Publications

Conference paper

Jeffries K, Huang DY, Brown J, Harput S, Dunsby C, Tang MX, Sidhu PS, Eckersley Ret al., 2017,

Notice of Removal: Super-resolution ultrasound to aid testicular lesion characterisation

, ISSN: 1948-5719

Changes in microvascular structure and flow is of clinical importance in the study of a number of disease processes such as cancer and diabetes. Ultrasound is often the primary imaging procedure performed to determine appropriate treatment or surgery for testicular lesions. Currently, however, differentiation and diagnosis of both benign and malignant testicular tumours such as seminomas, leydig cell tumours and lymphomas are often challenging. Contrast-enhanced ultrasound (CEUS) has been used to aid their characterisation [1]. There are, however, a variety of benign testicular lesions that can mimic testicular malignancies. Ultrasound super-resolution (US-SR) techniques have been able to visualise vascular structures in vitro and in vivo beyond the diffraction limit by localizing individual microbubble signals. In this work, we aim to apply US-SR processing to clinical data to aid diagnostic confidence.

Abstract
Cite

Conference paper

Jeffries KC, Schirmer M, Brown J, Harput S, Tang MX, Dunsby C, Aljabar P, Eckersley Ret al., 2017,

Notice of Removal: Automated super-resolution image processing in ultrasound using machine learning

, ISSN: 1948-5719

Clinical implementation of super-resolution (SR) ultrasound imaging requires accurate single microbubble detection, and would benefit greatly from automation in order to minimize time requirements and user dependence. We present a machine learning based post-processing tool for the application of SR ultrasound imaging, where we utilize superpixelation and support vector machines (SVMs) for foreground detection and signal differentiation.

Abstract
Cite

Conference paper

Jeffries KC, Harput S, Brown J, Dunsby C, Aljabar P, Tang MX, Eckersley Ret al., 2017,

Notice of Removal: Microbubble localization errors in ultrasonic super-resolution imaging

, ISSN: 1948-5719

Recently, acoustic super-resolution (SR) imaging has allowed visualization of microvascular structure and flow beyond the diffraction limit through the localization of many isolated microbubble signals. Each bubble position is typically estimated by calculating the centroid, finding a local maximum, or finding the peak of a 2-D Gaussian function fit. However, the backscattered signal from a microbubble depends not only on diffraction characteristics of the waveform, but also on the bubble behavior in the acoustic field, which if not accounted for, may cause localization errors.

Abstract
Cite

Conference paper

Brown J, Christensen-Jeffries K, Harput S, Dunsby C, Tang MX, Eckersley RJet al., 2017,

Investigation of microbubble detection methods for super-resolution imaging of microvasculature

, ISSN: 1948-5719

Super-resolution techniques that localise isolated bubble signals first require detection algorithms to separate the bubble and tissue responses. This work explores the available bubble detection techniques for super-resolution of tumour microvasculature. Pulse inversion (PI), differential imaging (DI) and singular value decomposition (SVD) filtering were compared in terms of the localisation accuracy, precision and contrast to tissue ratio (CTR). Bubble responses were simulated using the Marmottant model. Non-linear propagation through moving and stationary tissue was modelled using k-Wave. The results showed that PI signal was largely independent of flow direction and speed compared to SVD and DI which were less appropriate for lateral motion. At the lowest speeds, the bubble displacement between frames is not sufficient to generate a strong differential signal. SVD is unsuitable for stationary bubbles. For super-resolution of tumour microvasculature, the results suggest that non-linear techniques are preferential.

Abstract
Cite
Citations: 2

Book chapter

McCall MW, Kinsler P, 2017,

Space-time Cloaking

, World Scientific Handbook of Metamaterials and Plasmonics: In 4 Volumes, Editors: Craster, Guenneau, Publisher: World Scientific Series in Nan, Pages: 173-203, ISBN: 9789813227613

Journal article

Parali U, Sheng X, Minassian A, Tawy G, Sathian J, Thomas GM, Damzen MJet al., 2017,

Diode-pumped Alexandrite laser with passive SESAM Q-switching and wavelength tunability

, Optics Communications, Vol: 410, Pages: 970-976, ISSN: 0030-4018

We report the first experimental demonstration of a wavelength tunable passively Q-switched red-diode-endpumped Alexandrite laser using a semiconductor saturable absorber mirror (SESAM). We present the results ofthe study of passive SESAM Q-switching and wavelength-tuning in continuous diode-pumped Alexandritelasers in both linear cavity and X-cavity configurations. In the linear cavity configuration, pulsed operation upto 27 kHz repetition rate in fundamental TEM00 mode was achieved and maximum average power was 41 mW.The shortest pulse generated was 550 ns (FWHM) and the Q-switched wavelength tuning band spanned wasbetween 740 nm and 755 nm. In the X-cavity configuration, a higher average power up to 73 mW, and obtainedwith higher pulse energy 6.5 J at 11.2 kHz repetition rate, in fundamental TEM00 mode with excellent spatialquality M2 < 1.1. The Q-switched wavelength tuning band spanned was between 775 nm and 781 nm.

Journal article

Figueiredo GS, Bojic S, Rooney P, Wilshaw S-P, Connon CJ, Gouveia RM, Paterson C, Lepert G, Mudhar HS, Figueiredo FC, Lako Met al., 2017,

Gamma-irradiated human amniotic membrane decellularised with sodium dodecyl sulfate is a more efficient substrate for the <i>ex vivo</i> expansion of limbal stem cells

, ACTA BIOMATERIALIA, Vol: 61, Pages: 124-133, ISSN: 1742-7061

Author Web Link
Cite
Citations: 23

Journal article

Chen L, Li G, Li Y, Li Y, Zhu H, Tang L, French P, McGinty J, Ruan Set al., 2017,

UbasM: An effective balanced optical clearing method for intact biomedical imaging

, Scientific Reports, Vol: 7, ISSN: 2045-2322

Optical clearing methods can facilitate deep optical imaging in biological tissue by reducing light scattering and this has enabled accurate three-dimensional signal visualization and quantification of complex biological structures. Unfortunately, existing optical clearing approaches present a compromise between maximizing clearing capability, the preservation of fluorescent protein emission and membrane integrity and the speed of sample processing – with the latter typically requiring weeks for cm scale tissue samples. To address this challenge, we present a new, convenient, aqueous optical clearing agent, termed UbasM: Urea-Based Amino-Sugar Mixture, that rapidly renders fixed tissue samples highly transparent and reliably preserves emission from fluorescent proteins and lipophilic dyes in membrane integrity preserved tissues. UbasM is simple, inexpensive, reproducible and compatible with all labeling methods that we have encountered. It can enable convenient, volumetric imaging of tissue up to the scale of whole adult mouse organs and should be useful for a wide range of light microscopy and tomography techniques applied to biomedical research, especially the study on organism-level systems biology at multiple levels.

Conference paper

Quicke P, Neil M, Knopfel T, Schultz SR, Foust AJet al., 2017,

Source-Localized Multifocal Two-Photon Microscopy for High-Speed Functional Imaging

, 71st Annual Meeting of the Society-of-General-Physiologists (SGP) on Optical Revolution in Physiology - From Membrane to Brain, Publisher: ROCKEFELLER UNIV PRESS, Pages: 13A-14A, ISSN: 0022-1295

Journal article

Sherlock B, Warren SC, Alexandrov Y, Yu F, Stone J, Knight J, Neil MAA, Paterson C, French PMW, Dunsby CWet al., 2017,

In vivo multiphoton microscopy using a handheld scanner with lateral and axial motion compensation

, Journal of Biophotonics, Vol: 11, ISSN: 1864-063X

This paper reports a handheld multiphoton fluorescence microscope designed for clinical imaging that incorporates axial motion compensation and lateral image stabilization. Spectral domain optical coherence tomography is employed to track the axial position of the skin surface, and lateral motion compensation is realised by imaging the speckle pattern arising from the optical coherence tomography beam illuminating the sample. Our system is able to correct lateral sample velocities of up to ~65 μm s-1. Combined with the use of negative curvature microstructured optical fibre to deliver tunable ultrafast radiation to the handheld multiphoton scanner without the need of a dispersion compensation unit, this instrument has potential for a range of clinical applications. The system is used to compensate for both lateral and axial motion of the sample when imaging human skin in vivo.

Journal article

Christensen-Jeffries K, Harput S, Brown J, Wells PNT, Aljabar P, Dunsby CW, Tang M, Eckersley RJet al., 2017,

Microbubble Axial Localization Errors inUltrasound Super-Resolution Imaging

, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control, Vol: 64, Pages: 1644-1654, ISSN: 0885-3010

Acoustic super-resolution imaging has allowed visualization of microvascular structure and flow beyond the diffraction limit using standard clinical ultrasound systems through the localization of many spatially isolated microbubble signals. The determination of each microbubble position is typically performed by calculating the centroid, finding a local maximum, or finding the peak of a 2-D Gaussian function fit to the signal. However, the backscattered signal from a microbubble depends not only on diffraction characteristics of the waveform, but also on the microbubble behavior in the acoustic field. Here, we propose a new axial localization method by identifying the onset of the backscattered signal. We compare the accuracy of localization methods using in vitro experiments performed at 7 cm depth and 2.3 MHz center frequency. We corroborate these findings with simulated results based on the Marmottant model. We show experimentally and in simulations that detecting the onset of the returning signal provides considerably increased accuracy for super-resolution. Resulting experimental cross-sectional profiles in super-resolution images demonstrate at least 5.8 times improvement in contrast ratio and more than 1.8 reduction in spatial spread (provided by 90% of the localizations) for the onset method over centroiding, peak detection and 2D Gaussian fitting methods. Simulations estimate that these latter methods could create errors in relative bubble positions as high as 900 μ m at these experimental settings, while the onset method reduced the interquartile range of these errors by a factor of over 2.2. Detecting the signal onset is therefore expected to considerably improve the accuracy of super-resolution.

Journal article

Runcorn TH, Murray RT, Taylor JR, 2017,

High Average Power Second-harmonic Generation of a CW Erbium Fiber MOPA

, IEEE Photonics Technology Letters, Vol: 29, Pages: 1576-1579, ISSN: 1041-1135

We report the generation of 28 W of 780 nm radiation with near diffraction limited beam quality (M²≤1.15) by frequency-doubling a continuous-wave (CW) erbium fiber master oscillator power amplifier (MOPA) system in a periodically poled lithium niobate crystal. The second-harmonic generation conversion efficiency reached 45% with no roll-off observed, suggesting that further power scaling should be possible with higher fundamental pump powers. The generated second-harmonic had a 3 dB spectral bandwidth of 0.10 nm. The presented architecture represents a simple and effective route to generating high-brightness radiation around 780 nm.

Journal article

Christensen-Jeffries K, Brown J, Aljabar P, Tang M, Dunsby CW, Eckersley RJet al., 2017,

3-D In Vitro Acoustic Super-Resolution andSuper-Resolved Velocity Mapping UsingMicrobubbles

, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control, Vol: 64, Pages: 1478-1486, ISSN: 0885-3010

Standard clinical ultrasound (US) imaging frequencies are unable to resolve microvascular structures due to the fundamental diffraction limit of US waves. Recent demonstrations of 2D super-resolution both in vitro and in vivo have demonstrated that fine vascular structures can be visualized using acoustic single bubble localization. Visualization of more complex and disordered 3D vasculature, such as that of a tumor, requires an acquisition strategy which can additionally localize bubbles in the elevational plane with high precision in order to generate super-resolution in all three dimensions. Furthermore, a particular challenge lies in the need to provide this level of visualization with minimal acquisition time. In this work, we develop a fast, coherent US imaging tool for microbubble localization in 3D using a pair of US transducers positioned at 90°. This allowed detection of point scatterer signals in 3 dimensions with average precisions equal to 1.9 µm in axial and elevational planes, and 11 µm in the lateral plane, compared to the diffraction limited point spread function full widths at half maximum of 488 µm, 1188 µm and 953 µm of the original imaging system with a single transducer. Visualization and velocity mapping of 3D in vitro structures was demonstrated far beyond the diffraction limit. The capability to measure the complete flow pattern of blood vessels associated with disease at depth would ultimately enable analysis of in vivo microvascular morphology, blood flow dynamics and occlusions resulting from disease states.

Journal article

Watson, Andrews N, Davis S, Bugeon L, Dallman M, McGinty Jet al., 2017,

OPTiM: optical projection tomography integrated microscope using open-source hardware and software

, PLOS One, Vol: 12, ISSN: 1932-6203

We describe the implementation of an OPT plate to perform optical projection tomography (OPT) on a commercial wide-field inverted microscope, using our open-source hardware and software. The OPT plate includes a tilt adjustment for alignment and a stepper motor for sample rotation as required by standard projection tomography. Depending on magnification requirements, three methods of performing OPT are detailed using this adaptor plate: a conventional direct OPT method requiring only the addition of a limiting aperture behind the objective lens; an external optical-relay method allowing conventional OPT to be performed at magnifications >4x; a remote focal scanning and region-of-interest method for improved spatial resolution OPT (up to ~1.6 μm). All three methods use the microscope’s existing incoherent light source (i.e. arc-lamp) and all of its inherent functionality is maintained for day-to-day use. OPT acquisitions are performed on in vivo zebrafish embryos to demonstrate the implementations’ viability.

Journal article

McCall MW, Carter IE, Weir K, 2017,

Investigation of the variation of near-circular polarization in Scarabaeoidea beetles

, Materials Today: Proceedings, Vol: 4, Pages: 4942-4951, ISSN: 2214-7853

Variation in the reflection of circularly polarized light (CP) of a substantial number of beetles, of both the Hybosoridae and Scarabaeidae families, is discussed. Classifications of the spectral shapes were made for Cetonia aurata aurata beetles, which were related to variations within the chiral chitin structure and have been computationally modelled. It was seen that single peaked spectra were not the predominant spectral shape and that more complex structures are responsible for the spectra observed. Two structural perturbations methods to the single pitched structure are proposed to be responsible for the more complex spectral shapes. Further CP analysis of the genus rutelinae:Chrysina was undertaken with variations in broadband reflection observed within the optima species.

Journal article

Gorlitz F, Corcoran DS, Garcia Castano EA, Leitinger B, Neil MAA, Dunsby CW, French PMWet al., 2017,

Mapping molecular function to biological nanostructure: combining structured illumination microscopy with fluorescence lifetime imaging (SIM+FLIM)

, Photonics, Vol: 4, ISSN: 2304-6732

We present a new microscope integrating super-resolved imaging using structured illumination microscopy (SIM) with wide-field optically sectioned fluorescence lifetime imaging (FLIM) to provide optical mapping of molecular function and its correlation with biological nanostructure below the conventional diffraction limit. We illustrate this SIM + FLIM capability to map FRET readouts applied to the aggregation of discoidin domain receptor 1 (DDR1) in Cos 7 cells following ligand stimulation and to the compaction of DNA during the cell cycle.

Conference paper

Kerridge-Johns WR, Damzen MJ, 2017,