An investigation of real time ultrasound Doppler techniques for tissue motion and deformation analysis

Cardiovascular disease accounts for more than 50% of all deaths in the Western world. Atherosclerosis is responsible for the vast majority of these diseases. There are a range of risk factors for atherosclerosis that affect the endothelial lining vessel wall cells to cause endothelial dysfunction, which then predisposes to a localized build-up of 'plaque' tissue that narrows the lumen of the arteries. Plaque rupture promotes localized vasospasm, thrombosis and embolism causing downstream tissue death, resulting in severe disability or death from, for instance, heart attack (in the coronary circulation) or stroke (in the cerebral circulation). Narrowing of the lumen and plaque rupture are associated with high tissue stresses and tissue under perfusion, which will alter local arterial and myocardial wall dynamics and elastic properties. Hence visualization of tissue dynamic and deformation property changes is crucial to detect atherosclerosis in the earliest stages to prevent acute events.The objective of this dissertation research is to develop new techniques based on Doppler ultrasound to investigate and visualize changes in tissue dynamic and deformation properties due to atherosclerosis in cardiac and vascular applications. A new technique, to correct for the Doppler angle dependence for tissue motion analysis has been developed. It is based on multiple ultrasound beams, and has been validated in vitro to study tissue dynamic properties. It can measure tissue velocity magnitude with low bias (5%) and standard deviation (10%), and tissue velocity orientation with a bias less than 5 degrees and a standard deviation below 5 degrees. A new Doppler based method, called strain rate, has also been developed and validated in vitro for the quantification of regional vessel or myocardial wall deformation. Strain rate is derived from the velocity information and can assess tissue deformation with an accuracy of 5% and a standard deviation less than 10%. Some examples of cardiac strain rate imaging have been gathered and are described in this thesis. Strain rate, as all Doppler based techniques, suffers from angle dependence limitation. A method to estimate one-component strain rate in any direction in the two-dimensional image not necessarily along the ultrasound beam has been developed. The method allows correcting for the strain rate bias along any user-defined direction. It is also shown that the full strain rate tensor can theoretically be extracted from the velocity vector field acquired by multiple beam tissue vector velocity technique. In vitro experiments have shown that qualitative two-component strain rate tensor can be derived. Two-component vector velocity from the moving tissue was acquired and two two-component strain rate images were derived. The images showed agreement with the expected deformation pattern

Influence of wall thickness and diameter on arterial shear wave elastography: a phantom and finite element study

Quantitative, non-invasive and local measurements of arterial mechanical properties could be highly beneficial for early diagnosis of cardiovascular disease and follow up of treatment. Arterial shear wave elastography (SWE) and wave velocity dispersion analysis have previously been applied to measure arterial stiffness. Arterial wall thickness (h) and inner diameter (D) vary with age and pathology and may influence the shear wave propagation. Nevertheless, the effect of arterial geometry in SWE has not yet been systematically investigated. In this study the influence of geometry on the estimated mechanical properties of plates (h = 0.5–3 mm) and hollow cylinders (h = 1, 2 and 3 mm, D = 6 mm) was assessed by experiments in phantoms and by finite element method simulations. In addition, simulations in hollow cylinders with wall thickness difficult to achieve in phantoms were performed (h = 0.5–1.3 mm, D = 5–8 mm). The phase velocity curves obtained from experiments and simulations were compared in the frequency range 200–1000 Hz and showed good agreement (R2 = 0.80 ± 0.07 for plates and R2 = 0.82 ± 0.04 for hollow cylinders). Wall thickness had a larger effect than diameter on the dispersion curves, which did not have major effects above 400 Hz. An underestimation of 0.1–0.2 mm in wall thickness introduces an error 4–9 kPa in hollow cylinders with shear modulus of 21–26 kPa. Therefore, wall thickness should correctly be measured in arterial SWE applications for accurate mechanical properties estimation

Ultrafast Ultrasound Imaging

Among medical imaging modalities, such as computed tomography (CT) and magnetic resonance imaging (MRI), ultrasound imaging stands out due to its temporal resolution. Owing to the nature of medical ultrasound imaging, it has been used for not only observation of the morphology of living organs but also functional imaging, such as blood flow imaging and evaluation of the cardiac function. Ultrafast ultrasound imaging, which has recently become widely available, significantly increases the opportunities for medical functional imaging. Ultrafast ultrasound imaging typically enables imaging frame-rates of up to ten thousand frames per second (fps). Due to the extremely high temporal resolution, this enables visualization of rapid dynamic responses of biological tissues, which cannot be observed and analyzed by conventional ultrasound imaging. This Special Issue includes various studies of improvements to the performance of ultrafast ultrasoun

Transcutaneous measurement of volume blood flow

Blood flow velocity measurements, using Doppler velocimeter, are described. The ability to measure blood velocity using ultrasound is derived from the Doppler effect; the change in frequency which occurs when sound is reflected or transmitted from a moving target. When ultrasound of the appropriate frequency is transmitted through a moving blood stream, the blood cells act as point scatterers of ultrasonic energy. If this scattered ultrasonic energy is detected, it is found to be shifted in frequency according to the velocity of the blood cells, nu, the frequency of the incident sound, f sub o, the speed of sound in the medium, c, and the angle between the sound beam and the velocity vector, o. The relation describing this effect is known as the Doppler equation. Delta f = 2 f sub o x nu x cos alpha/c. The theoretical and experimental methods are evaluated

2-D and 3-D high frame-rate Pulse Wave Imaging for the characterization of focal vascular disease

Cardiovascular diseases are major causes of morbidity and mortality in Western-style populations. Atherosclerosis and Abdominal Aortic Aneurysms (AAAs) are two prevalent vascular diseases that may progress without symptoms and contribute to acute cardiovascular events such as stroke and AAA rupture, which are consistently among the leading causes of death worldwide. The imaging methods used in the diagnosis of these diseases, have been reported to present several limitations. Given that both are associated with mechanical changes in the arterial wall, imaging of the arterial mechanical properties may improve early disease detection and patient care. Pulse wave velocity (PWV) refers to the velocity at which arterial waves generated by ventricular ejection travel along the arterial tree. PWV is a surrogate marker of arterial stiffness linked to cardiovascular mortality. The foot-to-foot method that is typically used to calculate PWV suffers from errors of distance measurements and time-delay measurements. Additionally, a single PWV estimate is provided over a relatively long distance, thus inherently lacking the capability to provide regional arterial stiffness measurements. Pulse Wave Imaging (PWI) is a noninvasive, ultrasound-based technique for imaging the propagation of pulse waves along the wall of major arteries and providing a regional PWV value for the imaged artery. The aim of this work was to enable PWI to provide more localized PWV and stiffness measurements within the imaged arterial segment and to further extend it into a 2-D and 3-D technique for the detection and monitoring of focal vascular disease at high temporal and spatial resolution. The improved modality was integrated with blood flow imaging modalities aiming to render PWI a comprehensive methodology for the study of arterial biomechanics in vivo. Spatial information was increased with the introduction of piecewise PWI. This novel technique was used to measure PWV within small sub-regions of the imaged vessel in murine aneurysmal (n = 8) and atherosclerotic aortas (n = 11) in vivo. It provided PWV and stiffness maps while capturing the progressive arterial stiffening caused by atherosclerosis. PWI was further augmented with a sophisticated adaptive algorithm, enabling it to optimally partition the imaged artery into relatively homogeneous segments, automatically isolating arterial stiffness inhomogeneities. Adaptive PWI was validated in silicone phantoms consisting of segments of varying stiffness and then tested in murine aortas in vivo. Subsequently, the conventional tradeoff between spatial and temporal resolution was addressed with a plane wave compounding implementation of PWI, allowing the acquisition of full field of view frames at over 2000 Hz. A GPU-accelerated PWI post-processing framework was developed for the processing of the big bulk of generated data. The parameters of coherent compounding were optimized in vivo. The optimized sequences were then used in the clinic to assess the mechanical properties of atherosclerotic carotids (n=10) and carotids of patients after endarterectomy (n=7), a procedure to remove the plaque and restore blood flow to the brain. In the case of atherosclerotic patients undergoing carotid endarterectomy, the results were compared against the histology of the excised plaques. Investigation of the mechanical properties of plaques was also conducted for the first time with a high-frequency transducer (18.5 MHz). Additionally, 4-D PWI was introduced, utilizing high frame rate 3-D plane wave acquisitions with a 2-D matrix array transducer (16x16 elements, 2.5 MHz). A novel methodology for PWV estimation along the direction of pulse wave propagation was implemented and validated in silicone phantoms. 4-D PWI provided comprehensive views of the pulse wave propagation in a plaque phantom and the results were compared against conventional PWI. Finally, its feasibility was tested in the carotid arteries of healthy human subjects (n=6). PWVs derived in 3-D were within the physiological range and showed good agreement with the results of conventional PWI. Finally, PWI was integrated with flow imaging modalities (Color and Vector Doppler). Thus, full field-of-view, high frame-rate, simultaneous and co-localized imaging of the arterial wall dynamics and color flow as well as 2-D vector flow was implemented. The feasibility of both techniques was tested in healthy subjects (n=6) in vivo. The relationship between the timings of the flow and wall velocities was investigated at multiple locations of the imaged artery. Vector flow velocities were found to be aligned with the vessel’s centerline during peak systole in the common carotid artery and interesting flow patterns were revealed in the case of the carotid bifurcation Consequently, with the aforementioned improvements and the inclusion of 3-D imaging, PWI is expected to provide comprehensive information on the mechanical properties of pathological arteries, providing clinicians with a powerful tool for the early detection of vascular abnormalities undetectable on the B-mode, while also enabling the monitoring of fully developed vascular pathology and of the recovery of post-operated vessels

Enhancing Nonlinear Ultrasonic Methods for Laboratory and Clinical Applications

This thesis addresses the underlying physics associated with nonlinear ultrasonic field propagation, measurements of the nonlinear properties of materials, and mechanisms contributing to the observed systematic variation of backscattered ultrasonic energy from the heart over the heart cycle. Studies were performed to address the reliability of the methods of measurement used for the quantitative characterization of nonlinear phenomena and to explore the utility of these methods. This thesis examines the measurement of nonlinear acoustic properties of materials using several methods, including the transmission of ultrasound through the material, as well as the backscattered signal from a region of interest within the material. A method of transmitting ultrasound into the diffractive far field with a negligible amount of distortion is described, along with the consequences of working with different frequencies: and subsequently different diffractive regimes). This thesis also describes studies designed to assess the nature of backscattered ultrasound from the heart obtained by using harmonic imaging, which utilizes nonlinear phenomena to improve the overall quality of clinical ultrasonic images. Several investigators have previously reported a systematic cyclic variation in the backscattered ultrasonic signal from the tissue of the heart. However, a discrepancy in the reported magnitude of this variation seems to be present in the literature. This discrepancy is examined in the context of the multiple methods used to characterize the variation. Furthermore, the characteristics of this systematic variation of backscatter are compared with the dynamics of the left ventricle described using a damped harmonic oscillator model as an approach for identifying the underlying causes of the observed variation

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