the ones resulted from the subtractionalgorithm.The contrast values obtained from both experiments are used in driving the characterization ofPVA response to high MI.The result for the destruction pulse effectiveness shows that the pulse indeed managed toreduce number of MB, but not to the lowest. This is because of leaked gas from cracked shell,the shell acoustic enhancement effect, and large bubbles which managed to survive.The Triggered imaging has shown large improvement in CTR value with use of the subtractionalgorithm when compared to B-mode results. In addition, it has provided an experimental wayfor perfusion imaging and quantification by monitoring CTR value after the destructive pulse[2]. This sets the bases for experimental research relevant to tissue perfusion at ultrasound labof KTH.

Thesis deals with ultrasonographic contrast examinations, that are performed to assess tissue perfusion and non-invasive ultrasound method speckle tracking, overcoming the weaknesses of Doppler techniques used to scanning the movement of the tissue.

Introdução: Estudos pré-clínicos demonstraram que impulsos de alto índice mecânico (IM) de um transdutor de ultrassom diagnóstico durante uma infusão intravenosa de microbolhas (sonotrombólise) podem restaurar o fluxo epicárdico e microvascular no infarto agudo do miocárdio com supradesnivelamento do segmento ST (IAMCSST). Objetivo: Testamos a eficácia clínica da sonotrombólise em pacientes com IAMCSST medindo a taxa de recanalização coronariana precoce, tamanho do infarto do miocárdio por ressonância magnética e ecocardiograma e a evolução do defeito de perfusão e função ventricular esquerda à chegada, após a intervenção coronária percutânea (ICP), 72h a 96h e em um e seis meses de acompanhamento. Métodos: Pacientes com seu primeiro IAMCSST foram prospectivamente randomizados para receberem impulsos de alto IM guiados por ultrassom diagnóstico (grupo terapia) durante a infusão intravenosa de um agente de ultrassom antes e após a ICP ou para um grupo controle que recebeu apenas ICP (n = 50 em cada grupo). Um grupo de referência (n = 203) que chegou fora da janela de randomização também foi analisado. Recanalização angiográfica prévia à ICP, tamanho do infarto (TI) por ressonância magnética e alteração no defeito de perfusão e função sistólica pela ecocardiografia à chegada, após-ICP, 72h a 96h, em um e seis meses foram comparados. Resultados: A média de idade dos pacientes randomizados foi de 59 anos e não houve diferença de sexo, presença de diabetes, hipertensão arterial e dislipidemia entre os grupos estudados. Os tempos porta-balão não foram diferentes entre os grupos analisados (78 ± 32 minutos para o grupo controle versus 77 ± 26 minutos para o grupo terapia, p = 0,42), mas foram mais longos no grupo de referência (96 ± 49 minutos, p < 0,001 comparado aos grupos controle e terapia). A recanalização angiográfica foi de 48% no grupo terapia versus 20% no grupo controle e 21% no grupos de referência (p < 0,001). O TI foi reduzido (29 ± 22 gramas do grupo terapia versus 40 ± 20 gramas do grupo controle, p = 0,026). Da mesma forma, as taxas de fluxo TIMI 3 pré-ICP foram maiores no grupo terapia (32% versus 14% no grupo controle e 16% no grupo de referência, p = 0,02). Após a ICP, fluxo TIMI 3 foi observado no vaso culpado em 37/50 (74%) pacientes no grupo terapia e 30/50 (60%) pacientes do grupo controle. A fração de ejeção do ventrículo esquerdo (FEVE) não foi diferente entre os grupos antes do tratamento (44 ± 11% no grupo terapia versus 43 ± 10% no grupo controle, p = 0,39), mas aumentou imediatamente após a ICP no grupo terapia (p = 0,03) e permaneceu maior aos seis meses (p = 0,015). A correlação entre as medidas do tamanho do infarto (TI) em gramas por ressonância magnética e ecocardiografia com contraste, utilizando o coeficiente de correlação intraclasses foi de 0,672 (p < 0,001). Não houve diferença significativa na % de área acometida pelo infarto pelo ecocardiograma realizado pré-ICP, pós-ICP e durante a internação com 72h a 96h de evolução, mas no seguimento de 1 mês houve consolidação de maior redução da % de área infartada no grupo terapia 20,67 ± 8,99 a 11,87 ± 7,49 quando comparado ao grupo controle 19,16 ± 10,08 a 17,02 ± 10,02 (p = 0,016), mostrando uma diferença comportamental durante as avaliações temporais, com uma maior diminuição no tamanho do infarto no grupo terapia (p < 0,001). Ao comparar a porcentagem média de áreas infartadas naqueles pacientes com artérias coronárias obstruídas na primeira angiografia, houve um menor comprometimento microvascular naqueles do grupo terapia 12,99 ± 6,53 versus 18,87 ± 9,93 do grupo controle (p = 0,015 ). Ainda assim, como consequência das melhorias observadas na % do tamanho do infarto, notamos uma melhora progressiva na fração de ejeção nos pacientes do grupo terapia: 44,0% ± 11,0% para 53,0% ± 10% versus 43 % ± 10% para 48,0% ± 11,0% no grupo controles (p = 0,048) da chegada aos 6 meses de acompanhamento. Conclusões: A sonotrombólise adicionada à ICP melhora as taxas de recanalização e reduz o tamanho do infarto, resultando em melhorias sustentadas na perfusão miocárdica e na função sistólica após o IAMCSST / Background: Pre-clinical studies have demonstrated that high mechanical index (MI) impulses from a diagnostic ultrasound transducer during an intravenous microbubble infusion (sonothrombolysis) can restore epicardial and microvascular flow in acute ST-segment elevation myocardial infarction (STEMI). Objective: We tested the clinical effectiveness of sonothrombolysis in patients with STEMI by measuring early coronary recanalization rate, size of myocardial infarction by MRI and echocardiography and the evolution of the perfusion defect and left ventricular function at arrival, after PCI, 72h to 96h and at one- and six-months follow-up. Methods: Patients with their first STEMI were prospectively randomized to either diagnostic ultrasound-guided high MI impulses (therapy group) during an intravenous ultrasound agent infusion prior to, and following emergent percutaneous coronary intervention (PCI), or to a control group that received PCI only (n = 50 in each group). A reference group (n = 203) who arrived outside the randomization window was also analyzed. Angiographic recanalization prior to PCI, infarct size (IS) by magnetic resonance imaging, and change in perfusion defect and systolic function by echocardiography at arrival, post PCI, 72h to 96h, one and six months were compared. Results: The mean age of the randomized patients was 59 years and there was no difference in gender, presence of diabetes, arterial hypertension and dyslipidemia between the groups studied. Door to balloon times were not different between groups (78 ± 32 minutes for control versus 77 ± 26 minutes for therapy groups, p = 0.42), but were longer in the reference group (96 ± 49 minutes, p < 0.001 compared to control and therapy groups). Angiographic recanalization was 48% in therapy group versus 20% in control group and 21% in the reference group (p < 0.001). IS was reduced (29 ± 22 grams in therapy group versus 40 ± 20 grams in control group, p = 0.026). Likewise, pre-PCI TIMI 3 flow rates were higher in the therapy group (32% versus 14% in control group and 16% in the reference group, p = 0.02). After PCI, the TIMI 3 flow was observed in the culprit vessel in 37/50 (74%) patients in therapy group and 30/50 (60%) in patients in the control group. Left ventricular ejection fraction (LVEF) was not different between groups before treatment (44 ± 11% in therapy group versus 43 ± 10% in control group, p = 0.39), but increased immediately after PCI in the therapy group (p = 0.03) and remained higher at six months (p = 0.015). The correlation between the measurements of infarct size (IS) in grams by magnetic resonance and contrast echocardiography, using the intra-class correlation coefficient was 0.672 (p < 0.001). There was no significant difference in the % area affected by the infarction on echocardiography performed pre-PCI, post-PCI and during hospital stay with 72h to 96h of evolution, but in the follow-up of 1 month there was a consolidation of greater reduction of the % infarcted area in the therapy group 20.67 ± 8.99 to 11.87 ± 7.49 when compared to control group 19.16 ± 10.08 to 17.02 ± 10.02 (p = 0.016), showing a behavioral difference during the temporal evaluations, with a greater decrease in infarct size in the therapy group (p < 0.001). When comparing the mean % of infarcted areas in those patients with occluded coronary arteries at the first angiography, there was a lower microvascular impairment in those in the therapy group 12.99 ± 6.53 versus 18.87 ± 9,93 in control group (p = 0.015). Still, as a consequence of the improvements observed in the % of infarct size, we noticed a progressive improvement in the ejection fraction in patients in the therapy group 44.0% ± 11.0% to 53.0% ± 10% versus 43% ± 10% to 48.0% ± 11,0% in the control group (p = 0.048) from arrival to 6-month follow-up. Conclusions: Sonothrombolysis added to PCI improves recanalization rates and reduces infarct size, resulting in sustained improvements in myocardial perfusion and systolic function after STEMI

Thesis deals with ultrasonographic contrast examinations, that are performed to assess tissue perfusion and non-invasive ultrasound method speckle tracking, overcoming the weaknesses of Doppler techniques used to scanning the movement of the tissue.