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In the absence of suitable label-free techniques many groups have developed and used labels such as fluorophores and nanoparticles for biological discovery and in vitro diagnostics. This has led to extraordinary advances in our understanding of fundamental biological processes. However, they are typically toxic and may interfere with the biological process being studied. Furthermore, since they can typically not be used in humans, a disconnect arises between biological discovery and clinical translation. Many researchers worldwide are working to address this problem. For example, we are developing label-free methods for structure and functional information in biological systems including animals and humans. Label-free methods offer many advantages including simpler protocols less ethical dilemmas, less opportunity for interference with the biological process and faster translation to the clinic. Optical coherence tomography has had the fastest uptake of any medical imaging modality in the history of medicine. We have developed technologies based on OCT to visualise the microcirculation to sense structure and structural change at the nanoscale and to provide super resolution in a simple and cost-effective manner. Extracting this information from the existing OCT signal allows us to add structural and functional information which can be overlaid on the basic OCT image. A significant advantage of such methods is that the new information is intrinsically coregistered with the OCT data. In this paper we will show several examples from our own work and label free imaging and sensing with OCT. Correlation mapping OCT relies on speckle dynamics due to moving blood cells which cause a decorrelation with previous or adjacent frames which can be exploited to efficiently generate microcirculation maps. Sub-voxel sensing is very exciting avenue in OCT research since the OCT signal contains much more information than the basic structure provided in a typical OCT image. For example structures smaller than the resolution of the system impact on the spectrum which is detected and since we use a broad spectrum for probing with OCT we can with the help of a high resolution spectrometer determine the sizes of the structures within the voxel. We can furthermore see how they change over time. We can do this very fast, more robustly with better noise performance because the information can be obtained from a single frame unlike phase based imaging. Nanosensitive OCT (nsOCT) is rather different to other methods in that it relies on the fact that the structural size is encoded in the spectrum detected. With appropriate equipment and protocols this can provide nanometres sensitivity to structures and structural changes.
A novel approach to superresolution will also be presented where separation of voxels can be achieved by using the intensity or other variations in depth. Since we have already got this information in many microscopy and tomography techniques including OCT and confocal microscopy, we can use it to efficiently and cost-effectively provide superresolution. The superresolution can be achieved without breaking the rules of information theory because the extra information is in depth and can pass through the objective lens without being blocked by the diffractive limit. We will further discuss the applications of these techniques including an example of nanosensitive OCT being used to diagnose ottitis media in children.
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