Effects of Blood Pressure on Brain Tissue Pulsation Amplitude in a Phantom Model.

OBJECTIVE: The precise mechanism and determinants of brain tissue pulsations (BTPs) are poorly understood, and the impact of blood pressure (BP) on BTPs is relatively unexplored. This study aimed to explore the relationship between BP parameters (mean arterial pressure [MAP] and pulse pressure [PP]) and BTP amplitude, using a transcranial tissue Doppler prototype. METHODS: A phantom brain model generating arterial-induced BTPs was developed to observe BP changes in the absence of confounding variables and cerebral autoregulation feedback processes. A regression model was developed to investigate the relationship between bulk BTP amplitude and BP. The separate effects of PP and MAP were evaluated and quantified. RESULTS: The regression model (R2 = 0.978) revealed that bulk BTP amplitude measured from 27 gates significantly increased with PP but not with MAP. Every 1 mm Hg increase in PP resulted in a bulk BTP amplitude increase of 0.29 µm. CONCLUSION: Increments in BP were significantly associated with increments in bulk BTP amplitude. Further work should aim to confirm the relationship between BP and BTPs in the presence of cerebral autoregulation and explore further physiological factors having an impact on BTP measurements, such as cerebral blood flow volume, tissue distensibility and intracranial pressure.

Ultrasound shear wave elastography imaging of common carotid arteries in patients with Spontaneous Coronary Artery Dissection (SCAD).

BACKGROUND: Shear wave elastography (SWE) is emerging as a valuable clinical tool for a variety of conditions. The aim of this pilot study was to assess the potential of SWE imaging of the common carotid arteries (CCA) in patients with spontaneous coronary artery dissection (SCAD), a rare but potentially life-threatening condition, hypothesized to be linked to changes in vessel wall elasticity. METHODS: Ultrasound shear wave elastography (SWE) estimates of artery wall elasticity were obtained from the left and right CCAs of 89 confirmed SCAD patients and 38 non-dissection controls. SWE images obtained over multiple cardiac cycles were analysed by a blinded observer to estimate elasticity in the form of a Young's Modulus (YM) value, across regions of interest (ROI) located within the anterior and posterior CCA walls. RESULTS: YM estimates ranged from 17 to 133 kPa in SCAD patients compared to 34 to 87 kPa in non-dissection controls. The mean YM of 55 [standard deviation (SD): 21] kPa in SCAD patients was not significantly different to the mean of 57 [SD: 12] kPa in controls, p = 0.32. The difference between groups was 2 kPa [95% Confidence Interval - 11, 4]. CONCLUSIONS: SWE imaging of CCAs in SCAD patients is feasible although the clinical benefit is limited by relatively high variability of YM values which may have contributed to our finding of no significant difference between SCAD patients and non-dissection controls.

Pulsed Wave Doppler Measurements of Maximum Velocity: Dependence on Sample Volume Size.

Pulsed wave (PW) Doppler ultrasound is routinely used in the clinic to assess blood flow. Our annual Doppler quality assurance tests revealed unexpectedly large errors in measurement of maximum velocity, exceeding our tolerance (error >20%), when using certain scanners with small Doppler sample volume dimensions. The aim of this study was to assess the dependence of maximum velocity estimates on PW Doppler sample volume size. A flow phantom with known steady flow was used to acquire maximum velocity estimates (maximum velocities of 24, 39 and 85 cm/s and sample volume range of 0.3-20 mm) with a variety of transducers and scanners in clinical use (51 probes from 4 manufacturers). Selected acoustic outputs were characterized using free-field hydrophone measurements. All maximum velocity estimates were within our tolerance for sample volume sizes ≥1.5 mm, although maximum velocity estimates typically increased with decreasing sample volume size. Errors exceeding our tolerance were commonly found for one manufacturer when using smaller sample volumes, resulting in up to 75% overestimation. Although intrinsic spectral broadening based on transit time considerations may help explain our findings, the sample volume dependence raises potential clinical concerns that users should be aware of and which manufacturers should consider addressing.

A Novel Elastography Phantom Prototype for Assessment of Ultrasound Elastography Imaging Performance.

The aims of this study were firstly to manufacture and evaluate a novel elastography test phantom and secondly to assess the performance of an elastography system using this phantom. A novel Leicester-St. Thomas' Elastography Pipe (L-STEP) test phantom consisting of five soft polyvinyl acrylic-cryogel pipes of varying diameters (2-12 mm), embedded at 45° within an agar-based tissue-mimicking material was developed. A shear-wave elastography (SWE) scanner was used by two blinded operators to image and assess longitudinal sections of the pipes. Young's modulus estimates were dependent on the diameter of pipes and at superficial depths were greater than deeper depths (mean 98 kPa vs. 59 kPa) and had lower coefficients of variation (mean 21% vs. 53%). The penetration depth (maximum depth at which a SWE signal was obtained) increased with increasing pipe diameter. Penetration depth measurements had excellent inter- and intra-operator reproducibility (intra-class correlation coefficients >0.8) and coefficient of variation range of 2%-12%. A new metric, called the summative performance index, was defined as the sum of the ratios of the penetration depth/pipe diameter. The L-STEP phantom is suitable for assessing key aspects of elastography imaging performance: resolution, accuracy, reproducibility, depth dependence, sensitivity and our novel summative performance index.

A Polyvinyl Alcohol-Based Thermochromic Material for Ultrasound Therapy Phantoms.

Temperature estimation is a fundamental step in assessment of the efficacy of thermal therapy. A thermochromic material sensitive within the temperature range 52.5°C-75°C has been developed. The material is based on polyvinyl alcohol cryogel with the addition of a commercial thermochromic ink. It is simple to manufacture, low cost, non-toxic and versatile. The thermal response of the material was evaluated using multiple methods, including immersion in a temperature-controlled water bath, a temperature-controlled heated needle and high-intensity focused ultrasound (HIFU) sonication. Changes in colour were evaluated using both RGB (red, green, blue) maps and pixel intensities. Acoustic and thermal properties of the material were measured. Thermo-acoustic simulations were run with an open-source software, and results were compared with the HIFU experiments, showing good agreement. The material has good potential for the development of ultrasound therapy phantoms.

The EFSUMB Guidelines and Recommendations for the Clinical Practice of Elastography in Non-Hepatic Applications: Update 2018.

This manuscript describes the use of ultrasound elastography, with the exception of liver applications, and represents an update of the 2013 EFSUMB (European Federation of Societies for Ultrasound in Medicine and Biology) Guidelines and Recommendations on the clinical use of elastography.

A preclinical ultrasound method for the assessment of vascular disease progression in murine models.

INTRODUCTION: The efficacy of preclinical ultrasound at providing a quantitative assessment of mouse models of vascular disease is relatively unknown. In this study, preclinical ultrasound was used in combination with a semi-automatic image processing method to track arterial distension alterations in mouse models of abdominal aortic aneurysm and atherosclerosis. METHODS: Longitudinal B-mode ultrasound images of the abdominal aorta were acquired using a preclinical ultrasound scanner. Arterial distension was assessed using a semi-automatic image processing algorithm to track vessel wall motion over the cardiac cycle. A standard, manual analysis method was applied for comparison. RESULTS: Mean arterial distension was significantly lower in abdominal aortic aneurysm mice between day 0 and day 7 post-onset of disease (p < 0.01) and between day 0 and day 14 (p < 0.001), while no difference was observed in sham control mice. Manual analysis detected a significant decrease (p < 0.05) between day 0 and day 14 only. Atherosclerotic mice showed alterations in arterial distension relating to genetic modification and diet. Arterial distension was significantly lower (p < 0.05) in Ldlr-/- (++/--) mice fed high-fat western diet when compared with both wild type (++/++) mice and Ldlr-/- (++/--) mice fed chow diet. The manual method did not detect a significant difference between these groups. CONCLUSIONS: Arterial distension can be used as an early marker for the detection of arterial disease in murine models. The semi-automatic analysis method provided increased sensitivity to differences between experimental groups when compared to the manual analysis method.

Shear wave elastography imaging of carotid plaques: feasible, reproducible and of clinical potential.

BACKGROUND: Shear Wave Elastography (SWE) imaging is a novel ultrasound technique for quantifying tissue elasticity. Studies have demonstrated that SWE is able to differentiate between diseased and normal tissue in a wide range clinical applications. However its applicability to atherosclerotic carotid disease has not been established. The aim of this study was to assess the feasibility and potential clinical benefit of using SWE imaging for the assessment of carotid plaques. METHODS: Eighty-one patients (mean age 76 years, 51 male) underwent greyscale and SWE imaging. Elasticity was quantified by measuring mean Young's Modulus (YM) within the plaque and within the vessel wall. Echogenicity was assessed using the Gray-Weale classification scale and the greyscale median (GSM). RESULTS: Fifty four plaques with stenosis greater than 30% were assessed. Reproducibility of YM measurements, quantified by the inter-frame coefficient of variation, was 22% within the vessel wall and 19% within the carotid plaque. Correlation with percentage stenosis was significant for plaque YM (p = 0.003), but insignificant for plaque GSM (p = 0.46). Plaques associated with focal neurological symptoms had significantly lower mean YM than plaques in asymptomatic patients (62 kPa vs 88 kPa; p = 0.01). Logistic regression and Receiver Operating Characteristic (ROC) analysis showed improvements in sensitivity and specificity when percentage stenosis was combined with the YM (area under ROC = 0.78). CONCLUSIONS: Our study showed SWE is able to quantify carotid plaque elasticity and provide additional information that may be of clinical benefit to help identify the unstable carotid plaque.

An in vitro comparison of embolus differentiation techniques for clinically significant macroemboli: dual-frequency technique versus frequency modulation method.

The ability to distinguish harmful solid cerebral emboli from gas bubbles intra-operatively has potential to direct interventions to reduce the risk of brain injury. In this in vitro study, two embolus discrimination techniques, dual-frequency (DF) and frequency modulation (FM) methods, are simultaneously compared to assess discrimination of potentially harmful large pieces of carotid plaque debris (0.5-1.55 mm) and thrombus-mimicking material (0.5-2 mm) from gas bubbles (0.01-2.5 mm). Detection of plaque and thrombus-mimic using the DF technique yielded disappointing results, with four out of five particles being misclassified (sensitivity: 18%; specificity: 89%). Although the FM method offered improved sensitivity, a higher number of false positives were observed (sensitivity: 72%; specificity: 50%). Optimum differentiation was achieved using the difference between peak embolus/blood ratio and mean embolus/blood ratio (sensitivity: 77%; specificity: 81%). We conclude that existing DF and FM techniques are unable to confidently distinguish large solid emboli from small gas bubbles (<50 µm).

Shear wave elastography assessment of carotid plaque stiffness: in vitro reproducibility study.

This study assessed inter- and intra-observer reproducibility of shear wave elastography (SWE) measurements in vessel phantoms simulating soft and hard carotid plaque under steady and pulsatile flow conditions. Supersonic SWE was used to acquire cine-loop data and quantify Young's modulus in cryogel vessel phantoms. Data were acquired by two observers, each performing three repeat measurements. Mean Young's modulus was quantified within 2-mm regions of interest averaged across five frames and, depending on vessel model and observer, ranged from 28 to 240 kPa. The mean inter-frame coefficient of variation (CV) was 0.13 (range: 0.07-0.18) for observer 1 and 0.14 (range: 0.12-0.16) for observer 2, with mean intra-class correlation coefficients (ICCs) of 0.84 and 0.83, respectively. The mean inter-operator CV was 0.13 (range: 0.08-0.20), with a mean ICC of 0.76 (range: 0.69-0.82). Our findings indicate that SWE can quantify Young's modulus of carotid plaque phantoms with good reproducibility, even in the presence of pulsatile flow.

Quantitative assessment of carotid plaque surface irregularities and correlation to cerebrovascular symptoms.

BACKGROUND: The purpose of this study was to determine whether surface irregularities measured from ultrasound images of carotid artery plaques and quantified using a novel method, correlate with the presence of ipsilateral hemispheric cerebrovascular symptoms. METHODS: A plaque surface irregularity index (SII) was measured in 47 carotid artery plaques (32 subjects, stenosis range 10% -95%, 49% symptomatic) using ultrasound image sequences spanning several cardiac cycles. The differences in the distribution of SII in plaques with ipsilateral hemispheric symptoms versus those without symptoms and the correlation between the SII of plaques and the degrees of stenosis of the corresponding arteries were assessed. Diagnostic performance of plaque SII was evaluated on its own and in combination with the degree of stenosis. RESULTS: The mean SII was significantly greater for plaques with ipsilateral hemispheric symptoms (1.89 radians/mm) than for asymptomatic plaques (1.67 radians/mm, p = 0.03). There was no statistically significant association between the SII and the degree of stenosis (p = 0.30). SII predicted the presence of cerebrovascular symptoms with an accuracy of 66% (sensitivity 65%, specificity 67%) on its own and with an accuracy of 83% (sensitivity 96%, specificity 71%) in combination with the degree of stenosis. CONCLUSIONS: Quantitative assessment of carotid plaque surface irregularities using a novel SII parameter correlates with the presence ipsilateral hemispheric cerebrovascular symptoms and may increase diagnostic performance beyond that provided by the degree of stenosis.

Wall motion in the stenotic carotid artery: association with greyscale plaque characteristics, the degree of stenosis and cerebrovascular symptoms.

BACKGROUND: Systolic dilation of the atherosclerotic carotid artery depends on several factors including arterial compliance and the haemodynamic environment. The purpose of this study was to quantify wall motion in stenotic carotid arteries and investigate any associations with the ultrasound greyscale plaque characteristics, the degree of stenosis, and the presence of cerebrovascular symptoms. METHODS: Variations in the lumen diameters of 61 stenotic carotid arteries (stenosis range 10%-95%) from 47 patients were measured before the proximal shoulder of the atherosclerotic plaque using ultrasound image sequences over several cardiac cycles. Absolute and percentage diameter changes from diastole to systole were calculated and their relationship to the degree of stenosis, greyscale plaque characteristics, and the presence of ipsilateral hemispheric symptoms were studied. RESULTS: The mean absolute diameter change from diastole to systole was 0.45 mm (s.d. 0.17), and the mean percentage diameter change was 6.9% (s.d. 3.1%). Absolute and percentage diameter changes did not have a statistically significant relationship to the degree of stenosis, greyscale plaque characteristics, or the presence of ipsilateral hemispheric symptoms (p > 0.05). Parameters significantly correlated with the presence of symptoms were the degree of stenosis (p = 0.01), plaque greyscale median (p = 0.02) and the plaque surface irregularity index (p = 0.02). CONCLUSIONS: Our study confirmed the degree of stenosis, plaque greyscale median and our surface irregularity index were significant predictors of symptoms, but found no significant correlation between diameter changes of stenosed carotid arteries and the presence of ipsilateral hemispheric symptoms.

Dynamic variations in the ultrasound greyscale median of carotid artery plaques.

BACKGROUND: Several studies have found that the ultrasound greyscale median (GSM) of carotid artery plaques may be useful for predicting the risk of cerebrovascular events. However, measurements of GSM are typically performed on still ultrasound images ignoring any variations that may be observed on a frame-by-frame basis. The aim of this study was to establish the existence and investigate the nature and extent of these variations. METHODS: Employing a novel method that enabled plaque boundaries to be tracked semi-automatically, variations in the plaque GSM and observed cross-sectional area were measured for 27 carotid artery plaques (19 consecutive patients, stenosis range 10%-80%) over image sequences of up to 10 seconds in length acquired with a mean frame rate of 32 frames per second. RESULTS: Our results showed a mean inter-frame coefficient of variation (CV) of 5.2% (s.d. 2.5%) for GSM and 4.2% (s.d. 2.9%) for the plaque area. Thirteen of the 27 plaques (48%) exhibited CV in GSM greater than 5% whereas only six plaques (22%) had CV in plaque area of greater than 5%. There was no significant correlation between the CV of GSM and plaque area. CONCLUSIONS: Inter-frame variations in the plaque GSM such as those found in this study have implications on the reproducibility of GSM measurements and their clinical utility. Studies assessing the GSM of carotid artery plaques should consider these variations.

Sizing gaseous emboli using Doppler embolic signal intensity.

Extension of transcranial Doppler embolus detection to estimation of bubble size has historically been hindered by difficulties in applying scattering theory to the interpretation of clinical data. This article presents a simplified approach to the sizing of air emboli based on analysis of Doppler embolic signal intensity, by using an approximation to the full scattering theory that can be solved to estimate embolus size. Tests using simulated emboli show that our algorithm is theoretically capable of sizing 90% of "emboli" to within 10% of their true radius. In vitro tests show that 69% of emboli can be sized to within 20% of their true value under ideal conditions, which reduces to 30% of emboli if the beam and vessel are severely misaligned. Our results demonstrate that estimation of bubble size during clinical monitoring could be used to distinguish benign microbubbles from potentially harmful macrobubbles during intraoperative clinical monitoring.

Embolus trajectory through a physical replica of the major cerebral arteries.

BACKGROUND AND PURPOSE: The observed distribution of cerebral infarcts varies markedly from expectations based on blood-flow volume or Doppler embolus detection. In this study, we used an in vitro model of the cerebral arteries to test whether embolus microspheres encountering the circle of Willis are carried proportionally to volume flow or express a preferred trajectory related to arterial morphology or embolus size. METHODS: Our model consisted of a patient-specific silicone replica of the cerebral macrocirculation featuring physiologically realistic pulsatile flow of a blood-mimicking fluid at approximately 1000 mL/min and an input pressure of approximately 150/70 mm Hg. Particles of 200, 500, and 1000 microm diameter with equivalent density to thrombus were introduced to the carotid arteries and counted on exiting the model outlets. RESULTS: The middle cerebral arteries (MCAs) of the replica attracted a disproportionate number of emboli compared with the anterior cerebral arteries; 98%+/-3% of 1000 microm and 93%+/-2% of 500 microm emboli entered the MCA compared with 82%+/-5% of the flow. The observed distribution of large emboli was consistent with the ratio of MCA:anterior cerebral artery infarcts, approximately 95% of which occur in territories supplied by the MCA. With decreasing embolus size, the distribution of emboli approaches that of the flow (approximately 89% of 200 microm emboli took the MCA). CONCLUSIONS: Embolus trajectory through the cerebral arteries is dependent on embolus size and strongly favors the MCA for large emboli. The 70:30 ratio of MCA:anterior cerebral artery emboli observed by Doppler ultrasound is consistent with the trajectories of small emboli that tend to be asymptomatic.

Thrombus size and Doppler embolic signal intensity.

BACKGROUND: Migration of thrombus through the cerebral arteries is a common cause of stroke. Thrombus emboli can be detected non-invasively using Doppler ultrasound, but even where the embolus composition is known, there is currently no method for estimating the size of an embolus based on the returned ultrasound signal. Here we report the results of in vitro experiments investigating the relationship between size and embolic signal intensity for fresh thrombus emboli with a view to estimating the sizes of thrombi detected following carotid surgery. METHOD: Thrombi were formed from whole blood using the 'Chandler loop' method under flow conditions similar to those associated with arterial thrombus formation in vivo. A total of 390 Doppler embolic signals were then measured from 37 pieces of thrombus circulated in a pulsatile closed-flow circuit. The dimensions of each of the thrombi were measured before and after circulation using an optical microscope. Relationships between thrombus size and embolic signal properties were then investigated using standard statistical methods with a view to size estimation of thrombi during clinical monitoring. RESULTS: Although embolic signals generally became more intense with increasing thrombus size, strong oscillations due to resonance effects were observed. Pearson tests revealed strong positive correlations between embolus diameter, signal intensity and duration (r > 0.8, p < or = 0.01). CONCLUSIONS: This study provides experimental evidence supporting theoretical predictions relating Doppler embolic signal intensity to thrombus size. In our discussion, we tentatively suggest how this information might be used to size emboli in clinical practice.

Doppler ultrasound detection of side-vessel occlusion: an in vitro study.

BACKGROUND AND PURPOSE: Small-vessel knock is a recently reported Doppler ultrasound finding that has been identified in patients with cerebral ischemia. It has been hypothesized that knock-type signals are linked to the presence of either small-vessel occlusion or wall motion. The aim of this study was to investigate the origins of "knock-type" signals by reproducing occlusion of a peripheral artery model in vitro. METHODS: Synthetic bifurcations were fabricated from glass and latex and placed in a flow-rig mimicking physiological blood-flow conditions. The glass model permitted study of fluid flow in the absence of wall motion, whereas the latex model also produced wall motion effects. Vessels were artificially obstructed to examine Doppler signal characteristics associated with blood flow and wall motion. RESULTS: Complete obstruction of the peripheral branch of the glass model revealed discrete (<100 ms) knock-type signals caused by local fluid flow in the occluded branch. Imaging of the obstructed vessel using color Doppler revealed forward and reflected flow. The walls produced periodic bidirectional knock-type signals, which occurred during systole and were not related to the presence of an obstruction. CONCLUSIONS: In our laboratory model, transcranial Doppler ultrasound was found to be capable of detecting knock signals produced by circulating fluid within an occluded branch. However, because similar signals are also generated by nonpathological wall motion, these results cannot be directly translated to a clinical setting. Clinicians should be careful to avoid casual overinterpretation of transcranial Doppler ultrasound data.

Enhanced detection of thromboemboli with the use of targeted microbubbles.

BACKGROUND AND PURPOSE: Targeted ultrasound contrast agents have recently been developed to adhere selectively to specific pathogenic materials such as plaque or thrombus. Administration of such microbubbles has potential to aid transcranial Doppler ultrasound (TCD) detection of emboli and to act as markers for distinguishing one embolic material from another. The purpose of this study was to investigate whether TCD detection of circulating thrombus emboli would be enhanced by the addition of targeted microbubbles. METHODS: Binding of microbubbles to the surface of the thrombus was confirmed by scanning electron microscopy. Targeted and control bubbles were then introduced to thrombus and tissue-mimicking material circulated under pulsatile-flow conditions in an in vitro flow rig. Embolic signal intensities before and after introduction of the bubbles were measured by TCD. RESULTS: Targeted microbubbles enhanced TCD signal intensities from thrombus emboli by up to 13 dB. The bubbles were capable of binding to moving thrombus when injected into the flow circuit in low concentrations ( approximately 36 bubbles per 100 mL) and were retained on the thrombus under pulsatile-flow conditions. Signal intensities from similarly sized pieces of tissue-mimicking material were not enhanced by injection of targeted bubbles. CONCLUSIONS: Injection of appropriately targeted microbubbles significantly enhances TCD detection of circulating thrombus emboli in vitro.

Noninvasive simultaneous assessment of wall shear rate and wall distension in carotid arteries.

A novel technique has been developed for the noninvasive real-time simultaneous assessment of both blood velocity profile and wall displacements in human arteries. The novel technique is based on the use of two ultrasound beams, one set at optimal angle for wall motion measurements and the other for blood velocity profile measurements. The technique was implemented on a linear array probe divided into two subapertures. A modified commercial ultrasound machine and a custom PC board based on a high-speed digital signal processor was used to process the quadrature demodulated echo signals and display results in realtime. Flow phantom experiments demonstrated the validity of the technique, providing wall shear rate (WSR) estimates within 10% of the theoretical values. The system was also tested in the common carotid arteries of 16 healthy volunteers (age 30 to 53 y). Results of simultaneous diameter distension and WSR measurements were in agreement with published data.

An anthropomorphic tissue-mimicking phantom of the oesophagus for endoscopic ultrasound.

This study details the design and construct of an anthropomorphic phantom of the oesophagus suitable for use with endoscopic ultrasound (EUS) and 3-D volume measurements. The phantom was constructed using agar-based tissue-mimicking material (TMM) of different acoustical properties to simulate various anatomical and pathologic features. The acoustical properties were measured with a scanning acoustical macroscope. An Olympus GF-UM200 echo-endoscope and digital position measurement arm were used to scan the phantom at 7.5 and 12 MHz. Comparative dimensional measurements were performed on the phantom via 2-D and 3-D EUS. TMM attenuation varied between 0.1 and 0.5 dB/cm.MHz. Backscatter power, relative to normal TMM, was from 0 to -12.2 dB, with an average speed of sound of 1537 +/- 1.9 m/s. Measurements of objects within the phantom by 2-D and 3-D EUS had mean errors of 8% and 2.2%, respectively. The construction of the anthropomorphic EUS phantom facilitated EUS training and research and development studies.