Scan-less machine-learning-enabled incoherent microscopy for minimally-invasive deep-brain imaging

Opt Express. 2022 Jan 17;30(2):1546-1554. doi: 10.1364/OE.446241.

Abstract

Deep-brain microscopy is strongly limited by the size of the imaging probe, both in terms of achievable resolution and potential trauma due to surgery. Here, we show that a segment of an ultra-thin multi-mode fiber (cannula) can replace the bulky microscope objective inside the brain. By creating a self-consistent deep neural network that is trained to reconstruct anthropocentric images from the raw signal transported by the cannula, we demonstrate a single-cell resolution (< 10μm), depth sectioning resolution of 40 μm, and field of view of 200 μm, all with green-fluorescent-protein labelled neurons imaged at depths as large as 1.4 mm from the brain surface. Since ground-truth images at these depths are challenging to obtain in vivo, we propose a novel ensemble method that averages the reconstructed images from disparate deep-neural-network architectures. Finally, we demonstrate dynamic imaging of moving GCaMp-labelled C. elegans worms. Our approach dramatically simplifies deep-brain microscopy.

MeSH terms

  • Animals
  • Brain / diagnostic imaging*
  • Caenorhabditis elegans / cytology
  • Cells, Cultured
  • Green Fluorescent Proteins / metabolism
  • Image Processing, Computer-Assisted / methods
  • Machine Learning*
  • Mice
  • Microscopy, Fluorescence / methods*
  • Minimally Invasive Surgical Procedures
  • Neural Networks, Computer
  • Neuroimaging / methods*
  • Neurons / cytology
  • Neurons / metabolism

Substances

  • Green Fluorescent Proteins