Three-dimensional ultrasound localization microscopy (ULM) enables comprehensive visualization of the vasculature, thereby improving diagnostic reliability. Nevertheless, its clinical translation remains challenging, as the exponential growth in voxel count for full 3D reconstruction imposes heavy computational demands and extensive post-processing time. In this row-column array (RCA)-based 3Din vivopig kidney ULM study, we reformulate each step of the full 3D ULM pipeline, including beamforming, clutter filtering, motion estimation, microbubble separation and localization into a series of computational-efficient 2D operations, substantially reducing the number of voxels to be processed while maintaining comparable accuracy. The proposed framework reconstructs each 0.75-s ensemble acquired at volume rate of 400 Hz, covering a 25×27.4×27.4 mm3volume, in 0.52 s (70% of the acquisition time) on a single RTX A6000 Ada GPU, while maintaining ULM image quality comparable to conventional 3D processing. Quantitatively, it achieves a structural similarity index (SSIM) of 0.93 between density maps and a voxel-wise velocity agreement with slope of 0.93 andR² = 0.88, closely matching conventional 3D results, and for the first time, demonstrating potential for real-time feedback during scanning, which could improve robustness, reduce operator dependence and accelerate clinical workflows.

Ultrasound vascular imaging (UVI) is a valuable tool for monitoring the physiological states and evaluating the pathological diseases. Advancing from conventional two-dimensional (2D) to three-dimensional (3D) UVI would enhance the vasculature visualization, thereby improving its reliability. Row-column array (RCA) has emerged as a promising approach for cost-effective ultrafast 3D imaging with a low channel count. However, ultrafast RCA imaging is often hampered by high-level sidelobe artifacts and low signal-to-noise ratio (SNR), which makes RCA-based UVI challenging. In this study, we propose a spatial-temporal similarity weighting (St-SW) method to overcome these challenges by exploiting the incoherence of sidelobe artifacts and noise between datasets acquired using orthogonal transmissions. Simulation, in vitro blood flow phantom, and in vivo experiments were conducted to compare the proposed method with existing orthogonal plane wave imaging (OPW), row-column-specific frame-multiply-and-sum beamforming (RC-FMAS), and XDoppler techniques. Qualitative and quantitative results demonstrate the superior performance of the proposed method. In simulations, the proposed method reduced the sidelobe level by 31.3 dB, 20.8 dB, and 14.0 dB, compared to OPW, XDoppler, and RC-FMAS, respectively. In the blood flow phantom experiment, the proposed method significantly improved the contrast-to-noise ratio (CNR) of the tube by 26.8 dB, 25.5 dB, and 19.7 dB, compared to OPW, XDoppler, and RC-FMAS methods, respectively. In the human submandibular gland experiment, it not only reconstructed a more complete vasculature but also improved the CNR by more than 15 dB, compared to OPW, XDoppler, and RC-FMAS methods. In summary, the proposed method effectively suppresses the side-lobe artifacts and noise in images collected using an RCA under low SNR conditions, leading to improved visualization of 3D vasculatures.

Ultrasound localization microscopy (ULM) based on microbubble (MB) localization was recently introduced to overcome the resolution limit of conventional ultrasound. However, ULM is currently challenged by the requirement for long data acquisition times to accumulate adequate MB events to fully reconstruct vasculature. In this study, we present a curvelet transform-based sparsity promoting (CTSP) algorithm that improves ULM imaging speed by recovering missing MB localization signal from data with very short acquisition times. CTSP was first validated in a simulated microvessel model, followed by the chicken embryo chorioallantoic membrane (CAM), and finally, in the mouse brain. In the simulated microvessel study, CTSP robustly recovered the vessel model to achieve an 86.94% vessel filling percentage from a corrupted image with only 4.78% of the true vessel pixels. In the chicken embryo CAM study, CTSP effectively recovered the missing MB signal within the vasculature, leading to marked improvement in ULM imaging quality with a very short data acquisition. Taking the optical image as reference, the vessel filling percentage increased from 2.7% to 42.2% using 50ms of data acquisition after applying CTSP. CTSP used 80% less time to achieve the same 90% maximum saturation level as compared with conventional MB localization. We also applied CTSP on the microvessel flow speed maps and found that CTSP was able to use only 1.6s of microbubble data to recover flow speed images that have similar qualities as those constructed using 33.6s of data. In the mouse brain study, CTSP was able to reconstruct the majority of the cerebral vasculature using 1-2s of data acquisition. Additionally, CTSP only needed 3.2s of microbubble data to generate flow velocity maps that are comparable to those using 129.6s of data. These results suggest that CTSP can facilitate fast and robust ULM imaging especially under the circumstances of inadequate microbubble localizations.

Shear wave elastography methods are able to accurately measure tissue stiffness, allowing these techniques to monitor the progression of hepatic fibrosis. While many methods rely on acoustic radiation force to generate shear waves for 2-D imaging, probe oscillation shear wave elastography (PROSE) provides an alternative approach by generating shear waves through continuous vibration of the ultrasound probe while simultaneously detecting the resulting motion. The generated shear wave field in in vivo liver is complicated, and the amplitude and quality of these shear waves can be influenced by the placement of the vibrating probe. To address these challenges, a real-time shear wave visualization tool was implemented to provide instantaneous visual feedback to optimize probe placement. Even with the real-time display, it was not possible to fully suppress residual motion with established filtering methods. To solve this problem, the shear wave signal in each frame was decoupled from motion and other sources through the use of a parameter-free empirical mode decomposition before calculating shear wave speeds. This method was evaluated in a phantom as well as in in vivo livers from five volunteers. PROSE results in the phantom as well as in vivo liver correlated well with independent measurements using the commercial General Electric Logiq E9 scanner.

The development of ultrafast ultrasound imaging brings great opportunities to improve imaging technologies such as shear wave elastography and ultrafast Doppler imaging. In ultrafast imaging, several tilted plane or diverging wave images are coherently combined to form a compounded image, leading to trade-offs among image signal-to-noise ratio (SNR), resolution, and post-compounded frame rate. Multiplane wave (MW) imaging is proposed to solve this trade-off by encoding multiple plane waves with Hadamard matrix during one transmission event (i.e. pulse-echo event), to improve image SNR without sacrificing the resolution or frame rate. However, it suffers from stronger reverberation artifacts in B-mode images compared to standard plane wave compounding due to longer transmitted pulses. If harmonic imaging can be combined with MW imaging, the reverberation artifacts and other clutter noises such as sidelobes and multipath scattering clutters should be suppressed. The challenge, however, is that the Hadamard codes used in MW imaging cannot encode the 2ndharmonic component by inversing the pulse polarity. In this paper, we propose a delay-encoded harmonic imaging (DE-HI) technique to encode the 2ndharmonic with a one quarter period delay calculated at the transmit center frequency, rather than reversing the pulse polarity during multiplane wave emissions. Received DE-HI signals can then be decoded in the frequency domain to recover the signals as in single plane wave emissions, but mainly with improved SNR at the 2ndharmonic component instead of the fundamental component. DE-HI was tested experimentally with a point target, a B-mode imaging phantom, and in-vivo human liver imaging. Improvements in image contrast-to-noise ratio (CNR), spatial resolution, and lesion-signal-to-noise ratio (lSNR) have been achieved compared to standard plane wave compounding, MW imaging, and standard harmonic imaging (maximal improvement of 116% on CNR and 115% on lSNR as compared to standard HI around 55 mm depth in the B-mode imaging phantom study). The potential high frame rate and the stability of encoding and decoding processes of DE-HI were also demonstrated, which made DE-HI promising for a wide spectrum of imaging applications.

The development of ultrafast ultrasound imaging offers great opportunities to improve imaging technologies, such as shear wave elastography and ultrafast Doppler imaging. In ultrafast imaging, there are tradeoffs among image signal-to-noise ratio (SNR), resolution, and post-compounded frame rate. Various approaches have been proposed to solve this tradeoff, such as multiplane wave imaging or the attempts of implementing synthetic transmit aperture imaging. In this paper, we propose an ultrafast synthetic transmit aperture (USTA) imaging technique using Hadamard-encoded virtual sources with overlapping sub-apertures to enhance both image SNR and resolution without sacrificing frame rate. This method includes three steps: 1) create virtual sources using sub-apertures; 2) encode virtual sources using Hadamard matrix; and 3) add short time intervals (a few microseconds) between transmissions of different virtual sources to allow overlapping sub-apertures. The USTA was tested experimentally with a point target, a B-mode phantom, and in vivo human kidney micro-vessel imaging. Compared with standard coherent diverging wave compounding with the same frame rate, improvements on image SNR, lateral resolution (+33%, with B-mode phantom imaging), and contrast ratio (+3.8 dB, with in vivo human kidney micro-vessel imaging) have been achieved. The f-number of virtual sources, the number of virtual sources used, and the number of elements used in each sub-aperture can be flexibly adjusted to enhance resolution and SNR. This allows very flexible optimization of USTA for different applications.

Robust clutter filtering is essential for ultrasound small vessel imaging. Eigen-based clutter filtering techniques have recently shown great improvement in clutter rejection over conventional clutter filters in small animals. However, for in vivo human imaging, eigen-based clutter filtering can be challenging due to the complex spatially-varying tissue and noise characteristics. To address this challenge, we present a novel block-wise adaptive singular value decomposition (SVD) based clutter filtering technique. The proposed method divides the global plane wave data into overlapped local spatial segments, within which tissue signals are assumed to be locally coherent and noise locally stationary. This, in turn, enables effective separation of tissue, blood and noise via SVD. For each block, the proposed method adaptively determines the singular value cutoff thresholds based on local data statistics. Processing results from each block are redundantly combined to improve both the signal-to-noise-ratio (SNR) and the contrast-to-noise-ratio (CNR) of the small vessel perfusion image. Experimental results show that the proposed method achieved more than two-fold increase in SNR and more than three-fold increase in CNR in dB scale over the conventional global SVD filtering technique for an in vivo human native kidney study. The proposed method also showed substantial improvement in suppression of the depth-dependent background noise and better rejection of near field tissue clutter. The effects of different processing block size and block overlap percentage were systematically investigated as well as the tradeoff between imaging quality and computational cost.

Ultrasound shear wave elastography (SWE) utilizes the propagation of induced shear waves to characterize the shear modulus of soft tissue. Many methods rely on an acoustic radiation force (ARF) "push beam" to generate shear waves. However, specialized hardware is required to generate the push beams, and the thermal stress that is placed upon the ultrasound system, transducer, and tissue by the push beams currently limits the frame-rate to about 1 Hz. These constraints have limited the implementation of ARF to high-end clinical systems. This paper presents Probe Oscillation Shear Elastography (PROSE) as an alternative method to measure tissue elasticity. PROSE generates shear waves using a harmonic mechanical vibration of an ultrasound transducer, while simultaneously detecting motion with the same transducer under pulse-echo mode. Motion of the transducer during detection produces a "strain-like" compression artifact that is coupled with the observed shear waves. A novel symmetric sampling scheme is proposed such that pulse-echo detection events are acquired when the ultrasound transducer returns to the same physical position, allowing the shear waves to be decoupled from the compression artifact. Full field-of-view (FOV) two-dimensional (2D) shear wave speed images were obtained by applying a local frequency estimation (LFE) technique, capable of generating a 2D map from a single frame of shear wave motion. The shear wave imaging frame rate of PROSE is comparable to the vibration frequency, which can be an order of magnitude higher than ARF based techniques. PROSE was able to produce smooth and accurate shear wave images from three homogeneous phantoms with different moduli, with an effective frame rate of 300 Hz. An inclusion phantom study showed that increased vibration frequencies improved the accuracy of inclusion imaging, and allowed targets as small as 6.5 mm to be resolved with good contrast (contrast-to-noise ratio ≥ 19 dB) between the target and background.

In clinical practice, an overwhelming majority of biopsied thyroid nodules are benign. Therefore, there is a need for a complementary and noninvasive imaging tool to provide clinically relevant diagnostic information about thyroid nodules to reduce the rate of unnecessary biopsies. The goal of this study was to evaluate the feasibility of utilizing comb-push ultrasound shear elastography (CUSE) to measure the mechanical properties (i.e., stiffness) of thyroid nodules and use this information to help classify nodules as benign or malignant. CUSE is a fast and robust 2-D shear elastography technique in which multiple laterally distributed acoustic radiation force beams are utilized simultaneously to produce shear waves. Unlike other shear elasticity imaging modalities, CUSE does not suffer from limited field of view (FOV) due to shear wave attenuation and can provide a large FOV at high frame rates. To evaluate the utility of CUSE in thyroid imaging, a preliminary study was performed on a group of five healthy volunteers and 10 patients with ultrasound-detected thyroid nodules prior to fine needle aspiration biopsy. The measured shear wave speeds in normal thyroid tissue and thyroid nodules were converted to Young's modulus (E), indicating a measure of tissue stiffness. Our results indicate an increase in E for thyroid nodules compared to normal thyroid tissue. This increase was significantly higher in malignant nodules compared to benign. The Young's modulus in normal thyroid tissue, benign and malignant nodules were found to be 23.2 ±8.29 kPa, 91.2±34.8 kPa, and 173.0±17.1 kPa, respectively. Results of this study suggest the utility of CUSE in differentiating between benign and malignant thyroid nodules.

Shear wave speed can be used to assess tissue elasticity, which is associated with tissue health. Ultrasound shear wave elastography techniques based on measuring the propagation speed of the shear waves induced by acoustic radiation force are becoming promising alternatives to biopsy in liver fibrosis staging. However, shear waves generated by such methods are typically very weak. Therefore, the penetration may become problematic, especially for overweight or obese patients. In this study, we developed a new method called external vibration multi-directional ultrasound shearwave elastography (EVMUSE), in which external vibration from a loudspeaker was used to generate a multi-directional shear wave field. A directional filter was then applied to separate the complex shear wave field into several shear wave fields propagating in different directions. A 2-D shear wave speed map was reconstructed from each individual shear wave field, and a final 2-D shear wave speed map was constructed by compounding these individual wave speed maps. The method was validated using two homogeneous phantoms and one multi-purpose tissue-mimicking phantom. Ten patients undergoing liver magnetic resonance elastography (MRE) were also studied with EVMUSE to compare results between the two methods. Phantom results showed EVMUSE was able to quantify tissue elasticity accurately with good penetration. In vivo EVMUSE results were well correlated with MRE results, indicating the promise of using EVMUSE for liver fibrosis staging.

Comb-push ultrasound shear elastography (CUSE) has recently been shown to be a fast and accurate 2-D elasticity imaging technique that can provide a full field-of-view (FOV) shear wave speed map with only one rapid data acquisition. The initial version of CUSE was termed U-CUSE because unfocused ultrasound push beams were used. In this paper, we present two new versions of CUSE-focused CUSE (F-CUSE) and marching CUSE (M-CUSE), which use focused ultrasound push beams to improve acoustic radiation force penetration and produce stronger shear waves in deep tissues (e.g., kidney and liver). F-CUSE divides transducer elements into several subgroups which transmit multiple focused ultrasound beams simultaneously. M-CUSE uses more elements for each focused push beam and laterally marches the push beams. Both F-CUSE and M-CUSE can generate comb-shaped shear wave fields that have shear wave motion at each imaging pixel location so that a full FOV 2-D shear wave speed map can be reconstructed with only one data acquisition. Homogeneous phantom experiments showed that U-CUSE, F-CUSE, and M-CUSE can all produce smooth shear wave speed maps with accurate shear wave speed estimates. An inclusion phantom experiment showed that all CUSE methods could provide good contrast between the inclusion and background with sharp boundaries while F-CUSE and M-CUSE require shorter push durations to achieve shear wave speed maps with comparable SNR to U-CUSE. A more challenging inclusion phantom experiment with a very stiff and deep inclusion shows that better shear wave penetration could be gained by using F-CUSE and M-CUSE. Finally, a shallow inclusion experiment showed that good preservations of inclusion shapes could be achieved by both U-CUSE and F-CUSE in the near field. Safety measurements showed that all safety parameters are below FDA regulatory limits for all CUSE methods. These promising results suggest that, using various push beams, CUSE is capable of reconstructing a 2-D full FOV shear elasticity map using only one push-detection data acquisition in a wide range of depths for soft tissue elasticity imaging.

Ultrasound tissue harmonic imaging is widely used to improve ultrasound B-mode imaging quality thanks to its effectiveness in suppressing imaging artifacts associated with ultrasound reverberation, phase aberration, and clutter noise. In ultrasound shear wave elastography (SWE), because the shear wave motion signal is extracted from the ultrasound signal, these noise sources can significantly deteriorate the shear wave motion tracking process and consequently result in noisy and biased shear wave motion detection. This situation is exacerbated in in vivo SWE applications such as heart, liver, and kidney. This paper, therefore, investigated the possibility of implementing harmonic imaging, specifically pulse-inversion harmonic imaging, in shear wave tracking, with the hypothesis that harmonic imaging can improve shear wave motion detection based on the same principles that apply to general harmonic B-mode imaging. We first designed an experiment with a gelatin phantom covered by an excised piece of pork belly and show that harmonic imaging can significantly improve shear wave motion detection by producing less underestimated shear wave motion and more consistent shear wave speed measurements than fundamental imaging. Then, a transthoracic heart experiment on a freshly sacrificed pig showed that harmonic imaging could robustly track the shear wave motion and give consistent shear wave speed measurements of the left ventricular myocardium while fundamental imaging could not. Finally, an in vivo transthoracic study of seven healthy volunteers showed that the proposed harmonic imaging tracking sequence could provide consistent estimates of the left ventricular myocardium stiffness in end-diastole with a general success rate of 80% and a success rate of 93.3% when excluding the subject with Body Mass Index higher than 25. These promising results indicate that pulse-inversion harmonic imaging can significantly improve shear wave motion tracking and thus potentially facilitate more robust assessment of tissue elasticity by SWE.

Fast and accurate tissue elasticity imaging is essential in studying dynamic tissue mechanical properties. Various ultrasound shear elasticity imaging techniques have been developed in the last two decades. However, to reconstruct a full field-of-view 2-D shear elasticity map, multiple data acquisitions are typically required. In this paper, a novel shear elasticity imaging technique, comb-push ultrasound shear elastography (CUSE), is introduced in which only one rapid data acquisition (less than 35 ms) is needed to reconstruct a full field-of-view 2-D shear wave speed map (40 × 38 mm). Multiple unfocused ultrasound beams arranged in a comb pattern (comb-push) are used to generate shear waves. A directional filter is then applied upon the shear wave field to extract the left-to-right (LR) and right-to-left (RL) propagating shear waves. Local shear wave speed is recovered using a time-of-flight method based on both LR and RL waves. Finally, a 2-D shear wave speed map is reconstructed by combining the LR and RL speed maps. Smooth and accurate shear wave speed maps are reconstructed using the proposed CUSE method in two calibrated homogeneous phantoms with different moduli. Inclusion phantom experiments demonstrate that CUSE is capable of providing good contrast (contrast-to-noise ratio ≥ 25 dB) between the inclusion and background without artifacts and is insensitive to inclusion positions. Safety measurements demonstrate that all regulated parameters of the ultrasound output level used in CUSE sequence are well below the FDA limits for diagnostic ultrasound.