Rapid Quantification of Microvessels of Three-Dimensional Blood-Brain Barrier Model Using Optical Coherence Tomography and Deep Learning Algorithm.

Journal: Biosensors
PMID:

Abstract

The blood-brain barrier (BBB) is a selective barrier that controls the transport between the blood and neural tissue features and maintains brain homeostasis to protect the central nervous system (CNS). models can be useful to understand the role of the BBB in disease and assess the effects of drug delivery. Recently, we reported a 3D BBB model with perfusable microvasculature in a Transwell insert. It replicates several key features of the native BBB, as it showed size-selective permeability of different molecular weights of dextran, activity of the P-glycoprotein efflux pump, and functionality of receptor-mediated transcytosis (RMT), which is the most investigated pathway for the transportation of macromolecules through endothelial cells of the BBB. For quality control and permeability evaluation in commercial use, visualization and quantification of the 3D vascular lumen structures is absolutely crucial. Here, for the first time, we report a rapid, non-invasive optical coherence tomography (OCT)-based approach to quantify the microvessel network in the 3D BBB model. Briefly, we successfully obtained the 3D OCT images of the BBB model and further processed the images using three strategies: morphological imaging processing (MIP), random forest machine learning using the Trainable Weka Segmentation plugin (RF-TWS), and deep learning using pix2pix cGAN. The performance of these methods was evaluated by comparing their output images with manually selected ground truth images. It suggested that deep learning performed well on object identification of OCT images and its computation results of vessel counts and surface areas were close to the ground truth results. This study not only facilitates the permeability evaluation of the BBB model but also offers a rapid, non-invasive observational and quantitative approach for the increasing number of other 3D models.

Authors

  • Huiting Zhang
    College of Data Science, Taiyuan University of Technology, Jinzhong 030600, China; Technology Research Centre of Spatial Information Network Engineering of Shanxi, Jinzhong 030600, China; Key Laboratory of Big Data Fusion Analysis and Application of Shanxi Province, Taiyuan, China, 030024.
  • Dong-Hee Kang
    Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita 565-0871, Osaka, Japan.
  • Marie Piantino
    Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita 565-0871, Osaka, Japan.
  • Daisuke Tominaga
    Okinawa Study Center, the Open University of Japan.
  • Takashi Fujimura
    SCREEN Holdings Co., Ltd., 322 Furukawa-cho, Hazukashi, Fushimi-ku, Kyoto 612-8486, Kyoto, Japan.
  • Noriyuki Nakatani
    SCREEN Holdings Co., Ltd., 322 Furukawa-cho, Hazukashi, Fushimi-ku, Kyoto 612-8486, Kyoto, Japan.
  • J Nicholas Taylor
    Research Institute for Electronic Science , Hokkaido University , Kita 20, Nishi 10 , Kita-ku, Sapporo 001-0020 , Japan.
  • Tomomi Furihata
    School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji 192-0392, Tokyo, Japan.
  • Michiya Matsusaki
    AIST-Osaka University Advanced Photonics and Biosensing Open Innovation Laboratory, National Institute of Advanced Industrial Science and Technology (AIST), 2-1 Yamadaoka, Suita 565-0871, Osaka, Japan.
  • Satoshi Fujita
    Department of Neurosurgery, Toho University Ohashi Medical Center, Tokyo, Japan.