Medical Devices: Evidence and Research

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S h o rt R e p o rtOpen Access Full Text Article

Application of dynamic indocyanine green
perfusion imaging for evaluation of vasoactive
effect of acupuncture: a preliminary follow-up
study on normal healthy volunteers
This article was published in the following Dove Press journal:
Medical Devices: Evidence and Research
20 February 2014
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Yuri An 1
Jong Wook Jeon 2
Kihwan Kwon 3
Chulhee Choi 1
Department of Bio and Brain
Engineering, KAIST, Daejeon, SouthKorea; 2Acupuncture, Moxibustion
and Meridian Research Centre,
Korea Institute of Oriental Medicine,
Daejeon, South Korea; 3Departmentof Cardiology, College of Medicine,
Ewha Womans University, Seoul,
Korea
1Background: Even though acupuncture has long been used for alleviating symptoms related tovascular insufficiency, the clinical effect of acupuncture on peripheral circulation has not been
fully confirmed. In this study, we investigated whether a near-infrared optical imaging-based
method can be used to evaluate the efficacy of the acupuncture procedure to induce changes inperipheral tissue perfusion.
Methods: Two normal, healthy controls were treated with acupuncture on two acupoints(LI-4 and SI-3) three times within 1 week. At the first and third visits, participants were examinedusing indocyanine green (ICG) perfusion imaging before and 10 minutes after the acupuncture
procedure. Blood perfusion of the hands was determined after intravenous bolus injection ofICG and dynamic analysis of the fluorescence signals by near-infrared imaging system.
Results: The blood perfusion rates of the hands were markedly increased immediately after
acupuncture at the first trial in both cases. The baseline perfusion rates of the hands measured
at the third visit were higher compared to the original basal level in one case; there was nodifference in baseline perfusion rates of both hands in another case. In both cases, there was noacute effect of acupuncture on hand perfusion at the third trial.
Conclusions: These results collectively suggest a potential of the ICG perfusion imaging as
an effective evaluation tool to validate the vasoactive effect of acupuncture.
Keywords: vasodilation, blood perfusion, imaging, Raynaud syndrome

Introduction

Correspondence: Chulhee Choi
Department of Bio and Brain Engineering,
KAIST, 291 Daehak-ro, Yuseong-gu,Daejeon 305-701, South Korea
Tel 82 42 869 4321
Fax 82 42-869 4380
Email cchoi@kaist.ac.kr

Acupuncture has been a component of the health care system in Asia for at least
2,500 years.1 It also has been introduced in the US and practiced widely as an alternative medicine. However, the basic principles of acupuncture are still hypothetical andunknown.2 Hence, it is relevant and significant to study how acupuncture works andmeasure the quantitative effect of acupuncture in various clinical settings.
Many studies have shown beneficial effects of acupuncture on tissue perfusionby showing correlation between cutaneous blood flow and acupuncture3 or measuring changes in regional cerebral blood flow and glucose metabolism following
electroacupuncture.4 There are substantial numbers of trials to demonstrate the peripheral vasomotor effect of acupuncture.2,5,6 To measure the peripheral vasomotor activity,
laser Doppler imaging (LDI) has been widely used.2,6 Even though LDI is easy touse and noninvasive, the information provided by the method is not quantitative andtherefore cannot be used for longitudinal or comparison studies.717

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Medical Devices: Evidence and Research 2014:7 17–21

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http://dx.doi.org/10.2147/MDER.S56716

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An et al

We have recently developed a method enabling quantitative measurement of tissue blood perfusion rate using
indocyanine green (ICG) as a dye.7 Using this method,
peripheral tissue perfusion can be measured quantitativelyand sensitively compared to the other conventional methodssuch as LDI.7 This optical imaging-based technique can also
be applied for differential diagnosis of peripheral vascularinsufficiencies, including peripheral arterial occlusive diseases and functional Raynaud syndrome.8–10 In the present
study, we tested whether this method can be used for evaluating the vasoactive effect of acupuncture.

to have the function of speeding blood circulation of upper
extremities. It increases blood perfusion.2 Also, there wasa positive influence of acupuncture treatment in pregnant
women when using a combination of SP-6 (Sanyinjiao) andLI-4 (Hegu) acupuncture points.11 Houxi (SI-3) is believed
to soothe hand numbness (Figure 1A). Those two acupoints
are generally used, and have an effect to increase blood
perfusion.2,11,12
Both acupoints were sterilized with ethanol, and ­stainlessneedles (0.25 × 40 mm), also sterilized, were inserted
1.5–2.0 cm and manipulated for 10 seconds until deqi
sensation was achieved; they then remained untouched.
After 10 minutes, the needles were taken out without
manipulation.
On the first acupuncture treatment day, subjects wereasked to wait for 10 minutes to adjust to the room atmosphere, and the imaging was performed simultaneously with
the injection of ICG solution via catheter on median basilic
vein according to our customized ICG imaging model.
­Imaging takes 15 minutes or so; after imaging, acupuncture was performed for 10 minutes. Another imaging wasperformed 10 minutes after acupuncture to test the acuteeffect of acupuncture on the perfusion rate in the hands.
On the second acupuncture treatment day, acupuncture wasperformed without ICG imaging. The process of the firstday was repeated on the third acupuncture treatment day(Figure 1C).

Methods
Volunteers
Two healthy volunteers, a 39-year-old male and a 20-year-oldfemale, participated in this study. Neither participant wastreated with any therapeutic medication during the study.
They had no cardiovascular risk factors or symptoms related
to peripheral vascular insufficiency. The study protocol wasapproved by the institutional review board of Mokdong
Medical Center (Seoul, South Korea).

Acupuncture
All acupuncture procedures were done by an experienced
specialist in acupuncture having more than 5 years of clinicalpractice. The choice of acupoints was based on their specificcharacter based on traditional text. Hegu (LI-4) is believed

A

Metacarpal IIBdMidpoint

a: CCD camera
b: IR emitterc: ICG catheter
injection
d: darkroom

ab

LI-4

Metacarpal I

NIR light

c

SI-3

C

Acupuncture on
LI-4 and SI-3

Acupuncture on
LI-4 and SI-3
1stimaging

10min

10 min

1st day

10min

2ndimaging

2∼3 days

10 min
5 daysAcupuncture on
LI-4 and SI-3
3rdimaging

10min

10 min10min

4thimaging
Time

3rd days

Figure 1 Study protocol for acupuncture and ICG perfusion imaging.
Notes: (A) Acupoints (LI-4 and SI-3) used for the current study are illustrated. (B) Near infrared optical imaging setting for ICG fluorescence is shown. Hands of the subject
should be rested in the dark box during the acquisition of ICG fluorescence signals via CCD camera. (C) The study protocol for acupuncture and ICG perfusion imaging. On
the first day, the ICG perfusion imaging was performed before and after acupuncture. On the second visit, acupuncture was performed without ICG imaging. The process ofthe first day was repeated on the third acupuncture treatment day.
Abbreviations: CCD, charge-coupled device; ICG, indocyanine green; IR, infrared; NIR, near-infrared.

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Medical Devices: Evidence and Research 2014:7

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Indocyanine green perfusion imaging of acupuncture vasodilation

ICG imaging and analysis

For ICG time-series imaging, 40 to 80 images (768 × 512 pixels)of the dorsum of both hands were taken at 5-second intervals
for 5 minutes immediately after an intravenous bolus injectionof ICG (0.16 mg/kg) using a near-infrared (NIR) imaging system including two 760 nm LED arrays and a charge-coupleddevice with 830 nm long-pass filter (Vas View, Vieworks Corp,Seongnam, Gyeonggi-do, South Korea) (Figure 1B), as used
for previous studies.8–10 Regional ICG dynamics obtained fromeach pixel were analyzed to get the perfusion rate and Tmax
value. Perfusion rate (%/minute) was defined as the fractionof blood exchanged per minute in the vascular volume of theregion of interest.7 Tmax was defined as the time from ICG
injection to peak time of ICG dynamics.7 To visualize the segmental pattern of ICG dynamics, the perfusion rate and Tmax
value of each pixel in the hand was calculated and translated
into a pseudocolor-coded perfusion rate and Tmax map using
Visual C++ (2008 version, Microsoft Corporation, Redmond,WA, USA), as analyzed in previous studies.8–10

Results and discussion
To test the effect of acupuncture on LI-4 and SI-3 on blood
perfusion, volunteers were subjected to serial ICG perfusion
imaging before and immediate after acupuncture on the firstand third visits. The average values of the perfusion rate werecalculated for the fingertips, which are the first segment ofperfusion map and analyzed for the effect of acupuncture(Table 1). In the female subject, the baseline perfusion
rate was lower compared to the male subject. Even though
there is considerable difference in baseline perfusion rates,
the acupuncture treatment significantly increased the blood
perfusion in both cases on the first visit (Figure 2A and B).
However, such acute effects were not observed on the thirdtrial. On the contrary, the chronic effect of acupuncture wasonly observed in the female subject. The three trials of acupuncture increased the baseline blood perfusion up to 2.5-foldin the female; there was no significant difference in baseline
perfusion in the male subject. The acute and chronic effectsof acupuncture are in good concordance with the previous

studies using other conventional methods.2,11,12 These results
might indicate the beneficial effect of acupuncture on peripheral vascular function.
Acupuncture has also been used for treatment offunctional vascular insufficiencies such as Raynaud syndrome, even though the efficacy is still undetermined.13
Since Raynaud syndrome is quite common in young
females, we analyzed the Tmax kinetics of both subjects(Figure 2C and D). As the perfusion map, the Tmax value wasalso color-coded in relative linear scale. Segmental analysisof Tmax, the time-to-peak from ICG injection, can provide
information regarding peripheral vascular function.8 Bothvolunteers showed the normal pattern of Tmax map. Even
though the female showed lower baseline perfusion, theTmax analysis clearly demonstrated that both cases were freefrom Raynaud syndrome. We could not find any significant
changes in Tmax kinetics in both cases by acupuncture (datanot shown).
Even though the current study employed only two cases,
this pilot study clearly demonstrated the potential of theICG perfusion imaging for quantitative and reproducible
evaluation of acupuncture effects on peripheral vasculature.
There was considerable effect of acupuncture treatment inboth acute and chronic manner. However, the lack of acuteacupuncture effect on the repeated trials should be further
evaluated in a large number of subjects. Another issue is thevariation in chronic effect of acupuncture. The reason why
the repeated treatment of acupuncture had chronic beneficial
effect in the female case might be due to the lower baseline
perfusion (on the first visit). Even though the baseline
level of the subject was not low enough to be diagnosed as
peripheral vascular insufficiency, there might be more room
for improvement in cases with relatively poor perfusion.
One of the advantages of the ICG perfusion for evaluationof vasomotor activity of acupuncture is that the method canprovide information regarding not only vascular perfusion but
also functional integrity of peripheral vasculature.8 Therefore,
the effect of acupuncture on Raynaud syndrome can also be
tested as previously reported.14

Table 1 The effect of acupuncture on the blood perfusion rate
Case

Case 1(male, 39)Case 2(female, 20)

Hand

Right
Left
Right
Left

First visit

Third visit

Baseline perfusion(%/min)Postacupuncture(%/min)Change(%)

Baseline perfusion(%/min)Postacupuncture(%/min)Change(%)

99.6
83.5
52.9
45.0

124.4
119.5
72.2
64.9

24.9
43.1
36.6
44.3

95.0
79.9
123.8
114.7

97.8
80.8
131.7
110.6

3.0
1.1
6.4
-3.6

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An et alFigure 2 The effect of acupuncture on blood perfusion.
Notes: (A) A representative figure shows the blood perfusion of a healthy 39-year-old male before and 10 minutes after acupuncture on the first visit. The blood perfusion
rate of the hands was shown as a two-dimensional pseudocolored map. At each pixel point of A and B, the calculated blood perfusion rate is color-coded; red indicates goodperfusion, while blue corresponds to poor perfusion. It is in log scale, and it indicates from the minimum value 0 to a maximum value of 150. In both figures, the left side
hands show the blood perfusion rate map before applying acupuncture, and the right ones show after acupuncture. (B) A representative figure shows the blood perfusion ofa healthy 20-year-old female before and 10 minutes after acupuncture on the first visit. (C and D) Color-coded maps indicate Tmax values of the hands of two normal subjects.
For sequential analysis of Tmax, the dorsum of the hand was divided into four identical squares, and the average value of Tmax was measured. The value that is written next tothe square represents the average value of perfusion rate or Tmax of each square.

DisclosureThis research was supported by a National Research Foundation grant funded by the Korea government (MEST) (No.
2012M3A9C5048707). The authors report no other conflictsof interest in this work.

References

1. Acupuncture. NIH Consens Statement. 1997;15(5):1–34.
2. Zhang W-b, Wang L-l, Huang T, et al. Laser doppler perfusion imagingfor assessment of skin blood perfusion after acupuncture. Med Acupunct.
2008;20(2):109–118.
3. Jansen G, Lundeberg T, Kjartansson J, Samuelson UE. Acupuncture andsensory neuropeptides increase cutaneous blood flow in rats. Neurosci
Lett. 1989;97(3):305–309.
4. An YS, Moon SK, Min IK, Kim DY. Changes in regional cerebral bloodflow and glucose metabolism following electroacupuncture at LI 4 andLI 11 in normal volunteers. J Altern Complement Med. 2009;15(10):1075–1081.
5. Birch S, Hesselink JK, Jonkman FA, Hekker TA, Bos A. Clinical researchon acupuncture: Part l. What have reviews of the efficacy and safetyof acupuncture told us so far? J Altern Complement Med. 2004;10(3):468–480.
6. Litscher G, Wang L, Huber E, Nilsson G. Changed skin blood perfusionin the fingertip following acupuncture needle introduction as evaluated by laser Doppler perfusion imaging. Lasers Med Sci. 2002;17(1):19–25.

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7. Kang Y, Choi M, Lee J, Koh GY, Kwon K, Choi C. Quantitative
analysis of peripheral tissue perfusion using spatiotemporal moleculardynamics. PLoS One. 2009;4(1):e4275.
8. Kang Y, Lee J, An Y, Jeon J, Choi C. Segmental analysis of indocyanine
green pharmacokinetics for the reliable diagnosis of functional vascularinsufficiency. J Biomed Opt. 2011;16(3):030504.
9. Kang Y, Lee J, Kwon K, Choi C. Application of novel dynamic opticalimaging for evaluation of peripheral tissue perfusion. Int J Cardiol.
2010;145(3):e99–e101.
10. Kang Y, Lee J, Kwon K, Choi C. Dynamic fluorescence imaging ofindocyanine green for reliable and sensitive diagnosis of peripheral
vascular insufficiency. Microvasc Res. 2010;80(3):552–555.
11. Zeisler H, Eppel W, Husslein P, Bernaschek G, Deutinger J. Influenceof acupuncture on Doppler ultrasound in pregnant women. UltrasoundObstet Gynecol. 2001;17(3):229–232.
12. Naruse S, Mori K, Kurihara M, et al. [Chorioretinal blood flow changes
following acupuncture between thumb and forefinger]. Nihon Ganka
Gakkai Zasshi. 2000;104(10):717–723. Japanese.
13. Malenfant D, Catton M, Pope JE. The efficacy of complementary
and alternative medicine in the treatment of Raynaud’s ­phenomenon:
a literature review and meta-analysis. Rheumatology (Oxford).
2009;48(7):791–795.
14. Donoyama N, Ohkoshi N. Electroacupuncture therapy for arthralgia andRaynaud’s phenomenon in a patient with systemic lupus erythematosus.
Acupunct Med. 2010;28(1):49–51.

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Indocyanine green perfusion imaging of acupuncture vasodilation

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