title: Multiscale photoacoustic tomography using reversibly switchable bacterial phytochrome as a near-infrared photochromic probe.
abstract: Photoacoustic tomography (PAT) of genetically encoded probes allows for imaging of targeted biological processes deep in tissues with high spatial resolution; however, high background signals from blood can limit the achievable detection sensitivity. Here we describe a reversibly switchable nonfluorescent bacterial phytochrome for use in multiscale photoacoustic imaging, BphP1, with the most red-shifted absorption among genetically encoded probes. BphP1 binds a heme-derived biliverdin chromophore and is reversibly photoconvertible between red and near-infrared light-absorption states. We combined single-wavelength PAT with efficient BphP1 photoswitching, which enabled differential imaging with substantially decreased background signals, enhanced detection sensitivity, increased penetration depth and improved spatial resolution. We monitored tumor growth and metastasis with ∼ 100-μm resolution at depths approaching 10 mm using photoacoustic computed tomography, and we imaged individual cancer cells with a suboptical-diffraction resolution of ∼ 140 nm using photoacoustic microscopy. This technology is promising for biomedical studies at several scales.
authors.affiliation: Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri, USA.
authors.forename: Junjie
authors.initials: J
authors.lastname: Yao
authors.affiliation: Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York, USA.|Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Andrii A
authors.initials: AA
authors.lastname: Kaberniuk
authors.affiliation: Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York, USA.|Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Daria M
authors.initials: DM
authors.lastname: Shcherbakova
authors.affiliation: Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri, USA.
authors.forename: Ruiying
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri, USA.
authors.forename: Lidai
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri, USA.
authors.forename: Guo
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York, USA.|Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine, Bronx, New York, USA.|Department of Biochemistry and Developmental Biology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Vladislav V
authors.initials: VV
authors.lastname: Verkhusha
authors.affiliation: Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri, USA.
authors.forename: Lihong V
authors.initials: LV
authors.lastname: Wang
mesh_terms: D000162:Acoustics; D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D010834:Phytochrome / Q000737:chemistry*; D014054:Tomography / Q000379:methods*
chemical_list: D010834:Phytochrome