Photoacoustic imaging of tumour vascular permeability with indocyanine green in a mouse model

Kenichiro Okumura,Norihide Yoneda,Kotaro Yoshida,Satoshi Kobayashi,Kazuto Kozaka,Azusa Kitao,Sho Aki,Yoh Takuwa,Wataru Koda,Takahiro Ogi,Toshifumi Gabata,Kazuaki Yoshioka,Tetsuya Minami,Dai Inoue

doi:10.1186/s41747-018-0036-7

Kenichiro Okumura, Norihide Yoneda + Show 12 more

Open Access

https://doi.org/10.1186/s41747-018-0036-7

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Abstract

BackgroundWe analysed the haemodynamics of indocyanine green (ICG) in mouse organs and tumours and evaluated responses to anti-angiogenic agents in an allograft tumour mouse model by photoacoustic imaging.MethodsThirty-six male mice (aged 10–14 weeks; body weight 20–25 g) were used. Real-time photoacoustic imaging of organs and tumours after intravenous injection of ICG was conducted in mice until 10 min after ICG injection. ICG distribution in tumour tissues was assessed by immunohistochemical staining and observation of ICG-derived fluorescence. Vascular permeability changes induced by the vascular endothelial growth factor (VEGF)-blocking agent VEGF-trap on tumour photoacoustic signals were studied.ResultsThe photoacoustic signals in salivary glands and tumours after intravenous injection of iCG (0.604 ± 0.011 and 0.994 ± 0.175 [mean ± standard deviation], respectively) were significantly increased compared with those in the liver, kidney, and great vessel (0.234 ± 0.043, 0.204 ± 0.058 and 0.127 ± 0.040, respectively; p < 0.010). In tumours, the photoacoustic signal increased within 30 s after ICG injection in a dose-dependent manner (r2 = 0.899) and then decreased gradually. ICG was found to extravasate in tumour tissues. In VEGF-trap-treated mice, the photoacoustic signal in the tumour decreased at the early phase before inhibition of tumour growth was detected (0.297 ± 0.052 vs 1.011 ± 0.170 in the control; p < 0.001).ConclusionsPhotoacoustic imaging with ICG administration demonstrated extravasation of ICG in mouse organs and tumours, indicating the potential for early detection of changes in vascular permeability during cancer therapy.

Highlights

We analysed the haemodynamics of indocyanine green (ICG) in mouse organs and tumours and evaluated responses to anti-angiogenic agents in an allograft tumour mouse model by photoacoustic imaging
The purpose of this study was to analyse the haemodynamics of ICG in mouse organs and tumours and evaluate the tumour response to anti-angiogenic agents by photoacoustic imaging
In vitro experiment Cotton swabs presoaked with three different concentrations of ICG provided dose-dependent increases in photoacoustic signals (Fig. 3a), demonstrating a linear

Summary

Introduction

We analysed the haemodynamics of indocyanine green (ICG) in mouse organs and tumours and evaluated responses to anti-angiogenic agents in an allograft tumour mouse model by photoacoustic imaging. Photoacoustic imaging is an emerging non-invasive optical technology that proved to have potential for cellular and molecular specific visualisation at clinically relevant depths of various organs [1]. ICG has been used as a near-infrared (NIR) chromophore to visualise the target structures of organs during intraoperative microscopy coupled with a charge-coupled device camera, enabling real-time NIR imaging in vivo [7,8,9]. Bioluminescence imaging is a non-invasive modality with considerable potential for visualisation in deeper tissues and is widely used in the field of preclinical animal research, those studies have been limited by difficulties in non-invasively monitoring early disease progression in real time with high spatial resolution [11]

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