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  • Journal article
    Lagarto J, Dyer B, Talbot C, Peters N, French P, Lyon A, Dunsby Cet al., 2018,

    Characterization of NAD(P)H and FAD autofluorescence signatures in a Langendorff isolated-perfused rat heart model

    , Biomedical Optics Express, Vol: 9, Pages: 4978-4978, ISSN: 2156-7085

    Autofluorescence spectroscopy is a promising label-free approach to characterize biological samples with demonstrated potential to report structural and biochemical alterations in tissues in a number of clinical applications. We report a characterization of the ex vivo autofluorescence fingerprint of cardiac tissue, exploiting a Langendorff-perfused isolated rat heart model to induce physiological insults to the heart, with a view to understanding how metabolic alterations affect the autofluorescence signals. Changes in the autofluorescence intensity and lifetime signatures associated with reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavin adenine dinucleotide (FAD) were characterized during oxygen- or glucose-depletion protocols. Results suggest that both NAD(P)H and FAD autofluorescence intensity and lifetime parameters are sensitive to changes in the metabolic state of the heart owing to oxygen deprivation. We also observed changes in NAD(P)H fluorescence intensity and FAD lifetime parameter on reperfusion of oxygen, which might provide information on reperfusion injury, and permanent tissue damage or changes to the tissue during recovery from oxygen deprivation. We found that changes in the autofluorescence signature following glucose-depletion are, in general, less pronounced, and most clearly visible in NAD(P)H related parameters. Overall, the results reported in this investigation can serve as baseline for future investigations of cardiac tissue involving autofluorescence measurements.

  • Journal article
    Quicke P, Reynolds S, Neil M, Knopfel T, Schultz S, Foust AJet al., 2018,

    High speed functional imaging with source localized multifocal two-photon microscopy

    , Biomedical Optics Express, Vol: 9, Pages: 3678-3693, ISSN: 2156-7085

    Multifocal two-photon microscopy (MTPM) increases imaging speed over single-focus scanning by parallelizing fluorescence excitation. The imaged fluorescence’s susceptibility to crosstalk, however, severely degrades contrast in scattering tissue. Here we present a source-localized MTPM scheme optimized for high speed functional fluorescence imaging in scattering mammalian brain tissue. A rastered line array of beamlets excites fluorescence imaged with a complementary metal-oxide-semiconductor (CMOS) camera. We mitigate scattering-induced crosstalk by temporally oversampling the rastered image, generating grouped images with structured illumination, and applying Richardson-Lucy deconvolution to reassign scattered photons. Single images are then retrieved with a maximum intensity projection through the deconvolved image groups. This method increased image contrast at depths up to 112 μm in scattering brain tissue and reduced functional crosstalk between pixels during neuronal calcium imaging. Source-localization did not affect signal-to-noise ratio (SNR) in densely labeled tissue under our experimental conditions. SNR decreased at low frame rates in sparsely labeled tissue, with no effect at frame rates above 50 Hz. Our non-descanned source-localized MTPM system enables high SNR, 100 Hz capture of fluorescence transients in scattering brain, increasing the scope of MTPM to faster and smaller functional signals.

  • Journal article
    Wu P-J, Kabovka I, Ruberti J, Sherwood J, Dunlop IE, Paterson C, Torok P, Overby Det al., 2018,

    Water content, not stiffness, dominates Brillouin spectroscopy measurements in hydrated materials

    , Nature Methods, Vol: 15, Pages: 561-562, ISSN: 1548-7091
  • Journal article
    Sparks H, Kondo H, Hooper S, Munro I, Kennedy G, Dunsby C, French P, Sahai Eet al., 2018,

    Heterogeneity in tumor chromatin-doxorubicin binding revealed by in vivo fluorescence lifetime imaging confocal endomicroscopy

    , Nature Communications, Vol: 9, ISSN: 2041-1723

    We present an approach to quantify drug-target engagement using in vivo fluorescence endomicroscopy, validated with in vitro measurements. Doxorubicin binding to chromatin changes the fluorescence lifetime of histone-GFP fusions that we measure in vivo at single-cell resolution using a confocal laparo/endomicroscope. We measure both intra- and inter-tumor heterogeneity in doxorubicin chromatin engagement in a model of peritoneal metastasis of ovarian cancer, revealing striking variation in the efficacy of doxorubicin-chromatin binding depending on intra-peritoneal or intravenous delivery. Further, we observe significant variations in doxorubicin-chromatin binding between different metastases in the same mouse and between different regions of the same metastasis. The quantitative nature of fluorescence lifetime imaging enables direct comparison of drug-target engagement for different drug delivery routes and between in vitro and in vivo experiments. This uncovers different rates of cell killing for the same level of doxorubicin binding in vitro and in vivo.

  • Journal article
    Zhang G, Harput S, Lin S, Christensen-Jeffries K, Leow CH, Brown J, Dunsby C, Eckersley R, Tang Met al., 2018,

    Acoustic wave sparsely activated localization microscopy (AWSALM): super-resolution ultrasound imaging using acoustic activation and deactivation of nanodroplets

    , Applied Physics Letters, Vol: 113, Pages: 014101-1-014101-5, ISSN: 0003-6951

    Photo-activated localization microscopy (PALM) has revolutionized the field of fluorescence microscopy by breaking the diffraction limit in spatial resolution. In this study, “acoustic wave sparsely activated localization microscopy (AWSALM),” an acoustic counterpart of PALM, is developed to super-resolve structures which cannot be resolved by conventional B-mode imaging. AWSALM utilizes acoustic waves to sparsely and stochastically activate decafluorobutane nanodroplets by acoustic vaporization and to simultaneously deactivate the existing vaporized nanodroplets via acoustic destruction. In this method, activation, imaging, and deactivation are all performed using acoustic waves. Experimental results show that sub-wavelength micro-structures not resolvable by standard B-mode ultrasound images can be separated by AWSALM. This technique is flow independent and does not require a low concentration of contrast agents, as is required by current ultrasound super resolution techniques. Acoustic activation and deactivation can be controlled by adjusting the acoustic pressure, which remains well within the FDA approved safety range. In conclusion, this study shows the promise of a flow and contrast agent concentration independent super-resolution ultrasound technique which has potential to be faster and go beyond vascular imaging.

  • Journal article
    Alexandrov Y, Nikolic DS, Dunsby C, French PMWet al., 2018,

    Quantitative time domain analysis of lifetime-based FRET measurements with fluorescent proteins: static random isotropic fluorophore orientation distributions

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

    Förster resonant energy transfer (FRET) measurements are widely used to obtain information about molecular interactions and conformations through the dependence of FRET efficiency on the proximity of donor and acceptor fluorophores. Fluorescence lifetime measurements can provide quantitative analysis of FRET efficiency and interacting population fraction. Many FRET experiments exploit the highly specific labelling of genetically expressed fluorescent proteins, applicable in live cells and organisms. Unfortunately, the typical assumption of fast randomization of fluorophore orientations in the analysis of fluorescence lifetime-based FRET readouts is not valid for fluorescent proteins due to their slow rotational mobility compared to their upper state lifetime. Here, previous analysis of effectively static isotropic distributions of fluorophore dipoles on FRET measurements is incorporated into new software for fitting donor emission decay profiles. Calculated FRET parameters, including molar population fractions, are compared for the analysis of simulated and experimental FRET data under the assumption of static and dynamic fluorophores and the intermediate regimes between fully dynamic and static fluorophores, and mixtures within FRET pairs, is explored. Finally, a method to correct the artefact resulting from fitting the emission from static FRET pairs with isotropic angular distributions to the (incorrect) typically assumed dynamic FRET decay model is presented.

  • Journal article
    Kumar S, Bhuyan MK, Lovell BC, Iwahori Yet al., 2018,

    Hierarchical uncorrelated multiview discriminant locality preserving projection for multiview facial expression recognition

    , Journal of Visual Communication and Image Representation, Vol: 54, Pages: 171-181, ISSN: 1047-3203

    Existing multi-view facial expression recognition algorithms are not fully capable of finding discriminative directions if the data exhibits multi-modal characteristics. This research moves toward addressing this issue in the context of multi-view facial expression recognition. For multi-modal data, local preserving projection (LPP) or local Fisher discriminant analysis (LFDA)-based approach is quite appropriate to find a discriminative space. Also, the classification performance can be enhanced by imposing uncorrelated constraint onto the discriminative space. So for multi-view (multi-modal) data, we proposed an uncorrelated multi-view discriminant locality preserving projection (UMvDLPP)-based approach to find an uncorrelated common discriminative space. Additionally, the proposed UMvDLPP is implemented in a hierarchical fashion (H-UMvDLPP) to obtain an optimal performance. Extensive experiments on BU3DFE dataset show that UMvDLPP performs slightly better than the existing methods. However, an improvement of approximately 3% as compared to the existing state-of-the-art multi-view learning-based approaches is achieved by our H-UMvDLPP. This improvement is due to the fact that the proposed method enhances the discrimination between the classes more effectively, and classifies expressions category-wise followed by classification of the basic expressions embedded in each of the subcategories (hierarchical approach).

  • Journal article
    McCall M, Pendry J, Galdi V, Lai Y, Horsley S, Li J, Zhu J, Mitchell-Thomas R, Quevedo-Teruel O, Tassin P, Ginis V, Martini E, Manatti G, Maci S, Ebrahimpouri M, Hao Y, Kinsler P, Gratus J, Lukens J, Weiner A, Leonhardt U, Smolyaninov I, Smolyaninova V, Thompson R, Wegener M, Kadic M, Cummer Set al., 2018,

    Roadmap on transformation optics

    , Journal of Optics A: Pure and Applied Optics, Vol: 20, ISSN: 1464-4258

    Transformation Optics asks Maxwell’s equations what kind of electromagnetic medium recreate some smooth deformation of space. The guiding principle is Einstein’s principle of covariance: that any physical theory must take the same form in any coordinate system. This requirement fixes very precisely the required electromagnetic medium.The impact of this insight cannot be overestimated. Many practitioners were used to thinking that only a few analytic solutions to Maxwell’s equations existed, such as the monochromatic plane wave in a homogeneous, isotropic medium. At a stroke, Transformation Optics increases that landscape from ‘few’ to ‘infinity’, and to each of the infinitude of analytic solutions dreamt up by the researcher, corresponds an electromagnetic medium capable of reproducing that solution precisely. The most striking example is the electromagnetic cloak, thought to be an unreachable dream of science fiction writers, but realised in the laboratory a few months after the papers proposing the possibility were published. But the practical challenges are considerable, requiring meta-media that are at once electrically and magnetically inhomogeneous and anisotropic. How far have we come since the first demonstrations over a decade ago? And what does the future hold? If the wizardry of perfect macroscopic optical invisibility still eludes us in practice, then what compromises still enable us to create interesting, useful, devices? While 3D cloaking remains a significant technical challenge, much progress has been made in 2-dimensions. Carpet cloaking, wherein an object is hidden under a surface that appears optically flat, relaxes the constraints of extreme electromagnetic parameters. Surface wave cloaking guides sub-wavelength surface waves, making uneven surfaces appear flat. Two dimensions is also the setting in which conformal and complex coordinate transformations are realisable, and the possibilities in this restr

  • Software
    Sparks H, Munro I, Warren S, 2018,

    Sparks et al, Heterogeneity in tumor chromatin-doxorubicin binding revealed by in vivo fluorescence lifetime imaging confocal endomicroscopy: MATLAB code

    Abstract We present an approach to quantify drug-target engagement using in vivo fluorescence endomicroscopy, validated with in vitro measurements. Specifically, we demonstrate that doxorubicin binding to chromatin causes a change in the fluorescence lifetime of histone-GFP fusions that can be measured in vivo at single cell resolution using a confocal laparo/endomicroscope. We measure both intra- and inter-tumor heterogeneity in doxorubicin chromatin engagement in a model of peritoneal metastasis of ovarian cancer, revealing striking variation in the efficacy of doxorubicin-chromatin binding depending on intra-peritoneal or intra-venous delivery. In addition, we observe significant variations in doxorubicin-chromatin binding between different metastases in the same mouse and between different regions of the same metastasis. The quantitative nature of fluorescence lifetime imaging enables direct comparison of drug target engagement for different drug delivery modalities and between in vitro and in vivo experiments. This uncovers dramatically different rates of cell killing for the same level of doxorubicin binding in vitro and in vivo.

  • Journal article
    Lai J, Woodward R, Alexandrov Y, Munnee QA, Lees CC, Vaidyanathan R, Nowlan NCet al., 2018,

    Performance of a wearable acoustic system for fetal movement discrimination

    , PLoS One, Vol: 13, Pages: 1-14, ISSN: 1932-6203

    Fetal movements (FM) are a key factor in clinical management of high-risk pregnancies such as fetal growth restriction. While maternal perception of reduced FM can trigger self-referral to obstetric services, maternal sensation is highly subjective. Objective, reliable monitoring of fetal movement patterns outside clinical environs is not currently possible. A wearable and non-transmitting system capable of sensing fetal movements over extended periods of time would be extremely valuable, not only for monitoring individual fetal health, but also for establishing normal levels of movement in the population at large. Wearable monitors based on accelerometers have previously been proposed as a means of tracking FM, but such systems have difficulty separating maternal and fetal activity and have not matured to the level of clinical use. We introduce a new wearable system based on a novel combination of accelerometers and bespoke acoustic sensors as well as an advanced signal processing architecture to identify and discriminate between types of fetal movements. We validate the system with concurrent ultrasound tests on a cohort of 44 pregnant women and demonstrate that the garment is capable of both detecting and discriminating the vigorous, whole-body ‘startle’ movements of a fetus. These results demonstrate the promise of multimodal sensing for the development of a low-cost, non-transmitting wearable monitor for fetal movements.

  • Journal article
    Harput S, Christensen-Jeffries K, Brown J, Yuanwei L, Williams KJ, Davies AH, Eckersley R, Dunsby CW, Tang Met al., 2018,

    Two-stage motion correction for super-resolution ultrasound imaging in human lower limb

    , IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control, Vol: 65, Pages: 803-814, ISSN: 0885-3010

    The structure of microvasculature cannot be resolved using conventional ultrasound imaging due to the fundamental diffraction limit at clinical ultrasound frequencies. It is possible to overcome this resolution limitation by localizing individual microbubbles through multiple frames and forming a super-resolved image, which usually requires seconds to minutes of acquisition. Over this time interval, motion is inevitable and tissue movement is typically a combination of large and small scale tissue translation and deformation. Therefore, super-resolution imaging is prone to motion artefacts as other imaging modalities based on multiple acquisitions are. This study investigates the feasibility of a two-stage motion estimation method, which is a combination of affine and non-rigid estimation, for super-resolution ultrasound imaging. Firstly, the motion correction accuracy of the proposed method is evaluated using simulations with increasing complexity of motion. A mean absolute error of 12.2 μm was achieved in simulations for the worst case scenario. The motion correction algorithm was then applied to a clinical dataset to demonstrate its potential to enable in vivo super-resolution ultrasound imaging in the presence of patient motion. The size of the identified microvessels from the clinical super-resolution images were measured to assess the feasibility of the two-stage motion correction method, which reduced the width of the motion blurred microvessels approximately 1.5-fold.

  • Journal article
    Kabakova IV, Azuri I, Chen Z, Nayak PK, Snaith HJ, Kronik L, Paterson C, Bakulin AA, Egger DAet al., 2018,

    The effect of ionic composition on acoustic phonon speeds in hybrid perovskites from Brillouin spectroscopy and density functional theory

    , JOURNAL OF MATERIALS CHEMISTRY C, Vol: 6, Pages: 3861-3868, ISSN: 2050-7526
  • Conference paper
    Wisniewski L, Davis S, Lockwood N, Mcginty J, French P, Frankel Pet al., 2018,

    A role for p130Cas in venous sprouting and lymphangiogenesis in the zebrafish

    , 5th Congress of the ESC-Council-on-Basic-Cardiovascular-Science on Frontiers in Cardio Vascular Biology, Publisher: OXFORD UNIV PRESS, Pages: S90-S90, ISSN: 0008-6363
  • Journal article
    Kerridge-Johns WR, Damzen MJ, 2018,

    Temperature effects on tunable CW Alexandrite lasers under diode end-pumping

    , Optics Express, Vol: 26, Pages: 7771-7785, ISSN: 1094-4087

    Diode pumped Alexandrite is a promising route to high power, efficient and inexpensive lasers with a broad (701 nm to 858 nm) gain bandwidth; however, there are challenges with its complex laser dynamics. We present an analytical model applied to experimental red diode end-pumped Alexandrite lasers, which enabled a record 54 % slope efficiency with an output power of 1.2 W. A record lowest lasing wavelength (714 nm) and record tuning range (104 nm) was obtained by optimising the crystal temperature between 8 °C and 105 °C in the vibronic mode. The properties of Alexandrite and the analytical model were examined to understand and give general rules in optimising Alexandrite lasers, along with their fundamental efficiency limits. It was found that the lowest threshold laser wavelength was not necessarily the most efficient, and that higher and lower temperatures were optimal for longer and shorter laser wavelengths, respectively. The pump excited to ground state absorption ratio was measured to decrease from 0.8 to 0.7 by changing the crystal temperature from 10 °C to 90 °C.

  • Journal article
    Thomas G, Minassian A, Damzen MJ, 2018,

    Optical vortex generation from a diode-pumped alexandrite laser

    , Laser Physics Letters, Vol: 15, ISSN: 1612-2011

    We present the demonstration of an optical vortex mode directly generated from a diode-pumped alexandrite slab laser, operating in the bounce geometry. This is the first demonstration of an optical vortex mode generated from an alexandrite laser or from any other vibronic laser. An output power of 2 W for a vortex mode with a 'topological charge' of 1 was achieved and the laser was made to oscillate with both left- and right-handed vorticity. The laser operated at two distinct wavelengths simultaneously, 755 and 759 nm, due to birefringent filtering in the alexandrite gain medium. The result offers the prospect of broadly wavelength tunable vortex generation directly from a laser.

  • Conference paper
    Rutter GA, Haythorne EA, Georgiadou E, Xavier GDS, Pullen TJ, Rizzuto R, Martinez-Sanchez A, McGinty JA, French PMet al., 2018,

    Pancreatic beta cell-selective deletion of the mitochondrial calcium uniporter (MCU) impairs glucose-stimulated insulin secretion <i>in vitro</i> but not <i>in vivo</i>

    , Publisher: WILEY, Pages: 42-42, ISSN: 0742-3071
  • Journal article
    Runcorn TH, Murray R, Taylor JR, 2018,

    Highly efficient nanosecond 560 nm source by SHG of a combined Yb-Raman fiber amplifier

    , Optics Express, Vol: 26, Pages: 4440-4447, ISSN: 1094-4087

    We demonstrate a nanosecond 560 nm pulse source based on frequency-doubling the output of a combined Yb-Raman fiber amplifier, achieving a pulse energy of 2.0 µJ with a conversion efficiency of 32% from the 976 nm pump light. By introducing a continuous-wave 1120 nm signal before the cladding pumped amplifier of a pulsed Yb:fiber master oscillator power amplifier system operating at 1064 nm, efficient conversion to 1120 nm occurs within the fiber amplifier due to stimulated Raman scattering. The output of the combined Yb-Raman amplifier is frequency-doubled to 560 nm using a periodically poled lithium tantalate crystal with a conversion efficiency of 47%, resulting in an average power of 3.0 W at a repetition rate of 1.5 MHz. The 560 nm pulse duration of 1.7 ns and the near diffraction-limited beam quality (M2≤1.18) make this source ideally suited to biomedical imaging applications such as optical-resolution photoacoustic microscopy and stimulated emission depletion microscopy.

  • Journal article
    Kim Y, Warren S, Favero F, Stone J, Clegg J, Neil M, Paterson C, Knight J, French P, Dunsby CWet al., 2018,

    Semi-random multicore fibre design for adaptive multiphoton endoscopy

    , Optics Express, Vol: 26, Pages: 3661-3673, ISSN: 1094-4087

    This paper reports the development, modelling and application of a semi-random multicore fibre (MCF) design for adaptive multiphoton endoscopy. The MCF was constructed from 55 sub-units, each comprising 7 single mode cores, in a hexagonally close-packed lattice where each sub-unit had a random angular orientation. The resulting fibre had 385 single mode cores and was double-clad for proximal detection of multiphoton excited fluorescence. The random orientation of each sub-unit in the fibre reduces the symmetry of the positions of the cores in the MCF, reducing the intensity of higher diffracted orders away from the central focal spot formed at the distal tip of the fibre and increasing the maximum size of object that can be imaged. The performance of the MCF was demonstrated by imaging fluorescently labelled beads with both distal and proximal fluorescence detection and pollen grains with distal fluorescence detection. We estimate that the number of independent resolution elements in the final image – measured as the half-maximum area of the two-photon point spread function divided by the area imaged – to be ~3200.

  • Journal article
    Kumar S, Pandey A, Sai Ram Satwik K, Kumar S, Singh SK, Singh AK, Mohan Aet al., 2018,

    Deep learning framework for recognition of cattle using muzzle point image pattern

    , Measurement: Journal of the International Measurement Confederation, Vol: 116, Pages: 1-17, ISSN: 0263-2241

    Animal biometrics is a frontier area of computer vision, pattern recognition and cognitive science to plays the vital role for the registration, unique identification, and verification of livestock (cattle). The existing handcrafted texture feature extraction and appearance based feature representation techniques are unable to perform the animal recognition in the unconstrained environment. Recently deep learning approaches have achieved more attention for recognition of species or individual animal using visual features. In this research, we propose the deep learning based approach for identification of individual cattle based on their primary muzzle point (nose pattern) image pattern characteristics to addressing the problem of missed or swapped animals and false insurance claims. The major contributions of the work as follows: (1) preparation of muzzle point image database, which are not publically available, (2) extraction of the salient set of texture features and representation of muzzle point image of cattle using the deep learning based convolution neural network, deep belief neural network proposed approaches. The stacked denoising auto-encoder technique is applied to encode the extracted feature of muzzle point images and (3) experimental results and analysis of proposed approach. Extensive experimental results illustrate that the proposed deep learning approach outperforms state-of-the-art methods for recognition of cattle on muzzle point image database. The efficacy of the proposed deep learning approach is computed under different identification settings. With multiple test galleries, rank-1 identification accuracy of 98.99% is achieved.

  • Conference paper
    Kerridge-Johns WR, Geberbauer JW, Volpini A, Damzen MJet al., 2018,

    Vortex laser output with a fundamental Gaussian internal mode using a sagnac interferometer

    We experimentally demonstrate a simple technique to convert any linear laser cavity into an optical vortex source using a Sagnac interferometer as an output coupler. No specialist optics are needed, the vortex has controlled handedness.

  • Conference paper
    Murray RT, Runcorn TH, Taylor JR, 2018,

    Fibre-based sources from the UV to mid-infrared

    Extensive spectral and temporal versatility are achieved through the integration of nonlinear fibres and crystals with seeded master-oscillator power fibre amplifier configurations through diverse generation processes. Various schemes will be reviewed.

  • Conference paper
    Kumar S, McGinty J, 2018,

    Strategic capacity and investment road 0AP planning

    , Pages: 3111-3124, ISSN: 1551-6997

    An effective methodology for the strategic capacity and investment planning roadmap development was successfully deployed at several steel plants. There are a number of key issues that need to be considered in the development of the roadmap some of these include product mix, production scheduling, plant design / layout / logistics, operating practice, metallurgical aspects, environmental, discipline engineering, project / construction management, as well as financial viability analysis and risk assessment. Depending on the requirement of the steel plant, strategic roadmaps can be developed for individual process areas, the total melt shop or the entire steel works covering all processes (ironmaking, steelmaking and rolling / finishing). The objective of developing these strategic roadmaps is to determine / derive the best possible holistic solutions at early phases of the capital expansion projects to attain the corporate targets of key performance indicators (KPIs) with minimal capital investment, improved operating practices / procedures and lower operating costs.

  • Conference paper
    Coney AT, Minassian A, Damzen MJ, 2018,

    High-energy diode-pumped alexandrite oscillator and amplifier development for satellite-based LiDAR

    Development of a Q-switched diode-pumped Alexandrite oscillator producing 3.8mJ pulse energy is described with wavelength and temperature optimisation of a diode-pumped Alexandrite slab amplifier as part of a future Alexandrite design for satellite-based lidar.

  • Conference paper
    Harput S, Christensen-Jeffries K, Brown J, Eckersley RJ, Dunsby C, Tang M-Xet al., 2017,

    Ultrasound Super-Resolution with Microbubble Contrast Agents

    , 16th IEEE SENSORS CONFERENCE, Publisher: IEEE, Pages: 1104-1106, ISSN: 1930-0395

    Ultrasound super-resolution imaging can be achieved by localizing spatially isolated microbubble contrast agents over multiple imaging frames. In vivo images with resolutions of ~10-20 microns in deep tissue have been demonstrated. The technique has the potential to revolutionize the way micro-circulation can be visualized and quantified, and has implications in a wide range of clinical applications including cancer, diabetes and beyond. In this paper we describe the principle of the technique with in vivo results demonstrating the superior resolution achieved compared with existing ultrasound imaging. We also discuss the challenges and opportunities in the area of 3D imaging including, imaging speed, tissue motion and microbubble localization errors.

  • Journal article
    Kinsler P, McCall MW, 2017,

    Generalized transformation design: metrics, speeds, and diffusion

    , Wave Motion, Vol: 77, Pages: 91-106, ISSN: 0165-2125

    We show that a unified and maximally generalized approach to spatialtransformation design is possible, one that encompasses all second order waves,rays, and diffusion processes in anisotropic media. Until the final step, it isunnecessary to specify the physical process for which a specific transformationdesign is to be implemented. The principal approximation is the neglect of waveimpedance, an attribute that plays no role in ray propagation, and is thereforeirrelevant for pure ray devices; another constraint is that for waves thespatial variation in material parameters needs to be sufficiently smallcompared with the wavelength. The key link between our general formulation anda specific implementation is how the spatial metric relates to the speed ofdisturbance in a given medium, whether it is electromagnetic, acoustic, ordiffusive. Notably, we show that our generalised ray theory, in allowing foranisotropic indexes (speeds), generates the same predictions as does a wavetheory, and the results are closely related to those for diffusion processes.

  • Journal article
    Runcorn TH, Gorlitz F, Murray RT, Kelleheret al., 2017,

    Visible Raman-shifted Fiber Lasers for Biophotonic Applications

    , IEEE Journal of Selected Topics in Quantum Electronics, Vol: 24, ISSN: 1077-260X

    The efficient nonlinear conversion of Yb-doped fiber laser systems using a combination of stimulated Raman scattering and second-harmonic generation is an effective method for developing sources for biophotonic applications in the yellow-green spectral region. In this paper, we review recent progress in the development of these sources, compare the relative benefits of differing source architectures and demonstrate STED microscopy using an exemplar source.

  • Conference paper
    Harput S, Christensen-Jeffries K, Li Y, Brown J, Eckersley RJ, Dunsby C, Tang M-Xet al., 2017,

    Two Stage Sub-Wavelength Motion Correction in Human Microvasculature for CEUS Imaging

    , IEEE International Ultrasonics Symposium (IUS), Publisher: IEEE, ISSN: 1948-5719

    The structure of microvasculature cannot be resolved using clinical B-mode or contrast-enhanced ultrasound (CEUS) imaging due to the fundamental diffraction limit at clinical ultrasound frequencies. It is possible to overcome this resolution limitation by localizing individual microbubbles through multiple frames and forming a super-resolved image. However, ultrasound super-resolution creates its unique problems since the structures to be imaged are on the order of 10s of μm. Tissue movement much larger than 10 μm is common in clinical imaging, which can significantly reduce the accuracy of super-resolution images created from microbubble locations gathered through hundreds of frames. This study investigated an existing motion estimation algorithm from magnetic resonance imaging for ultrasound super-resolution imaging. Its correction accuracy is evaluated using simulations with increasing complexity of motion. Feasibility of the method for ultrasound super-resolution in vivo is demonstrated on clinical ultrasound images. For a chosen microvessel, the super-resolution image without motion correction achieved a sub-wavelength resolution; however after the application of proposed two-stage motion correction method the size of the vessel was reduced to half.

  • Conference paper
    Harput S, Christensen-Jeffries K, Brown J, Eckersley RJ, Dunsby C, Tang MXet al., 2017,

    Localisation of multiple non-isolated microbubbles with frequency decomposition in super-resolution imaging

    , IEEE International Ultrasonics Symposium, IUS, Publisher: IEEE, ISSN: 1948-5719

    Sub-diffraction imaging, also known as ultrasound localization microscopy, is a novel method that can overcome the fundamental diffraction limit by localizing spatially isolated microbubbles. This method requires the use of a low concentration of microbubbles to ensure that they are spatially isolated. For in vivo microvascular imaging, especially for cancer tissue with high microvascular density, spatial isolation cannot be always achieved, since vessels are close to each other and the speed of flow is slow. This study proposes a frequency decomposition method that uses the polydisperse nature of commercial contrast agents to separate spatially non-isolated microbubbles with different acoustic signatures. Zero-phase filters were applied to ensure that there is no relative phase delay between decomposed signals. Results showed that a super-resolution image after frequency decomposition can be generated with three times lower number of acquisitions without sacrificing image quality.

  • 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

    , IEEE International Ultrasonics Symposium (IUS), Publisher: IEEE, ISSN: 1948-5719
  • Journal article
    Kabakova IV, Xiang Y, Paterson C, Torok Pet al., 2017,

    Fiber-integrated Brillouin microspectroscopy: towards Brillouin endoscopy

    , Journal of Innovative Optical Health Sciences, Vol: 10, ISSN: 1793-5458

    Brillouin imaging (BI) for micromechanical characterization of tissues and biomaterials is a fast-developing field of research with a strong potential for medical diagnosis of disease-modified tissues and cells. Although the principles of BI imply its compatibility with in vivo and in situ measurements, the integration of BI with a flexible catheter, capable of reaching the region of interest within the body, is yet to be reported. Here, for the first time, we experimentally investigate integration of the Brillouin spectroscope with standard optical fiber components to achieve a Brillouin endoscope. The performance of single-fiber and dual-fiber endoscopes are demonstrated and analyzed. We show that a major challenge in construction of Brillouin endoscopes is the strong backward Brillouin scattering in the optical fiber and we present a dual-fiber geometry as a possible solution. Measurements of Brillouin spectra in test liquids (water, ethanol and glycerol) are demonstrated using the dual-fiber endoscope and its performance is analyzed numerically with the help of a beam propagation model.

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