A multi-angle plane wave imaging approach for high frequency 2D flow visualization in small animals: simulation study in the murine arterial system

To preclinically investigate the role of hemodynamics in atherogenesis, mouse models are particularly useful due to the rapid disease development. As such, murine blood flow visualization has become an important tool, with current US systems equipped with traditional 1D flow imaging techniques, lacking spatial and/or temporal resolution to accurately resolve in-vivo flow fields. Hence, we investigated multi-angle plane wave imaging for ultrafast, 2D vector flow visualization and compared this approach with conventional pulsed Doppler in the setting of a mouse aorta with abdominal aortic aneurysm. For this purpose, we used a multiphysics model which allowed direct comparison of synthetic US images with the true flow field behind the image. In case of the abdominal aorta, we showed the mean flow estimation improved 9 % when using 2D vector Doppler compared to conventional Doppler, but still underestimated the true flow because the full spatial velocity distribution remained unknown. We also evaluated a more challenging measurement location, the mesenteric artery (aortic side branch), often assessed in a short-axis view close to the origin of the branch to avoid the smaller dimensions downstream. Even so, complex out-ofplane flow dynamics hampered a reliable flow assessment for both techniques. Hence, both cases illustrated the need for 3D vascular imaging, allowing acquisition of the full 3D spatial velocity profile

Development of ultrasonic methods for hemodynamic measurements

A transcutanous method to measure instantaneous mean blood flow in peripheral arteries of the human body was defined. Transcutanous and implanted cuff ultrasound velocity measurements were evaluated, and the accuracies of velocity, flow, and diameter measurements were assessed for steady flow. Performance criteria were established for the pulsed Doppler velocity meter (PUDVM), and performance tests were conducted. Several improvements are suggested

Ultrasonic Doppler measurement of renal artery blood flow

An extensive evaluation of the practical and theoretical limitations encountered in the use of totally implantable CW Doppler flowmeters is provided. Theoretical analyses, computer models, in-vitro and in-vivo calibration studies describe the sources and magnitudes of potential errors in the measurement of blood flow through the renal artery, as well as larger vessels in the circulatory system. The evaluation of new flowmeter/transducer systems and their use in physiological investigations is reported

Application of DSP Concept for Ultrasound Doppler Image Processing System

Blood-flow measurements using Doppler ultrasound system are popular in ultrasonic diagnoses. But the blood-flow measurement inside the heart is difficult. There are many reasons behind it. The deep range and fast blood-flow are difficult to measure because of limitation of acoustic velocity. Moreover, strong heart valve signals mix into the blood-flow signal. Against such difficulties, the statistics mathematical model was applied to analyze many clinical data sets. The system identification method based on the mathematical model could realize a new blood-flow measurement system that has ultrasound Doppler information as input and electrocardiogram as output

The use of Fluid Haemodynamics in the Diagnosis of Cardiovascular Disease

Currently the diagnostic methods used to detect cardiovascular disease largely rely on the inference of the presence of arterial stenosis. There is a clinical interest in the development of a diagnostic screening technique which can indicate the risk of developing cardiovascular disease at an early stage so that non-surgical treatments can be applied. The goal of this work was to develop and validate a diagnostic screening technique for cardiovascular disease using the mechanical biomarker wall shear stress. Improvements in wall shear stress measurements were made by using a 2D Fourier transform to extract additional spectral information from the ultrasound pulse and decrease the spectral variance by integrating across the bandwidth of transmitted frequencies. This technique was validated for a series of anatomically realistic flow phantoms which precisely mimicked the progression of wall stiffening that characterises cardiovascular disease. The newly developed spectral analysis technique demonstrated a higher diagnostic performance than the other techniques tested, both in terms of a greater degree of significance in detecting differences in vessel wall stiffness and in terms of the sensitivity and specificity of the technique. The technique could not be tested in pulsatile flow due to hardware limitations, but preliminary testing indicated that the increased performance of the technique would likely transfer to a physiological flow regime. The results of this work indicated that the algorithm had the potential to rival the diagnostic power of the current gold standard while being applicable at an earlier stage of cardiovascular disease

Non Linear Ultrasound Doppler and the Detection of Targeted Contrast Agents

One of the main challenges in molecular imaging with targeted contrast agents is the detection and discrimination of attached agents from the rest of the signals originating from freely flowing agents and tissue. The aim of this thesis was to develop methods for the detection of targeted microbubbles. One approach consisted of investigating the use of nonlinear Doppler for this purpose. Nonlinear Doppler enables the differentiation of moving from non-moving and linear from nonlinear scattering. Targeted microbubbles are static and nonlinear scatterers and they should be detected using this technique. A novel nonlinear Doppler technique: Pulse subtraction Doppler, was developed and compared to pulse inversion Doppler. It is shown that both techniques lead to similar Doppler spectra and depending on the medical applications and the equipment limitations, both techniques have benefits. This served as a starting point for the derivation of a generalised nonlinear Doppler technique, based on combined linear pulse pair sequences and tested in a simulation study. The response from a single microbubble was simulated for different pulse combinations and the pulse sequences were compared with regards to criteria specific to imaging requirements. It was shown that depending on initially set criteria, such as transmitted energy, mechanical index or scanner characteristics, certain pulse combinations offer alternatives to the current imaging modalities and allow to take into account specific constrains due to the targeted application/equipment. Furthermore, the proposed approach is directly applicable in a strict non linear imaging approach, without Doppler processing. An in vitro phantom was designed in order to assess pulse subtraction Doppler for the detection and discrimination of static nonlinear microbubbles in the presence of free flowing ones. It was shown that pulse subtraction Doppler enables such discrimination and the practicability for in vivo situations is discussed. The pulse subtraction Doppler sequences were also tested on a phantom containing magnetic bubbles. It was shown that the magnetic bubbles can be immobilised through a magnetic field to a specific region of interest under flow conditions. The bubbles also showed to be acoustically detectable and to scatter linearly at diagnostic driving pressures. Preliminary work regarding experimental biotinylated microbubbles and their attachment to streptavidin coated surfaces is also presented. Due to their proximity to a wall, researchers have found that targeted microbubbles exhibit different acoustic signatures compared to free ones and this knowledge can improve their detection techniques. The behaviour of microbubbles against a membrane of varying stiffness was also studied through high speed camera observations. It was found both experimentally and by comparison to theoretical modelling that within the stiffness range of human blood vessels the change in acoustical behaviour of microbubbles is negligible. This thesis has taken two complementary research approaches which have shown to constitute advancements for the detection and discrimination of targeted microbubbles

Hemodynamics in the Stenosed Carotid Bifurcation with Plaque Ulceration

The presence of irregular plaque surface morphology or ulceration of the atherosclerotic lesion has been identified as an independent risk factor for ischemic stroke. Doppler ultrasound (DUS) is the most commonly performed non-invasive technique used to assess patients suspected of having carotid artery disease, but currently does not incorporate the diagnosis of plaque ulceration. Advanced Doppler analyses incorporating quantitative estimates of flow disturbances may result in diagnostic indices that identify plaque ulcerative conditions. A technique for the fabrication of DUS-compatible flow phantoms was developed, using a direct-machining method that is amenable to comprehensive DUS investigations. In vitro flow studies in an ensemble of matched model vessel geometries determined that ulceration as small as 2 mm can generate significant disturbances in the downstream flow field in a moderately stenosed carotid artery, which are detectable using the DUS velocity-derived parameter turbulence intensity (TI) measured with a clinical system. Further experimental results showed that distal TI was significantly elevated (P \u3c 0.001) due to proximal plaque ulceration in the mild and moderately stenosed carotid bifurcation (30%, 50%, 60% diameter reduction), and also increased with stenosis severity. Pulsatile computational fluid dynamics (CFD) models, with simulated particle tracking, demonstrated enhanced flow disruption of the stenotic jet and slight elevations in path-dependent shear exposure parameters in a stenosed carotid bifurcation model with ulceration. In addition, CFD models were used to evaluate the DUS index TI using finite volume sampling