Low-Field Actuating Magnetic Elastomer Membranes Characterized using Fibre-Optic Interferometry.

Smart robotic devices remotely powered by magnetic field have emerged as versatile tools for wide biomedical applications. Soft magnetic elastomer (ME) composite membranes with high flexibility and responsiveness are frequently incorporated to enable local actuation for wireless sensing or cargo delivery. However, the fabrication of thin ME membranes with good control in geometry and uniformity remains challenging, as well as the optimization of their actuating performances under low fields (milli-Tesla). In this work, the development of ME membranes comprising of low-cost magnetic powder and highly soft elastomer through a simple template-assisted doctor blading approach, is reported. The fabricated ME membranes are controllable in size (up to centimetre-scale), thickness (tens of microns) and high particle loading (up to 70 wt.%). Conflicting trade-off effects of particle concentration upon magnetic responsiveness and mechanical stiffness are investigated and found to be balanced off as it exceeds 60 wt.%. A highly sensitive fibre-optic interferometric sensing system and a customized fibre-ferrule-membrane probe are first proposed to enable dynamic actuation and real-time displacement characterization. Free-standing ME membranes are magnetically excited under low field down to 2 mT, and optically monitored with nanometer accuracy. The fast and consistent responses of ME membranes showcase their promising biomedical applications in nanoscale actuation and sensing.

Fiber-optic hydrophone for detection of high-intensity ultrasound waves.

Fiber-optic hydrophones (FOHs) are widely used to detect high-intensity focused ultrasound (HIFU) fields. The most common type consists of an uncoated single-mode fiber with a perpendicularly cleaved end face. The main disadvantage of these hydrophones is their low signal-to-noise ratio (SNR). To increase the SNR, signal averaging is performed, but the associated increased acquisition times hinder ultrasound field scans. In this study, with a view to increasing SNR while withstanding HIFU pressures, the bare FOH paradigm is extended to include a partially reflective coating on the fiber end face. Here, a numerical model based on the general transfer-matrix method was implemented. Based on the simulation results, a single-layer, 172 nm TiO2-coated FOH was fabricated. The frequency range of the hydrophone was verified from 1 to 30 MHz. The SNR of the acoustic measurement with the coated sensor was 21 dB higher than that of the uncoated one. The coated sensor successfully withstood a peak positive pressure of 35 MPa for 6000 pulses.

Modelling and measurement of laser-generated focused ultrasound: Can interventional transducers achieve therapeutic effects?

Laser-generated focused ultrasound (LGFU) transducers used for ultrasound therapy commonly have large diameters (6-15 mm), but smaller lateral dimensions (<4 mm) are required for interventional applications. To address the question of whether miniaturized LGFU transducers could generate sufficient pressure at the focus to enable therapeutic effects, a modelling and measurement study is performed. Measurements are carried out for both linear and nonlinear propagation for various illumination schemes and compared with the model. The model comprises several innovations. First, the model allows for radially varying acoustic input distributions on the surface of the LGFU transducer, which arise from the excitation light impinging on the curved transducer surfaces. This realistic representation of the source prevents the overestimation of the achievable pressures (shown here to be as high as 1.8 times). Second, an alternative inverse Gaussian illumination paradigm is proposed to achieve higher pressures; a 35% increase is observed in the measurements. Simulations show that LGFU transducers as small as 3.5 mm could generate sufficient peak negative pressures at the focus to exceed the cavitation threshold in water and blood. Transducers of this scale could be integrated with interventional devices, thereby opening new opportunities for therapeutic applications from inside the body.

Enhancement of instrumented ultrasonic tracking images using deep learning.

PURPOSE: Instrumented ultrasonic tracking provides needle localisation during ultrasound-guided minimally invasive percutaneous procedures. Here, a post-processing framework based on a convolutional neural network (CNN) is proposed to improve the spatial resolution of ultrasonic tracking images. METHODS: The custom ultrasonic tracking system comprised a needle with an integrated fibre-optic ultrasound (US) transmitter and a clinical US probe for receiving those transmissions and for acquiring B-mode US images. For post-processing of tracking images reconstructed from the received fibre-optic US transmissions, a recently-developed framework based on ResNet architecture, trained with a purely synthetic dataset, was employed. A preliminary evaluation of this framework was performed with data acquired from needle insertions in the heart of a fetal sheep in vivo. The axial and lateral spatial resolution of the tracking images were used as performance metrics of the trained network. RESULTS: Application of the CNN yielded improvements in the spatial resolution of the tracking images. In three needle insertions, in which the tip depth ranged from 23.9 to 38.4 mm, the lateral resolution improved from 2.11 to 1.58 mm, and the axial resolution improved from 1.29 to 0.46 mm. CONCLUSION: The results provide strong indications of the potential of CNNs to improve the spatial resolution of ultrasonic tracking images and thereby to increase the accuracy of needle tip localisation. These improvements could have broad applicability and impact across multiple clinical fields, which could lead to improvements in procedural efficiency and reductions in risk of complications.

Neural Network Kalman Filtering for 3-D Object Tracking From Linear Array Ultrasound Data.

Many interventional surgical procedures rely on medical imaging to visualize and track instruments. Such imaging methods not only need to be real time capable but also provide accurate and robust positional information. In ultrasound (US) applications, typically, only 2-D data from a linear array are available, and as such, obtaining accurate positional estimation in three dimensions is nontrivial. In this work, we first train a neural network, using realistic synthetic training data, to estimate the out-of-plane offset of an object with the associated axial aberration in the reconstructed US image. The obtained estimate is then combined with a Kalman filtering approach that utilizes positioning estimates obtained in previous time frames to improve localization robustness and reduce the impact of measurement noise. The accuracy of the proposed method is evaluated using simulations, and its practical applicability is demonstrated on experimental data obtained using a novel optical US imaging setup. Accurate and robust positional information is provided in real time. Axial and lateral coordinates for out-of-plane objects are estimated with a mean error of 0.1 mm for simulated data and a mean error of 0.2 mm for experimental data. The 3-D localization is most accurate for elevational distances larger than 1 mm, with a maximum distance of 6 mm considered for a 25-mm aperture.

Deep Learning for Instrumented Ultrasonic Tracking: From Synthetic Training Data to In Vivo Application.

Instrumented ultrasonic tracking is used to improve needle localization during ultrasound guidance of minimally invasive percutaneous procedures. Here, it is implemented with transmitted ultrasound pulses from a clinical ultrasound imaging probe, which is detected by a fiber-optic hydrophone integrated into a needle. The detected transmissions are then reconstructed to form the tracking image. Two challenges are considered with the current implementation of ultrasonic tracking. First, tracking transmissions are interleaved with the acquisition of B-mode images, and thus, the effective B-mode frame rate is reduced. Second, it is challenging to achieve an accurate localization of the needle tip when the signal-to-noise ratio is low. To address these challenges, we present a framework based on a convolutional neural network (CNN) to maintain spatial resolution with fewer tracking transmissions and enhance signal quality. A major component of the framework included the generation of realistic synthetic training data. The trained network was applied to unseen synthetic data and experimental in vivo tracking data. The performance of needle localization was investigated when reconstruction was performed with fewer (up to eightfold) tracking transmissions. CNN-based processing of conventional reconstructions showed that the axial and lateral spatial resolutions could be improved even with an eightfold reduction in tracking transmissions. The framework presented in this study will significantly improve the performance of ultrasonic tracking, leading to faster image acquisition rates and increased localization accuracy.

Flexible and directional fibre optic ultrasound transmitters using photostable dyes.

All-optical ultrasound transducers are well-suited for use in imaging during minimally invasive surgical procedures. This requires highly miniaturised and flexible devices. Here we present optical ultrasound transmitters for imaging applications based on modified optical fibre distal tips which allow for larger transmitter element sizes, whilst maintaining small diameter proximal optical fibre. Three optical ultrasound transmitter configurations were compared; a 400 µm core optical fibre, a 200 µm core optical fibre with a 400 µm core optical fibre distal tip, and a 200 µm core optical fibre with a 400 µm core capillary distal tip. All the transmitters used a polydimethylsiloxane-dye composite material for ultrasound generation. The material comprised a photostable infra-red absorbing dye to provide optical absorption for the ultrasound transduction. The generated ultrasound beam profile for the three transmitters was compared, demonstrating similar results, with lateral beam widths <1.7 mm at a depth of 10 mm. The composite material demonstrates a promising alternative to previously reported materials, generating ultrasound pressures exceeding 2 MPa, with corresponding bandwidths ca. 30 MHz. These highly flexible ultrasound transmitters can be readily incorporated into medical devices with small lateral dimensions.

Freehand and video-rate all-optical ultrasound imaging.

All-optical ultrasound (AOUS) imaging, which uses light to both generate and detect ultrasound, is an emerging alternative to conventional electronic ultrasound imaging. To date, AOUS imaging has been performed using paradigms that either resulted in long acquisition times or employed bench-top imaging systems that were impractical for clinical use. In this work, we present a novel AOUS imaging paradigm where scanning optics are used to rapidly synthesise an imaging aperture. This paradigm enabled the first AOUS system with a flexible, handheld imaging probe, which represents a critical step towards clinical translation. This probe, which provides video-rate imaging and a real-time display, is demonstrated with phantoms and in vivo human tissue.

Source Density Apodization: Image Artifact Suppression Through Source Pitch Nonuniformity.

Conventional ultrasound imaging probes typically comprise finite-sized arrays of periodically spaced transducer elements which, in the case of phased arrays, can result in severe grating and sidelobe artifacts. Whereas side lobes can be effectively suppressed through amplitude apodization ("AmpA"), grating lobes arising from periodicity in transducer placement can only be suppressed by decreasing the element pitch, which is technologically challenging and costly. In this work, we present source density apodization ("SDA") as an alternative apodization scheme, where the spatial source density (and, hence, the element pitch) is varied across the imaging aperture. Using an all-optical ultrasound imaging setup capable of video-rate 2-D imaging as well as dynamic and arbitrary reconfiguration of the source array geometry, we show both numerically and experimentally how SDA and AmpA are equivalent for large numbers of sources. For low numbers of sources, SDA is shown to yield superior image quality as both side and grating lobes are effectively suppressed. In addition, we demonstrate how asymmetric SDA schemes can be used to locally and dynamically improve the image quality. Finally, we demonstrate how a nonsmoothly varying spatial source density (such as that obtained for randomized arrays or in the presence of source positioning uncertainty or inaccuracy) can yield severe image artifacts. The application of SDA can, thus, yield high image quality even for low channel counts, which can ultimately result in higher imaging frame rates using acquisition systems of reduced complexity.

All-Optical Rotational Ultrasound Imaging.

Miniaturised high-resolution imaging devices are valuable for guiding minimally invasive procedures such as vascular stent placements. Here, we present all-optical rotational B-mode pulse-echo ultrasound imaging. With this device, ultrasound transmission and reception are performed with light. The all-optical transducer in the probe comprised an optical fibre that delivered pulsed excitation light to an optical head at the distal end with a multi-walled carbon nanotube and polydimethylsiloxane composite coating. This coating was photoacoustically excited to generate a highly directional ultrasound beam perpendicular to the optical fibre axis. A concave Fabry-Pérot cavity at the distal end of an optical fibre, which was interrogated with a tuneable continuous-wave laser, served as an omnidirectional ultrasound receiver. The transmitted ultrasound had a -6 dB bandwidth of 31.3 MHz and a peak-to-peak pressure of 1.87 MPa, as measured at 1.5 mm from the probe. The receiver had a noise equivalent pressure <100 Pa over a 20 MHz bandwidth. With a maximum outer probe diameter of 1.25 mm, the probe provided imaging with an axial resolution better than 50 µm, and a real-time imaging rate of 5 frames per second. To investigate the capabilities of the probe, intraluminal imaging was performed in healthy swine carotid arteries. The results demonstrate that the all-optical probe is viable for clinical rotational ultrasound imaging.

Video-rate all-optical ultrasound imaging.

All-optical ultrasound imaging, where ultrasound is generated and detected using light, has recently been demonstrated as a viable modality that is inherently insensitive to electromagnetic interference and exhibits wide bandwidths. High-quality 2D and 3D all-optical ultrasound images of tissues have previously been presented; however, to date, long acquisition times (ranging from minutes to hours) have hindered clinical application. Here, we present the first all-optical ultrasound imaging system capable of video-rate, real-time two-dimensional imaging of biological tissue. This was achieved using a spatially extended nano-composite optical ultrasound generator, a highly sensitive fibre-optic acoustic receiver, and eccentric illumination resulting in an acoustic source exhibiting optimal directivity. This source was scanned across a one-dimensional source aperture using a fast galvo mirror, thus enabling the dynamic synthesis of source arrays comprising spatially overlapping sources at non-uniform source separation distances. The resulting system achieved a sustained frame rate of 15 Hz, a dynamic range of 30 dB, a penetration depth of at least 6 mm, a resolution of 75 µm (axial) by 100 µm (lateral), and enabled the dynamics of a pulsating ex vivo carotid artery to be captured.

A reconfigurable all-optical ultrasound transducer array for 3D endoscopic imaging.

A miniature all-optical ultrasound imaging system is presented that generates three-dimensional images using a stationary, real acoustic source aperture. Discrete acoustic sources were sequentially addressed by scanning a focussed optical beam across the proximal end of a coherent fibre bundle; high-frequency ultrasound (156% fractional bandwidth centred around 13.5 MHz) was generated photoacoustically in the corresponding regions of an optically absorbing coating deposited at the distal end. Paired with a single fibre-optic ultrasound detector, the imaging probe (3.5 mm outer diameter) achieved high on-axis resolutions of 97 µm, 179 µm and 110 µm in the x, y and z directions, respectively. Furthermore, the optical scan pattern, and thus the acoustic source array geometry, was readily reconfigured. Implementing four different array geometries revealed a strong dependency of the image quality on the source location pattern. Thus, by employing optical technology, a miniature ultrasound probe was fabricated that allows for arbitrary source array geometries, which is suitable for three-dimensional endoscopic and laparoscopic imaging, as was demonstrated on ex vivo porcine cardiac tissue.

Correlation of Ultrasound Shear Wave Elastography with Pathological Analysis in a Xenografic Tumour Model.

The objective of this study was to evaluate the potential value of ultrasound (US) shear wave elastography (SWE) in assessing the relative change in elastic modulus in colorectal adenocarcinoma xenograft models in vivo and investigate any correlation with histological analysis. We sought to test whether non-invasive evaluation of tissue stiffness is indicative of pathological tumour changes and can be used to monitor therapeutic efficacy. US-SWE was performed in tumour xenografts in 15 NCr nude immunodeficient mice, which were treated with either the cytotoxic drug, Irinotecan, or saline as control. Ten tumours were imaged 48 hours post-treatment and five tumours were imaged for up to five times after treatment. All tumours were harvested for histological analysis and comparison with elasticity measurements. Elastic (Young's) modulus prior to treatment was correlated with tumour volume (r = 0.37, p = 0.008). Irinotecan administration caused significant delay in the tumour growth (p = 0.02) when compared to control, but no significant difference in elastic modulus was detected. Histological analysis revealed a significant correlation between tumour necrosis and elastic modulus (r = -0.73, p = 0.026). SWE measurement provided complimentary information to other imaging modalities and could indicate potential changes in the mechanical properties of tumours, which in turn could be related to the stages of tumour development.

Adaptive Light Modulation for Improved Resolution and Efficiency in All-Optical Pulse-Echo Ultrasound.

In biomedical all-optical pulse-echo ultrasound systems, ultrasound is generated with the photoacoustic effect by illuminating an optically absorbing structure with a temporally modulated light source. Nanosecond range laser pulses are typically used, which can yield bandwidths exceeding 100 MHz. However, acoustical attenuation within tissue or nonuniformities in the detector or source power spectra result in energy loss at the affected frequencies and in a reduced overall system efficiency. In this work, a laser diode is used to generate linear and nonlinear chirp optical modulations that are extended to microsecond time scales, with bandwidths constrained to the system sensitivity. Compared to those obtained using a 2-ns pulsed laser, pulse-echo images of a phantom obtained using linear chirp excitation exhibit similar axial resolution (99 versus 92 µm, respectively) and signal-to-noise ratios (SNRs) (10.3 versus 9.6 dB). In addition, the axial point spread function (PSF) exhibits lower sidelobe levels in the case of chirp modulation. Using nonlinear (time-stretched) chirp excitations, where the nonlinearity is computed from measurements of the spectral sensitivity of the system, the power spectrum of the imaging system was flattened and its bandwidth broadened. Consequently, the PSF has a narrower axial extent and still lower sidelobe levels. Pulse-echo images acquired with time-stretched chirps as optical modulation have higher axial resolution (64 µm) than those obtained with linear chirps, at the expense of a lower SNR (6.8 dB). Using a linear or time-stretched chirp, the conversion efficiency from optical power to acoustical pressure improved by a factor of 70 or 61, respectively, compared to that obtained with pulsed excitation.

Pencil beam all-optical ultrasound imaging.

A miniature, directional fibre-optic acoustic source is presented that employs geometrical focussing to generate a nearly-collimated acoustic pencil beam. When paired with a fibre-optic acoustic detector, an all-optical ultrasound probe with an outer diameter of 2.5 mm is obtained that acquires a pulse-echo image line at each probe position without the need for image reconstruction. B-mode images can be acquired by translating the probe and concatenating the image lines, and artefacts resulting from probe positioning uncertainty are shown to be significantly lower than those observed for conventional synthetic aperture scanning of a non-directional acoustic source. The high image quality obtained for excised vascular tissue suggests that the all-optical ultrasound probe is ideally suited for in vivo, interventional applications.

Perfectly matched layers for frequency-domain integral equation acoustic scattering problems.

Simulations of acoustic wavefields in inhomogeneous media are always performed on finite numerical domains. If contrasts actually extend over the domain boundaries of the numerical volume, unwanted, non-physical reflections from the boundaries will occur. One technique to suppress these reflections is to attenuate them in a locally reflectionless absorbing boundary layer enclosing the spatial computational domain, a perfectly matched layer (PML). This technique is commonly applied in time-domain simulation methods like finite element methods or finite-difference time-domain, but has not been applied to the integral equation method. In this paper, a PML formulation for the three-dimensional frequency-domain integral-equation-based acoustic scattering problem is derived. Three-dimensional acoustic scattering configurations are used to test the PML formulation. The results demonstrate that strong attenuation (a factor of 200 in amplitude) of the scattered pressure field is achieved for thin layers with a thickness of less than a wavelength, and that the PMLs themselves are virtually reflectionless. In addition, it is shown that the integral equation method, both with and without PMLs, accurately reproduces pressure fields by comparing the obtained results with analytical solutions.

Source camera identification for heavily JPEG compressed low resolution still images.

In this research, we examined whether fixed pattern noise or more specifically Photo Response Non-Uniformity (PRNU) can be used to identify the source camera of heavily JPEG compressed digital photographs of resolution 640 x 480 pixels. We extracted PRNU patterns from both reference and questioned images using a two-dimensional Gaussian filter and compared these patterns by calculating the correlation coefficient between them. Both the closed and open-set problems were addressed, leading the problems in the closed set to high accuracies for 83% for single images and 100% for around 20 simultaneously identified questioned images. The correct source camera was chosen from a set of 38 cameras of four different types. For the open-set problem, decision levels were obtained for several numbers of simultaneously identified questioned images. The corresponding false rejection rates were unsatisfactory for single images but improved for simultaneous identification of multiple images.