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Deep non-invasive imaging via scattered-light acoustically-mediated computational microscopy

Periodic Reporting for period 3 - DYNA-MIC (Deep non-invasive imaging via scattered-light acoustically-mediated computational microscopy)

Reporting period: 2019-04-01 to 2020-09-30

Optical microscopy, one of the most important tools in clinical diagnostics and biomedical investigations, is currently limited to the observation of superficial layers in tissue, and cannot be used for imaging deep inside the human body. This results in the requirement for dangerous invasive procedures such as biopsy in order to perform clinical diagnostic. The reason for this limitation is that light scattering in tissue randomizes the light propagation directions, and thus blurs any high-resolution imaging information. The inability of microscopes to look deep into tissue is the same as our inability to see through dense fog. The conventional wisdom is that the high resolution information is lost due to scattering, but our recent works have shown this is not necessarily true when one is able to correctly combine the novel digital tools of the information-age, with digital control and acquisition of light and ultrasound.
The objective of this project is to develop a new kind of microscope, one that can peer deep inside visually opaque samples, by combining novel physical insights on the propagation and interaction of light and ultrasound in complex samples with advanced computational reconstruction algorithms.
While ultrasound imaging allows investigations deep inside tissue, it lacks the microscopic resolution of optical microscopes, and thus does not permit microscopic studies of cellular structures, crucial for accurate diagnosis of cancer and other diseases. The goal of our work is to combine light and ultrasound to develop techniques that can combine the penetration depth of ultrasound with the sub-micron resolution of light.
Achieving our goals would have great impacts on medical diagnostics, as it will remove the requirement for invasive procedure such as biopsy, as well as a great impact on biomedical investigations, such as the challenges in studying the activity of neurons deep inside the brain.
Thus far we have been able to experimentally demonstrate improvements by factors of 2 to 3 in the imaging resolution of photo-acoustic tomography and acousto-optic tomography, two of the leading approaches for deep tissue optical imaging. Most importantly from the practical application point of view, we have been able to perform these improvements in dynamic samples using completely conventional imaging systems, without any change in hardware.
These breakthroughs have been possible by developing advanced image reconstruction procedures that simultaneously processes large image stacks to distill high-resolution imaging information.

In addition to these breakthroughs, we have developed novel all-optical reconstruction approaches to image objects hidden behind highly scattering layers, and to use miniaturised optical fibres for minimally-invasive endoscopic imaging, without the use of any optical elements, such as lenses.

Finally, we have studied the fundamental limitations of acousto-optic measurements, and developed a generalised framework to analyse any acousto-optic experiment, and using it to control light inside complex samples with a resolution exceeding the one available by ultrasound alone.
Our most important progress beyond the state of the art so far was the use of natural dynamic fluctuations of samples, such as those induced by blood flow, to increase the resolution of photo-acoustic and acousto-optic imaging, using conventional hardware.
Two additional results beyond the state of the art are the: (1) adaptation of approaches that were developed for astronomical observations through the atmosphere, to microscopic imaging through turbid layers, and (2) the use of inherent correlations of scattered light to digitally control light propagation inside scattering layers, and to undo the effects of scattering.
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