This document discusses using laser speckle flowgraphy (LSFG) to analyze retinal blood flow and waveform parameters. It provides several examples of how LSFG can be used clinically, including to evaluate arteriosclerosis, monitor blood flow changes with aging, assess blood flow in cases of diabetes or kidney transplantation, and help predict prognosis in central retinal vein occlusion. Various waveform parameters extracted from LSFG, such as mean blur rate, blowout time, and beat strength, provide information about blood flow quantity, resistivity, and circulation quality.

1. Waveform Parameters of LSFG:
Clinical Applications
Kenji Okamoto
Softcare Co.,Ltd.
English version .1.00

2. Does Retinal Blood Flow Tell Us
Only About Eye Disease?
Retinal Blood is a Window for
the Body’s Blood Circulation

3. Akiko Tamura, et al, Journal of Japanese Ophthalmological Society, 117, no.2, 110-116，2013.
MBR of papilla shows various individual differences
MBR is indicative of a nutrition delivery system based on individual's body condition,
heart rate, blood pressure, etc. A simple comparison of MBR may be meaningful when
the MBR is different from the standard value but is it effective for early diagnosis?
MBR Decreases with Age
Age

4. Aging does not affect MBR in the optic nerve head of
healthy adults
In the peripheral area where nutrition is consumed the quantity
of blood flow is supplied steadily
Peripheral Area Blood Circulation and Aging
Healthy adults supply nutrition to peripheral area effectively and steadily adjusting for
the individual’s heart rate and blood pressure. → Blood Supply to the
peripheral area is stable.

5. Waveform parameters in the peripheral area
such as the optic nerve head depend on age.
>It captures change in circulation system with
aging.
By analyzing waveform parameters you can evaluate the status of the circulation
system (arteriosclerosis, resistivity, et al…).
The Waveform Parameters indicate the
blood supply declining to the peripheral
area with aging

6. LSFG Can Do It!
Ophthalmoscopy Quantifies Blood Flow Quality
Brain infarction
Myocardial Infarction
Blood Flow = Infrastructure which supports whole body
Supply of Nutrition Excretion of Waste
Arteriosclerosis
Damage to the Infrastructure
• Life Style Related Disease
• Lack of Exercise
• High Blood Pressure
• Smoking, etc...
There are a variety of individual differences in blood flow
Let’s Listen to the voice of Blood Flow.
Because retina is directly observable it tells a lot about blood flow

7. 40
45
50
55
60
20 30 40 50 60 70 80 90
Blowouttime
Age (years)
BOT vs Age
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.
BOT = half-value width / beat width
High
Low
7
BOT at optic nerve head
is negatively correlated to
age and can be an index
of arteriosclerosis.
29-year-old man
52-year-old man
79-year-old man
Example of Waveform Parameter BOT

8. Correlation to HbA1C
Chieko Shiba, Tomoaki Shiba, Mao Takahashi, Tadashi Matsumoto and Yuichi Hori
Relationship between glycosylated hemoglobin A1c and ocular circulation by laser speckle flowgraphy in patients with/without diabetes mellitus
Graefe's Archive for Clinical and Experimental Ophthalmology, doi: 10.1007/s00417-016-3437-4, 2016..
BOT and BOS are related to
HbA1C. BOT at optic nerve
head is negatively correlated,
HbA1C < 5.9 It may become
useful for early detection of
DM.

9. Diurnal Variation of Healthy Adults
Blood flow on the optic nerve head shows diurnal variation even if automatically
regulated. Waveform parameters accurately capture fluctuation of blood flow.
Optic Nerve Head shows diurnal variation
of MBR, but its variation (Fluctuation?) is
larger than BOS.
At night the parasympathetic nerve
becomes significant (dominant?)
and resistivity decreases.

10. LSFG Waveform Parameters
MBR
Time
Peak
Skew
Max
Min
BOS
BOT
FAI
Length of A Heartbeat
To Peak
ATI
Average
RI
Rising Rate
Falling Rate
Fluctuation
Softcare Co., Ltd.
Averaging
Animation
補足資料

11. There are Various Waveform Parameters
To evaluate the quality of healthy and normal blood flow,
we should pay attention to the following parameters:
• Steady Flow seen during diastolic phase （Min)
• Fluctuation width of Blood Flow (≃BS or Max-Min)
• Resistivity (BOT, BOS, RI or BOM(=BS/MBR))
Note: Other parameters are also important depending on the patient’s condition.
For example, in the case of DM, peripheral vascular network is extended taking
time to get to the peak and ATI is expected to become larger.

12. Clinical Applications of Waveform
Parameters
We keep a list of publications clinical application of waveform parameters
with examples. Please send e-mail if you are interested.
Email: softcare@softcare-ltd.co.jp
Key Words are Strength and Resistivity of the blood
flow in the observed area

13. Application in Limb Ischemia
By courtesy of Dr.Yokoi
LSFG allows you to visualize blood
flow distribution in limb ischemia.
⇒ Helps decide the location of
amputation
Evaluation of Blood Flow before and after
bypass surgery for the patients of
arteriosclerosis obliterans
⇒Evaluation of hemodynamics
Kikuchi et al. (2018) Vascular
After the bypass surgery the strength of blood flow recovers and shaped width increases (BS ↑).
Because blood flow is recovered resistivity also increases (BOM ↑). Ａｓ ｒｅｇｉｓｔｉｃｉｔｙ
ｈａｐpｅｎｓ ｂｙ ｐｕｓｈｉｎｇ ｉｎ, ｉｆ quantity of blood flow increases resistivity also increases.

14. BS (Beat Strength）
Strength of heartbeat （BS: Beat Strength) is calculated.
• BS is the force of blood flow in the observed area based on the strength of the heart:
→ BS is proportional to amplitude of blood flow
→ Ｉｆ hｅａｒｔ ｂｅａｔ ｒａｔｅ ｃｈａｎｇｅｓ and width of fluctuation is homogeneous,
BS does not change
If the pulse is irregular the BS decreases because energy of blood flow
decreases for the missing pulses
• BOM represents resistivity. BOM=BS/MBR .
There is a report which shows a significant
negative correlation (r=-.94, P<0.0001) between
BOS and BOM. It means BOM indicates
resistivity. T.Komatsu,The122th Annual Meeting of the
Japanese Ophthalmological Society, 2018
In the latter pregnancy period
vascular residency reduces and
BOS increases.
Takahiro Sato, et al,
Longitudinal changes of ocular blood flow using laser speckle flowgraphy
during normal pregnancy
PLOS ONE, 12(3), e0173127, doi:10.1371/journal.pone.0173127, 2017.
When resistivity of flood flow
increases BOS ↓ and BOM ↑
BS is proportional to
amplitude of blood flow
補足資料

15. Application to Kidney Transplantation
Muramatsu, et al. (2018) The Efficacy of Laser Speckle Flowgraphy
Device for Intraoperative Evaluation of Renal Blood Flow after
Reperfusion, 2018 American Transplant Congress
The 55th Annual Congress of the Japan Society for Transplantation
MO3-8「成人・小児腎移植におけるLaser speckle flowgraphy を用いた再灌流後血流の比較検討」
Oct/12/2019
Significant difference between Fast Initial Urination Group and Slow Initial
Urination Group. -> Prediction of kidney function after the operation.
Donor Recipient
In a freshly transplanted kidney, peripheral vessels are tightened. Blood with
heartbeat burst into tight area and resistivity of the area is high. However,
peripheral vessels are expanded with time, and the kidney’s resistivity is
lowered and can accept the blood flow.

16. PROGNOSIS OF INJECTION TO
VITREOUS BODY - CRVO
NAGASAKI UNIVERSITY
USING TOTAL CAPILLARY RESISTANCE (TCR) OF
RETINAL BLOOD FLOW: TCR(=BS/(MV-MT))
17
The 58th Annual Meeting of Japanese Retina and Vitrecus Society

17. Prognosis Using Blood Flow Analysis
LSFG is useful for evaluation and decision in CRVO
treatment.
Affectedeye(MV-MT)/
FellowEye(MV-MT)*100
Before 1st IVB After 1st IVB After Final IVB
46.4% of the groups 4,5,6
do not respond to IVB
or poor prognosis
High Blood Flow groups 1,2,3
respond well to IVB and have
a good prognosis
Transition of Speed of Blood Flow
Set the speed of blood flow (MBR in the major vessel at Optic Nerve Head) of healthy fellow
eye at 100, and examine transition of the speed of blood flow (MBR in the eye with CRVO).
Groups 1, 2 and 3 show relatively better results with faster blood flows accompanying IVB
(treatment) . Groups 5 and 6 with Ischemia with the initial IVB are below 50%. In those cases,
the possibility of poor prognosis is suggested.
Group Recurre
nce
IVB Ischemia Respond prognosis
1 no onece no yes good
2 no multiple no yes good
3 yes no yes good
4 yes no no poor
5 no- > yes no poor
6 yes no poor
Kiyoshi S, NovelMechanismfOrRetinalVascularDiseases, Journal of Japanese Ophthalmological Society, 119(3), 216-227, 2015.

18. Ａｎａｌｙｓｉｓ Ｒｅｐｏｒｔ ｆｏｒ CRVO
20
Carefully select the
parameters to output
and compare them
between right and left.
If the VC is below the threshold,
colored bar-graph will be shown.
(initial value : 0.28)
In the graph of corrected values of
MV-MT, if the value is less than
50%, a pink-colored bar-graph is
shown.
TCR is a parameter which reflects the
resistivity of the retinal vein:
TCR=BS in the area V-M of ONH /(MV-
MT). In CRVO studies, blockage of vein
is thought to cause the elevation of the
resistivity in retinal vessels, and also
TCR will rise. As there is possibility of
the case that resistivity does not
increase while VC is present. Therefore,
TCR is a very useful parameter to
quantify the measure of vessel blockage.

19. Vascular Cloud (VC)
Spatial
Frequency
Analysis
Extract of a Blood Stream Map
around ONH
Vasculaｒ
cloud
Non-Vasculaｒ
cloud
f
Power
Digitization of
Brown Part
Higher cpm components
because blood stream is
sharp.
Because there is VC and
blood stream is not sharp,
less high cpm component.
Spectral
Analysis
VC High
VC Low
- Ｐａｒａｍｅｔｅｒ ｉｎｄｉｃａｔｉｎｇ ｃｌｅａｒｉｔｙ ｏｆ ｂｌｏｏｄ ｓｔｒｅａｍ -
補足資料
Power

20. Presentation Using BS
for Kidney Transplantation
2018 American Transplant Congress
https://atcmeetingabstracts.com/abstract/the-efficacy-of-laser-speckle-flowgraphy-device-for-intraoperative-evaluation-of-renal-blood-
flow-after-reperfusion/

21. MBR represents the quantity of blood flow which is being supplied to the peripheral blood
vessels after entire circulation system of the body was optimally controlled. The state of the
quality blood flow in the actual peripheral area may be captured by using waveform
parameters akin to the way we evaluate river management from a larger perspective.
Summary
Waveform parameters not only show quantity blood flow, but also show the
quality of blood flow. While there are studies which use waveform parameters,
we are presenting examples which used waveform parameters in clinical
applications:
－ Hemodynamics before and after bypass surgery in limb ischemia
－ Kidney Transplantation
－ Vascular occlusion such as Central Retina Vein Occlusion (CRVO)
We are presenting reports which show the BS as the remaining force of blood
flow in the observed area. In further application of BS, it may be useful to
observe the fluctuation of retinal blood flow in the case of DM. To deliver blood
to the peripheral area, your body raises your blood pressure. If the energy was
not consumed in the observed area, remaining energy may be observed as the
pulse wave in the vein side. We may be able to confirm this with BS parameter.

22. Appendix

23. Secular Variation of Blood Flow for One Subject
Over 8 years
視神経乳頭血流MAの経年変化
時間
血流値MBR[au]
010203040
2008 2009 2010 2011 2012 2013 2014 2015
― Average of healthy
adults
・a subject (male,43 y.o)
Bloodflow(AverageMBR[au])
Year

24. BOT at ONH is thought to
represent arteriosclerosis.
BOT and age is negatively
correlated.
視神経乳頭血流波形BOTの経年変化
時間
BOT[arb.unit]
4045505560
2008 2009 2010 2011 2012 2013 2014 2015
― Average BOT of healthy adults
・ BOT of a subject (43 y.o)
Year
Secular Variation of Waveform (BOT)

25. Secular Variation of Vascular
Registivity (BOS at ONH)
視神経乳頭血流波形BOSの経年変化
時間
BOS[arb.unit]
70758085
2008 2009 2010 2011 2012 2013 2014 2015
BOS at ONH represents
vascular resistivity.
There are reports showing
negative correlation between
BOT and age.
Jogging began in 2011.
After 3 months vascular (BOS started to
increase) meaning registivity started to
decline.
Year

26. Blood Flow Parameters of Registivity
Arteriole
Capillary Prexus
Venule
Arteriole Capillary Prexus Venule
BOS：Registivity parameter represents blood flow through the capillary prexus
BOT: Registivity parameter represents the elasticity of arteriole
Expand as balloon
Maintain blood flow

27. How Durable are Decreases in
Registivity after Jogging?
Heart Rate, Blood Pressure
Heart rate and blood pressure return
to normal after 2 hours.
Jogging 30min. Office work after jogging
BP
BF
Time (hour)

28. Results
Heart rate and blood pressure return to normal after exercise in 2 hours.
Total MBR of retina increase by exercise and decrease approximately 2 hours later. It shows a
similar pattern as blood pressure. On the other hand, retinal vessel BOS.V.T. and retinal organ
blood flow BOS.T maintained decrease of registivity 4 hours after exercise.
Duration of peripheral vescular plexus expansion is longer in duration while blood pressure
stays high.

29. Exercise for a Long and Healthy Life!
Jogging Course
photo by T. Yoshiura.