Wavenumber Beamforming With Sub-Nyquist Sampling for Focus-Beam Ultrasound Imaging.

Conventional medical ultrasound systems utilizing focus-beam imaging generally acquire multichannel echoes at frequencies in tens of megahertz after each transmission, resulting in significant data volumes for digital beamforming. Furthermore, integrating state-of-the-art beamformers with transmission compounding substantially increases the beamforming complexity. Except for upgrading the hardware system for better computing performance, an alternative strategy for accelerating ultrasound data processing is the wavenumber beamforming algorithm, which has not been effectively extended to synthetic focus-beam transmission imaging. In this study, we propose a novel wavenumber beamforming algorithm to efficiently reduce the computational complexity of traditional focus-beam ultrasound imaging. We further integrate the wavenumber beamformer with a sub-Nyquist sampling framework, enabling ultrasonic systems to acquire echoes within the active bandwidth at significantly reduced rates. Simulation and experimental results indicate that the proposed beamformer offers image quality comparable to the state-of-the-art spatiotemporal beamformer while reducing the sampling rate and runtime by nearly ninefold and fourfold, respectively. The proposed approach would potentially help the development of low-power consumption and portable ultrasound systems.

"Smart Knee Implants: An Overview of Current Technologies and Future Possibilities".

Background: This article focuses on clinical implementation of smart knee implants for total knee replacement and the future development of smart implant technology. With the number of total knee replacements undertaken growing worldwide, smart implants incorporating embedded sensor technology offer opportunity to improve post-operative recovery, reducing implant failure rates, and increasing overall patient satisfaction. Methods: A literature review on smart implants, historical prototypes, current clinically available smart implants, and the future potential for conventional implant instrumentation with embedded sensors and electronics was undertaken. Results: The overview of current and future technology describes use cases for various diagnostic and therapeutic treatment solutions. Conclusion: Smart knee implants are at an early development stage, with the first generation of smart implants being available to patients and with more novel technologies under development.

Enhancement of Ultrasound B-Mode Image Quality Using Nonlinear Filtered-Multiply-and-Sum Compounding for Improved Carotid Artery Segmentation.

In ultrasound B-mode imaging, the axial resolution (AR) is commonly determined by the duration or bandwidth of an excitation signal. A shorter-duration pulse will produce better resolution compared to a longer one but with compromised penetration depth. Instead of relying on the pulse duration or bandwidth to improve the AR, an alternative method termed filtered multiply and sum (FMAS) has been introduced in our previous work. For spatial-compounding, FMAS uses the autocorrelation technique as used in filtered-delay multiply and sum (FDMAS), instead of conventional averaging. FMAS enables a higher frame rate and less computational complexity than conventional plane-wave compound imaging beamformed with delay and sum (DAS) and FDMAS. Moreover, it can provide an improved contrast ratio and AR. In previous work, no explanation was given on how FMAS was able to improve the AR. Thus, in this work, we discuss in detail the theory behind the proposed FMAS algorithm and how it is able to improve the spatial resolution mainly in the axial direction. Simulations, experimental phantom measurements and in vivo studies were conducted to benchmark the performance of the proposed method. We also demonstrate how the suggested new algorithm may be used in a practical biomedical imaging application. The balloon snake active contour segmentation technique was applied to the ultrasound B-mode image of a common carotid artery produced with FMAS. The suggested method is capable of reducing the number of iterations for the snake to settle on the region-of-interest contour, accelerating the segmentation process.

Integrated Hybrid Sub-Aperture Beamforming and Time-Division Multiplexing for Massive Readout in Ultrasound Imaging.

This paper demonstrates hybrid sub-aperture beamforming (SAB) with time-division multiplexing (TDM) for massive interconnect reduction in ultrasound imaging systems. A single-chip front-end system prototype has been fabricated in 180-nm HV BCD technology that combines 5×1 SAB with 8×1 TDM to efficiently reduce the number of receive signal interconnects by a factor of 40. The system includes on-chip high-voltage (HV) pulsers capable of generating unipolar pulses up to 70 V in transmit (TX) mode. The receiver (RX) chain consists of a T/R switch, a variable-gain low-noise amplifier (VG-LNA) with 4-step gain control (15-32 dB) for time-gain compensation followed by a programmable switched-capacitor analog delay-and-sum beamformer. The proof-of-concept prototype operates at a 200-MHz clock frequency and the SAB provides 32-step fine delays with a maximum delay of 310 ns corresponding to better than λ/20 delay quantization at 5 MHz. With these specifications, the SAB is capable of beam steering from 0 ° to 45 ° for a 5-element subarray with 150-micron pitch ( λ/2), providing a near-ideal phased array imaging performance. The sub-aperture beamformer is followed by the TDM system where each of the 8 channels is sampled at a rate of 25 MS/s after an anti-aliasing bandpass filter. The full functionality of the prototype chip is validated through electrical and acoustic measurements on a 1-D capacitive micromachined ultrasonic transducer (CMUT) array designed for intracardiac echocardiography (ICE).

Optimised polymer trapped-air lenses for ultrasound focusing in water exploiting Fabry-Pérot resonance.

The concept of employing air volumes trapped inside polymer shells to make a lens for ultrasound focusing in water is investigated. The proposed lenses use evenly-spaced concentric rings, each having an air-filled polymer shell construction, defining concentric water-filled channels. Numerical simulations and experiments have shown that a plane wave can be focused, and that the amplification can be boosted by Fabry-Pérot resonances within the water channels with an appropriate choice of the lens thickness. The effect of the polymer shell thickness and the depth of the channels is discussed, as these factors can affect the geometry and hence the frequency of operation. The result was a lens with a Full Width at Half Maximum value of 0.65 of a wavelength at the focus. Results obtained on a metal-based counterpart are also shown for comparison. An advantage of this polymeric design is that it is easily constructed via additive manufacturing. This study shows that trapped-air lenses made of polymer are suitable for ultrasound focusing in water near 500 kHz.

Protein-conjugated microbubbles for the selective targeting of S. aureus biofilms.

Staphylococcus aureus (S. aureus) is an important human pathogen and a common cause of bloodstream infection. The ability of S. aureus to form biofilms, particularly on medical devices, makes treatment difficult, as does its tendency to spread within the body and cause secondary foci of infection. Prolonged courses of intravenous antimicrobial treatment are usually required for serious S. aureus infections. This work investigates the in vitro attachment of microbubbles to S. aureus biofilms via a novel Affimer protein, AClfA1, which targets the clumping factor A (ClfA) virulence factor - a cell-wall anchored protein associated with surface attachment. Microbubbles (MBs) are micron-sized gas-filled bubbles encapsulated by a lipid, polymer, or protein monolayer or other surfactant-based material. Affimers are small (∼12 kDa) heat-stable binding proteins developed as replacements for antibodies. The binding kinetics of AClfA1 against S. aureus ClfA showed strong binding affinity (KD = 62 ± 3 nM). AClfA1 was then shown to bind S. aureus biofilms under flow conditions both as a free ligand and when bound to microparticles (polymer beads or microbubbles). Microbubbles functionalized with AClfA1 demonstrated an 8-fold increase in binding compared to microbubbles functionalized with an identical Affimer scaffold but lacking the recognition groups. Bound MBs were able to withstand flow rates of 250 µL/min. Finally, ultrasound was applied to burst the biofilm bound MBs to determine whether this would lead to biofilm biomass loss or cell death. Application of a 2.25 MHz ultrasound profile (with a peak negative pressure of 0.8 MPa and consisting of a 22-cycle sine wave, at a pulse repetition rate of 10 kHz) for 2 s to a biofilm decorated with targeted MBs, led to a 25% increase in biomass loss and a concomitant 8% increase in dead cell count. The results of this work show that Affimers can be developed to target S. aureus biofilms and that such Affimers can be attached to contrast agents such as microbubbles or polymer beads and offer potential, with some optimization, for drug-free biofilm treatment.

Holey-structured tungsten metamaterials for broadband ultrasonic sub-wavelength imaging in water.

Metamaterials exhibiting Fabry-Pérot resonances are shown to achieve ultrasonic imaging of a sub-wavelength aperture in water immersion across a broad bandwidth. Holey-structured metamaterials of different thickness were additively manufactured using a tungsten substrate and selective laser melting, tungsten being chosen so as to create a significant acoustic impedance mismatch with water. Both broadband metamaterial behavior and sub-wavelength imaging in water are demonstrated experimentally and validated with finite element simulations over the 200-300 kHz range.

High-Power Gallium Nitride HIFU Transmitter With Integrated Real-Time Current and Voltage Measurement.

High-Intensity Focused Ultrasound (HIFU) therapy provides a non-invasive technique with which to destroy cancerous tissue without using ionizing radiation. To drive large single-element High-Intensity Focused Ultrasound (HIFU) transducers, ultrasound transmitters capable of delivering high powers at relevant frequencies are required. The acoustic power delivered to a transducers focal region will determine the treated area, and due to safety concerns and intervening layers of attenuation, control of this output power is critical. A typical setup involves large inefficient linear power amplifiers to drive the transducer. Switched mode transmitters allow for a more compact drive system with higher efficiencies, with multi-level transmitters allowing control over the output power. Real-time monitoring of power delivered can avoid damage to the transducer and injury to patients due to over treatment, and allow for precise control over the output power. This study demonstrates a transformer-less, high power, switched mode transmit transmitter based on Gallium-Nitride (GaN) transistors that is capable of delivering peak powers up to 1.8 kW at up to 600 Vpp, while operating at frequencies from DC to 5 MHz. The design includes a 12 b 16 MHz floating Current/Voltage (IV) measurement circuit to allow real-time high-side monitoring of the power delivered to the transducer allowing use with multi-element transducers.

Ultrasound-triggered therapeutic microbubbles enhance the efficacy of cytotoxic drugs by increasing circulation and tumor drug accumulation and limiting bioavailability and toxicity in normal tissues.

Most cancer patients receive chemotherapy at some stage of their treatment which makes improving the efficacy of cytotoxic drugs an ongoing and important goal. Despite large numbers of potent anti-cancer agents being developed, a major obstacle to clinical translation remains the inability to deliver therapeutic doses to a tumor without causing intolerable side effects. To address this problem, there has been intense interest in nanoformulations and targeted delivery to improve cancer outcomes. The aim of this work was to demonstrate how vascular endothelial growth factor receptor 2 (VEGFR2)-targeted, ultrasound-triggered delivery with therapeutic microbubbles (thMBs) could improve the therapeutic range of cytotoxic drugs. Methods: Using a microfluidic microbubble production platform, we generated thMBs comprising VEGFR2-targeted microbubbles with attached liposomal payloads for localised ultrasound-triggered delivery of irinotecan and SN38 in mouse models of colorectal cancer. Intravenous injection into tumor-bearing mice was used to examine targeting efficiency and tumor pharmacodynamics. High-frequency ultrasound and bioluminescent imaging were used to visualise microbubbles in real-time. Tandem mass spectrometry (LC-MS/MS) was used to quantitate intratumoral drug delivery and tissue biodistribution. Finally, 89Zr PET radiotracing was used to compare biodistribution and tumor accumulation of ultrasound-triggered SN38 thMBs with VEGFR2-targeted SN38 liposomes alone. Results: ThMBs specifically bound VEGFR2 in vitro and significantly improved tumor responses to low dose irinotecan and SN38 in human colorectal cancer xenografts. An ultrasound trigger was essential to achieve the selective effects of thMBs as without it, thMBs failed to extend intratumoral drug delivery or demonstrate enhanced tumor responses. Sensitive LC-MS/MS quantification of drugs and their metabolites demonstrated that thMBs extended drug exposure in tumors but limited exposure in healthy tissues, not exposed to ultrasound, by persistent encapsulation of drug prior to elimination. 89Zr PET radiotracing showed that the percentage injected dose in tumors achieved with thMBs was twice that of VEGFR2-targeted SN38 liposomes alone. Conclusions: thMBs provide a generic platform for the targeted, ultrasound-triggered delivery of cytotoxic drugs by enhancing tumor responses to low dose drug delivery via combined effects on circulation, tumor drug accumulation and exposure and altered metabolism in normal tissues.

Contrast-Enhanced High-Frame-Rate Ultrasound Imaging of Flow Patterns in Cardiac Chambers and Deep Vessels.

Cardiac function and vascular function are closely related to the flow of blood within. The flow velocities in these larger cavities easily reach 1 m/s, and generally complex spatiotemporal flow patterns are involved, especially in a non-physiologic state. Visualization of such flow patterns using ultrasound can be greatly enhanced by administration of contrast agents. Tracking the high-velocity complex flows is challenging with current clinical echographic tools, mostly because of limitations in signal-to-noise ratio; estimation of lateral velocities; and/or frame rate of the contrast-enhanced imaging mode. This review addresses the state of the art in 2-D high-frame-rate contrast-enhanced echography of ventricular and deep-vessel flow, from both technological and clinical perspectives. It concludes that current advanced ultrasound equipment is technologically ready for use in human contrast-enhanced studies, thus potentially leading to identification of the most clinically relevant flow parameters for quantifying cardiac and vascular function.