title: Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue.
abstract: Measurements of oxygen partial pressure (pO(2)) with high temporal and spatial resolution in three dimensions is crucial for understanding oxygen delivery and consumption in normal and diseased brain. Among existing pO(2) measurement methods, phosphorescence quenching is optimally suited for the task. However, previous attempts to couple phosphorescence with two-photon laser scanning microscopy have faced substantial difficulties because of extremely low two-photon absorption cross-sections of conventional phosphorescent probes. Here we report to our knowledge the first practical in vivo two-photon high-resolution pO(2) measurements in small rodents' cortical microvasculature and tissue, made possible by combining an optimized imaging system with a two-photon-enhanced phosphorescent nanoprobe. The method features a measurement depth of up to 250 microm, sub-second temporal resolution and requires low probe concentration. The properties of the probe allowed for direct high-resolution measurement of cortical extravascular (tissue) pO(2), opening many possibilities for functional metabolic brain studies.
authors.affiliation: Photon Migration Imaging Laboratory, Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
authors.forename: Sava
authors.initials: S
authors.lastname: Sakadzić
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Roussakis
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Yaseen
authors.forename: Emiri T
authors.initials: ET
authors.lastname: Mandeville
authors.forename: Vivek J
authors.initials: VJ
authors.lastname: Srinivasan
authors.forename: Ken
authors.initials: K
authors.lastname: Arai
authors.forename: Svetlana
authors.initials: S
authors.lastname: Ruvinskaya
authors.forename: Anna
authors.initials: A
authors.lastname: Devor
authors.forename: Eng H
authors.initials: EH
authors.lastname: Lo
authors.forename: Sergei A
authors.initials: SA
authors.lastname: Vinogradov
authors.forename: David A
authors.initials: DA
authors.lastname: Boas
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000098:blood supply*; D002560:Cerebrovascular Circulation; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D010100:Oxygen / Q000032:analysis* / Q000097:blood*; D010313:Partial Pressure; D011522:Protons; D051381:Rats
chemical_list: D011522:Protons; D010100:Oxygen