1. Phase-Resolved Optical Frequency Domain Imaging Of The Human Retina On The Reliable Discrimination Of Retinal Blood Flow Master of Physics Symposium Leah S. Wilk 11.04.2014

2. Leah S. WilkMaster of Physics Symposium – 11.04.2014 The Human Eye

3. Serlin et al. (2013), PLoS ONE 8(4) E61599; doi:10.1371/journal.pone.0061599 Giustolisi et al. (2011), Digit. J.Ophthalmol. 17(3); 23-30 Healthy Age Related Macular Degeneration Leah S. WilkMaster of Physics Symposium – 11.04.2014 Imaging of Ocular Hemodynamics: Fluorescein Angiography

4. Fox, Quantum Optics (2006); Oxford University Press; p. 15 Michaelson Interferometer Leah S. WilkMaster of Physics Symposium – 11.04.2014 Depth Resolved Imaging: OFDI

5. Leah S. WilkMaster of Physics Symposium – 11.04.2014 Intensity [A.U.] Wavevector [2 π/λ ] Fourier Transform De Boer, J F (2013) (VU Amsterdam) Master Course – Biomedical Optics: Optical Coherence Tomography (Amplitude α, Phase ϕ) Depth Resolved Imaging: OFDI

6. Amplitude [A.U.] Distance [  m] Leah S. WilkMaster of Physics Symposium – 11.04.2014 Intensity [A.U.] Wavevector [2 π/λ ] Fourier Transform De Boer, J F (2013) (VU Amsterdam) Master Course – Biomedical Optics: Optical Coherence Tomography Depth Resolved Imaging: OFDI

7. 2D – Scan: Cross sectional image (B-Scan) https://wiki.engr.illinois.edu /display/BIOE414/The+Princ iples+Behind+OCT Plot to greyscale Acquire adjacent depth profiles by scanning the sample 1D – Scan: Depth Profile (A-Line) Scan direction Depth Leah S. Wilk Phase π 0 - π Master of Physics Symposium – 11.04.2014 Rendering Images

8. Healthy, young volunteerAMD-Patient, 90 years old Leah S. Wilk (VU Amsterdam), Jan H. de Jong (Rotterdam Ophthalmic Institute), 2013, Unpublsihed Results Leah S. WilkMaster of Physics Symposium – 11.04.2014 Imaging of Ocular Hemodynamics: PR-OFDI

9. Leah S. Wilk (VU Amsterdam), Jan H. de Jong (Rotterdam Ophthalmic Institute), 2013, Unpublsihed Results Leah S. WilkMaster of Physics Symposium – 11.04.2014 Integration in depth Imaging of Ocular Hemodynamics: PR-OFDI

10. FA Leah S. Wilk (VU Amsterdam), Jan H. de Jong (Rotterdam Ophthalmic Institute), 2013, Unpublished Results Leah S. WilkMaster of Physics Symposium – 11.04.2014 PR-OFDI FA = Fluorescein Angiography PR-OFDI = Phase-Resolved Optical Frequency Domain Imaging Imaging of Ocular Hemodynamics: PR-OFDI

11. Leah S. WilkMaster of Physics Symposium – 11.04.2014 Blood Flow Discrimination

12. Until now an empirically derived value of 0.3 rad was used for when discriminating blood flow The approach presented here estimates for every pixel from local signal statistics: Leah S. WilkMaster of Physics Symposium – 11.04.2014 Improving Blood Flow Discrimination

13. Leah S. Wilk Master of Physics Symposium – 11.04.2014 Estimating Re-Visitation Error

14. Retina Choroid Discriminating Blood Flow in Retinal Layers Leah S. Wilk Master of Physics Symposium – 11.04.2014 Leah S. Wilk (VU Amsterdam) and Jan H. de Jong (Rotterdam Ophthalmic Institue), 2013, Unpublished Results

15. Results: Retinal Blood Flow Detection Leah S. WilkMaster of Physics Symposium – 11.04.2014 Leah S. Wilk (VU Amsterdam) and Jan H. de Jong (Rotterdam Ophthalmic Institue), 2013, Unpublished Results

16. Results: Noise Removal Leah S. WilkMaster of Physics Symposium – 11.04.2014 Leah S. Wilk (VU Amsterdam) and Jan H. de Jong (Rotterdam Ophthalmic Institue), 2013, Unpublished Results

17. Results: Lens Artefact Removal Leah S. Wilk Master of Physics Symposium – 11.04.2014 Leah S. Wilk (VU Amsterdam) and Jan H. de Jong (Rotterdam Ophthalmic Institue), 2013, Unpublished Results

18. Results: Lens Artefact Removal Leah S. Wilk Master of Physics Symposium – 11.04.2014 Leah S. Wilk (VU Amsterdam) and Jan H. de Jong (Rotterdam Ophthalmic Institue), 2013, Unpublished Results

19. Results: Choroidal Blood Flow Detection Leah S. WilkMaster of Physics Symposium – 11.04.2014 Leah S. Wilk (VU Amsterdam) and Jan H. de Jong (Rotterdam Ophthalmic Institue), 2013, Unpublished Results

20. B-Scan is considered motion artefact if the mean re- visitation error of the B-scan is not within one standard deviation of the mean re-visitation error of the entire volume Leah S. WilkMaster of Physics Symposium – 11.04.2014 Removal of Eye Motion Artefacts

21. Leah S. WilkMaster of Physics Symposium – 11.04.2014 Leah S. Wilk (VU Amsterdam) and Jan H. de Jong (Rotterdam Ophthalmic Institue), 2013, Unpublished Results

22. Estimation of data point-specific noise levels facilitates more reliable discrimination of retinal blood flow and can improve quality of PR-OFDI images PR-OFDI is capable of reliably, non-invasively and simultaneously visualising retinal and choroidal blood flow in the human eye in great detail Leah S. WilkMaster of Physics Symposium – 11.04.2014 Conclusions

23. Boy Braaf (ROI, VU) Dr. Koen A. Vermeer (ROI) Jan H. de Jong (ROI, Erasmus MC) Kari V. Vienola (ROI, VU) Prof. Johannes F. de Boer (VU, ROI) Acknowledgements Leah S. WilkMaster of Physics Symposium – 11.04.2014

24. Experimental Set-Up Braaf et al., Opt. Express 19 (2011); 20886-20903 Leah S. WilkMaster of Physics Symposium – 11.04.2014

25. Backstitching: Lateral scan width is segmented Every segment is re-scanned B-scan segments are concatenated (“backstitched”) Backstitching: B-Scan 1 and B-Scan 2 are created by “stitching” the individual scan segments “back” together: Data Acquisition : B-Scan 1 : B-Scan 2 : “Mirror Fly-Back“ Lateral Sample Scan Width Motion of X/Y Scanning Mirrors B-Scan 1: B-Scan 2: OCT - Beam Leah S. WilkMaster of Physics Symposium – 11.04.2014

26. Signal-to-noise ratio can be translated into uncertainty (i.e. noise) in phase difference: SNR Noise Signal-to-noise ratio Leah S. WilkMaster of Physics Symposium – 11.04.2014 * Park et al., Opt. Express 13(11) (2005); 3931-3944

27. Errors in re-visiting the first measurement location introduce additional difference in phase Phase difference noise due to re-visitation error: Re-Visitation Inaccuracy * Park et al., Opt. Express 13(11) (2005); 3931-3944 Beam displacement Beam diameter Leah S. WilkMaster of Physics Symposium – 11.04.2014

28. Interference term Depth Resolved Imaging: OFDI Leah S. WilkMaster of Physics Symposium – 11.04.2014 De Boer, J F (2013) (VU Amsterdam) Master Course – Biomedical Optics: Optical Coherence Tomography

29. Phase difference between two OFDI signals of structures with flow (moving scatterers) given by: Limiting Factors * Zhao et al., Opt. Lett. 25 (2) (2000); 1448-1450 Leah S. WilkMaster of Physics Symposium – 11.04.2014

30. To judge reliability of a measurement requires knowledge of its noise Total phase difference noise for a pixel is given by: This limits the smallest reliably observable flow velocity to: Blood Flow Discrimination Leah S. WilkMinor Master Project – 20.01.2014

31. 1.A layer without blood flow but high SNR is selected in the retina (RNFL) in every B-scan (RNFL = top layer of the retina) 2.Any measured phase differences there are attributed to noise (no flow) 3.A 3 x 3 kernel is moved across the layer and the re-visitation noise for the central pixel’s A-line (depth profile) is calculated using: Estimating The “Revisitation Noise” Leah S. WilkMinor Master Project – 20.01.2014

32. 4.Total noise for every pixel is then computed via: 5.Likely presence of blood flow in a pixel is determined by comparing a pixel’s phase difference to its noise: Estimating The Individual Noise Levels Leah S. WilkMinor Master Project – 20.01.2014

33. Results: Retrieving Micro-Details Maximum Intensity Projection Summed Intensity Projection Leah S. WilkMinor Master Project – 20.01.2014 Leah S. Wilk (VU Amsterdam) and Jan H. de Jong (Rotterdam Ophthalmic Institue), 2013, Unpublished Results

34. Results: Retinal Blood Flow Detection Leah S. WilkMinor Master Project – 20.01.2014 Leah S. Wilk (VU Amsterdam) and Jan H. de Jong (Rotterdam Ophthalmic Institue), 2013, Unpublished Results

35. Results: Retrieving Micro-Detail Maximum Intensity Projection Summed Intensity Projection Leah S. WilkMinor Master Project – 20.01.2014 Leah S. Wilk (VU Amsterdam) and Jan H. de Jong (Rotterdam Ophthalmic Institue), 2013, Unpublished Results

36. Results: Choroidal Blood Flow Detection Leah S. WilkMinor Master Project – 20.01.2014 Leah S. Wilk (VU Amsterdam) and Jan H. de Jong (Rotterdam Ophthalmic Institue), 2013, Unpublished Results

37. References 1.Serlin et al. (2013), PLoS ONE 8(4) E61599; doi:10.1371/journal.pone.0061599 2.Giustolisi et al. (2011), Digit. J. Ophthalmol. 17(3); 23-30 3.Fox, Quantum Optics (2006); Oxford University Press; p. 15 4.De Boer, J F (2013) (VU Amsterdam) Master Course – Biomedical Optics: Optical Coherence Tomography. A (minimally invasive) optical technique to visualise function and structure in biological tissue. 5.Braaf et al., Opt. Express 19 (2011); 20886-20903. 6. Zhao et al., Opt. Lett. 25 (2) (2000); 1448-1450. 7. Park et al., Opt. Express 13(11) (2005); 3931-3944. Leah S. WilkMinor Master Project – 20.01.2014