Mapping the 3D Connectivity of the Rat Inner Retinal Vascular Network Using OCT Angiography.

PURPOSE The purpose of this study is to demonstrate three-dimensional (3D) graphing based on optical coherence tomography (OCT) angiography for characterization of the inner retinal vascular architecture and determination of its topologic principles. METHODS Rat eyes (N = 3) were imaged with a 1300-nm spectral/Fourier domain OCT microscope. A topologic model of the inner retinal vascular network was obtained from OCT angiography data using a combination of automated and manually-guided image processing techniques. Using a resistive network model, with experimentally-quantified flow in major retinal vessels near the optic nerve head as boundary conditions, theoretical changes in the distribution of flow induced by vessel dilations were inferred. RESULTS A topologically-representative 3D vectorized graph of the inner retinal vasculature, derived from OCT angiography data, is presented. The laminar and compartmental connectivity of the vasculature are characterized. In contrast to sparse connectivity between the superficial vitreal vasculature and capillary plexuses of the inner retina, connectivity between the two capillary plexus layers is dense. Simulated dilation of single arterioles is shown to produce both localized and lamina-specific changes in blood flow, while dilation of capillaries in a given retinal vascular layer is shown to lead to increased total flow in that layer. CONCLUSIONS Our graphing and modeling data suggest that vascular architecture enables both local and lamina-specific control of blood flow in the inner retina. The imaging, graph analysis, and modeling approach presented here will help provide a detailed characterization of vascular changes in a variety of retinal diseases, both in experimental preclinical models and human subjects.

[1]  Eric A Newman,et al.  Functional Hyperemia and Mechanisms of Neurovascular Coupling in the Retinal Vasculature , 2013, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[2]  Carlo Tomasi,et al.  Automated non-rigid registration and mosaicing for robust imaging of distinct retinal capillary beds using speckle variance optical coherence tomography , 2013, Biomedical optics express.

[3]  Michel Paques,et al.  Structural and hemodynamic analysis of the mouse retinal microcirculation. , 2003, Investigative ophthalmology & visual science.

[4]  Dao-Yi Yu,et al.  Oxygen Distribution and Consumption within the Retina in Vascularised and Avascular Retinas and in Animal Models of Retinal Disease , 2001, Progress in Retinal and Eye Research.

[5]  E. Stefánsson,et al.  The impact of ocular blood flow in glaucoma , 2002, Progress in Retinal and Eye Research.

[6]  J. Izatt,et al.  In vivo bidirectional color Doppler flow imaging of picoliter blood volumes using optical coherence tomography. , 1997, Optics letters.

[7]  Edsger W. Dijkstra,et al.  A note on two problems in connexion with graphs , 1959, Numerische Mathematik.

[8]  David Kleinfeld,et al.  Threshold Relaxation is an Effective Means to Connect Gaps in 3 D Images of Complex Microvascular Networks , 2022 .

[9]  David A. Boas,et al.  Quantitative cerebral blood flow with Optical Coherence Tomography , 2010, Optics express.

[10]  J. Schuman,et al.  Optical coherence tomography. , 2000, Science.

[11]  Scott Barry,et al.  OCT methods for capillary velocimetry , 2012, Biomedical optics express.

[12]  J Flammer,et al.  Ocular blood flow alteration in glaucoma is related to systemic vascular dysregulation , 2004, British Journal of Ophthalmology.

[13]  M. Wong-Riley Energy metabolism of the visual system. , 2010, Eye and brain.

[14]  Teresa C. Chen,et al.  In vivo dynamic human retinal blood flow imaging using ultra-high-speed spectral domain optical Doppler tomography , 2003 .

[15]  Harsha Radhakrishnan,et al.  Compartment-resolved Imaging of Cortical Functional Hyperemia with Oct Angiography References and Links , 2022 .

[16]  Alejandro F. Frangi,et al.  Muliscale Vessel Enhancement Filtering , 1998, MICCAI.

[17]  D. Attwell,et al.  Capillary pericytes regulate cerebral blood flow in health and disease , 2014, Nature.

[18]  Ruikang K. Wang,et al.  Three dimensional optical angiography. , 2007, Optics express.

[19]  Brett E. Bouma,et al.  Statistical Properties of Phase-Decorrelation in Phase-Resolved Doppler Optical Coherence Tomography , 2009, IEEE Transactions on Medical Imaging.

[20]  W. Kruskal,et al.  Use of Ranks in One-Criterion Variance Analysis , 1952 .

[21]  Philip J. Morrow,et al.  Algorithms for digital image processing in diabetic retinopathy , 2009, Comput. Medical Imaging Graph..

[22]  Rui Bernardes,et al.  On the relevance of the 3D retinal vascular network from OCT data , 2012 .

[23]  Harsha Radhakrishnan,et al.  Total average blood flow and angiography in the rat retina , 2013, Journal of biomedical optics.

[24]  Rangasami L. Kashyap,et al.  Building Skeleton Models via 3-D Medial Surface/Axis Thinning Algorithms , 1994, CVGIP Graph. Model. Image Process..

[25]  Farshad Tajeripour,et al.  Computerized Medical Imaging and Graphics Automated Characterization of Blood Vessels as Arteries and Veins in Retinal Images , 2022 .

[26]  R. Klein,et al.  Retinal microvascular abnormalities and their relationship with hypertension, cardiovascular disease, and mortality. , 2001, Survey of ophthalmology.

[27]  J. Schmitt,et al.  Speckle in optical coherence tomography. , 1999, Journal of biomedical optics.

[28]  J. Izatt,et al.  Retinal blood flow measurement by circumpapillary Fourier domain Doppler optical coherence tomography. , 2008, Journal of biomedical optics.

[29]  David A Boas,et al.  Rapid volumetric angiography of cortical microvasculature with optical coherence tomography. , 2010, Optics letters.

[30]  Isabelle Bloch,et al.  A review of 3D vessel lumen segmentation techniques: Models, features and extraction schemes , 2009, Medical Image Anal..

[31]  J. Fujimoto,et al.  Optical coherence tomography of the human retina. , 1995, Archives of ophthalmology.

[32]  John P. Kaufhold,et al.  Vectorization of optically sectioned brain microvasculature: Learning aids completion of vascular graphs by connecting gaps and deleting open-ended segments , 2012, Medical Image Anal..

[33]  Wolfgang Drexler,et al.  State-of-the-art retinal optical coherence tomography , 2008, Progress in Retinal and Eye Research.

[34]  Philip Kollmannsberger,et al.  Architecture of the osteocyte network correlates with bone material quality , 2013, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[35]  J. Fujimoto,et al.  Optical Coherence Tomography , 1991, LEOS '92 Conference Proceedings.

[36]  Rui Bernardes,et al.  Two-dimensional segmentation of the retinal vascular network from optical coherence tomography , 2013, Journal of biomedical optics.

[37]  Eric A Newman,et al.  Regulation of Blood Flow in the Retinal Trilaminar Vascular Network , 2014, The Journal of Neuroscience.

[38]  Barry Cense,et al.  In vivo dynamic human retinal blood flow imaging using ultra-high-speed spectral domain optical coherence tomography. , 2003, Optics express.

[39]  B. Sagdullaev,et al.  Intersublaminar vascular plexus: the correlation of retinal blood vessels with functional sublaminae of the inner plexiform layer. , 2014, Investigative ophthalmology & visual science.

[40]  Laurent Risser,et al.  Gap Filling of 3-D Microvascular Networks by Tensor Voting , 2008, IEEE Transactions on Medical Imaging.

[41]  Zhongping Chen,et al.  Optical Doppler tomographic imaging of fluid flow velocity in highly scattering media. , 1997, Optics letters.

[42]  Yuankai K. Tao,et al.  Single-pass volumetric bidirectional blood flow imaging spectral domain optical coherence tomography using a modified Hilbert transform. , 2008, Optics express.

[43]  T. Yatagai,et al.  Optical coherence angiography. , 2006, Optics express.

[44]  Tao Ju,et al.  Interactive skeletonization of intensity volumes , 2009, The Visual Computer.

[45]  A. Pries,et al.  Blood flow in microvascular networks. Experiments and simulation. , 1990, Circulation research.

[46]  H. Novotny,et al.  A Method of Photographing Fluorescence in Circulating Blood in the Human Retina , 1961, Circulation.