The interaction of macro- and microvascular function underlies brachial artery flow-mediated dilation in humans.

Brachial artery flow-mediated dilation (BAFMD) is induced by hyperemic wall shear rate (WSR) following forearm ischemia. In older adults, there appears to be a reduced hyperemic WSR and altered stimulus-response relationship occurring at the brachial artery compared to young adults. However, it is unclear if an altered forearm microvascular response to ischemia influences brachial hyperemic WSR in older adults. We determined the association between brachial hyperemic WSR and forearm skeletal muscle oxygen saturation in young and older adults. Healthy young (n=17, 29±7 yrs) and older (n=32, 65±4 yrs) adults participated in the study. BAFMD by a multi-gate spectral Doppler system and forearm skeletal muscle oxygen saturation by near infrared spectroscopy were concurrently measured. Compared to the young, older adults showed reduced oxygen extraction kinetics [OE: 0.15 (0.12-0.17) vs 0.09 (0.05-0.12) %s-1] and magnitude (SO2deficit: 3810±1420 vs 2723±1240 %s) during ischemia, and oxygen re-saturation kinetics (SO2slope: 2.5±0.7 vs 1.7±0.7 %s-1) upon reperfusion (all p<0.05). When OE in the young and SO2slope in older adults were stratified by their median values, young adults with OE above median had greater hyperemic WSR parameters compared to those with OE below median (p<0.05), but SO2slope in older adults did not show clear differences in hyperemic WSR parameters between those with above/below median. This study demonstrates that, additionally to a reduced microvascular response to ischemia, there may be a possible dissociation of microvascular response to ischemia to brachial hyperemic WSR in older adults, which may result in a further impairment of BAFMD in this cohort.

High-Frame-Rate Volumetric Porcine Renal Vasculature Imaging.

OBJECTIVE: The aim of this study was to assess the feasibility and imaging options of contrast-enhanced volumetric ultrasound kidney vasculature imaging in a porcine model using a prototype sparse spiral array. METHODS: Transcutaneous freehand in vivo imaging of two healthy porcine kidneys was performed according to three protocols with different microbubble concentrations and transmission sequences. Combining high-frame-rate transmission sequences with our previously described spatial coherence beamformer, we determined the ability to produce detailed volumetric images of the vasculature. We also determined power, color and spectral Doppler, as well as super-resolved microvasculature in a volume. The results were compared against a clinical 2-D ultrasound machine. RESULTS: Three-dimensional visualization of the kidney vasculature structure and blood flow was possible with our method. Good structural agreement was found between the visualized vasculature structure and the 2-D reference. Microvasculature patterns in the kidney cortex were visible with super-resolution processing. Blood flow velocity estimations were within a physiological range and pattern, also in agreement with the 2-D reference results. CONCLUSION: Volumetric imaging of the kidney vasculature was possible using a prototype sparse spiral array. Reliable structural and temporal information could be extracted from these imaging results.

3-D Coherent Multi-Transducer Ultrasound Imaging with Sparse Spiral Arrays.

Coherent multi-transducer ultrasound (CoMTUS) creates an extended effective aperture through the coherent combination of multiple arrays, which results in images with enhanced resolution, extended field-of-view, and higher sensitivity. The subwavelength localization accuracy of the multiple transducers required to coherently beamform the data is achieved by using the echoes backscattered from targeted points. In this study, CoMTUS is implemented and demonstrated for the first time in 3-D imaging using a pair of 256-element 2-D sparse spiral arrays, which keep the channel count low and limit the amount of data to be processed. The imaging performance of the method was investigated using both simulations and phantom tests. The feasibility of free-hand operation is also experimentally demonstrated. Results show that, in comparison to a single dense array system using the same total number of active elements, the proposed CoMTUS system improves spatial resolution (up to 10 times) in the direction where both arrays are aligned, contrast-to-noise-ratio (CNR, up to 46%), and generalized CNR (up to 15%). Overall, CoMTUS shows a narrower main lobe and higher contrast-to-noise ratio, which results in an increased dynamic range and better target detectability.

Lung Ultrasound Artifacts Interpreted as Pathology Footprints.

BACKGROUND: The original observation that lung ultrasound provides information regarding the physical state of the organ, rather than the anatomical details related to the disease, has reinforced the idea that the observed acoustic signs represent artifacts. However, the definition of artifact does not appear adequate since pulmonary ultrasound signs have shown valuable diagnostic accuracy, which has been usefully exploited by physicians in numerous pathologies. METHOD: A specific method has been used over the years to analyze lung ultrasound data and to convert artefactual information into anatomical information. RESULTS: A physical explanation of the genesis of the acoustic signs is provided, and the relationship between their visual characteristics and the surface histopathology of the lung is illustrated. Two important sources of potential signal alteration are also highlighted. CONCLUSIONS: The acoustic signs are generated by acoustic traps that progressively release previously trapped energy. Consequently, the acoustic signs highlight the presence of acoustic traps and quantitatively describe their distribution on the lung surface; they are not artifacts, but pathology footprints and anatomical information. Moreover, the impact of the dynamic focusing algorithms and the impact of different probes on the visual aspect of the acoustic signs should not be neglected.

Sparse 2-D PZT-on-PCB Arrays With Density Tapering.

Two-dimensional (2-D) arrays offer volumetric imaging capabilities without the need for probe translation or rotation. A sparse array with elements seeded in a tapering spiral pattern enables one-to-one connection to an ultrasound machine, thus allowing flexible transmission and reception strategies. To test the concept of sparse spiral array imaging, we have designed, realized, and characterized two prototype probes designed at 2.5-MHz low-frequency (LF) and 5-MHz high-frequency (HF) center frequencies. Both probes share the same electronic design, based on piezoelectric ceramics and rapid prototyping with printed circuit board substrates to wire the elements to external connectors. Different center frequencies were achieved by adjusting the piezoelectric layer thickness. The LF and HF prototype probes had 88% and 95% of working elements, producing peak pressures of 21 and 96 kPa/V when focused at 5 and 3 cm, respectively. The one-way -3-dB bandwidths were 26% and 32%. These results, together with experimental tests on tissue-mimicking phantoms, show that the probes are viable for volumetric imaging.

Unfocused Field Analysis of a Density-Tapered Spiral Array for High-Volume-Rate 3-D Ultrasound Imaging.

Spiral array transducers with a sparse 2-D aperture have demonstrated their potential in realizing 3-D ultrasound imaging with reduced data rates. Nevertheless, their feasibility in high-volume-rate imaging based on unfocused transmissions has yet to be established. From a metrology standpoint, it is essential to characterize the acoustic field of unfocused transmissions from spiral arrays not only to assess their safety but also to identify the root cause of imaging irregularities due to the array's sparse aperture. Here, we present a field profile analysis of unfocused transmissions from a density-tapered spiral array transducer (256 hexagonal elements, 220- [Formula: see text] element diameter, and 1-cm aperture diameter) through both simulations and hydrophone measurements. We investigated plane- and diverging-wave transmissions (five-cycle, 7.5-MHz pulses) from 0° to 10° steering for their beam intensity characteristics and wavefront arrival time profiles. Unfocused firings were also tested for B-mode imaging performance (ten compounded angles, -5° to 5° span). The array was found to produce unfocused transmissions with a peak negative pressure of 93.9 kPa at 2 cm depth. All transmissions steered up to 5° were free of secondary lobes within 12 dB of the main beam peak intensity. All wavefront arrival time profiles were found to closely match the expected profiles with maximum root-mean-squared errors of [Formula: see text] for plane wave (PW) and [Formula: see text] for diverging wave. The B-mode images showed good spatial resolution with a penetration depth of 22 mm in PW imaging. Overall, these results demonstrate that the density-tapered spiral array can facilitate unfocused transmissions below regulatory limits (mechanical index: 0.034; spatial-peak, pulse-average intensity: 0.298 W/cm2) and with suppressed secondary lobes while maintaining smooth wavefronts.

High-Frame-Rate Speckle Tracking for Echocardiographic Stress Testing.

Stress echocardiography helps to diagnose cardiac diseases that cannot easily be detected or do not even manifest at rest. In clinical practice, assessment of the stress test is usually performed visually and, therefore, in a qualitative and subjective way. Although speckle tracking echocardiography (STE) has been proposed for the quantification of function during stress, its time resolution is inadequate at high heart rates. Recently, high-frame-rate (HFR) imaging approaches have been proposed together with dedicated STE algorithms capable of handling small interframe displacements. The aim of this study was to determine if HFR STE is effective in assessing strain and strain rate parameters during echocardiographic stress testing. Specifically, stress echocardiography, at four different workload intensities, was performed in 25 healthy volunteers. At each stress level, HFR images from the apical four-chamber view were recorded using the ULA-OP 256 experimental scanner. Then, the myocardium was tracked with HFR STE, and strain and strain rate biomarkers were extracted to further analyze systolic and diastolic (early and late) peaks, as well as a short-lived isovolumic relaxation peak during stress testing. The global systolic strain response was monophasic, revealing a significant (p < 0.001) increase at low stress but then reaching a plateau. In contrast, all strain rate indices linearly increased (p < 0.001) with increasing stress level. These findings are in line with those reported using tissue Doppler imaging and, thus, indicate that HFR STE can be a useful tool in assessing cardiac function during stress echocardiography.

Design, Implementation, and Medical Applications of 2-D Ultrasound Sparse Arrays.

An ultrasound sparse array consists of a sparse distribution of elements over a 2-D aperture. Such an array is typically characterized by a limited number of elements, which in most cases is compatible with the channel number of the available scanners. Sparse arrays represent an attractive alternative to full 2-D arrays that may require the control of thousands of elements through expensive application-specific integrated circuits (ASICs). However, their massive use is hindered by two main drawbacks: the possible beam profile deterioration, which may worsen the image contrast, and the limited signal-to-noise ratio (SNR), which may result too low for some applications. This article reviews the work done for three decades on 2-D ultrasound sparse arrays for medical applications. First, random, optimized, and deterministic design methods are reviewed together with their main influencing factors. Then, experimental 2-D sparse array implementations based on piezoelectric and capacitive micromachined ultrasonic transducer (CMUT) technologies are presented. Sample applications to 3-D (Doppler) imaging, super-resolution imaging, photo-acoustic imaging, and therapy are reported. The final sections discuss the main shortcomings associated with the use of sparse arrays, the related countermeasures, and the next steps envisaged in the development of innovative arrays.

Spatial Coherence Beamforming With Multi-Line Transmission to Enhance the Contrast of Coherent Structures in Ultrasound Images Degraded by Acoustic Clutter.

This work demonstrates that the combination of multi-line transmission (MLT) and short-lag spatial coherence (SLSC) imaging improves the contrast of highly coherent structures within soft tissues when compared to both traditional SLSC imaging and conventional delay and sum (DAS) beamforming. Experimental tests with small (i.e., [Formula: see text]-3 mm) targets embedded in homogeneous and heterogeneous backgrounds were conducted. DAS or SLSC images were reconstructed when implementing MLT with varying numbers of simultaneously transmitted beams. In images degraded by acoustic clutter, MLT SLSC achieved up to 34.1 dB better target contrast and up to 16 times higher frame rates when compared to the more conventional single-line transmission SLSC images, with lateral resolution improvements as large as 38.2%. MLT SLSC thus represents a promising technique for clinical applications in which ultrasound visualization of highly coherent targets is required (e.g., breast microcalcifications, kidney stones, and percutaneous biopsy needle tracking) and would otherwise be challenging due to the strong presence of acoustic clutter.

High Frame Rate Volumetric Imaging of Microbubbles Using a Sparse Array and Spatial Coherence Beamforming.

Volumetric ultrasound imaging of blood flow with microbubbles enables a more complete visualization of the microvasculature. Sparse arrays are ideal candidates to perform volumetric imaging at reduced manufacturing complexity and cable count. However, due to the small number of transducer elements, sparse arrays often come with high clutter levels, especially when wide beams are transmitted to increase the frame rate. In this study, we demonstrate with a prototype sparse array probe and a diverging wave transmission strategy, that a uniform transmission field can be achieved. With the implementation of a spatial coherence beamformer, the background clutter signal can be effectively suppressed, leading to a signal to background ratio improvement of 25 dB. With this approach, we demonstrate the volumetric visualization of single microbubbles in a tissue-mimicking phantom as well as vasculature mapping in a live chicken embryo chorioallantoic membrane.

Architecture for an Ultrasound Advanced Open Platform With an Arbitrary Number of Independent Channels.

Ultrasound open platforms are programmable and flexible tools for the development and test of novel methods. In most cases, they embed the electronics for the independent control of (maximum) 256 probe elements. However, a higher number of channels is needed for the control of 2-D array probes. This paper presents a system architecture that, through the hardware and software synchronization of multiple ULA-OP 256 scanners, may implement advanced open platforms with an arbitrary number of channels. The proposed solution needs a single personal computer, maintains real-time features, and preserves portability. A prototype demonstrator, composed of two ULA-OP 256 scanners connected to 512 elements of a matrix array, was implemented and tested according to different channel configurations. Experiments performed under MATLAB control confirmed that by doubling the number of elements (from 256 to 512) the signal-to-noise and contrast ratios improve by 9 dB and 3 dB, respectively. Furthermore, as a full 512-channel scanner, the demonstrator can produce real-time B-mode images at 18 Hz, high enough for probe positioning during acquisitions. Also, the demonstrator permitted the implementation of a new high frame rate, bi-plane, triplex modality. All probe elements are excited to simultaneously produce two planar, perpendicular diverging waves. Each scanner independently processes the echoes received by the 256 connected elements to beamform 1300 frames per second. For each insonified plane, good quality morphological (B-mode), qualitative (color flow-), and quantitative (spectral-) Doppler images are finally shown in real-time by a dedicated interface.

On the Depth-Dependent Accuracy of Plane-Wave-Based Vector Velocity Measurements With Linear Arrays.

High-frame-rate vector Doppler methods are used to measure blood velocities over large 2-D regions, but their accuracy is often estimated over a short range of depths. This article thoroughly examines the dependence of velocity measurement accuracy on the target position. Simulations were carried out on flat and parabolic flow profiles, for different Doppler angles, and considering a 2-D vector flow imaging (2-D VFI) method based on plane wave transmission and speckle tracking. The results were also compared with those obtained by the reference spectral Doppler (SD) method. Although, as expected, the bias and standard deviation generally tend to worsen at increasing depths, the measurements also show the following. First, the errors are much lower for the flat profile (from ≈ -4 ± 3% at 20 mm to ≈ -17 ± 4% at 100 mm) than for the parabolic profile (from ≈ -4 ± 3% to ≈ -38 ±%). Second, only part of the relative estimation error is related to the inherent low resolution of the 2-D VFI method. For example, even for SD, the error bias increases (on average) from -0.7% (20 mm) to -17% (60 mm) up to -26% (100 mm). Third, conversely, the beam divergence associated with the linear array acoustic lens was found to have a great impact on the velocity measurements. By simply removing such lens, the average bias for 2-D VFI at 60 and 100 mm dropped down to -9.4% and -19.4%, respectively. In conclusion, the results indicate that the transmission beam broadening on the elevation plane, which is not limited by reception dynamic focusing, is the main cause of velocity underestimation in the presence of high spatial gradients.

Real-Time 3-D Spectral Doppler Analysis With a Sparse Spiral Array.

2-D sparse arrays may push the development of low-cost 3-D systems, not needing to control thousands of elements by expensive application-specific integrated circuits (ASICs). However, there is still some concern about their suitability in applications, such as Doppler investigation, which inherently involve poor signal-to-noise ratios (SNRs). In this article, a novel real-time 3-D pulsed-wave (PW) Doppler system, based on a 256-element 2-D spiral array, is presented. Coded transmission (TX) and matched filtering were implemented to improve the system SNR. Standard sonograms as well as multigate spectral Doppler (MSD) profiles, along lines that can be arbitrarily located in different planes, are presented. The performance of the system was assessed quantitatively on experimental data obtained from a straight tube flow phantom. An SNR increase of 11.4 dB was measured by transmitting linear chirps instead of standard sinusoidal bursts. For a qualitative assessment of the system performance in more realistic conditions, an anthropomorphic phantom of the carotid arteries was used. Finally, real-time B-mode and MSD images were obtained from healthy volunteers.

In Vivo Comparison of Multiline Transmission and Diverging Wave Imaging for High-Frame-Rate Speckle-Tracking Echocardiography.

High-frame-rate (HFR) speckle-tracking echocardiography (STE) assesses myocardial function by quantifying motion and deformation at high temporal resolution. Among the proposed HFR techniques, multiline transmission (MLT) and diverging wave (DW) imaging have been used in this context both being characterized by specific advantages and disadvantages. Therefore, in this article, we directly contrast both approaches in an in vivo setting while operating at the same frame rate (FR). First, images were recorded at baseline (resting condition) from healthy volunteers and patients. Next, additional acquisitions during stress echocardiography were performed on volunteers. Each scan was contoured and processed by a previously proposed 2-D HFR STE algorithm based on cross correlation. Then, strain curves and their end-systolic (ES) values were extracted for all myocardial segments for further statistical analysis. The baseline acquisitions did not reveal differences in estimated strain between the acquisition modes ( ); myocardial segments ( ); or an interaction between imaging mode and depth ( ). Similarly, during stress testing, no difference ( p = 0.7 ) was observed for the two scan sequences, stress levels or an interaction sequence-stress level ( p = 0.94 ). Overall, our findings show that MLT and DW compoundings give comparable HFR STE strain values and that the choice for using one method or the other may thus rather be based on other factors, for example, system requirements or computational cost.

A Novel 2-D Speckle Tracking Method for High-Frame-Rate Echocardiography.

Speckle tracking echocardiography (STE) is a clinical tool to noninvasively assess regional myocardial function through the quantification of regional motion and deformation. Even if the time resolution of STE can be improved by high-frame-rate (HFR) imaging, dedicated HFR STE algorithms have to be developed to detect very small interframe motions. Therefore, in this article, we propose a novel 2-D STE method, purposely developed for HFR echocardiography. The 2-D motion estimator consists of a two-step algorithm based on the 1-D cross correlations to separately estimate the axial and lateral displacements. The method was first optimized and validated on simulated data giving an accuracy of ~3.3% and ~10.5% for the axial and lateral estimates, respectively. Then, it was preliminarily tested in vivo on ten healthy volunteers showing its clinical applicability and feasibility. Moreover, the extracted clinical markers were in the same range as those reported in the literature. Also, the estimated peak global longitudinal strain was compared with that measured with a clinical scanner showing good correlation and negligible differences (-20.94% versus -20.31%, p -value = 0.44). In conclusion, a novel algorithm for STE was developed: the radio frequency (RF) signals were preferred for the axial motion estimation, while envelope data were preferred for the lateral motion. Furthermore, using 2-D kernels, even for 1-D cross correlation, makes the method less sensitive to noise.

Impact of Aperture, Depth, and Acoustic Clutter on the Performance of Coherent Multi-Transducer Ultrasound Imaging.

Transducers with a larger aperture size are desirable in ultrasound imaging to improve resolution and image quality. A coherent multi-transducer ultrasound imaging system (CoMTUS) enables an extended effective aperture through the coherent combination of multiple transducers. In this study, the discontinuous extended aperture created by CoMTUS and its performance for deep imaging and through layered media are investigated by both simulations and experiments. Typical image quality metrics-resolution, contrast and contrast-to-noise ratio-are evaluated and compared with a standard single probe imaging system. Results suggest that the image performance of CoMTUS depends on the relative spatial location of the arrays. The resulting effective aperture significantly improves resolution, while the separation between the arrays may degrade contrast. For a limited gap in the effective aperture (less than a few centimetres), CoMTUS provides benefits to image quality compared to the standard single probe imaging system. Overall, CoMTUS shows higher sensitivity and reduced loss of resolution with imaging depth. In general, CoMTUS imaging performance was unaffected when imaging through a layered medium with different speed of sound values and resolution improved up to 80% at large imaging depths.

3-D Super-Resolution Ultrasound Imaging With a 2-D Sparse Array.

High-frame-rate 3-D ultrasound imaging technology combined with super-resolution processing method can visualize 3-D microvascular structures by overcoming the diffraction-limited resolution in every spatial direction. However, 3-D super-resolution ultrasound imaging using a full 2-D array requires a system with a large number of independent channels, the design of which might be impractical due to the high cost, complexity, and volume of data produced. In this study, a 2-D sparse array was designed and fabricated with 512 elements chosen from a density-tapered 2-D spiral layout. High-frame-rate volumetric imaging was performed using two synchronized ULA-OP 256 research scanners. Volumetric images were constructed by coherently compounding nine-angle plane waves acquired at a pulse repetition frequency of 4500 Hz. Localization-based 3-D super-resolution images of two touching subwavelength tubes were generated from 6000 volumes acquired in 12 s. Finally, this work demonstrates the feasibility of 3-D super-resolution imaging and super-resolved velocity mapping using a customized 2-D sparse array transducer.

Spectral Doppler Measurements With 2-D Sparse Arrays.

The 2-D sparse arrays, in which a few hundreds of elements are distributed on the probe surface according to an optimization procedure, represent an alternative to full 2-D arrays, including thousands of elements usually organized in a grid. Sparse arrays have already been used in B-mode imaging tests, but their application to Doppler investigations has not been reported yet. Since the sparsity of the elements influences the acoustic field, a corresponding influence on the mean frequency (Fm), bandwidth (BW), and signal-to-noise ratio (SNR) of the Doppler spectra is expected. This article aims to assess, by simulations and experiments, to what extent the use of a sparse rather than a full gridded 2-D array has an impact on spectral Doppler measurements. Parabolic flows were investigated by a 3 MHz, 1024-element gridded array and by a sparse array; the latter was obtained by properly selecting a subgroup of 256 elements from the full array. Simulations show that the mean Doppler frequency does not change between the sparse and the full array while there are significant differences on the BW (average reduction of 17.2% for the sparse array, due to different apertures of the two probes) and on the signal power (Ps) (22 dB, due to the different number of active elements). These results are confirmed by flow phantom experiments, which also highlight that the most critical difference between sparse and full gridded array in Doppler measurements is in terms of SNR (-16.8 dB).

High-Frame-Rate Color Doppler Echocardiography: A Quantitative Comparison of Different Approaches.

Ultrasound color Doppler imaging (CDI) provides a map of the axial blood flow velocities in a 2-D/3-D region of interest. While CDI is clinically effective for a qualitative analysis of abnormal blood flows, e.g., for valvular disease in cardiology, it is in limited use for quantitative measures, mainly hampered by low frame rate and measurement bias. These limitations can be reduced by different approaches toward high-frame-rate (HFR) imaging at the expense of reduced image quality and penetration depth. The aim of this study was to compare the impact of different HFR sequences on CDI quantitatively. Different cardiac scan sequences, including diverging waves and multiline transmission, were designed, implemented on a research system, and compared in terms of patient safety parameters, image quality, and penetration depth. Furthermore, in vivo images were acquired and compared for healthy volunteers. Results showed that the HFR techniques spread artifacts on larger areas than the standard single-line scans (> +50%). In addition, due to patient safety limitations, they reduce the penetration depth up to -5 cm. On the other hand, the HFR techniques provide comparable velocity estimates (relative difference <6%) and enhance the time resolution of the color Doppler images, achieving frame rates up to 625 Hz in continuous acquisition.

A Comparison of Coherence-Based Beamforming Techniques in High-Frame-Rate Ultrasound Imaging With Multi-Line Transmission.

One of the current challenges in ultrasound imaging is achieving higher frame rates, particularly in cardiac applications, where tracking the heart motion and other rapid events can provide potential valuable diagnostic information. The main drawback of ultrasound high-frame-rate strategies is that usually they partly sacrifice image quality in order to speed up the acquisition time. In particular, multi-line transmission (MLT), which consists in transmitting multiple ultrasound beams simultaneously in different directions, has been proven able to improve frame rates in echocardiography, unfortunately generating artifacts due to inter-beam crosstalk interferences. This work investigates the possibility to effectively suppress crosstalk artifacts in MLT while improving image quality by applying beamforming techniques based on backscattered signals spatial coherence. Several coherence-based algorithms (i.e., short-lag filtered-delay multiply and sum beamforming, coherence and generalized coherence factor, phase and sign coherence, and nonlinear beamforming with p th root compression) are implemented and compared, and their performance trends are evaluated when varying their design parameters. Indeed, experimental results of phantom and in vivo cardiac acquisitions demonstrate that this class of algorithms can provide significant benefits compared with delay and sum, well-suppressing artifacts (up to 48.5-dB lower crosstalk), and increasing image resolution (by up to 46.3%) and contrast (by up to 30 dB in terms of contrast ratio and 12.6% for generalized contrast-to-noise ratio) at the same time.