Design Considerations for Murine Retinal Imaging Using Scattering Angle Resolved Optical Coherence Tomography  
[PERSON]  
1 Department of Biomedical Engineering, The University of Texas at Austin, 107 W Dean Keeton St, Austin, TX 78712, USA; [EMAIL_ADDRESS] (N.K. ); [EMAIL_ADDRESS] (A.S.R. ); [EMAIL_ADDRESS] (H.G.R.III); [EMAIL_ADDRESS] (T.E.M.) 1  
[PERSON]  
1 Department of Biomedical Engineering, The University of Texas at Austin, 107 W Dean Keeton St, Austin, TX 78712, USA; [EMAIL_ADDRESS] (N.K. ); [EMAIL_ADDRESS] (A.S.R. ); [EMAIL_ADDRESS] (H.G.R.III); [EMAIL_ADDRESS] (T.E.M.) 1 Department of Biomedical Engineering, The University of Texas at Austin, 107 W Dean Keeton St, Austin, TX 78712, USA; [EMAIL_ADDRESS] (N.K. ); [EMAIL_ADDRESS] (A.S.  
another study reports an increase in the ratio of high- to low-angle light scattering (forward forward) for induced mitochondrial fission [4]. However, two other studies reported by the same authors indicate a decrease in the same ratio in apoptotic cells [5; 6]. In each case, shifts in scattering angle are associated specifically with changes in mitochondrial morphology, underscoring importance of mitochondria in light scattering [7]. Previously, angle-resolved interferometric imaging approaches have been used to detect sub-wavelength cellular properties such as the size distribution of nuclei and more recently to characterize nuclear morphology, in situ, of both a rodent model for esophageal carcinogenesis and murine retinas [8; 9]. Thus, while several cell culture and ex-vivo tissue studies have been reported involving angle-resolved imaging, similar optical imaging techniques have not been extensively explored for retinal imaging. Other publication threads also suggest a pathway to identify retinal scattering changes. First, a non-human primate study introduced a new contrast measure (\"reflectance index\") that decreases in eyes in response to elevated intraocular pressure [10]. In a follow-up study, a refined measure of reflection ratios (\"normalized reflectance index\") was introduced and reveals an early correlation with pre-perimetric glaucoma in human subjects [11]. Investigators suggested that a candidate biological mechanism for observed changes is modification of the scattering properties of sub-resolution cellular components. Consequently, a third study was conducted in which a scattering angle resolved (SAR-)OCT system was designed and constructed to inspect the optical properties of healthy human retinas [12]. In this study, ocular regions with lower retinal ganglion cell density correlate with the SAR-index, indicating sensitivity of SAR-OCT to morphological variations. SAR-OCT has been demonstrated to detect sub-resolution light scattering variations in the retina. More recent work in angle-resolved OCT imaging finds that multi-directional pathlength-multiplexed OCT imaging may be used to assess the directional reflectivity of retinal layers in human subjects [13], and for obtaining directional blood flow information [14]. An opportunity is recognized for exploring utility SAR-OCT as a new contrast mechanism in healthy and diseased retinas, with potential applications to detect a variety of neurodegenerative diseases that affect retinal morphology. Developing such a system for mouse retina imaging is a natural step in development of SAR-OCT frameworks. The SAR-OCT system previously reported is for human retinal imaging, but due to animal availability and ease of access for proof-of-concept work in accelerated studies, an animal SAR-OCT system for ocular imaging is a valuable tool to examine how diseases affect the scattering properties of the retina. Several well-documented murine disease models--both induced and transgenic--have retinal pathologies. In fact, many OCT studies involve murine disease models because of the mouse eye is strikingly similarity to the human eye (in particular, over that of a rat). The mouse eye has a large numerical aperture and thus higher order aberrations that resemble that in humans [15].