The Indiana Adaptive Optics SLOs

 

A Scanning Laser Ophthalmoscope (SLO) is a type of confocal microscope which is optimized for imaging the eye.  Currently our system can image multiple layers of the retina in real time.  This provides exquisite images of the cells of the retina.  The figure to the right shows images of the cone photoreceptors of a human eye.  The fovea is just off-screen in the upper left corner of the figure.  Here we can clearly see the increasing size of the cone photoreceptors with increasing distance from the fovea.  The scale bar indicates a retinal size of 50 microns.  Below we show a montage with a more extended view of the normal fovea. 

In recent years the Burns group has developed four different adaptive optics systems.  These include one capable of performing real-time polarimetric imaging of the human retina, on optimized for small clinical instrumentation, developed in collaboration with Boston Micromachines Corp and now being deployed at Joslin Diabetes Center, our main system which uses dual deformable mirrors to allow imaging individuals with large refractive errors over a large field of view and a new system that allows precise measurment of blood velocity as well as using programmable apertures using DLP technology.  This system, by having a final stage of the optics which provides almost 30 degrees of view of the retina, allows us to use clinical images taken with traditional low resolution devices such as the Heidelberg Spectralis, and quickly deploy our high resolution images to the regions of most interest.

Publications on AO Systems

Publications incorporating results from AO

New:  Matlab Code for Gang Huang's Lucky Averaging is available here.

 

The figure shows the concept of AO on the left, and examples of our first generation system when we go from no adaptive optics (1b) to adaptive optics (1c).   We also show how the system can quickly sample different retinal layers by changing its view from the cones (1d) to the nerve fiber layer  (1e).   Because the second generation system (Ferguson et al 2010, Zou et al 2011) allows us to measure the foveal cones,  we can build a montage of the fovea and then plot the actual photoreceptor distribution (below). 

Because AOSLO systems provide real time imaging we are able to look at blood flow dynamically for mid and small vessels (Zhong, Z, Petrig, BL, Qi X and Burns SA “In vivo measurement of erythrocyte velocity and retinal blood flow using adaptive optics scanning laser ophthalmoscopy”) as well as produce structural images of the smallest capillaries as seen below).   We have followed up on this capablility by using the erythrocyte measurements to actually measure the velocity of blood flow at different locations across a retinal vessel, which opens the possibility of improving volume estimates of nutrient delivery and the interaction of blood with the vascular endothelium. (Zhong et al, IOVS, 2011) and even used it to measure the upregulation of blood flow to visual stimulation.

 

Visualizing the Smallest Capillaries - here we show the peripapillary capillaries, as well as a capillary map.   These images are obtained using our technique for capturing forward scatter from the erythrocytes.

 

 

 

 

Foveal Cone Mosaic can be built up using montaging techniques that are potentiated by the retinal tracking and stabilization.  Large data sets of cone images and cone locations can be downloaded from the Journal of the Optical Society of America A (Chui, T. Y. P., H. Song, Burns, SA "Individual variations in human cone photoreceptor packing density" JOSA A 25:3021-3029 ,2008.).  There are links in the paper to access the experimental interface for viewing data sets.  This is open access.

Working with Charles Lin at MGH we have also helped to generate the first AO Images from a Mouse Eye by Dave Biss (see papers below).

 

  

 

 

 

 

 

 Polarization Sensitive AOSLO

We have also developed techniques to look at the Stokes Vector of microscopic structures in the retina.  The image below shows that the cone photoreceptors preserve polarization (they are bright in the central degree of Polarization Image, and dark in the Depolarization Image (center and right respectively).  This technology has now been moved to electro-optics devices, allowing us to make more than 540,000 Stokes Vector measurements per second!

 

Adaptive Optics Optical Coherence Tomograpy

Our original system has integrated OCT into the AOSLO imaging,.  This allows us to compare the excellent en face images available with the AOSLO, to obtain accurate depth profiles.   We have since become better integrated with the Heidelberg Spectralis system and to improve patient experience we removed the custom OCT and developed a customizable mapping of our steerable AOSLO with the Heidelberg system (Huang et al, reference below).

 

 

 

 

Relevant Publications for Adaptive Optics

System Design and Performance

  1. Burns, SA, Marcos, S, Elsner, AE, Bara, S, “Contrast Improvement for Confocal Retinal Imaging Using Phase Correcting Plates”  Optics Letters. 27: 400-402, 2002.(full text)
  2. Webb, RH, Albanese, MJ, Zhou, Y, Bifano, T and Burns, SA “A stroke amplifier for deformable mirrors” Applied Optics 43(28), 5330-5333 , 2004 (full text)
  3. Ferguson, RD, Hammer,DX,  Bigelow CD, Iftimia , NV, Ustun te, Burns, SA, Elsner, AE, Williams, DR, (2006) Tracking adaptive optics scanning laser ophthalmoscope, Proceeding, SPIE.
  4. Hammer,DX, Ferguson, RD,  Bigelow CD, Iftimia , NV, Ustun te, Burns, SA, "Adaptive optics scanning laser ophthalmoscope for stabilized retinal imaging", Opt. Express 14, 3354-3367 (2006)
  5. Burns, SA, Tumbar R, Elsner AE, Ferguson RD, Hammer DX “Large Field of View, Modular, Stabilized, Adaptive-Optics-Based Scanning Laser Ophthalmoscope” . J. Opt. Soc Amer,  JOSA A, 1313-1326 (2007).
  6. Hammer,DX, Iftimia , N, Bigelow CD, Ustun TE, Bloom B, Ferguson, RD, Burns, SA, (2007) High resolution retinal imaging with a compact adaptive optics spectral domain optical coherence tomography system Proceeding, SPIE.
  7. 70. Zhong, Z, Petrig, BL, Qi X and Burns SA “In vivo measurement of erythrocyte velocity and retinal blood flow using adaptive optics scanning laser ophthalmoscopy” Optics Express Vol. 16, Issue 17, pp. 12746-12756 , 2008, PMCID: PMC2738983Song, H, Zhao, Y, Chui, Y, Qi X, Burns, SA, Stokes Vector Analysis of Adaptive Optics Images of the Retina, Optics Letters, 33, 137-140. (2008)
  8.  Zou, W, Qi, X, Burns, SA, “Wavefront aberration sorting and correction for dual-deformable-mirror adaptive optics system” Optics Letters, Vol. 33, Issue 22, pp. 2602-2604, 2008
  9. Zou, W, Burns, SA, "High-accuracy wavefront control for retinal imaging with Adaptive-Influence-Matrix Adaptive Optics" Optics Express. Vol. 17 Issue 22, pp.20167-20177 (2009)
  10. Ferguson, RD, Zhong, Z, Hammer, DX, Mujat, M, Patel, AH, Deng, C, Zou, W, Burns, SA, "Adaptive optics SLO with integrated wide-field retinal imaging and tracking" " J. Opt. Soc. Am. A 27, A265-A277 (2010). PMC in process
  11. Song H, Qi X, Zou W, Zhong Z, Burns SA, Dual electro-optical modulator polarimeter based on adaptive optics scanning laser ophthalmoscope Optics Express, Vol. 18, Issue 21, pp. 21892-21904 (2010) doi:10.1364/OE.18.021892
  12. Zhong Z, Song H, Chui TYP, Petrig BL, and Burns SA “Non-invasive measurements and analysis of blood velocity profiles in human retinal vessels”, Investigative Ophthalmology and Vision Science. June 10, 2011 vol. 52 no. 7 4151-4157 (2011), PMC3175937 Zou, W, Qi, X, Burns, SA, “Woofer-tweeter adaptive optics scanning laser ophthalmoscopic imaging based on Lagrange-multiplier damped least-squares algorithm”, Biomedical Optics Express. Vol. 2, Issue 7, pp. 1986-2004 doi:10.1364/BOE.2.001986. (2011)
  13. Gang H, Zhong, Z, Zou W, Burns, SA “Lucky Averaging: Quality improvement on Adaptive Optics Scanning Laser Ophthalmoscope Images” Optics Letters, Vol. 36, No. 19 3786-3789 (2011).
  14. Zou, W, Qi, X, Huang, G, Burns, SA, Improving wavefront boundary condition for in vivo high resolution adaptive optics ophthalmic imaging, Biomedical Optics Express. Vol. 2, Issue 12, pp. 3309-3320 (2011)
  15. Zou W, Burns SA. Testing of Lagrange multiplier damped least-squares control algorithm for woofer-tweeter adaptive optics. Appl Opt. 2012 Mar 20;51(9):1198-208. doi: 10.1364/AO.51.001198. PubMed PMID: 2441462.
  16. Chui, T. Y. P., D. A. VanNasdale and S. A. Burns (2012). "The use of forward scatter to improve retinal vascular imaging with an adaptive optics scanning laser ophthalmoscope." Biomed. Opt. Express 3(10): 2537-2549.
  17. Huang G, Qi X, Chui TY, Zhong Z, Burns SA. A Clinical Planning Module for Adaptive Optics SLO Imaging. Optom Vis Sci. 2012 May;89(5):593-601. PubMed PMID: 22488269; PubMed Central PMCID: PMC3348407.

Investigations

  1. Biss, D, Sumorok, D, Burns, SA, Webb RH, Zhou Y, Bifano, T, Veilleux I, Zamiri P, and Lin C. “In vivo flourescent imaging of the mouse retina using adaptive optics” Optics Letters  659-661 (2007)
  2. Chui, Y, Song, H, Burns, SA, “Individual variations in human cone photoreceptor packing density: variations with refractive error.” Investigative Ophthalmology and Vision Science First published on Jun 14, 2008 as doi: doi:10.1167/iovs.08-2135
  3. Zhong, Z, Petrig, BL, Qi X and Burns SA “In vivo measurement of erythrocyte velocity and retinal blood flow using adaptive optics scanning laser ophthalmoscopy” Optics Express Vol. 16, Issue 17, pp. 12746-12756 (2008)
  4. Chui, T. Y. P., H. Song, Burns, SA "Individual variations in human cone photoreceptor packing density" JOSA A 25:3021-3029 ,2008.
  5. Chui, TYP, Thibos, LN, Bradley, A, Burns, SA " The mechanism of vision loss associated with a cotton-wool spot" Vision Research Volume 49, Pages 2826-2834
  6.  Zhong Z, Song H, Chui TYP, Petrig BL, and Burns SA “Non-invasive measurements and analysis of blood velocity profiles in human retinal vessels”, (2011), Investigative Ophthalmology and Vision Science.52 no. 7 4151-4157
  7.  Zou, W, Qi, X, Burns, SA, “Woofer-tweeter adaptive optics scanning laser ophthalmoscopic imaging based on Lagrange-multiplier damped least-squares algorithm”, Biomedical Optics Express. Vol. 2, Issue 7, pp. 1986-2004 doi:10.1364/BOE.2.001986. (2011)
  8. Song, H, Chui TYCP, Zhong, Z, Elsner, AE, Burns, SA “Variation of Cone Photoreceptor Packing Density with Retinal Eccentricity and Age”, Investigative Ophthalmology and Vision Science 52:7376-7384 2011.
  9. Chui, TYP, Zhong, Z, Burns, SA “The relationship between peripapillary crescent and axial length: implications for differential eye growth” , doi:10.1016/j.visres.2011.08.008
  10. Chui TY, Song H, Clark CA, Papay JA, Burns SA, Elsner AE. Cone photoreceptor packing density and the outer nuclear layer thickness in healthy subjects. Invest Ophthalmol Vis Sci. 2012 May 8. [Epub ahead of print] PubMed PMID: 22570340.
  11. Zhong, Z Huang, G, Chui TYCP, Petrig BL, Burns, SA. “Local Stimulus Flicker Evokes Local Retinal Blood Flow Changes” Journal of Vision (2012) 12(6):3, 1–8
  12. Chui, T. Y. P., D. A. VanNasdale and S. A. Burns (2012). "The use of forward scatter to improve retinal vascular imaging with an adaptive optics scanning laser ophthalmoscope." Biomed. Opt. Express 3(10): 2537-2549.
  13. Chui, T.Y., T.J. Gast, and S.A. Burns, Imaging of vascular wall fine structure in the human retina using adaptive optics scanning laser ophthalmoscopy. Invest Ophthalmol Vis Sci, 2013. 54(10): p. 7115-24. PMCID:3813321
  14. Burns, S.A., A.E. Elsner, T.Y. Chui, D.A. Vannasdale, Jr., C.A. Clark, T.J. Gast, V.E. Malinovsky, and A.D. Phan, In vivo adaptive optics microvascular imaging in diabetic patients without clinically severe diabetic retinopathy. Biomed Opt Express, 2014. 5(3): p. 961-74. PMCID:3959854
  15. Chui, T.Y.P, Elsner, AE, vanNasdale, DA, Burns S.A. “The association between the foveal avascular zone and retinal thickness" Investigative Ophthalmology and Vision Science, 2014. Sep 30;55(10):6870-7. doi: 10.1167/iovs.14-15446. PMID: 25270194

  16. Huang G, Luo T,Gast TJ,Burns SA,Malinovsky VE,Swanson WH.Imaging glaucomatous damage across the temporal raphe. Invest Ophthalmol VisSci. 2015; 56: 3496–3504.DOI:10.1167/iovs.15-16730 PMID: 26047040 PMCID: PMC4464103
  17. de Castro Alberto, Huang Gang, Sawides, Lucie, Luo, Ting, Burns, Stephen A., Rapid high resolution imaging with a dual-channel scanning technique, Optics Letters: 2016 41(8) 1881-1884 PMID: 27082369 PMCID in process
  18. Fu X, Gens JS, Glazier JA, Burns SA, Gast TJ (2016) Progression of Diabetic Capillary Occlusion: A Model. PLoS Comput Biol 12(6): e1004932. doi:10.1371/journal.pcbi.1004932, PMID: 27300722 PMCID:4907516

  19. Sawides L, De Castro A, Burns SA. The organization of the cone photoreceptor mosaic measured in the living human retina. Vision Res. 2016 Aug 3. pii: S0042-6989(16)30049-9. doi: 10.1016/j.visres.2016.06.006 PMCID in process
  20. Elsner AE. Chui TYP, Lei F, Song HX, Papay JA, and Burns SA. "Distribution differences of macular cones measured by AOSLO: variation in slope from fovea to periphery more pronounced than differences in total cones" Vision Res. 2016 Nov 3. pii: S0042-6989(16)30106-7. doi: 10.1016/j.visres.2016.06.015. PMCID in process
  21. Hillard, J, Gast TJ, Chui, TYP, Sapir D, Burns SA. Retinal Arterioles In Hypo-,Normo-, And Hypertensive Subjects Measured Using Adaptive Optics, Translational Vision Science & Technology August 2016, Vol.5, 16. doi:10.1167/tvst.5.4.16 PMC5015982
  22. King, BJ; Sapoznik, KA; Elsner, AE; Gast, TJ; Papay, JA; Clark, CA; Burns, SA, Spectral Domain Optical Coherence Tomography and Adaptive Optics Imaging of Outer Retinal Tubulation , Optometry and Visual Science (in press). PMCID in process
  23. Lammer J, Prager SG, Cheney MC, Ahmed A, Radwan SH, Burns SA, Silva PS, Sun, JK “Cone Photoreceptor Irregularity on Adaptive Optics Scanning Laser Ophthalmoscopy Correlates with Severity of Diabetic Retinopathy and Macular Edema" IOVS, (in press). PMCID in process

  24.  

MORE Pictures (large mosaics are available through the experimental interface for Interactive Science Publishing, a joint project of the Optical Society of America and The National Library of Medicine- our paper is here.