Optimization of array encoding for ultrasound imaging.

Objective. The transmit encoding model for synthetic aperture imaging is a robust and flexible framework for understanding the effects of acoustic transmission on ultrasound image reconstruction. Our objective is to use machine learning (ML) to construct scanning sequences, parameterized by time delays and apodization weights, that produce high-quality B-mode images.Approach. We use a custom ML model in PyTorch with simulated RF data from Field II to probe the space of possible encoding sequences for those that minimize a loss function that describes image quality. This approach is made computationally feasible by a novel formulation of the derivative for delay-and-sum beamforming.Main results. When trained for a specified experimental setting (imaging domain, hardware restrictions, etc), our ML model produces optimized encoding sequences that, when deployed in the REFoCUS imaging framework, improve a number of standard quality metrics over conventional sequences including resolution, field of view, and contrast. We demonstrate these results experimentally on both wire targets and a tissue-mimicking phantom.Significance. This work demonstrates that the set of commonly used encoding schemes represent only a narrow subset of those available. Additionally, it demonstrates the value for ML tasks in synthetic transmit aperture imaging to consider the beamformer within the model, instead of purely as a post-processing step.

Improved Spatiotemporal Resolution in Echocardiography Using Mixed Geometry Imaging Sequences.

Cardiac ultrasound seeks to image the most dynamic environment in the body-the moving heart. Many modern ultrasound imaging techniques address the tradeoff between spatial and temporal resolution using either narrow focused beams or with broad beam, synthetic aperture (SA) sequences that have been shown to suffer from motion artifacts. Retrospective encoding for conventional ultrasound sequences (REFoCUS) unifies the processing of these various geometric sequences, but the motion sensitivity of this approach has yet to be investigated. We hypothesize that a "mixed sequence" enabled by the REFoCUS method incorporating several beam geometries may better resolve cardiac motion over a wide field of view (FOV) and at a high frame rate. First, the motion sensitivity of REFoCUS was evaluated in simulation for several focused and broad transmit profiles. Focused transmissions resolve both lateral and axial motion much more effectively than broad transmissions, with performance similar to conventional beamforming techniques. Second, a mixed sequence was designed that insonifies the full field-of-view with plane wave (PW) transmissions and key moving targets with focused transmissions. This mixed sequence was tested in simulation and in vivo and was used to image the heart as well as the liver, a low-motion control. By combining a sparse PW sequence ( n=60 ) with a small group of targeted focused transmissions ( n = 10), the anterior mitral valve leaflet (AML) at its peak observed velocity was better resolved. We believe that mixed sequences have strong potential to resolve cardiac motion at clinically relevant frame rates.

Bubble-Based Microrobots with Rapid Circular Motions for Epithelial Pinning and Drug Delivery.

Remotely powered microrobots are proposed as next-generation vehicles for drug delivery. However, most microrobots swim with linear trajectories and lack the capacity to robustly adhere to soft tissues. This limits their ability to navigate complex biological environments and sustainably release drugs at target sites. In this work, bubble-based microrobots with complex geometries are shown to efficiently swim with non-linear trajectories in a mouse bladder, robustly pin to the epithelium, and slowly release therapeutic drugs. The asymmetric fins on the exterior bodies of the microrobots induce a rapid rotational component to their swimming motions of up to ≈150 body lengths per second. Due to their fast speeds and sharp fins, the microrobots can mechanically pin themselves to the bladder epithelium and endure shear stresses commensurate with urination. Dexamethasone, a small molecule drug used for inflammatory diseases, is encapsulated within the polymeric bodies of the microrobots. The sustained release of the drug is shown to temper inflammation in a manner that surpasses the performance of free drug controls. This system provides a potential strategy to use microrobots to efficiently navigate large volumes, pin at soft tissue boundaries, and release drugs over several days for a range of diseases.

Quantifying the Impact of Imaging Through Body Walls on Shear Wave Elasticity Measurements.

In the context of ultrasonic hepatic shear wave elasticity imaging (SWEI), measurement success has been determined to increase when using elevated acoustic output pressures. As SWEI sequences consist of two distinct operations (pushing and tracking), acquisition failures could be attributed to (i) insufficient acoustic radiation force generation resulting in inadequate shear wave amplitude and/or (ii) distorted ultrasonic tissue motion tracking. In the study described here, an opposing window experimental setup that isolated body wall effects separately between the push and track SWEI operations was implemented. A commonly employed commercial track configuration was used, harmonic multiple-track-location SWEI. The effects of imaging through body walls on the pushing and tracking operations of SWEI as a function of mechanical index (MI), spanning 5 different push beam MIs and 10 track beam MIs, were independently assessed using porcine body walls. Shear wave speed yield was found to increase with both increasing push and track MI. Although not consistent across all samples, measurements in a subset of body walls were found to be signal limited during tracking and to increase yield by up to 35% when increasing electronic signal-to-noise ratio by increasing harmonic track transmit pressure.

Implementation of constrained swept synthetic aperture using a mechanical fixture.

Resolution and target detectability in ultrasound imaging are directly tied to the size of the imaging array. This is especially important for imaging at depth, such as in the detection and diagnosis of hepatocellular carcinoma and other lesions in the liver. Swept synthetic aperture (SSA) imaging has shown promise for building large effective apertures from small physical arrays using motion, but has required bulky fixtures and external motion tracking for precise positioning. In this study we present an approach that constrains the transducer motion with a simple linear sliding fixture and estimates motion from the ultrasound data itself using either speckle tracking or channel correlation. We demonstrate in simulation and phantom experiments the ability of both techniques to accurately estimate lateral transducer motion and form SSA images with improved resolution and target detectability. We observed errors under 83 µm across a 50 mm sweep in simulation and found improvements of up to 61% in resolution and up to 33% in lesion detectability experimentally even imaging through ex vivo tissue layers. This approach will increase the accessibility of SSA imaging and allow us to test its use in clinical settings.

Correction: Martinez et al. Cavitation Characterization of Size-Isolated Microbubbles in a Vessel Phantom Using Focused Ultrasound. Pharmaceutics 2022, 14, 1925.

In the original publication [...].

Cavitation Characterization of Size-Isolated Microbubbles in a Vessel Phantom Using Focused Ultrasound.

Pharmaceutical delivery can be noninvasively targeted on-demand by microbubble (MB) assisted focused ultrasound (FUS). Passive cavitation detection (PCD) has become a useful method to obtain real-time feedback on MB activity due to a FUS pulse. Previous work has demonstrated the acoustic PCD response of MBs at a variety of acoustic parameters, but few have explored variations in microbubble parameters. The goal of this study was to determine the acoustic response of different MB size populations and concentrations. Four MB size distributions were prepared (2, 3, 5 µm diameter and polydisperse) and pulled through a 2% agar wall-less vessel phantom. FUS was applied by a 1.515 MHz geometrically focused transducer for 1 ms pulses at 1 Hz PRF and seven distinct mechanical indices (MI) ranging from 0.01 to 1.0 (0.0123 to 1.23 MPa PNP). We found that the onset of harmonic (HCD) and broadband cavitation dose (BCD) depends on the mechanical index, MB size and MB concentration. When matched for MI, the HCD and BCD rise, plateau, and decline as microbubble concentration is increased. Importantly, when microbubble size and concentration are combined into gas volume fraction, all four microbubble size distributions align to similar onset and peak; these results may help guide the planning and control of MB + FUS therapeutic procedures.

Spatial Coherence in Medical Ultrasound: A Review.

Traditional pulse-echo ultrasound imaging heavily relies on the discernment of signals based on their relative magnitudes but is limited in its ability to mitigate sources of image degradation, the most prevalent of which is acoustic clutter. Advances in computing power and data storage have made it possible for echo data to be alternatively analyzed through the lens of spatial coherence, a measure of the similarity of these signals received across an array. Spatial coherence is not currently explicitly calculated on diagnostic ultrasound scanners but a large number of studies indicate that it can be employed to describe image quality, to adaptively select system parameters and to improve imaging and target detection. With the additional insights provided by spatial coherence, it is poised to play a significant role in the future of medical ultrasound. This review details the theory of spatial coherence in pulse-echo ultrasound and key advances made over the last few decades since its introduction in the 1980s.

Enhanced visibility through microbubble-induced photoacoustic fluctuation imaging.

A photoacoustic contrast mechanism is presented based on the photoacoustic fluctuations induced by microbubbles flowing inside a micro-vessel filled with a continuous absorber. It is demonstrated that the standard deviation of a homogeneous absorber mixed with microbubbles increases non-linearly as the microbubble concentration and microbubble size is increased. This effect is then utilized to perform photoacoustic fluctuation imaging with increased visibility and contrast of a blood flow phantom.

Comparison of spatial encodings for ultrasound imaging.

Ultrasound pulse sequencing and receive signal focusing work hand-in-hand to determine image quality. These are commonly linked by geometry, for example using focused beams or planewaves in transmission paired with appropriate time-of-flight calculations for focusing. Spatial encoding allows a broader class of array transmissions but requires decoding of the recorded echoes before geometric focusing can be applied. Recent work has expanded spatial encoding to include not only element apodizations but also element time delays. This powerful technique allows for a unified beamforming strategy across different pulse sequences and increased flexibility in array signal processing given access to estimates of individual transmit element signals, but trade-offs in image quality between these encodings has not been previously studied. We evaluate in simulation several commonly used time delay and amplitude encodings and investigate optimization of the parameter space for each. Using signal-to-noise ratio, point resolution, and lesion detectability we found trade-offs between focused beams, planewaves, and Hadamard weight encodings. Beams with broader geometries maintained a wider field-of-view after decoding at the cost of signal-to-noise ratio (SNR) and lesion detectability. Focused beams and planewaves showed slightly reduced resolution compared to Hadamard weights in some cases, especially close to the array. We also found overall degraded image quality using random weight or random delay encodings. We validate these findings with experimental phantom imaging for select cases. We believe that these findings provide a starting point for sequence optimization and for improved image quality using the spatial encoding approach for imaging.

Occult Regions of Suppressed Coherence in Liver B-Mode Images.

Ultrasound is an essential tool for diagnosing and monitoring diseases, but it can be limited by poor image quality. Lag-one coherence (LOC) is an image quality metric that can be related to signal-to-noise ratio and contrast-to-noise ratio. In this study, we examine matched LOC and B-mode images of the liver to discern patterns of low image quality, as indicated by lower LOC values, occurring beneath the abdominal wall, near out-of-plane vessels and adjacent to hyperechoic targets such the liver capsule. These regions of suppressed coherence are often occult; they present as temporally stable uniform speckle on B-mode images, but the LOC measurements in these regions suggest substantially degraded image quality. Quantitative characterization of the coherence suppression beneath the abdominal wall reveals a consistent pattern both in simulations and in vivo; sharp drops in coherence occurring beneath the abdominal wall asymptotically recover to a stable coherence at depth. Simulation studies suggest that abdominal wall reverberation clutter contributes to the initial drop in coherence but does not influence the asymptotic LOC value. Clinical implications are considered for contrast loss in B-mode imaging and estimation errors for elastography and Doppler imaging.

Reverberation Clutter Suppression Using 2-D Spatial Coherence Analysis.

Diffuse reverberation clutter often significantly degrades the visibility of abdominal structures. Reverberation clutter acts as a temporally stationary haze that originates from the multiple scattering within the subcutaneous layers and has a narrow spatial correlation length. We recently presented an adaptive beamforming technique, Lag-one Spatial Coherence Adaptive Normalization (LoSCAN), which can recover the contrast suppressed by incoherent noise. LoSCAN successfully suppressed reverberation clutter in numerous clinical examples. However, reverberation clutter is a 3-D phenomenon and can often exhibit a finite partial correlation between receive channels. Due to a strict noise-incoherence assumption, LoSCAN does not eliminate correlated reverberation clutter. This work presents a 2-D matrix array-based LoSCAN method and evaluates matrix-LoSCAN-based strategies to suppress partially correlated reverberation clutter. We validated the proposed matrix LoSCAN method using Field II simulations of a 64×64 symmetric 2-D array. We show that a subaperture beamforming (SAB) method tuned to the direction of noise correlation is an effective method to enhance LoSCAN's performance. We evaluated the efficacy of the proposed methods using fundamental and harmonic channel data acquired from the liver of two healthy volunteers using a 64×16 custom 2-D array. Compared to azimuthal LoSCAN, the proposed approach increased the contrast by up to 5.5 dB and the generalized contrast-to-noise ratio (gCNR) by up to 0.07. We also present analytic models to understand the impact of partially correlated reverberation clutter on LoSCAN images and explain the proposed methods' mechanism of image quality improvement.

Forming Large Effective Ultrasound Arrays Using the Swept Synthetic Aperture Technique.

Ultrasound image quality is intrinsically linked to the hardware used to collect image data. For deep abdominal imaging, diffraction-limited resolution prevents the detection of small targets such as cancerous lesions. Larger ultrasound arrays produce finer lateral image resolution and improved image quality. We introduced a method called "swept synthetic aperture" (SSA) imaging to synthetically create large effective arrays with reduced complexity of both transducer and scanner hardware. A commercial 2-D transducer array and ultrasound scanner were used to form a large effective aperture. Array position and orientation were carefully prescribed throughout a sweep of the transducer using mechanical fixtures to rigidly control the motion. Calibration of the mechanical fixture was measured using a point target phantom and applied in post-processing. Improvements in resolution and contrast as functions of aperture size were measured from point and lesion target phantoms, respectively. SSA imaging presents a technique to both evaluate the performance of large array designs in the presence of clutter-inducing body wall targets and achieve high-quality imaging from reduced-complexity ultrasound hardware.

Ultrasound Lesion Detectability as a Distance Between Probability Measures.

Lesion detectability (LD) quantifies how easily a lesion or target can be distinguished from the background. LD is commonly used to assess the performance of new ultrasound imaging methods. The contrast-to-noise ratio (CNR) is the most popular measure of LD; however, recent work has exposed its vulnerability to manipulations of dynamic range. The generalized CNR (gCNR) has been proposed as a robust histogram-based alternative that is invariant to such manipulations. Here, we identify key shortcomings of CNR and strengths of gCNR as LD metrics for modern beamformers. Using the measure theory, we pose LD as a distance between empirical probability measures (i.e., histograms) and prove that: 1) gCNR is equal to the total variation distance between probability measures and 2) gCNR is one minus the error rate of the ideal observer. We then explore several consequences of measure-theoretic LD in simulation studies. We find that histogram distances depend on bin selection that LD must be considered in the context of spatial resolution and that many histogram distances are invariant under measure-preserving isomorphisms of the sample space (e.g., dynamic range transformations). Finally, we provide a mathematical interpretation for why quantitative values such as contrast ratio (CR), CNR, and signal-to-noise ratio should not be compared between images with different dynamic ranges or underlying units and demonstrate how histogram matching can be used to reenable such quantitative comparisons.

Frequency-Dependent Spatial Coherence in Conventional and Chirp Transmissions.

The development of adaptive imaging techniques is contingent on the accurate and repeatable characterization of ultrasonic image quality. Adaptive transmit frequency selection, filtering, and frequency compounding all offer the ability to improve target conspicuity by balancing the effects of imaging resolution, the signal-to-clutter ratio, and speckle texture, but these strategies rely on the ability to capture image quality at each desired frequency. We investigate the use of broadband linear frequency-modulated transmissions, also known as chirps, to expedite the interrogation of frequency-dependent tissue spatial coherence for real-time implementations of frequency-based adaptive imaging strategies. Chirp-collected measurements of coherence are compared to those acquired by individually transmitted conventional pulses over a range of fundamental and harmonic frequencies, in order to evaluate the ability of chirps to recreate conventionally acquired coherence. Simulation and measurements in a uniform phantom free of acoustic clutter indicate that chirps replicate not only the mean coherence in a region-of-interest but also the distribution of coherence values over frequency. Results from acquisitions in porcine abdominal and human liver models show that prediction accuracy improves with chirp length. Chirps are also able to predict frequency-dependent decreases in coherence in both porcine abdominal and human liver models for fundamental and pulse inversion harmonic imaging. This work indicates that the use of chirps is a viable strategy to improve the efficiency of variable frequency coherence mapping, thus presenting an avenue for real-time implementations for frequency-based adaptive strategies.

Development of a novel intravascular oxygenator catheter: Oxygen mass transfer properties across nonporous hollow fiber membranes.

Despite hypoxic respiratory failure representing a large portion of total hospitalizations and healthcare spending worldwide, therapeutic options beyond mechanical ventilation are limited. We demonstrate the technical feasibility of providing oxygen to a bulk medium, such as blood, via diffusion across nonporous hollow fiber membranes (HFMs) using hyperbaric oxygen. The oxygen transfer across Teflon® membranes was characterized at oxygen pressures up to 2 bars in both a stirred tank vessel (CSTR) and a tubular device mimicking intravenous application. Fluxes over 550 ml min-1 m-2 were observed in well-mixed systems, and just over 350 ml min-1 m-2 in flow through tubular systems. Oxygen flux was proportional to the oxygen partial pressure inside the HFM over the tested range and increased with mixing of the bulk liquid. Some bubbles were observed at the higher pressures (1.9 bar) and when bulk liquid dissolved oxygen concentrations were high. High-frequency ultrasound was applied to detect and count individual bubbles, but no increase from background levels was detected during lower pressure operation. A conceptual model of the oxygen transport was developed and validated. Model parametric sensitivity studies demonstrated that diffusion through the thin fiber walls was a significant resistance to mass transfer, and that promoting convection around the fibers should enable physiologically relevant oxygen supply. This study indicates that a device is within reach that is capable of delivering greater than 10% of a patient's basal oxygen needs in a configuration that readily fits intravascularly.

Histogram Matching for Visual Ultrasound Image Comparison.

The widespread development of new ultrasound image formation techniques has created a need for a standardized methodology for comparing the resulting images. Traditional methods of evaluation use quantitative metrics to assess the imaging performance in specific tasks, such as point resolution or lesion detection. Quantitative evaluation is complicated by unconventional new methods and nonlinear transformations of the dynamic range of data and images. Transformation-independent image metrics have been proposed for quantifying task performance. However, clinical ultrasound still relies heavily on visualization and qualitative assessment by expert observers. We propose the use of histogram matching to better assess differences across image formation methods. We briefly demonstrate the technique using a set of sample beamforming methods and discuss the implications of such image processing. We present variations of histogram matching and provide code to encourage the application of this method within the imaging community.

Resolution and Speckle Reduction in Cardiac Imaging.

Cardiac imaging depends on clear visualization of several different structural and functional components to determine left ventricular and overall cardiac health. Ultrasound imaging is confounded by the characteristic speckle texture resulting from subwavelength scatterers in tissues, which is similar to a multiplicative noise on underlying tissue structure. Reduction of this texture can be achieved through physical means, such as spatial or frequency compounding, or through adaptive image processing. Techniques in both categories require a tradeoff of resolution for speckle texture reduction, which together contribute to overall image quality and diagnostic value. We evaluate this tradeoff for cardiac imaging tasks using spatial compounding as an exemplary speckle reduction method. Spatial compounding averages the decorrelated speckle patterns formed by views of a target from multiple subaperture positions to reduce the texture at the expense of active aperture size (and, in turn, lateral resolution). We demonstrate the use of a novel synthetic aperture focusing technique to decompose harmonic backscattered data from focused beams to their aperture-domain spatial frequency components to enable combined transmit and receive compounding. This tool allows the evaluation of matched data sets from a single acquisition over a wide range of spatial compounding conditions. We quantified the tradeoff between resolution and texture reduction in an imaging phantom and demonstrated improved lesion detectability with increasing levels of spatial compounding. We performed a cardiac ultrasound on 25 subjects to evaluate the degree of compounding useful for diagnostic imaging. Of these, 18 subjects were included in both qualitative and quantitative analysis. We found that compounding improved detectability of the endocardial border according to the generalized contrast-to-noise ratio in all cases, and more aggressive compounding made further improvements in ten out of 18 cases. Three expert reviewers evaluated the images for their usefulness in several diagnostic tasks and ranked four compounding conditions ("none," "low," "medium," and "high"). Contrary to the quantitative metrics that suggested the use of high levels of compounding, the reviewers determined that "low" was usually preferred (77.9%), while "none" or "medium" was selected in 21.2% of cases. We conclude with a brief discussion of the generalization of these results to other speckle reduction methods using the imaging phantom data.

An Automated ALARA Method for Ultrasound: An Obstetric Ultrasound Feasibility Study.

OBJECTIVES: Ultrasound users are advised to observe the ALARA (as low as reasonably achievable) principle, but studies have shown that most do not monitor acoustic output metrics. We developed an adaptive ultrasound method that could suggest acoustic output levels based on real-time image quality feedback using lag-one coherence (LOC). METHODS: Lag-one coherence as a function of the mechanical index (MI) was assessed in 35 healthy volunteers in their second trimester of pregnancy. While imaging the placenta or the fetal abdomen, the system swept through 16 MI values ranging from 0.15 to 1.20. The LOC-versus-MI data were fit with a sigmoid curve, and the ALARA MI was selected as the point at which the fit reached 98% of its maximum. RESULTS: In this study, the ALARA MI values were between 0.35 and 1.03, depending on the acoustic window. Compared to a default MI of 0.8, the pilot acquisitions suggested a lower ALARA MI 80% of the time. The contrast, contrast-to-noise ratio, generalized contrast-to-noise ratio, and LOC all followed sigmoidal trends with an increasing MI. The R2 of the fit was statistically significantly greater for LOC than the other metrics (P < .017). CONCLUSIONS: These results suggest that maximum image quality can be achieved with acoustic output levels lower than the US Food and Drug Administration limits in many cases, and an automated tool could be used in real time to find the ALARA MI for specific imaging conditions. Our results support the feasibility of an automated, LOC-based implementation of the ALARA principle for obstetric ultrasound.

Coherence-based quantification of acoustic clutter sources in medical ultrasound.

The magnitudes by which aberration and incoherent noise sources, such as diffuse reverberation and thermal noise, contribute to degradations in image quality in medical ultrasound are not well understood. Theory predicting degradations in spatial coherence and contrast in response to combinations of incoherent noise and aberration levels is presented, and the theoretical values are compared to those from simulation across a range of magnitudes. A method to separate the contributions of incoherent noise and aberration in the spatial coherence domain is also presented and applied to predictions for losses in contrast. Results indicate excellent agreement between theory and simulations for beamformer gain and expected contrast loss due to incoherent noise and aberration. Error between coherence-predicted aberration contrast loss and measured contrast loss differs by less than 1.5 dB on average, for a -20 dB native contrast target and aberrators with a range of root-mean-square time delay errors. Results also indicate in the same native contrast target the contribution of aberration to contrast loss varies with channel signal-to-noise ratio (SNR), peaking around 0 dB SNR. The proposed framework shows promise to improve the standard by which clutter reduction strategies are evaluated.