The Ultrasound Window Into Vascular Ageing: A Technology Review by the VascAgeNet COST Action

Arteriosclerosis; Ultrasound; Vascular ageingArteriosclerosi; Ecografia; Envelliment vascularArteriosclerosis; Ecografía; Envejecimiento vascularNon-invasive ultrasound (US) imaging enables the assessment of the properties of superficial blood vessels. Various modes can be used for vascular characteristics analysis, ranging from radiofrequency (RF) data, Doppler- and standard B/M-mode imaging, to more recent ultra-high frequency and ultrafast techniques. The aim of the present work was to provide an overview of the current state-of-the-art non-invasive US technologies and corresponding vascular ageing characteristics from a technological perspective. Following an introduction about the basic concepts of the US technique, the characteristics considered in this review are clustered into: 1) vessel wall structure; 2) dynamic elastic properties, and 3) reactive vessel properties. The overview shows that ultrasound is a versatile, non-invasive, and safe imaging technique that can be adopted for obtaining information about function, structure, and reactivity in superficial arteries. The most suitable setting for a specific application must be selected according to spatial and temporal resolution requirements. The usefulness of standardization in the validation process and performance metric adoption emerges. Computer-based techniques should always be preferred to manual measures, as long as the algorithms and learning procedures are transparent and well described, and the performance leads to better results. Identification of a minimal clinically important difference is a crucial point for drawing conclusions regarding robustness of the techniques and for the translation into practice of any biomarker.This article is based upon work from COST Action CA18216 VascAgeNet, supported by COST (European Cooperation in Science and Technology, www.cost.eu). A.G. has received funding from “La Caixa” Foundation (LCF/BQ/PR22/11920008). R.E.C is supported by the National Health and Medical Research Council of Australia (reference: 2009005) and by a National Heart Foundation Future Leader Fellowship (reference: 105636). J.A. acknowledges support from the British Heart Foundation [PG/15/104/31913], the Wellcome EPSRC Centre for Medical Engineering at King's College London [WT 203148/Z/16/Z], and the Cardiovascular MedTech Co-operative at Guy's and St Thomas' NHS Foundation Trust [MIC-2016-019]

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

Monitoring of the central blood pressure waveform via a conformal ultrasonic device.

Continuous monitoring of the central-blood-pressure waveform from deeply embedded vessels, such as the carotid artery and jugular vein, has clinical value for the prediction of all-cause cardiovascular mortality. However, existing non-invasive approaches, including photoplethysmography and tonometry, only enable access to the superficial peripheral vasculature. Although current ultrasonic technologies allow non-invasive deep-tissue observation, unstable coupling with the tissue surface resulting from the bulkiness and rigidity of conventional ultrasound probes introduces usability constraints. Here, we describe the design and operation of an ultrasonic device that is conformal to the skin and capable of capturing blood-pressure waveforms at deeply embedded arterial and venous sites. The wearable device is ultrathin (240 μm) and stretchable (with strains up to 60%), and enables the non-invasive, continuous and accurate monitoring of cardiovascular events from multiple body locations, which should facilitate its use in a variety of clinical environments

Methods for Improved Estimation of Low Blood Velocities Using Vector Doppler Ultrasound

Accurate estimation of low 3D blood velocities, such as near the wall in recirculation or disturbed flow regions, is important for accurate mapping of velocities to improve estimations of wall shear stress and turbulence, which are associated risk factors for vascular disease and stroke. Doppler ultrasound non-invasively measures blood-velocities but suffers from two major limitations addressed in this thesis. These are angle dependence of the measurements, which requires the knowledge of beam-to-flow angle, and the wall-filter. The high-pass wall filter that is applied to attenuate the high-intensity low-frequency signal from tissue and slowly moving vessel wall also attenuates any low velocity signals from blood thus causing inaccurate estimation of these velocities. This thesis presents two methods to alleviate the angle-dependence limitation and to minimize the effect of the wall filter on low blood-velocity estimates: a multi-receiver technique – vector Doppler ultrasound (VDUS), and a novel method called aperture-translation technique. For the first method – VDUS, theoretical and experimental studies were performed to assess the comparative benefit of three to eight receivers (3R–8R) in Doppler ultrasound configurations in terms of the number of receiver beams, inter-beam angle, and beam- selection method (criterion for discriminating between tissue and blood Doppler signals) for a range of velocity orientations. Accuracy and precision for ≥5 receivers were consistently better over all flow velocity orientations and for all beam-selection methods. Asymmetry in the 5R configuration led to improved accuracy and precision compared to symmetrical 6R and 8R configurations. Second, a novel 2D-VDUS aperture-translation technique using mechanical or electronic translation of the transmit-receive apertures was introduced and assessed experimentally. Both versions of the technique outperformed the conventional 2D-VDUS method for detection of low flow velocities in terms of accuracy and precision. The electronic version, which is more relevant and feasible clinically, showed comparable reliability and better accuracy compared with the idealized mechanical version, therefore suggesting its potential for future development. This work demonstrated that a minimum of five receivers, preferably with an inherent asymmetry with respect to the flow direction, should be considered when designing a 2D-array configuration for improved estimation of low velocities. For estimation of low velocities not measurable with conventional VDUS methods, the aperture-translation technique could be a potential candidate

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

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