Super Resolution Ultrasound Imaging Using the Erythrocytes: II: Velocity Images.

Super resolution ultrasound imaging using the erythrocytes (SURE) has recently been introduced. The method uses erythrocytes as targets instead of fragile microbubbles (MBs). The abundance of erythrocyte scatterers makes it possible to acquire SURE data in just a few seconds compared to several minutes in ultrasound localization microscopy (ULM) using MBs. A high number of scatterers can reduce the acquisition time, however, the tracking of uncorrelated and high-density scatterers is quite challenging. This paper hypothesizes that it is possible to detect and track erythrocytes as targets to obtain vascular flow images. A SURE tracking pipeline is used with modules for beamforming, recursive synthetic aperture imaging, motion estimation, echo canceling, peak detection, and recursive nearest neighbor tracker. The SURE tracking pipeline is capable of distinguishing the flow direction and separating tubes of a simulated Field II phantom with 125 to 25 µm wall-to-wall tube distances, as well as a 3D-printed hydrogel micro-flow phantom with 100 to 60 µm wall-to-wall channel distances. The comparison of an in-vivo SURE scan of a Sprague-Dawley rat kidney with ULM and micro-CT scans with voxel sizes of 26.5µm and 5µm demonstrated consistent findings. A microvascular structure composed of 16 vessels exhibited similarities across all imaging modalities. The flow direction and velocity profiles in the SURE scan were found to be concordant with those from ULM.

Super Resolution Ultrasound Imaging using the Erythrocytes: I: Density Images.

A new approach for vascular super resolution imaging using the erythrocytes as targets (SURE imaging) is described and investigated. SURE imaging does not require fragile contrast agent bubbles, making it possible to use the maximum allowable mechanical index for ultrasound scanning for an increased penetration depth. A synthetic aperture ultrasound sequence was employed with 12 virtual sources using a 10 MHz GE L8-18i-D linear array hockey stick probe. The axial resolution was 1.20λ,(185.0µm) and the lateral resolution was 1.50λ,(231.3µm). Field IIpro simulations were conducted on 12.5 µm radius vessel pairs with varying separations. A vessel pair with a separation of 70 µm could be resolved, indicating a SURE image resolution below half a wavelength. A Verasonics research scanner was used for the in vivo experiments to scan the kidneys of Sprague-Dawley rats for up to 46 s to visualize their microvasculature by processing from 0.1 up to 45 s of data for SURE imaging, and for 46.8 s for super resolution (SR) imaging with a SonoVue contrast agent. Afterward, the renal vasculature was filled with the ex vivo micro-CT contrast agent Microfil, excised, and scanned in a micro-CT scanner at both a 22.6 µm voxel size for 11 hours, and for 20 hours in a 5 µm voxel size for validating the SURE images. Comparing the SURE and micro-CT images revealed that vessels with a diameter of 28 µm, five times smaller than the ultrasound wavelength, could be detected, and the dense grid of microvessels in the full kidney was shown for scan times between 1 to 10 s. The vessel structure in the cortex was also similar for the SURE and SR images. Fourier ring correlation indicated a resolution capability of 29 µm. SURE images are acquired in seconds rather than minutes without any patient preparation or contrast injection, making the method translatable to clinical use.

Diverging Polymer Acoustic Lens Design for High-Resolution Row-Column Array Ultrasound Transducers.

Spherical diverging acoustic lenses mounted on flat 2-D row-column-addressed (RCA) ultrasound transducers have shown the potential to extend the field of view (FOV) from a rectilinear to a curvilinear volume region and, thereby, enable 3-D imaging of large organs. Such lenses are usually designed for small aperture low-frequency transducers, which have limited resolution. Moreover, they are made of off-the-shelf pieces of materials, which leaves no room for optimization. We hypothesize that acoustic lenses can be designed to fit high-resolution transducers, and they can be fabricated in a fast, cost-effective, and flexible manner using a combination of 3-D printing and casting or computer numerical control (CNC) machining techniques. These lenses should increase the FOV of the array while preserving the image quality. In this work, such lenses are made in concave, convex, and compound spherical shapes and from thermoplastics and thermosetting polymers. Polymethylpentene (TPX), polystyrene (PS), polypropylene (PP), polymethyl methacrylate (PMMA), polydimethylsiloxane (PDMS), and room-temperature-vulcanizing (RTV) silicone diverging lenses have been fabricated and mounted on a 128 + 128 6-MHz RCA transducer. The performances of the lenses have been assessed and compared in terms of FOV, signal-to-noise ratio (SNR), bandwidth, and potential artifacts. The largest FOV (24.0.) is obtained with a 42.64-mm radius PMMA-RTV compound lens, which maintains a decent fractional bandwidth (53%) and SNR at 6 MHz (.9.1-dB amplitude drop compared with the unlensed transducer). The simple PMMA TPX, PS, PP, PDMS, and RTV lenses provide an FOV of 12.2°, 6.3°, 8.1°, 11.7°, 0.6°, and 10.4°; a fractional bandwidth of 97%, 46%, 103%, 46%, 97%, 53%, and 49%; and an amplitude drop of -5.2, -4.4, -2.8, -15.4, -6.0, and -1.8 dB, respectively. This work demonstrates that thermoplastics are suitable materials for fabricating low-attenuation convex diverging lenses for large-aperture, high-frequency 2-D transducers. This is highly desired to achieve high-resolution volumetric imaging of large organs.

Universal Synthetic Aperture Sequence for Anatomic, Functional, and Super Resolution Imaging.

Synthetic aperture (SA) can be used for both anatomic and functional imaging, where tissue motion and blood velocity are revealed. Often, sequences optimized for anatomic B-mode imaging are different from functional sequences, as the best distribution and number of emissions are different. B-mode sequences demand many emissions for a high contrast, whereas flow sequences demand short sequences for high correlations yielding accurate velocity estimates. This article hypothesizes that a single, universal sequence can be developed for linear array SA imaging. This sequence yields high-quality linear and nonlinear B-mode images as well as accurate motion and flow estimates for high and low blood velocities and super-resolution images. Interleaved sequences with positive and negative pulse emissions for the same spherical virtual source were used to enable flow estimation for high velocities and make continuous long acquisitions for low-velocity estimation. An optimized pulse inversion (PI) sequence with 2 ×12 virtual sources was implemented for four different linear array probes connected to either a Verasonics Vantage 256 scanner or the SARUS experimental scanner. The virtual sources were evenly distributed over the whole aperture and permuted in emission order for making flow estimation possible using 4, 8, or 12 virtual sources. The frame rate was 208 Hz for fully independent images for a pulse repetition frequency of 5 kHz, and recursive imaging yielded 5000 images per second. Data were acquired from a phantom mimicking the carotid artery with pulsating flow and the kidney of a Sprague-Dawley rat. Examples include anatomic high contrast B-mode, non-linear B-mode, tissue motion, power Doppler, color flow mapping (CFM), vector velocity imaging, and super-resolution imaging (SRI) derived from the same dataset and demonstrate that all imaging modes can be shown retrospectively and quantitative data derived from it.

Contrast-enhanced ultrasound imaging using capacitive micromachined ultrasonic transducers.

Capacitive micromachined ultrasonic transducers (CMUTs) have a nonlinear relationship between the applied voltage and the emitted signal, which is detrimental to conventional contrast enhanced ultrasound (CEUS) techniques. Instead, a three-pulse amplitude modulation (AM) sequence has been proposed, which is not adversely affected by the nonlinearly emitted harmonics. In this paper, this is shown theoretically, and the performance of the sequence is verified using a 4.8 MHz linear capacitive micromachined ultrasonic transducer (CMUT) array, and a comparable lead zirconate titanate (PZT) array, across 6-60 V applied alternating current (AC) voltage. CEUS images of the contrast agent SonoVue flowing through a 3D printed hydrogel phantom showed an average enhancement in contrast-to-tissue ratio (CTR) between B-mode and CEUS images of 49.9 and 37.4 dB for the PZT array and CMUT, respectively. Furthermore, hydrophone recordings of the emitted signals showed that the nonlinear emissions from the CMUT did not significantly degrade the cancellation in the compounded AM signal, leaving an average of 2% of the emitted power between 26 and 60 V of AC. Thus, it is demonstrated that CMUTs are capable of CEUS imaging independent of the applied excitation voltage when using a three-pulse AM sequence.

Fast 3-D Velocity Estimation in 4-D Using a 62 + 62 Row-Column Addressed Array.

This article presents an imaging scheme capable of estimating the full 3-D velocity vector field in a volume using row-column addressed arrays (RCAs) at a high volume rate. A 62 + 62 RCA array is employed with an interleaved synthetic aperture sequence. It contains repeated emissions with rows and columns interleaved with B-mode emissions. The sequence contains 80 emissions in total and can provide continuous volumetric data at a volume rate above 125 Hz. A transverse oscillation cross correlation estimator determines all three velocity components. The approach is investigated using Field II simulations and measurements using a specially built 3-MHz 62 + 62 RCA array connected to the SARUS experimental scanner. Both the B-mode and flow sequences have a penetration depth of 14 cm when measured on a tissue-mimicking phantom (0.5-dB/[ [Formula: see text]] attenuation). Simulations of a parabolic flow in a 12-mm-diameter vessel at a depth of 30 mm, beam-to-flow angle of 90°, and xy-rotation of 45° gave a standard deviation (SD) of (3.3, 3.4, 0.4)% and bias of (-3.3, -3.9, -0.1)%, for ( vx , vy , and vz ). Decreasing the beam-to-flow angle to 60° gave an SD of (8.9, 9.1, 0.8)% and bias of (-7.6, -9.5, -7.2)%, showing a slight increase. Measurements were carried out using a similar setup, and pulsing at 2 kHz yielded comparable results at 90° with an SD of (5.8, 5.5, 1.1)% and bias of (1.4, -6.4, 2.4)%. At 60°, the SD was (5.2, 4.7 1.2)% and bias (-4.6, 6.9, -7.4)%. Results from measurements across all tested settings showed a maximum SD of 6.8% and a maximum bias of 15.8% for a peak velocity of 10 cm/s. A tissue-mimicking phantom with a straight vessel was used to introduce clutter, tissue motion, and pulsating flow. The pulsating velocity magnitude was estimated across ten pulse periods and yielded an SD of 10.9%. The method was capable of estimating transverse flow components precisely but underestimated the flow with small beam-to-flow angles. The sequence provided continuous data in both time and space throughout the volume, allowing for retrospective analysis of the flow. Moreover, B-mode planes can be selected retrospectively anywhere in the volume. This shows that tensor velocity imaging (full 3-D volumetric vector flow imaging) can be estimated in 4-D ( x, y, z, and t ) using only 62 channels in receive, making 4-D volumetric imaging implementable on current scanner hardware.

Three-Dimensional Super-Resolution Imaging Using a Row-Column Array.

A 3-D super-resolution (SR) pipeline based on data from a row-column (RC) array is presented. The 3-MHz RC array contains 62 rows and 62 columns with a half wavelength pitch. A synthetic aperture (SA) pulse inversion sequence with 32 positive and 32 negative row emissions is used for acquiring volumetric data using the SARUS research ultrasound scanner. Data received on the 62 columns are beamformed on a GPU for a maximum volume rate of 156 Hz when the pulse repetition frequency is 10 kHz. Simulated and 3-D printed point and flow microphantoms are used for investigating the approach. The flow microphantom contains a 100- [Formula: see text] radius tube injected with the contrast agent SonoVue. The 3-D processing pipeline uses the volumetric envelope data to find the bubble's positions from their interpolated maximum signal and yields a high resolution in all three coordinates. For the point microphantom, the standard deviation on the position is (20.7, 19.8, 9.1) [Formula: see text]. The precision estimated for the flow phantom is below [Formula: see text] in all three coordinates, making it possible to locate structures on the order of a capillary in all three dimensions. The RC imaging sequence's point spread function has a size of 0.58 × 1.05 × 0.31 mm3 ( 1.17λ×2.12λ×0.63λ ), so the possible volume resolution is 28900 times smaller than for SA RC B-mode imaging.

CMUT Electrode Resistance Design: Modelling and Experimental Verification by a Row-Column Array.

This paper addresses the importance of having control over the resistivity of the electrodes for capacitive micromachined ultrasonic transducers (CMUT) devices. The electrode resistivity can vary depending on the fabrication technology used, and resistivity control becomes especially important in the cases where metal electrodes can not be used. This raises the question: When is the resistivity of an electrode sufficiently low? To answer this question we have developed a simple design criterion. The criterion describes the attenuation of AC signals along a CMUT element. It is shown that the non-dimensional product between angular excitation frequency, resistance, and capacitance ωRC of an element has to be smaller than 0.35 to ensure an AC potential drop along the element of less than 1%. The optimal magnitude and directionality of the transmit pressure will be achieved if CMUT elements are designed according to the developed criteria. Hence, the model can be used to estimate device parameters that will ensure the CMUT is suitable for generating ultrasound images. An example is given where the model is used to predict the required electrode thickness for structured electrodes made of Gold, Aluminium, and Indium-Tin-Oxide, respectively. To verify the model, two Row-Column addressed (RCA) CMUT transducers were used to illustrate the effect of high and low electrode resistivity. One transducer had a sufficient electrode resistivity, and the other had an insufficient electrode resistivity. The RCA CMUT transducers were fabricated using fusion bonding, where the top electrode is made of aluminium and the bottom electrode is made of doped silicon. The resistivity of the aluminium top electrode is 2×10-6 Ωcm for both transducers, whereas the resistivity for the bottom electrode is 0.1 Ωcm for the first transducer and 0.005 Ωcm for the second transducer. The transducer with low resistivity emits pressure uniformly along both the rows and columns, whereas the transmit pressure field from the other transducer has a uniformly distributed pressure field along the rows, but a decreasing pressure field along the columns due to the high resistivity in the bottom electrode. The pressure drop, along the columns is frequency dependent and has been observed to be 63%, 74%, and 82% for the excitation frequencies 2 MHz, 4.5 MHz, and 7 MHz, respectively.

Accuracy and Precision of a Plane Wave Vector Flow Imaging Method in the Healthy Carotid Artery.

The objective of the study described here was to investigate the accuracy and precision of a plane wave 2-D vector flow imaging (VFI) method in laminar and complex blood flow conditions in the healthy carotid artery. The approach was to study (i) the accuracy for complex flow by comparing the velocity field from a computational fluid dynamics (CFD) simulation to VFI estimates obtained from the scan of an anthropomorphic flow phantom and from an in vivo scan; (ii) the accuracy for laminar unidirectional flow in vivo by comparing peak systolic velocities from VFI with magnetic resonance angiography (MRA); (iii) the precision of VFI estimation in vivo at several evaluation points in the vessels. The carotid artery at the bifurcation was scanned using both fast plane wave ultrasound and MRA in 10 healthy volunteers. The MRA geometry acquired from one of the volunteers was used to fabricate an anthropomorphic flow phantom, which was also scanned using the fast plane wave sequence. The same geometry was used in a CFD simulation to calculate the velocity field. Results indicated that similar flow patterns and vortices were estimated with CFD and VFI in the phantom for the carotid bifurcation. The root-mean-square difference between CFD and VFI was within 0.12 m/s for velocity estimates in the common carotid artery and the internal branch. The root-mean-square difference was 0.17 m/s in the external branch. For the 10 volunteers, the mean difference between VFI and MRA was -0.17 m/s for peak systolic velocities of laminar flow in vivo. The precision in vivo was calculated as the mean standard deviation (SD) of estimates aligned to the heart cycle and was highest in the center of the common carotid artery (SD = 3.6% for velocity magnitudes and 4.5° for angles) and lowest in the external branch and for vortices (SD = 10.2% for velocity magnitudes and 39° for angles). The results indicate that plane wave VFI measures flow precisely and that estimates are in good agreement with a CFD simulation and MRA.

Safety Assessment of Advanced Imaging Sequences I: Measurements.

A method for rapid measurement of intensities (I(spta)), mechanical index (MI), and probe surface temperature for any ultrasound scanning sequence is presented. It uses the scanner's sampling capability to give an accurate measurement of the whole imaging sequence for all emissions to yield the true distributions. The method is several orders of magnitude faster than approaches using an oscilloscope, and it also facilitates validating the emitted pressure field and the scanner's emission sequence software. It has been implemented using the experimental synthetic aperture real-time ultrasound system (SARUS) scanner and the Onda AIMS III intensity measurement system (Onda Corporation, Sunnyvale, CA, USA). Four different sequences have been measured: a fixed focus emission, a duplex sequence containing B-mode and flow emissions, a vector flow sequence with B-mode and flow emissions in 17 directions, and finally a SA duplex flow sequence. A BK8820e (BK Medical, Herlev, Denmark) convex array probe is used for the first three sequences and a BK8670 linear array probe for the SA sequence. The method is shown to give the same intensity values within 0.24% of the AIMS III Soniq 5.0 (Onda Corporation, Sunnyvale, CA, USA) commercial intensity measurement program. The approach can measure and store data for a full imaging sequence in 3.8-8.2 s per spatial position. Based on I(spta), MI, and probe surface temperature, the method gives the ability to determine whether a sequence is within U.S. FDA limits, or alternatively indicate how to scale it to be within limits.

A transverse oscillation approach for estimation of three-dimensional velocity vectors, part II: experimental validation.

The 3-D transverse oscillation method is investigated by estimating 3-D velocities in an experimental flow-rig system. Measurements of the synthesized transverse oscillating fields are presented as well. The method employs a 2-D transducer; decouples the velocity estimation; and estimates the axial, transverse, and elevation velocity components simultaneously. Data are acquired using a research ultrasound scanner. The velocity measurements are conducted with steady flow in sixteen different directions. For a specific flow direction with [α, ß] = [45, 15]°, the mean estimated velocity vector at the center of the vessel is (v(x), v(y), v(z)) = (33.8, 34.5, 15.2) ± (4.6, 5.0, 0.6) cm/s where the expected velocity is (34.2, 34.2, 13.0) cm/s. The velocity magnitude is 50.6 ± 5.2 cm/s with a bias of 0.7 cm/s. The flow angles α and ß are estimated as 45.6 ± 4.9° and 17.6 ± 1.0°. Subsequently, the precision and accuracy are calculated over the entire velocity profiles. On average for all direction, the relative mean bias of the velocity magnitude is -0.08%. For α and ß, the mean bias is -0.2° and -1.5°. The relative standard deviations of the velocity magnitude ranges from 8 to 16%. For the flow angles, the ranges of the mean angular deviations are 5° to 16° and 0.7° and 8°.

SARUS: A Synthetic Aperture Real-time Ultrasound System.

The Synthetic Aperture Real-time Ultrasound System (SARUS) for acquiring and processing synthetic aperture (SA) data for research purposes is described. The specifications and design of the system are detailed, along with its performance for SA, nonlinear, and 3-D flow estimation imaging. SARUS acquires individual channel data simultaneously for up to 1024 transducer elements for a couple of heart beats, and is capable of transmitting any kind of excitation. The 64 boards in the system house 16 transmit and 16 receive channels each, where sampled channel data can be stored in 2 GB of RAM and processed using five field-programmable gate arrays (FPGAs). The fully parametric focusing unit calculates delays and apodization values in real time in 3-D space and can produce 350 million complex samples per channel per second for full non-recursive synthetic aperture B-mode imaging at roughly 30 high-resolution images/s. Both RF element data and beamformed data can be stored in the system for later storage and processing. The stored data can be transferred in parallel using the system's sixty-four 1-Gbit Ethernet interfaces at a theoretical rate of 3.2 GB/s to a 144-core Linux cluster.

Fast parametric beamformer for synthetic aperture imaging.

This paper describes the design and implementation of a real-time delay-and-sum synthetic aperture beamformer. The beamforming delays and apodization coefficients are described parametrically. The image is viewed as a set of independent lines that are defined in 3D by their origin, direction, and inter-sample distance. The delay calculation is recursive and inspired by the coordinate rotation digital computer (CORDIC) algorithm. Only 3 parameters per channel and line are needed for their generation. The calculation of apodization coefficients is based on a piece- wise linear approximation. The implementation of the beamformer is optimized with respect to the architecture of a novel synthetic aperture real-time ultrasound scanner (SARUS), in which 4 channels are processed by the same set of field-programmable gate arrays (FPGA). In synthetic transmit aperture imaging, low-resolution images are formed after every emission. Summing all low-resolution images produces a perfectly focused high-resolution image. The design of the beamformer is modular, and a single beamformation unit can produce 4600 low-resolution images per second, each consisting of 32 lines and 1024 complex samples per line. In its present incarnation, 3 such modules fit in a single device. The summation of low-resolution images is performed internally in the FPGA to reduce the required bandwidth. The delays are calculated with a precision of 1/16th of a sample, and the apodization coefficients with 7-bit precision. The accumulation of low-resolution images is performed with 24-bit precision. The level of the side- and grating lobes, introduced by the use of integer numbers in the calculations and truncation of intermediate results, is below -86 dB from the peak.

Compact FPGA-based beamformer using oversampled 1-bit A/D converters.

A compact medical ultrasound beamformer architecture that uses oversampled 1-bit analog-to-digital (A/D) converters is presented. Sparse sample processing is used, as the echo signal for the image lines is reconstructed in 512 equidistant focal points along the line through its in-phase and quadrature components. That information is sufficient for presenting a B-mode image and creating a color flow map. The high sampling rate provides the necessary delay resolution for the focusing. The low channel data width (1-bit) makes it possible to construct a compact beamformer logic. The signal reconstruction is done using finite impulse reponse (FIR) filters, applied on selected bit sequences of the delta-sigma modulator output stream. The approach allows for a multichannel beamformer to fit in a single field programmable gate array (FPGA) device. A 32-channel beamformer is estimated to occupy 50% of the available logic resources in a commercially available mid-range FPGA, and to be able to operate at 129 MHz. Simulation of the architecture at 140 MHz provides images with a dynamic range approaching 60 dB for an excitation frequency of 3 MHz.

Ultrasound research scanner for real-time synthetic aperture data acquisition.

Conventional ultrasound systems acquire ultrasound data sequentially one image line at a time. The architecture of these systems is therefore also sequential in nature and processes most of the data in a sequential pipeline. This often makes it difficult to implement radically different imaging strategies on the platforms and makes the scanners less accessible for research purposes. A system designed for imaging research flexibility is the prime concern. The possibility of sending out arbitrary signals and the storage of data from all transducer elements for 5 to 10 seconds allows clinical evaluation of synthetic aperture and 3D imaging. This paper describes a real-time system specifically designed for research purposes. The system can acquire multichannel data in real-time from multi-element ultrasound transducers, and can perform some real-time processing on the acquired data. The system is capable of performing real-time beamforming for conventional imaging methods using linear, phased, and convex arrays. Image acquisition modes can be intermixed, and this makes it possible to perform initial trials in a clinical environment with new imaging modalities for synthetic aperture imaging, 2D and 3D B-mode, and velocity imaging using advanced coded emissions. The system can be used with 128-element transducers and can excite 128 transducer elements and receive and sample data from 64 channels simultaneously at 40 MHz with 12-bit precision. Two-to-one multiplexing in receive can be used to cover 128 receive channels. Data can be beamformed in real time using the system's 80 signal processing units, or it can be stored directly in RAM. The system has 16 Gbytes RAM and can, thus, store more than 3.4 seconds of multichannel data. It is fully software programmable and its signal processing units can also be reconfigured under software control. The control of the system is done over a 100-Mbits/s Ethernet using C and Matlab. Programs for doing, e.g., B-mode imaging can be written directly in Matlab and executed on the system over the net from any workstation running Matlab. The overall system concept is presented along with its implementation and examples of B-mode and in vivo synthetic aperture flow imaging.