DUKE UNIVERSITY

Structured illumination(SI) is one of a new generation of techniques which have recently been demonstrated to break the diffraction limit in microscopy. The SI approach to super-resolution involves illuminating the object with a spatial frequency carrier which down-shifts the object#s high-frequency features to within the optical transfer function of the imaging system. Applying this methodology as a modification to standard tabletop microscopes, super-resolution imaging with <50nm resolution has been reported. Previous implementations of SI imaging have utilized straightforward sinusoidal illumination patterns, and relied upon deterministic phase shifting and multiple exposures at different angular orientations to acquire the full complex k-space data required for super-resolved image reconstruction. These approaches are practical in stable and well-characterized microscopes under laboratory conditions, for which these parameters are controllable. The principles of SI imaging represent a fundamental advance in imaging science, and carry the potential of resolution improvement in a variety of biophotonic imaging applications, including human clinical diagnostics. The advantages of SI imaging are particularly compelling in situations where specific features of either the object to be imaged or of the imaging device itself limit the numerical aperture and therefore the achievable resolution. An example of the former is in imaging of the human retina, where the anatomical iris and the optical quality of the cornea outside of the central zone limit the usable numerical aperture. An example of the latter is in endoscopic or catheter imaging, where the physical size of the optics in combination with the desired working distance conspire to severely limit numerical aperture. The proposed project will initiate a research program to investigate how SI imaging technology can be extended to meet the requirements of robustness and speed required of clinical optical instrumentation. The project will focus on the goal of super-resolved imaging of the human retina in the living human eye, where the investigators have considerable previous experience in the development of optical coherence tomography technology. Under the rubric of developing a structured illumination ophthalmoscope for clinical use, it is first proposed to implement and test a prototype structured illumination line-scanning laser ophthalmolscope design. Then, research will be conducted on the development of 3 specific advances in SI technology motivated by anticipated difficulties in transitioning from laboratory to clinical super-resolution imaging: 1)To increase system robustness by applying signal processing techniques previously developed for ophthalmic optical coherence tomography for phase estimation in SI imaging; 2)To design novel structured illumination patterns optimized for fast and efficient image reconstruction, and 3)To improve SI system speed and robustness by developing novel methods for simultaneous acquisition of phase-separated SI image datasets. The proposed work will develop novel biophotonic technology for super-resolution imaging with potential applications in clinical diagnostics. This work will advance the state of the art in coherent sensing and imaging technology. The significance of the technical objectives, if successful,will be to extend modern super-resolution imaging techniques from their current focus in microscopy to broader applications in medical diagnostics. The proposed research project will also support the dissertation research of a Biomedical Engineering graduate student, undergraduate projects for Duke engineering students, and three REU summer program experiences for underrepresented students at Duke University.

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