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Proceedings Paper

Recording membrane potential changes through photoacoustic voltage sensitive dye
Author(s): Haichong K. Zhang; Jeeun Kang; Ping Yan; Diane S. Abou; Hanh N. D. Le; Daniel L. J. Thorek; Jin U. Kang; Albert Gjedde; Arman Rahmim; Dean F. Wong; Leslie M. Loew; Emad M. Boctor
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Paper Abstract

Monitoring of the membrane potential is possible using voltage sensitive dyes (VSD), where fluorescence intensity changes in response to neuronal electrical activity. However, fluorescence imaging is limited by depth of penetration and high scattering losses, which leads to low sensitivity in vivo systems for external detection. In contrast, photoacoustic (PA) imaging, an emerging modality, is capable of deep tissue, noninvasive imaging by combining near infrared light excitation and ultrasound detection. In this work, we develop the theoretical concept whereby the voltage-dependent quenching of dye fluorescence leads to a reciprocal enhancement of PA intensity. Based on this concept, we synthesized a novel near infrared photoacoustic VSD (PA-VSD) whose PA intensity change is sensitive to membrane potential. In the polarized state, this cyanine-based probe enhances PA intensity while decreasing fluorescence output in a lipid vesicle membrane model. With a 3-9 μM VSD concentration, we measured a PA signal increase in the range of 5.3 % to 18.1 %, and observed a corresponding signal reduction in fluorescence emission of 30.0 % to 48.7 %. A theoretical model successfully accounts for how the experimental PA intensity change depends on fluorescence and absorbance properties of the dye. These results not only demonstrate the voltage sensing capability of the dye, but also indicate the necessity of considering both fluorescence and absorbance spectral sensitivities in order to optimize the characteristics of improved photoacoustic probes. Together, our results demonstrate photoacoustic sensing as a potential new modality for sub-second recording and external imaging of electrophysiological and neurochemical events in the brain.

Paper Details

Date Published: 22 March 2017
PDF: 10 pages
Proc. SPIE 10064, Photons Plus Ultrasound: Imaging and Sensing 2017, 1006407 (22 March 2017); doi: 10.1117/12.2252442
Show Author Affiliations
Haichong K. Zhang, Johns Hopkins Univ. (United States)
Jeeun Kang, Johns Hopkins Univ. (United States)
Ping Yan, Univ. of Connecticut School of Medicine (United States)
Diane S. Abou, Johns Hopkins Univ. School of Medicine (United States)
Hanh N. D. Le, Johns Hopkins Univ. (United States)
Daniel L. J. Thorek, Johns Hopkins Univ. School of Medicine (United States)
Jin U. Kang, Johns Hopkins Univ. (United States)
Albert Gjedde, Univ. of Copenhagen (Denmark)
Arman Rahmim, Johns Hopkins Univ. School of Medicine (United States)
Dean F. Wong, Johns Hopkins Univ. School of Medicine (United States)
Leslie M. Loew, Univ. of Connecticut School of Medicine (United States)
Emad M. Boctor, Johns Hopkins Univ. School of Medicine (United States)


Published in SPIE Proceedings Vol. 10064:
Photons Plus Ultrasound: Imaging and Sensing 2017
Alexander A. Oraevsky; Lihong V. Wang, Editor(s)

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