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Functional imaging and super-resolution imaging are promising research areas of medical ultrasound. For the purpose of tracking physiological changes and micro-bubbles, they require continuous data acquisition for minutes. One flexible and mobile research scanner that can be used for that purpose is the Verasonics Vantage, which however has a hardware limitation of approximately 132,000 emissions per data acquisition using the stock software library. Using an emission rate of 5 kHz gives an acquisition time of only 26 seconds, which is insufficient. This paper presents a technique for overcoming this limitation, achieving long acquisitions where the scan duration is limited by the computer RAM only. The technique has been already routinely used for 10-minute in-vivo scans of exposed rat kidneys, resulting in micro-bubble tracking maps for super-resolution imaging.

SUper-Resolution ultrasound imaging using the Erythrocytes (SURE) can visualize blood vessels at about 25 to 50 µm resolution, but validation is required to assess how accurately the vasculature and its morphology are represented. Previous work compared ultrasound imaging to maximum intensity projections (MIP) of micro-CT volumes at an insufficient voxel size of 22.6 µm. Here, a 5 µm voxel size micro-CT volume of a cortical region in an excised rat kidney was acquired to test the hypothesis that blood vessels down to 50 µm in diameter are detected with SURE imaging. For the micro-CT volume, the blood vessels were segmented by an intensity threshold, and local thickness estimates were computed using expanding spheres within the segmentation mask. An affine registration between the SURE image and the micro-CT volume was manually defined, and a MIP of the microCT volume across 2 mm from the ultrasound imaging plane was computed for vessels with diameter estimates greater than 50 µm. The SURE image depicts 12 cortical radial vessels with high intensities and 9 dimmer cortical radial vessels. Notably, the 12 high intensity vessels are also depicted in the microCT projection, but 5 cortical radial vessels and 2 arcuate blood vessels are only visible in the SURE image. Of the faintly depicted cortical radial vessels, 5 vessels are not readily matched to vessels in the micro-CT projection. On the other hand, the microCT projection contains 6 cortical radial vessel segments and 2 arcuate blood vessels not depicted in the SURE image. These discrepancies in the comparison may arise from the challenging registration of the ultrasound focus beam and the micro-CT volume that is complicated further by the different states of the imaged tissue. Despite these challenges, SURE depicts most vessels at least down to 50 µm and even resolves parallel vessels not visible in the micro-CT projection, thus highlighting its clinical potential.

Pressure gradient estimations are used as a biomarker for cardiovascular diseases. Here non-invasive pressure gradients are desired over invasive catheterization. This study estimates non-invasive pressure gradients from synthetic aperture ultrasound using the work-energy method. The method is translated to 2D synthetic aperture ultrasound by assuming rotational symmetric blood vessels and is hypothesised to yield more precise estimation compared to the unsteady Bernoulli method along a streamline. The method uses flow rates, blood velocities and acceleration for estimating the pressure gradient. Data are acquired using a 256 elements, 6.5 MHz GE L3-12-D linear array transducer connected to a Verasonics research scanner with a pulse repetition frequency equal to 5 kHz. A interleaved sequence using 12 virtual sources is used for both flow estimations and B-mode imaging. The interleaved sequence allows correlation frames to be separated by only the pulse repetition time, making it possible to estimate high velocities. The work energy method is compared to a previously validated unsteady Bernoulli method (streamline method) using experimental data from a blood vessel phantom with a 60% stenosis. The result shows that the work-energy method detects a maximum pressure difference of 3.42 Pa and a minimum pressure difference of -53.3 Pa with a precision of 3.04% across eleven pulse cycles. The unsteady Bernoulli method detected pressure differences changing from 5.44 Pa to -68.2 Pa with a precision of 3.23%.

Individuals with diabetes at risk of developing diabetic kidney disease (DKD) are challenging to identify using currently available clinical methods. Prognostic accuracy and initiation of treatment could be improved by a quantification of the renal microvascular rarefaction and the increased vascular tortuosity during the development of DKD. Super-resolution ultrasound (SRUS) imaging is an in vivo technique capable of visualizing blood vessels at sizes below 75 µm. This preclinical study aimed to investigate the alterations in renal blood vessels’ density and tortuosity in a type 2 diabetes rat model, Zucker diabetic fatty (ZDF) rats, as a prediction of DKD. Lean age-matched Zucker rats were used as controls. A total of 36 rats were studied, subdivided into ages of 12, 22, and 40 weeks. Measured albuminuria indicated the early stage of DKD, and the SRUS was compared with the ex vivo micro-computed tomography (µCT) of the same kidneys. Assessed using the SRUS imaging, a significantly decreased cortical vascular density was detected in the ZDF rats from 22 weeks of age compared to the healthy controls, concomitant with a significantly increased albuminuria. Already by week 12, a trend towards a decreased cortical vascular density was found prior to the increased albuminuria. The quantified vascular density in µCT corresponded with the in vivo SRUS imaging, presenting a consistently lower vascular density in the ZDF rats. Regarding vessel tortuosity, an overall trend towards an increased tortuosity was present in the ZDF rats. SRUS shows promise for becoming an additional tool for monitoring and prognosing DKD. In the future, large-scale animal studies and human trials are needed for confirmation.

This work presents a beamforming procedure that significantly reduces the number of operations when performing volumetric synthetic aperture imaging with row–column addressed arrays (RCAs). The proposed beamformer uses that the image values along the elevation direction of the low-resolution volume (LRV) are approximately constant. It is thus hypothesized that the entire LRV could be reconstructed from a single 2-D cross section of the LRV. The presented method contains two stages. The first stage beamforms, for each emission, a cross section using the conventional RCA beamformer. The second stage extrapolates the rest of the image points in the volume from the 2-D cross sections. Assuming the image volume is covered by 3-D grid coordinates with a size of ${N}_{w}\times {N}_{w} \times {N}_{z}$ , i.e., ${N}_{w}$ samples along the ${x}$ - and ${y}$ -axis and ${N}_{z}$ samples along the ${z}$ -axis, the proposed beamformer reduces the number of mathematical operations by a factor of approximately $\textit {NN}_{w}/{(}\textit {NS}+{N}_{w}{)}$ . Here, ${S}$ is the ratio between the first- and second-stage axial sampling rates, and ${N}$ is the receiving aperture’s number of channels. Beamforming a $128\times 128\times1024$ volume from data acquired with ${N}$ = 128 receiving channel can thus be achieved with 25.6 times fewer operations, when ${S}$ = 4. A 9.23 times increase in the beamforming rate for a $100\times 100\times200$ volume was demonstrated on complex data from a 128 + 128 Vermon RCA probe. Real-time volumetric beamformation can, with this increase, be performed with a pulse repetition frequency of up to 1804.80 Hz. The proposed and conventional beamformer’s output was visually indistinguishable, and the full width at half maximum (FWHM) and full width at tenth maximum (FWTM) were at most 1.19% larger with the proposed approach. The proposed beamformer can thus perform volumetric imaging significantly faster than the current approach, with a negligible differe

Purpose This paper investigates the accuracy of blood flow velocities simulated from a geometry prescribed computational fluid dynamics (CFD) pipeline by applying it to a dynamic heart phantom. The CFD flow patterns are compared to a direct flow measurement by ultrasound vector flow imaging (VFI). The hypothesis is that the simulated velocity magnitudes are within one standard deviation of the measured velocities. Methods The CFD pipeline uses computed tomography angiography (CTA) images with 20 volumes per cardiac cycle as geometry input. Fluid domain movement is prescribed from volumetric image registration using the CTA image data. Inlet and outlet conditions are defned by the experimental setup. VFI is systematically measured in parallel planes, and compared to the corresponding planes in the simulated time dependent three dimensional fluid velocity field. Results The measured VFI and simulated CFD have similar flow patterns when compared qualitatively. A quantitative comparison of the velocity magnitude is also performed at specific regions of interest. These are evaluated at 11 non-overlapping time bins and compared by linear regression giving R2 = 0.809, SD = 0.060 m/s, intercept = − 0.039 m/s, and slope = 1.09. Excluding an outlier at the inlet, the correspondence between CFD and VFI improves to: R2 = 0.823, SD = 0.048 m/s, intercept = -0.030 m/s, and slope = 1.01. Conclusion The direct comparison of flow patterns shows that the proposed CFD pipeline provide realistic flow patterns in a well-controlled experimental setup. The demanded accuracy is obtained close to the inlet and outlet, but not in locations far from these.

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.

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 paper hypothesizes that a single, universal sequence can be developed for linear array SA imaging. This sequence yields high quality linear and non-linear 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 5,000 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, vector velocity imaging and super resolution imaging derived from the same data set and demonstrates that all imaging modes can be shown retrospectively and quantitative data derived from it.

This study presents a method for noninvasive pressure gradient estimation, which allows the detection of small pressure differences with higher precision compared to invasive catheters. It combines a new method for estimating the temporal acceleration of the flowing blood with the Navier–Stokes equation. The acceleration estimation is based on a double cross-correlation approach, which is hypothesized to minimize the influence of noise. Data are acquired using a 256-element, 6.5-MHz GE L3-12-D linear array transducer connected to a Verasonics research scanner. A synthetic aperture (SA) interleaved sequence with 2 × 12 virtual sources evenly distributed over the aperture and permuted in emission order is used in combination with recursive imaging. This enables a temporal resolution between correlation frames equal to the pulse repetition time at a frame rate of half the pulse repetition frequency. The accuracy of the method is evaluated against a computational fluid dynamic simulation. Here, the estimated total pressure difference complies with the CFD reference pressure difference, which yields an R-square of 0.985 and an RMSE of 3.03 Pa. The precision of the method is tested on experimental data, measured on a carotid phantom of the common carotid artery. The volume profile used during measurement was set to mimic flow in the carotid artery with a peak flow rate of 12.9 mL/s. The experimental setup showed that the measured pressure difference changes from −59.4 to 31 Pa throughout a single pulse cycle. This was estimated with a precision of 5.44% (3.22 Pa) across ten pulse cycles. The method was also compared to invasive catheter measurements in a phantom with a 60% cross-sectional area reduction. The ultrasound method detected a maximum pressure difference of 72.3 Pa with a precision of 3.3% (2.22 Pa). The catheters measured a maximum pressure difference of 105 Pa with a precision of 11.2% (11.4 Pa). This was measured over the same constriction and with a peak flo

A key component of super-resolution ultrasound imaging (SRI) is the detection and tracking of scatterers. These scatterers can be microbubbles (MBs) in SRI, or erythrocytes in SUper Resolution ultrasound imaging using Erythrocytes (SURE). To ensure the reliability of MBs tracking in SRI, the MBs must be sparse. However, the sparse distribution of the MBs necessitates several minutes of acquisition. In contrast, there are large numbers of erythrocytes in SURE. Increasing the number of scatterers can reduce the acquisition time, however tracking uncorrelated and high-density scatterers is quite challenging. It is hypothesized that recursive Synthetic Aperture (SA) imaging will increase the detecting and tracking abilities of the high-density and non-separable scatterers. The hypothesis was verified using a hydrogel 3D-printed micro-flow phantom and a Sprague-Dawley rat kidney. The results show that using recursive SA imaging provides better detection and tracking of high-density and non-separable targets, as well as a smoother and more parabolic velocity profile than conventional SA imaging.