Gold nanoparticle nucleated cavitation for enhanced high intensity focused ultrasound therapy

High intensity focused ultrasound (HIFU) or focused ultrasound surgery is a non-invasive technique for the treatment of cancerous tissue, which is limited by difficulties in getting real-time feedback on treatment progress and long treatment durations. The formation and activity of acoustic cavitation, specifically inertial cavitation, during HIFU exposures has been demonstrated to enhance heating rates. However, without the introduction of external nuclei its formation an activity can be unpredictable, and potentially counter-productive. In this study, a combination of pulse laser illumination (839 nm), HIFU exposures (3.3 MHz) and plasmonic gold nanorods (AuNR) was demonstrated as a new approach for the guidance and enhancement of HIFU treatments. For imaging, short duration HIFU pulses (10 μs) demonstrated broadband acoustic emissions from AuNR nucleated cavitation with a signal-to-noise ranging from 5–35 dB for peak negative pressures between 1.19–3.19  ±  0.01 MPa. In the absence of either AuNR or laser illumination these emissions were either not present or lower in magnitude (e.g. 5 dB for 3.19 MPa). Continuous wave (CW) HIFU exposures for 15 s, were then used to generate thermal lesions for peak negative pressures from 0.2–2.71  ±  0.01 MPa at a fluence of 3.4 mJ ${\rm cm}^{-2}$ . Inertial cavitation dose (ICD) was monitored during all CW exposures, where exposures combined with both laser illumination and AuNRs resulted in the highest level of detectable emissions. This parameter was integrated over the entire exposure to give a metric to compare with measured thermal lesion area, where it was found that a minimum total ICD of $1.5 \times 10^3$ a.u. was correlated with the formation of thermal lesions in gel phantoms. Furthermore, lesion area (mm2) was increased for equivalent exposures without either AuNRs or laser illumination. Once combined with cancer targeting AuNRs this approach could allow for the future theranostic use of HIFU, such as providing the ability to identify and treat small multi-focal cancerous regions with minimal damage to surrounding healthy tissue

Phonon transport in large scale carbon-based disordered materials: Implementation of an efficient order-N and real-space Kubo methodology

We have developed an efficient order-N real-space Kubo approach for the calculation of the phonon conductivity which outperforms state-of-the-art alternative implementations based on the Green's function formalism. The method treats efficiently the time-dependent propagation of phonon wave packets in real space, and this dynamics is related to the calculation of the thermal conductance. Without loss of generality, we validate the accuracy of the method by comparing the calculated phonon mean free paths in disordered carbon nanotubes (isotope impurities) with other approaches, and further illustrate its upscalability by exploring the thermal conductance features in large width edge-disordered graphene nanoribbons (up to ~20 nm), which is out of the reach of more conventional techniques. We show that edge-disorder is the most important scattering mechanism for phonons in graphene nanoribbons with realistic sizes and thermal conductance can be reduced by a factor of ~10.Comment: Accepted for publication in Physical Review B - Rapid Communication

Wideband Excitation of Microbubbles to Maximize the Sonoporation Efficiency and Contrast in Ultrasound Imaging

The importance of the excitation bandwidth is well known in diagnostic ultrasound imaging. However, the effect of excitation bandwidth in therapeutic applications of microbubbles has been mostly overlooked. A majority of contrast agent production techniques generate polydisperse microbubble populations, so a wide range of resonance frequencies exist. Therefore, wideband excitation is necessary to fully utilize microbubble resonance behavior and maximize the reradiated energy from a microbubble population, both for imaging and therapy. Oscillations of sixty SonoVue microbubbles in proximity of a rigid boundary were captured on a high speed camera at 3 Mfps, excited with a peak negative pressure of 50 kPa at 1 MHz. Measurements were analyzed according to their peak radiated pressure, radial oscillations, root mean squared pressure, and shear stress generated by microbubbles. Results showed that long duration and wideband excitation at low intensity levels was preferable for sonoporation, where microbubbles can be driven in a stable oscillation state without experiencing inertial cavitation or destruction

A miniature HIFU excitation scheme to eliminate switching-induced grating lobes and nullify hard tissue attenuation

Phased array transducers are increasingly prevalent in a therapeutic contex as they facilitate precise control of the beam intensity and focus. To produce enough acoustic energy for ablation, large and costly amplifiers are required. Miniaturised switched circuits provide an alternative that is both more cost effective and more efficient. However, the high Q factor and curved geometry of a therapeutic transducer lends itself to grating lobes that deposit energy in undesirable areas when driven with switched circuitry. In this work, harmonic reduction pulse with modulation (HRPWM) is applied to a simulation of a therapeutic array. An array was simulated along with a skull that varied in attenuation. A number of switching schemes were tested and where possible, their amplitude was adjusted to reduce pressure variation in the acoustic field after propagation through the skull. Of the switched schemes tested, HRPWM performed best; reducing harmonically induced grating lobes by 12 dB and limiting pressure field variance to 0.1 dB which increases intensity at the focal point and makes therapy more efficient

Enhancement of contrast and resolution of B-mode plane wave imaging (PWI) with non-linear filtered delay multiply and sum (FDMAS) beamforming

FDMAS has been successfully used in microwave imaging for breast cancer detection. FDMAS gained its popularity due to its capability to produce results faster than any other adaptive beamforming technique such as minimum variance (MV) which requires higher computational complexity. The average computational time for single point spread function (PSF) at 40 mm depth for FDMAS is 87 times faster than MV. The new beamforming technique has been tested on PSF and cyst phantoms experimentally with the ultrasound array research platform version 2 (UARP II) using a 3-8 MHz 128 element clinical transducer. FDMAS is able to improve both imaging contrast and spatial resolution as compared to DAS. The wire phantom main lobes lateral resolution improved in FDMAS by 40.4% with square pulse excitation signal when compared to DAS. Meanwhile the contrast ratio (CR) obtained for an anechoic cyst located at 15 mm depth for PWI with DAS and FDMAS are -6.2 dB and -14.9 dB respectively. The ability to reduce noise from off axis with auto-correlation operation in FDMAS pave the way to display the B-mode image with high dynamic range. However, the contrast to noise ratio (CNR) measured at same cyst location for FDMAS give less reading compared to DAS. Nevertheless, this drawback can be compensated by applying compound plane wave imaging (CPWI) technique on FDMAS. In overall the new FDMAS beamforming technique outperforms DAS in laboratory experiments by narrowing its main lobes and increases the image contrast without sacrificing its frame rates

Gallium Nitride Based High-Power Switched HIFU Pulser with Real-Time Current/Voltage Monitoring

High-Intensity Focussed Ultrasound (HIFU) techniques make use of ultrasound transducers capable of delivering high powers to be delivered at high frequencies. Real-time monitoring of power delivered can avoid damage to the transducer and injury to patients due to overexposure. This paper demonstrates the real-time current and voltage monitoring capabilities of a new Gallium-Nitride (GaN) based switched mode transmit pulser developed for the University of Leeds High-Intensity Focussed Ultrasound Array Research Platform (HIFUARP) system, which uses a novel approach of using an Analog Front End (AFE) floating on the transmitter output to provide high bandwidth current measurement

Real-Time FIR Filter Equalisation of Analog Front Ends for Soft-Tissue Quantitative Ultrasound

A typical ultrasound imaging system analogue front end (AFE) consists of a series of stages, including transmit/receive switch, amplifiers and analog-digital converter (ADC). Each stage will have an impact on the signal in the form of noise, but also in the form of distortion from a frequency-dependent gain profile. This gain response will be applied to any ultrasound echo signal received by the system. This paper highlights the presence of this distortion and proposes a method of identifying the distortion caused by the front end and performing compensation in realtime using per-channel finite-impulse-response (FIR) filters. The University of Leeds Ultrasound Array Research Platform (UARP) was used as a typical example system for which the AFE frequency response was analysed, though any system using integrated analogue front ends will exhibit similar behaviour. The proposed method was used to determine the necessary inverse response filter for the UARP system. With the filter inserted into the digital signal processing path and the resulting frequency response is measured to verify functionality. The presented results demonstrate how digital FIR filters can be used to effectively equalise the gain profile of the AFE in real-time using hardware Finite Impulse Response (FIR) filters within the UARP research system

Using Heterogeneous Hardware for Simultaneous Diagnostic and Therapeutic Ultrasound

Within the Ultrasound Array Research Platform (UARP) open research system project, imaging and high-intensity focussed ultrasound (HIFU) implementations are used independently for diagnostic and therapeutic research respectively. In this paper, the hardware of each system remains unmodified, but the timing and control subsystems present on both implementations are used to control the discrete imaging and therapy systems in a precisely synchronised manner.Also presented is software interface that has been developed to allow any number of UARP systems to be used as one unified platform. The simple syntax of the software interface eases development of user code that controls ultrasound experiments, whilst preserving the individual capabilities of each the systems and leaving advanced control parameters exposed for complex use cases.The techniques discussed in this paper will enable future research into the development of advanced multi-mode sequencing techniques

Width-modulated square-wave pulses for ultrasound applications

A method of output pressure control for ultrasound transducers using switched excitation is described. The method generates width-modulated square-wave pulse sequences that are suitable for driving ultrasound transducers using MOSFETs or similar devices. Sequences are encoded using an optimized level-shifted, carrier-comparison, pulse-width modulation (PWM) strategy derived from existing PWM theory, and modified specifically for ultrasound applications. The modifications are: a reduction in carrier frequency so that the smallest number of pulses are generated and minimal switching is necessary; alteration of a linear carrier form to follow a trigonometric relationship in accordance with the expected fundamental output; and application of frequency modulation to the carrier when generating frequency-modulated, amplitude-tapered signals. The PWM method permits control of output pressure for arbitrary waveform sequences at diagnostic frequencies (approximately 5 MHz) when sampled at 100 MHz, and is applicable to pulse shaping and array apodization. Arbitrary waveform generation capability is demonstrated in simulation using convolution with a transducer¿s impulse response, and experimentally with hydrophone measurement. Benefits in coded imaging are demonstrated when compared with fixedwidth square-wave (pseudo-chirp) excitation in coded imaging, including reduction in image artifacts and peak side-lobe levels for two cases, showing 10 and 8 dB reduction in peak side-lobe level experimentally, compared with 11 and 7 dB reduction in simulation. In all cases, the experimental observations correlate strongly with simulated data

Improved shear wave-front reconstruction method by aligning imaging beam angles with shear-wave polarization: Applied for shear compounding application

In shear compounding, shear waves are generated at various angles and individual elasticity maps are averaged to reduce noise and improve accuracy. The steered shear waves tilt the tissue motion direction therefore conventional plane wave tracking is not capable of capturing true shear wave amplitude and direction. The proposed method aligns the tracking beams with the shear wave angles, enables beam-axis in the direction of tissue motion to estimate true shear wave motion vector. In this experimental work, shear waves are produced at five different angles and motion is captured using proposed and conventional method. All the experiments are conducted using inclusion-based elasticity phantom. In the results, the displacement maps show that proposed method accurately captured the steered push-beam wave-fronts while conventional method produced push-beam direction artefacts. In the final compounded elasticity maps, the proposed method slightly improved background-to-inclusion elasticity ratio, CNR by 2 dB, and produced inclusion boundary shape sharper than the conventional tracking