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  • Journal article
    Lerendegui M, Yan J, Stride E, Dunsby C, Tang M-Xet al., 2024,

    Understanding the effects of microbubble concentration on localization accuracy in super-resolution ultrasound imaging.

    , Phys Med Biol, Vol: 69

    Super-resolution ultrasound (SRUS) through localising and tracking of microbubbles (MBs) can achieve sub-wavelength resolution for imaging microvascular structure and flow dynamics in deep tissuein vivo. The technique assumes that signals from individual MBs can be isolated and localised accurately, but this assumption starts to break down when the MB concentration increases and the signals from neighbouring MBs start to interfere. The aim of this study is to gain understanding of the effect of MB-MB distance on ultrasound images and their localisation. Ultrasound images of two MBs approaching each other were synthesised by simulating both ultrasound field propagation and nonlinear MB dynamics. Besides the distance between MBs, a range of other influencing factors including MB size, ultrasound frequency, transmit pulse sequence, pulse amplitude and localisation methods were studied. The results show that as two MBs approach each other, the interference fringes can lead to significant and oscillating localisation errors, which are affected by both the MB and imaging parameters. When modelling a clinical linear array probe operating at 6 MHz, localisation errors between 20 and 30μm (∼1/10 wavelength) can be generated when MBs are ∼500μm (2 wavelengths or ∼1.7 times the point spread function (PSF)) away from each other. When modelling a cardiac probe operating at 1.5 MHz, the localisation errors were as high as 200μm (∼1/5 wavelength) even when the MBs were more than 10 wavelengths apart (2.9 times the PSF). For both frequencies, at smaller separation distances, the two MBs were misinterpreted as one MB located in between the two true positions. Cross-correlation or Gaussian fitting methods were found to generate slightly smaller localisation errors than centroiding. In conclusion, caution should be taken when generating and interpreting SRUS images obtained using high agent concentration with MBs separated by less than 1.7 to 3 times the PSF

  • Journal article
    Hansen-Shearer J, Yan J, Lerendegui M, Huang B, Toulemonde M, Riemer K, Tan Q, Tonko J, Weinberg PD, Dunsby C, Tang M-Xet al., 2024,

    Ultrafast 3-D Transcutaneous Super Resolution Ultrasound Using Row-Column Array Specific Coherence-Based Beamforming and Rolling Acoustic Sub-aperture Processing: In Vitro, in Rabbit and in Human Study.

    , Ultrasound Med Biol

    OBJECTIVE: This study aimed to realise 3-D super-resolution ultrasound imaging transcutaneously with a row-column array which has far fewer independent electronic channels and a wider field of view than typical fully addressed 2-D matrix arrays. The in vivo image quality of the row-column array is generally poor, particularly when imaging non-invasively. This study aimed to develop a suite of image formation and post-processing methods to improve image quality and demonstrate the feasibility of ultrasound localisation microscopy using a row-column array, transcutaneously on a rabbit model and in a human. METHODS: To achieve this, a processing pipeline was developed which included a new type of rolling window image reconstruction, which integrated a row-column array specific coherence-based beamforming technique with acoustic sub-aperture processing. This and other processing steps reduced the 'secondary' lobe artefacts, and noise and increased the effective frame rate, thereby enabling ultrasound localisation images to be produced. RESULTS: Using an in vitro cross tube, it was found that the procedure reduced the percentage of 'false' locations from ∼26% to ∼15% compared to orthogonal plane wave compounding. Additionally, it was found that the noise could be reduced by ∼7 dB and the effective frame rate was increased to over 4000 fps. In vivo, ultrasound localisation microscopy was used to produce images non-invasively of a rabbit kidney and a human thyroid. CONCLUSION: It has been demonstrated that the proposed methods using a row-column array can produce large field of view super-resolution microvascular images in vivo and in a human non-invasively.

  • Journal article
    Riemer K, Tan Q, Morse S, Bau L, Toulemonde M, Yan J, Zhu J, Wang B, Taylor L, Lerendegui M, Wu Q, Stride E, Dunsby C, Weinberg PD, Tang M-Xet al., 2024,

    3D Acoustic Wave Sparsely Activated Localization Microscopy With Phase Change Contrast Agents.

    , Invest Radiol, Vol: 59, Pages: 379-390

    OBJECTIVE: The aim of this study is to demonstrate 3-dimensional (3D) acoustic wave sparsely activated localization microscopy (AWSALM) of microvascular flow in vivo using phase change contrast agents (PCCAs). MATERIALS AND METHODS: Three-dimensional AWSALM using acoustically activable PCCAs was evaluated on a crossed tube microflow phantom, the kidney of New Zealand White rabbits, and the brain of C57BL/6J mice through intact skull. A mixture of C 3 F 8 and C 4 F 10 low-boiling-point fluorocarbon gas was used to generate PCCAs with an appropriate activation pressure. A multiplexed 8-MHz matrix array connected to a 256-channel ultrasound research platform was used for transmitting activation and imaging ultrasound pulses and recording echoes. The in vitro and in vivo echo data were subsequently beamformed and processed using a set of customized algorithms for generating 3D super-resolution ultrasound images through localizing and tracking activated contrast agents. RESULTS: With 3D AWSALM, the acoustic activation of PCCAs can be controlled both spatially and temporally, enabling contrast on demand and capable of revealing 3D microvascular connectivity. The spatial resolution of the 3D AWSALM images measured using Fourier shell correlation is 64 μm, presenting a 9-time improvement compared with the point spread function and 1.5 times compared with half the wavelength. Compared with the microbubble-based approach, more signals were localized in the microvasculature at similar concentrations while retaining sparsity and longer tracks in larger vessels. Transcranial imaging was demonstrated as a proof of principle of PCCA activation in the mouse brain with 3D AWSALM. CONCLUSIONS: Three-dimensional AWSALM generates volumetric ultrasound super-resolution microvascular images in vivo with spatiotemporal selectivity and enhanced microvascular penetration.

  • Journal article
    Zeng HJ, Xue WZ, Murray RT, Cui C, Wang L, Pan Z, Loiko P, Mateos X, Yuan F, Zhang G, Griebner U, Petrov V, Chen Wet al., 2024,

    In-band pumped Kerr-lens mode-locked Tm,Ho-codoped calcium aluminate laser

    , Optics Express, Vol: 32, Pages: 16083-16089

    We report on a Kerr-lens mode-locked Tm,Ho-codoped calcium aluminate laser with in-band pumping of the Tm ions by a spatially single-mode 1678 nm Raman fiber laser. The structurally disordered CaGdAlO4 host crystal is also codoped also with the passive Lu ion for additional inhomogeneous line broadening. The Tm,Ho,Lu:CaGdAlO4 laser generates soliton pulses as short as 79 fs at a central wavelength of 2073.6 nm via soft-aperture Kerr-lens mode-locking. The corresponding average output power amounts to 91 mW at a pulse repetition rate of ∼86 MHz. The average output power can be scaled to 842 mW at the expense of slightly longer pulses of 155 fs at 2045.9 nm, which corresponds to a peak power of ∼58 kW. To the best of our knowledge, this represents the first demonstration of an in-band pumped Kerr-lens mode-locked Tm,Ho solid-state laser at ∼2 µm.

  • Journal article
    Dent LG, Curry N, Sparks H, Bousgouni V, Maioli V, Kumar S, Munro I, Butera F, Jones I, Arias-Garcia M, Rowe-Brown L, Dunsby C, Bakal Cet al., 2024,

    Environmentally dependent and independent control of 3D cell shape.

    , Cell Rep

    How cancer cells determine their shape in response to three-dimensional (3D) geometric and mechanical cues is unclear. We develop an approach to quantify the 3D cell shape of over 60,000 melanoma cells in collagen hydrogels using high-throughput stage-scanning oblique plane microscopy (ssOPM). We identify stereotypic and environmentally dependent changes in shape and protrusivity depending on whether a cell is proximal to a flat and rigid surface or is embedded in a soft environment. Environmental sensitivity metrics calculated for small molecules and gene knockdowns identify interactions between the environment and cellular factors that are important for morphogenesis. We show that the Rho guanine nucleotide exchange factor (RhoGEF) TIAM2 contributes to shape determination in environmentally independent ways but that non-muscle myosin II, microtubules, and the RhoGEF FARP1 regulate shape in ways dependent on the microenvironment. Thus, changes in cancer cell shape in response to 3D geometric and mechanical cues are modulated in both an environmentally dependent and independent fashion.

  • Journal article
    Lerendegui M, Riemer K, Papageorgiou G, Wang B, Lachlan A, Chavignon A, Zhang T, Couture O, Huang P, Ashikuzzaman M, Dencks S, Dunsby C, Helfield B, Jensen ØA, Lisson T, Lowerison MR, Rivaz H, Samir AE, Schmitz G, Schoen S, Ruud VS, Pengfei S, Stevens T, Yan J, Sboros V, Tang Met al., 2024,

    ULTRA-SR challenge: assessment of UltrasoundLocalization and TRacking Algorithms for Super-Resolution Imaging

    , IEEE Transactions on Medical Imaging, ISSN: 0278-0062

    With the widespread interest and uptake of super-resolution ultrasound (SRUS) through localization and tracking of microbubbles, also known as ultrasound localization microscopy (ULM), many localization and tracking algorithms have been developed. ULM can image many centimeters into tissue in-vivo and track microvascular flow non-invasively with sub-diffraction resolution. In a significant community effort, we organized a challenge, Ultrasound Localization and TRacking Algorithms for Super-Resolution (ULTRA-SR). The aims of this paper are threefold: to describe the challenge organization, data generation, and winning algorithms; to present the metrics and methods for evaluating challenge entrants; and to report results and findings of the evaluation. Realistic ultrasound datasets containing microvascular flow for different clinical ultrasound frequencies were simulated, using vascular flow physics, acoustic field simulation and nonlinear bubble dynamics simulation. Based on these datasets, 38 submissions from 24 research groups were evaluated against ground truth using an evaluation framework with six metrics, three for localization and three for tracking. In-vivo mouse brain and human lymph node data were also provided, and performance assessed by an expert panel. Winning algorithms are described and discussed. The publicly available data with ground truth and the defined metrics for both localization and tracking present a valuable resource for researchers to benchmark algorithms and software, identify optimized methods/software for their data, and provide insight into the current limits of the field. In conclusion, Ultra-SR challenge has provided benchmarking data and tools as well as direct comparison and insights for a number of the state-of-the art localization and tracking algorithms.

  • Journal article
    Temel T, Murray RT, Wang L, Chen W, Schirrmacher A, Battle RA, Petrov Vet al., 2024,

    Narrowband-seeded PPLN non-resonant optical parametric oscillator

    , International Journal of Development and Conflict, Vol: 14, Pages: 889-895, ISSN: 2010-2690

    A PPLN non-resonant optical parametric oscillator injection-seeded by narrowband sub-100-mW CW radiation at the signal wavelength produces > 3 W idler average power at 2376 nm for a 20-kHz repetition rate, with a sub-2-nm spectral linewidth. The maximum quantum efficiency reaches 39.5%, roughly 1.4 times higher compared to narrowband operation achieved with a volume Bragg grating at the same pump level. Seed levels as low as 40 mW are sufficient to produce the desired spectral narrowing effect.

  • Journal article
    Xiao H, Jiang X, Damzen MJ, 2024,

    Transient pump-probe analysis of pump-induced lensing in laser amplifiers

    , Optics Express, Vol: 32, Pages: 12783-12799, ISSN: 1094-4087

    Understanding of pump-induced lensing in laser amplifiers is essential for the optimized design of high-power lasers with high spatial quality, but there is usually incomplete knowledge of the interplay between thermal and population induced lensing mechanisms, lensing under lasing and non-lasing conditions, and transient lensing effects under pulsed operation. This paper provides quantitative insight of pump-induced lensing effects by using experimental transient pump-probe measurements in an alexandrite laser amplifier end-pumped by a short pulse pump beam with Gaussian spatial intensity distribution. Lensing results are presented showing a large difference in lensing under both non-lasing and lasing conditions and distinction of the population lens and thermal lens contributions from their different response time. Different pump beam sizes are used to show the variation of the relative strength of the lensing mechanisms. Comparison of experimental results with the analytical transient theory developed in this paper for the Gaussian pump beam gives excellent agreement and quantitative information on the thermal and population contributions to the amplifier lens. This paper provides a methodology for quantitative investigation of pump-induced lensing in general laser amplifier systems, and potentially other classes of optical materials with residual optical absorption.

  • Conference paper
    Codescu M-A, Murray JM, Zawilski KT, Schunemann PG, Murray RT, Guha Set al., 2024,

    Optical Parametric Generation in Non-Critically Cut CdSiP2 with a Nanosecond 1.064 μm Nd:YAG Laser

    , Optica High-Brightness Sources and Light-Driven Interactions Congress
  • Journal article
    Temel T, Murray RT, Wang L, Chen W, Schirrmacher A, Divliansky IB, Mhibik O, Glebov LB, Petrov Vet al., 2024,

    Energy scaling of a narrowband, periodically poled LiNbO3, nanosecond, nonresonant optical parametric oscillator.

    , Appl Opt, Vol: 63, Pages: 1811-1814

    We demonstrate that 3-mm-thick, periodically poled L i N b O 3 enables energy scaling of a nonresonant optical parametric oscillator operated in the narrowband mode with a volume Bragg grating at the signal wavelength. Utilizing the full available pump power at 1064 nm, we obtained maximum average powers of 2.25 and 2.08 W for the signal (1.922 µm) and idler (2.383 µm) pulses at 10 kHz, at a total conversion efficiency of 32.8%, which represents a fourfold increase in terms of peak powers over our previous work. The signal and idler spectral linewidths were ∼1n m, with pulse lengths of ∼6n s and an idler beam propagation factor of ∼5.

  • Conference paper
    Murray JM, Codescu M-A, Zawilski KT, Schunemann PG, Murray R, Guha Set al., 2024,

    Optical Parametric Generation in Non-Critically Cut CdSiP2 with a Nanosecond 1.064 μm Nd:YAG Laser

    , Optica High-Brightness Sources and Light-Driven Interactions Congress
  • Journal article
    Bharadwaj A, Kalita R, Kumar A, Sarma A, Jaganathan BG, Kumar S, Gorlitz F, Lightley J, Dunsby C, Neil M, Hollick C, Graham J, French PMW, Boruah BRet al., 2024,

    A cost-effective, modular, research-grade optical microscope

    , Current Science, Vol: 126, Pages: 244-2554, ISSN: 0011-3891

    Optical microscopy is a ubiquitous tool in the physical and life sciences and in histopathology, where visible light microscopy is used to analyse clinical tissue sections at the micron scale to help diagnose diseases. In recent years, microscope technologies have dramatically evolved, but these have generally come with increased cost and complexity. To widen access to advanced microscopy capabilities, we have developed a cost-effective modular platform for optical microscopy (www.openscopes.com). Many of these instruments can be based around a new low-cost and flexible microscope stand, ‘openFrame’, for which the core components are open source. openFrame can support implementations of a wide range of microscope modalities for diverse applications, including research, pathology and training. Unlike many commercial microscopes that are often designed for specific applications and cannot be easily upgraded or adapted for different imaging modalities, openFramebased instruments can be relatively easily maintained, upgraded or adapted to another modality without requiring manufacturer support. To this end, openFramebased instruments are envisaged to operate with opensource software, enabling researchers to assemble and modify their microscopes with minimal challenges presented by proprietary (closed) hardware or software. Here, we describe the implementation of a low-cost, research-grade modular optical microscope applicable to research and pathology.

  • Conference paper
    Krawczyk B, Kudlinski A, Battle RA, Murray RT, Runcorn THet al., 2024,

    Enhancement of four-wave mixing via stimulated emission in a Yb-doped photonic crystal fiber

    , ISSN: 0277-786X

    We present a novel photonic crystal fiber (PCF), designed for degenerate four-wave mixing (FWM), with a Yb-doped core to amplify the FWM pump light via stimulated emission. Using a 1030 nm Q-switched microchip laser as the FWM pump, the generation of anti-Stokes light at 691 nm was enhanced by using a 976 nm CW laser diode to create a population inversion in the Yb-doped core of the PCF, which amplifies the 1030 nm pulses. For a 1030 nm incident average power of 15 mW (4 kW peak power), the 691 nm anti-Stokes power generated increased from 0 to 1.15 mW when the incident 976 nm power was increased from 0 to 287 mW. FWM was not observed for this 1030 nm input power level in a similar length of a conventional PCF with the same phase-matching properties. Hence, we demonstrate that amplification of the FWM pump pulse through stimulated emission boosts the generated anti-Stokes power, providing a promising route to increasing the pump to anti-Stokes conversion efficiency beyond what is possible with non-rare-earth-doped FWM PCFs.

  • Conference paper
    Runcorn TH, Murray RT, Taylor JR, 2024,

    Multi-watt red nanosecond frequency-doubled Raman-shifted fiber laser

    , ISSN: 0277-786X

    We present a nanosecond-pulsed 655 nm laser source based on frequency-doubling a Raman-shifted fiber laser. At a repetition rate of 1.5 MHz, the source generates an average power of 3.3 W, corresponding to a pulse energy of 2.2 µJ, with a pulse duration of 1.8 ns. The fundamental Raman-shifted fiber laser operating at 1310 nm has a novel configuration where the first Raman shift is performed in an Yb-doped fiber amplifier and the second Raman shift is performed in a phosphosilicate fiber. Both Raman shifting stages are seeded with narrow linewidth CW signals, enabling the temporal properties of an amplified 1064 nm modulated laser diode to be transferred to narrow-band light at 1310 nm with very high conversion efficiency. The resulting micro-Joule-level, nanosecond pulses at 1310 nm are frequency-doubled to 655 nm in a double LBO crystal setup with a conversion efficiency of 51%. The multi-Watt, micro-Joule-level red pulses have near diffraction limited beam quality (M2 ≤ 1.04), making this source ideally suited to biomedical imaging applications such as super-resolution and photoacoustic microscopy.

  • Journal article
    Paiè P, Calisesi G, Candeo A, Comi A, Sala F, Ceccarelli F, De Luigi A, Veglianese P, Muhlberger K, Fokine M, Valentini G, Osellame R, Neil M, Bassi A, Bragheri Fet al., 2023,

    Structured-light-sheet imaging in an integrated optofluidic platform.

    , Lab Chip, Vol: 24, Pages: 34-46

    Heterogeneity investigation at the single-cell level reveals morphological and phenotypic characteristics in cell populations. In clinical research, heterogeneity has important implications in the correct detection and interpretation of prognostic markers and in the analysis of patient-derived material. Among single-cell analysis, imaging flow cytometry allows combining information retrieved by single cell images with the throughput of fluidic platforms. Nevertheless, these techniques might fail in a comprehensive heterogeneity evaluation because of limited image resolution and bidimensional analysis. Light sheet fluorescence microscopy opened new ways to study in 3D the complexity of cellular functionality in samples ranging from single-cells to micro-tissues, with remarkably fast acquisition and low photo-toxicity. In addition, structured illumination microscopy has been applied to single-cell studies enhancing the resolution of imaging beyond the conventional diffraction limit. The combination of these techniques in a microfluidic environment, which permits automatic sample delivery and translation, would allow exhaustive investigation of cellular heterogeneity with high throughput image acquisition at high resolution. Here we propose an integrated optofluidic platform capable of performing structured light sheet imaging flow cytometry (SLS-IFC). The system encompasses a multicolor directional coupler equipped with a thermo-optic phase shifter, cylindrical lenses and a microfluidic network to generate and shift a patterned light sheet within a microchannel. The absence of moving parts allows a stable alignment and an automated fluorescence signal acquisition during the sample flow. The platform enables 3D imaging of an entire cell in about 1 s with a resolution enhancement capable of revealing sub-cellular features and sub-diffraction limit details.

  • Journal article
    Liang M, Minassian A, Damzen MJ, 2023,

    High-energy acousto-optic Q-switched alexandrite laser with wavelength tunable fundamental and UV second harmonic generation

    , Optics Express, Vol: 31, Pages: 42428-42438, ISSN: 1094-4087

    We investigate high-energy mJ-class diode-pumped acousto-optic (AO) Q-switched alexandrite lasers with broad tunability at both the fundamental near-IR wavelength range and second harmonic generation (SHG) in the UV wavelength range. An AO Q-switched alexandrite laser with continuous-wave diode-pumping has been operated at up to 10 kHz and producing pulse energy of 700 µJ at repetition rate of 1 kHz. With pulsed double-pass diode-pumping, we demonstrate higher pulse energy of 2.6 mJ. With wavelength tuning, this laser system demonstrated broad fundamental tuning range from 719 to 787 nm with diffraction-limited beam quality (M2 = 1.05). By external cavity second harmonic generation in a Type-I LBO crystal, pulse energy of 0.66 mJ is generated at 375 nm and with UV tuning range from 361 to 391 nm. To our knowledge, this is the first demonstration of AO Q-switched alexandrite laser with broad wavelength tuning in the near-IR and UV wavelength ranges and shows its excellent potential as a pulsed source for future applications.

  • Journal article
    Zeng H, Xue W, Murray RT, Chen W, Pan Z, Wang L, Cui C, Loiko P, Mateos X, Griebner U, Petrov Vet al., 2023,

    Continuous-Wave and Mode-Locked Operation of an In-Band Pumped Tm,Ho,Lu:CaGdAlO<inf>4</inf> Laser

    , Applied Sciences (Switzerland), Vol: 13

    We investigate in-band pumping of a Tm,Ho,Lu:CaGdAlO4 laser using a Raman-shifted Er-fiber laser (1678 nm), in the continuous-wave (CW) and mode-locked (ML) regimes. A maximum output power of 524 mW is obtained in the CW regime with a 5% output coupler at an absorbed pump power of 2.04 W, corresponding to a slope efficiency of 27.9%. A maximum CW wavelength tuning range of 160 nm at the zero level, from 1984 to 2144 nm, is obtained with a 0.2% output coupler. In the ML regime, pumping with 5.5 W (unpolarized), the average output power (0.2% output coupler) reaches 148 mW at a repetition rate of ~96 MHz. The output spectrum is centered at 2071.5 nm with a FWHM of 21.5 nm (σ-polarization). The pulse duration amounts to 218 fs (time-bandwidth product equal to 0.327).

  • Journal article
    Ahmad H, Roslan NA, Zaini MKA, Samion MZ, Reduan SA, Wang Y, Wang S, Sahu JK, Yasin Met al., 2023,

    Generation of multiwavelength bismuth-doped fiber laser based on all-fiber Lyot filter

    , Optical Fiber Technology, Vol: 81, ISSN: 1068-5200

    A stable multiwavelength fiber laser was proposed and demonstrated using a bismuth-doped fiber together with an all-fiber Lyot filter. The proposed multiwavelength bismuth-doped fiber laser (BDFL) spectrum can generate up to 21 output channels between 1309.88 nm and 1313.69 nm by carefully adjusting two polarization controllers (PCs). The multiwavelength BDFL shows good stability over time with a signal-to-noise ratio (SNR) of 48.69 dB, contributing to the average power fluctuations of 0.6 dB and wavelength drift of less than 0.1 nm in the laser output. In addition, the multiwavelength BDFL exhibits a free spectral range (FSR) of about 0.192 nm and a frequency bandwidth of 33.45 GHz. The characteristics of the multiwavelength BDFL can be observed by varying the pump power of the pump source, lasing output at different lengths of polarization maintaining fiber (PMF), and the generation in multiwavelengths using additional single mode-fiber (SMF).

  • Journal article
    Koufidis SF, McCall MW, 2023,

    Wavelength-independent Bragg-like reflection in uniaxial bi-anisotropic media

    , Journal of the Optical Society of America B, Vol: 40, Pages: 2829-2829, ISSN: 0740-3224

    <jats:p>We have recently shown that a uniform birefringent medium exhibits a circular Bragg phenomenon that relies solely on resonant tuning of the medium’s parameters, rather than on a particular wavelength resonance, thus rendering its electromagnetic response arbitrarily broadband. The resonant condition, however, necessitated a chirality parameter equal to the average refractive index. Here, we demonstrate that non-axial wave propagation in an axially bi-anisotropic uniaxial medium also enacts such a response and, moreover, relaxes the severity of the tuning condition, offering a convenient platform for controlling both the location of the resonance and the corresponding bandwidth. Anomalous wave propagation at a singular point is additionally identified, in the vicinity of which a remarkably high and intrinsically broadband refractive index can be realized. Recent demonstrations of meta-media with giant and controllable chirality pave the path towards the realistic embodiment of a highly efficient optical modulator.</jats:p>

  • Journal article
    Hong W, Sparks H, Dunsby C, 2023,

    Alignment and characterisation of remote-refocusingsystems

    , Applied Optics, Vol: 62, Pages: 7431-7440, ISSN: 1559-128X

    The technique of remote refocusing is used in optical microscopy to provide rapid axial scanning without mechanically perturbing the sample and in techniques such as oblique plane microscopy that build on remote refocusing to image a tilted plane within the sample. The magnification between the pupils of the primary (O1) and secondary (O2) microscope objectives of the remote-refocusing system has been shown previously by Mohanan and Corbett [J. Microsc. 288, 95 (2022) [CrossRef] ] to be crucial in obtaining the broadest possible remote-refocusing range. In this work, we performed an initial alignment of a remote-refocusing system and then studied the effect of axial misalignments of O1 and O2, axial misalignment of the primary tube lens (TL1) relative to the secondary tube lens (TL2), lateral misalignments of TL2, and changes in the focal length of TL2. For each instance of the setup, we measured the mean point spread function FWHMxy of 100 nm fluorescent beads and the normalized bead integrated fluorescence signal, and we calculated the axial and lateral distortion of the system; all of these quantities were mapped over the remote-refocusing range and as a function of lateral image position. This allowed us to estimate the volume over which diffraction-limited performance is achieved and how this changes with the alignment of the system.

  • Journal article
    Lightley J, Kumar S, Lim MQ, Garcia E, Goerlitz F, Alexandrov Y, Parrado T, Hollick C, Steele E, Rossmann K, Graham J, Broichhagen J, Mcneish IA, Roufosse CA, Neil MAA, Dunsby C, French PMWet al., 2023,

    <i>openFrame</i>: A modular, sustainable, open microscopy platform with single-shot, dual-axis optical autofocus module providing high precision and long range of operation

    , JOURNAL OF MICROSCOPY, ISSN: 0022-2720
  • Journal article
    Koufidis SF, Koutserimpas TT, McCall MW, 2023,

    Temporal analog of Bragg gratings

    , Optics Letters, Vol: 48, Pages: 4500-4500, ISSN: 0146-9592

    <jats:p>Recently, scalar coupled-wave theory has been employed to analyze a medium with periodic time-varying permittivity, providing simple expressions and, consequently, straightforward insights into the parametric amplification mechanism. Here, we combine such an approach with the Möbius transformation method to investigate the dispersion and optical response of a finite “time-slab” of the aforementioned medium. We demonstrate the temporal analog of a Bragg grating, discuss the differences with its spatial counterpart, and examine nontrivial scenarios of the permittivity’s time-modulation, such as chirping and apodization. Furthermore, we propose a highly selective and, moreover, single-spatial-interface optical sensor, based on phase delineation.</jats:p>

  • Journal article
    Tawy G, Davidson NP, Churchill G, Damzen MJ, Smith PGR, Gates JC, Gawith CBEet al., 2023,

    Temperature-tunable UV generation using an Alexandrite laser and PPLN waveguides

    , OPTICS EXPRESS, Vol: 31, Pages: 22757-22765, ISSN: 1094-4087
  • Journal article
    Taylor JR, 2023,

    Early optical soliton research at Imperial College London

    , OPTICS COMMUNICATIONS, Vol: 536, ISSN: 0030-4018
  • Journal article
    Codescu M-A, Kunze T, Weiß M, Brehm M, Kornilov O, Sebastiani D, Nibbering ETJet al., 2023,

    Ultrafast Proton Transfer Pathways Mediated by Amphoteric Imidazole

    , The Journal of Physical Chemistry Letters, Vol: 14, Pages: 4775-4785, ISSN: 1948-7185
  • Journal article
    Smith M, Sparks H, Almagro J, Chaigne A, Behrens A, Dunsby C, Salbreux Get al., 2023,

    Active mesh and neural network pipeline for cell aggregate segmentation

    , Biophysical Journal, Vol: 122, Pages: 1586-1599, ISSN: 0006-3495

    Segmenting cells within cellular aggregates in 3D is a growing challenge in cell biology due to improvements in capacity and accuracy of microscopy techniques. Here, we describe a pipeline to segment images of cell aggregates in 3D. The pipeline combines neural network segmentations with active meshes. We apply our segmentation method to cultured mouse mammary gland organoids imaged over 24 h with oblique plane microscopy, a high-throughput light-sheet fluorescence microscopy technique. We show that our method can also be applied to images of mouse embryonic stem cells imaged with a spinning disc microscope. We segment individual cells based on nuclei and cell membrane fluorescent markers, and track cells over time. We describe metrics to quantify the quality of the automated segmentation. Our segmentation pipeline involves a Fiji plugin that implements active mesh deformation and allows a user to create training data, automatically obtain segmentation meshes from original image data or neural network prediction, and manually curate segmentation data to identify and correct mistakes. Our active meshes-based approach facilitates segmentation postprocessing, correction, and integration with neural network prediction.

  • Journal article
    Riemer K, Toulemonde M, Yan J, Lerendegui M, Stride E, Weinberg PD, Dunsby C, Tang M-Xet al., 2023,

    Fast and selective super-resolution ultrasound in vivo with acoustically activated nanodroplets

    , IEEE Transactions on Medical Imaging, Vol: 42, Pages: 1056-1067, ISSN: 0278-0062

    Perfusion by the microcirculation is key to the development, maintenance and pathology of tissue. Its measurement with high spatiotemporal resolution is consequently valuable but remains a challenge in deep tissue. Ultrasound Localization Microscopy (ULM) provides very high spatiotemporal resolution but the use of microbubbles requires low contrast agent concentrations, a long acquisition time, and gives little control over the spatial and temporal distribution of the microbubbles. The present study is the first to demonstrate Acoustic Wave Sparsely-Activated Localization Microscopy (AWSALM) and fast-AWSALM for in vivo super-resolution ultrasound imaging, offering contrast on demand and vascular selectivity. Three different formulations of acoustically activatable contrast agents were used. We demonstrate their use with ultrasound mechanical indices well within recommended safety limits to enable fast on-demand sparse activation and destruction at very high agent concentrations. We produce super-localization maps of the rabbit renal vasculature with acquisition times between 5.5 s and 0.25 s, and a 4-fold improvement in spatial resolution. We present the unique selectivity of AWSALM in visualizing specific vascular branches and downstream microvasculature, and we show super-localized kidney structures in systole (0.25 s) and diastole (0.25 s) with fast-AWSALM outdoing microbubble based ULM. In conclusion, we demonstrate the feasibility of fast and selective measurement of microvascular dynamics in vivo with subwavelength resolution using ultrasound and acoustically activatable nanodroplet contrast agents.

  • Conference paper
    Hong Y, Taengnoi N, Bottrill KRH, Wang Y, Sahu JK, Petropoulos P, Richardson DJet al., 2023,

    Experimental investigation of BDFA-based O-band direct-detection transmission using an optical recirculating loop.

    , Pages: 10978-10990

    We implemented a bismuth-doped fiber amplifier (BDFA) based optical recirculating loop to investigate the performance of amplified O-band transmission over appreciable distances. Both single-wavelength and wavelength-division multiplexed (WDM) transmission were studied, with a variety of direct-detection modulation formats. We report on (a) transmission over lengths of up to 550 km in a single-channel 50-Gb/s system operating at wavelengths ranging from 1325 nm to 1350 nm, and (b) rate-reach products up to 57.6 Tb/s-km (after accounting for the forward error correction redundancy) in a 3-channel system.

  • Journal article
    Gleneadie HJJ, Fernandez-Ruiz B, Sardini A, Van de Pette M, Dimond A, Prinjha RKK, McGinty J, French PMW, Bagci H, Merkenschlager M, Fisher AGGet al., 2023,

    Endogenous bioluminescent reporters reveal a sustained increase in utrophin gene expression upon EZH2 and ERK1/2 inhibition

    , COMMUNICATIONS BIOLOGY, Vol: 6
  • Journal article
    McCall MW, Koufidis SF, 2023,

    Broadband Bragg phenomenon in a uniform birefringent medium

    , OPTICS LETTERS, Vol: 48, Pages: 1096-1099, ISSN: 0146-9592

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