Open AccessIn Vivo Single-Molecule Detection of Nanoparticles for Multiphoton Fluorescence Correlation Spectroscopy to Quantify Cerebral Blood Flow
Author(s) -
Xu Fu,
Pradoldej Sompol,
J. Anthony Brandon,
Christopher M. Norris,
Thomas Wilkop,
Lance A. Johnson,
Christopher I. Richards
Publication year - 2020
Publication title -
nano letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.853
H-Index - 488
eISSN - 1530-6992
pISSN - 1530-6984
DOI - 10.1021/acs.nanolett.0c02280
Subject(s) - fluorescence correlation spectroscopy , nanoparticle , temporal resolution , fluorescence , image resolution , materials science , resolution (logic) , spectroscopy , fluorescence spectroscopy , analytical chemistry (journal) , cerebral blood flow , blood flow , chemistry , biological system , biomedical engineering , nanotechnology , optics , chromatography , physics , computer science , medicine , cardiology , quantum mechanics , artificial intelligence , biology
We present the application of multiphoton in vivo fluorescence correlation spectroscopy (FCS) of fluorescent nanoparticles for the measurement of cerebral blood flow with excellent spatial and temporal resolution. Through the detection of single nanoparticles within the complex vessel architecture of a live mouse, this new approach enables the quantification of nanoparticle dynamics occurring within the vasculature along with simultaneous measurements of blood flow properties in the brain. In addition to providing high resolution blood flow measurements, this approach enables real-time quantification of nanoparticle concentration, degradation, and transport. This method is capable of quantifying flow rates at each pixel with submicron resolution to enable monitoring of dynamic changes in flow rates in response to changes in the animal's physiological condition. Scanning the excitation beam using FCS provides pixel by pixel mapping of flow rates with subvessel resolution across capillaries 300 μm deep in the brains of mice.