Download Quantitative Retinal Blood Flow Evaluation Using Doppler OCT

Phase-Resolved Optical Frequency
Domain Imaging Of The Human Retina
On The Reliable Discrimination Of Retinal Blood Flow
Master of Physics Symposium
11.04.2014
Leah S. Wilk
Master of Physics Symposium – 11.04.2014
Leah S. Wilk
The Human Eye
Master of Physics Symposium – 11.04.2014
Leah S. Wilk
Imaging of Ocular Hemodynamics:
Fluorescein Angiography
Healthy
Serlin et al. (2013), PLoS ONE 8(4)
E61599; doi:10.1371/journal.pone.0061599
Age Related Macular Degeneration
Giustolisi et al. (2011), Digit. J.Ophthalmol.
17(3); 23-30
Master of Physics Symposium – 11.04.2014
Leah S. Wilk
Depth Resolved Imaging: OFDI
Michaelson Interferometer
Fox, Quantum Optics (2006);
Oxford University Press; p. 15
Master of Physics Symposium – 11.04.2014
Leah S. Wilk
Depth Resolved Imaging: OFDI
Intensity [A.U.]
Fourier Transform
(Amplitude α , Phase ϕ)
Wavevector [2π/λ]
De Boer, J F (2013) (VU Amsterdam) Master Course –
Biomedical Optics: Optical Coherence Tomography
Master of Physics Symposium – 11.04.2014
Leah S. Wilk
Depth Resolved Imaging: OFDI
Wavevector [2π/λ]
De Boer, J F (2013) (VU Amsterdam) Master Course –
Biomedical Optics: Optical Coherence Tomography
Amplitude [A.U.]
Intensity [A.U.]
Fourier Transform
Distance [mm]
Master of Physics Symposium – 11.04.2014
Leah S. Wilk
Rendering Images
2D – Scan: Depth
Cross sectional
image (B-Scan)
1D
Profile (A-Line)
Scan direction
Phase
Depth
to greyscale
AcquirePlot
adjacent
depth
profiles by scanning the
sample
π
0
https://wiki.engr.illinois.edu
/display/BIOE414/The+Princ
iples+Behind+OCT
-π
Master of Physics Symposium – 11.04.2014
Leah S. Wilk
Imaging of Ocular Hemodynamics: PR-OFDI
Healthy, young volunteer
AMD-Patient, 90 years old
Leah S. Wilk (VU Amsterdam), Jan H. de Jong (Rotterdam
Ophthalmic Institute), 2013 , Unpublsihed Results
Master of Physics Symposium – 11.04.2014
Leah S. Wilk
Imaging of Ocular Hemodynamics: PR-OFDI
Leah S. Wilk (VU Amsterdam), Jan H. de Jong (Rotterdam
Ophthalmic Institute), 2013 , Unpublsihed Results
Master of Physics Symposium – 11.04.2014
Leah S. Wilk
Imaging of Ocular Hemodynamics: PR-OFDI
FA
FA
PR-OFDI
FA = Fluorescein Angiography
PR-OFDI = Phase-Resolved Optical
Frequency Domain Imaging
Leah S. Wilk (VU Amsterdam), Jan H. de Jong (Rotterdam
Ophthalmic Institute), 2013 , Unpublished Results
Master of Physics Symposium – 11.04.2014
Leah S. Wilk
Blood Flow Discrimination
• Reliably discriminating blood flow requires
knowledge of the measurement noise 𝜎𝛥𝜙
• Pixels with     are likely to contain blood
flow
Master of Physics Symposium – 11.04.2014
Leah S. Wilk
Improving 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:
    SNR   x
2
2
Master of Physics Symposium – 11.04.2014
Leah S. Wilk
Estimating Re-Visitation Error
 x , Aline
Master of Physics Symposium – 11.04.2014
Leah S. Wilk
Discriminating Blood Flow in Retinal Layers
Retina
Choroid
Leah S. Wilk (VU Amsterdam) and
Jan H. de Jong (Rotterdam Ophthalmic Institue), 2013, Unpublished Results
Master of Physics Symposium – 11.04.2014
Leah S. Wilk
Results: Retinal Blood Flow Detection
 0.3 rad
 Pixel
Pixel   ,Pixel
En-face (3 x 3 𝑚𝑚2 ) of the human retina: AMD-Patient, 67 years old
Leah S. Wilk (VU Amsterdam) and Jan H. de Jong (Rotterdam Ophthalmic Institue),
2013, Unpublished Results
Master of Physics Symposium – 11.04.2014
Leah S. Wilk
Results: Noise Removal
 Pixel    ,Pixel
 Pixel  0.3 rad
En-face (3 x 3 𝑚𝑚2 ) of the human retina: AMD-Patient, 67 years old
Leah S. Wilk (VU Amsterdam) and Jan H. de Jong (Rotterdam Ophthalmic Institue),
2013, Unpublished Results
Master of Physics Symposium – 11.04.2014
Leah S. Wilk
Results: Lens Artefact Removal
Leah S. Wilk (VU Amsterdam) and Jan H. de Jong (Rotterdam Ophthalmic Institue),
2013, Unpublished Results
Master of Physics Symposium – 11.04.2014
Leah S. Wilk
Results: Lens Artefact Removal
 Pixel    ,Pixel
 Pixel  0.3 rad
Leah S. Wilk (VU Amsterdam) and Jan H. de Jong (Rotterdam Ophthalmic Institue),
2013, Unpublished Results
Master of Physics Symposium – 11.04.2014
Leah S. Wilk
Results: Choroidal Blood Flow Detection
 Pixel    ,Pixel
 Pixel  0.3 rad
En-face (3 x 3 𝑚𝑚2 ) of the human choroid: AMD-Patient, 67 years old, 300µm 377µm in depth from retinal surface
Leah S. Wilk (VU Amsterdam) and Jan H. de Jong (Rotterdam Ophthalmic Institue),
2013, Unpublished Results
Master of Physics Symposium – 11.04.2014
Leah S. Wilk
Removal of Eye Motion Artefacts
• B-Scan is considered motion artefact if the mean revisitation error of the B-scan is not within one
standard deviation of the mean re-visitation error
of the entire volume
|σΔ𝑥,𝐵−𝑆𝑐𝑎𝑛 − σΔ𝑥,𝑉𝑜𝑙𝑢𝑚𝑒 | > std(σΔ𝑥,𝑉𝑜𝑙𝑢𝑚𝑒 )
Master of Physics Symposium – 11.04.2014
Leah S. Wilk
Removal of Eye Motion Artefacts
 Pixel    ,Pixel
 Pixel    ,Pixel
En-face (3 x 3 𝑚𝑚2 ) of the human retina: AMD-Patient, 67 years old
Leah S. Wilk (VU Amsterdam) and Jan H. de Jong (Rotterdam Ophthalmic Institue),
2013, Unpublished Results
Master of Physics Symposium – 11.04.2014
Leah S. Wilk
Conclusions
• 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
Master of Physics Symposium – 11.04.2014
Leah S. Wilk
Acknowledgements
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)
Master of Physics Symposium – 11.04.2014
Leah S. Wilk
Experimental Set-Up
Braaf et al., Opt. Express 19 (2011); 20886-20903
OCT - Beam
Master of Physics Symposium – 11.04.2014
Leah S. Wilk
Data Acquisition
• Backstitching:
• Lateral
is segmented
B-Scan scan
1 andwidth
B-Scan
2 are created by “stitching” the
individual
scan is
segments
“back” together:
• Every
segment
re-scanned
• B-scan segments are concatenated (“backstitched”)
Lateral Sample Scan Width
B-Scan 1:
B-Scan 2:
: “Mirror Fly-Back“
: B-Scan 1
: B-Scan 2
Motion of X/Y Scanning Mirrors
Master of Physics Symposium – 11.04.2014
Leah S. Wilk
SNR Noise
• Signal-to-noise ratio can be translated into
uncertainty (i.e. noise) in phase difference:
*
1
 SNR 
SNR
SNR  Signal-to-noise ratio
* Park et al., Opt. Express 13(11) (2005); 3931-3944
Master of Physics Symposium – 11.04.2014
Leah S. Wilk
Re-Visitation Inaccuracy
• Errors in re-visiting the first measurement location
introduce additional difference in phase
• Phase difference noise due to re-visitation error:
2 


4
 x  
1exp 2   
 x 
  d  
3



*
x  Beam displacement

 d = Beam diameter
* Park et al., Opt. Express 13(11) (2005); 3931-3944
Master of Physics Symposium – 11.04.2014
Leah S. Wilk
Depth Resolved Imaging: OFDI
Intensity at the detector as function of wavenumber k =
2π
λ
:
I (k )  I r (k )  2 I s (k ) I r (k )   n cos(k z n   n)  I s (k )
n
Interference term
De Boer, J F (2013) (VU Amsterdam) Master Course –
Biomedical Optics: Optical Coherence Tomography
Master of Physics Symposium – 11.04.2014
Leah S. Wilk
Limiting Factors
• Phase difference between two OFDI signals of
structures with flow (moving scatterers) given by:
 
4 n v flow cos( )
*
0
* Zhao et al., Opt. Lett. 25 (2) (2000); 1448-1450
Minor Master Project – 20.01.2014
Leah S. Wilk
Blood Flow Discrimination
• To judge reliability of a measurement requires
knowledge of its noise
• Total phase difference noise for a pixel is given by:
    SNR   x
2
2
• This limits the smallest reliably observable flow
velocity to:
 min  0

  0
v min = 4 n cos( ) > 4 n cos( )
Minor Master Project – 20.01.2014
Leah S. Wilk
Estimating The “Revisitation Noise”
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:
 x , Aline  
2
 , Kernel

2
SNR , Kernel

var( ) Kernel 
1
SNR Kernel
Minor Master Project – 20.01.2014
Leah S. Wilk
Estimating The Individual Noise Levels
4. Total noise for every pixel is then computed via:
  ,Pixel  
2
x , A Line

2
SNR , Pixel


2
x , A Line

1
SNR Pixel
5. Likely presence of blood flow in a pixel is
determined by comparing a pixel’s phase
difference to its noise:
 Pixel    ,Pixel
Minor Master Project – 20.01.2014
Leah S. Wilk
Results: Retrieving Micro-Details
 Pixel    ,Pixel
Maximum Intensity Projection
 Pixel  0.3 rad
Summed Intensity Projection
Leah S. Wilk (VU Amsterdam) and Jan H. de Jong (Rotterdam Ophthalmic Institue),
2013, Unpublished Results
Minor Master Project – 20.01.2014
Leah S. Wilk
Results: Retinal Blood Flow Detection
 Pixel    ,Pixel
 Pixel  0.3 rad
En-face (3 x 3 𝑚𝑚2 ) of the human retina: Healthy, young volunteer
Leah S. Wilk (VU Amsterdam) and Jan H. de Jong (Rotterdam Ophthalmic Institue),
2013, Unpublished Results
Minor Master Project – 20.01.2014
Leah S. Wilk
Results: Retrieving Micro-Detail
 Pixel    ,Pixel
Maximum Intensity Projection
 Pixel  0.3 rad
Summed Intensity Projection
Leah S. Wilk (VU Amsterdam) and Jan H. de Jong (Rotterdam Ophthalmic Institue),
2013, Unpublished Results
Minor Master Project – 20.01.2014
Leah S. Wilk
Results: Choroidal Blood Flow Detection
 Pixel    ,Pixel
 Pixel  0.3 rad
En-face (3 x 3 𝑚𝑚2 ) of the human choroid:
Healthy, young volunteer, 300µm - 377µm in depth from retinal surface
Leah S. Wilk (VU Amsterdam) and Jan H. de Jong (Rotterdam Ophthalmic Institue),
2013, Unpublished Results
Minor Master Project – 20.01.2014
Leah S. Wilk
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 .