The proposed study will assess the feasibility of a novel, all-optical technique for photoacoustic imaging that employs a photorefractive crystal (PRC) and potentially can provide anatomical and functional images of the retina, choroid, and the optic nerve with ultra-fine-resolution. Detailed visualization of retinal substructures and the optic nerve is critical for evaluation of ophthalmic diseases such as diabetic retinopathy (DR), age-related macular degeneration (AMD) and glaucoma. However, vascular function and local oxygen delivery also are relevant indicators of the diseased state. Existing diagnostic modalities such as optical coherence tomography (OCT) and ultrasound (US) do not provide this information. Our PRC-based implementation of PAI will address the shortcomings of other imaging modalities while providing sub-micron image resolution and an imaging depth that is 3 to 5 times that of OCT. Furthermore, PAI also can provide functional information such as the level of hemoglobin-oxygen saturation, which can improve clinical assessment of ophthalmic diseases. Our approach does not require fluid coupling or physical contact required by US. Because the proposed holographic implementation of PAI employs a continuous-wave laser and CCD-based full-field interferometry for detecting the photoacoustic (PA) signal, it potentially can acquire 3D-image data in 500 ms (limited only by the frame rate of the camera and the desired bandwidth for PA-signal detection). The CCD- based implementation also facilitates modification of the field of view (FOV) and resolution simply by changing the microscope objective employed to direct the optical beams to the retina. A prescribed FOV can be achieved by adjusting the distance between the ocular lens and the external objective. The performance of a prototypical system will be characterized using tissue-mimicking phantoms. Subsequently, using live animals, we will demonstrate the ability of our techniques to depict retinal/choroidal micro-circulation and the retinal-pigmented epithelium microstructure as well as functional changes related to altered oxygen saturation. Images obtained using the proposed methods will be compared with optical fundus images and histology- based ground truth. Successful completion of the proposed study will establish a basis for developing a versatile system for ophthalmic imaging that can be employed in pre-clinical research using a variety of animal models, and ultimately in clinical imaging.
We will assess the feasibility of a novel method of anatomical and functional imaging based on a photorefractive crystal for photoacoustic imaging of the retina, choroid, and the optic nerve with an imaging depth (1.5 mm) and a resolution (<1 m) that are far superior to optical coherence tomography.