Biomedical Imaging

Many of the group’s novel optical techniques are applied to real-world scenarios through collaborations with other university departments, both within the University  of Oxford and across the world. This includes applications in biomedical imaging, in which imaging tools are used to capture images of living tissues inside the body.

We are actively working on the following collaborations in biomedical imaging:

• High-resolution imaging of the human retina in collaboration with the Department of Experimental Psychology at the University of Oxford.
• Non-invasive imaging in the brain using fibre imaging techniques, in collaboration with the Department of Pharmacology at the University of Oxford.
• Advanced imaging techniques such as STORM, 4-Pi, SIM, and STED, for super-resolution microscopy of cells and neural activity, in collaboration with the Department of Biochemistry, and Department of Physiology, Anatomy and Genetics, both at the University of Oxford.
• Clinical imaging of pathological or bulk tissues using microscope- or endoscope-based multimodal imaging methods, in collaboration with the Vectorial Optics and Photonics (VOP) Group in the Department of Engineering Science and the Nuffield Department of Surgical Sciences at the University of Oxford.

 

Virtually stained label-free image of the living mouse hippocampus,
acquired through a compact neurosurgical microscope.

Retinal Imaging

The retina is a directly observable part of the central nervous system and cerebrovascular system. It can provide abundant information on the mechanisms of neural processing and disease progression, but elucidating such processes requires the precise visualisation of cellular or even subcellular changes in the living human retina.

The group has recently developed a multi-functional adaptive optics retinal imaging system that offers a unique set of functionalities to promote multi-directional research in visual neuroscience and disease diagnostics. This work allows retinal stimulation at the cellular scale to track and target single cone photoreceptors, and at the group level where extended displays are used to present peripheral stimuli or naturalistic scenes. By recording structural and functional retinal responses simultaneously, through either confocal or non-confocal imaging, we hope to gain deeper understanding of the following questions:

• how fixational eye movements (FEMs) support optimal spatial and chromatic sampling of the world;
• how FEMs are corrupted following the onset of neurodegenerative, systemic, and psychiatric diseases;
• how neurovascular responses to visual stimulation differ between patient cohorts and healthy controls as a measure of retinal metabolic demand.

This work is carried out in collaboration with the Oxford Perception Lab (OPL) in the Department of Experimental Psychology at the University of Oxford, as well as Newcastle University, University of Leeds, University of Pennsylvania, and University of California, Berkeley.

Image of the living perifovea (part of the human retina),
acquired through high-resolution imaging.

Publications

Extended-period AOSLO imaging in the living human retina without pupil dilation: a feasibility study
Jiahe Cui, Maria Villamil, Allie C. Schneider, Penelope F. Lawton, Laura K. Young, Martin J. Booth & Hannah E. Smithson, Biomed. Opt. Express 15, 4995-5008 (2024).

Evaluating the effect of pupil diameter change on AOSLO image quality without pupil dilation
Jiahe Cui, Maria Villamil, Sam Ponting, Martin J. Booth & Hannah E. Smithson, Optica Biophotonics Congress: Biomedical Optics 2024, Technical Digest Series (Optica Publishing Group, 2024), paper TTu3B.7.

Clinical Imaging

Surgical procedures that treat cancer endeavour to maximise tumour removal whilst minimising damage to adjacent normal tissue. Numerous technologies have been developed to provide real-time intraoperative guidance. However, most of these systems are not optimised to enable visualisation of individual cells, and they may also require the use of external contrast agents to distinguish between cancerous and normal cells.

The group develops label-free surgical microscopy and endoscopy technologies with single cell spatial resolution. We are especially interested in the application of adaptive optics, polarisation, and machine learning approaches to solve clinical problems, as well as developing compact instruments with a smaller footprint to use within operating theatres.

This research is in collaboration with the Department of Pharmacology at the University of Oxford, the Nuffield Department of Surgical Sciences at the University of Oxford, and Cologne Medical Centre.

Publications

Compact and contactless reflectance confocal microscope for neurosurgery
Jiahe Cui, Raphaël Turcotte, Karen M. Hampson, Matthew Wincott, Carla C. Schmidt, Nigel J. Emptage, Patra Charalampaki & Martin J. Booth, Biomed. Opt. Express 11, 4772-4785 (2020).

Remote-Focussing for Volumetric Imaging in a Contactless and Label-Free Neurosurgical Microscope
Jiahe Cui, Raphaël Turcotte, Karen M. Hampson, Nigel J. Emptage & Martin J. Booth, Biophotonics Congress 2021: Optics in the Life Sciences 2021, OSA Technical Digest (Optica Publishing Group, 2021), paper DTh2A.2

Multimode Optical Fibre Imaging

Multimode optical fibres (MMFs) are hair-thin endoscopic probes that allow minimally invasive in vivo neuroimaging in deep-brain regions. MMFs efficiently deliver light to and from an imaging site. They have a footprint of less than 200 μm and can achieve a diffraction-limited spatial resolution below 1 µm. However, a major limitation is distortions to the light propagation caused by physical deformations of the fibre. Bends in the fibre diminish the focal quality of light that travels through an MMF and significantly degrade image quality.

The group is actively researching methods to correct bending-induced distortions. We are working to integrate Fibre Bragg Gratings (FBGs) into MMFs to gather information about bending and subsequently achieve a bend correction. The goal is to achieve flexible MMFs that can be used to image neurons not only in vivo but also in awake-behaving animals.

This work is carried out in collaboration with the Emptage Group in the Department of Pharmacology at the University of Oxford.

MMF volumetric two-photon imaging in live brain tissue from the
rat hippocampus, showing (a) labelled neuronal cell bodies and
apical dendrites, and (b) smaller dendrites. Scale bar: 15 µm.

Publications

Volumetric two-photon fluorescence imaging of live neurons using a multimode optical fiber
Raphaël Turcotte, Carla C. Schmidt, Martin J. Booth & Nigel J. Emptage, Optics Letters, 45(24), 6599–6602 (2020)

Subcellular spatial resolution achieved for deep-brain imaging in vivo using a minimally invasive multimode fiber
Sebastian A. Vasquez-Lopez, Raphaël Turcotte, Vadim Koren, Martin Plöschner, Zahid Padamsey, Martin J. Booth, Tomáš Čižmár & Nigel J. Emptage, Light: Science & Applications, 7:110 (2018)

Multi-modal microscopy and endoscopy

An active area of research is in addressing key issues in pathological analysis, i.e., the analysis of diseased tissues. This includes:

• enabling fast, high-throughput whole-slide imaging, in which large numbers of samples are processed to produce digital images.
• precise cancer staging and early-stage scanning, as well as distinguishing between cancer and inflammation.
• describing the organisational microenvironment of tissues and quantifying the extracellular matrix.

This research integrates novel polarization imaging, multi-wavelength imaging, traditional wide-field imaging (H-E), and fluorescence imaging, along with advanced machine learning techniques and big data digital pathology strategies. The goal is to develop a multi-modal microscopic module to enhance the efficiency of pathological analysis. It is carried out in collaboration with the Vectorial Optics and Photonics (VOP) Group  in the Department of Engineering Science at the University of Oxford.

Publications

Complex vectorial optics through gradient index lens cascades
Chao He, Jintao Chang, Qi Hu, Jingyu Wang, Jacopo Antonello, Honghui He, Shaoxiong Liu, Jianyu Lin, Ben Dai, Daniel S. Elson, Peng Xi, Hui Ma & Martin J. Booth Nature Communications 10, 4264 (2019)