The emergence of optical elastography in biomedicine

The authors thank their colleagues past and present who have contributed to the evolution of optical elastography; in particular, S. Adie, W. Allen, L. Chin, B. Quirk, A. Curatolo, S. Es'hagian, K. Kennedy, R. Kirk, R. McLaughlin and P. Munro. This work has been supported in part by the Australian Research Council, the National Health and Medical Research Council, the National Breast Cancer Foundation, and the Western Australian Department of Health. P.W. thanks the Schrader Trust for a studentship.Optical elastography, the use of optics to characterize and map the mechanical properties of biological tissue, involves measuring the deformation of tissue in response to a load. Such measurements may be used to form an image of a mechanical property, often elastic modulus, with the resulting mechanical contrast complementary to the more familiar optical contrast. Optical elastography is experiencing new impetus in response to developments in the closely related fields of cell mechanics and medical imaging, aided by advances in photonics technology, and through probing the microscale between that of cells and whole tissues. Two techniques-optical coherence elastography and Brillouin microscopy-have recently shown particular promise for medical applications, such as in ophthalmology and oncology, and as new techniques in cell mechanics.PostprintPeer reviewe

Snapshot hyperspectral imaging of intracellular lasers

This work received financial support from a UK EPSRC Programme Grant (EP/P030017/1). PW was supported by the 1851 Research Fellowship from the Royal Commission. KD acknowledges support from the Australian Research Council (FL210100099). MCG acknowledges support from the Alexander von Humboldt Foundation (Humboldt professorship).Intracellular lasers are emerging as powerful biosensors for multiplexed tracking and precision sensing of cells and their microenvironment. This sensing capacity is enabled by quantifying their narrow-linewidth emission spectra, which is presently challenging to do at high speeds. In this work, we demonstrate rapid snapshot hyperspectral imaging of intracellular lasers. Using integral field mapping with a microlens array and a diffraction grating, we obtain images of the spatial and spectral intensity distribution from a single camera acquisition. We demonstrate widefield hyperspectral imaging over a 3×3 mm2 field of view and volumetric imaging over 250×250×800 µm3 volumes with a spatial resolution of 5 µm and a spectral resolution of less than 0.8 nm. We evaluate the performance and outline the challenges and strengths of snapshot methods in the context of characterising the emission from intracellular lasers. This method offers new opportunities for a diverse range of applications, including high-throughput and long-term biosensing with intracellular lasers.Preprin

Snapshot hyperspectral imaging of intracellular lasers

This work received financial support from a UK EPSRC Programme Grant (EP/P030017/1). PW was supported by the 1851 Research Fellowship from the Royal Commission. KD acknowledges support from the Australian Research Council (FL210100099). MCG acknowledges support from the Alexander von Humboldt Foundation (Humboldt professorship).Intracellular lasers are emerging as powerful biosensors for multiplexed tracking and precision sensing of cells and their microenvironment. This sensing capacity is enabled by quantifying their narrow-linewidth emission spectra, which is presently challenging to do at high speeds. In this work, we demonstrate rapid snapshot hyperspectral imaging of intracellular lasers. Using integral field mapping with a microlens array and a diffraction grating, we obtain images of the spatial and spectral intensity distribution from a single camera acquisition. We demonstrate widefield hyperspectral imaging over a 3 × 3 mm2 field of view and volumetric imaging over 250 × 250 × 800 µm3 (XYZ) volumes with a lateral (XY) resolution of 5 µm, axial (Z) resolution of 10 µm, and a spectral resolution of less than 0.8 nm. We evaluate the performance and outline the challenges and strengths of snapshot methods in the context of characterizing the emission from intracellular lasers. This method offers new opportunities for a diverse range of applications, including high-throughput and long-term biosensing with intracellular lasers.Publisher PDFPeer reviewe

Snapshot hyperspectral imaging of intracellular lasers

Intracellular lasers are emerging as powerful biosensors for multiplexed tracking and precision sensing of cells and their microenvironment. This sensing capacity is enabled by quantifying their narrow-linewidth emission spectra, which is presently challenging to do at high speeds. In this work, we demonstrate rapid snapshot hyperspectral imaging of intracellular lasers. Using integral field mapping with a microlens array and a diffraction grating, we obtain images of the spatial and spectral intensity distribution from a single camera acquisition. We demonstrate widefield hyperspectral imaging over a 3$\times$3 mm$^2$ field of view and volumetric imaging over 250$\times$250$\times$800 $\mu$m$^3$ volumes with a spatial resolution of 5 $\mu$m and a spectral resolution of less than 0.8 nm. We evaluate the performance and outline the challenges and strengths of snapshot methods in the context of characterising the emission from intracellular lasers. This method offers new opportunities for a diverse range of applications, including high-throughput and long-term biosensing with intracellular lasers.Comment: 15 pages, 6 figure

Does artificial intelligence have a role in the IVF clinic?

Funding: K R D is supported by a Mid-Career Fellowship from the Hospital Research Foundation (C-MCF-58-2019). K D is supported by the UK Engineering and Physical Sciences Research Council (grants EP/P030017/1 and EP/R004854/1).Lay summary The success of IVF has remained stagnant for a decade. The focus of a great deal of research is to improve on the current ~30% success rate of IVF. Artificial intelligence (AI), or machines that mimic human intelligence, has been gaining traction for its potential to improve outcomes in medicine, such as cancer diagnosis from medical images. In this commentary, we discuss whether AI has the potential to improve fertility outcomes in the IVF clinic. Based on existing research, we examine the potential of adopting AI within multiple facets of an IVF cycle, including egg/sperm and embryo selection, as well as formulation of an IVF treatment regimen. We discuss both the potential benefits and concerns of the patient and clinician in adopting AI in the clinic. We outline hurdles that need to be overcome prior to implementation. We conclude that AI has an important future in improving IVF success.Publisher PDFPeer reviewe

Experimentally unsupervised deconvolution for light-sheet microscopy with propagation-invariant beams

This project was funded by the UK Engineering and Physical Sciences Research Council (grants EP/P030017/1 and EP/R004854/1), and has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement (EC-GA 871212) and H2020 FETOPEN project "Dynamic” (EC-GA 863203). P.W. was supported by the 1851 Research Fellowship from the Royal Commission. KRD was supported by a Mid-Career Fellowship from the Hospital Research Foundation (C-MCF-58-2019). K.D. acknowledges support from the Australian Research Council through a Laureate Fellowship. S.S. was funded by BBSRC (BB/M00905X/1).Deconvolution is a challenging inverse problem, particularly in techniques that employ complex engineered point-spread functions, such as microscopy with propagation-invariant beams. Here, we present a deep-learning method for deconvolution that, in lieu of end-to-end training with ground truths, is trained using known physics of the imaging system. Specifically, we train a generative adversarial network with images generated with the known point-spread function of the system, and combine this with unpaired experimental data that preserve perceptual content. Our method rapidly and robustly deconvolves and super-resolves microscopy images, demonstrating a two-fold improvement in image contrast to conventional deconvolution methods. In contrast to common end-to-end networks that often require 1000–10,000s paired images, our method is experimentally unsupervised and can be trained solely on a few hundred regions of interest. We demonstrate its performance on light-sheet microscopy with propagation-invariant Airy beams in oocytes, preimplantation embryos and excised brain tissue, as well as illustrate its utility for Bessel-beam LSM. This method aims to democratise learned methods for deconvolution, as it does not require data acquisition outwith the conventional imaging protocol.Publisher PDFPeer reviewe

Optical coherence elastography for cellular-scale stiffness imaging of mouse aorta

We have developed a high-resolution optical coherence elastography system capable of estimating Young's modulus in tissue volumes with an isotropic resolution of 15 μm over a 1 mm lateral field of view and a 100 μm axial depth of field. We demonstrate our technique on healthy and hypertensive, freshly excised and intact mouse aortas. Our technique has the capacity to delineate the individual mechanics of elastic lamellae and vascular smooth muscle. Further, we observe global and regional vascular stiffening in hypertensive aortas, and note the presence of local micro-mechanical signatures, characteristic of fibrous and lipid-rich regions.Publisher PD

Optical palpation for the visualization of tumor in human breast tissue

Australian Research Council; Cancer Council Western Australia; Department of Health, Government of Western Australia; OncoResMedical; William and Marlene Schrader Trust of The University of Western AustraliaAccurate and effective removal of tumor in one operation is an important goal of breast-conserving surgery. However, it is not always achieved. Surgeons often utilize manual palpation to assess the surgical margin and/or the breast cavity. Manual palpation, however, is subjective and has relatively low resolution. Here, we investigate a tactile imaging technique, optical palpation, for the visualization of tumor. Optical palpation generates maps of the stress at the surface of tissue under static preload compression. Stress is evaluated by measuring the deformation of a contacting thin compliant layer with known mechanical properties using optical coherence tomography. In this study, optical palpation is performed on 34 freshly excised human breast specimens. Wide field-of-view (up to ~46 × 46 mm) stress images, optical palpograms, are presented from four representative specimens, demonstrating the capability of optical palpation to visualize tumor. Median stress reported for adipose tissue, 4 kPa, and benign dense tissue, 8 kPa, is significantly lower than for invasive tumor, 60 kPa. In addition, we demonstrate that optical palpation provides contrast consistent with a related optical technique, quantitative micro-elastography. This study demonstrates that optical palpation holds promise for visualization of tumor in breast-conserving surgery.PostprintPeer reviewe

Wide-field multiphoton imaging with TRAFIX

This work is supported by the UK Engineering and Physical Sciences Research Council for funding through grants EP/P030017/1 and EP/M000869/1, and has received funding from the European Union's Horizon 2020 Programme through the project Advanced BiomEdical OPTICAL Imaging and Data Analysis (BE-OPTICAL) under grant agreement no. 675512.Optical approaches have broadened their impact in recent years with innovations in both wide-field and super-resolution imaging, which now underpin biological and medical sciences. Whilst these advances have been remarkable, to date, the ongoing challenge in optical imaging is to penetrate deeper. TRAFIX is an innovative approach that combines temporal focusing illumination with single-pixel detection to obtain wide-field multiphoton images of fluorescent microscopic samples deep through scattering media without correction. It has been shown that it can image through biological samples such as rat brain or human colon tissue up to a depth of seven scattering mean-free-path lengths. Comparisons of TRAFIX with standard point-scanning two-photon microscopy show that the former can yield a five-fold higher signal-to-background ratio while signifcantly reducing photo bleaching of the specimen. Here, we show the first preliminary demonstration of TRAFIX with three-photon excitation imaging dielectric beads. We discuss the advantages of the TRAFIX approach combined with compressive sensing for biomedicine.Publisher PD