title: Ultrasensitive detection of 3D cerebral microvascular network dynamics in vivo.
abstract: Despite widespread applications of multiphoton microscopy in microcirculation, its small field of view and inability to instantaneously quantify cerebral blood flow velocity (CBFv) in vascular networks limit its utility in investigating the heterogeneous responses to brain stimulations. Optical Doppler tomography (ODT) provides 3D images of CBFv networks, but it suffers poor sensitivity for measuring capillary flows. Here we report on a new method, contrast-enhanced ODT with Intralipid that significantly improves quantitative CBFv imaging of capillary networks by obviating the errors from long latency between flowing red blood cells (low hematocrit ~20% in capillaries). This enhanced sensitivity allowed us to measure the ultraslow microcirculation surrounding a brain tumor and the abnormal ingrowth of capillary flows in the tumor as well as in ischemia triggered by chronic cocaine in the mouse brain that could not be detected by regular ODT. It also enabled significantly enhanced sensitivity for quantifying the heterogeneous CBFv responses of vascular networks to acute cocaine exposure. Inasmuch as lipid emulsions are widely used for parenteral nutrition the Intralipid contrast method has translational potential for clinical applications.
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794, USA. Electronic address: yingtian.pan@stonybrook.edu.
authors.forename: Yingtian
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Jiang
authors.initials: J
authors.lastname: You
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20857, USA.
authors.forename: Nora D
authors.initials: ND
authors.lastname: Volkow
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Kicheon
authors.initials: K
authors.lastname: Park
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Congwu
authors.initials: C
authors.lastname: Du
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply*; D002545:Brain Ischemia / Q000503:physiopathology; D001932:Brain Neoplasms / Q000098:blood supply; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004655:Emulsions; D005260:Female; D021621:Imaging, Three-Dimensional / Q000379:methods*; D008279:Magnetic Resonance Imaging; D051379:Mice; D055806:Microvessels / Q000648:ultrastructure*; D010743:Phospholipids; D013024:Soybean Oil; D041623:Tomography, Optical Coherence / Q000379:methods*
chemical_list: D004655:Emulsions; D010743:Phospholipids; C545823:soybean oil, phospholipid emulsion; D013024:Soybean Oil