An Automated Reference Frame Selection (ARFS) Algorithm for Cone Imaging with Adaptive Optics Scanning Light Ophthalmoscopy

Purpose To develop an automated reference frame selection (ARFS) algorithm to replace the subjective approach of manually selecting reference frames for processing adaptive optics scanning light ophthalmoscope (AOSLO) videos of cone photoreceptors. Methods Relative distortion was measured within individual frames before conducting image-based motion tracking and sorting of frames into distinct spatial clusters. AOSLO images from nine healthy subjects were processed using ARFS and human-derived reference frames, then aligned to undistorted AO-flood images by nonlinear registration and the registration transformations were compared. The frequency at which humans selected reference frames that were rejected by ARFS was calculated in 35 datasets from healthy subjects, and subjects with achromatopsia, albinism, or retinitis pigmentosa. The level of distortion in this set of human-derived reference frames was assessed. Results The average transformation vector magnitude required for registration of AOSLO images to AO-flood images was significantly reduced from 3.33 ± 1.61 pixels when using manual reference frame selection to 2.75 ± 1.60 pixels (mean ± SD) when using ARFS (P = 0.0016). Between 5.16% and 39.22% of human-derived frames were rejected by ARFS. Only 2.71% to 7.73% of human-derived frames were ranked in the top 5% of least distorted frames. Conclusion ARFS outperforms expert observers in selecting minimally distorted reference frames in AOSLO image sequences. The low success rate in human frame choice illustrates the difficulty in subjectively assessing image distortion. Translational Relevance Manual reference frame selection represented a significant barrier to a fully automated image-processing pipeline (including montaging, cone identification, and metric extraction). The approach presented here will aid in the clinical translation of AOSLO imaging.

[1]  C. K. Sheehy,et al.  Active eye-tracking for an adaptive optics scanning laser ophthalmoscope. , 2015, Biomedical optics express.

[2]  P. Lennie,et al.  Packing arrangement of the three cone classes in primate retina , 2001, Vision Research.

[3]  Christopher S. Langlo,et al.  Retinal structure and function in achromatopsia: implications for gene therapy. , 2014, Ophthalmology.

[4]  David R. Williams,et al.  Images of photoreceptors in living primate eyes using adaptive optics two-photon ophthalmoscopy , 2010, Biomedical optics express.

[5]  David Williams,et al.  Adaptive optics retinal imaging in the living mouse eye , 2012, Biomedical optics express.

[6]  Robert J Zawadzki,et al.  Multimodal assessment of microscopic morphology and retinal function in patients with geographic atrophy. , 2013, Investigative ophthalmology & visual science.

[7]  A. Dubra,et al.  In vivo dark-field imaging of the retinal pigment epithelium cell mosaic. , 2013, Biomedical optics express.

[8]  Zhuolin Liu,et al.  Adaptive optics optical coherence tomography at 1 MHz. , 2014, Biomedical optics express.

[9]  Austin Roorda,et al.  Correcting for miniature eye movements in high resolution scanning laser ophthalmoscopy , 2005 .

[10]  Alfredo Dubra,et al.  Registration of 2D Images from Fast Scanning Ophthalmic Instruments , 2010, WBIR.

[11]  A. G. Bennett,et al.  Improvements on Littmann's method of determining the size of retinal features by fundus photography , 1994, Graefe's Archive for Clinical and Experimental Ophthalmology.

[12]  Daniel X. Hammer,et al.  High resolution multimodal clinical ophthalmic imaging system , 2010, Optics express.

[13]  Christopher S. Langlo,et al.  In vivo imaging of human cone photoreceptor inner segments. , 2014, Investigative ophthalmology & visual science.

[14]  Radim Kolar,et al.  Registration of retinal sequences from new video-ophthalmoscopic camera , 2016, Biomedical engineering online.

[15]  Michael C. Roggemann,et al.  Image-spectrum signal-to-noise-ratio improvements by statistical frame selection for adaptive-optics imaging through atmospheric turbulence , 1994 .

[16]  A. Swaroop,et al.  High-resolution imaging with adaptive optics in patients with inherited retinal degeneration. , 2007, Investigative ophthalmology & visual science.

[17]  Xavier Levecq,et al.  Fast and robust image registration with local motion estimation for image enhancement and activity detection in retinal imaging , 2014, 2014 International Workshop on Computational Intelligence for Multimedia Understanding (IWCIM).

[18]  Austin Roorda,et al.  Retinal motion estimation in adaptive optics scanning laser ophthalmoscopy. , 2006, Optics express.

[19]  Christopher S. Langlo,et al.  Repeatability of In Vivo Parafoveal Cone Density and Spacing Measurements , 2012, Optometry and vision science : official publication of the American Academy of Optometry.

[20]  Scot S. Olivier,et al.  Two deformable mirror adaptive optics system for in vivo retinal imaging with optical coherence tomography , 2006 .

[21]  David Williams,et al.  Optical fiber properties of individual human cones. , 2002, Journal of vision.

[22]  Jennifer J. Hunter,et al.  Imaging individual neurons in the retinal ganglion cell layer of the living eye , 2017, Proceedings of the National Academy of Sciences.

[23]  Guy Le Besnerais,et al.  Robust processing of images sequences produced by an adaptive optics retinal camera , 2013 .

[24]  Nicholas Devaney,et al.  Pre‐processing, registration and selection of adaptive optics corrected retinal images , 2013, Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians.

[25]  Austin Roorda,et al.  Adaptive optics retinal imaging: emerging clinical applications. , 2010, Optometry and vision science : official publication of the American Academy of Optometry.

[26]  Ravi S. Jonnal,et al.  Imaging cone photoreceptors in three dimensions and in time using ultrahigh resolution optical coherence tomography with adaptive optics , 2011, Biomedical optics express.

[27]  David R. Williams,et al.  In Vivo Two-Photon Fluorescence Kinetics of Primate Rods and Cones , 2016, Investigative ophthalmology & visual science.

[28]  Atsushi Hayashi,et al.  Adaptive optics fundus images of cone photoreceptors in the macula of patients with retinitis pigmentosa , 2013, Clinical ophthalmology.

[29]  Omer P. Kocaoglu,et al.  A Review of Adaptive Optics Optical Coherence Tomography: Technical Advances, Scientific Applications, and the Future , 2016, Investigative ophthalmology & visual science.

[30]  John S Werner,et al.  Photoreceptor counting and montaging of en-face retinal images from an adaptive optics fundus camera. , 2007, Journal of the Optical Society of America. A, Optics, image science, and vision.

[31]  Mayank Goswami,et al.  Adaptive-optics SLO imaging combined with widefield OCT and SLO enables precise 3D localization of fluorescent cells in the mouse retina. , 2015, Biomedical Optics Express.

[32]  Alex R. Wade,et al.  A fast, robust pattern recognition asystem for low light level image registration and its application to retinal imaging. , 1998, Optics express.

[33]  Jennifer J. Hunter,et al.  Two-Photon Autofluorescence Imaging Reveals Cellular Structures Throughout the Retina of the Living Primate Eye , 2016, Investigative ophthalmology & visual science.

[34]  Christopher S. Langlo,et al.  Correlating Photoreceptor Mosaic Structure to Clinical Findings in Stargardt Disease , 2016, Translational vision science & technology.

[35]  Joseph Carroll,et al.  Methods for investigating the local spatial anisotropy and the preferred orientation of cones in adaptive optics retinal images , 2016, Visual Neuroscience.

[36]  David Williams,et al.  Noninvasive imaging of the human rod photoreceptor mosaic using a confocal adaptive optics scanning ophthalmoscope , 2011, Biomedical optics express.

[37]  Christopher S. Langlo,et al.  Residual Foveal Cone Structure in CNGB3-Associated Achromatopsia , 2016, Investigative ophthalmology & visual science.

[38]  R. D. Ferguson,et al.  Adaptive optics scanning laser ophthalmoscope for stabilized retinal imaging. , 2006, Optics express.

[39]  T. Hebert,et al.  Adaptive optics scanning laser ophthalmoscopy. , 2002, Optics express.

[40]  J. Yellott.  Spectral analysis of spatial sampling by photoreceptors: Topological disorder prevents aliasing , 1982, Vision Research.

[41]  Joseph A. Izatt,et al.  Automatic cone photoreceptor segmentation using graph theory and dynamic programming , 2013, Biomedical optics express.

[42]  Christopher S. Langlo,et al.  Noninvasive imaging of the thirteen-lined ground squirrel photoreceptor mosaic , 2016, Visual Neuroscience.

[43]  Nicholas Devaney,et al.  Registration of adaptive optics corrected retinal nerve fiber layer (RNFL) images. , 2014, Biomedical optics express.

[44]  A. Dubra,et al.  Reflective afocal broadband adaptive optics scanning ophthalmoscope , 2011, Biomedical optics express.

[45]  James G. Fujimoto,et al.  Motion correction in optical coherence tomography volumes on a per A-scan basis using orthogonal scan patterns , 2012, Biomedical optics express.

[46]  Sergei Vassilvitskii,et al.  k-means++: the advantages of careful seeding , 2007, SODA '07.

[47]  David Williams,et al.  The locus of fixation and the foveal cone mosaic. , 2005, Journal of vision.

[48]  R. Daniel Ferguson,et al.  High-resolution retinal imaging: enhancement techniques , 2015, Photonics West - Biomedical Optics.

[49]  Steven M. Jones,et al.  Adaptive-optics optical coherence tomography for high-resolution and high-speed 3D retinal in vivo imaging. , 2005, Optics express.

[50]  Nicusor Iftimia,et al.  Compact adaptive optics line scanning ophthalmoscope. , 2009, Optics express.

[51]  Donald T. Miller,et al.  Adaptive optics parallel spectral domain optical coherence tomography for imaging the living retina. , 2005, Optics express.

[52]  Kevin W Eliceiri,et al.  NIH Image to ImageJ: 25 years of image analysis , 2012, Nature Methods.

[53]  R. Zawadzki,et al.  Wavefront sensorless adaptive optics fluorescence biomicroscope for in vivo retinal imaging in mice. , 2016, Biomedical optics express.

[54]  Alfredo Dubra,et al.  Effects of Intraframe Distortion on Measures of Cone Mosaic Geometry from Adaptive Optics Scanning Light Ophthalmoscopy , 2016, Translational vision science & technology.

[55]  Maureen Neitz,et al.  Adaptive optics retinal imaging reveals S-cone dystrophy in tritan color-vision deficiency. , 2007, Journal of the Optical Society of America. A, Optics, image science, and vision.

[56]  D. Williams,et al.  Imaging translucent cell bodies in the living mouse retina without contrast agents. , 2015, Biomedical optics express.

[57]  Robert J Zawadzki,et al.  Evidence of outer retinal changes in glaucoma patients as revealed by ultrahigh-resolution in vivo retinal imaging , 2010, British Journal of Ophthalmology.

[58]  Austin Roorda,et al.  Automated identification of cone photoreceptors in adaptive optics retinal images. , 2007, Journal of the Optical Society of America. A, Optics, image science, and vision.

[59]  P. Rousseeuw.  Silhouettes: a graphical aid to the interpretation and validation of cluster analysis , 1987 .

[60]  D R Williams,et al.  Supernormal vision and high-resolution retinal imaging through adaptive optics. , 1997, Journal of the Optical Society of America. A, Optics, image science, and vision.

[61]  Sina Farsiu,et al.  Automatic detection of cone photoreceptors in split detector adaptive optics scanning light ophthalmoscope images , 2016, Biomedical optics express.

[62]  Christopher S. Langlo,et al.  Automatic detection of modal spacing (Yellott's ring) in adaptive optics scanning light ophthalmoscope images , 2013, Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians.

[63]  K. Takayama,et al.  Macular Cone Abnormalities in Retinitis Pigmentosa with Preserved Central Vision Using Adaptive Optics Scanning Laser Ophthalmoscopy , 2013, PloS one.

[64]  Bernd Hamann,et al.  Correction of eye-motion artifacts in AO-OCT data sets , 2011, BiOS.

[65]  Toco Y P Chui,et al.  Variation of cone photoreceptor packing density with retinal eccentricity and age. , 2011, Investigative ophthalmology & visual science.

[66]  Gang Huang,et al.  Lucky averaging: quality improvement of adaptive optics scanning laser ophthalmoscope images. , 2011, Optics letters.

[67]  David H Brainard,et al.  Multi-modal automatic montaging of adaptive optics retinal images. , 2016, Biomedical optics express.