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Imaging through tissue: seeing the unseeable

cells-1872666_1920A UK-wide research team, led by the University of St Andrews, has developed an innovative new way to optically image through tissue, which could allow for a more detailed understanding and diagnosis of the early stages of various diseases, including cancer.

The study, in collaboration with the University of Southampton and the Cancer Research UK Edinburgh Centre at the University of Edinburgh, published in Science Advances (Friday 12 October), paves the way to move from superficial to functional imaging, transforming studies in neuroscience.

Light is incredible. Its ability to image objects has had a profound impact across all of the sciences. However, as we know from everyday experience, light does not penetrate through our skin or a piece of Sellotape very well. The light scatters and is scrambled. This in turn makes it very hard to create images from deep within a sample.

The innovative new method developed by the team of researchers focused short pulses of patterned light in time through the tissue. By focusing in time, known as temporal focusing, the patterns retain their form despite the scattering from the tissue. However, this is not imaging. To image, the team collected just a fraction of the return light (fluorescence) from the sample onto a single-point detector. This means they did not have to know where that light came from within the sample. By simply appropriately summing the patterns projected on the sample weighted by the intensities recorded for the return light, the team were able to form a faithful image. Crucially this image was created without ever having any specific knowledge of the tissue itself.

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Laser light patterns are sequentially focused in time onto a region of interest inside biological tissue. Fluorescence emitted by the sample under each illumination pattern is collected with a single-pixel detector after passing back through the tissue. By adding up the projected patterns weighted by the intensities recorded, an image of the sample can be reconstructed.

The ability to see deeper into tissue with light is currently one of the hottest topics in imaging. The potential applications of the research findings could have wide-ranging implications to aid biomedical analysis and early detection of diseases, including furthering our understanding of neuroscience and degenerative brain diseases.

Researcher Adrià Escobet-Montalbán, Marie Curie Fellow from the University of St Andrews School of Physics and Astronomy, said: “Our approach shows an innovative way to tackle a longstanding problem in imaging. It is exciting to see the response we have got from the international community as many people thought what we have done is impossible with light.”

Professor Kishan Dholakia, from the University of St Andrews School of Physics and Astronomy added: “This is a timely breakthrough and I hope it leads to new ways of thinking about imaging at depth.”


The paper ‘Wide-field multiphoton imaging through scattering media without correction’ is published in Science Advances and is available online.

Please ensure that the paper’s DOI: dx.doi.org/10.1126/sciadv.aau1338 is included in all online stories and social media posts and that Science Advances is credited as the source.

Full author list: Adrià Escobet-Montalbán, Roman Spesyvtsev, Mingzhou Chen, Wardiya Afshar Saber, Melissa Andrews, C. Simon Herrington, Michael Mazilu and Kishan Dholakia.

The research was supported by the UK Engineering and Physical Sciences Research Council, the European Union’s Horizon 2020 Programme through the project Advanced BiomEdical OPTICAL Imaging and Data Analysis (BE-OPTICAL), The Cunningham Trust, The RS MacDonald Charitable Trust and other individual donors. The University of St Andrews has protected the intellectual property rights by filing a patent application.

Issued by the University of St Andrews Communications Office.

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