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

Conventional medical ultrasound systems utilizing focus-beam imaging generally acquire multi-channel 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 nine-fold and four-fold, 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.

Improving Plasmonic Photothermal Therapy of Lung Cancer Cells with Anti-EGFR Targeted Gold Nanorods.

Lung cancer is a particularly difficult form of cancer to diagnose and treat, due largely to the inaccessibility of tumours and the limited available treatment options. The development of plasmonic gold nanoparticles has led to their potential use in a large range of disciplines, and they have shown promise for applications in this area. The ability to functionalise these nanoparticles to target to specific cancer types, when combined with minimally invasive therapies such as photothermal therapy, could improve long-term outcomes for lung cancer patients. Conventionally, continuous wave lasers are used to generate bulk heating enhanced by gold nanorods that have accumulated in the target region. However, there are potential negative side-effects of heat-induced cell death, such as the risk of damage to healthy tissue due to heat conducting to the surrounding environment, and the development of heat and drug resistance. In this study, the use of pulsed lasers for photothermal therapy was investigated and compared with continuous wave lasers for gold nanorods with a surface plasmon resonance at 850 nm, which were functionalised with anti-EGFR antibodies. Photothermal therapy was performed with both laser systems, on lung cancer cells (A549) in vitro populations incubated with untargeted and targeted nanorods. It was shown that the combination of pulse wave laser illumination of targeted nanoparticles produced a reduction of 93 % ± 13 % in the cell viability compared with control exposures, which demonstrates a possible application for minimally invasive therapies for lung cancer.

Trapped air metamaterial concept for ultrasonic sub-wavelength imaging in water.

Acoustic metamaterials constructed from conventional base materials can exhibit exotic phenomena not commonly found in nature, achieved by combining geometrical and resonance effects. However, the use of polymer-based metamaterials that could operate in water is difficult, due to the low acoustic impedance mismatch between water and polymers. Here we introduce the concept of "trapped air" metamaterial, fabricated via vat photopolymerization, which makes ultrasonic sub-wavelength imaging in water using polymeric metamaterials highly effective. This concept is demonstrated for a holey-structured acoustic metamaterial in water at 200-300 kHz, via both finite element modelling and experimental measurements, but it can be extended to other types of metamaterials. The new approach, which outperforms the usual designs of these structures, indicates a way forward for exploiting additive-manufacturing for realising polymer-based acoustic metamaterials in water at ultrasonic frequencies.

HIFU Power Monitoring Using Combined Instantaneous Current and Voltage Measurement.

During high-intensity focused ultrasound (HIFU) therapy, it is important that the electrical power delivered to the transducer is monitored to avoid underexposure or overexposure, ensure patient safety, and to protect the transducer itself. Due to ease of measurement, the transducer's potential difference may be as an indicator of power delivery. However, even when a transducer's complex impedance is well characterized at small amplitudes and matching networks are used, voltage-only (VO) monitoring cannot account for the presence of drive waveform distortion, changes to the acoustic path, or damage to the transducer. In this study, combined current and voltage (CCV) is proposed as a magnetic resonance imaging (MRI)-compatible, miniature alternative to bidirectional power couplers, which is compatible with switched amplifiers. For CCV power measurement, current probe data were multiplied by the voltage waveform and integrated in the frequency domain. Transducer efficiency was taken into account to predict acoustic power. The technique was validated with a radiation force balance (RFB). When using a typical HIFU transducer and amplifier, VO predictions and acoustic power had a maximum difference of 20%. However, under the same conditions, CCV only had a maximum difference of 5%. The technique was applied to several lesioning experiments and it was shown that when VO was used as a control between two amplifiers, there was up to a 38% difference in lesion area. This greatly reduced to a maximum of 5% once CCV was used instead. These results demonstrate that CCV can accurately predict real-time electrical power delivery, leading to safer HIFU treatments.

Encapsulation of Emulsion Droplets with Metal Shells for Subsequent Remote, Triggered Release.

A two-step method to encapsulate an oil core with an impermeable shell has been developed. A thin metallic shell is deposited on the surface of emulsion droplets stabilized by metal nanoparticles. This thin shell is shown to prevent diffusion of the oil from within the core of the metal-shell microcapsules when placed in a continuous phase that fully dissolves the oil. The stabilizing nanoparticles are sterically stabilized by poly(vinyl pyrrolidone) chains and are here used as a catalyst/nucleation site at the oil-water interface to grow a secondary metal shell on the emulsion droplets via an electroless deposition process. This method provides the simplest scalable route yet to synthesize impermeable microcapsules with the added benefit that the final structure allows for drastically improving the overall volume of the encapsulated core to, in this case, >99% of the total volume. This method also allows for very good control over the microcapsule properties, and here we demonstrate our ability to tailor the final microcapsule density, capsule diameter, and secondary metal film thickness. Importantly, we also demonstrate that such impermeable microcapsule metal shells can be remotely fractured using ultrasound-based devices that are commensurate with technologies currently used in medical applications, which demonstrate the possibility to adapt these microcapsules for the delivery of cytotoxic drugs.

Molecular Effects of Glycerol on Lipid Monolayers at the Gas-Liquid Interface: Impact on Microbubble Physical and Mechanical Properties.

The production and stability of microbubbles (MBs) is enhanced by increasing the viscosity of both the formation and storage solution, respectively. Glycerol is a good candidate for biomedical applications of MBs, since it is biocompatible, although the exact molecular mechanisms of its action is not fully understood. Here, we investigate the influence glycerol has on lipid-shelled MB properties, using a range of techniques. Population lifetime and single bubble stability were studied using optical microscopy. Bubble stiffness measured by AFM compression is compared with lipid monolayer behavior in a Langmuir-Blodgett trough. We deduce that increasing glycerol concentrations enhances stability of MB populations through a 3-fold mechanism. First, binding of glycerol to lipid headgroups in the interfacial monolayer up to 10% glycerol increases MB stiffness but has limited impact on shell resistance to gas permeation and corresponding MB lifetime. Second, increased solution viscosity above 10% glycerol slows down the kinetics of gas transfer, markedly increasing MB stability. Third, above 10%, glycerol induces water structuring around the lipid monolayer, forming a glassy layer which also increases MB stiffness and resistance to gas loss. At 30% glycerol, the glassy layer is ablated, lowering the MB stiffness, but MB stability is further augmented. Although the molecular interactions of glycerol with the lipid monolayer modulate the MB lipid shell properties, MB lifetime continually increases from 0 to 30% glycerol, indicating that its viscosity is the dominant effect on MB solution stability. This three-fold action and biocompatibility makes glycerol ideal for therapeutic MB formation and storage and gives new insight into the action of glycerol on lipid monolayers at the gas-liquid interface.

Supply-Inverted Bipolar Pulser and Tx/Rx Switch for CMUTs Above the Process Limit for High Pressure Pulse Generation.

A combined supply-inverted bipolar pulser and a Tx/Rx switch is proposed to drive capacitive micromachined ultrasonic transducers (CMUTs). The supply-inverted bipolar pulser adopts a bootstrap circuit combined with stacked transistors, which guarantees high voltage (HV) operation above the process limit without lowering device reliability. This circuit generates an output signal with a peak-to-peak voltage that is almost twice the supply level. It generates a bipolar pulse with only positive supply voltages. The Tx/Rx switch adopts a diode-bridge structure with the protection scheme dedicated to this proposed pulser. A proof- of-concept ASIC prototype has been implemented in 0.18-µm HV CMOS/DMOS technology with 60 V devices. Measurement results show that the proposed pulser can safely generate a bipolar pulse of -34.6 to 45 V, from a single 45 V supply voltage. The Tx/Rx switch blocks the HV bipolar pulse, resulting in less than 1.6 V at the input of the receiver. Acoustic measurements are performed connecting the pulser to CMUTs with 2 pF capacitance and 8 MHz center frequency. The variation of acoustic output pressures for different pulse shapes were simulated with the large signal CMUT model and compared with the experimental results for transmit pressure optimization. A potential implementation of the methods using MEMS fabrication methods is also described.

Optimising gold nanorods for photoacoustic imaging in vitro.

Gold nanorods (AuNRs) can be synthesised with different sizes but similar aspect ratios and therefore similar surface plasmon resonances (SPRs). Their strong optical absorbance governed by their SPRs facilitates their ability to be used as molecular-targeted contrast agents for photoacoustic (PA) imaging. The size of AuNRs has an effect on the PA conversion efficiency, melting threshold, and cytotoxicity, indicating that size can have a significant impact on overall biomedical efficacy. We investigated these factors for four different AuNRs (widths of 10, 25, 40 and 50 nm) all with SPRs of 815 ± 26 nm. A size-dependent linear relationship between fluence and PA amplitude was observed, along with particle melting. Reshaping was confirmed via transmission electron microscopy and spectrophotometry at a laser fluence of 11 ± 1.7 mJ cm-2, 20 ± 2.2 mJ cm-2, and 40 ± 2.6 mJ cm-2. Cytotoxicity was tested on lung cancer cells (A549) via a colourimetric assay at a maximum concentration of 3 × 1010 NP ml-1. Results demonstrate the 40 nm and 50 nm AuNRs produced the highest signal for equivalent particle numbers, but displayed the highest toxicity. Conversely, the 10 nm AuNRs were the most efficient photoacoustic converters, at equivalent total mass. This study demonstrates the importance of AuNR size and concentration on selection of AuNRs for their eventual clinical use.

High-Frame-Rate Contrast-Enhanced Echocardiography Using Diverging Waves: 2-D Motion Estimation and Compensation.

Combining diverging ultrasound waves and microbubbles could improve contrast-enhanced echocardiography (CEE), by providing enhanced temporal resolution for cardiac function assessment over a large imaging field of view. However, current image formation techniques using coherent summation of echoes from multiple steered diverging waves (DWs) are susceptible to tissue and microbubble motion artifacts, resulting in poor image quality. In this study, we used correlation-based 2-D motion estimation to perform motion compensation for CEE using DWs. The accuracy of this motion estimation method was evaluated with Field II simulations. The root-mean-square velocity errors were 5.9% ± 0.2% and 19.5% ± 0.4% in the axial and lateral directions, when normalized to the maximum value of 62.8 cm/s which is comparable to the highest speed of blood flow in the left ventricle (LV). The effects of this method on image contrast ratio (CR) and contrast-to-noise ratio (CNR) were tested in vitro using a tissue mimicking rotating disk with a diameter of 10 cm. Compared against the control without motion compensation, a mean increase of 12 dB in CR and 7 dB in CNR were demonstrated when using this motion compensation method. The motion correction algorithm was tested in vivo on a CEE data set acquired with the Ultrasound Array Research Platform II performing coherent DW imaging. Improvement of the B-mode and contrast-mode image quality with cardiac motion and blood flow-induced microbubble motion was achieved. The results of motion estimation were further processed to interpret blood flow in the LV. This allowed for a triplex cardiac imaging technique, consisting of B mode, contrast mode, and 2-D vector flow imaging with a high frame rate of 250 Hz.

A Reduced-Wire ICE Catheter ASIC With Tx Beamforming and Rx Time-Division Multiplexing.

This paper presents a single chip reduced-wire active catheter application-specific integrated circuit (ASIC), equipped with programmable transmit (Tx) beamforming and receive (Rx) time-division multiplexing (TDM). The proposed front-end ASIC is designed for driving a 64-channel one-dimensional transducer array in intracardiac echocardiography (ICE) ultrasound catheters. The ASIC is implemented in 60 V 0.18-µm HV-BCD technology, integrating Tx beamformers with high voltage pulsers and Rx front end in the same chip, which occupies 2.6 × 11 mm2 that can fit in the catheter size of 9 F (<3 mm). The proposed system reduces the number of wires from >64 to only 22 by integrating Tx beamformer that is programmable using a single low-voltage differential signaling data line. In Rx mode, the system uses 8:1 TDM with direct digital demultiplexing providing raw channel data that enables dynamic Rx beamforming using individual array elements. This system has been successfully used for B-mode imaging on standard ultrasound phantom with 401 mW of average power consumption. The ASIC has a compact element pitch-matched layout, which is also compatible with capacitive micromachined ultrasound transducer on CMOS application. This system addresses cable number and dimensional restrictions in catheters to enable ICE imaging under magnetic resonance imaging by reducing radio frequency induced heating.

HIFU Drive System Miniaturization Using Harmonic Reduced Pulsewidth Modulation.

Switched excitation has the potential to improve on the cost, efficiency, and size of the linear amplifier circuitry currently used in high-intensity focused ultrasound (HIFU) systems. Existing switching schemes are impaired by high harmonic distortion or lack array apodisation capability, so require adjustable supplies and/or large power filters to be useful. A multilevel pulsewidth modulation (PWM) topology could address both of these issues but the switching-speed limitations of transistors mean that there are a limited number of pulses available in each waveform cycle. In this study, harmonic reduction PWM (HRPWM) is proposed as an algorithmic solution to the design of switched waveforms. Its appropriateness for HIFU was assessed by design of a high power five-level unfiltered amplifier and subsequent thermal-only lesioning of ex vivo chicken breast. Three switched waveforms of different electrical powers (16, 26, 35 W) were generated using the HRPWM algorithm. Lesion sizes were measured and compared with those made at the same electrical power using a linear amplifier and bi-level excitation. HRPWM produced symmetric, thermal-only lesions that were the same size as their linear amplifier equivalents ( ). At 16 W, bi-level excitation produced smaller lesions but at higher power levels large transients in the acoustic waveform nucleated undesired cavitation. These results demonstrate that HRPWM can minimize HIFU drive circuity size without the need for filters to remove harmonics or adjustable power supplies to achieve array apodisation.