Ultrasound imaging systems are a safe and affordable imaging modality with the disadvantage of low spatial resolution, especially for assessing smaller vessels. However, with the implementation of super-resolution ultrasound imaging techniques, studies have shown promising results in achieving a resolution below the diffraction limit. Super-resolution ultrasound imaging techniques takes advantage of the point spread function to localize the centroid of the ultrasound contrast agents in an image. By superimposing thousands of these images, a super-resolved image of the localized and tracked contrast agents can be created, which presents an image where vessels down to a few micrometers can be resolved. The purpose of this master’s thesis was to implement super-resolution ultrasound imaging, test different localization methods and analyze them by using different ultrasound contrast agent concentrations. Grayscale ultrasound images were acquired using the Verasonics system for three different microbubble concentrations. The super-resolution ultrasound imaging program was executed on the grayscale images using three different localization methods, Gaussian fit, No-shift and Interpolation based scheme. The microbubbles were localized and tracked over several frames to create a super-resolved image which had the pixel resolution of a 10th of the wavelength. Significant improvements were demonstrated in the super-resolved images compared to the grayscale images. The higher microbubble concentrations resulted in a higher number of localized and tracked microbubbles. While the low concentration exhibited lower values. Comparing the methods, Gaussian fit and No-shift detected higher number of microbubbles than the method Interpolation. Although further analysis is needed, the thesis concluded that using Gaussian fit as a localization method and higher microbubble concentrations, a super-resolved image can be produced even if the program is tested on fewer images. / Ultraljudsavbildning är en säker och billig avbildningsmodalitet med en låg spatial upplösning, framför allt vid avbildning av mindre kärl. Men med implementering av ultraljudsavbildningstekniker med superupplösning har studier visat lovande resultat för att uppnå en upplösning under diffraktionsgränsen. Ultraljudsavbildningstekniker med superupplösning utnyttjar punktspridningsfunktionen för att lokalisera ett ultraljudskontrastmedels centerpunkt i en bild. Genom att överlagra tusentals av dessa bilder skapas en superupplöst bild av det lokaliserade och spårade kontrastmedlet. Med hjälp av superupplösta bilden kan kärl som är några mikrometer urskiljas. Syftet med denna masteruppsats var att implementera ultraljudsavbildning med superupplösning, testa olika lokaliseringsmetoder och analysera de genom att använda olika koncentrationer av mikrobubblor. Gråskale ultraljudsbilder samlades in med hjälp av Verasonics systemet för tre olika koncentrationer av mikrobubblor. Superupplösningsprogrammet var exekverad på gråskalebilderna för tre olika lokaliseringsmetoder, Gaussian fit, No-shift och Interpolation based scheme. Mikrobubblorna lokaliserades och spårades över flera bilder för att skapa en superupplöst bild vilket hade en tiondel av våglängden som pixelupplösning. Resultatet presenterade en märkbar förbättring i de superupplösta bilderna jämfört med gråskalebilderna. De högre koncentrationerna med flera mikrobubblor resulterade i ett högre antal lokaliserade och spårade mikrobubblor, medan den lägre koncentrationen gav färre lokaliserade mikrobubblor. Metoderna Gaussian fit och No-shift detekterade flera mikrobubblor än metoden Interpolation. Slutsatsen visade att användningen av lokaliseingsmetoden Gaussian fit med högre koncentrationer av mikrobubblor ger en superupplöst bild även om programmet exekveras på färre bilder.

Each year million of babies are born pre-term, some of these pre-term births occur due to the motherhaving a too soft cervix which can not withstand the forces the baby exposes it to. The aim of thisstudy was to implement and evaluate a programmable shear wave elastography ultrasound system forcervical applications and investigate the optimal settings of shear wave elastography push voltage andshear wave elastography push focus depth. Shear wave elastography is an ultrasound based imagingmodality aiming to evaluate the tissue elasticity by using acoustic radiation forces to induce shear waves.The propagation of the shear waves through the tissue is then tracked in order to calculate the shearwave velocity which is related to the tissue elasticity. B-mode imaging, pushing sequence and planewave imaging have been implemented and measurements have been conducted on four cervical polyvinylalcohol phantoms. The acquired data has been post-processed using Loupas 2D-autocorrector to gainthe axial displacement and enabling tracking of the shear waves to allow evaluation and optimizationof the implemented method. The implemented shear wave technique showed to be able to distinguishcervical phantoms of dierent elasticity and a high pushing voltage and shallow focus push depth havebeen found to produce the most reliable results.

Acoustic droplet vaporization (ADV) is a process in which a phase shift of a liquified droplet into a gaseous microbubble, is triggered using an ultrasonic wave. In contrast to utilizing conventional contrast agents in ultrasound, the phase change contrast agents used in ADV can extravasate into tumor tissue, and they offer a greater circulatory lifespan, thereby increasing the potential applications in which they can be utilized. In this project, the impact of different ultrasound parameters on the efficiency of ADV was investigated, using a programmable ultrasound system. Two different ultrasound sequences were designed, for imaging and vaporization of droplets. Furthermore, three different sets of experiments were performed. Firstly, the vaporization effect of different imaging voltages was investigated, whereby a setting of 15V was identified as an able voltage for the remaining experiments. Secondly, experiments concerning the effect of vaporizing frequency on the ADV efficiency were performed, including the use of single and dual frequencies. Lastly, different frequency settings were combined with varying the number of cycles, to assess how the choice of pulse length influences the vaporization. The results from the project indicate that no substantial difference in ADV efficiency is achieved when using different frequency settings for perfluoropentane droplets encapsulated by cellulose nanofibers. However, the results provide clear indications of the benefit of using longer pulse durations on the vaporization efficiency. In conclusion, further studies are required before ADV can be translated into a clinical setting.

Ultrasound-mediated drug delivery has been proposed as a safe and non-invasive method to achieve localized drug release. Drug-loaded microbubbles are injected in the vascular system and ultrasound waves are then used to localize and burst the microbubbles at a specific targeted area. The relatively large size of microbubbles however limits both their lifetime and their reach in the human body. Phase-change liquid droplets can extend the use of ultrasound contrast agents for localized drug delivery. Their smaller size provides several advantages. The droplets can reach smaller capillaries, such as those in tumors vasculature. Their lifetime is also considerably prolonged. Through the phenomenon of Acoustic Droplet Vaporization (ADV), triggered by ultrasound stimulation, the liquid-filled droplets experience a phase change and are converted into gas-filled microbubbles. The newly created microbubbles can then be disrupted by further stimulation and release their drug load in the tumor tissue. In this project, a protocol to image and burst perfluoropentane-based micro-sized droplets using a single transducer is developed using the Verasonics Ultrasound System. The pulse sequences are developed to allow close monitoring of the drug delivery by capturing a series of images before and after the vaporization or destruction of the droplets. The droplets response was assessed for different pulse voltages and durations. Mean pixel value was calculated for the regions of interest, using the images captured before and after delivery of the ultrasound pulse. Vaporization of the droplets can be achieved with low voltage (10V), whereas high voltage (50V) triggers their destruction. Combined with high voltage, pulse duration affects the rate at which droplets can be destructed.

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.

For many years, microbubbles have been used as ultrasound contrast agents to improve the quality of diagnostics, seeing that they produce more backscattering ultrasound than blood does. Novel types of microbubbles and increased knowledge about their different behaviors have led to other suggested areas of use. One notable example is the poly-vinyl alcohol (PVA) microbubble, which has been discovered to have a unique fracturing mechanism referred to as the pumping-out behavior. The PVA microbubble has the potential to be used, for instance, in local drug delivery of therapeutic gases, but further studies are needed. In this study, the aim was to develop a tool for imaging the pumping-out behavior of the PVA microbubbles. A linear transducer connected to the programmable Verasonics Research System operated by MatLab software was used to achieve it. The designed ultrasound sequences were tested on a tissue-mimicking phantom containing one vessel filled with PVA microbubbles and one with degassed water. The design was divided into two steps. First, an ultrafast imaging sequence, based on plane waves, was developed to achieve adequate acquisition rate for detecting escaping air from the microbubbles. Furthermore, coherent compounding was implemented to compensate for some of the loss in image quality due to the use of plane waves instead of focused waves. The second step of the design was to combine the imaging sequence with destruction pulses so that the pumping-out behavior could be imaged. The designed ultrasound sequence was evaluated by calculating the mean pixel intensities, contrast-to-tissue ratio (CTR), and contrast-to-noise ratio (CNR) of different regions of interest (ROI) in the acquired images. The results of this project agree with the result previously reported in a study of PVA microbubbles made by Kothapalli et al.. Thus, the developed tool can image the pumping-out behavior. However, further improvements to the imaging tool, such as use of a contrast specific method, is recommended for it to become more reliable and useful. In conclusion, the developed imaging tool works for imaging the pumping-out behavior, but improvements should be made. With a useful imaging tool, further studies can be performed to understand the parameters affecting the pumping-out behavior. In the end, the PVA microbubbles can possibly be used as, for example, local drug deliverers in the clinic.

Ultrasound has been established as one of the most widely used imaging modalities for diagnostic purposes, due to the several advantages it provides in comparison with other techniques. Hence, ways to further improve the confidence in diagnoses provided by ultrasound are constantly being investigated. One of them is the introduction of Ultrasound Contrast Agents, which can enhance the weak echoes produced by the small vessels, improving the imaging performance. In this study, a setup was created and six ultrasound imaging techniques were implemented by using the Verasonics Research System®, in order to take advantage of the different behavior between the tissue and the Polyvinyl-Alcohol microbubbles, when exposed to ultrasound. These were: Fundamental B-mode, Ultraharmonic, PulseInversion, Subharmonic Pulse Inversion, Ultraharmonic Pulse Inversion, Combination of the Sub- and Ultraharmonic Pulse Inversion. For the assessment of the bubbles’ response, the amplitude spectra were used, which showed a limited detection around the ultraharmonic region. For the evaluation of the imaging performance of the techniques, the Contrast-to-Tissue (CTR) and Contrast-to-Noise Ratios (CNR) were calculated. The Combination of the Sub- and Ultraharmonic Pulse Inversion reported the highest imaging performance among all the techniques. A comparison with previous articles provided a similar pattern in terms of CTR. / Technology