The Indiana Adaptive Optics SLO

Project Director:  Stephen A. Burns, Ph.D. (Research Home Page)

The Indiana Adaptive Optics Scanning Laser Ophthalmoscopes have been developed under an NIH Bioengineering Partnership (NEI RO1 EY14375 – “Adaptive Optics Instrumentation for Advanced Ophthalmic Imaging” ).   Our center is working on combining high resolution SLO technology with both scattered light imaging, polarization state imaging, and image stabilization (See Reference List).  A special emphasis is the ability to quickly sample high resolution images over a wide retinal region.

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 three 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, and out main system which uses dual deformable mirrors to allow imaging inviduals with large refractive errors over a large field of view.   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

 

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 e ven the foveal cones,  we can build a montage of the fovea and then plot the actual photoreceptor distribution (below). 

 

 

 

This image shows our first generation system.  

We are able to look at blood flow dynamically (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)) as well as produce structural images of the smallest calillaries 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).

 

Visualizing the Smallest Capillaries

 

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 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.

 

 

 

 

 

 

 

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. Song, 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.  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. 85. Zou, W, Burns, SA “Testing of Lagrange-multiplier damped least-squares control algorithm for Woofer -Tweeter adaptive optics” in press Applied Optics

 

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

     

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.