Research Papers: Imaging

High-resolution contrast-enhanced optical coherence tomography in mice retinae

[+] Author Affiliations
Debasish Sen

Stanford University, Department of Structural Biology, 299 Campus Drive, Stanford, California 94305, United States

Stanford University, Molecular Imaging Program at Stanford, 299 Campus Drive, Stanford, California 94305, United States

Elliott D. SoRelle

Stanford University, Department of Structural Biology, 299 Campus Drive, Stanford, California 94305, United States

Stanford University, Biophysics Program, 299 Campus Drive, Stanford, California 94305, United States

Stanford University, Department of Electrical Engineering, 299 Campus Drive, Stanford, California 94305, United States

Orly Liba

Stanford University, Department of Structural Biology, 299 Campus Drive, Stanford, California 94305, United States

Stanford University, Molecular Imaging Program at Stanford, 299 Campus Drive, Stanford, California 94305, United States

Stanford University, Department of Electrical Engineering, 299 Campus Drive, Stanford, California 94305, United States

Stanford University, Bio-X Program, 299 Campus Drive, Stanford, California, 94305, United States

Roopa Dalal

Stanford University, Department of Ophthalmology, 300 Pasteur Drive, Palo Alto, California 94304, United States

Yannis M. Paulus, Tae-Wan Kim

Stanford University, Department of Structural Biology, 299 Campus Drive, Stanford, California 94305, United States

Darius M. Moshfeghi

Stanford University, Bio-X Program, 299 Campus Drive, Stanford, California, 94305, United States

Stanford University, Department of Ophthalmology, Stanford Byers Eye Institute, 2452 Watson Court, Palo Alto, California 94303, United States

Adam de la Zerda

Stanford University, Department of Structural Biology, 299 Campus Drive, Stanford, California 94305, United States

Stanford University, Molecular Imaging Program at Stanford, 299 Campus Drive, Stanford, California 94305, United States

Stanford University, Biophysics Program, 299 Campus Drive, Stanford, California 94305, United States

Stanford University, Department of Electrical Engineering, 299 Campus Drive, Stanford, California 94305, United States

Stanford University, Bio-X Program, 299 Campus Drive, Stanford, California, 94305, United States

J. Biomed. Opt. 21(6), 066002 (Jun 06, 2016). doi:10.1117/1.JBO.21.6.066002
History: Received August 28, 2015; Accepted May 2, 2016
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Abstract.  Optical coherence tomography (OCT) is a noninvasive interferometric imaging modality providing anatomical information at depths of millimeters and a resolution of micrometers. Conventional OCT images limit our knowledge to anatomical structures alone, without any contrast enhancement. Therefore, here we have, for the first time, optimized an OCT-based contrast-enhanced imaging system for imaging single cells and blood vessels in vivo inside the living mouse retina at subnanomolar sensitivity. We used bioconjugated gold nanorods (GNRs) as exogenous OCT contrast agents. Specifically, we used anti-mouse CD45 coated GNRs to label mouse leukocytes and mPEG-coated GNRs to determine sensitivity of GNR detection in vivo inside mice retinae. We corroborated OCT observations with hyperspectral dark-field microscopy of formalin-fixed histological sections. Our results show that mouse leukocytes that otherwise do not produce OCT contrast can be labeled with GNRs leading to significant OCT intensity equivalent to a 0.5 nM GNR solution. Furthermore, GNRs injected intravenously can be detected inside retinal blood vessels at a sensitivity of 0.5  nM, and GNR-labeled cells injected intravenously can be detected inside retinal capillaries by enhanced OCT contrast. We envision the unprecedented resolution and sensitivity of functionalized GNRs coupled with OCT to be adopted for longitudinal studies of retinal disorders.

Figures in this Article
© 2016 Society of Photo-Optical Instrumentation Engineers

Citation

Debasish Sen ; Elliott D. SoRelle ; Orly Liba ; Roopa Dalal ; Yannis M. Paulus, et al.
"High-resolution contrast-enhanced optical coherence tomography in mice retinae", J. Biomed. Opt. 21(6), 066002 (Jun 06, 2016). ; http://dx.doi.org/10.1117/1.JBO.21.6.066002


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