"This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)."
0933059 Izatt
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 superresolution 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. For objects which respond linearly to the incident illumination, a resolution increase of 2x is possible, whereas for objects which respond nonlinearly (such as saturation of fluorescence or of stimulated emission), the resolution improvement is theoretically unlimited (although it trades off with sensitivity). 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 superresolved 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 ornea 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 three specific advances in SI technology motivated by anticipated difficulties in transitioning from laboratory to clinical superresolution imaging.
