Nonlinear Harmonic Distortion of Complementary Golay Codes.

Recent advances in electronics miniaturization have led to the development of low-power, low-cost, point-of-care ultrasound scanners. Low-cost systems employing simple bi-level pulse generation devices need only utilize binary phase modulated coded excitations to significantly improve sensitivity; however the performance of complementary codes in the presence of nonlinear harmonic distortion has not been thoroughly investigated. Through simulation, it was found that nonlinear propagation media with little attenuative properties can significantly deteriorate the Peak Sidelobe Level (PSL) performance of complementary Golay coded pulse compression, resulting in PSL levels of -62 dB using nonlinear acoustics theory contrasted with -198 dB in the linear case. Simulations of 96 complementary pairs revealed that some pairs are more robust to sidelobe degradation from nonlinear harmonic distortion than others, up to a maximum PSL difference of 17 dB between the best and worst performing codes. It is recommended that users consider the effects of nonlinear harmonic distortion when implementing binary phase modulated complementary Golay coded excitations.

Spatiotemporal Dynamics of Dilute Red Blood Cell Suspensions in Low-Inertia Microchannel Flow.

Microfluidic technologies are commonly used for the manipulation of red blood cell (RBC) suspensions and analyses of flow-mediated biomechanics. To enhance the performance of microfluidic devices, understanding the dynamics of the suspensions processed within is crucial. We report novel, to our knowledge, aspects of the spatiotemporal dynamics of RBC suspensions flowing through a typical microchannel at low Reynolds number. Through experiments with dilute RBC suspensions, we find an off-center two-peak (OCTP) profile of cells contrary to the centralized distribution commonly reported for low-inertia flows. This is reminiscent of the well-known "tubular pinch effect," which arises from inertial effects. However, given the conditions of negligible inertia in our experiments, an alternative explanation is needed for this OCTP profile. Our massively parallel simulations of RBC flow in real-size microfluidic dimensions using the immersed-boundary-lattice-Boltzmann method confirm the experimental findings and elucidate the underlying mechanism for the counterintuitive RBC pattern. By analyzing the RBC migration and cell-free layer development within a high-aspect-ratio channel, we show that such a distribution is co-determined by the spatial decay of hydrodynamic lift and the global deficiency of cell dispersion in dilute suspensions. We find a cell-free layer development length greater than 46 and 28 hydraulic diameters in the experiment and simulation, respectively, exceeding typical lengths of microfluidic designs. Our work highlights the key role of transient cell distribution in dilute suspensions, which may negatively affect the reliability of experimental results if not taken into account.

Biomechanical Assessment Predicts Aneurysm Related Events in Patients with Abdominal Aortic Aneurysm.

OBJECTIVE: To test whether aneurysm biomechanical ratio (ABR; a dimensionless ratio of wall stress and wall strength) can predict aneurysm related events. METHODS: In a prospective multicentre clinical study of 295 patients with an abdominal aortic aneurysm (AAA; diameter ≥ 40 mm), three dimensional reconstruction and computational biomechanical analyses were used to compute ABR at baseline. Participants were followed for at least two years and the primary end point was the composite of aneurysm rupture or repair. RESULTS: The majority were male (87%), current or former smokers (86%), most (72%) had hypertension (mean ± standard deviation [SD] systolic blood pressure 140 ± 22 mmHg), and mean ± SD baseline diameter was 49.0 ± 6.9 mm. Mean ± SD ABR was 0.49 ± 0.27. Participants were followed up for a mean ± SD of 848 ± 379 days and rupture (n = 13) or repair (n = 102) occurred in 115 (39%) cases. The number of repairs increased across tertiles of ABR: low (n = 24), medium (n = 34), and high ABR (n = 44) (p = .010). Rupture or repair occurred more frequently in those with higher ABR (log rank p = .009) and ABR was independently predictive of this outcome after adjusting for diameter and other clinical risk factors, including sex and smoking (hazard ratio 1.41; 95% confidence interval 1.09-1.83 [p = .010]). CONCLUSION: It has been shown that biomechanical ABR is a strong independent predictor of AAA rupture or repair in a model incorporating known risk factors, including diameter. Determining ABR at baseline could help guide the management of patients with AAA.

Association between erythrocyte dynamics and vessel remodelling in developmental vascular networks.

Sprouting angiogenesis is an essential vascularization mechanism consisting of sprouting and remodelling. The remodelling phase is driven by rearrangements of endothelial cells (ECs) within the post-sprouting vascular plexus. Prior work has uncovered how ECs polarize and migrate in response to flow-induced wall shear stress (WSS). However, the question of how the presence of erythrocytes (widely known as red blood cells (RBCs)) and their impact on haemodynamics affect vascular remodelling remains unanswered. Here, we devise a computational framework to model cellular blood flow in developmental mouse retina. We demonstrate a previously unreported highly heterogeneous distribution of RBCs in primitive vasculature. Furthermore, we report a strong association between vessel regression and RBC hypoperfusion, and identify plasma skimming as the driving mechanism. Live imaging in a developmental zebrafish model confirms this association. Taken together, our results indicate that RBC dynamics are fundamental to establishing the regional WSS differences driving vascular remodelling via their ability to modulate effective viscosity.

Low Shear Stress at Baseline Predicts Expansion and Aneurysm-Related Events in Patients With Abdominal Aortic Aneurysm.

BACKGROUND: Low shear stress has been implicated in abdominal aortic aneurysm (AAA) expansion and clinical events. We tested the hypothesis that low shear stress in AAA at baseline is a marker of expansion rate and future aneurysm-related events. METHODS: Patients were imaged with computed tomography angiography at baseline and followed up every 6 months >24 months with ultrasound measurements of maximum diameter. From baseline computed tomography angiography, we reconstructed 3-dimensional models for automated computational fluid dynamics simulations and computed luminal shear stress. The primary composite end point was aneurysm repair and/or rupture, and the secondary end point was aneurysm expansion rate. RESULTS: We included 295 patients with median AAA diameter of 49 mm (interquartile range, 43-54 mm) and median follow-up of 914 (interquartile range, 670-1112) days. There were 114 (39%) aneurysm-related events, with 13 AAA ruptures and 98 repairs (one rupture was repaired). Patients with low shear stress (<0.4 Pa) experienced a higher number of aneurysm-related events (44%) compared with medium (0.4-0.6 Pa; 27%) and high (>0.6 Pa; 29%) shear stress groups (P=0.010). This association was independent of known risk factors (adjusted hazard ratio, 1.72 [95% CI, 1.08-2.73]; P=0.023). Low shear stress was also independently associated with AAA expansion rate (ß=+0.28 mm/y [95% CI, 0.02-0.53]; P=0.037). CONCLUSIONS: We show for the first time that low shear stress (<0.4 Pa) at baseline is associated with both AAA expansion and future aneurysm-related events. Aneurysms within the lowest tertile of shear stress, versus those with higher shear stress, were more likely to rupture or reach thresholds for elective repair. Larger prospective validation trials are needed to confirm these findings and translate them into clinical management.

Simulation and validation of arterial ultrasound imaging and blood flow.

We reviewed the simulation and validation of arterial ultrasound imaging and blood flow assessment. The physical process of ultrasound imaging and measurement is complex, especially in disease. Simulation of physiological flow in a phantom with tissue equivalence of soft tissue, vessel wall and blood is now achievable. Outstanding issues are concerned with production of anatomical models, simulation of arterial disease, refinement of blood mimics to account for non-Newtonian behavior and validation of velocity measurements against an independent technique such as particle image velocimetry. String and belt phantoms offer simplicity of design, especially for evaluation of velocity estimators, and have a role as portable test objects. Electronic injection and vibrating test objects produce nonphysiologic Doppler signals, and their role is limited. Computational models of the ultrasound imaging and measurement process offer considerable flexibility in their ability to alter multiple parameters of both the propagation medium and ultrasound instrument. For these models, outstanding issues are concerned with the inclusion of different tissue types, multilayer arteries, inhomogeneous tissues and diseased tissues.

A method to estimate wall shear rate with a clinical ultrasound scanner.

A simple technique to estimate the wall shear rate in healthy arteries using a clinical ultrasound scanner has been developed. This method uses the theory of fully developed oscillatory flow together with a spectral Doppler trace and an estimate of mean arterial diameter. A method using color flow imaging was compared with the spectral Doppler method in vascular phantoms and found to have errors that were on average 35% greater. Differences from the theoretic value for the time averaged wall shear rate using the spectral Doppler method varied by artery: brachial -9 (1) %; carotid -7 (1) %; femoral -22 (4) %; and fetal aorta -17 (10) %. Test measurements obtained from one healthy volunteer demonstrated the feasibility of the technique in vivo.

Characterization of an abdominal aortic velocity waveform in patients with abdominal aortic aneurysm.

Haemodynamics studies of abdominal aortic aneurysm require data on the velocity in the normal section of the aorta. Centreline velocity waveforms were measured in abdominal aortic aneurysm patients proximal to the aneurysm using spectral Doppler ultrasound. Characteristic points were automatically found on 21 of the waveforms and their parameters were used to create an archetypal centreline velocity waveform. The maximum velocity was 45 +/- 13 cm s(-1), the minimum velocity was -15 +/- 11 cm s(-1) and the maximum diastolic velocity was 2.7 +/- 4.7 cm s(-1). The velocity wave is suitable for use as an input to in vitro or in silico investigations of abdominal aortic aneurysm haemodynamics.

A reproducibility study of a TDI-based method to calculate indices of arterial stiffness.

The aim of the study was to investigate the reproducibility of estimation of Young's modulus E and pressure strain elastic modulus Ep, derived from a tissue Doppler imaging (TDI) wall motion technique. Healthy subjects had their arteries insonated at the same sitting by two different observers and at two different sittings by the same observer. From 32 subjects in the reproducibility study, within-scan coefficient of variation (CV) was 4.5%. Intraobserver between-scan CV for E was 12.7% and for Ep 11.0%. Interobserver CVs were 8.3% and 9.3%, respectively. TDI is a reproducible, valid and highly sensitive direct assessment of arterial wall parameters. It is at least as reproducible as other ultrasound based methods for assessing arterial stiffness and also provides increased information about the arterial distension waveform.

Wall Stress and Geometry of the Thoracic Aorta in Patients With Aortic Valve Disease.

BACKGROUND: Aortic valve disease increases velocity and changes the way blood enters the aorta. Over time, the biomechanical environment can cause aortic remodelling. We hypothesized that aortic geometry and wall stress would be different in patients with aortic valve disease compared with controls. METHODS: We examined 40 patients with aortic sclerosis (n = 10) or mild (n = 10), moderate (n = 10), and severe (n = 10) aortic stenosis, and also 10 control individuals. The thoracic aorta of each individual was reconstructed into a three-dimensional model from computed tomography. We measured geometric variables and used finite element analysis to compute aortic wall stress. Statistical analyses were performed to test our hypothesis. RESULTS: Aortic wall stress was significantly associated with tortuosity of the descending aorta (r = 0.35, p = 0.01), arch radius (r = 0.49, p < 0.01), ascending aortic diameter (r = 0.59, p < 0.01), and aortic centerline length (r = 0.39, p < 0.01). Wall stress was highest in patients with severe stenosis (p = 0.02), although elevations in wall stress were also noted in those with mild stenosis (p = 0.02), and aortic sclerosis (p = 0.02) compared with controls. Similar trends were observed when we corrected for difference in blood pressure. Total centerline tortuosity was higher in patients with severe aortic stenosis than in controls (p = 0.04), as was descending aorta tortuosity (p = 0.04). CONCLUSIONS: Aortic geometry is associated with aortic wall stress. Patients with aortic valve disease have higher aortic wall stress than controls, and those with severe aortic stenosis have more tortuous aortas. However, increases in geometric measures and wall stress are not stepwise with increasing disease severity.

On the optimization of low-cost FDM 3D printers for accurate replication of patient-specific abdominal aortic aneurysm geometry.

BACKGROUND: There is a potential for direct model manufacturing of abdominal aortic aneurysm (AAA) using 3D printing technique for generating flexible semi-transparent prototypes. A patient-specific AAA model was manufactured using fused deposition modelling (FDM) 3D printing technology. A flexible, semi-transparent thermoplastic polyurethane (TPU), called Cheetah Water (produced by Ninjatek, USA), was used as the flexible, transparent material for model manufacture with a hydrophilic support structure 3D printed with polyvinyl alcohol (PVA). Printing parameters were investigated to evaluate their effect on 3D-printing precision and transparency of the final model. ISO standard tear resistance tests were carried out on Ninjatek Cheetah specimens for a comparison of tear strength with silicone rubbers. RESULTS: It was found that an increase in printing speed decreased printing accuracy, whilst using an infill percentage of 100% and printing nozzle temperature of 255 °C produced the most transparent results. The model had fair transparency, allowing external inspection of model inserts such as stent grafts, and good flexibility with an overall discrepancy between CAD and physical model average wall thicknesses of 0.05 mm (2.5% thicker than the CAD model). The tear resistance test found Ninjatek Cheetah TPU to have an average tear resistance of 83 kN/m, higher than any of the silicone rubbers used in previous AAA model manufacture. The model had lower cost (4.50 GBP per model), shorter manufacturing time (25 h 3 min) and an acceptable level of accuracy (2.61% error) compared to other methods. CONCLUSIONS: It was concluded that the model would be of use in endovascular aneurysm repair planning and education, particularly for practicing placement of hooked or barbed stents, due to the model's balance of flexibility, transparency, robustness and cost-effectiveness.

Distribution of wall shear rate throughout the arterial tree: a case study.

The generally accepted assumption that the arterial system remodels itself to maintain constant wall shear stress throughout is based on Murray's law, utilising the principle of minimum work for steady flow. However, blood flow in the human arterial system is pulsatile. In this work we outline a method allowing for estimation of wall shear rate in arteries using the flow waveforms as the input signal and estimate wall shear rates in the common carotid, brachial, and femoral arteries to determine the uniformity of distribution of wall shear rates throughout the arterial system. Time-dependent wall shear rates occurring in fully developed pulsatile flow were obtained using Womersley's theory. Flow waveforms and radii of the arteries measured in a young healthy male subject without any known cardiac disease using magnetic resonance taken from the literature were used as the input to the model. Peak/mean wall shear rates were found to be (1640/403.2 s(-1)) in common carotid, (908.8/84.95 s(-1)) in brachial, and (1251/134.2 s(-1)) in femoral arteries. Our findings suggest a non-uniform distribution of wall shear rates throughout the arterial system. The advantage of using this method is that such input data are being routinely recorded during diagnostic ultrasonography.

Physical properties of tissues relevant to arterial ultrasound imaging and blood velocity measurement.

A review was undertaken of physical phenomena and the values of associated physical quantities relevant to arterial ultrasound imaging and measurement. Arteries are multilayered anisotropic structures. However, the requirement to obtain elasticity measurements from the data available using ultrasound imaging necessitates the use of highly simplified constitutive models involving Young's modulus, E. Values of E are reported for healthy arteries and for the constituents of diseased arteries. It is widely assumed that arterial blood flow is Newtonian. However, recent studies suggest that non-Newtonian behavior has a strong influence on arterial flow, and the balance of published evidence suggests that non-Newtonian behavior is associated primarily with red cell deformation rather than with aggregation. Hence, modeling studies should account for red cell deformation and the shear thinning effect that this produces. Published literature in healthy adults gives an average hematocrit and high-shear viscosity of 0.44 +/- 0.03 and 3.9 +/- 0.6 mPa.s, respectively. Published data on the acoustic properties of arteries and blood is sufficiently consistent between papers to allow compilation and derivation of best-fit equations summarizing the behavior across a wide frequency range, which then may be used in future modeling studies. Best-fit equations were derived for the attenuation coefficient vs. frequency in whole arteries (R(2) = 0.995), plasma (R(2) = 0.963) and blood with hematocrit near 45% (R(2) = 0.999), and for the backscatter coefficient vs. frequency from blood with hematocrit near 45% (R(2) = 0.958).

Factors affecting the arterial distension waveform derived from tissue Doppler imaging (TDI): an in vitro study on precision.

An investigation was made into the effect of acquisition parameters on the distension waveform estimated from tissue Doppler imaging (TDI). Physiological distension waveforms were generated using a compliant wall phantom. Distensions derived over a range of scanning geometries and transducer pressures were compared with those obtained in optimised scanning conditions. The estimated maximum distension decreased with scanning depth by 7% between 20 mm and 44 mm below the phantom surface, with an increase in transducer-vessel angle (by 22% from 0 degrees to 24 degrees ) and with a decrease in scan plane-vessel coincidence (by 34% from coincidence to 2 mm from the vessel central axis). An increase with transducer pressure was observed (by 20% from contact to high exerted pressure).

An arterial wall motion test phantom for the evaluation of wall motion software.

Increasing cardiovascular disease has led to new ultrasound methods of assessing artery disease such as arterial wall motion measurement. To validate arterial wall motion software, we developed a mechanically-controlled wall motion test phantom with straight upper and lower agar tissue mimicking material layers that resemble an artery cross section. The wall separation, displacements and wall velocities and accelerations can be controlled within physiologically realistic levels. A user-definable displacement or one of several pre-defined displacement waveforms can be created by the user with custom-written software. The test phantom is then controlled using the defined waveform with a stepper motor controller. Accuracy assessment of the test phantom with a laser vibrometer yielded a positional accuracy of 36+/-2 microm. A typical application of the test phantom is demonstrated by assessing a tissue Doppler imaging (TDI) method for estimating the distension waveform. The TDI-based method was found to have a minimum resolvable displacement of 22.5 microm, and a measurement accuracy of +/-8% using a physiological wall motion movement with a peak displacement of 689 microm. The accuracy of the TDI method was found to decrease with decreasing wall displacement and increasing wall velocity.

Testing a new surfactant in a widely-used blood mimic for ultrasound flow imaging.

BACKGROUND: A blood-mimicking fluid developed by Ramnarine et al. has been widely used in flow phantoms for ultrasound flow imaging research, and it has also been cited by IEC 61685 as a reference for making blood-mimicking fluid.However, the surfactant material Synperonic N in this blood-mimicking fluid recipe is phased out from the European market due to environmental issues. The aim of this study is to test whether Synperonic N can be substituted by biodegradable Synperonic A7 in making blood-mimicking fluid for ultrasound flow imaging research. METHODS AND MATERIALS: A flow phantom was fabricated to test the blood-mimicking fluid with Synperonic N and Synperonic A7 as surfactants separately. Doppler images and velocity data were collected using a clinical ultrasound scanner under constant and pulsatile flows; and images and measured velocities were compared. RESULTS: It was found that both blood mimics can provide exactly the same images under spectral Doppler ultrasound and colour Doppler ultrasound in terms of their image qualities. The maximum velocities under constant flow were measured by the spectral Doppler ultrasound as 0.4714 ± 0.001 m.s-1 and 0.4644 ± 0.001 m.s-1 for blood-mimicking fluid with Synperonic N and blood-mimicking fluid with Synperonic A7, respectively. Measured velocities using the two different blood-mimicking fluids were statistically different (p < 0.001), but this difference was less than 2%. The Synperonic A7 can be used as a substitute for Synperonic N as a surfactant material in making the blood-mimicking fluid for ultrasound flow imaging research.

Investigation of Ultrasound-Measured Flow Velocity, Flow Rate and Wall Shear Rate in Radial and Ulnar Arteries Using Simulation.

Parameters of blood flow measured by ultrasound in radial and ulnar arteries, such as flow velocity, flow rate and wall shear rate, are widely used in clinical practice and clinical research. Investigation of these measurements is useful for evaluating accuracy and providing knowledge of error sources. A method for simulating the spectral Doppler ultrasound measurement process was developed with computational fluid dynamics providing flow-field data. Specific scanning factors were adjusted to investigate their influence on estimation of the maximum velocity waveform, and flow rate and wall shear rate were derived using the Womersley equation. The overestimation in maximum velocity increases greatly (peak systolic from about 10% to 30%, time-averaged from about 30% to 50%) when the beam-vessel angle is changed from 30° to 70°. The Womersley equation was able to estimate flow rate in both arteries with less than 3% error, but performed better in the radial artery (2.3% overestimation) than the ulnar artery (15.4% underestimation) in estimating wall shear rate. It is concluded that measurements of flow parameters in the radial and ulnar arteries with clinical ultrasound scanners are prone to clinically significant errors.

Fabrication of Two Flow Phantoms for Doppler Ultrasound Imaging.

Flow phantoms are widely used in studies associated with Doppler ultrasound measurements, acting as an effective experimental validation system in cardiovascular-related research and in new algorithm/instrumentation development. The development of materials that match the acoustic and mechanical properties of the vascular system is of great interest while designing flow phantoms. Although recipes that meet the flow phantom standard defined by the International Electrotechnical Commission 61685 are already available in the literature, the standard procedure for material preparations and phantom fabrications has not been well established. In this paper, two types of flow phantoms, with and without blood vessel mimic, are described in detail in terms of the material preparation and phantom fabrication. The phantom materials chosen for the two phantoms are from published phantom studies, and their physical properties have been investigated previously. Both the flow phantoms have been scanned by ultrasound scanners and images from different modes are presented. These phantoms may be used in the validation and characterization of Doppler ultrasound measurements in blood vessels with a diameter above 1 mm.

Nonlinear multiscale regularisation in MR elastography: Towards fine feature mapping.

Fine-featured elastograms may provide additional information of radiological interest in the context of in vivo elastography. Here a new image processing pipeline called ESP (Elastography Software Pipeline) is developed to create Magnetic Resonance Elastography (MRE) maps of viscoelastic parameters (complex modulus magnitude |G*| and loss angle ϕ) that preserve fine-scale information through nonlinear, multi-scale extensions of typical MRE post-processing techniques. METHODS: A new MRE image processing pipeline was developed that incorporates wavelet-domain denoising, image-driven noise estimation, and feature detection. ESP was first validated using simulated data, including viscoelastic Finite Element Method (FEM) simulations, at multiple noise levels. ESP images were compared with MDEV pipeline images, both in the FEM models and in three ten-subject cohorts of brain, thigh, and liver acquisitions. ESP and MDEV mean values were compared to 2D local frequency estimation (LFE) mean values for the same cohorts as a benchmark. Finally, the proportion of spectral energy at fine frequencies was quantified using the Reduced Energy Ratio (RER) for both ESP and MDEV. RESULTS: Blind estimates of added noise (σ) were within 5.3% ± 2.6% of prescribed, and the same technique estimated σ in the in vivo cohorts at 1.7 ± 0.8%. A 5 × 5 × 5 truncated Gabor filter bank effectively detects local spatial frequencies at wavelengths λ ≤ 10px. For FEM inversions, mean |G*| of hard target, soft target, and background remained within 8% of prescribed up to σ=20%, and mean ϕ results were within 10%, excepting hard target ϕ, which required redrawing around a ring artefact to achieve similar accuracy. Inspection of FEM |G*| images showed some spatial distortion around hard target boundaries and inspection of ϕ images showed ring artefacts around the same target. For the in vivo cohorts, ESP results showed mean correlation of R=0.83 with MDEV and liver stiffness estimates within 7% of 2D-LFE results. Finally, ESP showed statistically significant increase in fine feature spectral energy as measured with RER for both |G*| (p<1×10-9) and ϕ (p<1×10-3). CONCLUSION: Information at finer frequencies can be recovered in ESP elastograms in typical experimental conditions, however scatter- and boundary-related artefacts may cause the fine features to have inaccurate values. In in vivo cohorts, ESP delivers an increase in fine feature spectral energy, and better performance with longer wavelengths, than MDEV while showing similar stability and robustness.