International Journal of Cardiology 145 (2010) e99 – e101
www.elsevier.com/locate/ijcard

Letter to the Editor

Application of novel dynamic optical imaging for evaluation of peripheral
tissue perfusion☆
Yujung Kang a , Jungsul Lee a , Kihwan Kwon b,⁎, Chulhee Choi a,c,⁎a

Department of Bio and Brain Engineering, KAIST, Daejeon 305-751, Korea
Department of Cardiology, School of Medicine, Ewha Womans University, Seoul 158-710, Korea
cGraduate School of Medical Science and Engineering, and KI for the BioCentury, KAIST, Daejeon 305-751, Koreab

Received 17 December 2008; accepted 22 December 2008
Available online 23 February 2009

Abstract
Measurement of functional tissue perfusion should be needed for preventive measures, early diagnosis, and adequate treatment especiallyin the patients with peripheral vascular diseases (PVD). Significant attention has also been given to in vivo near-infrared (NIR) fluorescenceimaging because of deep tissue penetration due to low absorbance and scattering. In this study, a new method, indocyanine green (ICG)
perfusion imaging to evaluate the peripheral tissue perfusion that employs the intravenous injection of ICG dye, planar imaging with a CCD
digital imaging system, and analysis of spatiotemporal dynamics have been applied to diagnose perfusion rate of human lower extremities
from a normal and a PVD case. The feet tissue perfusions of the PVD patient were measured as 25% to 50% compared with those of normal
feet tissue. The diagnostic result indicates that ICG perfusion imaging method is sensitive enough to diagnose PVD and take noninvasive
monitoring treatment effects of peripheral vascular diseases in clinical setting.
© 2008 Elsevier Ireland Ltd. All rights reserved.
Keywords: Peripheral vascular disease; Diagnostic tool; Tissue perfusion; Imaging

Optical imaging, especially indocyanine green (ICG)
fluorescence imaging, has been the focus of research due toits convenience and effectiveness in imaging vasculature andallowing estimation of tissue perfusion [1,2]. Because local
concentrations of ICG are dependent mainly on regional
tissue perfusion, time-series analysis of ICG pharmacokinetics can provide functional information about local tissueperfusion [1]. We have recently developed a novel opticalimaging-based technology for translating ICG time-series
images into quantitative perfusion maps [3]. An ICG
fluorescence imaging system (Fig. 1) has been developed
by Vieworks (Seongnam, Gyeonggi-do, Korea) to validate☆

Grant Support: This research was supported by Korea Health Industry
Development Institute Grant A062605.
⁎ Corresponding authors. Choi is to be contacted at Tel.: +82 42 869 4321;
fax: +82 42 869 4380. Kwon, Tel.: +82 2 2650 2567; fax: +82 2 2650 2640.
E-mail addresses: kankadin@ewha.ac.kr (K. Kwon),
cchoi@kaist.ac.kr (C. Choi).
0167-5273/$ - see front matter © 2008 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.ijcard.2008.12.166

the clinical feasibility of this novel technique in diagnosing
peripheral vascular diseases (PVDs). In total, 120 images(748 × 518 pixels) of both feet were taken at 5-s intervals for
10 min immediately after an intravenous bolus injection ofICG (0.16 mg/kg) for time-series analysis of ICG fluorescence and then translated into the perfusion rate of the pixel.
The perfusion rate (%/min) was defined as the fraction ofblood exchanged per min in the vascular volume. The
perfusion rate of each pixel was represented in a perfusion
map as a color-coded picture and the distributions of thepixel perfusion rates in each foot were expressed as ahistogram. To evaluate the time-series ICG fluorescenceimaging as a reliable tool for diagnosis of PVD, weperformed also Computed tomography (CT)-angiography
and ankle brachial index (ABI) to compare results. This
study was approved by the institutional review board ofMokdong Medical Center (Ewha Womans University).
A 76-year-old man with no previous medical history wasadmitted with claudication in the left calf which graduallye100

Y. Kang et al. / International Journal of Cardiology 145 (2010) e99–e101

Fig. 1. NIR fluorescence imaging system. (A) Diagram of the imaging system. The imaging system is composed of a CCD digital camera (RXD-500; Vieworks
Co., Seongnam, Korea) with an 830-nm long-pass filter (RG830; Edmund Optics, Barrington, NJ, USA) that uses 760-nm light-emitting diode arrays (SMC760;Marubeni America Co., Sunnyvale, CA, USA). (B) Outside view of the system. (C) Capturing an ICG perfusion image.

developed, and he had abnormal ABI values, 0.73 on the rightand 0.24 on the left side. CT-angiography of lower extremity
revealed occlusion at left external iliac artery, proximal andmid-portion of superficial femoral artery and left distal
posterior tibial artery (Fig. 2A). The patient's ICG dynamics

showed delayed filling with ICG (60–65 s), a notably delayed
time to peak (160–180 s), and significantly delayed washout
kinetics (Fig. 2B) compared to the normal control, 74-year
old woman who had an asymptomatic occlusion of bothanterior tibial arteries with normal ABI values (Fig. 3B).

Fig. 2. A 76-year-old patient with PVD. (A) CT-angiography. (B) Time-series ICG fluorescence images. The upper panel is from the right foot, and the lower
panel shows the left foot. A pseudocolor intensity scale bar is indicated on the right-hand side of the upper panel. The numbers in the figures indicates the time(seconds) after ICG injection. (C) A perfusion map with a pseudocolor intensity scale. The perfusion rate is defined as the fraction of blood exchanged per minutein the vascular volume, and the mathematical model was utilized for the translation from time-series ICG fluorescence images into functional perfusion maps.
(D) Histogram of the perfusion rate.

Y. Kang et al. / International Journal of Cardiology 145 (2010) e99–e101

e101Fig. 3. A 74-year-old healthy control. (A) CT-angiography. (B) Time-series ICG fluorescence images. (C) Perfusion map. (D) Histogram of the perfusion rate.

Consistent with the abnormal findings in CT-angiography andthe ABI test, the ICG perfusion map demonstrated that theperfusion rate was estimated to be lower than 150%/min inmost regions of both feet (Fig. 2C and D), whereas theperfusion rate was calculated to be over 150%/min in mostregions in the normal control (Fig. 3C and D).
These case studies clearly indicate that the novel ICG
dynamic perfusion imaging technique can be effectively
applied in clinical settings for the diagnosis of PVDs.
Even though CT angiography is widely used, it severely
underestimated the extent of atherosclerosis in PVD patientswith symptoms of intermittent claudication [4] and can offeronly structural information but not functional information ofblood flow. The other limitations of CT-angiography are thehigh cost, low availability, and limiting their application forscreening or early diagnosis of PVD. ICG perfusion imaging
can be a cost- and time-efficient tool for diagnosis of patientswith peripheral vascular insufficiencies. Although NIR
imaging is restricted to analysis of tissues at depths of lessthan several centimeters, the measurement of perfusion rate
through macrovessels such as the dorsalis pedis and themicrovasculature might provide sufficient information todiagnose PVD. Since ICG perfusion imaging can measure
the functional blood flow of peripheral tissues with long term
follow up, drug treatment can be improved by feedback onmeasured perfusion rate after drug treatments, and personal
response of medical treatment can be studied. Our method
has several potential limitations as well. First, the patientwith chronic occlusive disease such as progressive artheromatous stenosis and gradual collateralization, may bemeasured as normal tissue perfusion even with severe
arterial occlusions. Second, presence of open wounds orinflammations on instep can change perfusion rate, which
can affect to overestimate the actual perfusion rate. If above
points are considered, the multiple advantages of this novel
method necessitate the performance of large-scale clinicalstudies to validate its efficacy for the diagnosis of PVDs andother related vascular disorders.
Acknowledgments
The author of this manuscript has certified that hecomplies with the Principles of Ethical Publishing in theInternational Journal of Cardiology [5].
References[1] Gora F, Shinde S, Elwell CE, et al. Noninvasive measurement of cerebralblood flow in adults using near-infrared spectroscopy and indocyanine
green: a pilot study. J Neurosurg Anesthesiol 2002;14(3):218–22.
[2] Frangioni JV. In vivo near-infrared fluorescence imaging. Curr Opin
Chem Biol 2003;7(5):626–34.
[3] Kang Y, Choi M, Lee J, et al. Quantitative analysis of peripheral tissue
perfusion using spatiotemporal molecular dynamics. PLoS ONE 2009;4(1):e4275.
[4] Tirziu D, Moodie KL, Zhuang ZW, et al. Delayed arteriogenesis in
hypercholesterolemic mice. Circulation 2005;112(16):2501–9.
[5] Coats AJ. Ethical authorship and publishing. Int J Cardiol 2009;131:149–50.