Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 110, Issue 15, Pages 5759-5764Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1215578110
Keywords
photoacoustic microscopy; flow cytometry; oximetry; oxygenation; microenvironment
Categories
Funding
- National Institutes of Health [R01 EB000712, R43 HL106855, R01 EB008085, R01 CA134539, U54 CA136398, R01 CA157277, R01 EB010049]
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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 (del 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 502, del 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.
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