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

Leah S. WilkMaster of Physics Symposium – The Human Eye

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

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

Leah S. WilkMaster of Physics Symposium – 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

Amplitude [A.U.] Distance [  m] Leah S. WilkMaster of Physics Symposium – 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

2D – Scan: Cross sectional image (B-Scan) /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 – Rendering Images

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 – Imaging of Ocular Hemodynamics: PR-OFDI

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

FA Leah S. Wilk (VU Amsterdam), Jan H. de Jong (Rotterdam Ophthalmic Institute), 2013, Unpublished Results Leah S. WilkMaster of Physics Symposium – PR-OFDI FA = Fluorescein Angiography PR-OFDI = Phase-Resolved Optical Frequency Domain Imaging Imaging of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

Leah S. WilkMaster of Physics Symposium – Blood Flow Discrimination

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 – Improving Blood Flow Discrimination

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

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Master of Physics Symposium – Leah S. Wilk (VU Amsterdam) and Jan H. de Jong (Rotterdam Ophthalmic Institue), 2013, Unpublished Results

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WilkMaster of Physics Symposium – Leah S. Wilk (VU Amsterdam) and Jan H. de Jong (Rotterdam Ophthalmic Institue), 2013, Unpublished Results

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WilkMaster of Physics Symposium – Leah S. Wilk (VU Amsterdam) and Jan H. de Jong (Rotterdam Ophthalmic Institue), 2013, Unpublished Results

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Master of Physics Symposium – Leah S. Wilk (VU Amsterdam) and Jan H. de Jong (Rotterdam Ophthalmic Institue), 2013, Unpublished Results

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

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

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 – Removal of Eye Motion Artefacts

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

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 – Conclusions

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 –

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

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 –

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 – * Park et al., Opt. Express 13(11) (2005);

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); Beam displacement Beam diameter Leah S. WilkMaster of Physics Symposium –

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

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

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 –

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 –

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 –

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

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

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

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

References 1.Serlin et al. (2013), PLoS ONE 8(4) E61599; doi: /journal.pone Giustolisi et al. (2011), Digit. J. Ophthalmol. 17(3); Fox, Quantum Optics (2006); Oxford University Press; p 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); Zhao et al., Opt. Lett. 25 (2) (2000); Park et al., Opt. Express 13(11) (2005); Leah S. WilkMinor Master Project –