Fast fit-free analysis of fluorescence lifetime imaging via deep learning.

Journal: Proceedings of the National Academy of Sciences of the United States of America
Published Date:

Abstract

Fluorescence lifetime imaging (FLI) provides unique quantitative information in biomedical and molecular biology studies but relies on complex data-fitting techniques to derive the quantities of interest. Herein, we propose a fit-free approach in FLI image formation that is based on deep learning (DL) to quantify fluorescence decays simultaneously over a whole image and at fast speeds. We report on a deep neural network (DNN) architecture, named fluorescence lifetime imaging network (FLI-Net) that is designed and trained for different classes of experiments, including visible FLI and near-infrared (NIR) FLI microscopy (FLIM) and NIR gated macroscopy FLI (MFLI). FLI-Net outputs quantitatively the spatially resolved lifetime-based parameters that are typically employed in the field. We validate the utility of the FLI-Net framework by performing quantitative microscopic and preclinical lifetime-based studies across the visible and NIR spectra, as well as across the 2 main data acquisition technologies. These results demonstrate that FLI-Net is well suited to accurately quantify complex fluorescence lifetimes in cells and, in real time, in intact animals without any parameter settings. Hence, FLI-Net paves the way to reproducible and quantitative lifetime studies at unprecedented speeds, for improved dissemination and impact of FLI in many important biomedical applications ranging from fundamental discoveries in molecular and cellular biology to clinical translation.

Authors

  • Jason T Smith
    Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180; smithj28@rpi.edu intesx@rpi.edu.
  • Ruoyang Yao
    Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180.
  • Nattawut Sinsuebphon
    Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180.
  • Alena Rudkouskaya
    Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208.
  • Nathan Un
    Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180.
  • Joseph Mazurkiewicz
    Department of Neuroscience and Experimental Therapeutics, Albany Medical College, Albany, NY 12208.
  • Margarida Barroso
    Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208.
  • Pingkun Yan
    Philips Research North America, Briarcliff Manor, NY 10510, USA.
  • Xavier Intes
    Center for Modeling, Simulation and Imaging in Medicine, Rensselaer Polytechnic Institute, Troy, NY; Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY.