The document provides an introduction to Laser Speckle Flowgraphy (LSFG), a non-invasive technique for measuring relative blood flow velocity. LSFG uses a laser to illuminate moving blood cells, which produce dynamic speckle patterns that are analyzed to generate blood flow maps. Several key points are discussed, including: - LSFG provides time-varying maps of retinal and choroidal blood flow without needing dye injection. - Parameters like Mean Blur Rate (MBR) and Blow Out Time indicate relative blood flow velocity and are used to study conditions like glaucoma, macular diseases, and vascular occlusions. - Studies have shown LSFG measurements correlate with other

1. K.Okamoto Softcare Co., Ltd.
Introduction to
Laser Speckle Flowgraphy
(LSFG)

2. 1. Principle and features of LSFG
2. Brief review of papers using LSFG
Topic of this talk

3. Blood cells produce moving speckles in the image plane.
Principle of LSFG
Image Plane
Objective Lens
Speckles
Eye Ball
Diode Laser
Image Sensor
PC
Interface
Board
Lens
Blood Cells
Image Plane
Objective Lens
Speckles
Eye Ball
Diode Laser
Image Sensor
PC
Interface
Board
Lens
Blood Cells

4. Example of Speckle patterns
produced by moving scattering cells
Moving object Stopping object

5. Vessel
Contrast is seen to be lower at the vessel area
Mean Blur Rate (MBR) = 1/contrast2
indicates relative blood velocity in vessels or tissue.
Speckle image produced by retina

6. Motion picture of time-varying blood flow map
in human retina is observable by LSFG
Choroid Vein Artery
Blood vessels
without blood flow
are not visualized
MBR can respond
only to moving
scatters.

7. MBR on macula shows choroidal blood flow
Hiroaki Isono, et al. Arch Ophthalmol, 121, no.2, 225-231, 2003.
Existing retinal blood flow
without BRAO
None retinal blood flow
with BRAO
100% 92%
The average of MBR on
macula within rectangle
region, which is occluded
retinal vessels, shows 92%.
The average MBR in this
area is significantly affected
by choroidal blood flow.

8. MBR is linearly proportional to the velocity of
rotating opal glass disk in which a huge number of
scatterers are embedded.
Properties of MBR (1)

9. Properties of MBR (2)
Since LSFG is detecting not the image of blood cells
but interference of light scattered back and forth
among them,
1. It is difficult to convert it to absolute velocity.
2. The value is influenced by the scattering and
absorption properties of tissue covering foreground
and background of vessels or capillaries.
Important Notes on MBR

10. It is valid in most of the following cases, to
compare
1. the data taken for the same place before and
after treatments, eye drops, etc.,
2. the data of affected eye to that of fellow eye,
3. the data taken for the eyes with similar
degree of pigmentation.
Properties of MBR (3)

11. N+1
N+3
N+2
Min
Max
Max
Min
120
Max
Min
Heart Beat Map
N+K
1
K
2
Blood Flow
Map
Composite
Map Averaging
120 Blood Flow
Map
Definition of Blood Flow Map, Heart Beat Map and Composite Map.

12. Average blood flow map shown in gray scale
looks like combination of retinal and choroidal
angiography images.

13. Highly correlated with other methods for tissue region(1)
Hydrogen gas clearance method
In rabbit ONH
Hiroaki Takahashi et al, Experimental Eye
Research, 2012
http://dx.doi.org/10.1016/j.exer.2012.12.003
Naoko Aizawa et al, IOVS-14, 2014. doi:
10.1167/iovs.14-1537

14. Highly correlated with other methods for
tissue region (2)
Microsphere method in monkey ONH
Lin Wang et al, IOVS, 2012 IOVS-12-10911

15. Analysis For Retina vessel using RFV(1)
Yukihiro Shiga et al,
Relative flow volume, a novel blood flow index in the human retina derived from laser speckle flowgraphy
Investigative Ophthalmology & Visual Science, IOVS-14, 2014. doi: 10.1167/iovs.14-14116

16. Analysis For Retina vessel using RFV(2)
Comparable
Not comparable between
RB1 and RB2

17. Optic Nerve Head Analysis
Vessels and background separator
• MV: Mean BFV in Vessels including background (MT)
• MT: Mean BFV in Tissue
• MV-MT: Mean BFV in Vessels no including blood flow in tissue
• ARBS: Area ratio of Blood Stream
• VC: Vascular Cloud

18. Aging of Profile Observed
in ONH Blood Flow
20
50
70
High
Low

19. Waveform indicators
to characterize blood circulation
Skew > 0 Skew = 0 Skew <0
Skew
BOT
=Peak
Width
AC
DC
AC
DC
BOS
=Relative
Amplitude
Blow Out Score BOS=Hi BOS=Low

20. Blow Out Time (BOT=Peak width)
at ONH decreases with aging
40
45
50
55
60
20 40 60 80
Blow
out
time
Age (years)
r=0.85, P< 0.0001
Tomoaki Shiba, Mao Takahashi, Yuichi Hori and Takatoshi Maeno
Pulse-wave analysis of optic nerve head circulation is significantly correlated with brachial–ankle pulse-wave velocity, carotid intima–media thickness, and age
Graefe's Archive for Clinical and Experimental Ophthalmology (DOI: 10.1007/s00417-012-1952-5), 2012.

21. BOT values in the ONH and choroid were significantly correlated with the HbA1c
in the non-DM patients.
Chieko Shiba, Tomoaki Shiba, et
Graefe's Archive for Clinical and Experimental Ophthalmology, doi: 10.1007/s00417-016-3437-4, 2016.
BOT and HbA1C

22. PigMagic
It is known that difference in pigment has an effect on MBR when you evaluate
fundus blood flow using LSFG.
MBR increases as pigment becomes thinner.
With PigMagic
US patent No. 14391539
The caucasion MBR looks similar
color as Japanese composite map.
Caucasion MBR on
composite map without
PigMagic.
Pigmagic only applies to composite map
not blood flow map.

23. Specifications of LSFG-NAVI
• Laser class: Class 1.
• Field of View: W6mm x H3mm
on human retina
• Measuring time : 4 sec.
• Analyzing time: 15 sec.
• Time resolution: 30maps/s.
• Certified as Medical Instrument.
510(k) number K153239, FDA, Oct 2016
http://www.softcare-ltd.co.jp/510k_clearance.html

24. Brief review of papers
using LSFG

25. Norm
al
Glauco
ma
Compare Normal and Glaucoma
Yu Yokoyama et al,
Significant correlations between optic nerve head microcirculation and visual field defects and nerve fiber
layer loss in glaucoma patients with myopic glaucomatous disk
Clinical Ophthalmology, 2011:5, 1721 - 1727

26. Correlation between ONH blood flow
and Other parameter
OCT RNFLT HFA MD
Yu Yokoyama et al, Clin Ophthal, 2011
Naoki Chiba et al, Clin Ophtal, 2011

27. Tomoyuki Maekubo et al, Jpn. J. Ophthalmol., 2013
Between non-arteritic ischemic optic
neuropathy and anterior optic neuritis
NAION Anterior ON
-29.5 % 15.9 %
NAION Fellow eye
Anterior ON Fellow eye

28. CRVO report
Corrected [%]
=
This report is primarily focused on the
vascular part of the Optic Nerve Head as
this is the area where blood flow is high.
This report compares left and right eyes.
MV-MT (fellow eye)
MV-MT (Diseased eye)

29. CRVO: prognosis prediction
４６．４％
No response
Good blood flow
Good prognosis
Pre IVB After 1st IVB After final IVB
①No recurrent(s) ②No recurrent(m)
Recurrent:
Response +
Recurrent:
Response -
Ischemic
Non-
ischemic ->
Ischemic
Corrected
[%]

30. Macular choroidal blood flow velocity decreases with
regression of acute central serous chorioretinopathy
Saito Michiyuki, et al. Br J Ophthalmol 2013

31. Relationship between choroidal
thickness and Average MBR
VKH AMN AZOOR CSC
Choroidal
thickness
－
Ave MBR
(Blood flow)
VKH (Vogt–Koyanagi–Harada disease)
ＡＭＮ（acute macular neuroretinopathy）
AZOOR（Acute zonal occult outer retinopathy）
CSC（central serous chorioretinopathy）
Michiyuki Saito, et al, Br J Ophthalmol doi:10.1136/bjophthalmol-2012-302349
Yuki Hashimoto, et al. Relationship between Choroidal Thickness and Visual Field Impairment in Acute Zonal
Occult Outer Retinopathy J Ophthalmol, 2017

32. 1. Blood flow velocity or flow volume can be
evaluated in relative scale.
2. Noninvasive and repeatable measurement is
possible.
3. Waveform analysis of the periodic blood flow
change is possible.
4. Suitable for diagnoses of Glaucoma,
NAION,BRVO, CRVO, etc.
Conclusion Features of LSFG
There are many papers about Japanese subjects.
But papers for caucasian subjects exist a few.

33. Appendix.

34. Longitudinal Changes During Normal
Pregnancy
Takahiro Sato et al, PLOS ONE, 2017
T1. 11±13 weeks
T2. 19±21 weeks
T3. 28±30 weeks
T4. 34±36 weeks
MBR showed no significant changes throughout pregnancy.
BOS showed a tendency to increase in the 3rd trimester.

35. Blood flow autoregulation in monkey ONH
Jintao Yu et al, Int J Physiol Pathophysiol Pharmacol, 2014
IOP 10 -> 30 mmHg IOP 10 -> 40 mmHg IOP 10 -> 50 mmHg
Recovery ratio

36. Blood flow autoregulation in monkey ONH
Jintao Yu, Yi Liang, Simon Thompson, Grant Cull, Lin Wang
Parametric transfer function analysis and modeling of blood flow autoregulation in the optic nerve head
Int J Physiol Pathophysiol Pharmacol 2014;6(1):13-22
Recovery
ratio
AR fully
functional

37. Influence of Posture Change
Yukihiro Shiga et al, Current Eye Research, 2013
[0 min]
Initial sitting position
[0< min]
Supine position
Sitting
Supine
MBR in ONH temporary increased
MBR in choroid keeps increase

38. Diurnal Variations in Blood Flow
Takeshi Iwase et al, Medicine, 2015

39. Diurnal Variation of Waveform Parameters
Marie Fukami et al, Medicine, 2017
Waveform Parameters could be an
indicator of vascular resistance.