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This book sets out the physical and engineering principles of acoustics and ultrasound as used for medical applications. It covers the basics of linear acoustics, wave propagation, non-linear acoustics, acoustic properties of tissue, transducer components, and ultrasonic imaging modes, as well as the most common diagnostic and therapeutic applications. It offers students and professionals in medical physics and engineering a detailed overview of the technical aspects of medical ultrasonic imaging, whilst serving as a reference for clinical and research staff.

The application of atomization technology is common in fields such as agriculture, cosmetics, environmental sciences, and medicine. Aerosolized drugs are administered using nebulizers to treat both pulmonary and nonpulmonary diseases. The characterization and measurement of nebulizers are of great significance in analyzing the performance and accuracy of the nebulizing system and the advancement of the technology. Nevertheless, the characterization of aerosols has been a long-standing challenge in scientific disciplines ranging from atmospheric physics to health sciences. The study of factors that influence nebulization has not been undertaken systematically using experimental techniques. Numerical modeling (NM) and computational fluid dynamics (CFD) can address such issues. This article provides a concise overview of the literature on the application of computational fluid dynamics to medical nebulizers and aerosol measurements.

Medical ultrasound technology is available, affordable, and non-invasive. It is used to detect, quantify, and heat tissue structures. This review article gives a concise overview of the types of behaviour that biological cells experience under the influence of ultrasound only, i.e., without the presence of microbubbles. The phenomena are discussed from a physics and engineering perspective. They include proliferation, translation, apoptosis, lysis, transient membrane permeation, and oscillation. The ultimate goal of cellular acoustics is the detection, quantification, manipulation and eradication of individual cells.

Manipulating particles in the blood pool with noninvasive methods has been of great interest in therapeutic delivery. Recently, it was demonstrated experimentally that red blood cells can be forced to translate and accumulate in an ultrasound field. This acoustic response of the red blood cells has been attributed to sonophores, gas pockets that are formed under the influence of a sound field in the inner- membrane leaflets of biological cells. In this paper, we propose a simpler model: that of the compressible membrane. We derive the spatio-temporal cell dynamics for a spherically symmetric single cell, whilst regarding the cell bilayer membrane as two monolayer Newtonian viscous liquids, separated by a thin gas void. When applying the newly-derived equations to a red blood cell, it is observed that the void inside the bilayer expands to multiples of its original thickness, even at clinically safe acoustic pressure amplitudes. For causing permanent cell rupture during expansion, however, the acoustic pressure amplitudes needed would have to surpass the inertial cavitation threshold by a factor 10. Given the incompressibility of the inner monolayer, the radial oscillations of a cell are governed by the same set of equations as those of a forced antibubble. Evidently, these equations must hold for liposomes under sonication, as well.

Purpose In craniospinal irradiation, two or three isocenter groups along the craniocaudal axis are required to cover the long treatment target. Adapting the isocenter distance according to daily deviations in patient position is challenging because dosimetric hot or cold spots may occur in the field junction. The aim of this study was to quantify the effect of adapting the isocenter distance to patient position on the dose distribution of the field overlap region in craniospinal irradiation using partial‐arc volumetric modulated arc therapy. Methods The magnitude of isocenter distance deviations in craniocaudal direction was quantified by registering the setup images of 204 fractions of 12 patients to the planning images. The dosimetric effect of these deviations was determined by shifting the isocenters of the original treatment plan and calculating the resulting dose distribution. Results On fraction‐level, deviations larger than 3 mm caused more than 5 percentage point changes in the doses covering 2% (D2%) and 98% (D98%) of the junction volume in several patients. On treatment course‐level, the changes in D2% and D98% of the junction volume were less than 5 percentage points in all cases except for one patient. Conclusions Craniocaudal isocenter distance adaptation can be conducted provided that the mean isocenter distance deviation over the treatment course is within 3 mm.

Purpose Adenocarcinoma of the pancreas remains one of the most lethal human cancers. The high mortality rates associated with this form of cancer are subsequent to late-stage clinical presentation and diagnosis, when surgery is rarely possible and of modest chemotherapeutic impact. Survival rates following diagnosis with advanced pancreatic cancer are very low; typical mortality rates of 50 % are expected within 3 months of diagnosis. However, adjuvant chemotherapy improves the prognosis of patients even after palliative surgery, and successful newer neoadjuvant chemotherapeutical modalities have recently been reported. For patients whose tumours appear unresectable, chemotherapy remains the only option. During the past two decades, the nucleoside analogue gemcitabine has become the first-line chemotherapy for pancreatic adenocarcinoma. In this study, we aim to increase the delivery of gemcitabine to pancreatic tumours by exploring the effect of sonoporation for localised drug delivery of gemcitabine in an orthotopic xenograft mouse model of pancreatic cancer. Experimental Design An orthotopic xenograft mouse model of luciferase expressing MIA PaCa-2 cells was developed, exhibiting disease development similar to human pancreatic adenocarcinoma. Subsequently, two groups of mice were treated with gemcitabine alone and gemcitabine combined with sonoporation; saline-treated mice were used as a control group. A custom-made focused ultrasound transducer using clinically safe acoustic conditions in combination with SonoVue® ultrasound contrast agent was used to induce sonoporation in the localised region of the primary tumour only. Whole-body disease development was measured using bioluminescence imaging, and primary tumour development was measured using 3D ultrasound. Results Following just two treatments combining sonoporation and gemcitabine, primary tumour volumes were significantly lower than control groups. Additional therapy dramatically inhibited primary tumour growth throughout the course of the disease, with median survival increases of up to 10 % demonstrated in comparison to the control groups. Conclusion Combined sonoporation and gemcitabine therapy significantly impedes primary tumour development in an orthotopic xenograft model of human pancreatic cancer, suggesting additional clinical benefits for patients treated with gemcitabine in combination with sonoporation.

In clinical ultrasound, blood cells cannot be differentiated from surrounding tissue, due to the low acoustic impedance difference between blood cells and their surroundings. Resonant gas bubbles introduced in the bloodstream are ideal markers, if rapid dissolution can be prevented. Ultrasound contrast agents consist of microscopically small bubbles encapsulated by an elastic shell. These microbubbles oscillate upon ultrasound insonification. Microbubbles with thin lipid shells have demonstrated highly nonlinear behavior. To enhance diagnostic ultrasound imaging techniques and to explore therapeutic applications, these medical microbubbles have been modeled. Several detection techniques have been proposed to improve the detectability of the microbubbles. A new generation of contrast agents, with special targeting ligands attached to the shells, may assist the imaging of nonphysical properties of target tissue. Owing to microbubble-based contrast agents, ultrasound is becoming an even more important technique in clinical diagnostics.

This study presents the concept of spectral modulation and a time-frequency analysis, applied to broadband local (\\(5<\\Delta<200\\) km) seismic data from quarry blasts and micro-earthquakes, kindly supplied by the Institute for Petroleum Research and Geophysics (IPRG), Holon, Israel, from the so-called GIF-array. The aim of this research is verification of ripple-firing by recognition of scalloping trends in amplitude-spectra and hence discriminating quarry blasts from other events. Most quarry blasts are ripple-fired, in northern Israel open pit blasts; consequently the event discrimination method based on the recognition of ripple-firing patterns in the signal was chosen. The methods presented in this dissertation might also be applicable for deconvolution and dereverberation purposes in exploration seismology.

We study the sonication of stable particles that encapsulate a liquid core, so-called antibubbles. Acoustically active antibubbles can potentially be used for ultrasound-guided drug delivery. In this presentation, we derive the oscillating behaviour of acoustic antibubbles with a negligible outer shell, resulting in a Rayleigh-Plesset equation of antibubble dynamics. Furthermore,we compare the theoretical behaviour of antibubbles to that of regular gas bubbles. We conclude that antibubbles and regular bubbles are acoustically active in a very similar way, if the liquid core is less than half the antibubble radius. For larger cores, antibubbles demonstrate highly harmonic behaviour, which would make them suitable vehicles in ultrasonic imaging and ultrasound-guided drug delivery.

Purpose: Adenocarcinoma of the pancreas remains one of the most lethal human cancers. The high mortality rates associated with this form of cancer are subsequent to late-stage clinical presentation and diagnosis, when surgery is rarely possible and of modest chemotherapeutic impact. Survival rates following diagnosis with advanced pancreatic cancer are very low; typical mortality rates of 50 % are expected within 3 months of diagnosis. However, adjuvant chemotherapy improves the prognosis of patients even after palliative surgery, and successful newer neoadjuvant chemotherapeutical modalities have recently been reported. For patients whose tumours appear unresectable, chemotherapy remains the only option. During the past two decades, the nucleoside analogue gemcitabine has become the first-line chemotherapy for pancreatic adenocarcinoma. In this study, we aim to increase the delivery of gemcitabine to pancreatic tumours by exploring the effect of sonoporation for localised drug delivery of gemcitabine in an orthotopic xenograft mouse model of pancreatic cancer.Experimental Design: An orthotopic xenograft mouse model of luciferase expressing MIA PaCa-2 cells was developed, exhibiting disease development similar to human pancreatic adenocarcinoma. Subsequently, two groups of mice were treated with gemcitabine alone and gemcitabine combined with sonoporation; saline-treated mice were used as a control group. A custom-made focused ultrasound transducer using clinically safe acoustic conditions in combination with SonoVue® ultrasound contrast agent was used to induce sonoporation in the localised region of the primary tumour only. Whole-body disease development was measured using bioluminescence imaging, and primary tumour development was measured using 3D ultrasound.Results: Following just two treatments combining sonoporation and gemcitabine, primary tumour volumes were significantly lower than control groups. Additional therapy dramatically inhibited primary tumour growth throughout the course of the disease, with median survival increases of up to 10 % demonstrated in comparison to the control groups.