Using ultrahigh sensitive optical microangiography to achieve comprehensive depth resolved microvasculature mapping for human retina.

This paper presents comprehensive and depth-resolved retinal microvasculature images within human retina achieved by a newly developed ultrahigh sensitive optical microangiography (UHS-OMAG) system. Due to its high flow sensitivity, UHS-OMAG is much more sensitive to tissue motion due to the involuntary movement of the human eye and head compared to the traditional OMAG system. To mitigate these motion artifacts on final imaging results, we propose a new phase compensation algorithm in which the traditional phase-compensation algorithm is repeatedly used to efficiently minimize the motion artifacts. Comparatively, this new algorithm demonstrates at least 8 to 25 times higher motion tolerability, critical for the UHS-OMAG system to achieve retinal microvasculature images with high quality. Furthermore, the new UHS-OMAG system employs a high speed line scan CMOS camera (240 kHz A-line scan rate) to capture 500 A-lines for one B-frame at a 400 Hz frame rate. With this system, we performed a series of in vivo experiments to visualize the retinal microvasculature in humans. Two featured imaging protocols are utilized. The first is of the low lateral resolution (16 μm) and a wide field of view (4 × 3 mm(2) with single scan and 7 × 8 mm(2) for multiple scans), while the second is of the high lateral resolution (5 μm) and a narrow field of view (1.5 × 1.2 mm(2) with single scan). The great imaging performance delivered by our system suggests that UHS-OMAG can be a promising noninvasive alternative to the current clinical retinal microvasculature imaging techniques for the diagnosis of eye diseases with significant vascular involvement, such as diabetic retinopathy and age-related macular degeneration.

[1]  Benjamin J Vakoc,et al.  Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging , 2009, Nature Medicine.

[2]  Ruikang K. Wang,et al.  Theory, developments and applications of optical coherence tomography , 2005 .

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

[4]  Lingfeng Yu,et al.  Doppler variance imaging for three-dimensional retina and choroid angiography. , 2010, Journal of biomedical optics.

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

[6]  Ruikang K. Wang,et al.  Depth-resolved imaging of capillary networks in retina and choroid using ultrahigh sensitive optical microangiography. , 2010, Optics letters.

[7]  M. Wojtkowski,et al.  Flow velocity estimation using joint Spectral and Time domain Optical Coherence Tomography. , 2008, Optics express.

[8]  Zhongping Chen,et al.  Phase-resolved optical coherence tomography and optical Doppler tomography for imaging blood flow in human skin with fast scanning speed and high velocity sensitivity. , 2000, Optics letters.

[9]  Ruikang K. Wang,et al.  High-resolution wide-field imaging of retinal and choroidal blood perfusion with optical microangiography. , 2010, Journal of biomedical optics.

[10]  Robert J Zawadzki,et al.  Volumetric microvascular imaging of human retina using optical coherence tomography with a novel motion contrast technique. , 2009, Optics express.

[11]  Martin Leahy,et al.  In vivo imaging of the microcirculation of the volar forearm using correlation mapping optical coherence tomography (cmOCT) , 2011, Biomedical optics express.

[12]  Daniel M. Schwartz,et al.  In vivo volumetric imaging of human retinal circulation with phase-variance optical coherence tomography , 2011, Biomedical optics express.

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

[14]  Ruikang K. Wang,et al.  Doppler optical micro-angiography for volumetric imaging of vascular perfusion in vivo. , 2009, Optics express.

[15]  Shuliang Jiao,et al.  Simultaneous acquisition of sectional and fundus ophthalmic images with spectral-domain optical coherence tomography. , 2005, Optics express.

[16]  Shuichi Makita,et al.  Optical coherence angiography for the eye , 2009 .

[17]  Ruikang K. Wang,et al.  In vivo volumetric imaging of vascular perfusion within human retina and choroids with optical micro-angiography. , 2008, Optics express.

[18]  R. Leitgeb,et al.  Visualization of microvasculature by dual-beam phase-resolved Doppler optical coherence tomography. , 2011, Optics express.

[19]  Andrew G. Glen,et al.  APPL , 2001 .

[20]  Shuichi Makita,et al.  Comprehensive in vivo micro-vascular imaging of the human eye by dual-beam-scan Doppler optical coherence angiography. , 2011, Optics express.

[21]  E. Kohner,et al.  Retinal blood flow in diabetic retinopathy. , 1992, BMJ.

[22]  Joseph A Izatt,et al.  Velocity-resolved 3D retinal microvessel imaging using single-pass flow imaging spectral domain optical coherence tomography. , 2009, Optics express.

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

[24]  Ruikang K. Wang,et al.  Real-time flow imaging by removing texture pattern artifacts in spectral-domain optical Doppler tomography. , 2006, Optics letters.

[25]  Adrian Mariampillai,et al.  Speckle variance detection of microvasculature using swept-source optical coherence tomography. , 2008, Optics letters.

[26]  Ruikang K. Wang,et al.  Ultrahigh sensitive optical microangiography for in vivo imaging of microcirculations within human skin tissue beds. , 2010, Optics express.

[27]  Dao-Yi Yu,et al.  Microstructure and network organization of the microvasculature in the human macula. , 2010, Investigative ophthalmology & visual science.

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

[29]  M Palta,et al.  Abnormalities of the foveal avascular zone in diabetic retinopathy. , 1984, Archives of ophthalmology.

[30]  R. Leitgeb,et al.  Resonant Doppler flow imaging and optical vivisection of retinal blood vessels. , 2007, Optics express.

[31]  Ruikang K. Wang,et al.  Optical microangiography provides depth-resolved images of directional ocular blood perfusion in posterior eye segment. , 2010, Journal of biomedical optics.

[32]  E. Friedman A hemodynamic model of the pathogenesis of age-related macular degeneration. , 1997, American journal of ophthalmology.

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

[34]  A. Fercher,et al.  Optical coherence tomography - principles and applications , 2003 .

[35]  Rainer A. Leitgeb,et al.  Imaging of the parafoveal capillary network and its integrity analysis using fractal dimension , 2011 .

[36]  R. Zawadzki,et al.  Real-time assessment of retinal blood flow with ultrafast acquisition by color Doppler Fourier domain optical coherence tomography. , 2003, Optics express.

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