title: Listening to membrane potential: photoacoustic voltage-sensitive dye recording.
abstract: Voltage-sensitive dyes (VSDs) are designed to monitor membrane potential by detecting fluorescence changes in response to neuronal or muscle 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. By contrast, photoacoustic (PA) imaging, an emerging modality, is capable of deep tissue, noninvasive imaging by combining near-infrared light excitation and ultrasound detection. Here, we show that voltage-dependent quenching of dye fluorescence leads to a reciprocal enhancement of PA intensity. We synthesized a 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. A theoretical model accounts for how the experimental PA intensity change depends on fluorescence and absorbance properties of the dye. These results not only demonstrate PA voltage sensing but also emphasize the interplay of both fluorescence and absorbance properties in the design of optimized PA probes. Together, our results demonstrate PA sensing as a potential new modality for recording and external imaging of electrophysiological and neurochemical events in the brain.
authors.affiliation: Johns Hopkins University, Department of Computer Science, Baltimore, Maryland, United States.
authors.forename: Haichong K
authors.initials: HK
authors.lastname: Zhang
authors.affiliation: University of Connecticut School of Medicine, R. D. Berlin Center for Cell Analysis and Modeling, Farmington, Connecticut, United States.
authors.forename: Ping
authors.initials: P
authors.lastname: Yan
authors.affiliation: Johns Hopkins University, Department of Computer Science, Baltimore, Maryland, United States.
authors.forename: Jeeun
authors.initials: J
authors.lastname: Kang
authors.affiliation: Johns Hopkins University School of Medicine, Russell H. Morgan Department of Radiology, Baltimore, Maryland, United States.
authors.forename: Diane S
authors.initials: DS
authors.lastname: Abou
authors.affiliation: Johns Hopkins University, Department of Electrical and Computer Engineering, Baltimore, Maryland, United States.
authors.forename: Hanh N D
authors.initials: HN
authors.lastname: Le
authors.affiliation: Johns Hopkins University School of Medicine, Russell H. Morgan Department of Radiology, Baltimore, Maryland, United States.
authors.forename: Abhinav K
authors.initials: AK
authors.lastname: Jha
authors.affiliation: Johns Hopkins University School of Medicine, Russell H. Morgan Department of Radiology, Baltimore, Maryland, United StateseJohns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Baltimore, Maryland, United States.
authors.forename: Daniel L J
authors.initials: DL
authors.lastname: Thorek
authors.affiliation: Johns Hopkins University, Department of Electrical and Computer Engineering, Baltimore, Maryland, United States.
authors.forename: Jin U
authors.initials: JU
authors.lastname: Kang
authors.affiliation: Johns Hopkins University School of Medicine, Russell H. Morgan Department of Radiology, Baltimore, Maryland, United StateseJohns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Baltimore, Maryland, United States.
authors.forename: Arman
authors.initials: A
authors.lastname: Rahmim
authors.affiliation: Johns Hopkins University School of Medicine, Russell H. Morgan Department of Radiology, Baltimore, Maryland, United StatesfJohns Hopkins University, Department of Neuroscience, Baltimore, Maryland, United StatesgJohns Hopkins University, Department of Psychiatry and Behavioral Sciences, Baltimore, Maryland, United StateshJohns Hopkins University, Department of Neurology, Baltimore, Maryland, United States.
authors.forename: Dean F
authors.initials: DF
authors.lastname: Wong
authors.affiliation: Johns Hopkins University, Department of Computer Science, Baltimore, Maryland, United StatescJohns Hopkins University School of Medicine, Russell H. Morgan Department of Radiology, Baltimore, Maryland, United StatesdJohns Hopkins University, Department of Electrical and Computer Engineering, Baltimore, Maryland, United States.
authors.forename: Emad M
authors.initials: EM
authors.lastname: Boctor
authors.affiliation: University of Connecticut School of Medicine, R. D. Berlin Center for Cell Analysis and Modeling, Farmington, Connecticut, United States.
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Loew
mesh_terms: D000162:Acoustics; D000465:Algorithms; D000818:Animals; D001921:Brain / Q000503:physiopathology; D002232:Carbocyanines / Q000737:chemistry; D002462:Cell Membrane / Q000187:drug effects; D005456:Fluorescent Dyes / Q000737:chemistry*; D006801:Humans; D008563:Membrane Lipids / Q000737:chemistry; D008564:Membrane Potentials; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000187:drug effects; D019047:Phantoms, Imaging; D061088:Photoacoustic Techniques; D017785:Photons; D013050:Spectrometry, Fluorescence; D019265:Spectroscopy, Near-Infrared; D014634:Valinomycin / Q000494:pharmacology
chemical_list: D002232:Carbocyanines; D005456:Fluorescent Dyes; D008563:Membrane Lipids; C000657:cyanine dye 1; D014634:Valinomycin