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Published April 9, 2013 | Published + Supplemental Material
Journal Article Open

Single-cell label-free photoacoustic flowoxigraphy in vivo


Label-free functional imaging of single red blood cells (RBCs) in vivo holds the key to uncovering the fundamental mechanism of oxygen metabolism in cells. To this end, we developed single-RBC photoacoustic flowoxigraphy (FOG), which can image oxygen delivery from single flowing RBCs in vivo with millisecond-scale temporal resolution and micrometer-scale spatial resolution. Using intrinsic optical absorption contrast from oxyhemoglobin (HbO_2) and deoxyhemoglobin (HbR), FOG allows label-free imaging. Multiple single-RBC functional parameters, including total hemoglobin concentration (C_(Hb)), oxygen saturation (sO_2), sO_2 gradient (∇SO_2), flow speed (v_f), and oxygen release rate (rO_2), have been quantified simultaneously in real time. Working in reflection instead of transmission mode, the system allows minimally invasive imaging at more anatomical sites. We showed the capability to measure relationships among sO_2, ∇SO_2, v_f, and rO_2 in a living mouse brain. We also demonstrated that single-RBC oxygen delivery was modulated by changing either the inhalation gas or blood glucose. Furthermore, we showed that the coupling between neural activity and oxygen delivery could be imaged at the single-RBC level in the brain. The single-RBC functional imaging capability of FOG enables numerous biomedical studies and clinical applications.

Additional Information

© 2013 National Academy of Sciences. Edited by Rakesh K. Jain, Harvard Medical School and Massachusetts General Hospital, Boston, MA, and approved February 27, 2013 (received for review September 10, 2012). Published ahead of print March 27, 2013. The authors thank Feng Gao for discussion on statistics; Arie Krumholz, Sandra Matteucci, Seema Mukhi Dahlheimer, and James Ballard for manuscript editing; and Arie Krumholz, Dakang Yao, Junjie Yao, and Song Hu for helpful discussions. This work was sponsored in part by National Institutes of Health Grants R01 EB000712, R43 HL106855, R01 EB008085, R01 CA134539, U54 CA136398, R01 CA157277, and R01 EB010049. Author contributions: L.W., K.M., and L.V.W. designed research; L.W. performed research; L.W. analyzed data; and L.W. and L.V.W. wrote the paper. The authors declare no conflict of interest. Conflict of interest statement: L.V.W. has a financial interest in Microphotoacoustics, Inc. and Endra, Inc., which, however, did not support this work. K.M. has a financial interest in Microphotoacoustics, Inc., which also did not support this work. This Direct Submission article had a prearranged editor. This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1215578110/-/DCSupplemental.

Attached Files

Published - PNAS-2013-Wang-5759-64.pdf

Supplemental Material - pnas.201215578SI.pdf

Supplemental Material - sm01.wmv

Supplemental Material - sm02.wmv

Supplemental Material - sm03.wmv

Supplemental Material - sm04.wmv

Supplemental Material - sm05.wmv

Supplemental Material - sm06.wmv


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August 22, 2023
October 19, 2023